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Improved method for minimum inhibitory concentration testing of flavobacterium columnare
Technology Transfer Automated Retrieval System (TEKTRAN)
A simple and reliable microdilution method has been developed to test the susceptibility of Flavobacterium columnare to antibiotics in vitro. The method has been used to determine the minimum inhibitory concentration (MIC) of 23 F. columnare isolates. The tests were conducted at 28 °C using a stan...
Vancomycin minimum inhibitory concentrations and lethality in Staphylococcus aureus bacteremia
Sulla, Felipe; Bussius, Daniel T.; Acquesta, Felipe; Navarini, Alessandra; Sasagawa, Suzethe M.; Mimica, Marcelo J.
Background After the dissemination of penicillin and oxacillin resistance in Staphylococcus aureus, vancomycin-intermediate and vancomycin resistant isolates have been reported. Even between isolates with minimum inhibitory concentrations (MICs) within the susceptible range, some authors have demonstrated that higher MICs correlate with higher lethality. Methods To test this hypothesis in our setting, we compared vancomycin MICs evaluated by two methods and clinical outcomes in hospitalized patients with S. aureus bacteremia. Results We compared lethality in patients infected with isolates that had MICs under or over 2 mg/L. Among patients infected with isolates that had microdilution MICs <2 mg/L, the lethality was 25%; among patients infected with strains that had microdilution MICs ?2 mg/L, 33% died. Among patients infected with isolates that had Etest MICs <2 mg/L, 23% died; in comparison, patients infected with strains that had Etest MICs ?2 mg/L had a lethality of 44%. Conclusion Our results showed a slight tendency of higher lethality when higher MICs were present. However, this difference did not reach statistical significance, possibly due to the relatively small number of patients included in the study. Future prospective studies are needed to further evaluate this correlation and to help clinicians guide antimicrobial therapy. PMID:26097833
Minimum inhibitory concentrations of some antimicrobial drugs against bacteria causing uterine infections in cattle
I. M. Sheldon; M. Bushnell; J. Montgomery; A. N. Rycroft
The minimum inhibitory concentrations (MICs) of oxytetracycline, cephapirin, cephapirin\\/mecillinam, cefquinome, ceftiofur and enrofloxacin, candidate antibiotics for the principal bacteria associated with uterine infections: Escherichia coli, Arcanobacterium pyogenes and the anaerobic bacteria Fusobacterium necrophorum and Prevotella melaninogenicus, were determined by the agar dilution method. The bacteria were isolated from animals with clinical metritis and\\/or endometritis. For E coli, cefquinome and enrofloxacin
Minimum inhibitory concentrations of selected antimicrobials against Escherichia coli and Trueperella pyogenes of bovine uterine origin.
de Boer, Melvin; Heuer, Cord; Hussein, Hassan; McDougall, Scott
Minimum inhibitory concentrations (MIC) of 9 antimicrobials for isolates of 2 common bovine intrauterine bacterial pathogens, Escherichia coli (n=209) and Trueperella pyogenes (n=35), were determined using broth microdilution methodology. The isolates were recovered from dairy cows from 7 herds postpartum using the cytobrush technique. The pathogens were initially identified using phenotypic techniques. Additionally, PCR was used to confirm the identity of T. pyogenes isolates and to categorize the E. coli isolates into phylogenetic groups A, B1, B2, and D. Minimum inhibitory concentrations in excess of published cut-points or bimodal distributions of MIC indicated potential antimicrobial resistance to ampicillin, cefuroxime, cephapirin, and oxytetracycline for E. coli, and to oxytetracycline for T. pyogenes. Of the antimicrobials tested, ticarcillin/clavulanic acid, ceftiofur, and enrofloxacin had the lowest MIC for these 2 pathogens. Differences in MIC of some antimicrobials were found between herds, age, breeds, and E. coli phylogenetic groups. Isolation of E. coli with an MIC ?8?g/mL of oxytetracycline at 23d postpartum was associated with a lower probability of pregnancy within 6wk of commencement of breeding compared with those isolates with an MIC <8?g/mL (relative risk=0.66). Minimum inhibitory concentrations for uterine pathogens were determined for isolates from New Zealand dairy cows. However, in the absence of either epidemiological or clinical interpretive criteria, the interpretation of these MIC remains unclear. Further studies are required to define interpretative criteria, including determination of pharmacokinetic and pharmacodynamic profiles for antimicrobials. PMID:25935246
Minimum inhibitory concentrations of some antimicrobial drugs against bacteria causing uterine infections in cattle.
Sheldon, I M; Bushnell, M; Montgomery, J; Rycroft, A N
The minimum inhibitory concentrations (MICs) of oxytetracycline, cephapirin, cephapirin/mecillinam, cefquinome, ceftiofur and enrofloxacin, candidate antibiotics for the principal bacteria associated with uterine infections: Escherichia coli, Arcanobacterium pyogenes and the anaerobic bacteria Fusobacterium necrophorum and Prevotella melaninogenicus, were determined by the agar dilution method. The bacteria were isolated from animals with clinical metritis and/or endometritis. For E coli, cefquinome and enrofloxacin had the lowest MIC90 and MIC50 values (< 0.06 microg/ml), and oxytetracycline and cephapirin had the highest values. For A pyogenes, oxytetracycline had the highest MIC50 value (16 microg/ml), but all the cephalosporins had values below 0.06 microg/ml. For the anaerobic bacteria, enrofloxacin and oxytetracycline had the highest MIC50 values but all the cephalosporins had values of 0.06 microg/ml or below. PMID:15499809
Increased Minimum Inhibitory Concentrations with Anaerobiasis for Tobramycin, Gentamicin, and Amikacin, Compared to Latamoxef, Piperacillin, Chloramphenicol, and Clindamycin
Kenneth J. Tack; L. D. Sabath
Minimum inhibitory concentrations (MICs) were determined under both routine aerobic and anaerobic conditions for a total of 93 organisms representing nine genera. MICs for the aminoglycosides amikacin, gentamicin, and tobramycin were significantly increased under anaerobic conditions. Tobramycin was most sensitive to the loss of antimicrobial activity with anaerobiasis. MICs for staphylococci were increased by a higher factor than were MICs
Accessory Gene Regulator Polymorphism and Vancomycin Minimum Inhibitory Concentration in Methicillin-Resistant Staphylococcus aureus
Park, Min-Jeong; Kim, Hyun Soo; Kim, Jae-Seok; Song, Wonkeun; Kim, Mi Young; Lee, Young Kyung; Kang, Hee Jung
Background Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with a vancomycin minimum inhibitory concentration (MIC) of 2 µg/mL presents a high rate of therapeutic failure in response to vancomycin. In addition, polymorphism in accessory gene regulator (agr) is associated with vancomycin therapeutic effects. The association between agr polymorphism and vancomycin MICs was investigated in MRSA isolates. Methods Agr group-specific PCR was conducted on 118 MRSA bloodstream isolates. Vancomycin susceptibility tests were conducted, while E-test GRD (bioMérieux SA, France) was used to detect heterogeneous vancomycin-intermediate S. aureus (hVISA). Results Of the 118 MRSA isolates, 59 (50.0%), 43 (36.4%), and 10 (8.5%) isolates belonged to agr group I, II, and III, respectively. Six isolates could not be classified. Twenty-six, 73, and 19 isolates presented a vancomycin MIC of 2, 1, and 0.5 µg/mL, respectively. Nine (34.6%), 14 (53.8%), and 2 (7.7%) isolates with MICs of 2 µg/mL belonged to agr group I, II, and III, respectively. Thirty-seven (50.6%), 26 (35.6%), and 6 (8.2%) isolates with MICs of 1 µg/mL belonged to agr group I, II, and III, respectively. Thirteen (68.4%), 3 (15.8%), and 2 (10.5%) isolates with MICs of 0.5 µg/mL belonged to agr group I, II, and III, respectively. The agr group II presented more isolates with MIC of 2 µg/mL (32.6%) than the agr non-group II (16%). Four isolates tested positive for hVISA. Three of them belonged to agr group II. Conclusions MRSA isolates with vancomycin MIC of 2 µg/mL were more common in agr group II than in agr non-group II. PMID:26131410
In vitro efficacy of colistin against multi-drug resistant Pseudomonas aeruginosa by minimum inhibitory concentration.
Gill, Maria Mushtaql; Rao, Javaid Usman; Kaleem, Fatima; Hassan, Afreenish; Khalid, Ali; Anjum, Rabia
Multi-drug resistant bacteria are an important cause of mortality and morbidity. In the management of various infections, timely detection and appropriate treatment, in accordance with the culture and sensitivity reports can help improve the treatment outcome. Colistin is a bactericidal antibiotic which is emerging as a reliable solution for treating infections with multi-drug resistant Gram negative bacilli. The aim of this study was to find out the in-vitro efficacy of colistin against multidrug resistant Pseudomonas aeruginosa isolates by minimum inhibitory concentration. This cross sectional, descriptive study was conducted in the Department of Microbiology, Army Medical College, National University of Sciences and Technology, Islamabad from February 2010 to January 2011. Antimicrobial sensitivity testing was done on Pseudomonas aeruginosa isolated from routine clinical specimens received and the strains which appeared resistant to at least one antimicrobial agent in three or more anti-pseudomonal antimicrobial categories were subjected to the Colistin Etest. The MIC endpoint of colistin was read, as per manufacturers instructions (AB Biodisk, Solna, Sweden). The isolates showing MIC of 2?g/ml or less were considered sensitive, those with 4-6?g/ml as intermediate and >?g/ml as resistant. MIC(50) and MIC(90) of colistin against MDR Pseudomonas aeruginosa was determined. A total of 52 MDR Pseudomonas aeruginosa strains were isolated during the period of the study. The highest percentage was isolated from urine (36%) followed by respiratory tract infections (18%) and pus specimens (20%). The highest percentage of these isolates was found to be susceptible to colistin followed by piperacillin-tazobactam and cefoperazone-sulbactam. A total of 36(69%) isolates were sensitive, 10(20%) were intermediate and 6(11%) were resistant to colistin by Kirby Bauer disc diffusion method. MIC(50) was found to be 1.0?g/ml while MIC(90) was 3.0?g/ml. Colistin is a reliable solution in cases of infections with MDR, XDR or PDR Pseudomonas aeruginosa. PMID:23261721
Epidemiology and prognosis of coagulase-negative staphylococcal endocarditis: impact of vancomycin minimum inhibitory concentration.
García de la Mŕria, Cristina; Cervera, Carlos; Pericŕs, Juan M; Castańeda, Ximena; Armero, Yolanda; Soy, Dolors; Almela, Manel; Ninot, Salvador; Falces, Carlos; Mestres, Carlos A; Gatell, Jose M; Moreno, Asuncion; Marco, Francesc; Miró, José M
This study describes coagulase-negative staphylococcal (CoNS) infective endocarditis (IE) epidemiology at our institution, the antibiotic susceptibility profile, and the influence of vancomycin minimum inhibitory concentration (MIC) on patient outcomes. One hundred and three adults with definite IE admitted to an 850-bed tertiary care hospital in Barcelona from 1995-2008 were prospectively included in the cohort. We observed that CoNS IE was an important cause of community-acquired and healthcare-associated IE; one-third of patients involved native valves. Staphylococcus epidermidis was the most frequent species, methicillin-resistant in 52% of patients. CoNS frozen isolates were available in 88 patients. Vancomycin MICs of 2.0 ?g/mL were common; almost all cases were found among S. epidermidis isolates and did not increase over time. Eighty-five patients were treated either with cloxacillin or vancomycin: 38 patients (Group 1) were treated with cloxacillin, and 47 received vancomycin; of these 47, 27 had CoNS isolates with a vancomycin MIC <2.0 ?g/mL (Group 2), 20 had isolates with a vancomycin MIC ? 2.0 ?g/mL (Group 3). One-year mortality was 21%, 48%, and 65% in Groups 1, 2, and 3, respectively (P = 0.003). After adjusting for confounders and taking Group 2 as a reference, methicillin-susceptibility was associated with lower 1-year mortality (OR 0.12, 95% CI 0.02-0.55), and vancomycin MIC ? 2.0 ?g/mL showed a trend to higher 1-year mortality (OR 3.7, 95% CI 0.9-15.2; P=0.069). Other independent variables associated with 1-year mortality were heart failure (OR 6.2, 95% CI 1.5-25.2) and pacemaker lead IE (OR 0.1, 95%CI 0.02-0.51). In conclusion, methicillin-resistant S.epidermidis was the leading cause of CoNS IE, and patients receiving vancomycin had higher mortality rates than those receiving cloxacillin; mortality was higher among patients having isolates with vancomycin MICs ? 2.0 ?g/mL. PMID:25961578
Killing of Streptococcus pneumoniae by azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin using drug minimum inhibitory concentrations and mutant prevention concentrations.
Blondeau, J M; Shebelski, S D; Hesje, C K
Streptococcus pneumoniae continues to be a significant respiratory pathogen, and increasing antimicrobial resistance compromises the use of ?-lactam and macrolide antibiotics. Bacterial eradication impacts clinical outcome, and bacterial loads at the site of infection may fluctuate. Killing of two macrolide- and quinolone-susceptible clinical S. pneumoniae isolates by azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin against varying bacterial densities was determined using the measured minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC). For kill experiments, 10(6)-10(9) CFU/mL were exposed to the drug and were sampled at 0, 0.5, 1, 2, 3, 4, 6, 12 and 24h following drug exposure. The log10 reduction and percent reduction (kill) of viable cells was recorded. MICs and MPCs (mg/L) for azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin were 0.063-0.125/0.5-1, 0.031-0.063/0.25-0.5, 0.063/0.25-0.5, 0.008/0.016 and 0.031/0.25, respectively. Killing 10(6)-10(9) CFU/mL of bacteria by the drug MIC yielded incomplete killing, however log10 reductions occurred by 12h and 24h for all drugs. Exposure of 10(6)-10(9) CFU/mL to MPC drug concentrations resulted in the following log10 reduction by 6h of drug exposure: azithromycin, 1.3-3.9; clarithromycin, 1.9-5.8; erythromycin, 0.8-4.7; telithromycin, 0.3-1.7; and gemifloxacin, 1.8-4.2. Bacterial loads at the site of infection may range from 10(6) to 10(9), and kill experiments utilising a higher bacterial inoculum provided a more accurate measure of antibiotic performance in high biomass situations. Killing was slower with telithromycin. Kill was greater and fastest with MPC versus MIC drug concentrations. PMID:25752567
Minimum inhibitory concentrations of chloramphenicol, florfenicol, trimethoprim\\/sulfadiazine and flumequine in seawater of bacteria associated with scallops ( Pecten maximus) larvae
Lise Torkildsen; Ole B Samuelsen; Bjřrn T Lunestad; Řivind Bergh
The purpose of this study was to find the minimum inhibitory concentrations (MIC) for the following antibacterial agents: chloramphenicol, florfenicol, flumequine and the combination trimethoprim\\/sulfadiazine to bacteria associated with scallop (Pecten maximus) larvae. To evaluate possible effects of components in seawater to the antimicrobial activity of these agents, MIC values were established on Mueller Hinton agar dissolved in either distilled
Evaluation of Difloxacin for Shrimp Aquaculture: In Vitro Minimum Inhibitory Concentrations, Medicated Feed Palatability, and Toxicity to the Shrimp Penaeus vannamei
Eric D. Park; Donald V. Lightner; Rodney R. Williams; Leone L. Mohney; John M. Stamm
Standard in vitro minimum inhibitory concentrations (MICs) were determined for difloxacin and compared with the MICs of several other antimicrobials, against a standardized battery of 13 gram-negative bacterial isolates associated with shrimp disease. The palatability and safety (toxicity) of difloxacin to the shrimp Penaeus vannamei were also evaluated during 15 d of medicated feeding at 1× (100 mg\\/kg of feed),
Cefepime free minimum concentration to minimum inhibitory concentration (fCmin/MIC) ratio predicts clinical failure in patients with Gram-negative bacterial pneumonia.
Aitken, Samuel L; Altshuler, Jerry; Guervil, David J; Hirsch, Elizabeth B; Ostrosky-Zeichner, Luis L; Ericsson, Charles D; Tam, Vincent H
Cefepime is an antibiotic commonly used in nosocomial infections. The objective of this study was to elucidate the relationship between cefepime exposure and clinical outcome in patients with Gram-negative bacterial pneumonia. A previously published population pharmacokinetic model of cefepime was validated in 12 adult patients with normal renal function by measuring plasma concentrations at steady-state. Additionally, clinical outcomes for 33 patients with Gram-negative bacterial pneumonia who received cefepime monotherapy were determined. The free minimum concentration (fCmin) to MIC ratio for each patient was determined by conditioning the validated pharmacokinetic model using patient-specific creatinine clearance (CLCr), dosing regimen and cefepime MIC of the organism isolated, and was subsequently correlated with clinical failure. Classification and regression tree (CART) analysis was used to determine the most significant drug exposure breakpoint. Mean±S.D. CLCr and cefepime Cmin in the 12 patients were 87.5±21.2mL/min and 6.2±3.8mg/L, respectively. In comparison, the Cmin predicted by the pharmacokinetic model was 5.8mg/L using a CLCr of 90mL/min. MICs of organisms ranged from 0.5mg/L to 8mg/L. Percent time free drug above MIC of 100% was achieved in 32/33 patients, but 12 patients experienced clinical failure. CART analysis determined patients with an fCmin/MIC?2.1 had a significantly lower risk of clinical failure (OR=0.11, 95% CI 0.02-0.67; P=0.017). The fCmin/MIC ratio is a useful predictor of clinical failure in Gram-negative bacterial pneumonia. The clinical utility of fCmin/MIC in therapeutic drug monitoring should be further explored. PMID:25665726
Minimum inhibitory (MIC) and minimum microbicidal concentration (MMC) of polihexanide and triclosan against antibiotic sensitive and resistant Staphylococcus aureus and Escherichia coli strains
Assadian, Ojan; Wehse, Katrin; Hübner, Nils-Olaf; Koburger, Torsten; Bagel, Simone; Jethon, Frank; Kramer, Axel
Background: An in-vitro study was conducted investigating the antimicrobial efficacy of polihexanide and triclosan against clinical isolates and reference laboratory strains of Staphylococcus aureus and Escherichia coli. Methods: The minimal inhibitory concentration (MIC) and the minimal microbicidal concentration (MMC) were determined following DIN 58940-81 using a micro-dilution assay and a quantitative suspension test following EN 1040. Polihexanide was tested in polyethylene glycol 4000, triclosan in aqueous solutions. Results: Against all tested strains the MIC of polihexanide ranged between 1–2 µg/mL. For triclosan the MICs varied depending on strains ranging between 0.5 µg/mL for the reference strains and 64 µg/mL for two clinical isolates. A logRF >5 without and logRF >3 with 0.2% albumin burden was achieved at 0.6 µg/mL triclosan. One exception was S. aureus strain H-5-24, where a triclosan concentration of 0.6 µg/mL required 1 minute without and 10 minutes with albumin burden to achieve the same logRFs. Polihexanide achieved a logRF >5 without and logRF >3 with albumin burden at a concentration of 0.6 µg/mL within 30 sec. The exception was the North-German epidemic MRSA strain, were an application time of 5 minutes was required. Conclusion: The clinical isolates of E. coli generally showed higher MICs against triclosan, both in the micro-dilution assay as well in the quantitative suspension test than comparable reference laboratory strains. For polihexanide and triclosan strain dependant susceptibility was shown. However, both antimicrobial compounds are effective when used in concentrations common in practice. PMID:22242087
Vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations: study protocol for a phase IIB randomized controlled trial
Background Vancomycin is the standard first-line treatment for methicillin-resistant Staphylococcus aureus bacteremia. However, recent consensus guidelines recommend that clinicians consider using alternative agents such as daptomycin when the vancomycin minimum inhibitory concentration is greater than 1 ug/ml. To date however, there have been no head-to-head randomized trials comparing the safety and efficacy of daptomycin and vancomycin in the treatment of such infections. The primary aim of our study is to compare the efficacy of daptomycin versus vancomycin in the treatment of bloodstream infections due to methicillin-resistant Staphylococcus aureus isolates with high vancomycin minimum inhibitory concentrations (greater than or equal to 1.5 ug/ml) in terms of reducing all-cause 60-day mortality. Methods/Design The study is designed as a multicenter prospective open label phase IIB pilot randomized controlled trial. Eligible participants will be inpatients over 21-years-old with a positive blood culture for methicillin-resistant Staphylococcus aureus with vancomycin minimum inhibitory concentration of greater than or equal to 1.5ug/ml. Randomization into intervention or active control arms will be performed with a 1:1 allocation ratio. We aim to recruit 50 participants over a period of two years. Participants randomized to the active control arm will receive vancomycin dose-while those randomized to the intervention arm will receive daptomycin. Participants will receive a minimum of 14 days study treatment. The primary analysis will be conducted on the intention-to-treat principle. The Fisher's exact test will be used to compare the 60-day mortality rate from index blood cultures (primary endpoint) between the two treatment arms, and the exact two-sided 95% confidence interval will be calculated using the Clopper and Pearson method. Primary analysis will be conducted using a two sided alpha of 0.05. Discussion If results from this pilot study suggest that daptomycin shows significant efficacy in the treatment of bloodstream infections due to methicillin-resistant Staphylococcus aureus isolates with high vancomycin minimum inhibitory concentrations, we aim to proceed with a larger scale confirmatory study. This would help guide clinicians and inform practice guidelines on the optimal treatment for such infections. Trial registration The trial is listed on clinicaltrials.gov (NCT01975662, date of registration: 29 October 2013). PMID:24943129
Effect of sub-minimum inhibitory concentrations of ciprofloxacin, amikacin and colistin on biofilm formation and virulence factors of Escherichia coli planktonic and biofilm forms isolated from human urine
Wojnicz, Dorota; Tichaczek-Goska, Dorota
The aim of this study was to determine the effect of subinhibitory concentrations (sub-MICs) of ciprofloxacin, amikacin and colistin on biofilm formation, motility, curli fimbriae formation by planktonic and biofilm cells of E. coli strains isolated from the urine of patients with various urinary system infections. Quantification of biofilm formation was carried out using a microtiter plate assay and a spectrophotometric method. Bacterial enumeration was used to assess the viability of bacteria in the biofilm. Curli expression was determined by using YESCA agar supplemented with congo red. Using motility agar the ability to move was examined. All the antibiotics used at sub-MICs reduced biofilm formation in vitro, decreased the survival of bacteria, but had no effect on the motility of planktonic as well as biofilm cells. The inhibitory effect of sub-MICs of antimicrobial agents on curli fimbriae formation was dependent on the form in which the bacteria occurred, incubation time and antibiotic used. Our results clearly show that all the three antibiotics tested reduce biofilm production, interfere with curli expression but do not influence motility. This study suggests that ciprofloxacin, amikacin and colistin may be useful in the treatment of biofilm-associated infections caused by E. coli strains. PMID:24159313
Effect of sub-minimum inhibitory concentrations of ciprofloxacin, amikacin and colistin on biofilm formation and virulence factors of Escherichia coli planktonic and biofilm forms isolated from human urine.
Wojnicz, Dorota; Tichaczek-Goska, Dorota
The aim of this study was to determine the effect of subinhibitory concentrations (sub-MICs) of ciprofloxacin, amikacin and colistin on biofilm formation, motility, curli fimbriae formation by planktonic and biofilm cells of E. coli strains isolated from the urine of patients with various urinary system infections. Quantification of biofilm formation was carried out using a microtiter plate assay and a spectrophotometric method. Bacterial enumeration was used to assess the viability of bacteria in the biofilm. Curli expression was determined by using YESCA agar supplemented with congo red. Using motility agar the ability to move was examined. All the antibiotics used at sub-MICs reduced biofilm formation in vitro, decreased the survival of bacteria, but had no effect on the motility of planktonic as well as biofilm cells. The inhibitory effect of sub-MICs of antimicrobial agents on curli fimbriae formation was dependent on the form in which the bacteria occurred, incubation time and antibiotic used. Our results clearly show that all the three antibiotics tested reduce biofilm production, interfere with curli expression but do not influence motility. This study suggests that ciprofloxacin, amikacin and colistin may be useful in the treatment of biofilm-associated infections caused by E. coli strains. PMID:24159313
Flammability limits of dusts: Minimum inerting concentrations
Dastidar, A.G.; Amyotte, P.R. [Dalhousie Univ., Halifax, Nova Scotia (Canada). Dept. of Chemical Engineering] [Dalhousie Univ., Halifax, Nova Scotia (Canada). Dept. of Chemical Engineering; Going, J.; Chatrathi, K. [Fike Corp., Blue Springs, MO (United States)] [Fike Corp., Blue Springs, MO (United States)
A new flammability limit parameter has been defined as the Minimum Inerting Concentration (MIC). This is the concentration of inertant required to prevent a dust explosion regardless of fuel concentration. Previous experimental work at Fike in a 1-m{sup 3} spherical chamber has shown this flammability limit to exist for pulverized coal dust and cornstarch. In the current work, inerting experiments with aluminum, anthraquinone and polyethylene dusts as fuels were performed, using monoammonium phosphate and sodium bicarbonate as inertants. The results show that an MIC exists only for anthraquinone inerted with sodium bicarbonate. The other combustible dust and inertant mixtures did not show a definitive MIC, although they did show a strong dependence between inerting level and suspended fuel concentration. As the fuel concentration increased, the amount of inertant required to prevent an explosion decreased. Even though a definitive MIC was not found for most of the dusts an effective MIC can be estimated from the data. The use of MIC data can aid in the design of explosion suppression schemes.
6 CFR 27.204 - Minimum concentration by security issue.
Code of Federal Regulations, 2010 CFR
... 2010-01-01 false Minimum concentration by security issue. 27.204 Section...Security Program § 27.204 Minimum concentration by security issue. (a) Release...interest is present in a mixture, and the concentration of the chemical is equal to...
6 CFR 27.204 - Minimum concentration by security issue.
Code of Federal Regulations, 2011 CFR
... 2011-01-01 false Minimum concentration by security issue. 27.204 Section...Security Program § 27.204 Minimum concentration by security issue. (a) Release...interest is present in a mixture, and the concentration of the chemical is equal to...
Providencia isolates carrying bla (PER-1) and bla (VIM-2) genes: biofilm-forming capacity and biofilm inhibitory concentrations for carbapenem antibiotics.
Kim, Jungmin; Kim, Shukho; Lee, Hee Woo; Kim, Sung Min; Seol, Sung Yong
Multidrug-resistant clinical isolates of Providentia carrying bla (PER-1) and bla (VIM-2) were evaluated for the abilities to form biofilm and high biofilm forming capacity was demonstrated in them. Minimum biofilm inhibitory concentrations (MBICs), minimum biofilm eradication concentrations (MBECs), and minimum inhibitory concentrations (MICs) for imipenem and meropenem were also determined. In all tested strains, the MBICs were higher than the MICs for both drugs. Interestingly, the MBICs and the MBEC(50) for meropenem were lower than those for imipenem in the isolates producing high amounts of biofilm, suggesting that meropenem is superior to imipenem in the growth inhibition and eradication of biofilm forming Providentia strains. PMID:21717342
6 CFR 27.204 - Minimum concentration by security issue.
Code of Federal Regulations, 2013 CFR
...Chemical Weapons Precursors (CWP Chemicals: Where a theft/diversion-CWC/CWP chemical of interest is not designated by "CUM 100g" in appendix A, and the chemical is present in a mixture at or above the minimum concentration amount listed in the...
6 CFR 27.204 - Minimum concentration by security issue.
Code of Federal Regulations, 2012 CFR
...Chemical Weapons Precursors (CWP Chemicals: Where a theft/diversion-CWC/CWP chemical of interest is not designated by "CUM 100g" in appendix A, and the chemical is present in a mixture at or above the minimum concentration amount listed in the...
6 CFR 27.204 - Minimum concentration by security issue.
Code of Federal Regulations, 2014 CFR
...Chemical Weapons Precursors (CWP Chemicals: Where a theft/diversion-CWC/CWP chemical of interest is not designated by "CUM 100g" in appendix A, and the chemical is present in a mixture at or above the minimum concentration amount listed in the...
Spacecraft Minimum Allowable Concentrations: Determination, Application, and Contingency Situations
NASA Technical Reports Server (NTRS)
Marshburn, Thomas H.; Dawson, David L. (Technical Monitor)
This document is an outline of a presentation about the determination of minimum allowable concentrations in spacecraft. The presentation reviews the type of toxins and mechanisms to determine the acceptable concentrations of these toxic substances. The considerations for the unique situation that spaceflight entails including zero gravity, and the intense scrutiny are reviewed. The current measurement hardware is reviewed. The spacecraft atmospheres on the Shuttle, airflow, the Space Station and the EMU in respect to airflow, pressure, constituents are also summarized. Contingency situations and potential hazards are also discussed.
Production Responses of Channel Catfish to Minimum Daily Dissolved Oxygen Concentrations in Earthen Ponds
Eugene L. Torrans
This study determined the effects of the minimum daily dissolved oxygen (DO) concentration on the production parameters of channel catfish Ictalurus punctatus in earthen ponds. Fifteen 1-acre ponds (five ponds per treatment) were managed as high-oxygen (minimum DO concentrations averaging 4.37 ppm or 54% air saturation from June through September), medium-oxygen (minimum DO concentrations averaging 2.68 ppm or 33.2% air
13 CFR 120.828 - Minimum level of 504 loan activity and restrictions on portfolio concentrations.
Code of Federal Regulations, 2010 CFR
...Minimum level of 504 loan activity and restrictions on portfolio concentrations. 120.828 Section 120.828 Business Credit and...Minimum level of 504 loan activity and restrictions on portfolio concentrations. (a) A CDC is required to receive SBA approval...
13 CFR 120.828 - Minimum level of 504 loan activity and restrictions on portfolio concentrations.
Code of Federal Regulations, 2011 CFR
...Minimum level of 504 loan activity and restrictions on portfolio concentrations. 120.828 Section 120.828 Business Credit and...Minimum level of 504 loan activity and restrictions on portfolio concentrations. (a) A CDC is required to receive SBA approval...
Isolation of Neisseria meningitidis strains with increase of penicillin minimal inhibitory concentrations
Sáez-Nieto, J. A.; Fontanals, D.; De Jalon, J. Garcia; De Artola, V. Martinez; Peńa, P.; Morera, M. A.; Verdaguer, R.; Sanfeliu, I.; Belio-Blasco, C.; Perez-Saenz, J. L.; Casal, J.
We report the isolation and characterization of ten strains showing an increase in the minimal inhibitory concentrations to penicillin (MICs > 0·1 ?g/ml), and describe the epidemiological, clinical and microbiological features. The susceptibility of 3432 meningococcal strains isolated from patients in the recent epidemic wave (1978-86) in Spain, to several antimicrobial agents used in the treatment and chemoprophylaxis of meningococcal infection has been tested. Most were resistant to sulphadiazine but sensitive to other antibiotics. The possible existence of a new pattern of behaviour of meningococcal to penicillin is discussed. PMID:3119361
The influence of subminimal inhibitory concentrations of benzalkonium chloride on biofilm formation by Listeria monocytogenes.
Ortiz, Sagrario; López, Victoria; Martínez-Suárez, Joaquín V
Disinfectants, such as benzalkonium chloride (BAC), are commonly used to control Listeria monocytogenes and other pathogens in food processing plants. Prior studies have demonstrated that the resistance to BAC of L. monocytogenes was associated with the prolonged survival of three strains of molecular serotype 1/2a in an Iberian pork processing plant. Because survival in such environments is related to biofilm formation, we hypothesised that the influence of BAC on the biofilm formation potential of L. monocytogenes might differ between BAC-resistant strains (BAC-R, MIC?10mg/L) and BAC-sensitive strains (BAC-S, MIC?2.5mg/L). To evaluate this possibility, three BAC-R strains and eight BAC-S strains, which represented all of the molecular serotype 1/2a strains detected in the sampled plant, were compared. Biofilm production was measured using the crystal violet staining method in 96-well microtitre plates. The BAC-R strains produced significantly (p<0.05) less biofilm than the BAC-S in the absence of BAC, independent of the rate of planktonic growth. In contrast, when the biofilm values were measured in the presence of BAC, one BAC-R strain (S10-1) was able to form biofilm at 5mg/L of BAC, which prevented biofilm formation among the rest of the strains. A genetic determinant of BAC resistance recently described in L. monocytogenes (Tn6188) was detected in S10-1. When a BAC-S strain and its spontaneous mutant BAC-R derivative were compared, resistance to BAC led to biofilm formation at 5mg/L of BAC and to a significant (p<0.05) stimulation of biofilm formation at 1.25mg/L of BAC, which significantly (p<0.05) reduced the biofilm level in the parent BAC-S strain. Our results suggest that the effect of subminimal inhibitory concentrations of BAC on biofilm production by L. monocytogenes might differ between strains with different MICs and even between resistant strains with similar MICs but different genetic determinants of BAC resistance. For BAC-R strains similar to S10-1, subminimal inhibitory BAC may represent an advantage, compensating for the weak biofilm formation level that might be associated with resistance. Biofilm formation in the presence of increased subminimal inhibitory concentrations of the disinfectant may represent an important attribute among certain resistant and persistent strains of L. monocytogenes. PMID:25136789
Use of Pharmacodynamic Parameters To Predict Efficacy of Combination Therapy by Using Fractional Inhibitory Concentration Kinetics
den Hollander, Jan G.; Mouton, Johan W.; Verbrugh, Henri A.
Combination therapy with antimicrobial agents can be used against bacteria that have reduced susceptibilities to single agents. We studied various tobramycin and ceftazidime dosing regimens against four resistant Pseudomonas aeruginosa strains in an in vitro pharmacokinetic model to determine the usability of combination therapy for the treatment of infections due to resistant bacterial strains. For the selection of an optimal dosing regimen it is necessary to determine which pharmacodynamic parameter best predicts efficacy during combination therapy and to find a simple method for susceptibility testing. An easy-to-use, previously described E-test method was evaluated as a test for susceptibility to combination therapy. That test resulted in a MICcombi, which is the MIC of, for example, tobramycin in the presence of ceftazidime. By dividing the tobramycin and ceftazidime concentration by the MICcombi at each time point during the dosing interval, fractional inhibitory concentration (FIC) curves were constructed, and from these curves new pharmacodynamic parameters for combination therapy were calculated (i.e., AUCcombi, Cmax-combi, T>MIC-combi, and T>FICi, where AUCcombi, Cmax-combi, T>MIC-combi, and T>FICi are the area under the FICcombi curve, the peak concentration of FICcombi, the time that the concentration of the combination is above the MICcombi, and the time above the FIC index, respectively). By stepwise multilinear regression analysis, the pharmacodynamic parameter T>FICi proved to be the best predictor of therapeutic efficacy during combination therapy with tobramycin and ceftazidime (R2 = 0.6821; P < 0.01). We conclude that for combination therapy with tobramycin and ceftazidime the T>FICi is the parameter best predictive of efficacy and that the E-test for susceptibility testing of combination therapy gives promising results. These new pharmacodynamic parameters for combination therapy promise to provide better insight into the rationale behind combination therapy. PMID:9559776
Minimum detectable concentration as a function of gamma walkover survey technique.
King, David A; Altic, Nickolas; Greer, Colt
Gamma walkover surveys are often performed by swinging the radiation detector (e.g., a 2-inch by 2-inch sodium iodide) in a serpentine pattern at a near constant height above the ground surface. The objective is to survey an approximate 1-m swath with 100% coverage producing an equal probability of detecting contamination at any point along the swing. In reality, however, the detector height will vary slightly along the swing path, and in some cases the detector may follow a pendulum-like motion significantly reducing the detector response and increasing the minimum detectable concentration. This paper quantifies relative detector responses for fixed and variable height swing patterns and demonstrates negative impacts on the minimum detectable concentration. Minimum detectable concentrations are calculated for multiple contaminated surface areas (0.1, 1.0, 3, 10, and 30 m2), multiple contaminants (60Co, 137Cs, 241Am, and 226Ra), and two minimum heights (5 and 10 cm). Exposure rate estimates used in minimum detectable concentration calculations are produced using MicroShield™ v.7.02 (Grove Software, Inc., 4925 Boonsboro Road #257, Lynchberg, VA 24503) and MDCs are calculated as outlined in NUREG-1575. Results confirm a pendulum-like detector motion can significantly increase MDCs relative to a low flat trajectory, especially for small areas of elevated activity--up to a 47% difference is observed under worst-modeled conditions. PMID:22249469
Sub-Inhibitory Concentrations of Trans-Cinnamaldehyde Attenuate Virulence in Cronobacter sakazakii in Vitro
Amalaradjou, Mary Anne Roshni; Kim, Kwang Sik; Venkitanarayanan, Kumar
Cronobacter sakazakii is a foodborne pathogen, which causes a life-threatening form of meningitis, necrotizing colitis and meningoencephalitis in neonates and children. Epidemiological studies implicate dried infant formula as the principal source of C. sakazakii. In this study, we investigated the efficacy of sub-inhibitory concentrations (SIC) of trans-cinnamaldehyde (TC), an ingredient in cinnamon, for reducing C. sakazakii virulence in vitro using cell culture, microscopy and gene expression assays. TC significantly (p ? 0.05) suppressed C. sakazakii adhesion to and invasion of human and rat intestinal epithelial cells, and human brain microvascular endothelial cells. In addition, TC inhibited C. sakazakii survival and replication in human macrophages. We also observed that TC reduced the ability of C. sakazakii to cause cell death in rat intestinal cells, by inhibiting nitric oxide production. Results from gene expression studies revealed that TC significantly downregulated the virulence genes critical for motility, host tissue adhesion and invasion, macrophage survival, and LPS (Lipopolysaccharide) synthesis in C. sakazakii. The efficacy of TC in attenuating these major virulence factors in C. sakazakii underscores its potential use in the prevention and/or control of infection caused by this pathogen. PMID:24837831
A comparison of experimental methods to determine the minimum explosible concentration of dusts
Nagesh Chawla; Paul R. Amyotte; Michael J. Pegg
An experimental investigation of dust explosions was conducted using a 20 L Siwek explosion chamber, to examine test methods for determination of the minimum explosible concentration (MEC) of combustible dusts. Two methods, one proposed by the American Society for Testing and Materials (ASTM) and the other by the International Electrotechnical Commission (IEC), were compared. The MECs of gilsonite, Pittsburgh coal,
Inhaled Anesthetics Do Not Combine to Produce Synergistic Effects Regarding Minimum Alveolar Anesthetic Concentration in Rats
Edmond I Eger II; Michael Tang; Mark Liao; Michael J. Laster; Ken Solt; Pamela Flood; Andrew Jenkins; Douglas Raines; Jan F. Hendrickx; Steven L. Shafer; Tanifuji Yasumasa; James M. Sonner
BACKGROUND: We hypothesized that pairs of inhaled anesthetics having divergent potencies (one acting weakly at minimum alveolar anesthetic concentration (MAC); one acting strongly at MAC) on specific receptors\\/channels might act synergisti- cally, and that such deviations from additivity would support the notion that anesthetics act on multiple sites to produce anesthesia. METHODS: Accordingly, we studied the additivity of MAC for
BME BIOMEDICAL IMAGING CONCENTRATION F10 MS: 30 total credit hours minimum
Eustice, Ryan
(1) (I) Biomedical Research and Design (one course): BIOMED E 590 Directed Research (2) (I): BIOMED E 458 Biomedical Instrumentation and Design (4) (I,II) BIOMED E 510 Medical Imaging Laboratory (3BME BIOMEDICAL IMAGING CONCENTRATION F10 MS: 30 total credit hours minimum Advisor: Luis
BME BIOTECHNOLOGY CONCENTRATION F10 MS: 30 total credit hours minimum
Eustice, Ryan
BME BIOTECHNOLOGY CONCENTRATION F10 MS: 30 total credit hours minimum Students last name begins: Michael Mayer, Ph.D. (firstname.lastname@example.com) Biotechnology (one course): BIOMED E 410 Design and Application (Biotechnology only)5 (3) (I, II) BIOMED E 519 Quantitative Physiology (Tissue Engineering only)6 (4) (I) Other
BME BIOTECHNOLOGY CONCENTRATION F11 MS: 30 total credit hours minimum
Eustice, Ryan
BME BIOTECHNOLOGY CONCENTRATION F11 MS: 30 total credit hours minimum Students last name begins: Michael Mayer, Ph.D. (email@example.com) Biotechnology (one course): BIOMEDE 410 Design and Application of Engineering): At least one of the following: BIOLCHEM 515 Introductory Biochemistry (Biotechnology only)5 (3
BME BIOTECHNOLOGY CONCENTRATION F12 MS: 30 total credit hours minimum
Kamat, Vineet R.
BME BIOTECHNOLOGY CONCENTRATION F12 MS: 30 total credit hours minimum Advisor: Michael Mayer, Ph.D. (firstname.lastname@example.com) Biotechnology (one course): BIOMEDE 410 Design and Application of Biomaterials (3) (l)1 of Engineering): One course from this list: BIOLCHEM 515 Introductory Biochemistry (Biotechnology only)5 (3) (I
Sub-inhibitory concentrations of some antibiotics can drive diversification of Pseudomonas aeruginosa populations in artificial sputum medium
Background Pseudomonas aeruginosa populations within the cystic fibrosis lung exhibit extensive phenotypic and genetic diversification. The resultant population diversity is thought to be crucial to the persistence of infection and may underpin the progression of disease. However, because cystic fibrosis lungs represent ecologically complex and hostile environments, the selective forces driving this diversification in vivo remain unclear. We took an experimental evolution approach to test the hypothesis that sub-inhibitory antibiotics can drive diversification of P. aeruginosa populations. Replicate populations of P. aeruginosa LESB58 were cultured for seven days in artificial sputum medium with and without sub-inhibitory concentrations of various clinically relevant antibiotics. We then characterised diversification with respect to 13 phenotypic and genotypic characteristics. Results We observed that higher population diversity evolved in the presence of azithromycin, ceftazidime or colistin relative to antibiotic-free controls. Divergence occurred due to alterations in antimicrobial susceptibility profiles following exposure to azithromycin, ceftazidime and colistin. Alterations in colony morphology and pyocyanin production were observed following exposure to ceftazidime and colistin only. Diversification was not observed in the presence of meropenem. Conclusions Our study indicates that certain antibiotics can promote population diversification when present in sub-inhibitory concentrations. Hence, the choice of antibiotic may have previously unforeseen implications for the development of P. aeruginosa infections in the lungs of cystic fibrosis patients. PMID:23879797
Effect of cigarette smoke on human serum trypsin inhibitory capacity and antitrypsin concentration
Chowdhury, P.; Bone, R.C.; Louria, D.B.; Rayford, P.L.
Investigation of the effect of cigarette smoke on the serum trypsin inhibitory capacity (TIC) and antitrypsin content in 89 smokers compared with 37 nonsmokers revealed that cigarette smoking is associated with a significantly lower level of TIC. No alteration in serum antitrypsin content was found because of cigarette smoking. Further analysis of the data indicated a correlation between the magnitude of smoking and the reduction in serum TIC. The reduction of TIC in cigarette smokers is consistent with the recent findings of decreased alpha 1-antitrypsin activity in rat lung and the reduced elastase inhibitory capacity per mg of alpha 1-antitrypsin found in the serum of smokers. The decrease in TIC in the serum of smokers, in addition to the reported decrease in elastolytic activity, may be useful in explaining the pathogenesis of emphysema frequently found in smokers.
Inhibitory properties of pepsin digested lactoferrin in apple and carrot juice
Chantayasakorn, Panita
.0 and lyophilized to determine the activity of the digests in peptone-yeast-glucose broth, apple juice, and carrot juice using E. coli (ATCC 35343) as the test organism. The minimum inhibitory concentrations of lactoferrin and apolactoferrin in peptone...
Cytotoxicity and inhibitory effects of low-concentration triclosan on adipogenic differentiation of human mesenchymal stem cells
Guo, Li-Wu [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States)] [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); Wu, Qiangen [Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States)] [Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); Green, Bridgett; Nolen, Greg [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States)] [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); Shi, Leming [Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States)] [Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); LoSurdo, Jessica [Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892 (United States)] [Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892 (United States); Deng, Helen [Arkansas Department of Health, Little Rock, AR 72205 (United States)] [Arkansas Department of Health, Little Rock, AR 72205 (United States); Bauer, Steven [Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892 (United States)] [Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892 (United States); Fang, Jia-Long, E-mail: firstname.lastname@example.com [Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States)] [Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States); Ning, Baitang, E-mail: firstname.lastname@example.com [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States)] [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079 (United States)
Humans at all ages are continually exposed to triclosan (TCS), a widely used antimicrobial agent that can be found in many daily hygiene products, such as toothpastes and shampoos; however, the toxicological and biological effects of TCS in the human body after long-term and low-concentration exposure are far from being well understood. In the current study, we investigated the effects of TCS on the differentiation of human mesenchymal stem cells (hMSCs) by measuring the cytotoxicity, morphological changes, lipid accumulation, and the expression of adipocyte differentiation biomarkers during 21-day adipogenesis. Significant cytotoxicity was observed in un-induced hMSCs treated with high-concentration TCS (? 5.0 ?M TCS), but not with low-concentration treatments (? 2.5 ?M TCS). TCS inhibited adipocyte differentiation of hMSCs in a concentration-dependent manner in the 0.156 to 2.5 ?M range as indicated by morphological changes with Oil Red O staining, which is an index of lipid accumulation. The inhibitory effect was confirmed by a decrease in gene expression of specific adipocyte differentiation biomarkers including adipocyte protein 2, lipoprotein lipase, and adiponectin. Our study demonstrates that TCS inhibits adipocyte differentiation of hMSCs under concentrations that are not cytotoxic and in the range observed in human blood. -- Highlights: ? TCS is cytotoxic to un-induced hMSCs at concentrations ? 5.0 ?M. ? TCS at concentrations ? 2.5 ?M is not cytotoxic to induced hMSCs. ? TCS at non-cytotoxic concentrations inhibits lipid formation in induced hMSCs. ? TCS decreases the expression of specific biomarkers of adipocyte differentiation. ? TCS at concentrations observed in human blood inhibits adipogenesis of hMSCs.
Estimation of minimum detectable concentration of chlorine in the blast furnace slag cement concrete
NASA Astrophysics Data System (ADS)
Naqvi, A. A.; Maslehuddin, M.; Garwan, M. A.; Nagadi, M. M.; Al-Amoudi, O. S. B.; Khateeb-ur-Rehman; Raashid, M.
The Prompt Gamma Neutron Activation Analysis technique was used to measure the concentration of chloride in the blast furnace slag (BFS) cement concrete to assess the possibility of reinforcement corrosion. The experimental setup was optimized using Monte Carlo calculations. The BFS concrete specimens containing 0.8-3.5 wt.% chloride were prepared and the concentration of chlorine was evaluated by determining the yield of 6.11, 6.62, 7.41, 7.79 and 8.58 MeV gamma-rays. The Minimum Detectable Concentration (MDC) of chlorine in the BFS cement concrete was estimated. The best value of MDC limit of chlorine in the BFS cement concrete was found to be 0.034 ± 0.011 and 0.038 ± 0.012 wt.% for 6.11 and 6.62 MeV prompt gamma-rays. Within the statistical uncertainty the lower bound of the measured MDC of chlorine in the BFS cement concrete meets the maximum permissible limit of 0.03 wt.% of chloride set by the American Concrete Institute.
Calculation of Minimum-Detectable-Concentration Levels of Radioxenon Isotopes Using the PNNL ARSA System
McIntyre, Justin I.; Bowyer, Ted W.; Reeder, Paul L.
Measurement of xenon fission product isotopes is a key element in the global network being established to monitor the Comprehensive Nuclear-Test-Ban Treaty. The automated Radio-xenon Analyzer/Sampler (ARSA), built by Pacific Northwest National Laboratory, can detect 131mXe, 133mXe, 133Xe, and 135Xe via a beta-gamma counting system. Due to the variable background and sources of these four radio-xenon isotopes, it is important to have as sensitive a detection system as possible and to quantify the Minimum-Detectable-Concentrations (MDC) that such a system will be able to detect to preclude false negative and false positive results. From data obtained from IAR in Germany MDC values for 133Xe were well below the 1 mBq/SCMA as required by the PTS for the Comprehensive Test BAn Treaty [WGB TL-11,1999].
Dipeptidyl peptidase-IV inhibitory peptides generated by tryptic hydrolysis of a whey protein concentrate rich in ?-lactoglobulin.
Silveira, Silvana T; Martínez-Maqueda, Daniel; Recio, Isidra; Hernández-Ledesma, Blanca
Dipeptidyl peptidase-IV (DPP-IV) is a serine protease involved in the degradation and inactivation of incretin hormones that act by stimulating glucose-dependent insulin secretion after meal ingestion. DPP-IV inhibitors have emerged as new and promising oral agents for the treatment of type 2 diabetes. The purpose of this study was to investigate the potential of ?-lactoglobulin as natural source of DPP-IV inhibitory peptides. A whey protein concentrate rich in ?-lactoglobulin was hydrolysed with trypsin and fractionated using a chromatographic separation at semipreparative scale. Two of the six collected fractions showed notable DPP-IV inhibitory activity. These fractions were analysed by HPLC coupled to tandem mass spectrometry (HPLC-MS/MS) to identify peptides responsible for the observed activity. The most potent fragment (IPAVF) corresponded to ?-lactoglobulin f(78-82) which IC50 value was 44.7?M. The results suggest that peptides derived from ?-lactoglobulin would be beneficial ingredients of foods against type 2 diabetes. PMID:23790888
Identification of the major ACE-inhibitory peptides produced by enzymatic hydrolysis of a protein concentrate from cuttlefish wastewater.
Amado, Isabel Rodríguez; Vázquez, José Antonio; González, Pilar; Esteban-Fernández, Diego; Carrera, Mónica; Pińeiro, Carmen
The aim of this work was the purification and identification of the major angiotensin converting enzyme (ACE) inhibitory peptides produced by enzymatic hydrolysis of a protein concentrate recovered from a cuttlefish industrial manufacturing effluent. This process consisted on the ultrafiltration of cuttlefish softening wastewater, with a 10 kDa cut-off membrane, followed by the hydrolysis with alcalase of the retained fraction. Alcalase produced ACE inhibitors reaching the highest activity (IC?? = 76.8 ± 15.2 ?g mL?ą) after 8 h of proteolysis. Sequential ultrafiltration of the 8 h hydrolysate with molecular weight cut-off (MWCO) membranes of 10 and 1 kDa resulted in the increased activity of each permeate, with a final IC?? value of 58.4 ± 4.6 ?g mL?ą. Permeate containing peptides lower than 1 kDa was separated by reversed-phase high performance liquid chromatography (RP-HPLC). Four fractions (A-D) with potent ACE inhibitory activity were isolated and their main peptides identified using high performance liquid chromatography coupled to an electrospray ion trap Fourier transform ion cyclotron resonance-mass spectrometer (HPLC-ESI-IT-FTICR) followed by comparison with databases and de novo sequencing. The amino acid sequences of the identified peptides contained at least one hydrophobic and/or a proline together with positively charged residues in at least one of the three C-terminal positions. The IC?? values of the fractions ranged from 1.92 to 8.83 ?g mL?ą, however this study fails to identify which of these peptides are ultimately responsible for the potent antihypertensive activity of these fractions. PMID:24619242
Minimum inhibitory concentrations of selected antimicrobial compounds against Flavobacterium psychrophilum the causal agent of rainbow trout fry syndrome (RTFS)
R. E. Rangdale; R. H. Richards; D. J. Alderman
The in vitro susceptibilities of 48 isolates of Flavobacterium psychrophilum, the causal agent of rainbow trout fry syndrome (RTFS), to the major fish farming antimicrobial agents and to a selection of other antimicrobials were assessed using a broth microdilution method. These data were used along with previous published antibiograms for F. psychrophilum, drug serum and tissue levels and reports clinical
Estimation of the minimum uncertainty of DNA concentration in a genetically modified maize sample candidate certified reference material
J. Prokisch; R. Zeleny; S. Trapmann; L. Le Guern; H. Schimmel; G. N. Kramer; J. Pauwels
Homogeneity testing and the determination of minimum sample mass are an important part of the certification of reference\\u000a materials. The smallest theoretically achievable uncertainty of certified concentration values is limited by the concentration\\u000a distribution of analyte in the different particle size fractions of powdered biological samples. This might be of special\\u000a importance if the reference material is prepared by dry
Antibacterial activity against ?- lactamase producing Methicillin and Ampicillin-resistants Staphylococcus aureus: fractional Inhibitory Concentration Index (FICI) determination
Background The present study reports the antibacterial capacity of alkaloid compounds in combination with Methicillin and Ampicillin-resistants bacteria isolated from clinical samples. The resistance of different bacteria strains to the current antibacterial agents, their toxicity and the cost of the treatment have led to the development of natural products against the bacteria resistant infections when applied in combination with conventional antimicrobial drugs. Method The antibacterial assays in this study were performed by using inhibition zone diameters, MIC, MBC methods, the time-kill assay and the Fractional Inhibitory Concentration Index (FICI) determination. On the whole, fifteen Gram-positive bacterial strains (MRSA/ARSA) were used. Negative control was prepared using discs impregnated with 10 % DMSO in water and commercially available Methicillin and Ampicillin from Alkom Laboratories LTD were used as positive reference standards for all bacterial strains. Results We noticed that the highest activities were founded with the combination of alkaloid compounds and conventional antibiotics against all bacteria strains. Then, results showed that after 7 h exposition there was no viable microorganism in the initial inoculums. Conclusion The results of this study showed that alkaloid compounds in combination with conventional antibiotics (Methicillin, Ampicillin) exhibited antimicrobial effects against microorganisms tested. These results validate the ethno-botanical use of Cienfuegosia digitata Cav. (Malvaceae) in Burkina Faso. Moreover, this study demonstrates the potential of this herbaceous as a source of antibacterial agent that could be effectively used for future health care purposes. PMID:22716026
Inhibitory effects of ZnO nanoparticles on aerobic wastewater biofilms from oxygen concentration profiles determined by microelectrodes.
Hou, Jun; Miao, Lingzhan; Wang, Chao; Wang, Peifang; Ao, Yanhui; Qian, Jin; Dai, Shanshan
The presence of ZnO NPs in waste streams can negatively affect the efficiency of biological nutrient removal from wastewater. However, details of the toxic effects of ZnO NPs on microbial activities of wastewater biofilms have not yet been reported. In this study, the temporal and spatial inhibitory effects of ZnO NPs on the O2 respiration activities of aerobic wastewater biofilms were investigated using an O2 microelectrode. The resulting time-course microelectrode measurements demonstrated that ZnO NPs inhibited O2 respiration within 2h. The spatial distributions of net specific O2 respiration were determined in biofilms with and without treatment of 5 or 50mg/L ZnO NPs. The results showed that 50mg/L of nano-ZnO inhibited the microbial activities only in the outer layer (?200?m) of the biofilms, and bacteria present in the deeper parts of the biofilms became even more active. Scanning electron microscopy (SEM) analysis showed that the ZnO NPs were adsorbed onto the biofilm, but these NPs had no adverse effects on the cell membrane integrity of the biofilms. It was found that the inhibition of O2 respiration induced by higher concentrations of ZnO NPs (50mg/L) was mainly due to the release of zinc ions by dissolution of the ZnO NPs. PMID:24880618
Extracellular DNA-dependent biofilm formation by Staphylococcus epidermidis RP62A in response to subminimal inhibitory concentrations of antibiotics
Kaplan, Jeffrey B.; Jabbouri, Saďd; Sadovskaya, Irina
We measured the ability of Staphylococcus epidermidis to form biofilms in the presence of subminimal inhibitory (sub-MIC) concentrations of vancomycin, tigecycline, linezolid and novobiocin. Six strains that produce different amounts of biofilm were tested. The three strains that produced the highest amounts of biofilm exhibited steady-state or decreased biofilm formation in the presence of sub-MIC antibiotics, whereas the three strains that produced lower amounts of biofilm exhibited up to 10-fold-increased biofilm formation in the presence of sub-MIC antibiotics. In two of the inducible strains (9142 and 456a), antibiotic-induced biofilm formation was inhibited by dispersin B, an enzyme that degrades poly-N-acetylglucosamine (PNAG) biofilm polysaccharide. In the third inducible strain (RP62A), dispersin B inhibited biofilm formation in response to sub-MIC vancomycin, but not to sub-MIC tigecycline. In contrast, DNase I efficiently inhibited biofilm formation by strain RP62A in response to sub-MIC tigecycline and vancomycin. DNase I had no effect on antibiotic-induced biofilm formation in strains 9142 and 456a. Our findings indicate that antibiotic-induced biofilm formation in S. epidermidis is both strain- and antibiotic-dependent and that S. epidermidis RP62A utilizes an extracellular DNA-dependent mechanism to form biofilms in response to sub-MIC antibiotics. PMID:21402153
Extracellular DNA-dependent biofilm formation by Staphylococcus epidermidis RP62A in response to subminimal inhibitory concentrations of antibiotics.
Kaplan, Jeffrey B; Jabbouri, Saďd; Sadovskaya, Irina
We measured the ability of Staphylococcus epidermidis to form biofilms in the presence of subminimal inhibitory concentrations (sub-MICs) of vancomycin, tigecycline, linezolid and novobiocin. Six strains that produce different amounts of biofilm were tested. The three strains that produced the highest amounts of biofilm exhibited steady-state or decreased biofilm formation in the presence of sub-MIC antibiotics, whereas the three strains that produced lower amounts of biofilm exhibited up to 10-fold-increased biofilm formation in the presence of sub-MIC antibiotics. In two of the inducible strains (9142 and 456a), antibiotic-induced biofilm formation was inhibited by dispersin B, an enzyme that degrades poly-N-acetylglucosamine (PNAG) biofilm polysaccharide. In the third inducible strain (RP62A), dispersin B inhibited biofilm formation in response to sub-MIC vancomycin, but not to sub-MIC tigecycline. In contrast, DNase I efficiently inhibited biofilm formation by strain RP62A in response to sub-MIC tigecycline and vancomycin. DNase I had no effect on antibiotic-induced biofilm formation in strains 9142 and 456a. Our findings indicate that antibiotic-induced biofilm formation in S. epidermidis is both strain- and antibiotic-dependent and that S. epidermidis RP62A utilizes an extracellular DNA-dependent mechanism to form biofilms in response to sub-MIC antibiotics. PMID:21402153
Subminimal Inhibitory Concentrations of the Disinfectant Benzalkonium Chloride Select for a Tolerant Subpopulation of Escherichia coli with Inheritable Characteristics
Moen, Birgitte; Rudi, Knut; Bore, Erlend; Langsrud, Solveig
Exposure of Escherichia coli to a subminimal inhibitory concentration (25% below MIC) of benzalkonium chloride (BC), an antimicrobial membrane-active agent commonly used in medical and food-processing environments, resulted in cell death and changes in cell morphology (filamentation). A small subpopulation (1–5% of the initial population) survived and regained similar morphology and growth rate as non-exposed cells. This subpopulation maintained tolerance to BC after serial transfers in medium without BC. To withstand BC during regrowth the cells up regulated a drug efflux associated gene (the acrB gene, member of the AcrAB-TolC efflux system) and changed expression of outer membrane porin genes (ompFW) and several genes involved in protecting the cell from the osmotic- and oxidative stress. Cells pre-exposed to osmotic- and oxidative stress (sodium chloride, salicylic acid and methyl viologen) showed higher tolerance to BC. A control and two selected isolates showing increased BC-tolerance after regrowth in BC was genome sequenced. No common point mutations were found in the BC- isolates but one point mutation in gene rpsA (Ribosomal protein S1) was observed in one of the isolates. The observed tolerance can therefore not solely be explained by the observed point mutation. The results indicate that there are several different mechanisms responsible for the regrowth of a tolerant subpopulation in BC, both BC-specific and general stress responses, and that sub-MIC of BC may select for phenotypic variants in a sensitive E. coli culture. PMID:22605968
Determining detection limits and minimum detectable concentrations for noble gas detectors utilizing beta-gamma coincidence systems
K. M. Foltz Biegalski; S. R. Biegalski
Beta-gamma coincidence counting is one of two acceptable noble gas monitoring measurement modes for Comprehensive Nuclear-Test-Ban-Treaty (CTBT) verification purposes defined in CTBT\\/PC\\/II\\/WG.B\\/1. Rigorous derivations of detection limits and minimum detectable activity concentrations for - coincidence data are derived in this paper. Different sampling methodologies are modeled to show how the MDC is affected by different sample collection times, spectral collection
13 CFR 120.828 - Minimum level of 504 loan activity and restrictions on portfolio concentrations.
Code of Federal Regulations, 2013 CFR
...504 loan activity and restrictions on portfolio concentrations. 120.828 Section...504 loan activity and restrictions on portfolio concentrations. (a) A CDC is required...fiscal years. (b) A CDC's 504 loan portfolio must be diversified by business...
13 CFR 120.828 - Minimum level of 504 loan activity and restrictions on portfolio concentrations.
Code of Federal Regulations, 2014 CFR
...504 loan activity and restrictions on portfolio concentrations. 120.828 Section...504 loan activity and restrictions on portfolio concentrations. (a) A CDC is required...fiscal years. (b) A CDC's 504 loan portfolio must be diversified by business...
13 CFR 120.828 - Minimum level of 504 loan activity and restrictions on portfolio concentrations.
Code of Federal Regulations, 2012 CFR
...504 loan activity and restrictions on portfolio concentrations. 120.828 Section...504 loan activity and restrictions on portfolio concentrations. (a) A CDC is required...fiscal years. (b) A CDC's 504 loan portfolio must be diversified by business...
Ferroportin (SLC40A1) Q248H mutation is associated with lower circulating plasma tumor necrosis factor-? and macrophage migration inhibitory factor concentrations in African children
Kasvosve, Ishmael; Debebe, Zufan; Nekhai, Sergei; Gordeuk, Victor R.
Background Iron deficiency and the Q248H mutation in the gene, SLC40A1, that encodes for the cellular iron exporter, ferroportin, are both common in African children. The iron status of macrophages influences the pro-inflammatory response of these cells. We hypothesized that Q248H mutation may modify the inflammatory response by influencing iron levels within macrophages. Methods The Q248H mutation and circulating concentrations of ferritin, C-reactive protein and selected pro-inflammatory cytokines (interleukin-12, interferon-?, TNF-?, and macrophage migration inhibitory factor) and anti-inflammatory cytokines (interleukin-4 and interleukin-10) were measured in 69 pre-school children recruited from well-child clinics in Harare, Zimbabwe. Results In multivariate analysis, both ferroportin Q248H and ferritin <10 ug/L were associated with significantly lower circulating concentrations of tumor necrosis factor-?. Ferroportin Q248H but not low iron stores was associated with lower circulating macrophage migration inhibitory factor as well. Anti-inflammatory cytokine levels were not significantly associated with either ferroportin Q248H or iron status. Conclusions Ferroportin Q248H and low iron stores are both associated with lower circulating tumor necrosis factor-alpha, while only ferroportin Q248H is associated with lower circulating macrophage migration inhibitory factor. Whether the reduced production of tumor necrosis factor-? observed in ferroportin Q248H heterozygotes may be of significance in anemia of chronic disease is yet to be determined. PMID:20460119
Sub-inhibitory concentrations of antibiotics and wastewater influencing biofilm formation and gene expression of multi-resistant Pseudomonas aeruginosa wastewater isolates.
Bruchmann, Julia; Kirchen, Silke; Schwartz, Thomas
Sub-inhibitory concentrations of antibiotics, which are found in environmental water systems and sewage plants due to an increased use in therapeutical and preventive fields, influence bacterial behavior in biofilms. The application of sulfamethoxazole, erythromycin, and roxithromycin induced changes in biofilm dynamics regarding biomass formation, spatial structure and specific gene expression in different Pseudomonas aeruginosa isolates. Exposing multi-resistant environmental isolated strains for 17 h to environmental concentrations of antibiotics or wastewater, directly, an increase in biofilm biomass and thickness could be observed for each strain. Additionally, multi-resistant strains responded to the applied growth conditions with changes in transcriptional activity. Here, sub-inhibitory concentrations of macrolides specifically upregulated expression of quorum sensing genes (rhlR, lasI), whereas sulfonamides and municipal wastewater, instead upregulated expression of specific resistant genes (sul1) and efflux pumps (mexD). Antibiotic sensitive isolates demonstrated an overall higher transcriptionally activity, but did not show a specific gene response to the applied exogenous stimuli. Furthermore, the presence of low concentrated antibiotics induced also phenotypical change in the biofilm architecture observed by 3D-imaging. PMID:23392972
Inhibitory effects of antimicrobial agents against Fusarium species.
Kawakami, Hideaki; Inuzuka, Hiroko; Hori, Nobuhide; Takahashi, Nobumichi; Ishida, Kyoko; Mochizuki, Kiyofumi; Ohkusu, Kiyofumi; Muraosa, Yasunori; Watanabe, Akira; Kamei, Katsuhiko
We investigated the inhibitory effects of antibacterial, biocidal, and antifungal agents against Fusarium spp. Seven Fusarium spp: four F. falciforme (Fusarium solani species complex), one Fusarium spp, one Fusarium spp. (Fusarium incarnatum-equiseti species complex), and one F. napiforme (Gibberella fujikuroi species complex), isolated from eyes with fungal keratitis were used in this study. Their susceptibility to antibacterial agents: flomoxef, imipenem, gatifloxacin, levofloxacin, moxifloxacin, gentamicin, tobramycin, and Tobracin® (contained 3,000 ?g/ml of tobramycin and 25 ?g/ml of benzalkonium chloride (BAK), a biocidal agent: BAK, and antifungal agents: amphotericin B, pimaricin (natamycin), fluconazole, itraconazole, miconazole, voriconazole, and micafungin, was determined by broth microdilution tests. The half-maximal inhibitory concentration (IC50), 100% inhibitory concentration (IC100), and minimum inhibitory concentration (MIC) against the Fusarium isolates were determined. BAK had the highest activity against the Fusarium spp. except for the antifungal agents. Three fluoroquinolones and two aminoglycosides had inhibitory effects against the Fusarium spp. at relatively high concentrations. Tobracin® had a higher inhibitory effect against Fusarium spp. than tobramycin alone. Amphotericin B had the highest inhibitory effect against the Fusarium spp, although it had different degrees of activity against each isolate. Our findings showed that fluoroquinolones, aminoglycosides, and BAK had some degree of inhibitory effect against the seven Fusarium isolates, although these agents had considerably lower effect than amphotericin B. However, the inhibitory effects of amphotericin B against the Fusarium spp. varied for the different isolates. Further studies for more effective medications against Fusarium, such as different combinations of antibacterial, biocidal, and antifungal agents are needed. PMID:25841054
Estimation of the minimum uncertainty of DNA concentration in a genetically modified maize sample candidate certified reference material.
Prokisch, J; Zeleny, R; Trapmann, S; Le Guern, L; Schimmel, H; Kramer, G N; Pauwels, J
Homogeneity testing and the determination of minimum sample mass are an important part of the certification of reference materials. The smallest theoretically achievable uncertainty of certified concentration values is limited by the concentration distribution of analyte in the different particle size fractions of powdered biological samples. This might be of special importance if the reference material is prepared by dry mixing, a dilution technique which is used for the production of the new and third generation of genetically modified (GMO) plant certified reference materials. For the production of dry mixed PMON 810 maize reference material a computer program was developed to calculate the theoretically smallest uncertainty for a selected sample intake. This model was used to compare three differently milled maize samples, and the effect of dilution on the uncertainty of the DNA content of GMO maize was estimated as well. In the case of a 50-mg sample mass the lowest achievable standard deviation was 2% for the sample containing 0.1% GMO and the minimum deviation was less than 0.5% for the sample containing 5% GMO. PMID:11569879
Assessment of Antioxidant and Phenolic Compound Concentrations as well as Xanthine Oxidase and Tyrosinase Inhibitory Properties of Different Extracts of Pleurotus citrinopileatus Fruiting Bodies
Alam, Nuhu; Yoon, Ki Nam; Lee, Kyung Rim; Kim, Hye Young; Shin, Pyung Gyun; Cheong, Jong Chun; Yoo, Young Bok; Shim, Mi Ja; Lee, Min Woong
Cellular damage caused by reactive oxygen species has been implicated in several diseases, thus establishing a significant role for antioxidants in maintaining human health. Acetone, methanol, and hot water extracts of Pleurotus citrinopileatus were evaluated for their antioxidant activities against ?-carotene-linoleic acid and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, reducing power, ferrous ion-chelating abilities, and xanthine oxidase inhibitory activities. In addition, the tyrosinase inhibitory effects and phenolic compound contents of the extracts were also analyzed. Methanol and acetone extracts of P. citrinopileatus showed stronger inhibition of ?-carotene-linoleic acid compared to the hot water extract. Methanol extract (8 mg/mL) showed a significantly high reducing power of 2.92 compared to the other extracts. The hot water extract was more effective than the acetone and methanole extracts for scavenging DPPH radicals. The strongest chelating effect (92.72%) was obtained with 1.0 mg/mL of acetone extract. High performance liquid chromatography analysis detected eight phenolic compounds, including gallic acid, protocatechuic acid, chlorogenic acid, ferulic acid, naringenin, hesperetin, formononetin, and biochanin-A, in an acetonitrile and hydrochloric acid (5 : 1) solvent extract. Xanthine oxidase and tyrosinase inhibitory activities of the acetone, methanol, and hot water extracts increased with increasing concentration. This study suggests that fruiting bodies of P. citrinopileatus can potentially be used as a readily accessible source of natural antioxidants. PMID:22783067
Sparing Effect of Robenacoxib on the Minimum Alveolar Concentration for Blunting Adrenergic Response (MAC-BAR) of Sevoflurane in Dogs
TAMURA, Jun; ITAMI, Takaharu; ISHIZUKA, Tomohito; FUKUI, Sho; OOYAMA, Norihiko; MIYOSHI, Kenjiro; SANO, Tadashi; YAMASHITA, Kazuto
ABSTRACT Robenacoxib is a newer nonsteroidal anti-inflammatory drug approved for dogs and cats. This study was designed to evaluate the effect of robenacoxib on the minimum alveolar concentration for blunting adrenergic response (MAC-BAR) of sevoflurane in dogs. Sevoflurane MAC-BAR was determined by judging dogs' response to a noxious electrical stimulus (50 V, 50 Hz and 10 msec) for 10 sec in 6 beagle dogs on two occasions at least a 7-day interval. In each occasion, saline (0.1 ml/kg) or robenacoxib (2 mg/kg) was administered subcutaneously at 1 hr prior to the MAC-BAR determination. Robenacoxib significantly decreased the sevoflurane MAC-BAR (3.44 ± 0.53% for saline vs. 2.84 ± 0.38% for robenacoxib, P=0.039). These results suggest that subcutaneous robenacoxib provides a clinically relevant sparing effect on anesthetic requirement. PMID:24004933
Mechanism of inhibition of P-glycoprotein mediated efflux by Pluronic P123/F127 block copolymers: relationship between copolymer concentration and inhibitory activity.
Wei, Zhang; Yuan, Shi; Hao, Junguo; Fang, Xiaoling
The aim of this study was to clarify the relationship between the concentration of Pluronic P123/F127 block copolymers and P-glycoprotein (P-gp) inhibitory potency. Modulation of multidrug resistance (MDR) by Pluronic P123/F127 was evaluated in P-gp over-expressing human breast cancer cell line MCF-7/ADR and its non-P-gp over-expressing counterpart MCF-7 cells. Four different probes (known as P-gp substrates) including rhodamine 123 (R-123), rhodamine 6G (R-6G), doxorubicin (DOX), and paclitaxel (PTX) were applied to investigate the impact of Pluronic P123/F127 copolymers with different concentrations on the intracellular accumulation of these probes. Additionally, the intracellular ATP and mitochondrial transmembrane potential in MCF-7/ADR cells were determined over a wide concentration range of Pluronic P123/F127. Furthermore, the endocytic mechanisms of Pluronic micelles were performed. It was suggested that P-gp substrate hydrophobicity and the concentration of P123/F127 copolymers had little impact on P-gp inhibitory activity of Pluronic P123/F127 itself. Intracellular ATP depletion was the main mechanism of Pluronic P123/F127 for P-gp inhibition. In vitro cytotoxicity study was also conducted in order to compare cytotoxic effect among different PTX formulations. It indicated that the IC50 of PTX-loaded Pluronic P123/F127 mixed micelles was 6.3-fold lower than free PTX and 2.3-fold lower than Taxol, respectively. Therefore, Pluronic P123/F127 polymeric micelles could be considered a promising drug delivery system to overcome MDR in cancer therapy. PMID:23089310
A growth inhibitory model with SOx influenced effective growth rate for estimation of algal biomass concentration under flue gas atmosphere
Technology Transfer Automated Retrieval System (TEKTRAN)
A theoretical model for the prediction of biomass concentration under real flue gas emission has been developed. The model considers the CO2 mass transfer rate, the critical SOx concentration and its role on pH based inter-conversion of bicarbonate in model building. The calibration and subsequent v...
Construction of STOX oxygen sensors and their application for determination of O2 concentrations in oxygen minimum zones.
Revsbech, Niels Peter; Thamdrup, Bo; Dalsgaard, Tage; Canfield, Donald Eugene
Until recently, it has not been possible to measure O(2) concentrations in oxygen minimum zones (OMZs) with sufficient detection limits and accuracy to determine whether OMZs are anoxic or contain 1-2 ?M O(2). With the introduction of the STOX (switchable trace oxygen) sensor, the level for accurate quantification has been lowered by a factor of 1000. By analysis with STOX sensors, O(2) can be prevented from reaching the sensing cathode by another cathode (front guard cathode), and it is the amplitude in signal by polarization/depolarization of this front guard that is used as a measure of the O(2) concentration. The STOX sensors can be used in situ, most conveniently connected to a conventional CTD (conductivity, temperature, and depth analyzer) along with a conventional oxygen sensor, and they can be used for monitoring O(2) dynamics during laboratory incubations of low-O(2) media such as OMZ water. The limiting factors for use of the STOX sensors are a relatively slow response, with measuring cycle of at least 30 s with the current design, and fragility. With improved procedures for construction, the time for a complete measuring cycle is expected to come down to about 10 s. PMID:21185442
The effect of inversion times on the minimum signal intensity of the contrast agent concentration using inversion recovery t1-weighted fast imaging sequence
Nazarpoor, Mahmood
Background: Inversion recovery (IR) pulse sequences can generate T1-weighted images with a different range of inversion time (TI) to suppress or null the signal intensity (SI) for a specified tissue. In this study, we aimed to investigate the effect of TI values on the concentration of the contrast agent, which leads to a minimum signal intensity, using an inversion recovery T1-weighted 3-dimensional fast-gradient echo imaging sequence. Methods: A phantom was designed to hold 25 vials which contained different (between 0 and 19.77mmol/L of (Gd-DTPA)) concentrations of the contrast agent. We used the vials of different concentrations to measure SI using IR sequences with different inversion times (TI, 100-3000ms). Results: The results of this study revealed that the T1 recovery curve did not cross the x- axis for the lower TI. Therefore, a minimum SI can be observed from the concentration of the contrast agent versus SI curves. The findings of this study also revealed that the concentration of the contrast agent, which leads to a minimum SI, is dependent on the TI and the minimum SI will be increased at higher TI concentrations. Conclusion: In conclusion, when the TI parameter is used to suppress the SI of the specified tissues in clinical studies (e.g., fat suppression or blood suppression in perfusion measurements), it should be chosen with great caution. PMID:25679007
Dissolved Trace Metal Concentrations over the Peru Shelf and in the Subsurface Oxygen Minimum Zone Off Peru
NASA Astrophysics Data System (ADS)
Parker, C.; Bruland, K. W.
The Peru coast is the site of one of the largest fisheries in the world, and home to some of the highest f-ratios ever recorded. As a result of this highly productive surface water, an intense subsurface oxygen minimum zone (OMZ) persists. Despite the import of the effect of OMZs due to their predicted increase with global warming, there is very little trace metal data from this region. Here we present dissolved trace metal data from the U.S. GEOTRACES Eastern Pacific Zonal Transect over the Peru shelf and through the OMZ. Results suggest a sink of Pb, Cd, Sc, Cu and Ga in the suboxic region of the shelf, and a shelf source of Co and Fe. Trace metal concentrations within the OMZ will also be discussed. As many of these metals have not been analyzed in this region previously, this work can serve as a baseline for future comparison and adds to the understanding of global trace metal distributions.
Relation between body temperature and dexmedetomidine-induced minimum alveolar concentration and respiratory changes in isoflurane-anesthetized miniature swine.
Vainio, O M; Bloor, B C
Dexmedetomidine (DEX), an alpha 2-receptor agonist, is the pharmacologically active d-isomer of medetomidine, a compound used as a sedative in veterinary medicine. Isoflurane anesthetic requirement (minimum alveolar concentration; MAC), rectal temperature, and cardiorespiratory variables were studied in chronically instrumented Yucatan miniature swine during DEX (20 micrograms/kg of body weight)-induced changes in body temperature. All studies were performed at room temperature of 22 C. The DEX was given as a 2-minute infusion into the left atrium. Each pig was studied twice. For protocol 1, the core temperature of the pigs was maintained at (mean +/- SD) 38.2 +/- 0.5 C by use of a thermostatically controlled water blanket and a heating lamp. For protocol 2, the core temperature was not externally manipulated and it decreased from 38.2 +/- 0.4 C to 32.2 +/- 1.2 C during the more than 3 hours of the protocol. Control isoflurane MAC was 1.66 +/- 0.2% and was 1.74 +/- 0.3% for protocols 1 and 2, respectively; DEX decreased MAC by 34 and 44%, respectively. For protocol 1, reduction in MAC after DEX administration returned by 50 and 80% at 84 and 138 minutes, respectively. If rectal temperature was not maintained (eg, allowed to decrease), MAC was reduced by 57% at the same time as the return to 80% in the swine with maintained body temperature. Respiratory rate and minute ventilation were significantly higher in swine with maintained temperature. The PaCO2 was lower and, accordingly, pH was higher in these swine. Blood pressure and heart rate were not affected by temperature changes. PMID:7978616
In Vitro Interaction of Flucytosine Combined with Amphotericin B or Fluconazole against Thirty-Five Yeast Isolates Determined by both the Fractional Inhibitory Concentration Index and the Response Surface Approach
D. T. A. Te Dorsthorst; P. E. Verweij; J. Meletiadis; M. Bergervoet; N. C. Punt; J. F. G. M. Meis; J. W. Mouton
Combination therapy could be of benefit for the treatment of invasive yeast infections. However, in vitro interaction studies are relatively scarce and the interpretation of the fractional inhibitory concentration (FIC) index can be contradictory due to various definitions used; not all information on the interaction study is used in the index, and different MIC end points exist for different classes
Vancomycin and daptomycin minimum inhibitory concentration distribution and occurrence of heteroresistance among methicillin-resistant Staphylococcus aureus blood isolates in Turkey
Background The aim of this study was to determine the distribution of vancomycin and daptomycin MICs among methicillin-resistant Staphylococcus aureus (MRSA) blood isolates, the prevalence of heterogeneous vancomycin-intermediate S. aureus (hVISA) and the relationship between hVISA and vancomycin MIC values. Methods A total of 175 MRSA blood isolates were collected from seven university hospitals in Turkey. All isolates were tested for susceptibility to vancomycin and daptomycin by reference broth microdilution (BMD) and by standard Etest method. BMD test was performed according to CLSI guidelines and Etest was performed according to the instructions of the manufacturer. All isolates were screened for the presence of the hVISA by using macro Etest (MET) and population analysis profile-area under the curve (PAP-AUC) methods. Results The vancomycin MIC50, MIC90 and MIC ranges were 1, 2, and 0.5-2 ?g/ml, respectively, by both of BMD and Etest. The daptomycin MIC50, MIC90 and MIC ranges were 0.5, 1 and 0.125 -1 ?g/ml by BMD and 0.25, 0.5 and 0.06-1 ?g/ml by Etest, respectively. The vancomycin MIC for 40.6% (71/175) of the MRSA isolates tested was >1 ?g/ml by BMD. No vancomycin and daptomycin resistance was found among MRSA isolates. Percent agreement of Etest MICs with BMD MICs within ±1 doubling dilution was 100% and 73.1% for vancomycin and daptomycin, respectively. The prevalence of hVISA among MRSA blood isolates was 13.7% (24/175) by PAP-AUC method. MET identified only 14 of the hVISA strains (sensitivity, 58.3%), and there were 12 strains identified as hVISA that were not subsequently confirmed by PAP-AUC (specificity, 92.1%). Conclusions Agreement between BMD and Etest MICs is high both for vancomycin and daptomycin. Daptomycin was found to be highly active against MRSA isolates including hVISA. A considerable number of isolates are determined as hVISA among blood isolates. As it is impractical to use the reference method (PAP-AUC) for large numbers of isolates, laboratory methods for rapid and accurate identification of hVISA need to be developed. PMID:24325260
Free Energies of Molecular Bound States in Lipid Bilayers: Lethal Concentrations of Antimicrobial Peptides
Huey W. Huang; Ming-Tao Lee
The lipid matrix, or the lipid bilayer, of cell membranes is a natural binding site for amphipathic molecules, including antimicrobial peptides, pore-forming proteins, and many drugs. The unique property of pore-forming antimicrobial peptides is that they exhibit a threshold concentration (called the lethal concentration or the minimum inhibitory concentration) for activity, below which no effect is seen. Without this property,
Nearest Neighbor Averaging and its Effect on the Critical Level and Minimum Detectable Concentration for Scanning Radiological Survey Instruments that Perform Facility Release Surveys.
Fournier, Sean Donovan; Beall, Patrick S [Sandia National Laboratories, Livermore, CA; Miller, Mark L.
Through the SNL New Mexico Small Business Assistance (NMSBA) program, several Sandia engineers worked with the Environmental Restoration Group (ERG) Inc. to verify and validate a novel algorithm used to determine the scanning Critical Level (L c ) and Minimum Detectable Concentration (MDC) (or Minimum Detectable Areal Activity) for the 102F scanning system. Through the use of Monte Carlo statistical simulations the algorithm mathematically demonstrates accuracy in determining the L c and MDC when a nearest-neighbor averaging (NNA) technique was used. To empirically validate this approach, SNL prepared several spiked sources and ran a test with the ERG 102F instrument on a bare concrete floor known to have no radiological contamination other than background naturally occurring radioactive material (NORM). The tests conclude that the NNA technique increases the sensitivity (decreases the L c and MDC) for high-density data maps that are obtained by scanning radiological survey instruments.
Influence of electron donor on the minimum sulfate concentration required for sulfate reduction in a petroleum hydrocarbon-contaminated aquifer
Vroblesky, D.A.; Bradley, P.M.; Chapelle, F.H. [Geological Survey, Columbia, SC (United States)] [Geological Survey, Columbia, SC (United States)
Fluctuations in the availability of electron donor (petroleum hydrocarbons) affected the competition between sulfate-reducing bacteria (SRB) and methanogenic bacteria (MB) for control of electron flow in a petroleum hydrocarbon-contaminated aquifer. The data suggest that abundant electron donor availability allowed MB to sequester a portion of the electron flow even when sulfate was present in sufficient concentrations to support sulfate reduction. For example, in an area of abundant electron-donor availability, SRB appeared to be unable to sequester the electron flow from MB in the presence of 1.4 mg/L sulfate. The data also suggest that when electron-donor availability was limited, SRB outcompeted MB for available substrate at a lower concentration of sulfate than when electron donor was plentiful. For example, in an area of limited electron-donor availability, SRB appeared to maintain dominance of electron flow at sulfate concentrations less than 1 mg/L. The presence of abundant electron donor and a limited amount of sulfate reduced competition for available substrate, allowing both SRB and MB to metabolize available substrates concurrently. 34 refs., 5 figs.
The effect of midazolam on the recovery quality, recovery time and the minimum alveolar concentration for extubation in the isoflurane-anesthetized pig.
Kleine, S A; Quandt, J E; Hofmeister, E H; Peroni, J
There are no reported studies evaluating the effect of midazolam on recovery quality, recovery time or minimum alveolar concentration (MAC) at which extubation occurs (MAC extubation). Our hypotheses were that midazolam administered prior to recovery would decrease MAC extubation, prolong recovery time but provide a smoother recovery. Sixteen Yorkshire pigs were anesthetized with isoflurane for approximately 5 h. The end-tidal isoflurane concentration was then stabilized at 1.4% for 20 min. Pigs were randomly assigned to receive midazolam or saline. The vaporizer was decreased by 10% every 10 min until extubation. Pigs were declared awake by a blinded observer and were assigned a recovery score by the same observer. Mean MAC extubation was not significantly different for pigs receiving saline prior to recovery compared with those pigs receiving midazolam. The overall mean MAC extubation for both groups was 0.6 ± 0.4 vol%. Time to extubation was not significantly longer with midazolam (124 ± 36 min) compared with the saline group (96 ± 61 min; P = 0.09). Recovery score was not significantly different between groups (midazolam, 0.86 ± 1.1; saline 0.5 ± 0.5; P = 0.26). In conclusion, midazolam did not affect MAC extubation. There was no advantage of administering midazolam in the recovery period when performing step-down titration of isoflurane anesthesia. PMID:25378139
Synergistic effect between two bacteriocin-like inhibitory substances produced by Lactobacilli Strains with inhibitory activity for Streptococcus agalactiae.
Ruíz, Francisco O; Gerbaldo, Gisela; García, María J; Giordano, Walter; Pascual, Liliana; Barberis, Isabel L
Group B streptococci (GBS) are bacterial species that colonize the vagina in pregnant women and as such may cause serious infections in neonates that passed through the birth channel. The objective of this work was to study the inhibitory activities produced by each bacteriocin-like inhibitory substance (BLIS) of Lactobacillus rhamnosus L60 and Lactobacillus fermentum L23, and the effects of the combined BLIS-es of these lactobacilli on GBS. The interactions between the BLIS-es were assessed by qualitative and quantitative methods on agar plates. The minimum inhibitory concentrations (MICs) and fractional inhibitory concentrations (FICs) were determined by a modification of the broth microdilution and checkerboard methods, respectively. Antibiotic susceptibilities of all S. agalactiae strains were assayed and the results of these tests were evaluated for statistical significance. A 7.5% of GBS isolates were recovered from 760 pregnant women and 91% of those strains were susceptible to each BLIS produced by L. fermentum, L. rhamnosus, and also to a mixture of them. The comparisons among the BLIS-es showed statistically significant differences, with a combination of the BLIS-es from the two Lactobacillus species being better than the BLIS of each one alone (P < 0.05) as GBS growth inhibitors. Synergistic activities between the BLIS-es were found on 100% of susceptible GBS strains, MICs ranges of BLIS of L23 and L60 were 80-160 and 160-320 UA ml(-1), respectively. By the checkerboard method, the BLIS-es combination showed synergistic effect on all sensitive strains tested, with values of FICs ranging from 0.131 to 0.218. The BLIS-es produced by these lactobacilli of vaginal origin were able to inhibit S. agalactiae isolates. The results indicate that these strains may have probiotic potential for the control of GBS in women and may consequently prevent GBS infections in newborns. PMID:22231454
Comparison of equi-minimum alveolar concentration of sevoflurane and isoflurane on bispectral index values during both wash in and wash out phases: A prospective randomised study
Gupta, Madhu; Shri, Iti; Sakia, Prashant; Govil, Deepika
Background and Aims: At equal minimum alveolar concentration (MAC), volatile agents may produce different bispectral index (BIS) values especially at low BIS levels when the effect is volatile agent specific. The present study was performed to compare the BIS values produced by sevoflurane and isoflurane at equal MAC and thereby assessing which is a better hypnotic agent. Methods: Sixty American Society of Anaesthesiologists I and II patients undergoing elective mastoidectomy were divided into groups receiving either isoflurane or sevoflurane, and at equi-MAC. BIS value was measured during both wash in and wash out phase, keeping other parameters same. Statistical analysis was performed using the Friedman two-way analysis and Mann-Whitney U-test. A P < 0.05 was considered significant. Results: BIS value was significantly lower with sevoflurane at all MAC values as compared to isoflurane, except in the beginning and at MAC awake. However, both the drugs proved to be cardiostable. Conclusion: At equi-MAC sevoflurane produces lower BIS values during wash in as well as wash out phase as compared to isoflurane, reflecting probably an agent specific effect and a deficiency in BIS algorithm for certain agents and their interplay. PMID:25788739
Measurement of minimum substrate concentration (Smin) in a recycling fermentor and its prediction from the kinetic parameters of Pseudomonas strain B13 from batch and chemostat cultures.
Tros, M E; Bosma, T N; Schraa, G; Zehnder, A J
The minimum substrate concentration required for growth, Smin, was measured for Pseudomonas sp. strain B13 with 3-chlorobenzoate (3CB) and acetate in a recycling fermentor. The substrates were provided alone or in a mixture. Smin values predicted with kinetic parameters from resting-cell batches and chemostat cultures differed clearly from the values measured in the recycling fermentor. When 3CB and acetate were fed as single substrates, the measured Smin values were higher than the individual Smin values in the mixture. The Smin in the mixture reflected the relative energy contributions of the two substrates in the fermentor feed. The energy-based maintenance coefficients during zero growth in the recycling fermentor were comparable for all influent compositions (mean +/- standard deviation, 0.34 +/- 0.07 J mg [dry weight]-1 h-1). Maintenance coefficient values for acetate were significantly higher in chemostat experiments than in recycling-fermentor experiments. 3CB maintenance coefficients were comparable in both experimental systems. The parameters for 3CB consumption kinetics varied remarkably with the experimental growth conditions in batch, chemostat, and recycling-fermentor environments. The results demonstrate that the determination of kinetic parameters in the laboratory for prediction of microbial activity in complex natural systems should be done under conditions which best mimic the system under consideration. PMID:8967775
Anesthesia with Isoflurane and Sevoflurane in the Crested Serpent Eagle (Spilornis cheela hoya): Minimum Anesthetic Concentration, Physiological Effects, Hematocrit, Plasma Chemistry and Behavioral Effects
CHAN, Fang-Tse; CHANG, Geng-Ruei; WANG, Hsien-Chi; HSU, Tien-Huan
ABSTRACT The initial goal of this study was to determine the minimum anesthetic concentration (MAC) for isoflurane (ISO) and sevoflurane (SEVO) for the crested serpent eagle. Next, we compared the anesthetic effects of each on the physiological effects, hematocrit, plasma chemistry values and behavior in spontaneously breathing captive adult crested serpent eagles. Sixteen eagles were randomly allocated to two groups for anesthesia with ISO (n=8) or SEVO (n=8). First, we measured the MAC values of ISO and SEVO, and four weeks later, we investigated the effect of each on the physiological effects, hematocrit (HCT) and plasma chemistry values. The MAC values of ISO and SEVO for crested serpent eagles were 1.46 ± 0.30 and 2.03 ± 0.32%, respectively. The results revealed no significant differences between the two anesthetics in induction time, while time of extubation to recovery was significantly shorter with SEVO. A time-related increase in end-tidal CO2 and decreases in body temperature and respiratory rates were observed during anesthesia with each anesthetic. There were no significant differences between the effect of the two anesthetics on heart rate, hematocrit, plasma chemistry values or respiration, although each caused minor respiration depression. We concluded that SEVO is a more effective inhalant agent than ISO for use in eagles, showing the most rapidest induction and recovery from anesthesia. PMID:23955396
Growth inhibitory and biocidal activity of some isothiazolone biocides.
Collier, P J; Ramsey, A J; Austin, P; Gilbert, P
Similar patterns of growth inhibition were observed for the three biocides, benzisothiazol-3-one (BIT), 5-chloro-N-methylisothiazol-3-one (CMIT) and N-methylisothiazol-3-one (MIT) against Escherichia coli ATCC 8739 and Schizosaccharomyces pombe NCYC 1354. After periods of induced stasis, proportional to biocide concentration, growth proceeded at an inhibited rate. Extrapolation of the static periods and inhibited growth rates against biocide concentration gave minimum growth inhibitory concentration estimates of 0.1-0.5 micrograms/ml for CMIT, 15-20 micrograms/ml for BIT and 40-250 micrograms/ml for MIT. Patterns of growth inhibition by CMIT and induced morphological changes in inhibited cultures suggested this compound to also inhibit initiation of DNA replication. Growth inhibitory activity was rapidly quenched by the addition of thiol-containing materials such as glutathione and cysteine. The activity of CMIT was additionally quenched by the presence of the non-thiol amino acids valine and/or histidine. These results suggest that the chlorinated isothiazolones can react with amines as well as with essential thiol groups. PMID:2292520
Enhanced HIV-1 Reverse Transcriptase Inhibitory and Antibacterial Properties in Callus of Catha edulis Forsk.
Kumari, Aloka; Baskaran, Ponnusamy; Van Staden, Johannes
Developing tissue culture systems for medicinal plants is important in that they may offer an alternative to protect wild populations. However, analysis of bioactivity for tissue culture developed plant tissues is required to offer support and allow acceptance in traditional medicine. The use of propagated callus could provide potential material for therapeutic purposes. This study was aimed at evaluating the anti-HIV and antibacterial properties of a three-month-old tissue culture-derived calli and leaves of cultivated mother plants of Catha edulis Forsk. The calli were derived from leaf explants using different plant growth regulators. The calli obtained from callus cultured on 9.8??M indole-3-butyric acid plus 2.7??M naphthalene acetic acid exhibited the highest HIV-1 reverse transcriptase inhibitory effects when compared with other treatments and the mother plants. Different extracts of callus exhibited high antibacterial activity (<1?mg/mL: minimum inhibitory concentration from 0.098 to 0.78?mg/mL) against both gram-positive and gram-negative bacteria. Leaf acetone extracts showed moderate activity (minimum inhibitory concentration of 0.78?mg/mL) against Staphylococcus aureus. The present study indicated that tissue culture-derived calli could be used as therapeutic agents for traditional medicine. The choice of treatment used in the tissue culture system and the age of the callus for production of biomass may significantly influence its therapeutic potential. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25753483
NSDL National Science Digital Library
This NCTM iOS app of the familiar online Illuminations game, "Concentration" (cataloged separately) challenges a user to match whole numbers, shapes, fractions, or multiplication facts to equivalent representations. This game can be played by one or two players taking turns and can be played in clear pane mode, or for added challenge, with the windows closed.
Effects of sub-lethal neurite outgrowth inhibitory concentrations of chlorpyrifos oxon on cytoskeletal proteins and acetylcholinesterase in differentiating N2a cells
Flaskos, J., E-mail: firstname.lastname@example.com [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Nikolaidis, E. [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece)] [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Harris, W. [School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom)] [School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom); Sachana, M. [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece)] [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Hargreaves, A.J., E-mail: email@example.com [School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom)
Previous work in our laboratory has shown that sub-lethal concentrations (1-10 {mu}M) of chlorpyrifos (CPF), diazinon (DZ) and diazinon oxon (DZO) inhibit the outgrowth of axon-like neurites in differentiating mouse N2a neuroblastoma cells concomitant with altered levels and/or phosphorylation state of axonal cytoskeleton and growth-associated proteins. The aim of the present work was to determine whether chlorpyrifos oxon (CPO) was capable of inhibiting N2a cell differentiation in a similar manner. Using experimental conditions similar to our previous work, sub-lethal concentrations (1-10 {mu}M) of CPO were found to inhibit N2a cell differentiation. However, unlike previous studies with DZ and DZO, there was a high level of sustained inhibition of acetylcholinesterase (AChE) in CPO treated cells. Impairment of neurite outgrowth was also associated with reduced levels of growth associated protein-43 and neurofilament heavy chain (NFH), and the distribution of NFH in cells stained by indirect immunofluorescence was disrupted. However, in contrast to previous findings for DZO, the absolute level of phosphorylated NFH was unaffected by CPO exposure. Taken together, the findings suggest that sub-lethal concentrations of CPO inhibit axon outgrowth in differentiating N2a cells and that this effect involves reduced levels of two proteins that play key roles in axon outgrowth and maintenance. Although the inhibition of neurite outgrowth is unlikely to involve AChE inhibition directly, further work will help to determine whether the persistent inhibition of AChE by CPO can account for the different effects induced by CPO and DZO on the levels of total and phosphorylated NFH. -- Highlights: Black-Right-Pointing-Pointer Sub-lethal levels of chlorpyrifos oxon inhibit neurite outgrowth in N2a cells Black-Right-Pointing-Pointer Acetylcholinesterase exhibits sustained inhibition throughout exposure Black-Right-Pointing-Pointer The levels of neurofilament heavy chain and GAP-43 protein are reduced Black-Right-Pointing-Pointer Neurofilament heavy chain forms aggregates in cell bodies Black-Right-Pointing-Pointer Thus at least two axon-associated cytoskeletal proteins are disrupted by this agent.
A population pharmacokinetic modeling approach shows that serum penicillin G concentrations are below inhibitory concentrations by two weeks after benzathine penicillin G injection in the majority of young adults.
Neely, Michael; Kaplan, Edward L; Blumer, Jeffrey L; Faix, Dennis J; Broderick, Michael P
Serum penicillin G falls to low levels 2 weeks after injection as benzathine penicillin G (BPG) in young adults. Using Pmetrics and previously reported penicillin G pharmacokinetic data after 1.2 million units were given as BPG to 329 male military recruits, here we develop the first reported population pharmacokinetic model of penicillin G after BPG injection. We simulated time-concentration profiles over a broad range of pediatric and adult weights after alternative doses and dose frequencies to predict the probability of maintaining serum penicillin G concentrations of >0.02 mg/liter, a proposed protective threshold against group A Streptococcus pyogenes (GAS). The final population model included linear absorption into a central compartment, distribution to and from a peripheral compartment, and linear elimination from the central compartment, with allometrically scaled volumes and rate constants. With 1.2 million units of BPG given intramuscularly every 4 weeks in four total doses, only 23.2% of 5,000 simulated patients maintained serum penicillin G trough concentrations of >0.02 mg/liter 4 weeks after the last dose. When the doses were 1.8 million units and 2.4 million units, the percentages were 30.2% and 40.7%, respectively. With repeated dosing of 1.2 million units every 3 weeks and every 2 weeks for 4 doses, the percentages of simulated patients with a penicillin G trough concentration of >0.02 mg/liter were 37.8% and 65.2%, respectively. Our simulations support recommendations for more frequent rather than higher BPG doses to prevent recurrent rheumatic heart disease in areas of high GAS prevalence or during outbreaks. PMID:25182635
A Population Pharmacokinetic Modeling Approach Shows that Serum Penicillin G Concentrations Are Below Inhibitory Concentrations by Two Weeks after Benzathine Penicillin G Injection in the Majority of Young Adults
Kaplan, Edward L.; Blumer, Jeffrey L.; Faix, Dennis J.; Broderick, Michael P.
Serum penicillin G falls to low levels 2 weeks after injection as benzathine penicillin G (BPG) in young adults. Using Pmetrics and previously reported penicillin G pharmacokinetic data after 1.2 million units were given as BPG to 329 male military recruits, here we develop the first reported population pharmacokinetic model of penicillin G after BPG injection. We simulated time-concentration profiles over a broad range of pediatric and adult weights after alternative doses and dose frequencies to predict the probability of maintaining serum penicillin G concentrations of >0.02 mg/liter, a proposed protective threshold against group A Streptococcus pyogenes (GAS). The final population model included linear absorption into a central compartment, distribution to and from a peripheral compartment, and linear elimination from the central compartment, with allometrically scaled volumes and rate constants. With 1.2 million units of BPG given intramuscularly every 4 weeks in four total doses, only 23.2% of 5,000 simulated patients maintained serum penicillin G trough concentrations of >0.02 mg/liter 4 weeks after the last dose. When the doses were 1.8 million units and 2.4 million units, the percentages were 30.2% and 40.7%, respectively. With repeated dosing of 1.2 million units every 3 weeks and every 2 weeks for 4 doses, the percentages of simulated patients with a penicillin G trough concentration of >0.02 mg/liter were 37.8% and 65.2%, respectively. Our simulations support recommendations for more frequent rather than higher BPG doses to prevent recurrent rheumatic heart disease in areas of high GAS prevalence or during outbreaks. PMID:25182635
Nootropic dipeptide noopept enhances inhibitory synaptic transmission in the hippocampus.
Povarov, I S; Kondratenko, R V; Derevyagin, V I; Ostrovskaya, R U; Skrebitskii, V G
Application of nootropic agent Noopept on hippocampal slices from Wistar rats enhanced the inhibitory component of total current induced by stimulation of Shaffer collaterals in CA1 pyramidal neurons, but did not affect the excitatory component. A direct correlation between the increase in the amplitude of inhibitory current and agent concentration was found. The substance did not affect the release of inhibitory transmitters from terminals in the pyramidal neurons, which indicated changes in GABAergic interneurons. PMID:25573367
The inhibitory effect of Zingiber corallinum Hance essential oil on drug-resistant bacteria and evaluation of its acute toxicity
Yang, Ce; Zhou, Lin-Lin; Wang, Hai-Yan; Huang, Su-Na; Liu, Qing; Hu, Shi-Lin; Li, Ting-Rong; Chen, Yan-Bing; Jiang, Jian-Xin
Summary Background The excessive and irregular use of antibiotics could result in the generation and diffusion of drug-resistant bacteria. The aim of this study was to investigate the inhibitory effect of Zingiber corallinum Hance essential oil (ZCHO) on drug-resistant bacteria, especially on drug-resistant Acinetobacter baumannii. Material/Methods Susceptibility testing was used to evaluate the effect of ZCHO on growth inhibition of drug-resistant bacteria by paper disk method. Mice orally administered with ZCHO were used to observe acute toxicity and to determine median lethal dose (LD50) of ZCHO. Broth dilution method was used to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of ZCHO on drug-resistant Acinetobacter baumannii. Results ZCHO exhibited an obvious inhibitory effect not only on gram-negative drug-resistant bacteria including Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae and Acinetobacter baumannii, but also on gram-positive drug-resistant bacteria including Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus. The ZCHO containing 79% terpinen-4-ol revealed better bacteriostatic effect than ZCHO with 34% terpinen-4-ol. The LD50 of ZCHO was 1790.427 mg/kg. The MIC and MBC of ZCHO on drug-resistant Acinetobacter baumannii were 1457.81 mg/L. Conclusions ZCHO has obvious bacteriostasis and bactericidal effects, especially against drug-resistant Acinetobacter baumannii. Therefore, ZCHO is a promising natural bioactive component with antibacterial effect and satisfactory safety due to its low toxicity. PMID:21525802
Inhibitory zinc sites in enzymes.
Maret, Wolfgang
Several pathways increase the concentrations of cellular free zinc(II) ions. Such fluctuations suggest that zinc(II) ions are signalling ions used for the regulation of proteins. One function is the inhibition of enzymes. It is quite common that enzymes bind zinc(II) ions with micro- or nanomolar affinities in their active sites that contain catalytic dyads or triads with a combination of glutamate (aspartate), histidine and cysteine residues, which are all typical zinc-binding ligands. However, for such binding to be physiologically significant, the binding constants must be compatible with the cellular availability of zinc(II) ions. The affinity of inhibitory zinc(II) ions for receptor protein tyrosine phosphatase ? is particularly high (K i = 21 pM, pH 7.4), indicating that some enzymes bind zinc almost as strongly as zinc metalloenzymes. The competitive pattern of zinc inhibition for this phosphatase implicates its active site cysteine and nearby residues in the coordination of zinc. Quantitative biophysical data on both affinities of proteins for zinc and cellular zinc(II) ion concentrations provide the basis for examining the physiological significance of inhibitory zinc-binding sites in proteins and the role of zinc(II) ions in cellular signalling. Regulatory functions of zinc(II) ions add a significant level of complexity to biological control of metabolism and signal transduction and embody a new paradigm for the role of transition metal ions in cell biology. PMID:23456096
Do N-Methyl-d-Aspartate Receptors Mediate the Capacity of Inhaled Anesthetics to Suppress the Temporal Summation that Contributes to Minimum Alveolar Concentration?
Robert C. Dutton; Michael J. Laster; Yilei Xing; James M. Sonner; Douglas E. Raines; Ken Solt; Edmond I Eger II
Antagonism of N-methyl-d-aspartate (NMDA) recep- torsmarkedlydecreasestheminimumalveolarconcen- tration (MAC) of inhaled anesthetics. To assess the im- portance of suppression of the temporal summation NMDA receptor component of MAC, we stimulated the tail of rats with trains of electrical pulses of varying interstimulus intervals (ISIs) and determined the in- haled anesthetic concentrations (crossover concentra- tions) that suppressed movement at different ISIs. The
Decreasing prevalence of isolates with vancomycin heteroresistance and vancomycin minimum inhibitory concentrations ?2mg/L in methicillin-resistant Staphylococcus aureus over 11years: potential impact of vancomycin treatment guidelines.
Khatib, Riad; Sharma, Mamta; Johnson, Leonard B; Riederer, Kathleen; Shemes, Stephen; Szpunar, Susan
We evaluated vancomycin MIC (V-MIC) and the prevalence of intermediately susceptible (VISA) and heteroresistant (hVISA) isolates trends in methicillin-resistant Staphylococcus aureus bacteremia among 720 adults (?18years) inpatients over 4 study periods (2002-2003, 2005-2006, 2008-2009, and 2010-2012). V-MIC (Etest) and the prevalence of hVISA and VISA (determined by population analysis profile-area under the curve) were stratified according to the study period. Mean vancomycin MIC was 1.78±0.39, 1.81±0.47, 1.68±0.26, and 1.54±0.28mg/L in 2002-2003, 2005-2006, 2008-2009, and 2010-2012, respectively (P<0.0001). We noted a steadily decreasing prevalence of isolates with V-MIC ?2mg/L (50.0%, 45.2%, 35.4%, and 18.7%; P<0.0001) and hVISA (9.7%, 6.6%, 3.0%, and 2.1%; P=0.0003). VISA prevalence remained low (0-2%). These changes coincided with steadily increasing vancomycin trough levels (9.9±7.8, 11.1±8.4, 16.6±7.8, and 19.7±5.9mg/L in 2002-2003, 2005-2006, 2008-2009, and 2010-2012, respectively; P<0.0001). These changes imply that adherence to vancomycin treatment guidelines may suppress the development of less susceptible isolates. PMID:25935628
In vitro inhibitory properties of ferrocene-substituted chalcones and aurones on bacterial and human cell cultures.
Tiwari, Keshri Nath; Monserrat, Jean-Philippe; Hequet, Arnaud; Ganem-Elbaz, Carine; Cresteil, Thierry; Jaouen, Gérard; Vessičres, Anne; Hillard, Elizabeth A; Jolivalt, Claude
Two series of ten chalcones and ten aurones, where ferrocene replaces the C ring and with diverse substituents on the A ring were synthesized. The compounds were tested against two antibiotic-sensitive bacterial strains, E. coli ATCC 25922 and S. aureus ATCC 25923, and two antibiotic-resistant strains, S. aureus SA-1199B and S. epidermidis IPF896. The unsubstituted compound and those with methoxy substitution showed an inhibitory effect on all bacterial strains at minimum inhibitory concentrations ranging between 2 and 32 mg L(-1). For four of these compounds, the effect was bactericidal, as opposed to bacteriostatic. The corresponding organic aurones did not show growth inhibition, underscoring the role of the ferrocene group. The methoxy-substituted aurones and the unsubstituted aurone also showed low micromolar (IC(50)) activity against MRC-5 non-tumoral lung cells and MDA-MB-231 breast cancer cells, suggesting non-specific toxicity. PMID:22240736
In vitro interaction of flucytosine combined with amphotericin B or fluconazole against thirty-five yeast isolates determined by both the fractional inhibitory concentration index and the response surface approach.
Te Dorsthorst, D T A; Verweij, P E; Meletiadis, J; Bergervoet, M; Punt, N C; Meis, J F G M; Mouton, J W
Combination therapy could be of benefit for the treatment of invasive yeast infections. However, in vitro interaction studies are relatively scarce and the interpretation of the fractional inhibitory concentration (FIC) index can be contradictory due to various definitions used; not all information on the interaction study is used in the index, and different MIC end points exist for different classes of drugs. Fitting an interaction model to the whole response surface and estimation of an interaction coefficient alpha (IC(alpha)) would overcome these objections and has the additional advantage that confidence intervals of the interaction are obtained. The efficacy of flucytosine (5FC) in combination with amphotericin B (AB) and fluconazole (FCZ) was studied against 35 yeast isolates in triplicate (Candida albicans [n = 9], Candida glabrata [n = 9], Candida krusei [n = 9], and Cryptococcus neoformans [n = 8]) using a broth microdilution checkerboard method and measuring growth after 48 h by a spectrophotometer. The FIC index and IC(alpha) were determined, the latter by estimation from the response surface approach described by Greco et al. (W. R. Greco, G. Bravo, and J. C. Parsons, Pharmacol. Rev. 47:331-385, 1995) by using a computer program developed for that purpose. For the 5FC-FCZ combination, the interactions determined by the IC(alpha) generally were in concordance with the interactions determined by the FIC index, but large discrepancies were found between both methods for the 5FC-AB combination. These could mainly be explained by shortcomings in the FIC approach. The in vitro interaction of 5FC-AB demonstrated variable results depending on the tested Candida isolate. In general, the 5FC-FCZ combination was antagonistic against Candida species, but for some Candida isolates synergism was found. For C. neoformans the interaction for both combinations was highly dependent on the tested isolate and the method used. Response surface approach is an alternative method for determining the interaction between antifungal agents. By using this approach, some of the problems encountered with the FIC were overcome. PMID:12183257
Fox, P.B.
This report provides minimum critical values for various 30-cm water-reflected uranium and plutonium oxide and nitrate aqueous mixtures as calculated by the SCALE CSAS1X sequence using the 238-group ENDF/B-V neutron cross-section library. The minimum values were determined through parametric searches in one-dimensional geometry. The calculations have been performed to obtain the minimum values: critical volume and mass for spheres, critical radius for cylinders, critical thickness for slabs, and minimum critical concentration (infinite geometry) for the following homogeneous mixtures: (1) UO{sub 2}-H{sub 2}O for 3, 4, 5, 20, and 100 wt % {sup 235}U; (2) UNH for 3, 4, 5, 20, and 100 wt % {sup 235}U; (3) PuO{sub 2}-H{sub 2}O for 100/0/0, 95/5/0, 90/5/5, 80/10/10, and 71/17/11/1 wt % of {sup 239}Pu/{sup 240}Pu/{sup 241}Pu(/{sup 242}Pu); and (4) PuNH for 100/0/0, 95/5/0, 90/5/5, 80/10/10, and 71/17/11/1 wt % of {sup 239}Pu/{sup 240}Pu/{sup 241}Pu(/{sup 242}Pu). All bounding surfaces were fully reflected by 30 cm of H{sub 2}O.
Cardiovascular effects of 1.0, 1.5, and 2.0 minimum alveolar concentrations of isoflurane in experimentally induced hypothyroidism in dogs.
McMurphy, R M; Hodgson, D S; Bruyette, D S; Fingland, R B
This study was performed to determine the cardiovascular responses to isoflurane in euthyroid and hypothyroid dogs. Four healthy mixed-breed dogs were studied prior to thyroidectomy (PRE), 6 months after thyroidectomy (HYP), and after 2 months of oral supplementation with 1-thyroxine (SUP). Heart rate (HR), cardiac output (Q), stroke volume (SV), systolic, diastolic, mean arterial blood pressure (SAP, DAP, MAP), and total peripheral resistance (TPR) were determined in awake dogs and in the same dogs when end-tidal isoflurane concentration were 1.28%, 1.92%, and 2.56%. Ventilation was controlled in anesthetized dogs and PACO2 maintained between 38 to 42 mm Hg. Isoflurane caused significant (P < .05) dose-dependent reduction in Q, SV, SAP, DAP, and MAP in the PRE, HYP, and SUP dogs. Cardiac output was lower in the HYP dogs than in the PRE or SUP dogs during awake measurement. TPR was increased in the awake HYP dogs compared with the PRE or SUP dogs. During anesthesia, HYP dogs tended to have lower Q, SV, SAP, and MAP PRE or SUP groups, but the only significant reduction was SAP during 1.5 MAC. The cardiovascular responses to isoflurane in hypothyroid dogs are similar to euthyroid animals with a dose-dependent depression in Q, SV, and arterial pressure. PMID:8928395
Candida inhibitory effects of six commercial mouthwashes
Nuntana Aroonrerk; Nirada Dhanesuan
TheCandida inhibitory activities of commercial mouthwashes with various, active ingredients — fluoride (FLO), cethylpyridinium chloride\\u000a (CPC), chlorhexidine gluconate (CHX), triclosan (TRI) and herbal extracts: Twin Lotus (TLO) and Herbric concentrated (HBC)\\u000a — were determined. TheCandida activities included growth, germ tube formation and adhesion ofCandida albicans to human buccal mucosa. This study showed that TRI, TLO and CHX mouthwashes had growth
Inhibitory and resistance-modifying potential of plant-based alkaloids against methicillin-resistant Staphylococcus aureus (MRSA).
Mohtar, Mastura; Johari, Saiful Azmi; Li, Abdul Rashid; Isa, Mazurah Mohamed; Mustafa, Shuhaimi; Ali, Abdul Manaf; Basri, Dayang Fredalina
Increased prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has become a major threat to the health sector worldwide due to their virulence, limited therapeutic options and their distribution in both hospital and community settings. Discovery and development of new anti-MRSA agents as alternatives to the very few antibiotics left in the armamentarium are, thus, urgently required. Recently, an efflux mechanism in MRSA has been identified as one of the main contributors of resistance towards various structurally unrelated antibiotics. The potential of reserpine (a phytoalkaloid) as efflux pump inhibitor (EPI) against various microbes remains limited as the concentration needed for inhibition is toxic to humans. This study therefore aimed to evaluate 13 alkaloid compounds as potential inhibitory agents and/or potential EPIs against a panel of three MRSA isolates which not only differ in their susceptibility to vancomycin (amongst the last drugs available to treat serious MRSA infection), but also exhibited active efflux activity. Results indicated berberine's moderate inhibitiory activity against two MRSA isolates scoring a minimum inhibitory concentration (MIC) value of 125 microg/ml. Notable efflux inhibitory activity (ranging from two- to eightfold Ethidium Bromide MIC reduction) meanwhile was detected from quinine, piperine and harmaline using reserpine as the positive control. Findings from this study support the opinion that a vast number of potential phytocompounds with pharmacological potential await discovery. Therapeutic application of these compounds, however, warrants further investigation to ascertain their pharmacodynamics and safety aspects. PMID:19475447
Inhibitory effects of brown algae extracts on histamine production in mackerel muscle via inhibition of growth and histidine decarboxylase activity of Morganella morganii.
Kim, Dong Hyun; Kim, Koth Bong Woo Ri; Cho, Ji Young; Ahn, Dong Hyun
This study was performed to investigate the inhibitory effects of brown algae extracts on histamine production in mackerel muscle. First, antimicrobial activities of brown algae extracts against Morganella morganii were investigated using a disk diffusion method. An ethanol extract of Ecklonia cava (ECEE) exhibited strong antimicrobial activity. The minimum inhibitory concentration (MIC) of ECEE was 2 mg/ml. Furthermore, the brown algae extracts were examined for their ability to inhibit crude histidine decarboxylase (HDC) of M. morganii. The ethanol extract of Eisenia bicyclis (EBEE) and ECEE exhibited significant inhibitory activities (19.82% and 33.79%, respectively) at a concentration of 1 mg/ml. To obtain the phlorotannin dieckol, ECEE and EBEE were subjected to liquid-liquid extraction, silica gel column chromatography, and HPLC. Dieckol exhibited substantial inhibitory activity with an IC50 value of 0.61 mg/ml, and exhibited competitive inhibition. These extracts were also tested on mackerel muscle. The viable cell counts and histamine production in mackerel muscle inoculated with M. morganii treated with ?2.5 MIC of ECEE (weight basis) were highly inhibited compared with the untreated sample. Furthermore, treatment of crude HDC-inoculated mackerel muscle with 0.5% ECEE and 0.5% EBEE (weight basis), which exhibited excellent inhibitory activities against crude HDC, reduced the overall histamine production by 46.29% and 56.89%, respectively, compared with the untreated sample. Thus, these inhibitory effects of ECEE and EBEE should be helpful in enhancing the safety of mackerel by suppressing histamine production in this fish species. PMID:24394193
Angiotensin I converting enzyme inhibitory peptide extracted from freshwater zooplankton.
Lee, Jung Kwon; Lee, Min-Su; Park, Heum Gi; Kim, Se-Kwon; Byun, Hee-Guk
In this study, hydrolysates obtained from the freshwater rotifer Brachionus calyciflonus were investigated for angiotensin I converting enzyme (ACE) inhibitory peptides. Freshwater rotifer protein was hydrolyzed using six separate enzymes in a batch reactor. The peptic hydrolysate had the highest ACE inhibitory activity compared to the other hydrolysates. The highest ACE inhibitory peptide was separated using Sephadex G-25 column chromatography and high-performance liquid chromatography on a C18 column. The 50% inhibitory concentration (IC(50)) value of purified ACE inhibitory peptide was 40.01 microg/mL. ACE inhibitory peptide was identified as being seven amino acid residues of Ala-Gln-Gly-Glu-Arg-His-Arg by N-terminal amino acid sequence analysis. The IC(50) value of purified ACE inhibitory peptide was 47.1 microM, and Lineweaver-Burk plots suggested that the peptide purified from rotifer protein acts as a competitive inhibitor against ACE. The results of this study suggest that peptides derived from freshwater rotifers may be beneficial as antihypertension compounds in functional foods or as pharmaceuticals. PMID:20170338
Effect of stiripentol on carbamazepine plasma concentration and metabolism in epileptic children
A. Tran; F. Vauzelle-Kervroedan; E. Rey; G. Pons; Ph d'Athis; C. Chiron; O. Dulac; F. Renard; G. Olive
Objective: To study the relationship between the plasma concentration of stiripentol (STP), a new antiepileptic drug, and its inhibitory\\u000a effect on the formation of carbamazepine epoxide (CBZE) in epileptic children treated with carbamazepine (CBZ) either alone\\u000a or in combination with another antiepileptic drug.\\u000a \\u000a Methods:\\u000a \\u000a \\u000a Minimum plasma concentration of antiepileptic drugs was measured before initiation of STP therapy (day 0) and
The inhibitory effect of vanadium oxoanions on the activity of copper-zinc superoxide dismutase.
Apella, M C; González, S N; Baran, E J
The inhibitory effect of vanadate species on the enzymatic activity of bovine copper-zinc superoxide dismutase has been investigated at different pH values and vanadium concentrations. A definite inhibitory effect, clearly related to the main negative charge of each of the vanadate solutions, has been found. The results suggest that the origin of the inhibitory effect may be similar to that found for the phosphate ion, i.e., a diminution of the effectiveness of the substrate electronic guidance mechanism by partial neutralization of the charges close to the active site. Under physiological conditions, the inhibitory effect of vanadate is somewhat smaller than the phosphate. PMID:2484557
Influence of Sublethal Antibiotic Concentrations on Bacterial Adherence to Saliva-Treated Hydroxyapatite
Peros, W. J.; Gibbons, R. J.
The influence of growth in the presence of sublethal concentrations of nine antibiotics on the ability of certain potentially odontopathic bacteria to attach to saliva-treated hydroxyapatite surfaces which mimic teeth was studied. Cells of Actinomyces viscosus LY7 and S2, Bacteroides gingivalis 381, Capnocytophaga ochraceus 6, and Actinobacillus actinomycetemcomitans N27 attached in lower numbers to saliva-treated hydroxyapatite when grown in the presence of 50% of the minimum inhibitory concentration of tetracycline. Electron microscopic observations of negatively stained preparations indicated that tetracycline-grown A. viscosus LY7 cells had fewer fimbriae than did untreated cells, which may account for the impaired ability of the treated cells to attach. However, cells of Actinomyces naeslundii L13 and S4 attached in higher numbers when grown in the presence of tetracycline, clindamycin, erythromycin, chloramphenicol, or neomycin. Streptococcus mutans strains H12 and JBP also exhibited increased adherence to saliva-treated hydroxyapatite when grown in the presence of 50 or 25% of the minimum inhibitory concentration of penicillin. Thus, growth in the presence of sublethal antibiotic concentrations could increase as well as decrease the adherence of bacteria to saliva-treated hydroxyapatite. Antibiotic-grown cells of the Actinomyces strains showed enhanced hemagglutination activity, but this did not correlate with their ability to attach to saliva-treated hydroxyapatite. Sublethal concentrations of antibiotics in the growth media also affected the coaggregation reactions of several organisms; the effects were specific for one member of the coaggregation pair. Images PMID:6274799
Inhibitory Control in Childhood Stuttering
ERIC Educational Resources Information Center
Eggers, Kurt; De Nil, Luc F.; Van den Bergh, Bea R. H.
Purpose: The purpose of this study was to investigate whether previously reported parental questionnaire-based differences in inhibitory control (IC; Eggers, De Nil, & Van den Bergh, 2010) would be supported by direct measurement of IC using a computer task. Method: Participants were 30 children who stutter (CWS; mean age = 7;05 years) and 30…
Antifungal susceptibility and growth inhibitory response of oral Candida species to Brucea javanica Linn. extract
Background Candida species have been associated with the emergence of resistant strains towards selected antifungal agents. Plant products have been used traditionally as alternative medicine to ease candidal infections. The present study was undertaken to investigate the antifungal susceptibility patterns and growth inhibiting effect of Brucea javanica seeds extract against Candida species. Methods A total of seven Candida strains that includes Candida albicans ATCC14053, Candida dubliniensis ATCCMYA-2975, Candida glabrata ATCC90030, Candida krusei ATCC14243, Candida lusitaniae ATCC64125, Candida parapsilosis ATCC22019 and Candida tropicalis ATCC13803 were used in this study. The antifungal activity, minimum inhibitory concentration and minimum fungicidal concentration of B. javanica extract were evaluated. Each strain was cultured in Yeast Peptone Dextrose broth under four different growth environments; (i) in the absence and presence of B. javanica extract at respective concentrations of (ii) 1 mg/ml (iii) 3 mg/ml and (iv) 6 mg/ml. The growth inhibitory responses of the candidal cells were determined based on changes in the specific-growth rates (?) and doubling time (g). The values in the presence of extract were computed as percentage in the optical density relative to that of the total cells suspension in the absence of extract. Results B. javanica seeds extract exhibited antifungal properties. C. tropicalis showed the highest growth rate; 0.319?±?0.002 h-1, while others were in the range of 0.141?±?0.001 to 0.265?±?0.005 h-1. In the presence of extract, the lag and log phases were extended and deviated the ?- and g-values. B. javanica extract had significantly reduced the ?-values of C. dubliniensis, C. krusei and C. parapsilosis at more than 80% (??0.05), while others were reduced within the range of 2.28% to 57.05%. The g-values of most candidal strains were extended and significantly reduced (??0.05) in relative to the untreated. The candidal population was reduced from an average of 10 x 106 to 6 x 106 CFU/ml. Conclusions B. javanica extract exhibited in vitro antifungal activity against seven oral Candida species. The fungistatic and growth inhibiting effects of B. javanica extract have shown that it has potential to be considered as a promising candidate for the development of antifungal agent in oral health products. PMID:24305010
NSDL National Science Digital Library
United States. Employment Standards Administration.
The US Department of Labor has produced a set of web pages to help employers and employees understand the implementation of the new minimum wage law, signed by President Clinton on August 20. The main page has links to information for employers, a summary of employees' rights, coverage of minimum wage laws in each state, and 1996 amendments to the Fair Labor Standards Act. Users may also follow a link to the DoL's Wage and Hour Division for more complete information about workplace regulations. A new minimum wage poster, for posting in the workplace, is available in Adobe Acrobat (.pdf) format.
Assessment of long-term storage on antimicrobial and cyclooxygenase-inhibitory properties of South African medicinal plants.
Amoo, Stephen O; Aremu, Adeyemi O; Moyo, Mack; Van Staden, Johannes
In traditional medicine, plant materials are often stored by traditional healers, plant gatherers and traders before they are eventually consumed or sold. The critical point is whether stored medicinal plants are as active as freshly harvested dried material. We evaluated the effects of long-term storage (12 or 16?years) on the antimicrobial (microplate dilution method) and anti-inflammatory (COX-1 and COX-2 inhibition) potencies of 21 extensively used traditional medicinal plants in treating pain and infection-related ailments. The minimum inhibitory concentration (MIC) values obtained against Staphylococcus aureus and Pseudomonas aeruginosa in the stored plant materials were generally either lower or roughly the same as in the fresh material. Most of the stored plant material had comparable minimum microbicidal concentration (MMC) values as the fresh material against S. aureus and P. aeruignosa. Similarly, the majority (71%) of the stored plant material had similar MIC and/or MMC values as fresh material against the fungus Candida albicans. The percentage inhibition of COX-1 by the majority (88%) of the stored material was not significantly different when compared to those freshly collected. Stored material of Clausena anisata, Ekebergia capensis and Trichilia dregeana showed a significantly higher COX-1 inhibition than the fresh material. The therapeutic and conservation implications of the results are discussed. PMID:22933443
Cortical Neurodynamics of Inhibitory Control
Ghuman, Avniel S.; Manoach, Dara S.; Jones, Stephanie R.; Luna, Beatriz
The ability to inhibit prepotent responses is critical for successful goal-directed behaviors. To investigate the neural basis of inhibitory control, we conducted a magnetoencephalography study where human participants performed the antisaccade task. Results indicated that neural oscillations in the prefrontal cortex (PFC) showed significant task modulations in preparation to suppress saccades. Before successfully inhibiting a saccade, beta-band power (18–38 Hz) in the lateral PFC and alpha-band power (10–18 Hz) in the frontal eye field (FEF) increased. Trial-by-trial prestimulus FEF alpha-band power predicted successful saccadic inhibition. Further, inhibitory control enhanced cross-frequency amplitude coupling between PFC beta-band (18–38 Hz) activity and FEF alpha-band activity, and the coupling appeared to be initiated by the PFC. Our results suggest a generalized mechanism for top-down inhibitory control: prefrontal beta-band activity initiates alpha-band activity for functional inhibition of the effector and/or sensory system. PMID:25031398
Inhibitory effects of Thyme oils on growth and aflatoxin production by Aspergillus parasiticus
Iraj Rasooli; Mehdi Razzaghi Abyaneh
Inhibition of Aspergillus parasiticus growth and its aflatoxin production exposed to the essential oils extracted from two varieties of Thyme i.e. Thymus eriocalyx and Thymus x-porlock were studied. The disc diffusion method was used to evaluate the zone of fungal growth inhibition at various concentrations of the oils. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of the oils
Protease-Sensitive Inhibitory Activity of Cell-free Supernatant of Lactobacillus crispatus 156 Synergizes with Ciprofloxacin, Moxifloxacin and Streptomycin Against Pseudomonas aeruginosa: An In Vitro Study.
Kaur, Sukhraj; Sharma, Preeti
Ciprofloxacin and streptomycin are frequently prescribed for the treatment of medical conditions originating due to infection by Pseudomonas aeruginosa. However, fluoroquinolone administration has been linked to the outgrowth of Clostridium difficile pathogen, especially in immunocompromised patients. Secondly, frequent administration of antibiotics may lead to development of resistance in the pathogens. Thus, there is a need to explore innovative adjunct therapies to lower the therapeutic doses of the antibiotics. Herein, we evaluated the synergism, if any, between conventional antibiotics and the cell-free supernatant (CFS) of vaginal Lactobacillus crispatus 156 against P. aeruginosa MTCC 741. L. crispatus 156 was isolated from the human vaginal tract, and its CFS had broad-spectrum antimicrobial activity against various Gram-positive and Gram-negative pathogens, including P. aeruginosa. The inhibitory substance present in the CFS completely lost its activity after treatment with proteinases and was resistant to temperatures up to 80 °C and pH ranging from 2 to 6. The cumulative production of the inhibitory substance in CFS was studied, and it showed that the secretion of the inhibitory substance was initiated in middle log phase of growth and peaked in late log phase. Further, CFS synergized the activities of ciprofloxacin, moxifloxacin, and streptomycin as evaluated in terms of checkerboard titrations. It lowered the minimum inhibitory concentration (MIC) of ciprofloxacin by almost 30 times and MIC of both moxifloxacin and streptomycin by 8 times. Interestingly, pepsin treatment of CFS caused the complete abrogation of its synergistic effect with all the three antibiotics. Thus, from the study, it can be concluded that probiotic-based alternative therapeutic regimen can be designed for the treatment of P. aeruginosa infections. PMID:25693845
Minimum Description Length Principle
Remco R. Bouckaert
Probabilistic networks can be constructed from a database of cases by selecting anetwork that has highest quality with respect to this database according to a givenmeasure. A new measure is presented for this purpose based on a minimum descriptionlength (MDL) approach. This measure is compared with a commonly usedmeasure based on a Bayesian approach both from a theoretical and an
Minimum variance geographic sampling
NASA Technical Reports Server (NTRS)
Terrell, G. R. (principal investigator)
Resource inventories require samples with geographical scatter, sometimes not as widely spaced as would be hoped. A simple model of correlation over distances is used to create a minimum variance unbiased estimate population means. The fitting procedure is illustrated from data used to estimate Missouri corn acreage.
Generalized minimum shift keying
NASA Astrophysics Data System (ADS)
Korn, I.
A generalized minimum shift keying (GMSK) signal is defined, and its equivalence to a modified offset quadrature shift keying signal is shown. A simple formula for the spectrum of a GMSK signal is presented and the spectrum and out-of-band power are computed for two examples.
Inhibitory effects of emodin, baicalin, schizandrin and berberine on hefA gene: Treatment of Helicobacter pylori-induced multidrug resistance
Huang, Yan-Qiang; Huang, Gan-Rong; Wu, Ming-Hui; Tang, Hua-Ying; Huang, Zan-Song; Zhou, Xi-Han; Yu, Wen-Qiang; Su, Jian-Wei; Mo, Xiao-Qiang; Chen, Bing-Pu; Zhao, Li-Juan; Huang, Xiao-Feng; Wei, Hong-Yu; Wei, Lian-Deng
AIM: To investigate the inhibitory effects of emodin, baicalin, etc. on the hefA gene of multidrug resistance (MDR) in Helicobacter pylori (H. pylori). METHODS: The double dilution method was used to screen MDR H. pylori strains and determine the minimum inhibitory concentrations (MICs) of emodin, baicalin, schizandrin, berberine, clarithromycin, metronidazole, tetracycline, amoxicillin and levofloxacin against H. pylori strains. After the screened MDR stains were treated with emodin, baicalin, schizandrin or berberine at a 1/2 MIC concentration for 48 h, changes in MICs of amoxicillin, tetracycline, levofloxacin, metronidazole and clarithromycin were determined. MDR strains with reduced MICs of amoxicillin were selected to detect the hefA mRNA expression by real-time quantitative PCR. RESULTS: A total of four MDR H. pylori strains were screened. Treatment with emodin, baicalin, schizandrin and berberine significantly decreased the MICs of amoxicillin and tetracycline against some strains, decreased by 1 to 2 times, but did not significantly change the MICs of clarithromycin, levofloxacin, and metronidazole against MDR strains. In the majority of strains with reduced MICs of amoxicillin, hefA mRNA expression was decreased; one-way ANOVA (SPSS 12.0) used for comparative analysis, P < 0.05. CONCLUSION: Emodin, baicalin, schizandrin and berberine significantly decreased the MICs of amoxicillin and tetracycline against some H. pylori strains, possibly by mechanisms associated with decreasing hefA mRNA expression. PMID:25892872
Synthetic Antigens Reveal Dynamics of BCR Endocytosis During Inhibitory Signaling
Courtney, Adam H.; Bennett, Nitasha R.; Zwick, Daniel B.; Hudon, Jonathan; Kiessling, Laura L.
B cells detect foreign antigens through their B cell antigen receptor (BCR). The BCR, when engaged by antigen, initiates a signaling cascade. Concurrent with signaling is endocytosis of the BCR complex, which acts to downregulate signaling and facilitate uptake of antigen for processing and display on the cell surface. The relationship between signaling and BCR endocytosis is poorly defined. Here, we explore the interplay between BCR endocytosis and antigens that either promote or inhibit B cell activation. Specifically, synthetic antigens were generated that engage the BCR alone or both the BCR and the inhibitory co-receptor CD22. The lectin CD22, a member of the Siglec family, binds sialic acid-containing glycoconjugates found on host tissues, inhibiting BCR signaling to prevent erroneous B cell activation. At low concentrations, antigens that can co-cluster the BCR and CD22 promote rapid BCR endocytosis; whereas, slower endocytosis occurs with antigens that bind only the BCR. At higher antigen concentrations, rapid BCR endocytosis occurs upon treatment with either stimulatory or inhibitory antigens. Endocytosis of the BCR, in response to synthetic antigens, results in its entry into early endocytic compartments. Although the CD22-binding antigens fail to activate key regulators of antigen presentation (e.g., Syk), they also promote BCR endocytosis, indicating that inhibitory antigens can be internalized. Indeed, at low concentrations inhibitory antigens induce more rapid BCR uptake than do stimulatory antigens. Together, our observations support a functional role for BCR endocytosis in downregulating BCR signaling. The reduction of cell surface BCR levels in the absence of B cell activation should raise the threshold for BCR activation. The ability of the activating synthetic antigens to trigger both signalling and entry of the BCR into early endosomes suggests strategies for targeted antigen delivery. PMID:24131142
[Inhibitory effect of green tea polyphenols varnish on oral main cariogenic bacteria.].
Liu, Y L; Feng, X P; Zhu, M
This study observed the bacteriostatic effect of green tea polyphenols varnish,found green tea polyphenols varnish had significant inhibitory action on Streptococcus mutans,Streptococcus sobrinus and Lactobacilli.growth test showed the growth inhibitory rate of S.mutans and S.sobrinus was positive proportion with the concentration of green tea polyphenols varnish,demonstrated green tea polyphenols varnish possess certain anticariogenic effect. PMID:16538358
Inhibitory activity of Syzygium aromaticum and Cymbopogon citratus (DC.) Stapf. essential oils against Listeria monocytogenes inoculated in bovine ground meat
de Oliveira, Thales Leandro Coutinho; das Graças Cardoso, Maria; de Araújo Soares, Rodrigo; Ramos, Eduardo Mendes; Piccoli, Roberta Hilsdorf; Tebaldi, Victor Maximiliano Reis
This research evaluated the antimicrobial effect of the clove (Syzygium aromaticum) and lemongrass (Cymbopogon citratus (DC.) Stapf.) essential oils (EOs) against Listeria monocytogenes ATCC 19117 growth added to bovine ground meat stored under refrigeration (5 ± 2 °C) for three days. The EOs, extracted by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS), were tested in vitro using an agar well diffusion methodology for determination of Minimum Inhibitory Concentration (MIC). The MIC concentrations for both essential oils on culture tested of L. monocytogenes were 1.56%. The EOs concentrations applied in contaminated ground beef were 1.56, 3.125 and 6.25% (w/v) based on MIC levels and possible activity reductions by food constituents. The bacteria populations were significantly reduced (p ? 0.05) after one day of storage in ground meat samples treated with clove and lemongrass EOs at concentrations of 1.56%. There were no significant counts of L. monocytogenes in samples at the other concentrations of the two oils applied after the second day of storage. The sensory acceptability evaluation of the bovine ground meat samples treated with EOs showed that the addition at concentrations higher than 1.56% promote undesirable alterations of taste, odor and characteristic color. The application of EOs at low concentrations in food products can be used in combination with other preservation methods, such as refrigeration, to control pathogens and spoilage bacteria during shelf-life; which goes according to current market trends, where consumers are requesting natural products. PMID:24294222
Inhibitory effect of essential oils against Trichosporon ovoides causing Piedra Hair Infection
Saxena, Seema; Uniyal, Veena; Bhatt, R.P.
Piedra, is an asymptomatic fungal infection of the hair shaft, resulting in the formation of nodules of different hardness on the infected hair. The infection also known as Trichomycosis nodularis is a superficial fungal infection arising from the pathogen being restricted to the stratum corneum with little or no tissue reaction. The nodules are a concretion of hyphae and fruiting bodies of the fungus. Two varieties of Piedra may be seen, Black Piedra and White Piedra. The fungus Trichosporon ovoides is involved in the occurrence of both types of Piedras. The purpose of this study was to examine the effectiveness of selected essential oils for the control of growth of the fungus and to determine whether the antifungal effect was due to the major compounds of the oils. Two screening methods viz. Agar well diffusion assay and Minimum Inhibitory Concentration were adopted for the study. MIC and MFC were determined by tube dilution method. Essential oils from Eucalyptus, Ocimum basilicum, Mentha piperita, Cymbopogon flexuosus, Cymbopogon winterians, Trachyspermum ammi, Zingiber officinalis, Citrus limon, Cinnamomon zeylanicum, Salvia sclarea, Citrus aurantifolia, Melaleuca alternifolia, Citrus aurantium, Citrus bergamia, Pogostemon pathchouli, Cedrus atlantica, Jasminum officinale, Juniperus communis, Abelmoschus moschatus, Cyperus scariosus, Palargonium graveolens, Boswellia carterii, Rosa damascene, Veteveria zizanoides and Commiphora myrrha were evaluated. The essential oils of Cymbopogon winterians, Mentha piperita, Cinnamomum zeylanicum, Melaleuca alternifolia and Eucalyptus globulus were proved to be most effective against the fungus Trichosporon ovoides. PMID:24031963
Inhibitory effect of essential oils against Trichosporon ovoides causing Piedra Hair Infection.
Saxena, Seema; Uniyal, Veena; Bhatt, R P
Piedra, is an asymptomatic fungal infection of the hair shaft, resulting in the formation of nodules of different hardness on the infected hair. The infection also known as Trichomycosis nodularis is a superficial fungal infection arising from the pathogen being restricted to the stratum corneum with little or no tissue reaction. The nodules are a concretion of hyphae and fruiting bodies of the fungus. Two varieties of Piedra may be seen, Black Piedra and White Piedra. The fungus Trichosporon ovoides is involved in the occurrence of both types of Piedras. The purpose of this study was to examine the effectiveness of selected essential oils for the control of growth of the fungus and to determine whether the antifungal effect was due to the major compounds of the oils. Two screening methods viz. Agar well diffusion assay and Minimum Inhibitory Concentration were adopted for the study. MIC and MFC were determined by tube dilution method. Essential oils from Eucalyptus, Ocimum basilicum, Mentha piperita, Cymbopogon flexuosus, Cymbopogon winterians, Trachyspermum ammi, Zingiber officinalis, Citrus limon, Cinnamomon zeylanicum, Salvia sclarea, Citrus aurantifolia, Melaleuca alternifolia, Citrus aurantium, Citrus bergamia, Pogostemon pathchouli, Cedrus atlantica, Jasminum officinale, Juniperus communis, Abelmoschus moschatus, Cyperus scariosus, Palargonium graveolens, Boswellia carterii, Rosa damascene, Veteveria zizanoides and Commiphora myrrha were evaluated. The essential oils of Cymbopogon winterians, Mentha piperita, Cinnamomum zeylanicum, Melaleuca alternifolia and Eucalyptus globulus were proved to be most effective against the fungus Trichosporon ovoides. PMID:24031963
Minimum Changeover Cost Arborescence
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Inhibitory effects of gossypol-related compounds on growth of Aspergillus flavus
Technology Transfer Automated Retrieval System (TEKTRAN)
Gossypolone demonstrated growth inhibitory activity against Aspergillus flavus isolate AF13. Growth inhibition was concentration dependent, with a 50% effective dose of 90 µg gossypolone per mL of medium (165 µM). Growth inhibition levels of up to 95% were achieved with gossypolone concentrations ...
Probing inhibitory effects of nanocrystalline cellulose: inhibition versus surface charge.
Male, Keith B; Leung, Alfred C W; Montes, Johnny; Kamen, Amine; Luong, John H T
NCC derived from different biomass sources was probed for its plausible cytotoxicity by electric cell-substrate impedance sensing (ECIS). Two different cell lines, Spodoptera frugiperda Sf9 insect cells and Chinese hamster lung fibroblast V79, were exposed to NCC and their spreading and viability were monitored and quantified by ECIS. Based on the 50%-inhibition concentration (ECIS(50)), none of the NCC produced was judged to have any significant cytotoxicity on these two cell lines. However, NCC derived from flax exhibited the most pronounced inhibition on Sf9 compared to hemp and cellulose powder. NCCs from flax and hemp pre-treated with pectate lyase were also less inhibitory than NCCs prepared from untreated flax and hemp. Results also suggested a correlation between the inhibitory effect and the carboxylic acid contents on the NCC. PMID:22252333
Probing inhibitory effects of nanocrystalline cellulose: inhibition versus surface charge
NASA Astrophysics Data System (ADS)
Male, Keith B.; Leung, Alfred C. W.; Montes, Johnny; Kamen, Amine; Luong, John H. T.
NCC derived from different biomass sources was probed for its plausible cytotoxicity by electric cell-substrate impedance sensing (ECIS). Two different cell lines, Spodoptera frugiperda Sf9 insect cells and Chinese hamster lung fibroblast V79, were exposed to NCC and their spreading and viability were monitored and quantified by ECIS. Based on the 50%-inhibition concentration (ECIS50), none of the NCC produced was judged to have any significant cytotoxicity on these two cell lines. However, NCC derived from flax exhibited the most pronounced inhibition on Sf9 compared to hemp and cellulose powder. NCCs from flax and hemp pre-treated with pectate lyase were also less inhibitory than NCCs prepared from untreated flax and hemp. Results also suggested a correlation between the inhibitory effect and the carboxylic acid contents on the NCC.
Studies of the in vitro cytotoxic, antioxidant, lipase inhibitory and antimicrobial activities of selected Thai medicinal plants
Background Traditional folk medicinal plants have recently become popular and are widely used for primary health care. Since Thailand has a great diversity of indigenous (medicinal) plant species, this research investigated 52 traditionally used species of Thai medicinal plants for their in vitro cytotoxic, antioxidant, lipase inhibitory and antimicrobial activities. Methods The 55 dried samples, derived from the medicinally used parts of the 52 plant species were sequentially extracted by hexane, dichloromethane, ethanol and water. These 220 extracts were then screened for in vitro (i) cytotoxicity against four cell lines, derived from human lung (A549), breast (MDA-MB-231), cervical (KB3-1) and colon (SW480) cancers, using the MTT cytotoxicity assay; (ii) antioxidant activity, analyzed by measuring the scavenging activity of DPPH radicals; (iii) lipase inhibitory activity, determined from the hydrolytic reaction of p-nitrophenyllaurate with pancreatic lipase; and (iv) antimicrobial activity against three Gram-positive and two Gram-negative bacteria species plus one strain of yeast using the disc-diffusion method and determination of the minimum inhibitory concentration by the broth micro-dilution assay. Results The crude dichloromethane and/or ethanol extracts from four plant species showed an effective in vitro cytotoxic activity against the human cancer cell lines that was broadly similar to that of the specific chemotherapy drugs (etoposide, doxorubicin, vinblastine and oxaliplatin). In particular, this is the first report of the strong in vitro cytotoxic activity of Bauhinia strychnifolia vines. The tested tissue parts of only six plant species (Allium sativum, Cocoloba uvifera, Dolichandrone spathacea, Lumnitzera littorea, Sonneratia alba and Sonneratia caseolaris) showed promising potential antioxidant activity, whereas lipase inhibitory activity was only found in the ethanol extract from Coscinum fenestratum and this was weak at 17-fold lower than Orlistat, a known lipase inhibitor. The highest antimicrobial activity was observed in the extracts from S. alba and S. caseolaris against Pseudomonas aeruginosa and Candida albicans, respectively. Conclusion The Thai medicinal plant B. strychnifolia is first reported to exert strong in vitro cytotoxic activities against human cancer cell lines and warrants further enrichment and characterization. The broad spectrum of the biological activities from the studied plant extracts can be applied as the guideline for the selection of Thai medicinal plant species for further pharmacological and phytochemical investigations. PMID:23145786
Plasticity of Cortical Excitatory-Inhibitory Balance.
Froemke, Robert C
Synapses are highly plastic and are modified by changes in patterns of neural activity or sensory experience. Plasticity of cortical excitatory synapses is thought to be important for learning and memory, leading to alterations in sensory representations and cognitive maps. However, these changes must be coordinated across other synapses within local circuits to preserve neural coding schemes and the organization of excitatory and inhibitory inputs, i.e., excitatory-inhibitory balance. Recent studies indicate that inhibitory synapses are also plastic and are controlled directly by a large number of neuromodulators, particularly during episodes of learning. Many modulators transiently alter excitatory-inhibitory balance by decreasing inhibition, and thus disinhibition has emerged as a major mechanism by which neuromodulation might enable long-term synaptic modifications naturally. This review examines the relationships between neuromodulation and synaptic plasticity, focusing on the induction of long-term changes that collectively enhance cortical excitatory-inhibitory balance for improving perception and behavior. PMID:25897875
[Antioxidant function of solanesol and its inhibitory effect on tyrosinase].
Bai, Qix; Yu, Jia; Su, Mei; Bai, Rui; Katumata, Goroh; Katumata, Masahiro; Chen, Xiushen
The present paper intends to discuss the antioxidant and tyrosinase inhibition effect of solanesol from three aspects of ultraviolet radiation and free radical scavenging. The paper makes a survey on diurnal variation rule of the minimum ultraviolet transmittance and ultraviolet transmittance of solanesol, hydroxyl (OH) free radical scavenging method of Smirnoff reaction system model, superoxide anion O2- free radical scavenging method of pyrogallol autoxidation, and the inhibitory effect of solanesol on tyrosinase activity by enzyme kinetic method. The experiment results showed that solanesol could effectively scavenge lipid radicals to block lipid peroxidation, and inhibit effects on tyrosinase. Solanesol is a natural extract which could be used to prevent senile atrophy of human skin and senile plaque. PMID:25508428
[Antioxidant function of solanesol and its inhibitory effect on tyrosinase].
Bai, Qix; Yu, Jia; Su, Mei; Bai, Rui; Katumata, Goroh; Katumata, Masahiro; Chen, Xiushen
The present paper intends to discuss the antioxidant and tyrosinase inhibition effect of solanesol from three aspects of ultraviolet radiation and free radical scavenging. The paper makes a survey on diurnal variation rule of the minimum ultraviolet transmittance and ultraviolet transmittance of solanesol, hydroxyl (OH) free radical scavenging method of Smirnoff reaction system model, superoxide anion O2- free radical scavenging method of pyrogallol autoxidation, and the inhibitory effect of solanesol on tyrosinase activity by enzyme kinetic method. The experiment results showed that solanesol could effectively scavenge lipid radicals to block lipid peroxidation, and inhibit effects on tyrosinase. Solanesol is a natural extract which could be used to prevent senile atrophy of human skin and senile plaque. PMID:25464797
Inhibitory effects of nisin and potassium sorbate alone or in combination on vegetative cells growth and spore germination of Bacillus sporothermodurans in milk.
Aouadhi, Chedia; Mejri, Slah; Maaroufi, Abderrazak
The inhibitory activities of nisin or/and potassium sorbate on spores and vegetative cells of Bacillus sporothermodurans LTIS27, which are known to be a contaminant of dairy products and to be extremely heat-resistant, were investigated. First, the tested concentrations of nisin or potassium sorbate inhibited vegetative cell growth; with the minimum inhibitory concentrations were 5 × 10(3) IU/ml and 2% (w/v), respectively. Then, the behaviour of vegetative cells and spores in presence of sub-lethal concentrations of nisin (50 UI/ml) or/and potassium sorbate (0.2%), in milk at 37 °C for 5 days, were evaluated. In the absence of inhibitors, strain grew and sporulated at the end of the exponential phase. Nisin (50 UI/ml) was able to inhibit spore outgrowth but didn't affect their germination. It induced an immediate and transitory reduction (1.6log(10) after 1 h and 2.8log(10) after 6 h of incubation) of vegetative cell growth which reappeared between 10 h and 24 h. Potassium sorbate (0.2%) had a durable bacteriostatic effect (1.1log(10) after 6 h), on vegetative cells, followed by a slower regrowth. It was able to inhibit both germination and outgrowth of spores. Association of nisin and potassium sorbate, at sub-lethal concentrations, showed a synergistic effect and resulted in a total inhibition of cells growth after 5 days. The results illustrate the efficacy of nisin and potassium sorbate in combination, and the commercial potential of applying such treatment to decontaminate any product that has a problem with persistence of bacterial spores. PMID:25475264
Inhibitory effect of allyl isothiocyanate on platelet aggregation.
Lee, Do-Seop; Kim, Tae-Ho; Jung, Yi-Sook
Allyl isothiocyanate (AITC) is one of the major components of mustard. The present study for the first time attempted to evaluate the effect of AITC on platelet aggregation. In the in vitro study using platelet-rich plasma (PRP) from rats and humans, AITC at concentrations of 100 and 300 ?M significantly inhibited platelet aggregation induced by collagen, thrombin, ADP, and arachidonic acid. AITC also attenuated thromboxane A2 production and ATP release in rat and human PRP. AITC elicited inhibitory effects on cellular Ca(2+) increase and platelet shape change in rat PRP. AITC further showed inhibitory effects on the phosphorylation of PKC?, p38, ERK, and Akt in rat PRP. In the rat ex vivo study, 1 and 3 mg/kg (po) of AITC showed significant inhibitory effect on platelet aggregation. Furthermore, AITC showed a protective effect in thromboembolism attack model in mouse. These results suggest that AITC has remarkable antiplatelet effects and maybe a therapeutic potential for the prevention of aberrant platelet activation-related disorders. PMID:24980285
Prenylated flavonoids from the stems and leaves of Desmodium caudatum and evaluation of their inhibitory activity against the film-forming growth of Zygosaccharomyces rouxii F51.
Sasaki, Hisako; Shibata, Hirofumi; Imabayashi, Kiyoshi; Takaishi, Yoshihisa; Kashiwada, Yoshiki
In order to provide scientific evidence for the relationship between the traditional usage, stems and leaves of Desmodium caudatum being used for protecting miso from spoilage, and its Japanese name (miso-naoshi), phytochemical study on the stems and leaves of this plant was carried out. Seven new prenylated flavonoids (1-3, 15-18), together with 19 known compounds (4-14, 19-26), were isolated, and the structures of new compounds were elucidated by extensive spectroscopic analyses. The minimum inhibitory concentrations (MICs) of 28 flavonoids, including 17 compounds (1, 2, 4, 5, 7-14, 20-22, 24, 25) isolated in this study and 11 flavonoids (27-37) previously isolated from the roots of this plant, against the film-forming yeast of Zygosaccharomyces rouxii F51 were determined. Fifteen compounds (2, 4, 5, 11, 12, 14, 21, 22, 25, 27, 28, 32-35) inhibited the film-forming growth of Z. rouxii F51 (MIC values, 7.8-62.5 ?g/mL), among which 2",2"-dimethylpyran-(5",6":7,8)-5,2'-dihydroxy-4'-methoxy-(2R,3R)-dihydroflavonol (11) demonstrated potent inhibitory activity with an MIC value of 7.8 ?g/mL. PMID:24956381
NASA Technical Reports Server (NTRS)
Wetherholt, Jon; Heimann, Timothy J.
Design for Minimum Risk (DFMR) is a term used by NASA programs as an expansion of the general hazard reduction process where if an identified hazard cannot be eliminated, the design is modified to reduce the associated mishap risk to an acceptable level. DFMR is a set of specific requirements to minimize risk. DFMR is not well understood and there are many misconceptions concerning the meaning and use. This paper will provide insight into the use of DFMR for space applications; it s comparison to other hazard mitigation strategies and examples of how the approach has been used in the past. It will also highlight documents used by NASA on various programs to determine DFMR.
In glucose-limited continuous culture the minimum substrate concentration for growth, smin, is crucial in the competition between the enterobacterium Escherichia coli and Chelatobacter heintzii, an environmentally abundant bacterium
Füchslin, Hans Peter; Schneider, Christian; Egli, Thomas
The competition for glucose between Escherichia coli ML30, a typical copiotrophic enterobacterium and Chelatobacter heintzii ATCC29600, an environmentally successful strain, was studied in a carbon-limited culture at low dilution rates. First, as a base for modelling, the kinetic parameters ?max and Ks were determined for growth with glucose. For both strains, ?max was determined in batch culture after different precultivation conditions. In the case of C. heintzii, ?max was virtually independent of precultivation conditions. When inoculated into a glucose-excess batch culture medium from a glucose-limited chemostat run at a dilution rate of 0.075?h?1 C. heintzii grew immediately with a ?max of 0.17±0.03?h?1. After five transfers in batch culture, ?max had increased only slightly to 0.18±0.03?h?1. A different pattern was observed in the case of E. coli. Inoculated from a glucose-limited chemostat at D=0.075?h?1 into glucose-excess batch medium E. coli grew only after an acceleration phase of ?3.5?h with a ?max of 0.52?h?1. After 120 generations and several transfers into fresh medium, ?max had increased to 0.80±0.03?h?1. For long-term adapted chemostat-cultivated cells, a Ks for glucose of 15??g?l?1 for C. heintzii, and of 35??g?l?1 for E. coli, respectively, was determined in 14C-labelled glucose uptake experiments. In competition experiments, the population dynamics of the mixed culture was determined using specific surface antibodies against C. heintzii and a specific 16S rRNA probe for E. coli. C. heintzii outcompeted E. coli in glucose-limited continuous culture at the low dilution rates of 0.05 and 0.075?h?1. Using the determined pure culture parameter values for Ks and ?max, it was only possible to simulate the population dynamics during competition with an extended form of the Monod model, which includes a finite substrate concentration at zero growth rate (smin). The values estimated for smin were dependent on growth rate; at D=0.05?h?1, it was 12.6 and 0??g?l?1 for E. coli and C. heintzii, respectively. To fit the data at D=0.075?h?1, smin for E. coli had to be raised to 34.9??g?l?1 whereas smin for C. heintzii remained zero. The results of the mathematical simulation suggest that it is not so much the higher Ks value, which is responsible for the unsuccessful competition of E. coli at low residual glucose concentration, but rather the existence of a significant smin. PMID:22030672
Sequence requirements for oligodeoxyribonucleotide inhibitory activity
Robert F. Ashman; J. Adam Goeken; Jennifer Drahos; Petar Lenert
Inhibitory oligonucleotides (IN-ODN) differing from stimulatory CpG ODN (ST-ODN) by as few as two bases can block ST-ODN-induced proliferation, apoptosis protection and IL-6 secretion in B lymphocytes and the production of IL-12p40 by non-B cells. The main objective of this study was to determine the ODN sequence requirements for inhibition in mice. Starting with a strongly inhibitory 15-mer prototype phosphorothioate
Antimicrobial assays of natural extracts and their inhibitory effect against Listeria innocua and fish spoilage bacteria, after incorporation into biopolymer edible films.
Iturriaga, L; Olabarrieta, I; de Marańón, I Martínez
The antimicrobial activity of twelve natural extracts was tested against two fish spoilage bacteria (Pseudomonas fluorescens and Aeromonas hydrophila/caviae) and Listeria innocua, in order to assess their potential utilization in the preservation and safety of minimally processed fish products. After a screening of the active extracts by agar diffusion and vapour diffusion methods, oregano and thyme essential oils and citrus extract were selected. The minimum inhibitory concentration (MIC) of the selected extracts was determined by disc diffusion method against target bacteria and at two temperatures: bacteria's optimal growth temperature (30 °C or 37 °C) and refrigeration temperature (4 °C). Due to its better solubility, lack of odour and greater inhibitory effect obtained against L. innocua at refrigerated temperature, citrus extract was selected and incorporated at 1% (v/v) into different biopolymer film forming solutions (gelatin, methyl cellulose and their blend 50:50 w/w). The antimicrobial activity of the developed films was then evaluated, just after preparation of the films and after one month of storage at 43±3% relative humidity and 24±3 °C. Regardless of the biopolymer matrix, all the developed films showed antimicrobial activity against the target bacteria. The most sensitive bacterium towards active films was L. innocua while P. fluorescens appeared as the most resistant one, in accordance with the previously performed antimicrobial tests for pure extracts. The differences in activity of the films between the tested two temperatures were not significant except for L. innocua, for which three times higher inhibition diameters were observed at refrigerated temperature. The inhibitory effectiveness of the films against the tested strains was maintained regardless of the biopolymer matrix for at least one month. Therefore, these edible films show potential for their future use in fresh fish fillets preservation. PMID:22824340
Social Security's special minimum benefit.
Olsen, K A; Hoffmeyer, D
Social Security's special minimum primary insurance amount (PIA) provision was enacted in 1972 to increase the adequacy of benefits for regular long-term, low-earning covered workers and their dependents or survivors. At the time, Social Security also had a regular minimum benefit provision for persons with low lifetime average earnings and their families. Concerns were rising that the low lifetime average earnings of many regular minimum beneficiaries resulted from sporadic attachment to the covered workforce rather than from low wages. The special minimum benefit was seen as a way to reward regular, low-earning workers without providing the windfalls that would have resulted from raising the regular minimum benefit to a much higher level. The regular minimum benefit was subsequently eliminated for workers reaching age 62, becoming disabled, or dying after 1981. Under current law, the special minimum benefit will phase out over time, although it is not clear from the legislative history that this was Congress's explicit intent. The phaseout results from two factors: (1) special minimum benefits are paid only if they are higher than benefits payable under the regular PIA formula, and (2) the value of the regular PIA formula, which is indexed to wages before benefit eligibility, has increased faster than that of the special minimum PIA, which is indexed to inflation. Under the Social Security Trustees' 2000 intermediate assumptions, the special minimum benefit will cease to be payable to retired workers attaining eligibility in 2013 and later. Their benefits will always be larger under the regular benefit formula. As policymakers consider Social Security solvency initiatives--particularly proposals that would reduce benefits or introduce investment risk--interest may increase in restoring some type of special minimum benefit as a targeted protection for long-term low earners. Two of the three reform proposals offered by the President's Commission to Strengthen Social Security would modify and strengthen the current-law special minimum benefit. Interest in the special minimum benefit may also increase because of labor force participation and marital trends that suggest that enhancing workers' benefits may be a more effective means of reducing older women's poverty rates than enhancing spousal or widow's benefits. By understanding the Social Security program's experience with the special minimum benefit, policymakers will be able to better anticipate the effectiveness of other initiatives to enhance benefits for long-term low earners. This article presents the most recent and comprehensive information available about the special minimum benefit in order to help policymakers make informed decisions about the provision's future. Highlights of the current special minimum benefit include the following: Very few persons receive the special minimum benefit. As of December 2001, about 134,000 workers and their dependents and survivors were entitled to a benefit based on the special minimum. Of those, only about 79,000 received a higher total benefit because of the special minimum; the other 55,000 were dually entitled. (In effect, when persons are eligible for more than one type of benefit--that is, they are dually eligible--the highest benefit payable determines total benefits. If the special minimum benefit is not the highest benefit payable, it does not increase total benefits paid.) As of February 2000, retired workers who were special minimum beneficiaries with unreduced benefits and were not dually entitled were receiving, on average, a monthly benefit of $510 per month. That amount is approximately $2,000 less than the annual poverty threshold for an aged individual. Special minimum benefits provide small increases in total benefits. For special minimum beneficiaries who were not dually entitled as of December 2001, the average special minimum monthly PIA was just $39 higher than the regular PIA. Most special minimum beneficiaries are female retired workers. About 90 percent of special minimum beneficiaries are retired work
Inhibitory receptors as targets for cancer immunotherapy.
Turnis, Meghan E; Andrews, Lawrence P; Vignali, Dario A A
Inhibitory receptors expressed on T cells control immune responses while limiting autoimmunity. However, tumors can hijack these "checkpoints" for protection from immune attack. Tumor-specific T cells that exhibit an exhausted, unresponsive phenotype express high levels of inhibitory receptors including CTLA4, PD1, and LAG3, among others. Intratumoral regulatory T cells promote immunosuppression and also express multiple inhibitory receptors. Overcoming this inhibitory receptor-mediated immune tolerance has thus been a major focus of recent cancer immunotherapeutic developments. Here, we review how boosting the host's immune system by blocking inhibitory receptor signaling with antagonistic mAbs restores the capacity of T cells to drive durable antitumor immune responses. Clinical trials targeting the CTLA4 and PD1 pathways have shown durable effects in multiple tumor types. Many combinatorial therapies are currently being investigated with encouraging results that highlight enhanced antitumor immunogenicity and improved patient survival. Finally, we will discuss the ongoing identification and dissection of novel T-cell inhibitory receptor pathways, which could lead to the development of new combinatorial therapeutic approaches. PMID:26018646
Novel method to assess antiretroviral target trough concentrations using in vitro susceptibility data.
Acosta, Edward P; Limoli, Kay L; Trinh, Lan; Parkin, Neil T; King, Jennifer R; Weidler, Jodi M; Ofotokun, Ighovwerha; Petropoulos, Christos J
Durable suppression of HIV-1 replication requires the establishment of antiretroviral drug concentrations that exceed the susceptibility of the virus strain(s) infecting the patient. Minimum plasma drug concentrations (C(trough)) are correlated with response, but determination of target C(trough) values is hindered by a paucity of in vivo concentration-response data. In the absence of these data, in vitro susceptibility measurements, adjusted for serum protein binding, can provide estimations of suppressive in vivo drug concentrations. We derived serum protein binding correction factors (PBCF) for protease inhibitors, nonnucleoside reverse transcriptase inhibitors, and an integrase inhibitor by measuring the effect of a range of human serum concentrations on in vitro drug susceptibility measured with the PhenoSense HIV assay. PBCFs corresponding to 100% HS were extrapolated using linear regression and ranged from 1.4 for nevirapine to 77 for nelfinavir. Using the mean 95% inhibitory concentration (IC(95)) for ?1,200 drug-susceptible viruses, we calculated protein-bound IC(95) (PBIC(95)) values. PBIC(95) values were concordant with the minimum effective C(trough) values that were established in well-designed pharmacodynamic studies (e.g., indinavir, saquinavir, and amprenavir). In other cases, the PBIC(95) values were notably lower (e.g., darunavir, efavirenz, and nevirapine) or higher (nelfinavir and etravirine) than existing target recommendations. The establishment of PBIC(95) values as described here provides a convenient and standardized approach for estimation of the minimum drug exposure that is required to maintain viral suppression and prevent the emergence of drug-resistant variants, particularly when in vivo concentration-response relationships are lacking. PMID:22964257
Screening for acetylcholinesterase inhibitory activity in plants used in Thai traditional rejuvenating and neurotonic remedies.
Ingkaninan, Kornkanok; Temkitthawon, Prapapan; Chuenchom, Kanchanaporn; Yuyaem, Thitaree; Thongnoi, Warawit
Acetylcholinesterase (AChE) inhibitor has been used as a drug for the symptomatic treatment of Alzheimer's disease. In order to search for new AChE inhibitors, 32 plants used in Thai traditional rejuvenating and neurotonic remedies were collected. The plant methanolic extracts were tested for AChE inhibitory activity using Ellman's colorimetric method in 96-welled microplates. The results showed that the methanolic extracts from roots of Stephania suberosa Forman. and Tabernaemontana divaricata (L.) R.Br. ex Roem. & Schult. at concentration of 0.1 mg/ml inhibited more than 90% of AChE activity. At the same concentration, four extracts, i.e. stems of Piper interruptum Opiz., seeds of Piper nigrum L., rootbarks of Butea superba Roxb. and roots of Cassia fistula L. extracts showed 50-65% inhibitory activity on AChE. The rest of the extracts showed the AChE inhibitory activity below 50%. PMID:14611889
Increased circulating macrophage migration inhibitory factor levels are associated with coronary artery disease
Yüksel, Arif; Bilgir, Ferda; Bilgir, Oktay; Calan, Mehmet; Bozkaya, Giray
BACKGROUND: To evaluate the macrophage migration inhibitory factor and E-selectin levels in patients with acute coronary syndrome. MATERIALS/METHODS: We examined the plasma migration inhibitory factor and E-selectin levels in 87 patients who presented with chest pain at our hospital. The patients were classified into two groups according to their cardiac status. Sixty-five patients had acute myocardial infarction, and 22 patients had non-cardiac chest pain (non-coronary disease). We designated the latter group of patients as the control group. The patients who presented with acute myocardial infarction were further divided into two subgroups: ST-elevated myocardial infarction (n = 30) and non-ST elevated myocardial infarction (n = 35). RESULTS: We found higher plasma migration inhibitory factor levels in both acute myocardial infarction subgroups than in the control group. However, the E-selectin levels were similar between the acute myocardial infarction and control patients. In addition, we did not find a significant difference in the plasma migration inhibitory factor levels between the ST elevated myocardial infarction and NST-elevated myocardial infarction subgroups. DISCUSSION: The circulating concentrations of migration inhibitory factor were significantly increased in acute myocardial infarction patients, whereas the soluble E-selectin levels were similar between acute myocardial infarction patients and control subjects. Our results suggest that migration inhibitory factor may play a role in the atherosclerotic process. PMID:26017646
Stability and cytotoxicity of angiotensin-I-converting enzyme inhibitory peptides derived from bovine casein*
Wu, Wei; Yu, Pan-pan; Zhang, Feng-yang; Che, Hong-xia; Jiang, Zhan-mei
This study investigated the effect of heat treatment combined with acid and alkali on the angiotensin-I-converting enzyme (ACE) inhibitory activity of peptides derived from bovine casein. The free amino group content, color, and cytotoxicity of the peptides were measured under different conditions. When heated at 100 °C in the pH range from 9.0 to 12.0, ACE inhibitory activity was reduced and the appearance of the peptides was significantly darkened. After thermal treatment in the presence of acid and alkali, the free amino group content of ACE inhibitory peptides decreased markedly. High temperature and prolonged heating also resulted in the loss of ACE inhibitory activity, the loss of free amino groups, and the darker coloration of bovine casein-derived peptides. However, ACE inhibitory peptides, within a concentration range of from 0.01 to 0.2 mg/ml, showed no cytotoxicity to Caco-2 and ECV-304 cell lines after heat treatment. This indicated that high temperature and alkaline heat treatment impaired the stability of bovine casein-derived ACE inhibitory peptides. PMID:24510707
Inhibitory effects of pomegranate extracts on recombinant human maltase-glucoamylase.
Kawakami, Kayoko; Li, Peng; Uraji, Misugi; Hatanaka, Tadashi; Ito, Hideyuki
?-Glucosidase inhibitors are currently used in the treatment of type 2 diabetes. In this study, we investigated the inhibitory activities of aril and pericarp extracts from pomegranates obtained various regions against recombinant human maltase-glucoamylase (MGAM). The inhibitory activities of the aril extracts tended to be stronger than those of the pericarp extracts. The Iranian aril extract was the most effective inhibitor. We investigated the polyphenol content of the pomegranate extracts using the Folin-Ciocalteu method. Among the aril extracts, the Iranian aril extract showed the highest polyphenol content. We further evaluated inhibitory activity against ?-glucosidase from the rat small intestine. Pomegranate extract used in this study showed slightly different inhibitory activities according to ?-glucosidase origin. Iranian aril extract was the most effective inhibitor of ?-glucosidases, especially recombinant human MGAM. Bioassay-guided fractionation of the pomegranate arils led to identification of punicalagin and oenothein B as potent inhibitors of ?-glucosidase. Oenothein B showed inhibitory activity with a half-maximal inhibitory concentration (IC(50)) value of 174 ?M. Its potency was comparable to that of the ?-glucosidase inhibitor acarbose with an IC(50) value of 170 ?M. Dixon plot kinetic analysis of oenothein B showed a noncompetitive inhibition with a K(i) value of 102 ?M. These results suggest that pomegranate arils would be useful for suppressing postprandial hyperglycemia. PMID:25154971
Characterization of angiotensin-converting enzyme inhibitory activity of fermented milk produced by Lactobacillus helveticus.
Chen, Yongfu; Li, Changkun; Xue, Jiangang; Kwok, Lai-Yu; Yang, Jie; Zhang, Heping; Menghe, Bilige
Hypertension affects up to 30% of the adult population in most countries. It is a known risk factor for cardiovascular diseases, including coronary heart disease, peripheral artery disease, and stroke. Owing to the increased health awareness of consumers, the application of angiotensin-converting enzyme (ACE)-inhibitory peptides produced by Lactobacillushelveticus to prevent or control high blood pressure has drawn wide attention. A total of 59 L. helveticus strains were isolated from traditional fermented dairy products and the ACE-inhibitory activity of the fermented milks produced with the isolated microorganisms was assayed. The ACE-inhibitory activity of 38 L. helveticus strains was more than 50%, and 3 strains (IMAU80872, IMAU80852, and IMAU80851) expressing the highest ACE-inhibitory activity were selected for further studies. Particularly, the gastrointestinal protease tolerance and thermostability of the ACE-inhibitory activity in the fermented milks were assessed. Based on these 2 criteria, IMAU80872 was found to be superior over the other 2 strains. Furthermore, IMAU80872 exhibited a high in vitro ACE-inhibitory activity at the following fermentation conditions: fermentation temperature at 40°C, inoculation concentration of 1×10(6) cfu/mL, and fermentation for 18h. Finally, by using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry analysis, we observed changes of the metabolome along the milk fermentation process of IMAU80872. Furthermore, 6 peptides were identified, which might have ACE-inhibitory activity. In conclusion, we identified a novel ACE-inhibitory L. helveticus strain suitable for the production of fermented milk or other functional dairy products. PMID:26004829
Pharmacokinetics and tissue concentrations of tylosin in selected avian species.
Locke, D; Bush, M; Carpenter, J W
Tissue and plasma concentrations and the biological half-life of tylosin in avian species of a variety of body sizes and metabolic rates were studied. The species chosen were eastern bobwhite quail (Colinus virginianus virginianus), pigeons (Columba livia), greater sandhill cranes (Grus canadensis tabida), and emus (Dromaius novaehollandiae). In the 1st phase of this study, tylosin was administered IM to quail, pigeons, and emus at a dosage rate of 25 mg/kg of body weight and to cranes at a dosage rate of 15 mg/kg. The average peak plasma concentrations of tylosin in quail, pigeons, cranes, and emus were 4.31, 5.63, 3.62, and 3.26 microgram/ml, respectively. These peak concentrations occurred at 0.5 to 1.5 hours after administration. The biological half-life of tylosin averaged 1.2 hours in quail, pigeons, and cranes, and was 4.7 hours in emus. In the 2nd phase of this study, tylosin concentrations in the tissues of quail, pigeons, and cranes were markedly higher than were plasma concentrations at corresponding sampling times. Six hours after antibiotic administration, tissue concentrations of tylosin in all species remained within the minimum inhibitory concentration for most pathogenic organisms. Dosage regimens of 25 mg of tylosin/kg 4 times daily for quail and pigeons, 15 mg/kg 3 times daily for cranes, and 25 mg/kg 3 times daily for emus would be needed to establish and maintain therapeutic tissue concentrations. PMID:7149381
Pharmacokinetics and tissue concentrations of tylosin in selected avian species
Locke, D.; Bush, M.; Carpenter, J.W.
Tissue and plasma concentrations and the biological half-life of tylosin in avian species of a variety of body sizes and metabolic rates were studied. The species chosen were eastern bobwhite quail (Colinus virginianus virginianus), pigeons (Columba livia), greater sandhill cranes (Grus canadensis tabida), and emus (Dromaius novaehollandiae). In the 1st phase of this study, tylosin was administered IM to quail, pigeons, and emus at a dosage rate of 25 mg/kg of body weight and to cranes at a dosage rate of 15 mg/kg. The average peak plasma concentrations of tylosin in quail, pigeons, cranes, and emus were 4.31, 5.63, 3.62, and 3.26 microgram/ml, respectively. These peak concentrations occurred at 0.5 to 1.5 hours after administration. The biological half-life of tylosin averaged 1.2 hours in quail, pigeons, and cranes, and was 4.7 hours in emus. In the 2nd phase of this study, tylosin concentrations in the tissues of quail, pigeons, and cranes were markedly higher than were plasma concentrations at corresponding sampling times. Six hours after antibiotic administration, tissue concentrations of tylosin in all species remained within the minimum inhibitory concentration for most pathogenic organisms. Dosage regimens of 25 mg of tylosin/kg 4 times daily for quail and pigeons, 15 mg/kg 3 times daily for cranes, and 25 mg/kg 3 times daily for emus would be needed to establish and maintain therapeutic tissue concentrations.
March 2006 MINIMUM SECURITY REQUIREMENTS FOR FEDERAL INFORMATION AND INFORMATION SYSTEMS: FEDERAL INFORMATION PROCESSING STANDARD (FIPS) 200 APPROVED BY THE SECRETARY OF COMMERCE MINIMUM SECURITY REQUIREMENTS BY THE SECRETARY OF COMMERCE Shirley Radack, EditorShirley Radack, Editor Computer Security Division
Growth-Inhibitory Effect of Heparin on Babesia Parasites
Bork, Sabine; Yokoyama, Naoaki; Ikehara, Yuzuru; Kumar, Sanjay; Sugimoto, Chihiro; Igarashi, Ikuo
We examined the inhibitory effects of three heparins on the growth of Babesia parasites. The multiplication of Babesia bovis, B. bigemina, B. equi, and B. caballi in in vitro cultures and that of B. microti in vivo were significantly inhibited in the presence of heparins, as determined by light microscopy. Treatment with various concentrations of heparin showed complete clearance of the intracellular parasites. Interestingly, a higher percentage of abnormally multidividing B. bovis parasites was observed in the presence of low concentrations of heparin. Furthermore, fluorescein isothiocyanate-labeled heparin was preferably found on the surfaces of extracellular merozoites, as detected by confocal laser scanning microscopy. These findings indicate that the heparin covers the surfaces of babesial merozoites and inhibits their subsequent invasion of erythrocytes. PMID:14693545
Immunotherapies: The Blockade of Inhibitory Signals
Wu, Yan-Ling; Liang, Jing; Zhang, Wen; Tanaka, Yoshimasa; Sugiyama, Hiroshi
T lymphocytes require signaling by the T cell receptor and by nonclonotypic cosignaling receptors. The costimulatory and inhibitory signals profoundly influence the course of immune responses by amplifying or reducing the transcriptional effects of T cell receptor triggering. The inhibitory receptors such as CTLA-4, PD-1, and BTLA have recently drawn much attention as potential targets for immunotherapies. This review focuses on the progress that has been made with the mentioned receptors in the field of immunotherapies for autoimmune diseases, malignancies, infectious diseases, and transplantation. PMID:23197939
The United States Environmental Protection Agency's (EPA) Office of Ground Water and Drinking Water (OGWDW) has developed a single-laboratory quantitation procedure: the lowest concentration minimum reporting level (LCMRL). The LCMRL is the lowest true concentration for which fu...
Predicting the DPP-IV Inhibitory Activity pIC50 Based on Their Physicochemical Properties
Gu, Tianhong; Yang, Xiaoyan; Li, Minjie; Su, Qiang; Lu, Wencong; Zhang, Yuhui
The second development program developed in this work was introduced to obtain physicochemical properties of DPP-IV inhibitors. Based on the computation of molecular descriptors, a two-stage feature selection method called mRMR-BFS (minimum redundancy maximum relevance-backward feature selection) was adopted. Then, the support vector regression (SVR) was used in the establishment of the model to map DPP-IV inhibitors to their corresponding inhibitory activity possible. The squared correlation coefficient for the training set of LOOCV and the test set are 0.815 and 0.884, respectively. An online server for predicting inhibitory activity pIC50 of the DPP-IV inhibitors as described in this paper has been given in the introduction. PMID:23865065
Inhibitory neurosteroids and the GABAA receptor.
Seljeset, Sandra; Laverty, Duncan; Smart, Trevor G
?-Aminobutyric acid type A receptors (GABAARs) are vital proteins that are engaged in regulating neural circuit activity in the central nervous system. Their effectiveness in this task is dependent on the extent of receptor modulation by naturally occurring ligands that are released in the brain. One of the foremost examples of such ligands is the neurosteroids that can either potentiate GABAAR function or cause direct inhibition. To fully understand the underlying mechanisms by which neurosteroids modulate GABAARs, it is necessary to identify their binding sites on the receptors. For potentiating neurosteroids, recent work has made substantive progress in identifying a binding site located in the transmembrane domains of GABAAR ? subunits. However, for the inhibitory neurosteroids, several possibilities exist including an ion channel site as well as potential sites in the transmembrane domain. This review systematically analyzes the evidence behind possible binding sites for the inhibitory neurosteroids. We consider the chemical structure-function properties of such inhibitory neurosteroids, their physiological effects on synaptic inhibition, and whether a binding site exists in the GABA ion channel or in other areas of the transmembrane domain. Finally, we discuss how structural homology modeling and Cys-loop receptor homologues may help to locate the inhibitory neurosteroid-binding site on GABAARs. PMID:25600370
DNA gyrase of Staphylococcus aureus and inhibitory effect of quinolones on its activity.
Takahata, M; Nishino, T
DNA gyrase from Staphylococcus aureus FDA 209P was partially purified by lysostaphin treatment, saturation with ammonium sulfate, and affinity chromatography on heparin-Sepharose and with a concentrator (Centricon 30). It was found to consist of two subunits: alpha and beta. The ability of new quinolone antibacterial agents such as norfloxacin, ofloxacin, and ciprofloxacin to inhibit DNA gyrase activity and cell growth was investigated. The inhibitory effects of the new quinolones against the activity of S. aureus DNA gyrase were in parallel with their antibacterial activities. The 50% inhibitory doses of norfloxacin, ofloxacin, and ciplofloxacin were 0.34, 0.31, and 0.24 micrograms/ml, respectively, while the 50% inhibitory doses of nalidixic acid and cinoxacin, which were less active against S. aureus FDA 209P, were 100 micrograms/ml or more. PMID:2847648
Minimum energy mobile wireless networks
Volkan Rodoplu; Teresa H. Meng
We describe a distributed position-based network protocol optimized for minimum energy consumption in mobile wireless networks that support peer-to-peer communications. Given any number of randomly deployed nodes over an area, we show that a simple local optimization scheme executed at each node guarantees strong connectivity of the entire network and attains the global minimum energy solution for the stationary case.
A virtual screening method for inhibitory peptides of Angiotensin I-converting enzyme.
Wu, Hongxi; Liu, Yalan; Guo, Mingrong; Xie, Jingli; Jiang, XiaMin
Natural small peptides from foods have been proven to be efficient inhibitors of Angiotensin I-converting enzyme (ACE) for the regulation of blood pressure. The traditional ACE inhibitory peptides screening method is both time consuming and money costing, to the contrary, virtual screening method by computation can break these limitations. We establish a virtual screening method to obtain ACE inhibitory peptides with the help of Libdock module of Discovery Studio 3.5 software. A significant relationship between Libdock score and experimental IC(50) was found, Libdock score = 10.063 log(1/IC(50)) + 68.08 (R(2) = 0.62). The credibility of the relationship was confirmed by testing the coincidence of the estimated log(1/IC(50)) and measured log(1/IC(50)) (IC(50) is 50% inhibitory concentration toward ACE, in ?mol/L) of 5 synthetic ACE inhibitory peptides, which was virtual hydrolyzed and screened from a kind of seafood, Phascolosoma esculenta. Accordingly, Libdock method is a valid IC(50) estimation tool and virtual screening method for small ACE inhibitory peptides. PMID:25154376
Production of goat milk protein hydrolysate enriched in ACE-inhibitory peptides by ultrafiltration.
Espejo-Carpio, Francisco Javier; Pérez-Gálvez, Raúl; Almécija, María del Carmen; Guadix, Antonio; Guadix, Emilia M
A global process for the production of goat milk hydrolysates enriched in angiotensin converting enzyme (ACE) inhibitory peptides was proposed. Firstly, the protein fractions (caseins and whey proteins) were separated by ultrafiltration through a 0·14 ?m ceramic membrane. The casein fraction obtained in the retentate stream of the above filtration step was subsequently hydrolysed with a combination of subtilisin and trypsin. After 3 h of reaction, the hydrolysate produced presented an IC50 of 218·50 ?g/ml, which represent a relatively high ACE inhibitory activity. Finally, this hydrolysate was filtered through a 50 kDa ceramic membrane until reaching a volume reduction factor of 3. The permeate produced presented an improvement of more than 30% in the ACE inhibitory activity. In contrast, the retentate was concentrated in larger and inactive peptides which led to a decrease of more than 80% in its inhibitory activity. The process suggested in this work was suitable to obtain a potent ACE inhibitory activity product able to be incorporated into food formulas intended to control or lower blood pressure. Moreover, the liquid product could be easily stabilised by spray dried if it would be necessary. PMID:25003564
Design, Synthesis and Inhibitory Activity of Photoswitchable RET Kinase Inhibitors
Ferreira, Rubén; Nilsson, Jesper R.; Solano, Carlos; Andréasson, Joakim; Grřtli, Morten
REarranged during Transfection (RET) is a transmembrane receptor tyrosine kinase required for normal development and maintenance of neurons of the central and peripheral nervous systems. Deregulation of RET and hyperactivity of the RET kinase is intimately connected to several types of human cancers, most notably thyroid cancers, making it an attractive therapeutic target for small-molecule kinase inhibitors. Novel approaches, allowing external control of the activity of RET, would be key additions to the signal transduction toolbox. In this work, photoswitchable RET kinase inhibitors based on azo-functionalized pyrazolopyrimidines were developed, enabling photonic control of RET activity. The most promising compound displays excellent switching properties and stability with good inhibitory effect towards RET in cell-free as well as live-cell assays and a significant difference in inhibitory activity between its two photoisomeric forms. As the first reported photoswitchable small-molecule kinase inhibitor, we consider the herein presented effector to be a significant step forward in the development of tools for kinase signal transduction studies with spatiotemporal control over inhibitor concentration in situ. PMID:25944708
Original article Effect of immunisation against leukaemia inhibitory
Boyer, Edmond
Original article Effect of immunisation against leukaemia inhibitory factor on the establishment; accepted 23 June 1997) Summary ― Leukaemia inhibitory factor (LIF), a pleiotropic cytokine'est pas obligatoire. LIF / immunisation / début de gestation / implantation INTRODUCTION Leukaemia
An extract of Gymnema sylvestre leaves and purified gymnemic acid inhibits glucose-stimulated gastric inhibitory peptide secretion in rats.
Fushiki, T; Kojima, A; Imoto, T; Inoue, K; Sugimoto, E
Gastric inhibitory peptide release into the portal vein in response to duodenal infusion of D-glucose was studied in the presence of a leaf extract of Gymnema sylvestre, purified gymnemic acid and inhibitors of some putative glucose sensors and carriers in the intestinal lumen. Intraduodenal infusion of D-glucose significantly increased the portal immunoreactive gastric inhibitory peptide concentration in a dose-dependent manner. The increase in the portal immunoreactive gastric inhibitory peptide induced by glucose was significantly depressed by concomitantly infused leaf extract of Gymnema sylvestre, purified gymnemic acid and phlorizin but not by cytochalasin B. Mannoheptulose, which inhibits glycolysis, and procaine and lidocaine, which inhibit the vagal glucoreceptor in the lumen, did not affect portal immunoreactive gastric inhibitory peptide concentrations. These results suggest that a glucose receptor, which interacts with the leaf extract of Gymnema sylvestre, purified gymnemic acid and phlorizin, exists for the release of immunoreactive gastric inhibitory peptide and that the glucose receptor for gastric inhibitory peptide release is not likely to be identical with a glucose transporter or a vagal glucoreceptor in the lumen. PMID:1453221
School concentration and school travel
E. De Boer
The purpose of the research as described in this Doctor's thesis is twofold. Firstly it is to define in how far Dutch facilities for primary and secondary education were subjected to spatial concentration during recent decades. Secondly it is intended to assess what this concentration implied for the development of the minimum necessary travel distances to school, with its consequences
Inhibitory Control and Emotion Regulation in Preschool Children
ERIC Educational Resources Information Center
Carlson, Stephanie M.; Wang, Tiffany S.
This research investigated the relation between individual differences in inhibitory control and emotion regulation. Preschool children (N=53) ages 4-6 (M=5; 0) were assessed on brief batteries of inhibitory control of prepotent responses and emotion regulation. Individual differences in inhibitory control were significantly correlated with…
78 FR 63873 - Minimum Internal Control Standards
Federal Register 2010, 2011, 2012, 2013, 2014
...follows: PART 543--MINIMUM INTERNAL CONTROL STANDARDS FOR CLASS...17 What are the minimum internal control standards for drop...appropriate department (cage or accounting) for reconciliation. (5...21 What are the minimum internal control standards for...
Alcohol and single-cell protein production by Kluyveromyces in concentrated whey permeates with reduced ash
Mahmoud, M.M.; Kosikowski, F.V.
Five Kluyveromyces yeasts were grown in concentrated whey permeates under aerobic and anaerobic conditions to produce single-cell protein and ethanol. K. fragilis NRRL Y2415 produced the highest yield of alcohol, 9.1%, and K. bulgaricus ATCC 1605 gave the highest yield of biomass, 13.5 mg/mL. High ash, apparently through Na and K effects, inhibited production of biomass and alcohol. A 0.77% ash was optimum. Lactose utilization was more rapid under aerobic than anaerobic conditions. (NH/sub 4/)/sub 2/SO/sub 4/ and urea supplementation were without effect on yeast growth or were slightly inhibitory. A 1% peptone inclusion gave the highest biomass yield with minimum alcohol production.
Minimum accelerations from quantised inertia
McCulloch, M E
It has recently been observed that there are no disc galaxies with masses less than 10^9 M_solar and this cutoff has not been explained. It is shown here that this minimum mass can be predicted using a model that assumes that 1) inertia is due to Unruh radiation, and 2) this radiation is subject to a Hubble-scale Casimir effect. The model predicts that as the acceleration of an object decreases, its inertial mass eventually decreases even faster stabilising the acceleration at a minimum value, which is close to the observed cosmic acceleration. When applied to rotating disc galaxies the same model predicts that they have a minimum rotational acceleration, ie: a minimum apparent mass of 1.1x10^9 M_solar, close to the observed minimum mass. The Hubble mass can also be predicted. It is suggested that assumption 1 above could be tested using a cyclotron to accelerate particles until the Unruh radiation they see is short enough to be supplemented by manmade radiation. The increase in inertia may be detectable.
A peptide with HIV-1 reverse transcriptase inhibitory activity from the medicinal mushroom Russula paludosa.
Wang, Jianbin; Wang, H X; Ng, T B
Hot water extracts of 16 species of mushrooms, including both edible and medicinal mushrooms, were screened for human immunodeficiency virus (HIV)-1 reverse transcriptase (RT) inhibitory activity. Extracts of Lactarius camphoratus, Trametes suaveolens, Sparassis crispa, Pleurotus sajor-caju, Pleurotus pulmonarius, and Russula paludosa elicited over 50% inhibition when tested at the concentration of 1 mg/ml. The extract of R. paludosa demonstrated the highest inhibitory activity on HIV-1 RT (97.6%). Fraction SU2, purified from R. paludosa extract by anion exchange chromatography on DEAE-cellulose and gel filtration on Superdex 75, exhibited potent inhibitory activity on HIV-1 RT. At the concentrations of 1 mg/ml, 0.2 mg/ml, and 0.04 mg/ml, the inhibition ratios were 99.2%, 89.3%, and 41.8%, respectively, giving an IC50 of 11 microM. The molecular mass of SU2 was 4.5 kDa and its N-terminal amino acid sequence was determined to be KREHGQHCEF. The peptide was devoid of hemagglutinating, ribonuclease, antifungal, protease, protease inhibitory, and laccase activities. PMID:17113195
Inhibitory effect of essential oils against herpes simplex virus type 2.
Koch, C; Reichling, J; Schneele, J; Schnitzler, P
Essential oils from anise, hyssop, thyme, ginger, camomile and sandalwood were screened for their inhibitory effect against herpes simplex virus type 2 (HSV-2) in vitro on RC-37 cells using a plaque reduction assay. Genital herpes is a chronic, persistent infection spreading efficiently and silently as sexually transmitted disease through the population. Antiviral agents currently applied for the treatment of herpesvirus infections include acyclovir and its derivatives. The inhibitory concentrations (IC50) were determined at 0.016%, 0.0075%, 0.007%, 0.004%, 0.003% and 0.0015% for anise oil, hyssop oil, thyme oil, ginger oil, camomile oil and sandalwood oil, respectively. A clearly dose-dependent virucidal activity against HSV-2 could be demonstrated for all essential oils tested. In order to determine the mode of the inhibitory effect, essential oils were added at different stages during the viral infection cycle. At maximum noncytotoxic concentrations of the essential oils, plaque formation was significantly reduced by more than 90% when HSV-2 was preincubated with hyssop oil, thyme oil or ginger oil. However, no inhibitory effect could be observed when the essential oils were added to the cells prior to infection with HSV-2 or after the adsorption period. These results indicate that essential oils affected HSV-2 mainly before adsorption probably by interacting with the viral envelope. Camomile oil exhibited a high selectivity index and seems to be a promising candidate for topical therapeutic application as virucidal agents for treatment of herpes genitalis. PMID:17976968
Evaluation of traditional Indian antidiabetic medicinal plants for human pancreatic amylase inhibitory effect in vitro.
Ponnusamy, Sudha; Ravindran, Remya; Zinjarde, Smita; Bhargava, Shobha; Ravi Kumar, Ameeta
Pancreatic ?-amylase inhibitors offer an effective strategy to lower the levels of post prandial hyperglycemia via control of starch breakdown. Eleven Ayurvedic Indian medicinal plants with known hypoglycemic properties were subjected to sequential solvent extraction and tested for ?-amylase inhibition, in order to assess and evaluate their inhibitory potential on pancreatic ?-amylase. Analysis of 91 extracts, showed that 10 exhibited strong Human Pancreatic Amylase (HPA) inhibitory potential. Of these, 6 extracts showed concentration dependent inhibition with IC(50) values, namely, cold and hot water extracts from Ficus bengalensis bark (4.4 and 125??gmL(-1)), Syzygium cumini seeds (42.1 and 4.1??gmL(-1)), isopropanol extracts of Cinnamomum verum leaves (1.0??gmL(-1)) and Curcuma longa rhizome (0.16??gmL(-1)). The other 4 extracts exhibited concentration independent inhibition, namely, methanol extract of Bixa orellana leaves (49??gmL(-1)), isopropanol extract from Murraya koenigii leaves (127??gmL(-1)), acetone extracts from C. longa rhizome (7.4??gmL(-1)) and Tribulus terrestris seeds (511??gmL(-1)). Thus, the probable mechanism of action of the above fractions is due to their inhibitory action on HPA, thereby reducing the rate of starch hydrolysis leading to lowered glucose levels. Phytochemical analysis revealed the presence of alkaloids, proteins, tannins, cardiac glycosides, flavonoids, saponins and steroids as probable inhibitory compounds. PMID:20953430
Inhibitory effects on bacterial growth and beta-ketoacyl-ACP reductase by different species of maple leaf extracts and tannic acid.
Wu, Dan; Wu, Xiao-Dong; You, Xue-Fu; Ma, Xiao-Feng; Tian, Wei-Xi
It is important to develop new antibiotics aimed at novel targets. The investigation found that the leaf extracts from five maples (Acer platanoides, Acer campestre, Acer rubrum, Acer saccharum and Acer truncatum Bunge collected in Denmark, Canada and China) and their component tannic acid displayed antibacterial ability against 24 standard bacteria strains with the minimum inhibitory concentration of 0.3-8.0 mg/mL. Unlike the standard antibiotic levofloxacin (LFX), these samples inhibited Gram-positive bacteria more effectively than they inhibited Gram-negative bacteria. These samples effectively inhibited two antidrug bacterial strains. The results show that these samples inhibit bacteria by a different mechanism from LFX. These samples potently inhibited b-ketoacyl-ACP reductase (FabG), which is an important enzyme in bacterial fatty acid synthesis. Tannic acid showed the strongest inhibition on FabG with a half inhibition concentration of 0.78 microM (0.81 microg/mL). Furthermore, tannic acid and two maple leaf extracts showed time-dependent irreversible inhibition of FabG. These three samples also exhibited better inhibition on bacteria. It is suggested that FabG is the antibacteria target of maple leaf extracts and tannic acid, and both reversible and irreversible inhibitions of FabG are important for the antibacterial effect. PMID:19444866
Inhibitory Interneurons, Oxidative Stress, and Schizophrenia
Sullivan, Elyse M.; O'Donnell, Patricio
Translational studies are becoming more common in schizophrenia research. The past couple of decades witnessed the emergence of novel ideas regarding schizophrenia pathophysiology that originated from both human and animal studies. The findings that glutamate and gamma-aminobutyric acid transmission are affected in the disease led to the hypothesis of altered inhibitory neurotransmission as critical for cognitive deficits and to an exploration of novel therapeutic approaches aimed at restoring excitation-inhibition balance. Much is to be done yet to elucidate the ultimate mechanisms by which excitation and inhibition are affected in this disorder; a comprehensive translational effort is necessary to address what may cause altered GABA function, for example. Here, we present an overview of the excitation-inhibition imbalance hypothesis in schizophrenia and discuss ongoing efforts aimed at determining whether cortical inhibitory interneurons are affected by oxidative stress during development. PMID:22461483
Acetylcholinesterase and butyrylcholinesterase inhibitory activity of some Turkish medicinal plants.
Orhan, I; Sener, B; Choudhary, M I; Khalid, A
The chloroform:medianol (1:1) extracts of a number of the plant species belonging to eight families, namely Corydalis solida (L.) Swartz subsp. solida and Glaucium corniculatum (L.) J. H. Rudolph (Papaveraceae), Rhododendron ponticum L. subsp. ponticum and Rhododendron luteum Sweet. (Ericaceae), Buxus sempervirens L. (Buxaceae), Vicia faba L. (Fabaceae), Robinia pseudoacacia L. (Caeselpiniaceae), Tribulus terrestris L. and Zygophyllum fabago L. (Zygophyllaceae), Lycopodium clavatum L. (Lycopodiaceae), Fumaria vaillantii Lois., Fumaria capreolata L., Fumaria kralikii Jordan, Fumaria asepala Boiss., Fumaria densiflora DC., Fumaria flabellata L., Fumaria petteri Reichb. subsp. thuretii (Boiss.) Pugsley, Fumaria macrocarpa Boiss. ex Hausskn., Fumaria cilicica Hauskkn., Fumaria parviflora Lam. and Fumaria judaica Boiss. (Fumariaceae) were screened for their anticholinesterase activity on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes by in vitro Ellman method at 10 microg/ml and 1 mg/ml concentrations. The extracts did not show any noticeable inhibitory activity against both of the enzymes at 10 microg/ml. The extracts of Rhododendron ponticum subsp. ponticum, Rhododendron luteum, Corydalis solida subsp. solida, Glaucium corniculatum, and Buxus sempervirens showed remarkable inhibitory activity above 50% inhibition rate on AChE at 1 mg/ml. Among them, Rhododendron ponticum subsp. ponticum, Corydalis solida subsp. solida and Buxus sempervirens were the most active extracts against BChE having 95.46 +/- 1.03%, 93.08 +/- 0.97%, and 93.45 +/- 0.88% inhibition rates, respectively. Among the extracts screened, all of the Fumaria extracts displayed highly potent inhibition against both of the enzymes at 1 mg/ml concentration compared to the standard. PMID:15036468
Screening of tea extract and theaflavins for inhibitory effects on the biological activity and production of staphylococcal enterotoxin A.
Shimamura, Yuko; Aoki, Natsumi; Sugiyama, Yuka; Nakayama, Tsutomu; Masuda, Shuichi
This study aimed to develop a novel method with tea extracts and its components, to reduce the risk of foodborne illnesses caused by the bacterial toxin staphylococcal enterotoxin A (SEA). The potential effect of tea extracts, theaflavins, and epitheaflagallin on staphylococcal growth was studied. A broth microdilution method was used to determine the minimum inhibitory concentration of these samples against an SEA-producing strain, Staphylococcus aureus C-29. The following assays were performed to evaluate various effects on concentrations of no effect on staphylococcal growth. The interactions of theaflavin-rich green tea extracts (TGE), theaflavins, and epitheaflagallin to cultured S. aureus C-29 were determined using Western blot analysis. As a result, all samples suppressed the binding affinity of the anti-SEA antibody to SEA. Since these samples could react directly with SEA, we examined whether they could bind to SEA. Our results demonstrated that binding of the anti-SEA antibody to 4 theaflavins-treated SEA was inhibited in a dose-dependent manner. On the other hand, the production of SEA was significantly decreased by treatment with TGE and epitheaflagallin. Based on the finding that TGE and epitheaflagallin inhibit the production of SEA, we further examined the relative expression levels of sea toxin-encoding genes after treatment with TGE and epitheaflagallin with real-time RT-PCR. TGE and epitheaflagallin significantly supressed the gene transcription of SEA in S. aureus C-29. We then tested whether the samples block the biological activity of SEA in murine spleen cells. TGE, theaflavins, and epitheaflagallin became inactivated the biological activity of SEA. These results suggest that edible and safe compounds in tea can be used to inactivate both pathogens and toxins. PMID:25307624
Spinal inhibitory neurotransmission in neuropathic pain
Bradley K. Taylor
Nerve injury increases the spinal cord expression and\\/or activity of voltage- and ligand-gated ion channels, peptide receptors,\\u000a and neuroimmune factors, which then drive dorsal horn neuron hyperexcitability. The intensity and duration of this central\\u000a sensitization is determined by the net activity of local excitatory and inhibitory neurotransmitter systems, together with\\u000a ongoing\\/evoked primary afferent activity and descending supraspinal control. Spinal endogenous
Bilingualism influences inhibitory control in auditory comprehension
Henrike K. Blumenfeld; Viorica Marian
Bilinguals have been shown to outperform monolinguals at suppressing task-irrelevant information. The present study aimed to identify how processing linguistic ambiguity during auditory comprehension may be associated with inhibitory control. Monolinguals and bilinguals listened to words in their native language (English) and identified them among four pictures while their eye-movements were tracked. Each target picture (e.g., hamper) appeared together with
Leukemia inhibitory factor in human reproduction
Amir Lass; Weishui Weiser; Alain Munafo; Ernest Loumaye
Objective: To describe the clinical findings, expressions, interactions, and clinical implications of leukemia inhibitory factor (LIF) in human reproduction.Design: Review of published articles.Setting: Clinical development unit of biotechnology company.Intervention(s): None.Result(s): In the endometrium, LIF is expressed in a menstrual cycle–dependent manner, with the highest level occurring at the time of implantation. LIF is also detected in uterine flushing, and its
Context specificity of inhibitory control in dogs
MacLean, Evan L.; Hare, Brian A.
Across three experiments, we explored whether a dog's capacity for inhibitory control is stable or variable across decision-making contexts. In the social task, dogs were first exposed to the reputations of a stingy experimenter that never shared food and a generous experimenter who always shared food. In subsequent test trials, dogs were required to avoid approaching the stingy experimenter when this individual offered (but withheld) a higher-value reward than the generous experimenter did. In the A-not-B task, dogs were required to inhibit searching for food in a previously rewarded location after witnessing the food being moved from this location to a novel hiding place. In the cylinder task, dogs were required to resist approaching visible food directly (because it was behind a transparent barrier), in favor of a detour reaching response. Overall, dogs exhibited inhibitory control in all three tasks. However, individual scores were not correlated between tasks, suggesting that context has a large effect on dogs' behavior. This result mirrors studies of humans, which have highlighted intra-individual variation in inhibitory control as a function of the decision-making context. Lastly, we observed a correlation between a subject's age and performance on the cylinder task, corroborating previous observations of age-related decline in dogs' executive function. PMID:23584618
Effective concentration-based serum pharmacodynamics for antifungal azoles in a murine model of disseminated Candida albicans infection.
Maki, Katsuyuki; Kaneko, Shuji
An assessment of the effective in vivo concentrations of antifungal drugs is important in determining their pharmacodynamics, and therefore, their optimal dosage regimen. Here we establish the effective in vivo concentration-based pharmacodynamics of three azole antifungal drugs (fluconazole, itraconazole, and ketoconazole) in a murine model of disseminated Candida albicans infection. A key feature of this study was the use of a measure of mycelial (m) growth rather than of yeast growth, and pooled mouse sera rather than synthetic media as a growth medium, for determining the minimum inhibitory concentrations (MICs) of azoles for C. albicans (denoted serum mMICs). The serum mMIC assay was then used to measure antifungal concentrations and effects as serum antifungal titers in the serum of treated mice. Both serum mMIC and sub-mMIC values reflected the effective in vivo serum concentrations. Supra-mMIC and mMIC effects exhibited equivalent efficacies and were concentration-independent, while the sub-mMIC effect was concentration-dependent. Following administration of the minimum drug dosage that inhibited an increase in mouse kidney fungal burden, the duration periods of these effects were similar for all drugs tested. The average duration of either the mMIC effect including the supra-mMIC effect, the sub-mMIC effect, or the post-antifungal effect (PAFE) were 6.9, 6.5 and 10.6 h, respectively. Our study suggests that the area under the curve for serum drug concentration versus time, between the serum mMIC and the sub-mMIC, and exposure time above the serum sub-mMIC after the mMIC effect, are major pharmacodynamic parameters. These findings have important implications for effective concentration-based pharmacodynamics of fungal infections treated with azoles. PMID:23539473
Elevated Vancomycin Trough Concentration: Increased Efficacy and/or Toxicity?
Elyasi, Sepideh; Khalili, Hossein; Dashti-Khavidaki, Simin; Emadi-Koochak, Hamid; Mohammadpour, Amirhooshang; Abdollahi, Alireza
Vancomycin susceptibility of methicillin-resistant Staphylococcus aureus has been changed over time and its average minimum inhibitory concentration increased from 1.5 to 1.75 mg/L.A recently published guideline by the American Society of Health Pharmacist recommended a daily dose of 15-20 mg/Kg every 8 to 12 hours of vancomycin to achieve a trough concentration between 15-20 mg/L for treatment of severe infections. Medical records of 69 patients from infectious ward of Imam Khomeini hospital, with suspected or confirmed gram-positive infection who had at least one trough level of vancomycin, were evaluated regarding vancomycin therapeutic goal; efficacy and renal safety. Most of patients (60.6%) with severe infections did not achieve the recommended vancomycin trough level during treatment course. Time to normalization of the signs and symptoms of infection did not correlate with the patients' serum vancomycin trough levels. At the end of treatment course, there was no significant correlation between patients' creatinine clearance and vancomycin trough levels (P=0.32). However, patients'cratinine clearance showed a negatively significant correlation with trough level of vancomycin (P=0.01). Vancomycin induced nephrotoxicity was detected in 4.3% of the patients. These data showed that vancomycin trough level may not necessarily assure treatment success, and also it would not essentially predict the risk of vancomycin induced nephrotoxicity. However, more well designed studies with larger sample size needed for better clinical and practical judgment. PMID:25587313
Inhibitory effects of pepstatin A and mefloquine on the growth of Babesia parasites.
Munkhjargal, Tserendorj; AbouLaila, Mahmoud; Terkawi, Mohamad Alaa; Sivakumar, Thillaiampalam; Ichikawa, Madoka; Davaasuren, Batdorj; Nyamjargal, Tserendorj; Yokoyama, Naoaki; Igarashi, Ikuo
We evaluated the inhibitory effects of pepstatin A and mefloquine on the in vitro and in vivo growths of Babesia parasites. The in vitro growth of Babesia bovis, B. bigemina, B. caballi, and B. equi was significantly inhibited (P < 0.05) by micromolar concentrations of pepstatin A (50% inhibitory concentrations = 38.5, 36.5, 17.6, and 18.1 ?M, respectively) and mefloquine (50% inhibitory concentrations = 59.7, 56.7, 20.7, and 4 ?M, respectively). Furthermore, both reagents either alone at a concentration of 5 mg/kg or in combinations (2.5/2.5 and 5/5 mg/kg) for 10 days significantly inhibited the in vivo growth of B. microti in mice. Mefloquine treatment was highly effective and the combination treatments were less effective than other treatments. Therefore, mefloquine may antagonize the actions of pepstatin A against babesiosis and aspartic proteases may play an important role in the asexual growth cycle of Babesia parasites. PMID:22890034
Inhibitory Effects of Pepstatin A and Mefloquine on the Growth of Babesia Parasites
Munkhjargal, Tserendorj; AbouLaila, Mahmoud; Terkawi, Mohamad Alaa; Sivakumar, Thillaiampalam; Ichikawa, Madoka; Davaasuren, Batdorj; Nyamjargal, Tserendorj; Yokoyama, Naoaki; Igarashi, Ikuo
We evaluated the inhibitory effects of pepstatin A and mefloquine on the in vitro and in vivo growths of Babesia parasites. The in vitro growth of Babesia bovis, B. bigemina, B. caballi, and B. equi was significantly inhibited (P < 0.05) by micromolar concentrations of pepstatin A (50% inhibitory concentrations = 38.5, 36.5, 17.6, and 18.1 ?M, respectively) and mefloquine (50% inhibitory concentrations = 59.7, 56.7, 20.7, and 4 ?M, respectively). Furthermore, both reagents either alone at a concentration of 5 mg/kg or in combinations (2.5/2.5 and 5/5 mg/kg) for 10 days significantly inhibited the in vivo growth of B. microti in mice. Mefloquine treatment was highly effective and the combination treatments were less effective than other treatments. Therefore, mefloquine may antagonize the actions of pepstatin A against babesiosis and aspartic proteases may play an important role in the asexual growth cycle of Babesia parasites. PMID:22890034
Inhibitory effect of Crocus sativus (saffron) on histamine (H1) receptors of guinea pig tracheal chains.
Boskabady, M H; Ghasemzadeh Rahbardar, M; Nemati, H; Esmaeilzadeh, M
The inhibitory effects of aqueous-ethanolic extracts of Crocus sativus (Iridaceae), on histamine (H1) receptors was examined on tracheal chains of guinea pigs. The effects of three concentrations of aqueous-ethanolic extract, 10 nM chlorpheniramine, and saline on histamine (H1) receptors were tested on three groups of guinea pig tracheal chains as follows; incubated trachea with: 1) indomethacin, 2) indomethacin, propranolol, and atropine and 3) indomethacin and propranolol. The EC50 (effective concentration of histamine causing 50% of maximum response) obtained in the presence of chlorpheniramine and all concentrations of the extract in all three groups were significantly greater than those of saline (p<0.05 to p<0.001) except low concentration of the extract in groups 1 and 3. The EC50 obtained in the presence of two higher concentrations of extract in group 2 were greater than group 1 and 3 (p<0.05 to p<0.001). Maximum response obtained in the presence of two higher concentrations of extract in group 2 were greater than those of group 1 and group 3 (p<0.001 for all cases). There were parallel right ward shift in concentration response curves obtained in the presence of only low and medium concentrations of the extract in group 2 compared to the those of saline. These results indicated an inhibitory effect of Crocus sativus at histamine H1 receptors. PMID:20432629
The Minimum Description Length Principle
Peter D. Grünwald
The minimum description length (MDL) principle is a powerful method of inductive inference, the basis of statistical modeling, pattern recognition, and machine learning. It holds that the best explanation, given a limited set of observed data, is the one that permits the greatest compression of the data. MDL methods are particularly well-suited for dealing with model selection, prediction, and estimation
Inventory Management for Minimum Cost
David P. Herron
One of the most popular types of inveatoiy management is the (Q, r) system, in which a quantity Q of an item is reordered whenever the inventory position reaches the reorder point r. A number of packaged computer programs are available for this system. However, these programs seldom give the minimum-cost values of Q and r, since they usually employ
Resizing structures for minimum weight
NASA Technical Reports Server (NTRS)
Fleury, C.; Schmit, L. A.
Approximation concepts and dual-method algorithms are combined in method of minimum-weight design for structures. Approximation Concepts Code for Efficient Structural Synthesis (ACCESS3) program is powerful research tool in which mathematical programming and optimality criteria are coalesced in efficient structural weight-minimization method.
Minimum Wages and Tipped Servers
Walter John Wessels
Tips allow restaurants to pay servers lower wages. As more servers are hired, each serves fewer meals and earns less in tips. As a result, restaurants must pay a higher wage. This gives them monopsony power over wages. Over some range, a higher minimum wage should increase employment. Empirically, the author found the full 'reverse C' monopsony pattern of employment
Inhibitory effect of compounds from Goniothalamus tapis Miq. and Goniothalamus uvaroides King on platelet-activating factor receptor binding.
Moharam, Bushra Abdulkarim; Jantan, Ibrahim; Jalil, Juriyati; Ahmad, Fasihuddin
Phytochemical investigation on the bark of Goniothalamus tapis Miq. and G. uvaroides King has resulted in the isolation of eight styryl-lactones, (-)-cryptomeridiol, liriodenine, 3-methyl-1H-benz[f]indole-4,9-dione, (-)-stigmasterol and dimethyl terephthalate. The structures of the compounds were elucidated by spectroscopic techniques. The compounds were evaluated for their effect on platelet-activating factor (PAF) receptor binding on rabbit platelets using (3) H-PAF as a ligand. Among the compounds tested, (-)-cryptomeridiol, (+)-goniothalamin and (+)-isoaltholactone exhibited a significant and concentration-dependent inhibitory effect on PAF receptor binding, with inhibitory concentration (IC)(50) values of 17.5, 19.7 and 46.5 µm, respectively. The inhibitory effects of the first two compounds were comparable to that obtained from the positive control, cedrol. The results indicated that these compounds were strong PAF receptor binding inhibitors. PMID:22002630
Compounds from Gum Ammoniacum with Acetylcholinesterase Inhibitory Activity
Adhami, Hamid-Reza; Lutz, Johannes; Kählig, Hanspeter; Zehl, Martin; Krenn, Liselotte
The use of herbal medicinal preparations in dementia therapy has been studied based on experience from traditional medicine. A dichloromethane extract of gum ammoniacum, the gum-resin from Dorema ammoniacum D. Don had shown acetylcholinesterase (AChE) inhibitory activity in a previous study. The aim of this study was the isolation and characterization of the active compounds from this resin. The extract was investigated by a respective colorimetric microplate assay and the active zones were identified via TLC bioautography and isolated using several chromatographic techniques. The structures of the active components were characterized by one- and two-dimensional 1H and 13C NMR spectroscopy and mass spectrometry as (2?S,5?S)-2?-ethenyl-5?-(3-hy-droxy-6-methyl-4-oxohept-5-en-2-yl)-7-methoxy-2?-methyl-4H-spiro[chromene-3,1?-cyclopentane]-2,4-dione (1), which is an analogue of doremone A and a new natural compound, and as (2?S,5?R)-2?-ethenyl-5?-[(2R,4R)-4-hydroxy-6-methyl-3-oxohept-5-en-2-yl]-7-methoxy-2?-methyl-4H-spiro[chromene-3,1?-cyclo-pentane]-2,4-dione (2 = doremone A), (4E,8E)-1-(2,4-dihydroxyphenyl)-5,9,13-trimethyltetradeca-4,8,12-trien-1-one (3 = dshamirone), and 4,7-dihydroxy-3-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl]-2H-chromen-2-one (4 = am-moresinol). Dshamirone turned out to be the most active compound with an IC50 value for AChE inhibitory activity of 23.5 ?M, whereas the other substances showed weak activity. The concentrations of the analytes in the resin were determined by HPLC as 3.1%, 4.6%, 1.9%, and 9.9%, respectively. PMID:24106674
Essential Oils from Ugandan Aromatic Medicinal Plants: Chemical Composition and Growth Inhibitory Effects on Oral Pathogens
Ocheng, Francis; Bwanga, Freddie; Joloba, Moses; Softrata, Abier; Azeem, Muhammad; Pütsep, Katrin; Borg-Karlson, Anna-Karin; Obua, Celestino; Gustafsson, Anders
The study assessed the growth inhibitory effects of essential oils extracted from ten Ugandan medicinal plants (Bidens pilosa, Helichrysum odoratissimum, Vernonia amygdalina, Hoslundia opposita, Ocimum gratissimum, Cymbopogon citratus, Cymbopogon nardus, Teclea nobilis, Zanthoxylum chalybeum, and Lantana trifolia) used traditionally in the management of oral diseases against oral pathogens. Chemical compositions of the oils were explored by GC-MS. Inhibitory effects of the oils were assessed on periodontopathic Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans and cariogenic Streptococcus mutans and Lactobacillus acidophilus using broth dilution methods at concentrations of 1%, 0.1%, and 0.01%. The most sensitive organism was A. actinomycetemcomitans. Its growth was markedly inhibited by six of the oils at all the concentrations tested. Essential oil from C. nardus exhibited the highest activity with complete growth inhibition of A. actinomycetemcomitans and P. gingivalis at all the three concentrations tested, the major constituents in the oil being mainly oxygenated sesquiterpenes. Most of the oils exhibited limited effects on L. acidophilus. We conclude that essential oils from the studied plants show marked growth inhibitory effects on periodontopathic A. actinomycetemcomitans and P. gingivalis, moderate effects on cariogenic S. mutans, and the least effect on L. acidophilus. The present study constitutes a basis for further investigations and development of certain oils into alternative antiplaque agents. PMID:26170872
Inhibitory effect of hexane fraction from Myagropsis myagroides on pancreatic ?-amylase in vitro.
Pak, Won-Min; Kim, Koth-Bong-Woo Ri; Kim, Min-Ji; Cho, Ji-Young; Ahn, Dong-Hyun
A Myagropsis myagroides (Mm) methanol extract showed ?-amylase inhibitory activity of 13% at a concentration of 5 mg/ml. Results showed that the hexane fraction from the Mm methanol extract exhibited ?-amylase inhibitory activity with an IC50 value of 4.24 mg/ml. The hexane fraction was separated using silica-gel column chromatography, and six subfractions were obtained. The fraction eluted with CHCl3:MeOH = 50:1 showed the highest ?-amylase inhibitory activity with an IC50 value of 0.72 mg/ml. This fraction was purified using Sephadex LH-20 column chromatography and an octadecyl silica (ODS) Sepak cartridge, obtaining seven subfractions. Fraction (Fr.) 4 also showed a strong ?-amylase inhibitory activity with an IC50 value of 0.75 mg/ml. Fr. 4 was purified by Sephadex LH-20 column chromatography and ODS Sepak cartridge, obtaining six subfractions. Fr. 4-2 was identified as sargachromanol I with an IC50 value of 0.40 mg/ml, and the inhibition pattern analyzed from Lineweaver-Burk plots revealed it to be an uncompetitive inhibitor. These results suggest that Mm has potential as a natural antidiabetes agent. PMID:25315050
Molecular docking studies and in vitro cholinesterase enzyme inhibitory activities of chemical constituents of Garcinia hombroniana.
Jamila, Nargis; Yeong, Khaw Kooi; Murugaiyah, Vikneswaran; Atlas, Amir; Khan, Imran; Khan, Naeem; Khan, Sadiq Noor; Khairuddean, Melati; Osman, Hasnah
Garcinia species are reported to possess antimicrobial, anti-inflammatory, anticancer, anti-HIV and anti-Alzheimer's activities. This study aimed to investigate the in vitro cholinesterase enzyme inhibitory activities of garcihombronane C (1), garcihombronane F (2), garcihombronane I (3), garcihombronane N (4), friedelin (5), clerosterol (6), spinasterol glucoside (7) and 3?-hydroxy lup-12,20(29)-diene (8) isolated from Garcinia hombroniana, and to perform molecular docking simulation to get insight into the binding interactions of the ligands and enzymes. The cholinesterase inhibitory activities were evaluated using acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. In this study, compound 4 displayed the highest concentration-dependent inhibition of both AChE and BChE. Docking studies exhibited that compound 4 binds through hydrogen bonds to amino acid residues of AChE and BChE. The calculated docking and binding energies also supported the in vitro inhibitory profiles of IC50. In conclusion, garcihombronanes C, F, I and N (1-4) exhibited dual and moderate inhibitory activities against AChE and BChE. PMID:25219673
Safe Minimum Internal Temperature Chart
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Ioannis Psaras; Vassilis Tsaoussidis
We re-examine the two reasons for the conservative 1-second Minimum TCP-RTO to protect against spurious timeouts: i) the OS clock granularity and ii) the Delayed ACKs. We find that reason (i) is canceled in modern OSs; we carefully design a mechanism to deal with reason (ii). Simulation results show that in next generation's high-speed, wireless- access networks, TCP-RTO should not
Venus ionopause during solar minimum
Mahajan, K.K.; Mayr, H.G.
During solar minimum, the Venus ionosphere is weak and the solar wind depresses the ionopause to a limiting altitude (Knudsen et al., 1987). With the knowledge gained from the ion composition measurements on Pioneer Venus during solar maximum and during conditions of high solar wind pressure, the authors argue that the typical topside electron density profile at Venus during solar minimum has two distinct regimes; one from about 140 km (the altitude of peak electron density) to 180 km and the other above 180 km. While the former is dominated by O{sub 2}{sup +} ions which are in photochemical equilibrium, the latter is dominated by O{sup +} ions which are strongly disturbed by the solar wind induced plasma transport. The disturbed ionosphere is formed in the photodynamical regime and has a scale height which is several times smaller than that expected under undisturbed conditions when the ionosphere is in diffusive equilibrium. The small scale height of the disturbed ionosphere is nearly equal to that of the ionizable constituent, atomic oxygen, and is only slightly larger than the chemical equilibrium scale height of the underlying chemical equilibrium region. While the photodynamical ionopause occurs rarely during solar maximum and only when the solar wind pressure is large, we believe that this kind of ionopause is observed much more frequently during solar minimum. The authors find evidence for this in the radio occultation data from Pioneer Venus, Mariner 10 and Venera 9 and 10.
Inhibitory control at a synaptic relay.
Awatramani, Gautam B; Turecek, Rostislav; Trussell, Laurence O
The mammalian medial nucleus of the trapezoid body (MNTB) harbors one of the most powerful terminals in the CNS, the calyx of Held. The mechanisms known to regulate this synaptic relay are relatively ineffective. Here, we report the presence of a remarkably robust and fast-acting glycinergic inhibitory system capable of suppressing calyceal transmission. Evoked glycinergic IPSCs were relatively small in 2-week-old rats, an age by which calyceal maturation has reportedly neared completion. However, by postnatal day 25 (P25), glycinergic transmission had undergone a vigorous transformation, resulting in peak synaptic conductances as high as 280 nS. These are comparable with glutamatergic conductances activated by calyceal inputs. Decay kinetics for IPSCs were severalfold faster than for glycinergic synaptic events reported previously. At physiological temperatures in P25 rats, IPSCs decayed in approximately 1 msec and could be elicited at frequencies up to 500 Hz. Moreover, EPSPs triggered by glutamatergic signals derived from the calyx or simulated by conductance clamp were suppressed when preceded by simulated glycinergic IPSPs. The matching of excitatory transmission in the calyx of Held by a powerful, precision inhibitory system suggests that the relay function of the MNTB may be rapidly modified during sound localization. PMID:15028756
Rational Decision-Making in Inhibitory Control
Shenoy, Pradeep; Yu, Angela J.
An important aspect of cognitive flexibility is inhibitory control, the ability to dynamically modify or cancel planned actions in response to changes in the sensory environment or task demands. We formulate a probabilistic, rational decision-making framework for inhibitory control in the stop signal paradigm. Our model posits that subjects maintain a Bayes-optimal, continually updated representation of sensory inputs, and repeatedly assess the relative value of stopping and going on a fine temporal scale, in order to make an optimal decision on when and whether to go on each trial. We further posit that they implement this continual evaluation with respect to a global objective function capturing the various reward and penalties associated with different behavioral outcomes, such as speed and accuracy, or the relative costs of stop errors and go errors. We demonstrate that our rational decision-making model naturally gives rise to basic behavioral characteristics consistently observed for this paradigm, as well as more subtle effects due to contextual factors such as reward contingencies or motivational factors. Furthermore, we show that the classical race model can be seen as a computationally simpler, perhaps neurally plausible, approximation to optimal decision-making. This conceptual link allows us to predict how the parameters of the race model, such as the stopping latency, should change with task parameters and individual experiences/ability. PMID:21647306
Social inhibitory control in five lemur species.
Reddy, Rachna B; MacLean, Evan L; Sandel, Aaron A; Hare, Brian
We tested five lemur species-ring-tailed lemurs, ruffed lemurs, mongoose lemurs, black lemurs, and Coquerel's sifakas-(N = 52) in an experiment that evaluated skills for inhibitory control in a social context. First, two human experimenters presented identical food rewards; the "generous" experimenter allowed the subject to eat from her hand, whereas the "competitive" experimenter always withheld the reward. Lemurs quickly learned to approach the generous experimenter and avoid the competitive one. In the inhibition test phase, we endowed the competitive experimenter with a more valuable food reward but the competitive experimenter continued to withhold food from the subject. Thus, lemurs were required to inhibit approaching the more desirable reward in favor of the lesser but obtainable reward presented by the generous experimenter. In test trials, lemurs' tendency to approach the competitive experimenter increased from the reputation phase, demonstrating sensitivity to the experimental manipulation. However, subjects approached the larger reward less frequently in test trials compared with pretest food-preference trials, evidencing some capacity for inhibitory control in this context. Despite differences in sociality and ecology, the five lemur species did not differ in this ability. Although the study did not uncover species differences, this experimental task may provide a useful measure of social inhibition in broader comparative studies. PMID:25822664
New Cholinesterase Inhibitory Constituents from Lonicera quinquelocularis
Khan, Dilfaraz; Khan, Hidayat Ullah; Khan, Farmanullah; Khan, Shafiullah; Badshah, Syed; Khan, Abdul Samad; Samad, Abdul; Ali, Farman; Khan, Ihsanullah; Muhammad, Nawshad
A phytochemical investigation on the ethyl acetate soluble fraction of Lonicera quinquelocularis (whole plant) led to the first time isolation of one new phthalate; bis(7-acetoxy-2-ethyl-5-methylheptyl) phthalate (3) and two new benzoates; neopentyl-4-ethoxy-3, 5-bis (3-methyl-2-butenyl benzoate (4) and neopentyl-4-hydroxy-3, 5-bis (3-methyl-2-butenyl benzoate (5) along with two known compounds bis (2-ethylhexyl phthalate (1) and dioctyl phthalate (2). Their structures were established on the basis of spectroscopic analysis and by comparison with available data in the literature. All the compounds (1–5) were tested for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities in dose dependent manner. The IC50 (50% inhibitory effect) values of compounds 3 and 5 against AChE were 1.65 and 3.43 µM while the values obtained against BChE were 5.98 and 9.84 µM respectively. Compounds 2 and 4 showed weak inhibition profile. PMID:24733024
Lipoxygenase inhibitory activity of alkyl protocatechuates.
Ha, Tae Joung; Shimizu, Kuniyoshi; Kubo, Isao
Alkyl 3,4-dihydroxybenzoates (protocatechuates) inhibited linoleic acid peroxidation catalyzed by soybean lipoxygenase-1 (EC 18.104.22.168, Type 1). Their inhibitory activities displayed a parabolic function of their lipophilicity and maximized with alkyl chain lengths of between C11 and C14. Tetradecanyl protocatechuate exhibited the most potent inhibition with an IC50 of 0.05 ?M, followed by dodecyl (lauryl) protocatechuate with an IC50 of 0.06 ?M. However, their parent compound, protocatechuic acid, did not show this inhibitory activity up to 200 ?M, indicating that the alkyl chain length is significantly related to the inhibition activity. The allosteric (or cooperative) inhibition of soybean lipoxygenase-1 of longer alkyl protocatechuates is reversible but in combination with their iron binding ability to disrupt the active site competitively and to interact with the hydrophobic portion surrounding near the active site (sequential action). In the case of dodecyl protocatechuate, the enzyme quickly binds this protocatechuate and then its dodecyl group undergoes a slow interaction with the hydrophobic domain in close proximity to the active site in the enzyme. The inhibition kinetics analyzed by Lineweaver-Burk plots indicates that octyl protocatechuate is a competitive inhibitor and the inhibition constant (Ki) was obtained as 0.23 ?M but dodecyl protocatechuate is a slow binding inhibitor. PMID:24767084
Maximizing Exposure Therapy: An Inhibitory Learning Approach
Craske, Michelle G.; Treanor, Michael; Conway, Chris; Zbozinek, Tomislav; Vervliet, Bram
Exposure therapy is an effective approach for treating anxiety disorders, although a substantial number of individuals fail to benefit or experience a return of fear after treatment. Research suggests that anxious individuals show deficits in the mechanisms believed to underlie exposure therapy, such as inhibitory learning. Targeting these processes may help improve the efficacy of exposure-based procedures. Although evidence supports an inhibitory learning model of extinction, there has been little discussion of how to implement this model in clinical practice. The primary aim of this paper is to provide examples to clinicians for how to apply this model to optimize exposure therapy with anxious clients, in ways that distinguish it from a 'fear habituation' approach and 'belief disconfirmation' approach within standard cognitive-behavior therapy. Exposure optimization strategies include 1) expectancy violation, 2) deepened extinction, 3) occasional reinforced extinction, 4) removal of safety signals, 5) variability, 6) retrieval cues, 7) multiple contexts, and 8) affect labeling. Case studies illustrate methods of applying these techniques with a variety of anxiety disorders, including obsessive-compulsive disorder, posttraumatic stress disorder, social phobia, specific phobia, and panic disorder. PMID:24864005
Effects of temperature and medium composition on inhibitory activities of gossypol-related compounds against aflatoxigenic fungi
Technology Transfer Automated Retrieval System (TEKTRAN)
Effects of temperature and medium composition on growth/aflatoxin inhibitory activities of gossypol, gossypolone and apogossypolone against Aspergillus flavus and A. parasiticus were investigated. The compounds were tested in a Czapek agar medium at 25 C, 31 C and 37 C at a concentration of 100 µg ...
Routing with Minimum Wire Length in the Dogleg-Free Manhattan Model is NP-Complete
Tibor Szkaliczki
The present article concentrates on the dogleg-free Manhattan model where hori- zontal and vertical wire segments are positioned on different sides of the board and each net (wire) has at most one horizontal segment. While the minimum width can be found in linear time in the single row routing, apparently there was no efficient algorithm to find the minimum wire
40 CFR 1065.546 - Verification of minimum dilution ratio for PM batch sampling.
Code of Federal Regulations, 2014 CFR
...minimum dilution ratio for PM batch sampling. Use continuous flows and/or tracer gas concentrations for transient and ramped-modal cycles to verify the minimum dilution ratios for PM batch sampling as specified in § 1065.140(e)(2) over the...
A Lectin with Highly Potent Inhibitory Activity toward Breast Cancer Cells from Edible Tubers of Dioscorea opposita cv. Nagaimo
Chan, Yau Sang; Ng, Tzi Bun
A 70-kDa galactose-specific lectin was purified from the tubers of Dioscorea opposita cv. nagaimo. The purification involved three chromatographic steps: anion exchange chromatography on a Q-Sepharose column, FPLC-anion exchange chromatography on a Mono Q column, and FPLC-gel filtration on a Superdex 75 column. The purified nagaimo lectin presented as a single 35-kDa band in reducing SDS-PAGE while it exhibited a 70-kDa single band in non-reducing SDS-PAGE suggesting its dimeric nature. Nagaimo lectin displayed moderate thermostability, retaining full hemagglutinating activity after heating up to 62°C for 30 minutes. It also manifested stability over a wide pH range from pH 2 to 13. Nagaimo lectin was a galactose-specific lectin, as evidenced by binding with galactose and galactose-containing sugars such as lactose and raffinose. The minimum concentration of galactose, lactose and raffinose required to exert an inhibitory effect on hemagglutinating activity of nagaimo lectin was 20 mM, 5 mM and 40 mM, respectively. Nagaimo lectin inhibited the growth of some cancer cell lines including breast cancer MCF7 cells, hepatoma HepG2 cells and nasopharyngeal carcinoma CNE2 cells, with IC50 values of 3.71 µM, 7.12 µM and 19.79 µM, respectively, after 24 hour treatment with nagaimo lectin. The induction of phosphatidylserine externalization and mitochondrial depolarization indicated that nagaimo lectin evoked apoptosis in MCF7 cells. However, the anti-proliferative activity of nagaimo lectin was not blocked by application of galactose, signifying that the activity was not related to the carbohydrate binding specificity of the lectin. PMID:23349827
Even high-dose extended infusions may not yield desired concentrations of ?-lactams: the value of therapeutic drug monitoring.
Cotta, Menino Osbert; Gowen, Belinda; Truloff, Natasha; Bursle, Evan; McWhinney, Brett; Ungerer, Jacobus P J; Roberts, Jason A; Lipman, Jeffrey
A 35-year-old patient in intensive care with severe burn injury developed episodes of sepsis. Blood culture yielded a multidrug-resistant Pseudomonas aeruginosa and treatment was commenced with amikacin (minimum inhibitory concentration (MIC) 2-4 mg/L, dose 20 mg/kg adjusted body weight 24-hourly) and meropenem (MIC 8 mg/L, dose 2 g IV 8-hourly and later 6-hourly). Despite the use of extended infusions with ?-lactam therapeutic drug monitoring and doses that were more than 2.5 times higher than standard meropenem doses, resistance emerged. This case report describes the application of therapeutic drug monitoring to optimize ?-lactam therapy in a difficult-to-treat critically ill patient. PMID:25753768
A Novel Lectin with Antiproliferative and HIV-1 Reverse Transcriptase Inhibitory Activities from Dried Fruiting Bodies of the Monkey Head Mushroom Hericium erinaceum
Li, Yanrui; Zhang, Guoqing; Ng, Tzi Bun; Wang, Hexiang
A lectin designated as Hericium erinaceum agglutinin (HEA) was isolated from dried fruiting bodies of the mushroom Hericium erinaceum with a chromatographic procedure which entailed DEAE-cellulose, CM-cellulose, Q-Sepharose, and FPLC Superdex 75. Its molecular mass was estimated to be 51?kDa and its N-terminal amino acid sequences was distinctly different from those of other isolated mushroom lectins. The hemagglutinating activity of HEA was inhibited at the minimum concentration of 12.5?mM by inulin. The lectin was stable at pH 1.9–12.1 and at temperatures up to 70°C, but was inhibited by Hg2+, Cu2+, and Fe3+ ions. The lectin exhibited potent mitogenic activity toward mouse splenocytes, and demonstrated antiproliferative activity toward hepatoma (HepG2) and breast cancer (MCF7) cells with an IC50 of 56.1??M and 76.5??M, respectively. It manifested HIV-1 reverse transcriptase inhibitory activity with an IC50 of 31.7??M. The lectin exhibited potent mitogenic activity toward murine splenocytes but was devoid of antifungal activity. PMID:20625408
Tyrosinase Inhibitory Effects and Antioxidative Activities of Saponins from Xanthoceras Sorbifolia Nutshell
Zhang, Hongmei; Zhou, Quancheng
Certain saponins are bioactive compounds with anticancer, antivirus and antioxidant activities. This paper discussed inhibitory effects of saponins from Xanthoceras Sorbifolia on tyrosinase, through the research of the rate of tyrosinase catalyzed L-DOPA oxidation. The inhibition rate of tyrosinase activity presented non-linear changes with the saponins concentration. The rate reached 52.0% when the saponins concentration was 0.96 mg/ml. Antioxidant activities of saponins from Xanthoceras Sorbifolia were evaluated by using hydroxyl and superoxide radical scavenging assays. The hydroxyl radical scavenging effects of the saponins were 15.5–68.7%, respectively at the concentration of 0.18–2.52 mg/ml. The superoxide radical scavenging activity reduced from 96.6% to 7.05% with the time increasing at the concentration of 1.44 mg/ml. All the above antioxidant evaluation indicated that saponins from Xanthoceras Sorbifolia exhibited good antioxidant activity in a concentration- dependent manner. PMID:23990897
The inhibitory effect of selenium nanoparticles on protein glycation in vitro
NASA Astrophysics Data System (ADS)
Yu, Shaoxuan; Zhang, Wentao; Liu, Wei; Zhu, Wenxin; Guo, Ruochen; Wang, Yashan; Zhang, Daohong; Wang, Jianlong
Selenium nanoparticles (Se NPs) possess well-known excellent biological activities and low toxicity, and have been employed for numerous applications except as inhibitors to protein glycation. Herein, the present study is carried out to investigate the inhibitory effect of Se NPs on protein glycation in a bovine serum albumin (BSA)/glucose system. By measuring the amount of glucose covalently bound onto BSA, the formation of fructosamine and fluorescent products, it is found that Se NPs can hinder the development of protein glycation in a dose-dependent but time-independent manner under the selected reaction conditions (55 °C, 40 h). And after comparing the increase of inhibitory rate in different stages, it is observed that Se NPs show the greatest inhibitory effect in the early stage, then in the advanced stage, but no effect in the intermediate stage. Fourier transform infrared spectroscopy characterization of Se NPs collected after glycation and determination of ·OH influence and glyoxal formation show that the mechanism for the inhibitory efficacy of Se NPs is related to their strong competitive activity against available amino groups in proteins, their great scavenging activity on reactive oxygen species and their inhibitory effect on ?-dicarbonyl compounds' formation. In addition, it is proved that Se NPs protect proteins from structural modifications in the system and they do not exhibit significant cytotoxicity towards BV-2 and BRL-3A cells at low concentrations (10 and 50 ?g mL?1). Consequently, Se NPs may be suitable for further in vivo studies as novel anti-glycation agents.
Co-clustering activating and inhibitory receptors: impact at varying expression levels of the latter.
Licht, Arieh; Abramson, Jakub; Pecht, Israel
Clustering the mast cell function-associated antigen (MAFA) has earlier been shown to inhibit mast cells' secretory response to the type 1 Fcepsilon receptor (FcepsilonRI) stimulus. MAFA is a type II membrane glycoprotein first identified on rat mast cells and contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytosolic domain. This inhibition is induced already upon clustering MAFA alone. Still, the inhibitory capacity of MAFA-FcepsilonRI co-clustering has recently been characterized and co-clustered MAFA molecules were found to exhibit a markedly higher inhibition capacity than MAFA-clusters alone. We have now compared the inhibitory capacity of FcepsilonRI co-clustered MAFA on the secretory response of rat mucosal-type mast cells (RBL-2H3 line) expressing different levels of this inhibitory protein. Reacting these cells carrying an IgE class, 2,4 dinitrophenyl (DNP)-specific monoclonal antibody with DNP-conjugated F(ab')2 fragments of non-specific polyclonal mouse IgG causes clustering of the FcepsilonRI-IgE. Reaction of these cells with DNP-conjugated F(ab')2 fragments of the MAFA-specific, monoclonal antibody G63 co-aggregates MAFA together with the FcepsilonRI-IgE thereby producing FcepsilonRI-IgE-MAFA co-clusters. Results of measurements of the secretory responses of RBL-2H3 cells expressing higher or lower MAFA levels than those of unmodified cells provided further support to the notion that co-clustered MAFA molecules exhibit a markedly higher inhibition capacity than MAFA-clusters alone. The molecular basis for this enhanced inhibition is most probably the increased concentration of the inhibitory cell components in the immediate proximity of the co-clustered FcepsilonRI-MAFA. PMID:16423412
The inhibitory effect of selenium nanoparticles on protein glycation in vitro.
Yu, Shaoxuan; Zhang, Wentao; Liu, Wei; Zhu, Wenxin; Guo, Ruochen; Wang, Yashan; Zhang, Daohong; Wang, Jianlong
Selenium nanoparticles (Se NPs) possess well-known excellent biological activities and low toxicity, and have been employed for numerous applications except as inhibitors to protein glycation. Herein, the present study is carried out to investigate the inhibitory effect of Se NPs on protein glycation in a bovine serum albumin (BSA)/glucose system. By measuring the amount of glucose covalently bound onto BSA, the formation of fructosamine and fluorescent products, it is found that Se NPs can hinder the development of protein glycation in a dose-dependent but time-independent manner under the selected reaction conditions (55 °C, 40 h). And after comparing the increase of inhibitory rate in different stages, it is observed that Se NPs show the greatest inhibitory effect in the early stage, then in the advanced stage, but no effect in the intermediate stage. Fourier transform infrared spectroscopy characterization of Se NPs collected after glycation and determination of ·OH influence and glyoxal formation show that the mechanism for the inhibitory efficacy of Se NPs is related to their strong competitive activity against available amino groups in proteins, their great scavenging activity on reactive oxygen species and their inhibitory effect on ?-dicarbonyl compounds' formation. In addition, it is proved that Se NPs protect proteins from structural modifications in the system and they do not exhibit significant cytotoxicity towards BV-2 and BRL-3A cells at low concentrations (10 and 50 ?g mL(-1)). Consequently, Se NPs may be suitable for further in vivo studies as novel anti-glycation agents. PMID:25785463
Ceramic veneers with minimum preparation
da Cunha, Leonardo Fernandes; Reis, Rachelle; Santana, Lino; Romanini, Jose Carlos; Carvalho, Ricardo Marins; Furuse, Adilson Yoshio
The aim of this article is to describe the possibility of improving dental esthetics with low-thickness glass ceramics without major tooth preparation for patients with small to moderate anterior dental wear and little discoloration. For this purpose, a carefully defined treatment planning and a good communication between the clinician and the dental technician helped to maximize enamel preservation, and offered a good treatment option. Moreover, besides restoring esthetics, the restorative treatment also improved the function of the anterior guidance. It can be concluded that the conservative use of minimum thickness ceramic laminate veneers may provide satisfactory esthetic outcomes while preserving the dental structure. PMID:24932126
Resistance minimum and heavy fermions.
Jun, Kondo
The phenomenon of the resistance minimum in dilute magnetic alloys is explained in terms of the s-d interaction which takes account of scattering of the conduction electron off the magnetic impurities in metals. Some of the intermetallic compounds which involve rare earth elements or uranium show a very large electronic specific heat and remain non-magnetic even though they show a Curie-like susceptibility at higher temperatures. These phenomena are also explained based on the s-d interaction model. PMID:25792794
5 CFR 630.206 - Minimum charge.
Code of Federal Regulations, 2010 CFR
...OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS ABSENCE AND LEAVE Definitions and General Provisions for Annual and Sick Leave § 630.206 Minimum charge. (a) Unless an agency establishes a minimum charge of less than one hour,...
Bounds for the minimum oriented diameter
Sascha Kurz; Martin Laetsch
We consider the problem of finding an orientation with minimum diameter of a connected bridgeless graph. Fomin et. al. discovered a relation between the minimum oriented diameter an the size of a minimal dominating set. We improve their upper bound.
?-glucuronidase inhibitory studies on coumarin derivatives.
Khan, Khalid Mohammed; Fakhri, Muhammad Imran; Shaikh, Nimra Naveed; Saad, Syed Muhammad; Hussain, Shafqat; Perveen, Shahnaz; Choudhary, Muhammad Iqbal
Twenty-three (23) derivatives of coumarin (5-27) were synthesized and screened for their in vitro ?- glucuronidase (E. coli) inhibitory activities. Only three compounds, 7,8-dihydroxy-4-methyl-2H-chromen-2-one (9) (IC50 = 52.39 ± 1.85 µM), 3-chloro-6-hexyl-7-hydroxy-4-methyl-2H-chromen-2-one (18) (IC50 = 60.50 ± 0.87 µM), and 3,6- dichloro-7-hydroxy-4-methyl-2H-chromen-2-one (15) (IC50 = 380.26 ± 0.92 µM) displayed activities against ?- glucuronidase as compared to standard D-saccharic acid 1,4-lactone (IC50 = 45.75 ± 2.16 µM). The results indicated that the activity of the synthetic coumarins depends upon the substituents present on the coumarin skeleton. PMID:24611780
Timing control by redundant inhibitory neuronal circuits
NASA Astrophysics Data System (ADS)
Tristan, I.; Rulkov, N. F.; Huerta, R.; Rabinovich, M.
Rhythms and timing control of sequential activity in the brain is fundamental to cognition and behavior. Although experimental and theoretical studies support the understanding that neuronal circuits are intrinsically capable of generating different time intervals, the dynamical origin of the phenomenon of functionally dependent timing control is still unclear. Here, we consider a new mechanism that is related to the multi-neuronal cooperative dynamics in inhibitory brain motifs consisting of a few clusters. It is shown that redundancy and diversity of neurons within each cluster enhances the sensitivity of the timing control with the level of neuronal excitation of the whole network. The generality of the mechanism is shown to work on two different neuronal models: a conductance-based model and a map-based model.
Timing control by redundant inhibitory neuronal circuits
Tristan, I., E-mail: firstname.lastname@example.com; Rulkov, N. F.; Huerta, R.; Rabinovich, M. [BioCircuits Institute, University of California, San Diego, La Jolla, California 92093-0402 (United States)] [BioCircuits Institute, University of California, San Diego, La Jolla, California 92093-0402 (United States)
Rhythms and timing control of sequential activity in the brain is fundamental to cognition and behavior. Although experimental and theoretical studies support the understanding that neuronal circuits are intrinsically capable of generating different time intervals, the dynamical origin of the phenomenon of functionally dependent timing control is still unclear. Here, we consider a new mechanism that is related to the multi-neuronal cooperative dynamics in inhibitory brain motifs consisting of a few clusters. It is shown that redundancy and diversity of neurons within each cluster enhances the sensitivity of the timing control with the level of neuronal excitation of the whole network. The generality of the mechanism is shown to work on two different neuronal models: a conductance-based model and a map-based model.
Inhibitory Action of Auxin on Root Elongation Not Mediated by Ethylene
Eliasson, Lennart; Bertell, Gertrud; Bolander, Eva
The inhibitory effects of indole-3-acetic acid (IAA) and 1-aminocyclopropane-1-carboxylic acid (ACC) on elongation growth of pea (Pisum sativum L.) seedling roots were investigated in relation to the effects of these compounds on ethylene production by the root tips. When added to the growth solution both compounds caused a progressively increasing inhibition of growth within the concentration range of 0.01 to 1 micromolar. However, only ACC increased ethylene production in root tips excised from the treated seedlings after 24 hours. High auxin concentrations caused a transitory increase of ethylene production during a few hours in the beginning of the treatment period, but even in 1 micromolar IAA this increase was too low to have any appreciable effect on growth. ACC, but not IAA, caused growth curvatures, typical of ethylene treatment, in the root tips. IAA caused conspicuous swelling of the root tips while ACC did not. Cobalt and silver ions reversed the growth inhibitory effects induced by ACC but did not counteract the inhibition of elongation or swelling caused by IAA. The growth effects caused by the ACC treatments were obviously due to ethylene production. We found no evidence to indicate that the growth inhibition or swelling caused by IAA is mediated by ethylene. It is concluded that the inhibitory action of IAA on root growth is caused by this auxin per se. PMID:16667017
Screening of traditional European herbal medicines for acetylcholinesterase and butyrylcholinesterase inhibitory activity.
Wszelaki, Natalia; Kuciun, Agnieszka; Kiss, Anna Karolina
Acetylcholinesterase (AChE) inhibitors are widely used for the symptomatic treatment of Alzheimer's disease (AD) to enhance central cholinergic transmission. On the other hand, butyrylcholinesterase (BuChE) inhibitors were reported to produce a significant increase in brain extracellular AChE without triggering severe peripheral or central side effects. In the present study, we selected twelve plants used in traditional European medicine to treat different central nervous system (CNS) disorders or to improve memory. Methanolic and hexane extracts of these plants were tested for the AChE and BuChE inhibitory activity using Ellman's colorimetric method. The most potent AChE and BuChE inhibition was observed in the hexane extracts of the flowers of Arnica chamissonis Less. subs. foliosa and Ruta graveolens L. herb at a concentration of 400 microg mL(-1). However, methanolic extracts of the flowers of Arnica chamissonis Less. subs. foliosa and the Hypericum perforatum L. herb demonstrated at the same concentration, selective inhibition only against AChE but not against BuChE. The other extracts did not show any significant AChE or BuChE inhibitory activity. Our results show that further investigations of the extracts of arnica, rue and St. John's Wort are needed to identity the compounds responsible for the AChE and BuChE inhibitory activity. PMID:20228046
Immunological Studies in Acute Myeloid Leukaemia: PHA Responsiveness and Serum Inhibitory Factors
Walker, J. S.; Davis, D.; Davies, P.; Freeman, C. B.; Harris, R.
Sera from 16 of 20 patients with AML at some stage of the disease inhibited the in vitro PHA transformation of normal lymphocytes assessed by measuring the rate of DNA synthesis after 67-70 hours; 42% of pretreatment sera were inhibitory. Inhibitory activity was overcome at PHA concentrations 2-3 times greater than the concentration which allowed maximum discrimination between NHS and leukaemia sera. PHA transformation of washed lymphocytes obtained from AML patients before treatment and when receiving induction or consolidation (cytoreductive) chemotherapy was reduced only when cultures contained a high proportion of primitive cells. Even in primitive cell contaminated cultures significant responses to PHA could be measured if conditions were modified to prevent increasing acidity. Reports of reduced in vitro immunological reactions in pretreatment and poor prognosis patients may therefore be due to the presence of primitive cells in culture, and in treated patients to the failure of chemotherapy to reduce the circulating primitive cell count. Serum inhibitory factors may have a significant immunosuppressive effect in vivo, but the accurate assessment of the role of immune mechanisms in AML should attempt the measurement of specific immunity. PMID:4511988
Macrophage migration inhibitory factor (MIF) in meningococcal septic shock and experimental human endotoxemia.
Sprong, Tom; Pickkers, Peter; Geurts-Moespot, Anneke; van der Ven-Jongekrijg, Johanna; Neeleman, Chris; Knaup, Marlies; Leroy, Didier; Calandra, Thierry; van der Meer, Jos W M; Sweep, Fred; van Deuren, Marcel
Macrophage migration inhibitory factor (MIF) is a mediator of innate immunity and important in the pathogenesis of septic shock. Lipopolysaccharide (LPS) and tumor necrosis factor (TNF) alpha are reported to be inducers of MIF. We studied MIF and cytokines in vivo in patients with meningococcal disease, in human experimental endotoxemia, and in whole blood cultures using a newly developed sensitive and specific enzyme-linked immunosorbent assay. Twenty patients with meningococcal disease were investigated. For the human endotoxemia model, 8 healthy volunteers were intravenously injected with 2 ng/kg Escherichia coli LPS. Whole blood from healthy volunteers was incubated with LPS or heat-killed meningococci. Macrophage migration inhibitory factor concentration in blood was increased during meningococcal disease and highest in the patients presenting with shock compared with patients without shock. Plasma concentration of MIF correlated with disease severity, the presence of shock and with the cytokines interleukin (IL) 1beta, IL-10, IL-12, and vascular endothelial growth factor, but not with TNF-alpha. MIF was not detected in blood in experimental endotoxemia, nor after stimulation of whole blood with LPS or meningococci, although high levels of TNF-alpha were seen in both models. In conclusion, MIF is increased in patients with meningococcal disease and highest in the presence of shock. Macrophage migration inhibitory factor cannot be detected in a human endotoxemia model and is not produced by whole blood cells incubated with LPS or meningococci. PMID:17438452
Epithelial chloride channel. Development of inhibitory ligands
Chloride channels are present in the majority of epithelial cells, where they mediate absorption or secretion of NaCl. Although the absorptive and secretory channels are well characterized in terms of their electrophysiological behavior, there is a lack of pharmacological ligands that can aid us in further functional and eventually molecular characterization. To obtain such ligands, we prepared membrane vesicles from bovine kidney cortex and apical membrane vesicles from trachea and found that they contain a chloride transport process that is electrically conductive. This conductance was reduced by preincubating the vesicles in media containing ATP or ATP-gamma-S, but not beta- methylene ATP, which suggests that the membranes contain a kinase that can close the channels. We then screened compounds derived from three classes: indanyloxyacetic acid (IAA), anthranilic acid (AA), and ethacrynic acid. We identified potent inhibitors from the IAA and the AA series. We tritiated IAA-94 and measured binding of this ligand to the kidney cortex membrane vesicles and found a high-affinity binding site whose dissociation constant (0.6 microM) was similar to the inhibition constant (1 microM). There was a good correlation between the inhibitory potency of several IAA derivatives and their efficacy in displacing [3H]IAA-94 from its binding site. Further, other chloride channel inhibitors, including AA derivatives, ethacrynic acid, bumetanide, and DIDS, also displaced the ligand from its binding site. A similar conductance was found in apical membrane vesicles from bovine trachea that was also inhibited by IAA-94 and AA-130B, but the inhibitory effects of these compounds were weaker than their effects on the renal cortex channel. The two drugs were also less potent in displacing [3H]IAA-94 from the tracheal binding site. PMID:2450168
Approximating Minimum Manhattan Networks (Extended Abstract)
Approximating Minimum Manhattan Networks (Extended Abstract) Joachim Gudmundsson 1 ? , Christos them. A Minimum Manhattan Network on S is a Manhat- tan network of minimum possible length. A Manhattan connecting points in S [S 0 . A Manhattan network can also be thought of as a 1-spanner (for the L1-metric
Approximating Minimum Manhattan Networks (Extended Abstract)
Narasimhan, Giri
Approximating Minimum Manhattan Networks (Extended Abstract) Joachim Gudmundsson 1 ? , Christos, USA Abstract. Given a set S of n points in the plane, we define a Manhattan Network the shortest rectilinear path between them. A Minimum Manhattan Network on S is a Manhattan network of minimum
Hochreiter, Sepp
. In the terminology of the theory of minimum description length (MDL 45, 39]), fewer bits of information are required to describe a at minimum (corresponding to a \\simple" or low complexity-network). The MDL principle suggestsFLAT MINIMUM SEARCH FINDS SIMPLE NETS Technical Report FKI-200-94 Sepp Hochreiter Jurgen
Gambardella, Luca Maria
the probability of detection by enemy radar. In this paper, we focus on the minimum power topology problemMINIMUM POWER SYMMETRIC CONNECTIVITY PROBLEM IN WIRELESS NETWORKS: A NEW APPROACH Roberto preprocessing technique. Keywords: Wireless networks, minimum power topology, exact algorithms. 1. Introduction
Minimum-energy mobile wireless networks revisited
Li Li; J. Y. Halpern
We propose a protocol that, given a communication network, computes a subnetwork such that, for every pair (u, υ) of nodes connected in the original network, there is a a minimum-energy path between u and υ in the subnetwork (where a minimum-energy path is one that allows messages to be transmitted with a minimum use of energy). The network computed
Tyrosinase and 5 a Reductase Inhibitory Components from Artocarpus incisus Tree
Kuniyoshi Shimizu
The inhibitory components on tyrosinase and 5 a reductase from Papua New Guinean (PNG) and Thai woody plants were investigated . First, the inhibitory components of Artocarpus incisus heartwood which showed the strongest inhibitory activity in 23 PNG wood species, their structureactivity relationships and inhibitory mechanism were evaluated. Tyrosinase inhibitory activityguided fractionation led to the isolation of seven active compounds
Inhibitory compound of tyrosinase activity from the sprout of Polygonum hydropiper L. (Benitade).
Miyazawa, Mitsuo; Tamura, Naotaka
A tyrosinase inhibitor was isolated from the sprout of Polygonum hydropiper L. (Benitade) by activity-guided fractionation and identified as (2R,3R)-+-taxifolin (1) by spectroscopic means. Compound 1 inhibited 70% of tyrosinase activity at a concentration of 0.50 mM. ID50 (50% inhibition dose) value of compound 1 was 0.24 mM. As compared with tyrosinase inhibitor known cosmetic agent such as arbutin and kojic acid, compound 1 was more inhibited than the former and showed inhibitory effect equal to that of the latter. To study the inhibitory effect of (2R,3R)-+-taxifolin derivatives against tyrosinase activity, 3,7,3',4'-taxifolin tetraacetate (2) and 5,7,3',4'-taxifolin teramethyl ether (3) were also assayed together with compound 1. PMID:17329865
Residential Mobility, Inhibitory Control, and Academic Achievement in Preschool
ERIC Educational Resources Information Center
Schmitt, Sara A.; Finders, Jennifer K.; McClelland, Megan M.
The present study investigated the direct effects of residential mobility on children's inhibitory control and academic achievement during the preschool year. It also explored fall inhibitory control and academic skills as mediators linking residential mobility and spring achievement. Participants included 359 preschool children (49% female)…
Myelin-associated inhibitory signaling and strategies to overcome inhibition
Nagarathnamma Chaudhry; Marie T Filbin
Numerous studies in the last two decades have resulted in significant progress in our understanding of the role of inhibitors on axonal regeneration and conditions that influence mature neurons to regrow in an inhibitory environment. These studies have revealed putative therapeutic targets and strategies to interfere in the inhibitory signaling cascade and promote axonal regeneration. Some agents that were successful
Neural Mechanisms of Inhibitory Specification in Cognitive and Linguistic Complexity
Don M. Tucker
We theorize that the ability to organize a complex linguistic structure such as a hierarchic clause may depend upon the capacity for what may be called inhibitory specification, in which certain meanings are isolated within working memory, such that they can be sustained and grouped within hierarchic structures. Clues to the neural mechanisms of inhibitory specification can be gained from
Residential Mobility, Inhibitory Control, and Academic Achievement in Preschool
ERIC Educational Resources Information Center
Schmitt, Sara A.; Finders, Jennifer K.; McClelland, Megan M.
Research Findings: The present study investigated the direct effects of residential mobility on children's inhibitory control and academic achievement during the preschool year. It also explored fall inhibitory control and academic skills as mediators linking residential mobility and spring achievement. Participants included 359 preschool…
Glutamate is an inhibitory neurotransmitter in the Drosophila olfactory system
Wilson, Rachel
Glutamate is an inhibitory neurotransmitter in the Drosophila olfactory system Wendy W. Liu acts as an inhibitory neurotransmitter in the antennal lobe, broadly similar to the role of GABA is concen- trated within glomeruli, these neurotransmitters may act on different spatial and temporal scales
Inhibitory Control Predicts Language Switching Performance in Trilingual Speech Production
ERIC Educational Resources Information Center
Linck, Jared A.; Schwieter, John W.; Sunderman, Gretchen
This study investigated the role of domain-general inhibitory control in trilingual speech production. Taking an individual differences approach, we examined the relationship between performance on a non-linguistic measure of inhibitory control (the Simon task) and a multilingual language switching task for a group of fifty-six native English (L1)…
Lipoxygenase Inhibitory Activity of Korean Indigenous Mushroom Extracts and Isolation of an Active Compound from Phellinus baumii.
Lee, Seung Woong; Song, Ja-Gyeong; Hwang, Byung Soon; Kim, Dae-Won; Lee, Yoon-Ju; Woo, E-Eum; Kim, Ji-Yul; Lee, In-Kyoung; Yun, Bong-Sik
We investigated a total of 335 samples of Korean native mushroom extracts as part of our lipoxygenase (LOX) inhibitor screening program. Among the mushroom-methanolic extracts we investigated, 35 exhibited an inhibitory activity greater than 30% against LOX at a concentration of 100 µg/mL. Especially, Collybia maculata, Tylopilus neofelleus, Strobilomyces confusus, Phellinus gilvus, P. linteus, P. baumii, and Inonotus mikadoi exhibited relatively potent LOX inhibitory activities of 73.3%, 51.6%, 52.4%, 66.7%, 59.5%, 100.0%, and 85.2%, respectively. Bioassay-guided fractionation led to the isolation of inoscavin A from the methanolic extract of P. baumii, which showed the most potent activity and was identified by spectroscopic methods. Specifically, inoscavin A exhibited potent LOX inhibitory activity with an IC50 value of 6.8 µM. PMID:25071389
Lipoxygenase Inhibitory Activity of Korean Indigenous Mushroom Extracts and Isolation of an Active Compound from Phellinus baumii
Lee, Seung Woong; Song, Ja-Gyeong; Hwang, Byung Soon; Kim, Dae-Won; Lee, Yoon-Ju; Woo, E-Eum; Kim, Ji-Yul; Lee, In-Kyoung
We investigated a total of 335 samples of Korean native mushroom extracts as part of our lipoxygenase (LOX) inhibitor screening program. Among the mushroom-methanolic extracts we investigated, 35 exhibited an inhibitory activity greater than 30% against LOX at a concentration of 100 µg/mL. Especially, Collybia maculata, Tylopilus neofelleus, Strobilomyces confusus, Phellinus gilvus, P. linteus, P. baumii, and Inonotus mikadoi exhibited relatively potent LOX inhibitory activities of 73.3%, 51.6%, 52.4%, 66.7%, 59.5%, 100.0%, and 85.2%, respectively. Bioassay-guided fractionation led to the isolation of inoscavin A from the methanolic extract of P. baumii, which showed the most potent activity and was identified by spectroscopic methods. Specifically, inoscavin A exhibited potent LOX inhibitory activity with an IC50 value of 6.8 µM. PMID:25071389
Inhibitory processes in visual perception: a bilingual advantage.
Wimmer, Marina C; Marx, Christina
Bilingual inhibitory control advantages are well established. An open question is whether inhibitory superiority also extends to visual perceptual phenomena that involve inhibitory processes. This research used ambiguous figures to assess inhibitory bilingual superiority in 3-, 4-, and 5-year-old mono- and bilingual children (N=141). Findings show that bilinguals across all ages are superior in inhibiting a prevalent interpretation of an ambiguous figure to perceive the alternative interpretation. In contrast, mono- and bilinguals revealed no differences in understanding that an ambiguous figure can have two distinct referents. Together, these results suggest that early bilingual inhibitory control superiority is also evident in visual perception. Bilinguals' conceptual understanding of figure ambiguity is comparable to that of their monolingual peers. PMID:24878102
Variations of tropospheric ozone concentration of Syowa Station, Antarctica
Shohei Murayama; Takakiyo Nakazawa; Masayuki Tanaka; Shuhji Aoki; Sadao Kawaguchi
The paper reports aircraft measurements of the tropospheric O3 concentration made over Syowa Station, Antarctica, from May 1989 to January 1990. The O3 concentration increased with height for the entire period. Lower tropospheric O3 exhibited a prominent seasonal variation with maximum concentration in winter and minimum concentration in summer. In the upper troposphere, the concentration reached high values in winter,
Minimum distance classification in remote sensing
NASA Technical Reports Server (NTRS)
Wacker, A. G.; Landgrebe, D. A.
The utilization of minimum distance classification methods in remote sensing problems, such as crop species identification, is considered. Literature concerning both minimum distance classification problems and distance measures is reviewed. Experimental results are presented for several examples. The objective of these examples is to: (a) compare the sample classification accuracy of a minimum distance classifier, with the vector classification accuracy of a maximum likelihood classifier, and (b) compare the accuracy of a parametric minimum distance classifier with that of a nonparametric one. Results show the minimum distance classifier performance is 5% to 10% better than that of the maximum likelihood classifier. The nonparametric classifier is only slightly better than the parametric version.
Mice lacking the transcriptional coactivator PGC-1? exhibit alterations in inhibitory synaptic transmission in the motor cortex.
Dougherty, S E; Bartley, A F; Lucas, E K; Hablitz, J J; Dobrunz, L E; Cowell, R M
Peroxisome proliferator-activated receptor ? coactivator 1? (PGC-1?) is a transcriptional coactivator known to regulate gene programs in a cell-specific manner in energy-demanding tissues, and its dysfunction has been implicated in numerous neurological and psychiatric disorders. Previous work from the Cowell laboratory indicates that PGC-1? is concentrated in inhibitory interneurons and is required for the expression of the calcium buffer parvalbumin (PV) in the cortex; however, the impact of PGC-1? deficiency on inhibitory neurotransmission in the motor cortex is not known. Here, we show that mice lacking PGC-1? exhibit increased amplitudes and decreased frequency of spontaneous inhibitory postsynaptic currents in layer V pyramidal neurons. Upon repetitive train stimulation at the gamma frequency, decreased GABA release is observed. Furthermore, PV-positive interneurons in PGC-1? -/- mice display reductions in intrinsic excitability and excitatory input without changes in gross interneuron morphology. Taken together, these data show that PGC-1? is required for normal inhibitory neurotransmission and cortical PV-positive interneuron function. Given the pronounced motor dysfunction in PGC-1? -/- mice and the essential role of PV-positive interneurons in maintenance of cortical excitatory:inhibitory balance, it is possible that deficiencies in PGC-1? expression could contribute to cortical hyperexcitability and motor abnormalities in multiple neurological disorders. PMID:24769433
Interpreting 10Be changes during the Maunder Minimum
Christy V. Field; Gavin A. Schmidt; Drew T. Shindell
Beryllium-10 archives are important resources for understanding how solar activity may have varied in the past. Climate simulations using the Goddard Institute for Space Studies ModelE general circulation model are used to calibrate the impacts of production changes, solar forcings, and volcanic aerosol forcing on 10Be concentration during periods such as the Maunder Minimum (1645–1715 A.D.). We find that for
Inhibitory effects of ?-ionone on amyloid fibril formation of ?-lactoglobulin.
Ma, Baoliang; You, Xiong; Lu, Fujiao
?-Lactoglobulin (?-LG) is the major constituent of whey food, which has been shown to interact with a wide range of aroma compounds. In the present work, a model aroma compound, ?-ionone, is used to investigate the influence of aroma compounds on the urea-induced unfolding of ?-LG at pH 7.0. ?-Ionone is observed to enhance the stability of ?-LG at pH 7.0. Moreover, the amyloid fibrils are observed when ?-LG at pH 7.0 is incubated for 12-20 days at 37 °C in the presence of 3-5M urea. However, the formation of amyloid fibrils is inhibited when ?-ionone is added into the samples and the inhibitory effects follow a concentration-dependent fashion. There is a clear correlation between Cm and lag time. The correlation demonstrates that protein stability affects the amyloid fibril formation of ?-LG. The results highlight the critical role of protein stability and provide an approach to prevent the formation of amyloid fibrils in vitro. PMID:24325860
Inhibitory Effect of Resveratrol against Duck Enteritis Virus In Vitro
Cheng, Anchun; Jia, Renyong; Song, Xu; Lu, Hongke; Dai, Shujun; Lv, Cheng; Liang, Xiaoxia; He, Changliang; Zhao, Ling; Su, Gang; Ye, Gang; Shi, Fei
Duck viral enteritis (DVE) is an acute, contagious herpesvirus infection of ducks, geese, and swans of all ages and species. This disease has been responsible for significant economic losses in domestic and wild waterfowl as a result of mortality, and decreased egg production. Resveratrol is a naturally occurring phytoalexin in specific plants and exhibits inhibitory activity against many kinds of virus. In this paper, resveratrol was found to inhibit duck enteritis virus (DEV) replication in a dose-dependent manner, with a 50% inhibition concentration of 3.85 ?g/mL. The inhibition in virus multiplication in the presence of resveratrol was not attributed to direct inactivation or inhibition of virus attachment to the host cells, but to the inhibition of viral multiplication in host cells. The assay of the time of addition limited the drug effect during the first 8 h of infection. This conclusion was supported by the ultrastructure images of the early stage of DEV infection, which showed that the replication of virus nucleic acid and the formation of the capsid in the cell nucleus were suppressed. In the indirect immunofluorescence assay, proteins expression in DEV infected duck embryo fibroblasts (DEFs) within 24 h post-infection (p.i.) was also effectively suppressed by resveratrol. In summary, the resveratrol has a good activity against DEV infection in vitro, which could be attributed to that fact that several essential immediate early viral proteins for virus replication were impacted by resveratrol. PMID:23776451
Intracellular activity of clinical concentrations of phenothiazines including thioridiazine against phagocytosed Staphylococcus aureus.
Ordway, Diane; Viveiros, Miguel; Leandro, Clara; Arroz, Maria Jorge; Amaral, Leonard
The effect of thioridazine (TZ) was studied on the killing activity of human peripheral blood monocyte derived macrophages (HPBMDM) and of human macrophage cell line THP-1 at extracellular concentrations below those achievable clinically. These macrophages have nominal killing activity against bacteria and therefore, would not influence any activity that the compounds may have against intracellular localised Staphylococcus aureus. The results indicated that whereas TZ has an in vitro minimum inhibitory concentration (MIC) against the strains of S. aureus of 18, 0.1 mg/l of TZ in the medium completely inhibits the growth of S. aureus that has been phagocytosed by macrophages. The latter concentration was non-toxic to macrophages, did not cause cellular expression of activation marker CD69 nor induction of CD3+ T cell production of IFN-gamma, but blocked cellular proliferation and down-regulated the production of T cell-derived cytokines (IFN-gamma, IL-5). These results suggest that TZ induces intracellular bactericidal activities independent of the capacity to generate Type 1 responses against S. aureus. PMID:12127709
Design of rat renin inhibitory peptides.
Hui, K Y; Holtzman, E J; Quinones, M A; Hollenberg, N K; Haber, E
Because several well-studied strains of rats manifest spontaneous hypertension, we set out to design a renin inhibitor suitable for use in this species. On the basis of the sequence of the renin substrate, a series of substrate analogue inhibitory peptides were synthesized by systematically modifying the P5, P3, P2, P1P1', P2', P3', and P4' positions. In assays against rat plasma renin, we found that modifications at the C-terminal segment have a marked influence on potency, and that a secondary butyl side chain at the P2' position is important for obtaining optimal activity. The structure at the P3' position, however, could vary considerably without significant effect. The steric effect of the P2 position was important; there an isopropyl side chain provided optimal binding between the inhibitor and the enzyme. At the P3 and P5 positions, potency appeared to depend on aromatic side chains. The effects at the P1P1' position of the transition-state residue (3S,4S)-4-amino-3-hydroxy -6-methylheptanoic acid (statine) and its congeners (3S,4S)-4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA) and (3S,4S)-4-amino-3-hydroxy-5-cyclohexylpentanoic acid (ACHPA) were found to depend on the sequence of the C-terminal segment. For peptides with an unfavorable C-terminal segment (-Ile-Phe-NH2), AHPPA and ACHPA resulted in a surprising retention of potency. For peptides with a favorable C-terminal segment (-Leu-Phe-NH2), the effect of AHPPA was mild, even though ACHPA still significantly enhanced potency. The hypotensive and plasma renin inhibitory effects of three of the analogues were then studied in anesthetized sodium-depleted rats. One of the compounds, acetyl-His-Pro-Phe-Val-Statine-Leu-Phe-NH2 (IC50 against rat plasma renin of 30 nM at pH 7.4), proved to be a potent hypotensive agent and a potentially useful probe for the study of the renin-angiotensin system in rats. PMID:3045320
Antioxidant Activities and Tyrosinase Inhibitory Effects of Different Extracts from Pleurotus ostreatus Fruiting Bodies
Alam, Nuhu; Yoon, Ki Nam; Lee, Kyung Rim; Shin, Pyung Gyun; Cheong, Jong Chun; Yoo, Young Bok; Shim, Ja Mi; Lee, Min Woong; Lee, U Youn
We evaluated the antioxidant activity and tyrosinase inhibitory effects of Pleurotus ostreatus fruiting bodies extracted with acetone, methanol, and hot water. The antioxidant activities were tested against ?-carotene-linoleic acid, reducing power, 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity, and ferrous chelating ability. Furthermore, phenolic acid and flavonoid contents were also analyzed. The methanol extract showed the strongest ?-carotene-linoleic acid inhibition as compared to the other exracts. The acetone extract (8 mg/mL) showed a significantly high reducing power of 1.54 than the other extracts. The acetone extract was more effective than other extracts for scavenging on 1,1-diphenyl-2-picrylhydrazyl radicals. The strongest chelating effect (85.66%) was obtained from the acetone extract at 1.0 mg/mL. The antioxidant activities of the extracts from the P. ostreatus fruiting bodies increased with increasing concentration. A high performance liquid chromatography analysis detected seven phenolic compounds, including gallic acid, protocatechuic acid, chlorogenic acid, naringenin, hesperetin, formononetin, and biochanin-A in an acetonitrile and 0.1 N hydrochloric acid (5 : 1) solvent extract. The total phenolic compound concentration was 188 µg/g. Tyrosinase inhibition of the acetone, methanol, and hot water P. ostreatus extracts increased with increasing concentration. The results revealed that the methanol extract had good tyrosinase inhibitory ability, whereas the acetone and hot water extracts showed moderate activity at the concentrations tested. The results suggested that P. ostreatus may have potential as a natural antioxidant. PMID:23956669
Additivity and synergy between an antimicrobial peptide and inhibitory ions.
Walkenhorst, William F; Sundrud, Justine N; Laviolette, Joshua M
Recently we described the pH dependence of activity for a family of cationic antimicrobial peptides (CAMPs) selected from a combinatorial library. In the current work we report on the effects of toxic ions (Cu(2+), Zn(2+), and F(-)) and the chelator EDTA on the activity profiles of one member of this family, the 12-residue cationic antimicrobial peptide *ARVA, against a panel of microorganisms. All four ions exhibited either synergy or additivity with *ARVA for all organisms tested with the exception of *ARVA combined with NaF against Candida albicans which exhibited indifference. CuCl2 and ZnCl2 exhibited synergy with *ARVA against both the Gram negative Pseudomonas aeruginosa and the Gram positive Staphylococcus aureus as well as strong additivity against Escherichia coli at submillimolar concentrations. The chelator EDTA was synergistic with *ARVA against the two Gram negative organisms but showed only simple additivity with S. aureus and C. albicans despite their much lower MICs with EDTA. This effect may be related to the known differences in the divalent ion binding properties of the Gram negative LPS layer as compared to the peptidoglycan layer of the Gram positive organism. Unlike the other ions, NaF showed only additivity or indifference when combined with *ARVA and required much higher concentrations for activity. The yeast C. albicans did not show synergy or strong additivity with any of the inhibitory compounds tested. The effects of toxic ions and chelators observed here have important implications for applications using CAMPs and for the design of novel formulations involving CAMPs. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova. PMID:24841756
The direct relationship between inhibitory currents and local field potentials.
Trevelyan, Andrew J
The frequency profiles of various extracellular field oscillations are known to reflect functional brain states, yet we lack detailed explanations of how these brain oscillations arise. Of particular clinical relevance are the high-frequency oscillations (HFOs) associated with interictal events and the onset of seizures. These time periods are also when pyramidal firing appears to be vetoed by high-frequency volleys of inhibitory synaptic currents, thereby providing an inhibitory restraint that opposes epileptiform spread (Trevelyan et al., 2006, 2007). The pattern and timing of this inhibitory volley is suggestive of a causal relationship between the restraint and HFOs. I show that at these times, isolated inhibitory currents from single pyramidal cells have a similarity to the extracellular signal that significantly exceeds chance. The ability to extrapolate from discrete currents in single cells to the extracellular signal arises because these inhibitory currents are synchronized in local populations of pyramidal cells. The visibility of these inhibitory currents in the field recordings is greatest when local pyramidal activity is suppressed: the correlation between the inhibitory currents and the field signal becomes worse when local activity increases, suggestive of a switch from one source of HFO to another as the restraint starts to fail. This association suggests that a significant component of HFOs reflects the last act of defiance in the face of an advancing ictal event. PMID:19955382
Xanthine oxidase inhibitory lanostanoids from Ganoderma tsugae.
Lin, Kai-Wei; Chen, Yen-Ting; Yang, Shyh-Chyun; Wei, Bai-Luh; Hung, Chi-Feng; Lin, Chun-Nan
Two new lanostanoids, 3?-acetoxy-22-oxo-5?-lanosta-8,24-dien-21-oic acid, named tsugaric acid D (1) and 16?-hydroxy-3-oxo-5?-lanosta-6,8,24(24(1))-trien-21-oic acid, named tsugaric acid E (2) were isolated from the fruit bodies of Ganoderma tsugae. The structures 1 and 2 were determined by spectroscopic methods. Compound 1 and known compounds 3 and 6 exhibited significant inhibitory effects on xanthine oxidase (XO) activity with an IC50 values of 90.2±24.2, 116.1±3.0, and 181.9±5.8 ?M, respectively. Known compound 5 was able to protect human keratinocytes against damage induced by UVB light, which showed 5 could protect keratinocytes from photodamage. The 1 and 5 ?M 1 combined with 5 ?M cisplatin, respectively, enhanced the cytotoxicity induced by cisplatin. It suggested that 1 and 5 ?M 1 combined with low dose of cisplatin may enhance the therapeutic efficacy of cisplatin and reduce side effect and cisplatin resistant. PMID:23769935
Pancreatic lipase inhibitory stilbenoids from the roots of Vitis vinifera.
Kim, Young-Mog; Lee, Eun-Woo; Eom, Sung-Hwan; Kim, Tae Hoon
Bioassay-guided isolation of an aqueous methanolic extract of Vitis vinifera using pancreatic lipase inhibitory activity led to isolation of seven stilbenoids, wilsonol C (1), heyneanol A (2), ampelopsin A (3), pallidol A (4), cis-piceid (5), trans-piceid (6) and trans-resveratrol (7). The structures were established on the basis of NMR and MS spectroscopic data interpretation. All isolates were evaluated for their inhibitory effects on pancreatic lipase, and stilbenoid 1 exhibited potent inhibitory effect on pancreatic lipase with IC?? values of 6.7?±?0.7?µM. PMID:24020412
NSDL National Science Digital Library
AMPS GK-12 Program,
Students quantify the percent of light reflected from solutions containing varying concentrations of red dye using LEGO© MINDSTORMS© NXT bricks and light sensors. They begin by analyzing a set of standard solutions with known concentrations of food coloring, and plot data to graphically determine the relationship between percent reflected light and dye concentration. Then they identify dye concentrations for two unknown solution samples based on how much light they reflect. Students gain an understanding of light scattering applications and how to determine properties of unknown samples based on a set of standard samples.
Antioxidant and lipase inhibitory activities and essential oil composition of pomegranate peel extracts.
Hadrich, Fatma; Cher, Slim; Gargouri, Youssef Talel; Adel, Sayari
The chemical composition of essential oil, antioxidant and pancreatic lipase inhibitory activities of various solvent extracts obtained from pomegranate peelTunisian cultivar was evaluated. Gas chromatography/mass spectrometry was used to determine the composition of the PP essential oil. Nine-teen components were identified and the main compounds were the camphor (60.32%) and the benzaldehyde (20.98%). The phenolic and flavonoids content varied from 0 to 290.10 mg Gallic acid equivalent and from 5.2 to 20.43 mg catechin equivalent/g dried extract. The antioxidant activity of various solvent extracts from pomegranate peel was also investigated using various in vitro assays as the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical method, ?-carotene bleaching and reducing power assays.Methanol and ethanol extracts showed the most potent antioxidant activity in all assays tested followed by water and acetone extracts. The inhibitory effect of the pomegranate peelextracts on porcine pancreatic lipase was evaluated and the results showed that ethanol and methanol extracts markedly reduced lipase activity. Generally, the highestlipase activity inhibitory (100%) was observed at a concentration of 1 mg/ml after 30 min of incubation. LC-MS analysis of ethanol extract showed the presence of four components which are cholorogenic acid, mannogalloylhexoside, gallic acid and ellagic acid. Our findings demonstrate that the ethanol extract from pomegranate peel might be a good candidate for furtherinvestigations of new bioactive substances. PMID:24770478
Inhibitory effect of the plant flavonoid galangin on rat vas deferens in vitro.
Capasso, Raffaele; Mascolo, Nicola
Flavonoids are phenolic compounds that are widely distributed in higher plants and therefore are ingested by humans and animals with their regular foods, but also have various pharmacological properties. In the present study we have investigated the effect of galangin, a member of the flavonol class, on the contractile response elicited by electrical field stimulation (EFS) in the rat isolated vas deferens. Galangin (10(-8)-3 x 10(-4) M) produced a concentration- dependent inhibition of the EFS-evoked contractile response, with only a minimal inhibitory effect on phenylephrine-induced contractions. The inhibitory effect of galangin was unaffected by atropine (10(-6) M) plus hexamethonium (10(-4) M), a combination of the NK(1) receptor antagonist SR 140333 (10(-7) M), the NK(2) receptor antagonist SR 48968 (10(-6) M) and the NK(3) receptor antagonist SR 142801 (10(-7) M), L-NAME (3 x 10(-4) M), naloxone (10(-6) M) or yohimbine (10(-7) M). However, the vanilloid receptor antagonist capsazepine (10(-5) M) significantly reduced the inhibitory effect of galangin. It is concluded that the galangin inhibits excitatory transmission of the rat vas deferens with a mechanism involving, at least in part, vanilloid receptors. PMID:12706486
An inhibitory effect of isoprenaline on stimulation-induced noradrenaline release from rat atria.
Mian, M A; Majewski, H; Rand, M J
Isoprenaline (0.1 microM), in the presence of phentolamine (1 microM) to block autoinhibitory alpha-adrenoceptors, significantly increased the efflux of radioactivity produced by field stimulation (2 Hz for 60 s) from rat isolated atria in which the noradrenergic transmitter stores had been labelled with [3H]noradrenaline. This facilitatory effect of isoprenaline on noradrenergic transmission was not affected by the selective beta 1-adrenoceptor antagonist CGP 20712A (0.3 microM). However, the selective beta 2-adrenoceptor antagonist ICI 118551 (0.1 microM) not only abolished the facilitatory effect of isoprenaline but reversed it to an inhibitory effect, indicating that the prejunctional beta-adrenoceptors subserving facilitation of noradrenergic transmission in rat atria are of the beta 2-subtype. The inhibitory effect of isoprenaline that was revealed by blockade of beta 2-adrenoceptors was abolished by atenolol (3 microM) in a concentration which markedly reduced the effect of isoprenaline on the rate of atrial beating. This finding suggests that activation of beta 1-adrenoceptors on atrial myocytes by isoprenaline may have resulted in release of one or more substance(s) which inhibited stimulation-induced release of noradrenaline, presumably by activating prejunctional receptors. The inhibitory effect of isoprenaline on noradrenergic transmission was not affected by the prostaglandin synthesis inhibitor indomethacin (10 microM) suggesting that prostaglandins were not involved. PMID:1354162
Evaluation of 5?-reductase inhibitory activity of certain herbs useful as antiandrogens.
Nahata, A; Dixit, V K
This study demonstrates 5?-reductase inhibitory activity of certain herbs useful in the management of androgenic disorders. Ganoderma lucidum (Curtis) P. Karst (GL), Urtica dioica Linn. (UD), Caesalpinia bonducella Fleming. (CB), Tribulus terrestris Linn. (TT), Pedalium murex Linn. (PM), Sphaeranthus indicus Linn. (SI), Cuscuta reflexa Roxb. (CR), Citrullus colocynthis Schrad. (CC), Benincasa hispida Cogn. (BH), Phyllanthus niruri Linn. (PN) and Echinops echinatus Linn. (EE) were included in the study. Petroleum ether, ethanol and aqueous extracts of these herbs were tested for their 5?-reductase inhibitory activity against the standard 5?-reductase inhibitor, finasteride. A biochemical method to determine the activity of 5?-reductase was used to evaluate the inhibition of different extracts to the enzyme. The optical density (OD) value of each sample was measured continuously with ultraviolet spectrophotometer for the reason that the substrate NADPH has a specific absorbance at 340 nm. As the enzyme 5?-reductase uses NADPH as a substrate, so in the presence of 5?-reductase inhibitor, the NADPH concentration will increase with the function of time. This method thus implicates the activity of 5?-reductase. The method proved to be extremely useful to screen the herbs for their 5?-reductase inhibitory potential. GL, UD, BH, SI and CR came out to be promising candidates for further exploring their antiandrogenic properties. PMID:23710567
Melanogenesis-Inhibitory Activity and Cancer Chemopreventive Effect of Glucosylcucurbic Acid from Shea (Vitellaria paradoxa) Kernels.
Zhang, Jie; Kurita, Masahiro; Ebina, Kodai; Ukiya, Motohiko; Tokuda, Harukuni; Yasukawa, Ken; Masters, Eliot T; Shimizu, Naoto; Akihisa, Momoko; Feng, Feng; Akihisa, Toshihiro
Two jasmonate derivatives, glucosylcucurbic acid (1) and methyl glucosylcucurbate (2), were isolated from the MeOH extract of defatted shea (Vitellaria paradoxa; Sapotaceae) kernels. These and their deglucosylated derivatives, cucurbic acid (3) and methyl cucurbate (4), were evaluated for their melanogenesis-inhibitory and cancer chemopreventive potencies. Compounds 1, 3, and 4 exhibited potent melanogenesis-inhibitory activities in ?-melanocyte-stimulating hormone (?-MSH)-stimulated B16 melanoma cells. Western-blot analysis revealed that compounds 1 and 3 reduced the protein levels of MITF (=microphthalmia-associated transcription factor), tyrosinase, TRP-1 (=tyrosine-related protein 1), and TRP-2 mostly in a concentration-dependent manner. In addition, compound 1 exhibited inhibitory effects against Epstein?Barr virus early antigen (EBV-EA) activation induced with 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, against TPA-induced inflammation in mice, and against skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as promoter. PMID:25879500
NASA Astrophysics Data System (ADS)
Showstack, Randy
The extent of Arctic sea ice dropped to 3.41 million square kilometers on 16 September, 760,000 square kilometers below the minimum ice extent in 2007, which had been the low mark since the satellite record began in 1979, the National Snow and Ice Data Center (NSIDC) announced. Overall ice extent is 50% below where it was in the 1970s, NSIDC research scientist Walt Meier said during a 19 September briefing. He added that there is also a decrease in ice thickness. Meier said that sea ice varies from year to year with lots of ups and downs. "We wouldn't expect it to keep going down, straight off the map so to speak," he said. "Typically after a record low, we've seen it rebound." Meier added that the general long-term trend is for the Arctic to continue to become generally ice free. He said it is difficult to know how long it will take for that condition to be reached; because of strong variations, Arctic sea ice extent could plateau for some time.
Effects of clozapine and N-desmethylclozapine on synaptic transmission at hippocampal inhibitory and excitatory synapses.
Ohno-Shosaku, Takako; Sugawara, Yuto; Muranishi, Chiho; Nagasawa, Keisuke; Kubono, Kozue; Aoki, Nami; Taguchi, Mitsuki; Echigo, Ryousuke; Sugimoto, Naotoshi; Kikuchi, Yui; Watanabe, Ryoko; Yoneda, Mitsugu
Clozapine is the first atypical antipsychotic, and improves positive and negative symptoms of many patients with schizophrenia resistant to treatment with other antipsychotic agents. Clozapine induces minimal extrapyramidal side effects, but is more often associated with seizures. A large number of studies have been conducted to elucidate pharmacological profiles of clozapine and its major active metabolite, N-desmethylclozapine (NDMC). However, there are only a limited number of electrophysiological studies examining their effects on synaptic transmission. In this study, we examined effects of clozapine and NDMC on synaptic transmission by measuring inhibitory and excitatory postsynaptic currents in rat cultured hippocampal neurons. We found that clozapine and NDMC have qualitatively similar actions. They depressed the inhibitory transmission at 1-30 ?M, and the excitatory transmission at 30 ?M, the former being much more sensitive. The depression of IPSCs by 30 ?M of these drugs was associated with an increase in the paired-pulse ratio. The GABA-induced currents were suppressed by these drugs, but less sensitive than IPSCs. The AMPA-induced currents were slightly potentiated by these drugs at 30 ?M. At 30 ?M, clozapine and NDMC slightly suppressed Ca(2+) and Na(+) channels. These results strongly suggest that clozapine and NMDC depress the inhibitory synaptic transmission mainly by antagonizing postsynaptic GABA(A) receptors, but at higher concentrations additionally by acting on presynaptic site, possibly in part through inhibition of presynaptic Ca(2+) and Na(+) channels. Preferential depression of inhibitory synaptic transmission by clozapine and NDMC might contribute to therapeutic actions and/or side-effects of clozapine. PMID:21945084
Inhibitory action of novel hydrogen sulfide donors on bovine isolated posterior ciliary arteries.
Kulkarni-Chitnis, Madhura; Njie-Mbye, Ya Fatou; Mitchell, Leah; Robinson, Jenaye; Whiteman, Matthew; Wood, Mark E; Opere, Catherine A; Ohia, Sunny E
In the present study, we investigate the inhibitory effect of novel H2S donors, AP67 and AP72 on isolated bovine posterior ciliary arteries (PCAs) under conditions of tone induced by an adrenoceptor agonist. Furthermore, we examined the possible mechanisms underlying the AP67- and AP72-induced relaxations. Isolated bovine PCA were set up for measurement of isometric tension in organ baths containing oxygenated Krebs solution. The relaxant action of H2S donors was studied on phenylephrine-induced tone in the absence or presence of enzyme inhibitors for the following pathways: cyclooxygenase (COX); H2S; nitric oxide and the ATP-sensitive K(+) (KATP) channel. The H2S donors, NaSH (1 nM - 10 ?M), AP67 (1 nM - 10 ?M) and AP72 (10 nM - 1 ?M) elicited a concentration-dependent relaxation of phenylephrine-induced tone in isolated bovine PCA. While the COX inhibitor, flurbiprofen (3 ?M) blocked significantly (p < 0.05) the inhibitory response elicited by AP67, it had no effect on relaxations induced by NaSH and AP72. Both aminooxyacetic acid (30 ?M) and propargylglycine (1 mM), enzyme inhibitors of H2S biosynthesis caused significant (p < 0.05) rightward shifts in the concentration-response curve to AP67 and AP72. Furthermore, the KATP channel antagonist, glibenclamide (300 ?M) and the NO synthase inhibitor, l-NAME (100 ?M) significantly attenuated (p < 0.05) the relaxation effect induced by AP67 and AP72 on PCA. We conclude that H2S donors can relax pre-contracted isolated bovine PCA, an effect dependent on endogenous production of H2S. The inhibitory action of only AP67 on pre-contracted PCA may involve the production of inhibitory endogenous prostanoids. Furthermore, the observed inhibitory action of H2S donors on PCA may depend on the endogenous biosynthesis of NO and by an action of KATP channels. PMID:25845295
Birth Control Vaccine Targeting Leukemia Inhibitory Factor
SUMMARY The population explosion and unintended pregnancies resulting in elective abortions continue to impose major public health issues. This calls for a better method of contraception. Immunocontraception has been proposed as a valuable alternative that can fulfill most, if not all, of the properties of an ideal contraceptive. There are several targets that are being explored for contraceptive vaccine development. Leukemia inhibitory factor (LIF), a member of interleukin-6 family, is required for embryo development and successful blastocyst implantation in several mammalian species. The present study was conducted to examine if LIF can be a target for the development of a birth control vaccine. Three sequences from LIF and two sequences from LIF-receptor (LIF-R) that span the regions involved in ligand-receptor binding were delineated, and peptides were synthesized based upon these sequences. Antibodies raised against these five peptides reduced LIF bioactivity in the in vitro culture assay using BA/F3 mLIF-R-mpg130 cells. Vaccines were prepared by conjugating these peptides to various carrier proteins. Immunization of female mice with these peptide vaccines induced a long-lasting, circulating as well as local antibody response in various parts of the genital tract, and resulted in a significant (p?0.05) inhibition in fertility in all the three trials; the LIF-R peptide vaccines proved to be a better vaccine target. The data indicate that LIF/LIF-R is an excellent target for the development of a birth control vaccine. This is the first study, to our knowledge, that examined LIF/LIF-R as a target for immunocontraception. The findings of this study can be easily translated to humans since LIF/LIF-R is also important for implantation and pregnancy in women. PMID:22139866
Inhibitory Receptors Beyond T Cell Exhaustion
Fuertes Marraco, Silvia A.; Neubert, Natalie J.; Verdeil, Grégory; Speiser, Daniel E.
Inhibitory receptors (iRs) are frequently associated with "T cell exhaustion". However, the expression of iRs is also dependent on T cell differentiation and activation. Therapeutic blockade of various iRs, also referred to as "checkpoint blockade", is showing unprecedented results in the treatment of cancer patients. Consequently, the clinical potential in this field is broad, calling for increased research efforts and rapid refinements in the understanding of iR function. In this review, we provide an overview on the significance of iR expression for the interpretation of T cell functionality. We summarize how iRs have been strongly associated with "T cell exhaustion" and illustrate the parallel evidence on the importance of T cell differentiation and activation for the expression of iRs. The differentiation subsets of CD8 T cells (naďve, effector, and memory cells) show broad and inherent differences in iR expression, while activation leads to strong upregulation of iRs. Therefore, changes in iR expression during an immune response are often concomitant with T cell differentiation and activation. Sustained expression of iRs in chronic infection and in the tumor microenvironment likely reflects a specialized T cell differentiation. In these situations of prolonged antigen exposure and chronic inflammation, T cells are "downtuned" in order to limit tissue damage. Furthermore, we review the novel "checkpoint blockade" treatments and the potential of iRs as biomarkers. Finally, we provide recommendations for the immune monitoring of patients to interpret iR expression data combined with parameters of activation and differentiation of T cells.
Destexhe, Alain
INHIBITORY CONTROL OF SOMATODENDRITIC INTERACTIONS UNDERLYING ACTION POTENTIALS IN NEOCORTICALThe effect of synaptic inputs on somatodendritic interactions during action potentials was investigated synaptic inputs to different somatodendritic regions. Relative to action potentials evoked by current
(?)Loliolide and Other Germination Inhibitory Active Constituents in Equisetum Arvense
Yoshikazu Hiraga; Kazuya Taino; Masashi Kurokawa; Ryukichi Takagi; Katsuo Ohkata
(-)-Loliolide (1) showing an inhibitory activity for lettuce seed germination was isolated from leaves of Equisetum arvense. It is rare that this active compound occurred from the family Equisetaceae.
Inhibitory Receptors on Lymphocytes: Insights from Infections1
Odorizzi, Pamela; Wherry, E. John
Co-stimulatory and inhibitory receptors are critical regulators of adaptive immune cell function. These pathways regulate the initiation and termination of effective immune responses to infections while limiting autoimmunity and/or immunopathology. This review focuses on recent advances in our understanding of inhibitory receptor pathways and their roles in different diseases and/or infections, emphasizing potential clinical applications and important unanswered mechanistic questions. While significant progress has been made in defining the influence of inhibitory receptors at the cellular level, relatively little is known about the underlying molecular pathways. We will discuss our current understanding of the molecular mechanisms for key inhibitory receptor pathways, highlight major gaps in knowledge and explore current and future clinical applications. PMID:22442493
Centrifugal inhibitory processes affecting neurones in the cat cochlear nucleus
Comis, S. D.
1. Stimulation of the lateral part of the olivary S-segment in the cat inhibited neurones in the ipsilateral cochlear nucleus. A smaller number of neurones located in the ventral division of the cochlear nucleus were excited. 2. It is suggested that inhibition in the ipsilateral cochlear nucleus may be mediated directly by fibres making synaptic connexions on the cochlear nucleus neurones, or indirectly by inhibitory fibres acting at the cochlea. 3. The direct inhibitory process at the cochlear nucleus is unaffected by strychnine, whereas the inhibitory process at the cochlea is abolished by strychnine. 4. A cochlear nucleus neurone can be influenced simultaneously by excitatory and inhibitory processes. ImagesFig. 1 PMID:5499823
12 CFR 3.6 - Minimum capital ratios.
Code of Federal Regulations, 2010 CFR
... 2010-01-01 false Minimum capital ratios. 3.6 Section 3.6 Banks and Banking...DEPARTMENT OF THE TREASURY MINIMUM CAPITAL RATIOS; ISSUANCE OF DIRECTIVES Minimum Capital Ratios § 3.6 Minimum capital ratios....
Evaluation of antioxidant and xanthine oxidase inhibitory activity of different solvent extracts of leaves of Citrullus colocynthis
Nessa, Fazilatun; Khan, Saeed A.
Background: Citrullus colocynthis is a folk medicinal plan of United Arab Emirates. Several studies on this plant reported and focused on the biological and toxicological profile of fruits pulp. The present study focused on the antioxidant potency of leaf extract of this plant. Aim: To evaluate the antioxidant and xanthine oxidase (XO) inhibitory activities of C. colocynthis by chemical method. Materials and Methods: Four different solvent extracts (methanol-CCM, methanol: water (1:1)-CCMW, chloroform-CCC and hexane-CCH) of leaves of C. colocynthis were investigated for their free radical scavenging activity using DPPH radical as a substrate, lipid peroxidation (LPO) inhibitory activity using a model system consisting of ?-carotene-linoleic acid, superoxide radical scavenging activity (enzymatically/nonenzymatically) and XO inhibitory activity. A dose response curve was plotted for determining SC50 and IC50 values for expressing the results of free radical scavenging activity and XO inhibitory activities respectively. Results: The high polyphenolic content of CCM and CCMW extract showed highest antioxidant activity irrespective the method used for this investigation. The overall results decreased in the order of: CCM > CCMW > CCC > CCH. CCH extract was inactive towards chemically generated superoxide radical and poor DPPH radical scavengers. The results of LPO inhibitory activities of leaves extract (0.1, 0.5 and 1.0 mg/mL) also decreased in the order of: CCM > CCMW > CCC > CCH. Overall 1.0 mg/mL leaves extract showed highest antioxidant potency amongst the studied concentration. Conclusion: CCMW and CCM extract of C. colocynthis exhibited promising antioxidants and XO inhibitory activities. PMID:25002802
Inhibitory effects of plant extracts on tyrosinase, L-DOPA oxidation, and melanin synthesis.
Hwang, Jung-Hee; Lee, Byung Mu
For medical, pharmacological, and cosmetic reasons, the demand for effective and safe depigmentating agents has increased. In this study, 101 plant extracts (methanol or water extracts) were screened for their inhibitory activities against tyrosinase, (L-3, 4,-dihydroxyphenylalanine) L-DOPA oxidation, and melanin biosynthesis in B16 mouse melanoma cells. Of the extracts examined, 31 showed over 50% inhibition of mushroom tyrosinase at a concentration of 666 microg/Ml, and 11 inhibited L-DOPA auto-oxidation at this concentration. In particular, extracts of Broussonetia kazinoki var. humilis (leaves and stems), Broussonetia papyrifera (leaves and bark), Cornus officinalis (fruit), Rhus javanica (gallnut), and Pinus densiflora (leaves) inhibited both tyrosinase activity and L-DOPA oxidation in a concentration-dependent manner. Seventeen plant extracts that inhibited tyrosinase were further tested for their inhibitory effects on melanogenesis. In B16 mouse melanoma cells, extracts of Acorus gramineus, Capsella bursa-pastoris, Morus bombycis, Perilla frutescens var. crispa, Quercus dentate (bark), Rhus javanica (gallnut), Schizopepon bryoniaefolius, or Sophora flavescens markedly inhibited (>50%) melanin synthesis at 50 microg/Ml. These plants represent a potential source of novel whitening agents for ultraviolet (UV)-sensitive skin. PMID:17454565
Flavanone glycosides from viscum coloratum and their inhibitory effects on osteoclast formation.
Han, Na; Huang, Ting; Wang, Yi-Chun; Yin, Jun; Kadota, Shigetoshi
Two novel flavanone glycosides, homoeriodictyol 7-O-?-D-[6-(3-hydroxybutanoyl)glucopyranoside] (viscumneoside IX; 1) and homoeriodictyol 7-O-?-D-[6-(3-hydroxybutanoyl)glucopyranosyl](1?2)-?-D-glucopyranoside (viscumneoside X; 2), together with four known flavanoids, 2-homoeriodictyol 7-O-?-D-glucopyranoside (3), viscumneoside I (4), viscumneoside III (5), and 4',5-dihydroxy-3'-methoxy-7-(2-O-?-L-rhamnopyranosyl-?-D-glucopyranosyloxy)flavanone (6) were isolated from stems and leaves of Viscum coloratum. Their structures were elucidated on the basis of their NMR spectra, HR-FAB-MS data, and acid hydrolysis. Inhibitory effects of the four compounds 1-4 on the formation of osteoclast-like multinucleated cells were investigated. As a result, all the four flavanoids showed significant inhibitory effects on the formation of osteoclast-like multinuclear cells even at a low concentration of 2??g/ml. The activities of 1-4 at such a concentration exceeded or approximated to that of elcitonin, the positive control drug at a concentration of 2?U/ml, suggesting that they may be of interest for the development of new anti-osteoporosis drugs. PMID:21922656
[Inhibitory and fatal activity of amoxicillin, erythromycin and josamycin against Streptococci].
Savoia, D; Angeretti, A
23 Streptococcus sp. of different serological groups were assayed to evaluate the susceptibility to amoxycillin, erythromycin and josamycin. Inhibitory (CMI) and bactericidal (CMB) activity were compared to minimal lethal concentration (CML) observed at different times from the beginning of incubation to study the kinetic of lethal effect of the three antibiotics. Erythromycin shows an earlier bactericidal efficacy against most of the strains assayed. CMB and CML evaluated after 18 hours of incubation are generally similar, while CML against Streptococci group G, Streptococci group D assayed with macrolides and CML against alpha-haemolytic Streptococci assayed with amoxycillin are higher. PMID:7347699
Inhibitory Effects of Dichlorophenoxyacetones on Auxin-induced Growth of Avena Coleoptile Sections 1
Masingale, Robert E.; Lewis, Janet E.; Bryant, Sarah R.; Skinner, Charles G.
Six dichlorophenoxyacetones were synthesized and examined as potential metabolic antagonists utilizing Avena coleoptile sections and the straight growth assay procedure. Supplements of indoleacetic acid promoted growth of the sections which were inhibited by the analogs; the most inhibitory derivatives were 2,3-; 2,4-; 2,5-; and 3,4-dichlorophenoxyacetone which produced half-maximal growth responses (relative to the unaug-mented control growth) at concentrations of 106, 86, 80, and 62 ?g/ml, respectively. A Lineweaver-Burk plot of the data for the inhibition by 2,4-dichlorophenoxyacetone and its reversal by indoleacetic acid appeared to represent an uncompetitive-like inhibition. PMID:16656819
Feedforward Mechanisms of Excitatory and Inhibitory Cortical Receptive Fields
Randy M. Bruno; Daniel J. Simons
Excitatory and inhibitory cortical layer IV neurons have distinc- tive response properties. Thalamocortical connectivity that may underlie differences was examined using cross-correlation analyses of pairs of thalamic and cortical neurons in the rat whisker\\/barrel system. Cortical layer IV cells discharging fast spikes, presumed inhibitory neurons, were distinguished from regular-spike units, presumed excitatory neurons, by the extra- cellular waveform shape. Regular-spike
Alcoholic fermentation: on the inhibitory effect of ethanol
M. Novak; P. Strehaiano; M. Moreno; G. Goma
The inhibitory effect of ethanol was studied during alcoholic fermentation under strictly anaerobic conditions assured by stripping dissolved oxygen with pure nitrogen. It is shown that ehthanol produced during batch fermentation is more inhibitory than added ethanol in the range of 0 to 76 g\\/liter. Thus, the inhibition constant is 105.2 and 3.8 g\\/liter for added and produced ethanol, respectively.
-talk Critical, comparative or perfectionist thinking Lack of career direction Lack of clarity or confusion materials or resources to complete the task Physical danger or threat Other: Spontaneously answer ..................................................... Strategies for Improving Concentration #12;4 Remember: Concentration strategies will require practice before
Approximating Minimum Manhattan Networks in Higher Dimensions
Kobourov, Stephen G.
Approximating Minimum Manhattan Networks in Higher Dimensions Aparna Das1 , Emden R. Gansner2¨urzburg, Germany Abstract. We consider the minimum Manhattan network problem, which is defined as follows. Given's Manhattan (that is, L1-) distance. The problem is NP-hard in 2D and there is no PTAS for 3D (unless P = NP
Approximating the Generalized Minimum Manhattan Network Problem
Kobourov, Stephen G.
Approximating the Generalized Minimum Manhattan Network Problem Aparna Das1 , Krzysztof Fleszar2¨urzburg, Germany Abstract. We consider the generalized minimum Manhattan network problem (GMMN). The input-length rectilinear network that connects every pair in R by a Manhattan path, that is, a path of axis-parallel line
School Health Services. Minimum Standards Implementation Series.
ERIC Educational Resources Information Center
Ohio State Dept. of Education, Columbus. Div. of Elementary and Secondary Education.
One of a series of documents prepared in conjuntion with the revised minimum standards adopted in 1983 by the Ohio State Board of Education for elementary and secondary schools, this publication is an elaboration of those portions of the minimum standards pertaining to school health services. Following the text of the standard and a brief…
Minimum entropy approach for multisensor data fusion
Yifeng Zhou; Henry Leung
In this paper, we present a minimum entropy fusion approach for multisensor data fusion in non-Gaussian environments. We represent the fused data in the form of the weighted sum of the multisensor outputs and use the varimax norm as the information measure. The optimum weights are obtained by maximizing the varimax norm of the fused data. The minimum entropy fusion
Toxic Concentrations of Exogenously Supplied Methylglyoxal in Hybridoma Cell Culture
Benjamin M. Roy; Tiffany D. Rau; R. Robert Balcarcel
Concentrations at which methylglyoxal, a by-product of cellular metabolism, can be toxic to hybridoma cell cultures were determined\\u000a using exogenously supplied doses. Trypan blue cell counts of 6-well cultures incubated for 24 h with various methylglyoxal\\u000a concentrations revealed inhibition of cell growth at 300 ?M and higher, with a median inhibitory concentration of 490±20 ?M. The primary mode of death was apoptosis, as
Short-Term Plasticity of Unitary Inhibitory-to-Inhibitory Synapses Depends on the Presynaptic Interneuron Subtype
Ma, Yunyong; Hu, Hang; Agmon, Ariel
Excitatory-to-inhibitory cortical synapses exhibit either short-term facilitation or depression, depending on the subtype identity of the postsynaptic interneuron, while the short-term plasticity (STP) of inhibitory-to-excitatory synapses depends on the presynaptic interneuron. However, the rules governing STP of inhibitory-to-inhibitory synapses have not yet been determined. We recorded 109 unitary connections made by the two major inhibitory interneuron subtypes in layer 4 of mouse somatosensory cortex, fast-spiking (FS) and somatostatin-containing (SOM) interneurons, on each other and on excitatory, regular-spiking (RS) neurons. In all pairs we measured dynamic changes in the postsynaptic response to a 20 Hz train of presynaptic action potentials. In half of our dataset, we also measured kinetic properties of the unitary IPSC: latency, rise-time and decay time-constant. We found a pronounced dependency of STP on the presynaptic, but not the postsynaptic identity: FS interneurons made strongly depressing connections on FS, SOM and RS targets, while in synapses made by SOM interneurons on FS and RS targets, weak early depression was followed by weak late facilitation. IPSC latency and rise-time were also strongly dependent on the presynaptic interneuron subtype, being 1.5–2x slower in output synapses of SOM, compared to FS interneurons. In contrast, the IPSC decay time-constant depended only on the postsynaptic class, with 1.5x slower decay on excitatory, compared to inhibitory targets. The properties of the inhibitory outputs of FS and SOM interneurons reciprocate the properties of their excitatory inputs, and imply a dynamic spatio-temporal division of labor between these two major inhibitory subsystems. PMID:22262896
Sea Ice Yearly Minimum 1979-2007
NSDL National Science Digital Library
At the end of each summer, sea ice cover in the Arctic Ocean reaches its minimum extent and what is left is what is called the perennial ice cover (mainly thick multi-year ice floes). The area of perennial ice has been steadily decreasing since the satellite record began in 1979, at a rate of about 10 percent per decade. This visualization shows the annual minimum extent of sea ice in the Arctic Ocean from 1979 to 2007. A graph is overlaid that shows the area in millions of square kilometers for each year's minimum day. The previous record minimum (2005) and the new 2007 record minimum, far below the previous record and 38 percent lower than the climatological average, are highlighted. The visualization may be streamed from the website or downloaded in several formats.
Inhibitory effect of some amino acids on corrosion of Pb–Ca–Sn alloy in sulfuric acid solution
M. A. Kiani; M. F. Mousavi; S. Ghasemi; M. Shamsipur; S. H. Kazemi
The present article describes the inhibition effect of amino acids cysteine (Cys), methionine (Met) and alanine (Ala), towards the corrosion of lead-alloy (Pb–Ca–Sn) in H2SO4 solution by potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), weight loss measurement and scanning electron microscopy (SEM) methods. The influence of inhibitor concentration, temperature and time on inhibitory behavior of the amino acids was investigated. The
Neutrophil Inhibitory Factor Abrogates Neutrophil Adhesion by Blockade of CD11a and CD11b b2 Integrins
We studied the basis of inhibition of polymorphonuclear leuko- cyte (PMN) adhesion induced by neutrophil inhibitory factor (NIF), a 41-kDa CD11\\/CD18 b2 integrin-binding protein isolated from the canine hookworm (Ancylostoma caninum). NIF blocked PMN adhesion in a concentration-dependent manner with complete blockade occurring at ;10 nM NIF. Because CD11a and CD11b b2 integrins are functionally active on stim- ulated PMNs,
Sequence-dependent growth-inhibitory effects of the in vitro combination of fluorouracil, cisplatin, and dipyridamole
M. Barberi-Heyob; G. Griffon; J. L. Merlin; B. Weber
The present study was designed to analyze the growth-inhibitory effects of the combination of fluorouracil (FUra), cisplatin (CDDP), and dipyridamole (DP). These toxic effects were assessed on the human breast-carcinoma cell line MCF-7 using the MTT (tetrazolium bromide) assay in 96-well culture dishes. Data were analyzed using the median-effect principle. The drug combinations tested included FUra concentrations ranging from 0.8
Dose dependent inhibitory effects of dietary 8-methoxypsoralen on NNK-induced lung tumorigenesis in female A\\/J mice
Hijiri Takeuchi; Kousuke Saoo; Yoko Matsuda; Masanao Yokohira; Keiko Yamakawa; Yu Zeng; Masafumi Miyazaki; Masaki Fujieda; Tetsuya Kamataki; Katsumi Imaida
We have reported that pretreatment by stomach tube with 8-methoxypsoralen (methoxsalen; 8-MOP), a potent human CYP2A6 inhibitor, strongly suppresses lung tumorigenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female A\\/J mice (Cancer Res. 2003). Here, we examined inhibitory effects with adminstration in the diet. When the mice were 7 weeks of age, they received dietary supplementation with 8-MOP at concentrations of 1, 10
Decorrelation of Neural-Network Activity by Inhibitory Feedback
Einevoll, Gaute T.; Diesmann, Markus
Correlations in spike-train ensembles can seriously impair the encoding of information by their spatio-temporal structure. An inevitable source of correlation in finite neural networks is common presynaptic input to pairs of neurons. Recent studies demonstrate that spike correlations in recurrent neural networks are considerably smaller than expected based on the amount of shared presynaptic input. Here, we explain this observation by means of a linear network model and simulations of networks of leaky integrate-and-fire neurons. We show that inhibitory feedback efficiently suppresses pairwise correlations and, hence, population-rate fluctuations, thereby assigning inhibitory neurons the new role of active decorrelation. We quantify this decorrelation by comparing the responses of the intact recurrent network (feedback system) and systems where the statistics of the feedback channel is perturbed (feedforward system). Manipulations of the feedback statistics can lead to a significant increase in the power and coherence of the population response. In particular, neglecting correlations within the ensemble of feedback channels or between the external stimulus and the feedback amplifies population-rate fluctuations by orders of magnitude. The fluctuation suppression in homogeneous inhibitory networks is explained by a negative feedback loop in the one-dimensional dynamics of the compound activity. Similarly, a change of coordinates exposes an effective negative feedback loop in the compound dynamics of stable excitatory-inhibitory networks. The suppression of input correlations in finite networks is explained by the population averaged correlations in the linear network model: In purely inhibitory networks, shared-input correlations are canceled by negative spike-train correlations. In excitatory-inhibitory networks, spike-train correlations are typically positive. Here, the suppression of input correlations is not a result of the mere existence of correlations between excitatory (E) and inhibitory (I) neurons, but a consequence of a particular structure of correlations among the three possible pairings (EE, EI, II). PMID:23133368
Characterization of Melanogenesis Inhibitory Constituents of Morus alba Leaves and Optimization of Extraction Conditions Using Response Surface Methodology.
Jeong, Ji Yeon; Liu, Qing; Kim, Seon Beom; Jo, Yang Hee; Mo, Eun Jin; Yang, Hyo Hee; Song, Dae Hye; Hwang, Bang Yeon; Lee, Mi Kyeong
Melanin is a natural pigment that plays an important role in the protection of skin, however, hyperpigmentation cause by excessive levels of melatonin is associated with several problems. Therefore, melanogenesis inhibitory natural products have been developed by the cosmetic industry as skin medications. The leaves of Morus alba (Moraceae) have been reported to inhibit melanogenesis, therefore, characterization of the melanogenesis inhibitory constituents of M. alba leaves was attempted in this study. Twenty compounds including eight benzofurans, 10 flavonoids, one stilbenoid and one chalcone were isolated from M. alba leaves and these phenolic constituents were shown to significantly inhibit tyrosinase activity and melanin content in B6F10 melanoma cells. To maximize the melanogenesis inhibitory activity and active phenolic contents, optimized M. alba leave extraction conditions were predicted using response surface methodology as a methanol concentration of 85.2%; an extraction temperature of 53.2 °C and an extraction time of 2 h. The tyrosinase inhibition and total phenolic content under optimal conditions were found to be 74.8% inhibition and 24.8 ?g GAE/mg extract, which were well-matched with the predicted values of 75.0% inhibition and 23.8 ?g GAE/mg extract. These results shall provide useful information about melanogenesis inhibitory constituents and optimized extracts from M. alba leaves as cosmetic therapeutics to reduce skin hyperpigmentation. PMID:26007176
Antimicrobial and beta-lactamase inhibitory activities of carpetimycins A and B, new carbapenem antibiotics.
Kobayashi, F; Saino, Y; Koshi, T; Hattori, Y; Nakayama, M; Iwasaki, A; Mori, T; Mitsuhashi, S
Carpetimycins A and B showed widely broad spectra and potent activity against gram-positive and gram-negative bacteria, including various species of anaerobic bacteria. The antimicrobial activity of carpetimycin A was 8 to 64 times greater than that of carpetimycin B and 4 to 128 times greater than that of cefoxitin. The inhibitory concentration of carpetimycin A required to inhibit more than 90% of clinical isolates was 0.39 micrograms/ml for Escherichia coli and klebsiella and 1.56 microgram/ml for Proteus and Staphylococcus aureus. At a concentration of 3.13 micrograms/ml, carpetimycin A inhibited almost all clinical isolates of Enterobacter and Citrobacter, which showed resistance to many clinically used beta-lactam antibiotics. Carpetimycins A and B furthermore were shown to have potent inhibitory activities against several kinds of beta-lactamases produced by beta-lactam-resistant strains; they inhibited not only penicillinase-type beta-lactamases but also cephalosporinase-type beta-lactamases, which were insensitive to clavulanic acid. In combination with beta-lactam antibiotics such as ampicillin, carbenicillin, and cefazolin, carpetimycins A and B showed synergistic activities against beta-lactam-resistant bacteria. PMID:6979308
In vitro inhibitory effect of miltefosine against strains of Histoplasma capsulatum var. capsulatum and Sporothrix spp.
Brilhante, Raimunda Sâmia Nogueira; Malaquias, Angela Donato Maia; Caetano, Erica Pacheco; Castelo-Branco, Débora de Souza Collares Maia; Lima, Rita Amanda Chaves de; Marques, Francisca Jakelyne de Farias; Silva, Natalya Fechine; Alencar, Lucas Pereira de; Monteiro, André Jalles; Camargo, Zoilo Pires de; Bandeira, Tereza de Jesus Pinheiro Gomes; Rodrigues, Anderson Messias; Cordeiro, Rossana de Aguiar; Moreira, José Luciano Bezerra; Sidrim, José Júlio Costa; Rocha, Marcos Fábio Gadelha
Miltefosine (MIL), originally developed for use in cancer chemotherapy, has been shown to have important antifungal activity against several pathogenic fungi. Our aim in this study was to determine the in vitro activity of MIL against the dimorphic fungi Histoplasma capsulatum and Sporothrix spp. This was done using the broth microdilution method. MIL had an in vitro inhibitory effect against all strains of H. capsulatum var. capsulatum and Sporothrix spp. analyzed. The minimal inhibitory concentrations (MIC) varied from 0.25??g/ml to 2??g/ml for H. capsulatum var. capsulatum in the filamentous phase and from 0.125??g/ml to 1??g/ml in the yeast phase. The MIC interval for Sporothrix spp. in the filamentous phase was 0.25-2??g/ml. The minimal fungicidal concentrations (MFCs) were ?4??g/ml for isolates of both analyzed species. This study demonstrates that MIL has an antifungal effect in vitro against two potentially pathogenic fungi and that more studies should be performed in order to evaluate its applicability in vivo. PMID:24662247
Inhibitory effects of Ginsenoside Rb1 on apoptosis caused by HSV-1 in human glioma cells.
Liang, Yuan-Yuan; Wang, Bin; Qian, Dong-Meng; Li, Ling; Wang, Zhi-Hao; Hu, Ming; Song, Xu-Xia
To investigate the inhibitory effects of Ginsenoside Rb1 (GRb1) on apoptosis caused by Herpes Simplex Virus-1(HSV-1) in Human Glioma Cells (U251), U251 cells were infected by HSV-1 at a multiplicity of infection of 5 and GRb1, GRb1+HSV-1, HSV-1 and control groups. MTT and cell apoptosis assays were used to detect the inhibitory effects of GRb1 on the apoptosis of U251 cells that caused by HSV-1 infection for various concentrations of drug and virus treatments by MTT assay. We found that in the 400 ?g/mL GRb1 and 400 ?g/mL GRb1+HSV-1 groups, MTT values were higher than control group at all times (P<0. 05). Moreover, the apoptosis rate in the 400 ?g/mL GRb1+HSV-1 group was lower than the HSV-1 group (P<0. 05). These results confirmed that, at appropriate concentrations, GRb1 could inhibit nerve cell apoptosis in HSV-1 infections. PMID:22270803
Noninvasive cell-based impedance spectroscopy for real-time probing inhibitory effects of graphene derivatives.
Male, Keith B; Lam, Edmond; Montes, Johnny; Luong, John H T
Three water-dispersible graphene derivatives, graphene oxide (GO), sulfonated graphene oxide (SGO), and sulfonated graphene (SG), were prepared and probed for their plausible cytotoxicity by non-invasive electric cell-substrate impedance sensing (ECIS). With Spodoptera frugiperda Sf9 insect cells adhered on gold microelectrodes as an active interface, it is feasible to monitor changes in impedance upon exposure to different graphene derivatives. Sf9 insect cells were then exposed to different concentrations of graphene derivatives and their spreading and viability were monitored and quantified by ECIS in real-time. On the basis of the 50% inhibition concentration (ECIS50), none of the graphene derivatives were judged to have any significant cytotoxicity with respect to the chosen cell line as the ECIS50 values were all above 100 ?g/mL. However, all graphene derivatives exhibited inhibitory effects on the Sf9 response at the cell spreading level with the following order: SG (ECIS50 = 121 ± 8 ?g/mL), SGO (ECIS50 = 151 ± 9 ?g/mL), and GO (ECIS50 = 232 ± 27 ?g/mL), reflecting differences observed in their ?-potential and surface area. The presence of phenyl sulfonyl groups in SGO and SG improves their aqueous dispersity which enables these materials to have a greater inhibitory effect on Sf9 insect cells in comparison to GO. Such results were corroborated well with the cell count and viability by the Trypan Blue exclusion assay. PMID:22746697
Flavonoids from Machilus japonica Stems and Their Inhibitory Effects on LDL Oxidation
Joo, Se-Jin; Park, Hee-Jung; Park, Ji-Hae; Cho, Jin-Gyeong; Kang, Ji-Hyun; Jeong, Tae-Sook; Kang, Hee Cheol; Lee, Dae-Young; Kim, Hack-Soo; Byun, Sang-Yo; Baek, Nam-In
Stems of Machilus japonica were extracted with 80% aqueous methanol (MeOH) and the concentrated extract was successively extracted with ethyl acetate (EtOAc), normal butanol (n-BuOH), and water. Six flavonoids were isolated from the EtOAc fraction: (+)-taxifolin, afzelin, (?)-epicatechin, 5,3'-di-O-methyl-(?)-epicatechin, 5,7,3'-tri-O-methyl-(?)-epicatechin, and 5,7-di-O-methyl-3',4'-methylenedioxyflavan-3-ol. The chemical structures were identified using spectroscopic data including NMR, mass spectrometry and infrared spectroscopy. This is the first report of isolation of these six compounds from M. japonica. The compounds were evaluated for their diphenyl picryl hydrazinyl scavenging activity and inhibitory effects on low-density lipoprotein oxidation. Compounds 1 and 3–6 exhibited DPPH antioxidant activity equivalent with that of ascorbic acid, with half maximal inhibitory concentration (IC50) values of 0.16, 0.21, 0.17, 0.15 and 0.07 mM, respectively. The activity of compound 1 was similar to the positive control butylated hydroxytoluene, which had an IC50 value of 1.9 µM, while compounds 3 and 5 showed little activity. Compounds 1, 3, and 5 exhibited LDL antioxidant activity with IC50 values of 2.8, 7.1, and 4.6 µM, respectively. PMID:25229822
acetylcholinesterase inhibitory potential and insecticidal activity of an endophytic Alternaria sp. from Ricinus communis.
Singh, Bahaderjeet; Thakur, Abhinay; Kaur, Sanehdeep; Chadha, B S; Kaur, Amarjeet
Keeping in view the vast potential of endophytic fungi to produce bioactive molecules, this study aimed at isolating and screening endophytes for the production of acetylcholinesterase inhibitors. Fifty-four endophytic fungi were isolated from Ricinus communis and screened for their AChE inhibitory activity using Ellman's colorimetric assay method. Six isolates were found to possess AChE inhibitory activity with maximum inhibition of 78 % being evinced by culture Cas1 which was identified to be Alternaria sp. on the basis of molecular as well as microscopic methods. Optimization of inhibitor production was carried out using one factor at a time approach. Maximum production of inhibitor was obtained on potato dextrose broth after 10 days incubation. The IC(50) of the chloroform extract was observed to be 40 ?g/ml. The extract was purified on silica gel and eluted stepwise with a gradient of chloroform/methanol. The insecticidal potential of the extract was evaluated by feeding the larvae of Spodoptera litura on diet containing varying concentrations of the extract. It was observed that with increase in the concentration of the extract, mortality of the larvae increased. The culture has the potential of being exploited in medicine as well as a biocontrol agent. PMID:22945561
Minimum emittance in TBA and MBA lattices
NASA Astrophysics Data System (ADS)
Xu, Gang; Peng, Yue-Mei
For reaching a small emittance in a modern light source, triple bend achromats (TBA), theoretical minimum emittance (TME) and even multiple bend achromats (MBA) have been considered. This paper derived the necessary condition for achieving minimum emittance in TBA and MBA theoretically, where the bending angle of inner dipoles has a factor of 31/3 bigger than that of the outer dipoles. Here, we also calculated the conditions attaining the minimum emittance of TBA related to phase advance in some special cases with a pure mathematics method. These results may give some directions on lattice design.
Modeling Inhibitory Interneurons in Efficient Sensory Coding Models
Zhu, Mengchen; Rozell, Christopher J.
There is still much unknown regarding the computational role of inhibitory cells in the sensory cortex. While modeling studies could potentially shed light on the critical role played by inhibition in cortical computation, there is a gap between the simplicity of many models of sensory coding and the biological complexity of the inhibitory subpopulation. In particular, many models do not respect that inhibition must be implemented in a separate subpopulation, with those inhibitory interneurons having a diversity of tuning properties and characteristic E/I cell ratios. In this study we demonstrate a computational framework for implementing inhibition in dynamical systems models that better respects these biophysical observations about inhibitory interneurons. The main approach leverages recent work related to decomposing matrices into low-rank and sparse components via convex optimization, and explicitly exploits the fact that models and input statistics often have low-dimensional structure that can be exploited for efficient implementations. While this approach is applicable to a wide range of sensory coding models (including a family of models based on Bayesian inference in a linear generative model), for concreteness we demonstrate the approach on a network implementing sparse coding. We show that the resulting implementation stays faithful to the original coding goals while using inhibitory interneurons that are much more biophysically plausible. PMID:26172289
Parallel language activation and inhibitory control in bimodal bilinguals.
Giezen, Marcel R; Blumenfeld, Henrike K; Shook, Anthony; Marian, Viorica; Emmorey, Karen
Findings from recent studies suggest that spoken-language bilinguals engage nonlinguistic inhibitory control mechanisms to resolve cross-linguistic competition during auditory word recognition. Bilingual advantages in inhibitory control might stem from the need to resolve perceptual competition between similar-sounding words both within and between their two languages. If so, these advantages should be lessened or eliminated when there is no perceptual competition between two languages. The present study investigated the extent of inhibitory control recruitment during bilingual language comprehension by examining associations between language co-activation and nonlinguistic inhibitory control abilities in bimodal bilinguals, whose two languages do not perceptually compete. Cross-linguistic distractor activation was identified in the visual world paradigm, and correlated significantly with performance on a nonlinguistic spatial Stroop task within a group of 27 hearing ASL-English bilinguals. Smaller Stroop effects (indexing more efficient inhibition) were associated with reduced co-activation of ASL signs during the early stages of auditory word recognition. These results suggest that inhibitory control in auditory word recognition is not limited to resolving perceptual linguistic competition in phonological input, but is also used to moderate competition that originates at the lexico-semantic level. PMID:25912892
Head-to-Head Comparison of Inhibitory and Fungicidal Activities of Fluconazole, Itraconazole, Voriconazole, Posaconazole, and Isavuconazole against Clinical Isolates of Trichosporon asahii
Hazirolan, Gulsen; Canton, Emilia; Sahin, Selma
Treatment of disseminated Trichosporon infections still remains difficult. Amphotericin B frequently displays inadequate fungicidal activity and echinocandins have no meaningful antifungal effect against this genus. Triazoles are currently the drugs of choice for the treatment of Trichosporon infections. This study evaluates the inhibitory and fungicidal activities of five triazoles against 90 clinical isolates of Trichosporon asahii. MICs (?g/ml) were determined according to Clinical and Laboratory Standards Institute microdilution method M27-A3 at 24 and 48 h using two endpoints, MIC-2 and MIC-0 (the lowest concentrations that inhibited ?50 and 100% of growth, respectively). Minimum fungicidal concentrations (MFCs; ?g/ml) were determined by seeding 100 ?l of all clear MIC wells (using an inoculum of 104 CFU/ml) onto Sabouraud dextrose agar. Time-kill curves were assayed against four clinical T. asahii isolates and the T. asahii ATCC 201110 strain. The MIC-2 (?50% reduction in turbidity compared to the growth control well)/MIC-0 (complete inhibition of growth)/MFC values that inhibited 90% of isolates at 48 h were, respectively, 8/32/64 ?g/ml for fluconazole, 1/2/8 ?g/ml for itraconazole, 0.12/0.5/2 ?g/ml for voriconazole, 0.5/2/4 ?g/ml for posaconazole, and 0.25/1/4 ?g/ml for isavuconazole. The MIC-0 endpoints yielded more consistent MIC results, which remained mostly unchanged when extending the incubation to 48 h (98 to 100% agreement with 24-h values) and are easier to interpret. Based on the time-kill experiments, none of the drugs reached the fungicidal endpoint (99.9% killing), killing activity being shown but at concentrations not reached in serum. Statistical analysis revealed that killing rates are dose and antifungal dependent. The lowest concentration at which killing activity begins was for voriconazole, and the highest was for fluconazole. These results suggest that azoles display fungistatic activity and lack fungicidal effect against T. asahii. By rank order, the most active triazole is voriconazole, followed by itraconazole ? posaconazole ? isavuconazole > fluconazole. PMID:23877683
Minimum complexity echo state network.
Rodan, Ali; Tino, Peter
Reservoir computing (RC) refers to a new class of state-space models with a fixed state transition structure (the reservoir) and an adaptable readout form the state space. The reservoir is supposed to be sufficiently complex so as to capture a large number of features of the input stream that can be exploited by the reservoir-to-output readout mapping. The field of RC has been growing rapidly with many successful applications. However, RC has been criticized for not being principled enough. Reservoir construction is largely driven by a series of randomized model-building stages, with both researchers and practitioners having to rely on a series of trials and errors. To initialize a systematic study of the field, we concentrate on one of the most popular classes of RC methods, namely echo state network, and ask: What is the minimal complexity of reservoir construction for obtaining competitive models and what is the memory capacity (MC) of such simplified reservoirs? On a number of widely used time series benchmarks of different origin and characteristics, as well as by conducting a theoretical analysis we show that a simple deterministically constructed cycle reservoir is comparable to the standard echo state network methodology. The (short-term) MC of linear cyclic reservoirs can be made arbitrarily close to the proved optimal value. PMID:21075721
Screening for inhibitory activities of essential oils on the growth of Colletotrichum gloeosporioides (Penz.) Penz. & Sacc., the causal agent of leaf spot disease of Murraya koenigii L
Midhila Padman; G. R. Janardhana
Seven essential oils namely clove, cedar wood, lemongrass, peppermint, eucalyptus, citronella and neem oils were tested for their inhibitory effect on spore germination, growth of germ tube and mycelial growth of Colletotrichum gloeosporioides isolated from diseased Murraya koenigii. All essential oils inhibited the germination and growth of germ tube at different concentrations. However, significant reduction in colony growth was observed
Inhibitory effects of trospium chloride on cytochrome P450 enzymes in human liver microsomes.
Beckmann-Knopp, S; Rietbrock, S; Weyhenmeyer, R; Böcker, R H; Beckurts, K T; Lang, W; Fuhr, U
Trospium chloride, an atropine derivative used for the treatment of urge incontinence, was tested for inhibitory effects on human cytochrome P450 enzymes. Metabolic activities were determined in liver microsomes from two donors using the following selective substrates: dextromethorphan (CYP2D6), denitronifedipine (CYP3A4), caffeine (CYP1A2), chlorzoxazone (CYP2E1), S-(+)-mephenytoin (CYP2C19), S-(-)-warfarin (CYP2C9) and coumarin (CYP2A6). Incubations with each substrate were carried out without a possible inhibitor and in the presence of trospium chloride at varying concentrations (37-3000 microM) at 37 degrees in 0.1 M KH2PO4 buffer containing up to 3% DMSO. Metabolite concentrations were determined by high-performance liquid chromatography (HPLC) in all cases except CYP2A6 where direct fluorescence spectroscopy was used. First, trospium chloride IC50 values were determined for each substrate at respective K(M) concentrations. Trospium chloride did not show relevant inhibitory effects on the metabolism of most substrates (IC50 values considerably higher than 1 mM). The only clear inhibition was seen for the CYP2D6-dependent high-affinity O-demethylation of dextromethorphan, where IC50 values of 27 microM and 44 microM were observed. Therefore, additional dextromethorphan concentrations (0.4-2000 microM) were tested. Trospium chloride was a competitive inhibitor of the reaction with Ki values of 20 and 51 microM, respectively. Thus, trospium chloride has negligible inhibitory effects on CYP3A4, CYP1A2, CYP2E1, CYP2C19, CYP2C9 and CYP2A6 activity but is a reasonably potent inhibitor of CYP2D6 in vitro. Compared to therapeutic trospium chloride peak plasma concentrations below 50 nM, the 1000-times higher competitive inhibition constant Ki however suggests that inhibition of CYP2D6 by trospium chloride is without any clinical relevance. PMID:10628907
NASA Technical Reports Server (NTRS)
Simpson, J. G. (inventor)
An improved solar concentrator is characterized by a number of elongated supporting members arranged in substantial horizontal parallelism with the axis and intersecting a common curve. A tensioned sheet of flexible reflective material is disposed in engaging relation with the supporting members in order to impart to the tensioned sheet a catenary configuration.
Edinburgh, University of
Sampling methods 210 Rain : Preliminary rain results show that the concentrations of 210 Pb and 7(roughly 5 halflives of 210 Pb)[Nozaki et al. 1978]. On the basis of these criteria, soil samples were a 10 cmdiameter corer into the soil, five sets of samples were obtained at each sites(10 sites), from
Dual Regulatory Functions of the Thin Filament Revealed by Replacement of the Troponin I Inhibitory Peptide with a Linker*
Kozaili, Julie Mouannes; Leek, Daniel; Tobacman, Larry S.
Striated muscles are relaxed under low Ca2+ concentration conditions due to actions of the thin filament protein troponin. To investigate this regulatory mechanism, an 11-residue segment of cardiac troponin I previously termed the inhibitory peptide region was studied by mutagenesis. Several mutant troponin complexes were characterized in which specific effects of the inhibitory peptide region were abrogated by replacements of 4–10 residues with Gly-Ala linkers. The mutations greatly impaired two of troponin's actions under low Ca2+ concentration conditions: inhibition of myosin subfragment 1 (S1)-thin filament MgATPase activity and cooperative suppression of myosin S1-ADP binding to thin filaments with low myosin saturation. Inhibitory peptide replacement diminished but did not abolish the Ca2+ dependence of the ATPase rate; ATPase rates were at least 2-fold greater when Ca2+ rather than EGTA was present. This residual regulation was highly cooperative as a function of Ca2+ concentration, similar to the degree of cooperativity observed with WT troponin present. Other effects of the mutations included 2-fold or less increases in the apparent affinity of the thin filament regulatory Ca2+ sites, similar decreases in the affinity of troponin for actin-tropomyosin regardless of Ca2+, and increases in myosin S1-thin filament ATPase rates in the presence of saturating Ca2+. The overall results indicate that cooperative myosin binding to Ca2+-free thin filaments depends upon the inhibitory peptide region but that a cooperatively activating effect of Ca2+ binding does not. The findings suggest that these two processes are separable and involve different conformational changes in the thin filament. PMID:20889978
2011 Sea Ice Minimum - Duration: 61 seconds.
This video shows Arctic sea ice from March 7, 2011, to Sept. 9, 2011, ending with a comparison of the 30-year average minimum extent, shown in yellow, and the Northwest Passage, in red. (no audio) ...
7 CFR 35.13 - Minimum quantity.
Code of Federal Regulations, 2012 CFR
...COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS EXPORT GRAPES AND PLUMS Exemptions § 35.13 Minimum quantity...a shipment of 25 packages or less of vinifera species table grapes, either a single variety or a combination of two or more...
7 CFR 35.13 - Minimum quantity.
Code of Federal Regulations, 2014 CFR
...COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS EXPORT GRAPES AND PLUMS Exemptions § 35.13 Minimum quantity...a shipment of 25 packages or less of vinifera species table grapes, either a single variety or a combination of two or more...
7 CFR 35.13 - Minimum quantity.
Code of Federal Regulations, 2013 CFR
...COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS EXPORT GRAPES AND PLUMS Exemptions § 35.13 Minimum quantity...a shipment of 25 packages or less of vinifera species table grapes, either a single variety or a combination of two or more...
Determining minimum lubrication film for machine parts
NASA Technical Reports Server (NTRS)
Hamrock, B. J.; Dowson, D.
Formula predicts minimum film thickness required for fully-flooded ball bearings, gears, and cams. Formula is result of study to determine complete theoretical solution of isothermal elasto-hydrodynamic lubrication of fully-flooded elliptical contacts.
7 CFR 4280.136 - Minimum retention.
Code of Federal Regulations, 2012 CFR
...RURAL BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE LOANS AND GRANTS Rural Energy for America Program General Renewable Energy System and Energy Efficiency Improvement Guaranteed Loans § 4280.136 Minimum...
7 CFR 4280.136 - Minimum retention.
Code of Federal Regulations, 2014 CFR
...RURAL BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE LOANS AND GRANTS Rural Energy for America Program General Renewable Energy System and Energy Efficiency Improvement Guaranteed Loans § 4280.136 Minimum...
49 CFR 639.27 - Minimum criteria.
Code of Federal Regulations, 2010 CFR
...to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CAPITAL LEASES Cost-Effectiveness § 639.27 Minimum criteria. In making the comparison between leasing and purchasing or constructing an...
New insights into the acetylcholinesterase inhibitory activity of Lycopodium clavatum.
Rollinger, Judith M; Ewelt, Julia; Seger, Christoph; Sturm, Sonja; Ellmerer, Ernst P; Stuppner, Hermann
Looking for acetylcholinesterase (AChE) inhibiting compounds within the plant kingdom, we came across the triterpene alpha-onocerin, which has recently been described as the active principle (IC(50) of 5.2 microM) of Lycopodium clavatum L. In order to discover related terpenoid structures with similar AChE inhibitory activity, we investigated the roots of Ononis spinosa L. using Ellman's reagent in a microplate assay. No inhibitory effect could be measured, not even with the isolated alpha-onocerin (1), which is in contrast to previous findings. Bioassay-guided fractionation of L. clavatum resulted in the isolation of lyclavatol (2), showing a weak, but dose-dependent inhibitory effect on AChE. (1)H- and (13)C NMR shift assignments for 1 and 2 are presented and discussed. PMID:16320206
Adaptive Proactive Inhibitory Control for Embedded Real-Time Applications
Yang, Shufan; McGinnity, T. Martin; Wong-Lin, KongFatt
Psychologists have studied the inhibitory control of voluntary movement for many years. In particular, the countermanding of an impending action has been extensively studied. In this work, we propose a neural mechanism for adaptive inhibitory control in a firing-rate type model based on current findings in animal electrophysiological and human psychophysical experiments. We then implement this model on a field-programmable gate array (FPGA) prototyping system, using dedicated real-time hardware circuitry. Our results show that the FPGA-based implementation can run in real-time while achieving behavioral performance qualitatively suggestive of the animal experiments. Implementing such biological inhibitory control in an embedded device can lead to the development of control systems that may be used in more realistic cognitive robotics or in neural prosthetic systems aiding human movement control. PMID:22701420
Minimum weight aerospace structural synthesis program
Walker, John Michael
Webs Weight Equations General 12 15 16 Multirib Weight Multispar Weight III. PROGRAM DEVELOPMENT 21 27 30 IV. Minimum Weight Analysis of Multirib and Multiweb Wing Box Structures Minimum Weight Aerospace Structural Synthesis Program... The Desk Top Calculator Plot Routines Increased Efficiency PLASTICITY CORRECTION FACTORS Upper Cover ? Multirib Upper Cover ? Multispar 30 35 35 36 37 53 CHAPTER VI. Shear Webs ? Multirib and Multispar Ribs ? Multirib EFFECTIVE DEPTH FACTOR...
The minimum wage and tipped employees
Walter John Wessels
Using data from theCensus of Retail Trade, I estimate that allowing restaurants to use servers' tipped income to satisfy minimum wage requirements would create at\\u000a least 360,000 new high-paying jobs and increase total income for tipped workers by at least 8 percent. Conversely, if the\\u000a minimum wage were increased 10 percent, tipped workers would experience a 4 percent decrease in
Knots and Minimum Distance Energy Rosanna Speller
Denne, Elizabeth
| is denoted md(X, Y ). Definition 2 ([11]). The Minimum Distance Energy for a pair of nonconsecutive edges, X. Definition 3 ([1, 11]). The M¨obius Energy (or O'Hara Energy) of a smooth knot, K is E0(K) = C�C 1 |x(t) - xKnots and Minimum Distance Energy Rosanna Speller (Dated: May 11, 2008) Professor Elizabeth Denne
Tumor cell proliferation and cyclooxygenase inhibitory constituents in horseradish (Armoracia rusticana) and Wasabi (Wasabia japonica).
Weil, Marvin J; Zhang, Yanjun; Nair, Muraleedharan G
Cyclooxygenase and human tumor cell growth inhibitory extracts of horseradish (Armoracia rusticana) and wasabi (Wasabia japonica) rhizomes upon purification yielded active compounds 1-3 from horseradish and 4 and 5 from wasabi rhizomes. Spectroscopic analyses confirmed the identities of these active compounds as plastoquinone-9 (1), 6-O-acyl-beta-d-glucosyl-beta-sitosterol (2), 1,2-dilinolenoyl-3-galactosylglycerol (3), linolenoyloleoyl-3-beta-galactosylglycerol (4), and 1,2-dipalmitoyl-3-beta-galactosylglycerol (5). 3-Acyl-sitosterols, sinigrin, gluconasturtiin, and phosphatidylcholines isolated from horseradish and alpha-tocopherol and ubiquinone-10 from wasabi rhizomes isolated were inactive in our assays. At a concentration of 60 microg/mL, compounds 1 and 2 selectively inhibited COX-1 enzyme by 28 and 32%, respectively. Compounds 3, 4, and 5 gave 75, 42, and 47% inhibition of COX-1 enzyme, respectively, at a concentration of 250 microg/mL. In a dose response study, compound 3 inhibited the proliferation of colon cancer cells (HCT-116) by 21.9, 42.9, 51.2, and 68.4% and lung cancer cells (NCI-H460) by 30, 39, 44, and 71% at concentrations of 7.5, 15, 30, and 60 microg/mL, respectively. At a concentration of 60 microg/mL, compound 4 inhibited the growth of colon, lung, and stomach cancer cells by 28, 17, and 44%, respectively. This is the first report of the COX-1 enzyme and cancer cell growth inhibitory monogalactosyl diacylglycerides from wasabi and horseradish rhizomes. PMID:15740020
The inhibitory effects of antirheumatic drugs on the activity of human leukocyte elastase and cathepsin G.
Steinmeyer, J; Kalbhen, D A
The serine proteinases elastase and cathepsin G from polymorphonuclear granulocytes play a critical role in articular cartilage degradation, not only as proteolytic enzymes able to degrade the extracellular matrix but also by additionally modulating the level of active matrix metalloproteinases, key enzymes of the proteolytic destruction of cartilage during rheumatoid arthritis. The aim of our study was to examine whether anti-inflammatory drugs and selected compounds inhibited elastase and cathepsin G, and also to determine whether it is necessary to use a highly purified elastase preparation to screen drugs for their ability to block the activity of this enzyme. Eglin C and the glycosaminoglycan-peptide complex DAK-16, at concentrations ranging from 10(-9) to 10(-4) M, dose-dependently inhibited elastase and cathepsin G while the nonsteroidal anti-inflammatory drugs oxyphenbutazone, phenylbutazone, sulfinpyrazone and diclofenac-Na required high concentrations to demonstrate some inhibitory effects on the activity of both enzymes. None of the other anti-inflammatory drugs tested at a concentration of 10(-4) M such as acetylsalicylic acid, dexamethasone, indomethacin, ketoprofen, naproxen, oxaceprol, pirprofen and tiaprofenic acid demonstrated any marked inhibitory activity on either of these proteinases. Only a few drugs, when dosed therapeutically, achieved synovial fluid concentrations sufficient to inhibit the activities of both proteinases. The antirheumatic drugs demonstrated similar inhibition profiles in purified or partially purified elastase preparations. Thus the leukocyte extract containing the partially purified elastase and cathepsin G which can be rapidly and easily prepared at low costs appears to be an efficient mean of screening potentially new therapeutic agents for their ability to inhibit leukocyte elastase and cathepsin G. PMID:8841833
Changes in spinal inhibitory networks induced by furosemide in humans
Klomjai, Wanalee; Lackmy-Vallée, Alexandra; Katz, Rose; Bussel, Bernard; Bensmail, Djamel; Lamy, Jean-Charles; Roche, Nicolas
During neural development in animals, GABAergic and glycinergic neurons are first excitatory, and then become inhibitory in the mature state. This developmental shift is due mainly to strong expression of the cation-chloride K–Cl cotransporter 2 (KCC2) and down-regulation of Na–K–Cl cotransporter 1 (NKCC1) during maturation. The down-regulation of co-transporter KCC2 after spinal cord transection in animals leads to the depolarising (excitatory) action of GABA and glycine and thus results in a reduction of inhibitory synaptic efficiency. Furosemide, a loop diuretic, has been shown to selectively and reversibly block inhibitory postsynaptic potentials without affecting excitatory postsynaptic potentials in animal spinal neurons. Moreover, this diuretic has been also demonstrated to block the cation-chloride co-transporters. Here, we used furosemide to demonstrate changes in spinal inhibitory networks in healthy human subjects. Non-invasive electrophysiological techniques were used to assess presynaptic inhibition, postsynaptic inhibition and the efficacy of synaptic transmission between muscle afferent terminals and soleus motoneurons in the spinal cord. Orally administered furosemide, at doses commonly used in the clinic (40 mg), significantly reduced spinal inhibitory interneuronal activity for at least 70 min from intake compared to control experiments in the same subjects while no changes were observed in the efficacy of synaptic transmission between muscle afferent terminals and soleus motoneurons. The reduction of inhibition was dose-dependent. Our results provide indirect evidence that reversible changes in the cation-chloride transport system induce modulations of inhibitory neuronal activity at spinal cord level in humans. PMID:24835171
Changes in spinal inhibitory networks induced by furosemide in humans.
Klomjai, Wanalee; Lackmy-Vallée, Alexandra; Katz, Rose; Bussel, Bernard; Bensmail, Djamel; Lamy, Jean-Charles; Roche, Nicolas
During neural development in animals, GABAergic and glycinergic neurons are first excitatory, and then become inhibitory in the mature state. This developmental shift is due mainly to strong expression of the cation-chloride K-Cl cotransporter 2 (KCC2) and down-regulation of Na-K-Cl cotransporter 1 (NKCC1) during maturation. The down-regulation of co-transporter KCC2 after spinal cord transection in animals leads to the depolarising (excitatory) action of GABA and glycine and thus results in a reduction of inhibitory synaptic efficiency. Furosemide, a loop diuretic, has been shown to selectively and reversibly block inhibitory postsynaptic potentials without affecting excitatory postsynaptic potentials in animal spinal neurons. Moreover, this diuretic has been also demonstrated to block the cation-chloride co-transporters. Here, we used furosemide to demonstrate changes in spinal inhibitory networks in healthy human subjects. Non-invasive electrophysiological techniques were used to assess presynaptic inhibition, postsynaptic inhibition and the efficacy of synaptic transmission between muscle afferent terminals and soleus motoneurons in the spinal cord. Orally administered furosemide, at doses commonly used in the clinic (40 mg), significantly reduced spinal inhibitory interneuronal activity for at least 70 min from intake compared to control experiments in the same subjects while no changes were observed in the efficacy of synaptic transmission between muscle afferent terminals and soleus motoneurons. The reduction of inhibition was dose-dependent. Our results provide indirect evidence that reversible changes in the cation-chloride transport system induce modulations of inhibitory neuronal activity at spinal cord level in humans. PMID:24835171
The inhibitory avoidance discrimination task to investigate accuracy of memory
Atucha, Erika; Roozendaal, Benno
The present study was aimed at developing a new inhibitory avoidance task, based on training and/or testing rats in multiple contexts, to investigate accuracy of memory. In the first experiment, male Sprague-Dawley rats were given footshock in an inhibitory avoidance apparatus and, 48 h later, retention latencies of each rat were assessed in the training apparatus (Shock box) as well as in a novel, contextually modified, apparatus. Retention latencies in the Shock box were significantly longer than those in the Novel box, indicating accurate memory of the training context. When the noradrenergic stimulant yohimbine (0.3 mg/kg, sc) was administered after the training, 48-h retention latencies in the Shock box, but not Novel box, were increased, indicating that the noradrenergic activation enhanced memory of the training experience without reducing memory accuracy. In the second experiment, rats were trained on an inhibitory avoidance discrimination task: They were first trained in an inhibitory avoidance apparatus without footshock (Non-Shock box), followed 1 min later by footshock training in a contextually modified apparatus (Shock box). Forty-eight-hour retention latencies in the Shock and Non-Shock boxes did not differ from each other but were both significantly longer than those in a Novel box, indicating that rats remembered the two training contexts but did not have episodic-like memory of the association of footshock with the correct training context. When the interval between the two training episodes was increased to 2 min, rats showed accurate memory of the association of footshock with the training context. Yohimbine administered after the training also enhanced rats' ability to remember in which training context they had received actual footshock. These findings indicate that the inhibitory avoidance discrimination task is a novel variant of the well-established inhibitory avoidance task suitable to investigate accuracy of memory. PMID:25814942
Dissecting inhibitory brain circuits with genetically-targeted technologies
Murphey, Dona K.; Herman, Alexander M.; Arenkiel, Benjamin R.
The evolution of genetically targeted tools has begun to allow us to dissect anatomically and functionally heterogeneous interneurons, and to probe circuit function from synapses to behavior. Over the last decade, these tools have been used widely to visualize neurons in a cell type-specific manner, and engage them to activate and inactivate with exquisite precision. In this process, we have expanded our understanding of interneuron diversity, their functional connectivity, and how selective inhibitory circuits contribute to behavior. Here we discuss the relative assets of genetically encoded fluorescent proteins (FPs), viral tracing methods, optogenetics, chemical genetics, and biosensors in the study of inhibitory interneurons and their respective circuits. PMID:25368555
Galanin-immunoreactivity identifies a distinct population of inhibitory interneurons in laminae I-III of the rat spinal cord
Background Inhibitory interneurons constitute 30-40% of neurons in laminae I-III and have an important anti-nociceptive role. However, because of the difficulty in classifying them we know little about their organisation. Previous studies have identified 3 non-overlapping groups of inhibitory interneuron, which contain neuropeptide Y (NPY), neuronal nitric oxide synthase (nNOS) or parvalbumin, and have shown that these differ in postsynaptic targets. Some inhibitory interneurons contain galanin and the first aim of this study was to determine whether these form a different population from those containing NPY, nNOS or parvalbumin. We also estimated the proportion of neurons and GABAergic axons that contain galanin in laminae I-III. Results Galanin cells were concentrated in laminae I-IIo, with few in laminae IIi-III. Galanin showed minimal co-localisation with NPY, nNOS or parvalbumin in laminae I-II, but most galanin-containing cells in lamina III were nNOS-positive. Galanin cells constituted ~7%, 3% and 2% of all neurons in laminae I, II and III, and we estimate that this corresponds to 26%, 10% and 5% of the GABAergic neurons in these laminae. However, galanin was only found in ~6% of GABAergic boutons in laminae I-IIo, and ~1% of those in laminae IIi-III. Conclusions These results show that galanin, NPY, nNOS and parvalbumin can be used to define four distinct neurochemical populations of inhibitory interneurons. Together with results of a recent study, they suggest that the galanin and NPY populations account for around half of the inhibitory interneurons in lamina I and a quarter of those in lamina II. PMID:21569622
NASA Technical Reports Server (NTRS)
Owen, W. A.
During the years of technology development by the Parabolic Dish program, the problems peculiar to tracking dishes have been explored in depth with particular emphasis on economics. Starting with the Precursor Concentrator, testing techniques and apparatus such as calorimeters and the flux mapper were developed. At the same time, mirrors were developed to have a long operating life as well as high performance. Commercially available equipment was evaluated as well. Building on all these elements, the Test Bed Concentrators were designed and built. With a peak intensity in the focal plane of over 17,500 suns and an average concentrator ratio over 3000 on an eight inch diameter aperture, they have proven to be the work horses of the technology. With a readily adjustable mirror array, they have proved to be an essential tool in the development of dish components, receivers, heat transport systems, instrumentation, controls, engines, and materials - all necessary to cost effective modules and plants. Utilizing the lessons learned from this technology, most cost effective systems were designed. These included Parabolic Dish Number 1 (PDC-1) and PDC-2 currently in final design by Acurex Corporation. Even more advanced concepts are being worked on, such as the Cassegranian systems by BDM Corporation.
Subinhibitory Concentrations of Perilla Oil Affect the Expression of Secreted Virulence Factor Genes in Staphylococcus aureus
Luo, Mingjing; Li, Hongen; Dong, Jing; Wang, Jianfeng; Leng, Bingfeng; Wang, Xiaoliang; Feng, Haihua; Ren, Wenzhi; Deng, Xuming
Background The pathogenicity of staphylococcus aureus is dependent largely upon its ability to secrete a number of virulence factors, therefore, anti-virulence strategy to combat S. aureus-mediated infections is now gaining great interest. It is widely recognized that some plant essential oils could affect the production of staphylococcal exotoxins when used at subinhibitory concentrations. Perilla [Perilla frutescens (L.) Britton], a natural medicine found in eastern Asia, is primarily used as both a medicinal and culinary herb. Its essential oil (perilla oil) has been previously demonstrated to be active against S. aureus. However, there are no data on the influence of perilla oil on the production of S. aureus exotoxins. Methodology/Principal Findings A broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of perilla oil against S. aureus strains. Hemolysis, tumour necrosis factor (TNF) release, Western blot, and real-time RT-PCR assays were performed to evaluate the effects of subinhibitory concentrations of perilla oil on exotoxins production in S. aureus. The data presented here show that perilla oil dose-dependently decreased the production of ?-toxin, enterotoxins A and B (the major staphylococcal enterotoxins), and toxic shock syndrome toxin 1 (TSST-1) in both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). Conclusions/Significance The production of ?-toxin, SEA, SEB, and TSST-1 in S. aureus was decreased by perilla oil. These data suggest that perilla oil may be useful for the treatment of S. aureus infections when used in combination with ?-lactam antibiotics, which can increase exotoxins production by S. aureus at subinhibitory concentrations. Furthermore, perilla oil could be rationally applied in food systems as a novel food preservative both to inhibit the growth of S. aureus and to repress the production of exotoxins, particularly staphylococcal enterotoxins. PMID:21283822
Comparative study of the vasorelaxant activity, superoxide-scavenging ability and cyclic nucleotide phosphodiesterase-inhibitory effects of hesperetin and hesperidin
Francisco Orallo; Ezequiel Álvarez; Hélčne Basaran; Claire Lugnier
This study investigated the vasorelaxant activity, superoxide radicals (O 2 •?)-scavenging capacity and cyclic nucleotide phosphodiesterase (PDE)-inhibitory effects of hesperidin and hesperetin, two flavonoids mainly isolated from citrus fruits. Hesperetin concentration-dependently relaxed the isometric contractions induced by noradrenaline (NA, 1 ?M) or by a high extracellular KCl concentration (60 mM) in intact rat isolated thoracic aorta rings. However, hesperetin (10
Evidence for inhibitory SH groups in the thiol activated K:Cl cotransporter of low K sheep red blood cells.
Ryu, K H; Lauf, P K
The monofunctional thiol reagents N-ethylmaleimide (NEM) and methyl methanethiosulfonate (MMTS) stimulate ouabain resistant (OR) electroneutral K:Cl cotransport in LK sheep red blood cells at low, but not at high concentrations. Diamide (DM), on the other hand, only stimulates OR K:Cl flux (Lauf, P.K., J. Memb. Biol. 101: 179-188, 1988). The DM stimulated K:Cl cotransport was decreased toward the control value prior to DM stimulation when NEM or MMTS were added, subsequently. The inhibitory effect was dependent on the compound's concentration and exposure time and, in the case of MMTS, was reversed upon addition of dithiothreitol (DTT). The inhibition was more prominent when NEM treatment was performed at pH 8.0 and disappeared at pH 6.0. In contrast the NEM stimulatory effect was most effective when the pH of NEM treatment was 6.0 (Bauer, J. & Lauf, P.K., J. Memb. Biol. 73: 257-261, 1983). The results suggest the existence of additional, however, inhibitory thiol groups in the already thiol-activated K:Cl cotransporter, with a different pKa value and a lower affinity for NEM or MMTS as compared to the stimulatory thiol groups. Like the activating thiols, the inhibitory sulfhydryls appeared to be inaccessible to non-penetrating thiol reagents and hence, must be located deeper within the red cell membrane. PMID:2287344
Anti-proliferative lichen compounds with inhibitory activity on 12(S)-HETE production in human platelets.
Bucar, F; Schneider, I; Ogmundsdóttir, H; Ingólfsdóttir, K
Several lichen compounds, i.e. lobaric acid (1), a beta-orcinol depsidone from Stereocaulon alpinum L., (+)-protolichesterinic acid (2), an aliphatic alpha-methylene-gamma-lactone from Cetraria islandica Laur. (Parmeliaceae), (+)-usnic acid (3), a dibenzofuran from Cladonia arbuscula (Wallr.) Rabenh. (Cladoniaceae), parietin (4), an anthraquinone from Xanthoria elegans (Link) Th. Fr. (Calaplacaceae) and baeomycesic acid (5), a beta-orcinol depside isolated from Thamnolia vermicularis (Sw.) Schaer. var. subuliformis (Ehrh.) Schaer. were tested for inhibitory activity on platelet-type 12(S)-lipoxygenase using a cell-based in vitro system in human platelets. Lobaric acid (1) and (+)-protolichesterinic acid (2) proved to be pronounced inhibitors of platelet-type 12(S)-lipoxygenase, whereas baeomycesic acid (5) showed only weak activity (inhibitory activity at a concentration of 100 microg/ml: (1) 93.4+/-6.62%, (2) 98,5+/-1.19%, 5 14.7+/-2.76%). Usnic acid (3) and parietin (4) were not active at this concentration. 1 and 2 showed a clear dose-response relationship in the range of 3.33-100 microg/ml. According to the calculated IC50 values the highest inhibitory activity was observed for the depsidone 1 (IC50 = 28.5 microM) followed by 2 (IC50 = 77.0 microM). The activity of 1 was comparable to that of the flavone baicalein, which is known as a selective 12(S)-lipoxygenase inhibitor (IC50 = 24.6 microM). PMID:15636173
A new method for simultaneous quantification of uncoupling and inhibitory activity of organic pollutants in energy-transducing membranes
Escher, B.I.; Snozzi, M.; Haeberli, K.; Schwarzenbach, R.P. [Swiss Federal Inst. for Environmental Science and Technology, Duebendorf (Switzerland)]|[Swiss Federal Inst. of Tech., Duebendorf (Switzerland)
A new, mechanistically based approach is presented for the quantitative determination of the uncoupling and inhibitory activity of compounds interfering with energy transduction. Time-resolved spectroscopy of single-turnover events in the photosystem of the photosynthetic bacterium Rhodobacter sphaeroides can quantitatively distinguish uncoupling from inhibition. The decay kinetics of the membrane potential after a single turnover flash are used as a measure of uncoupling activity, and the redox kinetics of several components of the electron transfer chain are used as indicators of specific inhibition at various potential inhibitory sites. Results are presented for 21 nitrated and chlorinated phenols, some reference uncouplers, and some anisoles. Inhibition was exclusively detected at one specific quinone binding site, the quinone reductase site Q{sub i}. For most phenols, uncoupling was observed at lower concentrations than inhibition with the exception of alkylated 2,6-dinitrophenols and 2,4,6-trichlorophenol, where both effects occurred in the same concentration range. No direct correlation was observed between the uncoupling and inhibitory activity of a given compound. The data obtained with this new method correlate well with data from various bioassays on energy-transducing systems, indicating that this method may also be well suited as a screening tool for compounds suspected to interfere with energy transduction.
CYP51 structures and structure-based development of novel, pathogen-specific inhibitory scaffolds
Hargrove, Tatiana Y.; Kim, Kwangho; de Nazaré Correia Soeiro, Maria; da Silva, Cristiane França; da Gama Jaen Batista, Denise; Batista, Marcos Meuser; Yazlovitskaya, Eugenia M.; Waterman, Michael R.; Sulikowski, Gary A.; Lepesheva, Galina I.
CYP51 (sterol 14?-demethylase) is a cytochrome P450 enzyme essential for sterol biosynthesis and the primary target for clinical and agricultural antifungal azoles. The azoles that are currently in clinical use for systemic fungal infections represent modifications of two basic scaffolds, ketoconazole and fluconazole, all of them being selected based on their antiparasitic activity in cellular experiments. By studying direct inhibition of CYP51 activity across phylogeny including human pathogens Trypanosoma brucei, Trypanosoma cruzi and Leishmania infantum, we identified three novel protozoa-specific inhibitory scaffolds, their inhibitory potency correlating well with antiprotozoan activity. VNI scaffold (carboxamide containing ?-phenyl-imidazoles) is the most promising among them: killing T. cruzi amastigotes at low nanomolar concentration, it is also easy to synthesize and nontoxic. Oral administration of VNI (up to 400 mg/kg) neither leads to mortality nor reveals significant side effects up to 48 h post treatment using an experimental mouse model of acute toxicity. Trypanosomatidae CYP51 crystal structures determined in the ligand-free state and complexed with several azole inhibitors as well as a substrate analog revealed high rigidity of the CYP51 substrate binding cavity, which must be essential for the enzyme strict substrate specificity and functional conservation. Explaining profound potency of the VNI inhibitory scaffold, the structures also outline guidelines for its further development. First steps of the VNI scaffold optimization have been undertaken; the results presented here support the notion that CYP51 structure-based rational design of more efficient, pathogen-specific inhibitors represents a highly promising direction. PMID:23504044
Cytotoxic and melanogenesis-inhibitory activities of limonoids from the leaves of Azadirachta indica (Neem).
Takagi, Mio; Tachi, Yosuke; Zhang, Jie; Shinozaki, Takuro; Ishii, Kenta; Kikuchi, Takashi; Ukiya, Motohiko; Banno, Norihiro; Tokuda, Harukuni; Akihisa, Toshihiro
Seventeen limonoids (tetranortriterpenoids), 1-17, including three new compounds, i.e., 17-defurano-17-(2,5-dihydro-2-oxofuran-3-yl)-28-deoxonimbolide (14), 17-defurano-17-(2?-2,5-dihydro-2-hydroxy-5-oxofuran-3-yl)-28-deoxonimbolide (15), and 17-defurano-17-(5?-2,5-dihydro-5-hydroxy-2-oxofuran-3-yl)-2',3'-dehydrosalannol (17), were isolated from an EtOH extract of the leaf of neem (Azadirachta indica). The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines, seven compounds, i.e., 1-3, 12, 13, 15, and 16, exhibited potent cytotoxicities with IC50 values in the range of 0.1-9.9??M against one or more cell lines. Among these compounds, cytotoxicity of nimonol (1; IC50 2.8??M) against HL60 cells was demonstrated to be mainly due to the induction of apoptosis by flow cytometry. Western blot analysis suggested that compound 1 induced apoptosis via both the mitochondrial and death receptor-mediated pathways in HL60 cells. In addition, when compounds 1-17 were evaluated for their inhibitory activities against melanogenesis in B16 melanoma cells, induced with ?-melanocyte-stimulating hormone (?-MSH), seven compounds, 1, 2, 4-6, 15, and 16, exhibited inhibitory activities with 31-94% reduction of melanin content at 10??M concentration with no or low toxicity to the cells (82-112% of cell viability at 10??M). All 17 compounds were further evaluated for their inhibitory effects against the Epstein?Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. PMID:24634075
Could tuning of the inhibitory tone involve graded changes in neuronal chloride transport?
Titz, Stefan; Sammler, Esther M; Hormuzdi, Sheriar G
Hyperpolarizing synaptic inhibition through GABAA and glycine receptors depends on the presence of the neuronal cation-chloride-cotransporter protein, KCC2. Several transcriptional and post-transcriptional mechanisms have been shown to regulate KCC2 and thereby influence the polarity and efficacy of inhibitory synaptic transmission. It is unclear however whether regulation of KCC2 enables the transporter to attain different levels of activity thus allowing a neuron to modulate the strength of inhibitory synaptic transmission to its changing requirements. We therefore investigated whether phosphorylation can allow KCC2 to achieve distinct levels of [Cl(-)]i in neurons. We generated a variety of KCC2 alanine dephosphorylation mimics and used NH4(+)-induced pHi shifts in cultured hippocampal neurons to quantify the rate of KCC2 transport activity exhibited by these mutants. To explore the relationship between KCC2 transport and GABAA receptor-mediated current amplitudes we performed gramicidine perforated-patch recordings. The correlation between EGABA and NH4(+)-induced pHi shifts enabled an estimate of the range of chloride extrusion possible by kinase/phosphatase regulation of KCC2. Our results demonstrate that KCC2 transport can vary considerably in magnitude depending on the combination of alanine mutations present on the protein. Transport can be enhanced to sufficiently high levels that hyperpolarizing GABAA responses may be obtained even in neurons with an extremely negative resting membrane potential and at high extracellular K(+) concentrations. Our findings highlight the significant potential for regulating the inhibitory tone by KCC2-mediated chloride extrusion and suggest that cellular signaling pathways may act combinatorially to alter KCC2 phosphorylation/dephosphorylation and thereby tune the strength of synaptic inhibition. PMID:25843644
Inhibitory effects of indicaxanthin on mouse ileal contractility: analysis of the mechanism of action.
Baldassano, Sara; Rotondo, Alessandra; Serio, Rosa; Livrea, Maria Antonietta; Tesoriere, Luisa; Mulč, Flavia
Recently, we have showed that indicaxanthin, the yellow betalain pigment abundant in the fruit of Opuntia ficus indica, has remarkable spasmolytic effects on the intestinal contractility in vitro. Thus, the purpose of the present study was to investigate the mechanism of action underlying the observed response. We used organ bath technique to record the mechanical activity of the mouse ileum longitudinal muscle and ELISA to measure the levels of cAMP. Indicaxanthin induced inhibitory effects on spontaneous mechanical activity, which were unaffected by indomethacin, a non-selective inhibitor of cycloxygenase; 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a selective inhibitor of nitric oxide-dependent guanylyl cyclase; 2'5'dideoxyadenosine, an adenylyl cyclase inhibitor; and zaprinast, a selective inhibitor of the cGMP phosphodiesterase isoenzyme. Indicaxanthin effects were reduced significantly in the presence of 3-isobutyl-1-methylxanthine (IBMX), a non selective inhibitor of phosphodiesterases (PDEs). Indicaxanthin and IBMX significantly reduced the carbachol-evoked contractions and the joint application of both drugs did not produce any additive effect. Indicaxanthin and IBMX increased the inhibitory effects of forskolin, an adenylyl cyclase activator, and the joint application of both drugs did not produce any additive effect. Indicaxanthin, contrarily to IBMX, did not affect the inhibitory action of sodium nitroprusside, a soluble guanylyl cyclase activator. Indicaxanthin increased both basal and forskolin-induced cAMP content of mouse ileal muscle. The present data show that indicaxanthin reduces the contractility of ileal longitudinal muscle by inhibition of PDEs and increase of cAMP concentration and raise the possibility of using indicaxanthin in the treatment of motility disorders, such as abdominal cramps. PMID:21371457
Inhibitory effects of antiviral compounds on respiratory syncytial virus replication in vitro.
Kawana, F; Shigeta, S; Hosoya, M; Suzuki, H; De Clercq, E
We examined the inhibitory effect of 20 antiviral compounds, including ribavirin, on the replication of respiratory syncytial virus in HeLa and HEp-2 cell cultures. Of the compounds studied, pyrazofurin and 3-deazaguanine emerged as more potent inhibitors of respiratory syncytial virus than ribavirin. Based on their inhibitory effect on the cytopathogenicity of respiratory syncytial virus in HeLa cells, the average 50% effective dose of pyrazofurin and 3-deazaguanine for eight strains was 0.07 and 1.65 micrograms/ml, respectively; that of ribavirin was 5.82 micrograms/ml. The cytotoxicity of these compounds for HeLa cells was examined by monitoring the incorporation of radiolabeled uridine into cellular RNA. The selectivity indexes of pyrazofurin and 3-deazaguanine exceeded that of ribavirin by 70- and 11-fold, respectively. Pyrazofurin, 3-deazaguanine, and ribavirin inhibited both viral antigen expression and syncytium formation in HeLa cell cultures, as assessed by an indirect immunofluorescence assay. In these assays, pyrazofurin and 3-deazaguanine again proved more potent than ribavirin. 2,5-Diamidinoindole and carbodine were less potent than ribavirin. Various other compounds, i.e., 3-adenin-9-yl-2-hydroxypropanoic acid isobutyl ester, 3-deazauridine, 3'-C-methyluridine, 5'-deoxy-5-fluorouridine, 5-cyanoimidazole-4-carboxamide, and its ribofuranosyl derivative, did not inhibit the cytopathic effect of the Long strain of respiratory syncytial virus at concentrations greater than or equal to 125 micrograms/ml. Tubercidin, 5-chlorotubercidin, xylotubercidin, neplanocin A, thiosemicarbazone R, and 3-methylquercetine were too toxic to HeLa cells for their inhibitory effects on respiratory syncytial virus to be examined. PMID:3307618
Minimum Description Length Principle for Linear Mixed Effects Models
Craiu, V. Radu
Minimum Description Length Principle for Linear Mixed Effects Models Li Li, Fang Yao , Radu V July 14, 2013 Abstracts The minimum description length (MDL) principle originated from data compression, Linear mixed effects, Minimum description length. Corresponding author, Email: fyao
7 CFR 701.10 - Qualifying minimum cost of restoration.
Code of Federal Regulations, 2010 CFR
... false Qualifying minimum cost of restoration. 701.10 Section 701.10 Agriculture...701.10 Qualifying minimum cost of restoration. (a) To qualify for assistance...establish the minimum qualifying cost of restoration. Each affected State may be...
Inhibitory effects of Turkish folk remedies on inflammatory cytokines: interleukin-1alpha, interleukin-1beta and tumor necrosis factor alpha.
Ye?ilada, E; Ustün, O; Sezik, E; Takaishi, Y; Ono, Y; Honda, G
In this study, in vitro inhibitory effects of 55 extracts or fractions obtained from 10 plant species on interleukin-1 (IL-1alpha, IL-1beta) and tumor necrosis factor (TNF-alpha) biosynthesis were studied. The following plant materials from Turkish folk medicine for the treatment of various diseases which are thought to be inflammatory in nature e.g. rheumatism, fever, infections, edemas or related inflammatory diseases were selected as the subject of this study: Cistus laurifolius leaves, Clematis flammna flowering herbs, Crataegus orientalis roots, Daphne oleoides ssp. oleoides whole plant, Ecbalium elaterium roots, Rosa canina roots, Rubus discolor roots, Rubus hirtus roots, Sambucus ebulus flowers and leaves, Sambucus nigra flowers and leaves. All plants showed inhibitory activity against at least one of these models in various percentages depending upon the concentration, thus supporting the folkloric utilization. Daphne oleoides was found to be the most active plant against the test models. PMID:9324006
Cardiovascular inhibitory effects of Hyoscyamus niger.
Khan, A-U; Gilani, A H
This study describes the hypotensive, cardiosuppressant and vasodilator activities of Hyoscyamus niger crude extract (Hn.Cr). Hn.Cr, which tested positive for alkaloids, coumarins, flavonoids, sterols, tannins and terpenes, caused a dose-dependent (10-100 mg/kg) fall in the arterial blood pressure (BP) of rats under anesthesia. In guinea-pig atria, Hn.Cr exhibited a cardiodepressant effect on the rate and force of spontaneous atrial contractions. In isolated rabbit aorta, Hn.Cr (0.01-1.0 mg/ml) relaxed the phenylephrine (PE, 1 microM) and K(+) (80 mM)-induced contractions and suppressed PE (1 microM) control peaks obtained in Ca(++)-free medium similar to that caused by verapamil. The vasodilator effect of Hn.Cr was endothelium-independent as it was not opposed by N (omega)-nitro-L-arginine methyl ester in endothelium-intact rat aortic preparations and also occurred at a similar concentration in endothelium-denuded tissues. These data indicate that Hyoscyamus niger lowers BP through a Ca(++)-antagonist mechanism. PMID:18773124
Growth inhibitory effect of peel extract from Citrus junos
Shinsuke Fujihara; Tokurou Shimizu
Extract from yuzu fruit peel (Citrus junos Sieb. ex Tanaka) strongly suppressed the germination of lettuce seeds while that from the peel of other citrus fruits such as navel orange (C. sinensis) and lemon (C. limon Burm. f.) had very little or no effect. The highest inhibitory activity was located in the peel followed by the segment but no significant
Novel inhibitory effect of the antidiabetic drug voglibose on melanogenesis.
Bin, Bum-Ho; Seo, Juyeon; Yang, Seung Ha; Lee, Eunkyung; Choi, Hyunjung; Kim, Kyu-Han; Cho, Eun-Gyung; Lee, Tae Ryong
Overproduction of melanin can lead to medical disorders such as postinflammatory melanoderma and melasma. Therefore, developing antimelanogenic agents is important for both medical and cosmetic purposes. In this report, we demonstrated for the first time that the antidiabetic drug voglibose is a potent antimelanogenic agent. Voglibose is a representative antidiabetic drug possessing inhibitory activity towards human ?-glucosidase; it blocked the proper N-glycan modification of tyrosinase, resulting in a dramatic reduction of the tyrosinase protein level by altering its stability and subsequently decreasing melanin production. Acarbose, another antihyperglycaemic drug that has a lower inhibitory effect on human intracellular ?-glucosidase compared with voglibose, did not cause any changes in either the N-glycan modification of tyrosinase or the tyrosinase protein level, indicating that voglibose was the most efficient antimelanogenic agent among the widely used antihyperglycaemic agents. Considering that voglibose was originally selected from the valiolamine derivatives in a screen for an oral antidiabetic drug with a strong inhibitory activity towards intestinal ?-glucosidase and low cell permeability, we propose an alternative strategy for screening compounds from valiolamine derivatives that show high inhibitory activity towards human intracellular ?-glucosidases and high cell permeability, with the goal of obtaining antimelanogenic agents that are effective inside the cells. PMID:23879813
Inhibitory circuits in sensory maps develop through Naoum P. Issa
Issa, Naoum
nucleus of the trapezoid body (MNTB) sends glycinergic inputs to the lateral superior olive (LSO) which brain slice. The inhibitory projections between the MNTB and LSO are part of an auditory circuit. An LSO neuron receives excitatory inputs from the ipsilateral side directly from the ventral cochlear
Inhibitory Control during Emotional Distraction across Adolescence and Early Adulthood
ERIC Educational Resources Information Center
Cohen-Gilbert, Julia E.; Thomas, Kathleen M.
This study investigated the changing relation between emotion and inhibitory control during adolescence. One hundred participants between 11 and 25 years of age performed a go-nogo task in which task-relevant stimuli (letters) were presented at the center of large task-irrelevant images depicting negative, positive, or neutral scenes selected from…
GABA as an Inhibitory Neurotransmitter in Human Cerebral Cortex
1. The possible role of y-aminobutyric acid (GABA) as an in- hibitory neurotransmitter in the human cerebral cortex was in- vestigated with the use of intracellular recordings from neocorti- cal slices maintained in vitro. 2. Electrical stimulation of afferents to presumed pyramidal cells resulted in an initial excitatory postsynaptic potential (EPSP) followed by fast and slow inhibitory postsynaptic potentials (IPSPs).
Transplant restoration of spinal cord inhibitory controls ameliorates neuropathic itch
Braz, Joao M.; Juarez-Salinas, Dina; Ross, Sarah E.; Basbaum, Allan I.
The transmission of pruritoceptive (itch) messages involves specific neural circuits within the spinal cord that are distinct from those that transmit pain messages. These itch-specific circuits are tonically regulated by inhibitory interneurons in the dorsal horn. Consistent with these findings, it has previously been reported that loss of GABAergic interneurons in mice harboring a deletion of the transcription factor Bhlhb5 generates a severe, nonremitting condition of chronic itch. Here, we tested the hypothesis that the neuropathic itch in BHLHB5-deficient animals can be treated by restoring inhibitory controls through spinal cord transplantation and integration of precursors of cortical inhibitory interneurons derived from the embryonic medial ganglionic eminence. We specifically targeted the transplants to segments of the spinal cord innervated by areas of the body that were most severely affected. BHLHB5-deficient mice that received transplants demonstrated a substantial reduction of excessive scratching and dramatic resolution of skin lesions. In contrast, the scratching persisted and skin lesions worsened over time in sham-treated mice. Together, these results indicate that cell-mediated restoration of inhibitory controls has potential as a powerful, cell-based therapy for neuropathic itch that not only ameliorates symptoms of chronic itch, but also may modify disease. PMID:25003193
Obesity, macrophage migration inhibitory factor, and weight loss
T S Church; M S Willis; E L Priest; M J LaMonte; C P Earnest; W J Wilkinson; D A Wilson; B P Giroir
OBJECTIVE:Elevated macrophage migration inhibitory factor (MIF) has been implicated as a causal mechanism in a number of disease conditions including cardiovascular disease (CVD), diabetes, and cancer. Excess body fat is associated with an increased risk of numerous health conditions including CVD, diabetes, and cancer. To our knowledge, the association between MIF and obesity status and the effect of weight loss
Inhibitory control and children's risk for dog bites
A L Davis; D C Schwebel; B A Morrongiello; J Stewart; M Bell; E E Oneal
IntroductionApproximately 400 000 US children seek medical attention for dog bites annually (CDC, 2008). A dozen die. Inhibitory control, the capacity to plan and suppress inappropriate approach responses under instruction or in novel situations (Rothbart et al, 2001), is linked to broad child injury risk (Schwebel & Plumert, 1999), but is poorly understood as a risk factor for pediatric dog
Conflict Inhibitory Control Facilitates Pretense Quality in Young Preschoolers
ERIC Educational Resources Information Center
Van Reet, Jennifer
The present research explores the role of inhibitory control (IC) in young preschoolers' pretense ability using an ego depletion paradigm. In Experiment 1 (N = 56), children's pretense ability was assessed either before or after participating in conflict IC or control tasks, and in Experiment 2 (N = 36), pretense ability was measured after…
Severe Osteoporosis in Mice Lacking Osteoclastogenesis Inhibitory Factor\\/Osteoprotegerin
Atsuko Mizuno; Norio Amizuka; Kazuharu Irie; Akihiko Murakami; Nobuaki Fujise; Takeshi Kanno; Yasushi Sato; Nobuaki Nakagawa; Hisataka Yasuda; Shin-ichi Mochizuki; Takashi Gomibuchi; Kazuki Yano; Nobuyuki Shima; Naohiro Washida; Eisuke Tsuda; Tomonori Morinaga; Kanji Higashio; Hidehiro Ozawa
Osteoclasts are multinucleated cells that resorb bone. Osteoclastogenesis inhibitory factor (OCIF), also called osteoprotegerin (OPG), acts as a naturally occurring decoy receptor for osteoclast differentiation factor, which mediates an essential signal to osteoclast progenitors for their differentiation into osteoclasts. Here we show that the OCIF\\/OPG knockout mice exhibited severe osteoporosis due to enhanced osteoclastogenesis when they grew to be adults.
Hunger, inhibitory control and distress-induced emotional eating.
van Strien, Tatjana; Ouwens, Machteld A; Engel, Carmen; de Weerth, Carolina
Self-reported emotional eating has been found to significantly moderate distress-induced food intake, with low emotional eaters eating less after a stress task than after a control task and high emotional eaters eating more. The aim of the present study was to explore possible underlying mechanisms by assessing possible associations with (1) ability to experience the typical post-stress reduction of hunger and (2) inhibitory control. We studied these effects in 54 female students who were preselected on the basis of extremely high or low scores on an emotional eating questionnaire. Using a within subject design we measured the difference of actual food or snack intake after a control or a stress task (Trier Social Stress Test). As expected, the moderator effect of emotional eating on distress-induced food intake was found to be only present in females with a failure to report the typical reduction of hunger immediately after a stress task (an a-typical hunger stress response). Contrary to our expectations, this moderator effect of emotional eating was also found to be only present in females with high ability to stop motor impulses (high inhibitory control). These findings suggest that an a-typical hunger stress response but not poor inhibitory control may underlie the moderator effect of emotional eating on distress-induced food intake. However, inhibitory control may play a role whether or not there is a moderator effect of self-reported emotional eating on distress-induced food intake. PMID:24768894
Inducible Mixotrophy in the Dinoflagellate Prorocentrum minimum.
Johnson, Matthew D
Prorocentrum minimum is a neritic dinoflagellate that forms seasonal blooms and red tides in estuarine ecosystems. While known to be mixotrophic, previous attempts to document feeding on algal prey have yielded low grazing rates. In this study, growth and ingestion rates of P. minimum were measured as a function of nitrogen (-N) and phosphorous (-P) starvation. A P. minimum isolate from Chesapeake Bay was found to ingest cryptophyte prey when in stationary phase and when starved of N or P. Prorocentrum minimum ingested two strains of Teleaulax amphioxeia at higher rates than six other cryptophyte species. In all cases -P treatments resulted in the highest grazing. Ingestion rates of -P cells on T. amphioxeia saturated at ~5 prey per predator per day, while ingestion by -N cells saturated at 1 prey per predator per day. In the presence of prey, -P treated cells reached a maximum mixotrophic growth rate (?max ) of 0.5 d(-1) , while -N cells had a ?max of 0.18 d(-1) . Calculations of ingested C, N, and P due to feeding on T. amphioxeia revealed that phagotrophy can be an important source of all three elements. While P. minimum is a proficient phototroph, inducible phagotrophy is an important nutritional source for this dinoflagellate. PMID:25510417
BACE1 and cholinesterase inhibitory activities of Nelumbo nucifera embryos.
Jung, Hyun Ah; Karki, Subash; Kim, Ji Hye; Choi, Jae Sue
The aim of the present study was to evaluate the comparative anti-Alzheimer's disease (AD) activities of different parts of Nelumbo nucifera (leaves, de-embryo seeds, embryos, rhizomes, and stamens) in order to determine the selectivity and efficient use of its individual components. Anti-AD activities of different parts of N. nucifera were evaluated via inhibitory activities on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and ?-site amyloid precursor protein-cleaving enzyme 1 (BACE1) along with scavenging activity on peroxynitrite (ONOO(-)). Among the evaluated parts of N. nucifera, the embryo extract exhibited significant inhibitory potential against BACE1 and BChE as well as scavenging activity against ONOO(-). Thus, the embryo extract was selected for detailed investigation on anti-AD activity using BACE1- and ChEs-inhibitory assays. Among the different solvent-soluble fractions, the dichloromethane (CH2Cl2), ethyl acetate (EtOAc), and n-butanol (n-BuOH) fractions showed promising ChEs and BACE1 inhibitory activities. Repeated column chromatography of the CH2Cl2, EtOAc and n-BuOH fractions yielded compounds 1-5, which were neferine (1), liensinine (2), vitexin (3), quercetin 3-O-glucoside (4) and northalifoline (5). Compound 2 exhibited potent inhibitory activities on BACE1, AChE, and BChE with respective IC50 values of 6.37 ± 0.13, 0.34 ± 0.02, and 9.96 ± 0.47 µM. Likewise, compound 1 showed potent inhibitory activities on BACE1, AChE, and BChE with IC50 values of 28.51 ± 4.04, 14.19 ± 1.46, and 37.18 ± 0.59 µM, respectively; the IC50 values of 3 were 19.25 ± 3.03, 16.62 ± 1.43, and 11.53 ± 2.21 µM, respectively. In conclusion, we identified potent ChEs- and BACE1-inhibitory activities of N. nucifera as well as its isolated constituents, which may be further explored to develop therapeutic and preventive agents for AD and oxidative stress related diseases. PMID:25300425
The Inhibitory Effect of Grasshopper's Cyperus (Cyperus iria L.) on the Seedling Growth of Five Malaysian Rice Varieties
Ismail, B. S.; Siddique, Mohammed Abu Bakar
Experiments were carried out in the laboratory and greenhouse to determine the growth inhibitory effects of Grassohopper's cyperus (Cyperus iria L.) on the seedlings of 5 Malaysian rice varieties namely MR211, MRQ74, MR220, MR84 and MR232. Three concentrations of the aqueous extract of the weed (12.5, 25.0 and 50.0 g/l) and weed debris (5, 10 and 20 g dry debris/1000 g soil) were used to test the allelopathic effect of C. iria on the growth of the rice plants. The weed leaf, stem and root extracts reduced the growth of the rice seedlings and showed selective activity in the varieties. The C. iria leaf and stem extracts showed comparatively higher growth inhibitory effects than those from the root. The weed extract caused more reduction in the root length of the rice plant compared to the shoot length. Among the rice varieties tested, MR232 was found to be more susceptible to the weed inhibitory effect. The leaf extract of C. iria at full strength caused root and shoot reduction of MR232 by 88.1% and 73.1% respectively (compared to the control). In most cases the fresh weight of the rice seedlings were more affected than the plant height. Weed debris caused significant reduction of leaf chlorophyll content in all the rice varieties tested with the exception of MR211. The chlorophyll content of MR232 was greatly affected by the weed debris which caused reduction of 36.4% compared to the control. The inhibitory effects of weed extracts and debris on rice growth parameters were found to be concentration dependent. PMID:24575211
In vitro inhibitory effect of piperlonguminine isolated from Piper longum on human cytochrome P450 1A2.
Song, Min; Hwang, Jae Yun; Lee, Min Young; Jee, Jun-Goo; Lee, You Mie; Bae, Jong-Sup; Kim, Jeong Ah; Lee, Seung Ho; Lee, Sangkyu
Piperlonguminine (PL), a major alkaloid isolated from Piper longum fruits, shows several biological activities including anti-tumor, anti-hyperlipidemic and anti-inflammatory effects. Although there have been studies of the biological effects of PL, the potential drug-interaction effect of PL following evaluation of inhibitory effects of cytochrome P450 (CYP) activities was not investigated. Here, to investigate the inhibitory effects of PL on the activities of CYP isoforms, CYP inhibition assays were conducted using a cocktail of probe substrates in pooled human liver microsome (HLMs) and human recombinant cDNA-expressed CYP. PL strongly inhibited CYP1A2-mediated phenacetin O-deethylation with an IC50 value of 8.8 ?M, as NADPH-independent inhibition, while other CYPs were not significantly inhibited. A Lineweaver-Burk plot resulted in the inhibition mechanism of PL being divided into two different modes, reversible competitive inhibition in a low concentration range of 0-16 ?M with a Ki value of 1.39 ?M and uncompetitive inhibitory behavior at a high concentration range of 16-40 ?M. In addition, PL only decreased CYP 1A2-catalyzed phenacetin O-deethylase activity with IC50 values of 10.0 ?M in human recombinant cDNA-expressed 1A2, not 1A1. Overall, this is the first investigation of potential herb-drug interactions associated with PL conducted by identifying the competitive inhibitory effects of PL on CYP1A2 in HLMs. PMID:24194261
Inhibitory effect of tocotrienol on eukaryotic DNA polymerase {lambda} and angiogenesis
Mizushina, Yoshiyuki [Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180 (Japan) and High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180 (Japan)]. E-mail: email@example.com; Nakagawa, Kiyotaka [Food and Biodynamic Chemistry Laboratory, Graduate School of Life Science and Agriculture, Tohoku University, Sendai 981-8555 (Japan); Shibata, Akira [Food and Biodynamic Chemistry Laboratory, Graduate School of Life Science and Agriculture, Tohoku University, Sendai 981-8555 (Japan); Awata, Yasutoshi [Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180 (Japan); Kuriyama, Isoko [Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180 (Japan); Shimazaki, Noriko [Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba 278-8510 (Japan); Koiwai, Osamu [Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba 278-8510 (Japan); Uchiyama, Yukinobu [Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba 278-8510 (Japan); Sakaguchi, Kengo [Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba 278-8510 (Japan); Miyazawa, Teruo [Food and Biodynamic Chemistry Laboratory, Graduate School of Life Science and Agriculture, Tohoku University, Sendai 981-8555 (Japan); Yoshida, Hiromi [Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180 (Japan); High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180 (Japan)
Tocotrienols, vitamin E compounds that have an unsaturated side chain with three double bonds, selectively inhibited the activity of mammalian DNA polymerase {lambda} (pol {lambda}) in vitro. These compounds did not influence the activities of replicative pols such as {alpha}, {delta}, and {epsilon}, or even the activity of pol {beta} which is thought to have a very similar three-dimensional structure to the pol {beta}-like region of pol {lambda}. Since {delta}-tocotrienol had the strongest inhibitory effect among the four ({alpha}- to {delta}-) tocotrienols, the isomer's structure might be an important factor in the inhibition of pol {lambda}. The inhibitory effect of {delta}-tocotrienol on both intact pol {lambda} (residues 1-575) and a truncated pol {lambda} lacking the N-terminal BRCA1 C-terminus (BRCT) domain (residues 133-575, del-1 pol {lambda}) was dose-dependent, with 50% inhibition observed at a concentration of 18.4 and 90.1 {mu}M, respectively. However, del-2 pol {lambda} (residues 245-575) containing the C-terminal pol {beta}-like region was unaffected. Tocotrienols also inhibited the proliferation of and formation of tubes by bovine aortic endothelial cells, with {delta}-tocotrienol having the greatest effect. These results indicated that tocotrienols targeted both pol {lambda} and angiogenesis as anti-cancer agents. The relationship between the inhibition of pol {lambda} and anti-angiogenesis by {delta}-tocotrienol was discussed.
The inhibitory activity of pomelo essential oil on the bacterial biofilms development on soft contact lenses.
Saviuc, Crina; Dasc?lu, Luminita; Chifiriuc, Mariana Carmen; R?dulescu, Valeria; Oprea, Eliza; Popa, Marcela; Hristu, Radu; Stanciu, George; Laz?r, Veronica
The aim of present study was to investigate the microbial colonization of worn contact lenses (CLs) and to evaluate the inhibitory effect of pomelo (Citrus maxima) peels essential oil on the biofilm development on unworn CLs. The essential oil was isolated by steam distillation and analyzed by gas chromatography coupled with mass spectrometry, twenty compounds being isolated. The antimicrobial activity of pomelo oil was tested against S. epidermidis and P. aeruginosa strains, known for their ability to develop biofilms on prosthetic devices, by qualitative screening methods and quantitative assay of the minimal inhibitory concentrations (MIC) in order to evaluate the antibiofilm activity. Our study revealed that all worn CLs where 100% colonized by staphylococci and Enterobacteriaceae strains. The pomelo essential oil inhibited the development of bacterial biofilms formed by Gram-positive and Gram-negative microorganisms on soft CLs, its antibiofilm activity being specific and dependent on different physical parameters (contact time and temperature). The architecture of bacterial biofilms developed on soft contact lenses was analyzed using confocal scanning laser microscopy (CSLM). PMID:21434591
Hypocholesterolemic Effect and In Vitro Pancreatic Lipase Inhibitory Activity of an Opuntia ficus-indica Extract
Flores-Fernandez, Jose Miguel; Fernandez-Flores, Ofelia; Gutierrez-Mercado, Yanet; Carmona-de la Luz, Joel; Sandoval-Salas, Fabiola; Mendez-Carreto, Carlos
Cholesterol control is fundamental for prevention of cardiovascular disorders. In this work, the hypocholesterolemic activity of an aqueous Opuntia ficus-indica extract (AOE) was tested in triton-induced mice. The inhibitory activity on pancreatic lipase enzyme was evaluated in vitro by the same extract. Furthermore, polyphenol content of the extract was evaluated. Hypercholesterolemia was induced in three groups of mice by intraperitoneal administration of Triton WR-1339. After induction of hypercholesterolemia, the groups were treated with an AOE (500?mg/kg) and saline solution and the positive control group with orlistat, respectively. Cholesterol levels were measured 24?h later in peripheral blood. The levels of blood cholesterol after administration of AOE significantly decreased compared to negative control. The inhibitory activity of AOE on pancreatic lipase enzyme was evaluated at concentrations from 60 to 1000??g/mL. The AOE inhibited the pancreatic lipase with an IC50 = 588.5??g/mL. The AOE had a high content of polyphenolic compounds. These results show that AOE is able to prevent hypercholesterolemia by pancreatic lipase inhibition, in part due to its polyphenolic compounds.
Xanthine oxidase inhibitory activity and hypouricemic effect of aspalathin from unfermented rooibos.
Kondo, Makoto; Hirano, Yoshiaki; Nishio, Masahiro; Furuya, Yutaka; Nakamura, Hiromichi; Watanabe, Tsuyoshi
Rooibos is rich in flavonoids such as aspalathin, which is a unique C-glycosyl dihydrochalcone, that is used as a traditional herbal tea. This study was designed to evaluate the in vitro xanthine oxidase (XOD) inhibitory activity of the aspalathin-rich fraction (ARF) and purified aspalathin from rooibos. The hypouricemic effects of the ARF and aspalathin on hyperuricemic mice were also assessed. The ARF was prepared from aqueous extract of unfermented rooibos leaves and stems, and it was collected by column chromatography; the aspalathin content in this fraction was 21.4%. The ARF and aspalathin inhibited XOD in a dose-dependent manner. The concentrations of the ARF and aspalathin required to inhibit XOD at 50% (IC50 ) were 20.4 ?g/mL (4.4 ?g/mL aspalathin equivalents) and 4.5 ?g/mL, respectively. Lineweaver-Burk plot analysis indicated that aspalathin was a competitive inhibitor of XOD, and the inhibition constant (Ki) was 3.1 ?M. In hyperuricemic mice induced by inosine-5'-monophosphate, treatment with the ARF and aspalathin significantly suppressed the increased plasma uric acid level in a dose-dependent manner. The suppressed plasma uric acid level in mice could be attributed to the XOD inhibitory activity of the ARF and aspalathin. Further study is required to determine the effect of aspalathin or its metabolites on XOD activity in vivo. PMID:24261664
Inhibitory simple partial (non-convulsive) status epilepticus after intracranial surgery
Armon, C.; Radtke, R.; Friedman, A.
OBJECTIVES—To report on five patients who developed, 2 to 4 days after an intracranial neurosurgical procedure, new, persistent, focal neurological deficits which were due to inhibitory simple partial (non-convulsive) status epilepticus, and resolved with anticonvulsant treatment.?METHODS—The age range of the five patients was 15-74 years. The operations were: aneurysm clipping (three patients) and resections of an oligodendroglioma and a cavernous haemangioma (one patient each). The new focal deficits were: right hemiparesis and aphasia (two patients), aphasia alone (two patients), and left hemiparesis (one patient). The deficits were not explained by CT (obtained in all patients) or cerebral angiography (performed in two).?RESULTS—Electroencephalography showed, in all patients, continuous or intermittent focal seizures arising from cortex regionally relevant to the clinical dysfunction. Subtle positive epileptic phenomena (jerking) occurred intermittently in three patients as a late concommitant. Administration of anticonvulsant drugs resulted in significant improvement within 24 hours in four patients, with parallel resolution of ictal EEG activity. The fifth patient improved more slowly. Two patients relapsed when anticonvulsant concentrations fell, and improved again when they were raised.?CONCLUSIONS—It is suggested that inhibitory simple partial (non-convulsive) status epilepticus be considered in the differential diagnosis when a new unexplained neurological deficit develops after an intracranial neurosurgical procedure. An EEG may help to diagnose this condition, leading to definitive treatment.?? PMID:10864598
Glutathione peroxidase inhibitory assay for electrophilic pollutants in diesel exhaust and tobacco smoke.
Staimer, Norbert; Nguyen, Tran B; Nizkorodov, Sergey A; Delfino, Ralph J
We developed a rapid kinetic bioassay demonstrating the inhibition of glutathione peroxidase 1 (GPx-1) by organic electrophilic pollutants, such as acrolein, crotonaldehyde, and p-benzoquinone, that are frequently found as components of tobacco smoke, diesel exhaust, and other combustion sources. In a complementary approach, we applied a high-resolution proton-transfer reaction time-of-flight mass spectrometer to monitor in real-time the generation of electrophilic volatile carbonyls in cigarette smoke. The new bioassay uses the important antioxidant selenoenzyme GPx-1, immobilized to 96-well microtiter plates, as a probe. The selenocysteine bearing subunits of the enzyme's catalytic site are viewed as cysteine analogues and are vulnerable to electrophilic attack by compounds with conjugated carbonyl systems. The immobilization of GPx-1 to microtiter plate wells enabled facile removal of excess reactive inhibitory compounds after incubation with electrophilic chemicals or aqueous extracts of air samples derived from different sources. The inhibitory response of cigarette smoke and diesel exhaust particle extracts were compared with chemical standards of a group of electrophilic carbonyls and the arylating p-benzoquinone. GPx-1 activity was directly inactivated by millimolar concentrations of highly reactive electrophilic chemicals (including acrolein, glyoxal, methylglyoxal, and p-benzoquinone) and extracts of diesel and cigarette smoke. We conclude that the potential of air pollutant components to generate oxidative stress may be, in part, a result of electrophile-derived covalent modifications of enzymes involved in the cytosolic antioxidant defense. PMID:22349402
Thailandepsins: Bacterial Products with Potent Histone Deacetylase Inhibitory Activities and Broad-Spectrum Antiproliferative Activities
Wang, Cheng; Henkes, Leonhard M.; Doughty, Leah B.; He, Min; Wang, Difei; Meyer-Almes, Franz-Josef; Cheng, Yi-Qiang
Histone deacetylase (HDAC) inhibitors have emerged as a new class of anticancer drugs, with one synthetic compound, SAHA (vorinostat, Zolinza®; 1), and one natural product, FK228 (depsipeptide, romidepsin, Istodax®; 2), approved by FDA for clinical use. Our studies of FK228 biosynthesis in Chromobacterium violaceum No. 968 led to the identification of a cryptic biosynthetic gene cluster in the genome of Burkholderia thailandensis E264. Genome mining and genetic manipulation of this gene cluster further led to the discovery of two new products, thailandepsin A (6) and thailandepsin B (7). HDAC inhibition assays showed that thailandepsins have selective inhibition profiles different from that of FK228, with comparable inhibitory activities to those of FK228 toward human HDAC1, HDAC2, HDAC3, HDAC6, HDAC7 and HDAC9, but weaker inhibitory activities than FK228 toward HDAC4 and HDAC8, the later of which could be beneficial. NCI-60 anticancer screening assays showed that thailandepsins possess broad-spectrum antiproliferative activities with GI50 for over 90% of the tested cell lines at low nanomolar concentrations, and potent cytotoxic activities towards certain types of cell lines, particularly for those derived from colon, melanoma, ovarian and renal cancers. Thailandepsins thus represent new naturally produced HDAC inhibitors that are promising for anticancer drug development. PMID:21793558
Inhibitory effects of kale ingestion on metabolism by cytochrome P450 enzymes in rats.
Yamasaki, Izumi; Yamada, Masayoshi; Uotsu, Nobuo; Teramoto, Sachiyuki; Takayanagi, Risa; Yamada, Yasuhiko
Kale (Brassica oleracea L. var acephala DC) is a leafy green vegetable belonging to the cabbage family (Brassicaceae) that contains a large amount of health-promoting phytochemicals. There are any reports about the effects of kale ingestion on the chemoprevention function and mechanism, but the interactions between kale and drugs have not been researched. We investigated the effects of kale intake on cytochrome P450 (CYP) metabolism by using cocktail probe drugs, including midazolam (for CYP3A4), caffeine (for CYP1A2), dextromethorphan (for CYP2D6), tolbutamide (for CYP2C9), omeprazole (for CYP2C19), and chlorzoxazone (for CYP2E1). Cocktail drugs were administered into rats treated with kale and cabbage (2000 mg/kg) for a week. The results showed that kale intake induced a significant increase in plasma levels and the AUC of midazolam, caffeine, and dextromethorphan. In addition, the plasma concentration and AUC of omeprazole tended to increase. Additionally, no almost differences in the mRNA expression levels of CYP enzymes in the liver were observed. In conclusion, kale ingestion was considered to have an inhibitory effect on the activities of CYP3A4, 1A2, 2D6, and 2C19 for a reason competitive inhibition than inhibitory changes in the mRNA expressions. PMID:22975634
Inhibitory effects of sea buckthorn procyanidins on fatty acid synthase and MDA-MB-231 cells.
Wang, Yi; Nie, Fangyuan; Ouyang, Jian; Wang, Xiaoyan; Ma, Xiaofeng
Fatty acid synthase (FAS) is overexpressed in many human cancers including breast cancer and is considered to be a promising target for therapy. Sea buckthorn has long been used to treat a variety of maladies. Here, we investigated the inhibitory effect of sea buckthorn procyanidins (SBPs) isolated from the seeds of sea buckthorn on FAS and FAS overexpressed human breast cancer MDA-MB-231 cells. The FAS activity and FAS inhibition were measured by a spectrophotometer at 340 nm of nicotinamide adenine dinucleotide phosphate (NADPH) absorption. We found that SBP potently inhibited the activity of FAS with a half-inhibitory concentration (IC50) value of 0.087 ?g/ml. 3-4,5-Dimethylthiazol-2-yl-2,3-diphenyl tetrazolium bromide (MTT) assay was used to test the cell viability. SBP reduced MDA-MB-231 cell viability with an IC50 value of 37.5 ?g/ml. Hoechst 33258/propidium iodide dual staining and flow cytometric analysis showed that SBP induced MDA-MB-231 cell apoptosis. SBP inhibited intracellular FAS activity with a dose-dependent manner. In addition, sodium palmitate could rescue the cell apoptosis induced by SBP. These results showed that SBP was a promising FAS inhibitor which could induce the apoptosis of MDA-MB-231 cells via inhibiting FAS. These findings suggested that SBP might be useful for preventing or treating breast cancer. PMID:24957042
Structure-activity relationships of 44 halogenated compounds for iodotyrosine deiodinase-inhibitory activity.
Shimizu, Ryo; Yamaguchi, Masafumi; Uramaru, Naoto; Kuroki, Hiroaki; Ohta, Shigeru; Kitamura, Shigeyuki; Sugihara, Kazumi
The aim of this study was to investigate the possible influence of halogenated compounds on thyroid hormone metabolism via inhibition of iodotyrosine deiodinase (IYD) activity. The structure-activity relationships of 44 halogenated compounds for IYD-inhibitory activity were examined in vitro using microsomes of HEK-293 T cells expressing recombinant human IYD. The compounds examined were 17 polychlorinated biphenyls (PCBs), 15 polybrominated diphenyl ethers (PBDEs), two agrichemicals, five antiparasitics, two pharmaceuticals and three food colorants. Among them, 25 halogenated phenolic compounds inhibited IYD activity at the concentration of 1×10(-4)M or 6×10(-4)M. Rose bengal was the most potent inhibitor, followed by erythrosine B, phloxine B, benzbromarone, 4'-hydroxy-2,2',4-tribromodiphenyl ether, 4-hydroxy-2,3',3,4'-tetrabromodiphenyl ether, 4-hydroxy-2',3,4',5,6'-pentachlorobiphenyl, 4'-hydroxy-2,2',4,5'-tetrabromodiphenyl ether, triclosan, and 4-hydroxy-2,2',3,4',5-pentabromodiphenyl ether. However, among PCBs and PBDEs without a hydroxyl group, including their methoxylated metabolites, none inhibited IYD activity. These results suggest that halogenated compounds may disturb thyroid hormone homeostasis via inhibition of IYD, and that the structural requirements for IYD-inhibitory activity include halogen atom and hydroxyl group substitution on a phenyl ring. PMID:24012475
Inhibitory effect of alpha-fetoprotein on the binding of myasthenia gravis antibody to acetylcholine receptor.
Brenner, T; Beyth, Y; Abramsky, O
The binding of myasthenia gravis antibody acetylcholine receptor (AcChoR) as measured in vitro by Radioimmunoassay with 125I-labeled alpha-bungarotoxin (alpha-BuTx), can be blocked by amniotic fluid, maternal serum, and umbilical cord serum. This inhibitory effect is due to alpha-fetoprotein present in high concentrations in amniotic fluid and serum, as shown by: (i) selective removal of several components from amniotic fluid and serum; (ii) selective addition of different components present in amniotic fluid and serum, including alpha-fetoprotein, to be radioimmunoassay; (iii) correlation between the inhibitory effect of both amniotic fluid and serum and between the amounts of alpha-fetoprotein they contain; (iv) blocking of the alpha-fetoprotein in vitro suggests a similar effect in vivo in pregnant women with myasthenia gravis. This effect may explain in part the variability in the development of neonatal myasthenia gravis in the babies, due to transplacental transfer of maternal anti-AcChoR antibody, only after delivery and only in the minority of the cases. It also may explain the appearnace of remissions in females with myasthenia gravis during the second and third trimesters of pregnancy. Similar phenomena observed during pregnancy in other autoimmune and immunopathogenic diseases also might be attributed to activity of alpha-fetoprotein. PMID:6158053
In vitro xanthine oxidase inhibitory and in vivo hypouricemic activity of herbal coded formulation (Gouticin).
Akram, Muhammad; Usmanghani, Khan; Ahmed, Iqbal; Azhar, Iqbal; Hamid, Abdul
Currently, natural products have been used in treating gouty arthritis and are recognized as xanthine oxidase inhibitors. Current study was designed to evaluate in vitro xanthine oxidase inhibitory potential of Gouticin and its ingredients extracts and in vivo hypouricemic activity of gouticin tablet 500 mg twice daily. Ethanol extracts of Gouticin and its ingredients were evaluated in vitro, at 200, 100, 50, 25 ? g/ml concentrations for xanthine oxidase inhibitory activity. IC(50) values of Gouticin and its ingredients were estimated. Further, in vivo therapeutic effect of Gouticin was investigated in comparison with allopathic medicine (Allopurinol) to treat gout. Total patients were 200 that were divided into test and control group. Herbal coded medicine (Gouticin) was given to test group and allopathic medicine allopurinol was administered to control group. In vitro, Gouticin has the highest percent inhibition at 96% followed by Allopurinol with 93% inhibition. In vivo study, mean serum uric acid level of patients was 4.62 mg/dl and 5.21mg/dl by use of Gouticin and Allopurinol at end of therapy. The study showed that herbal coded formulation gouticin and its ingredients are potential sources of natural xanthine oxidase inhibitors. Gouticin 500 mg twice daily is more effective than the allopurinol 300mg once daily in the management of gout. PMID:24811815
Inhibitory Effect of Arctigenin from Fructus Arctii Extract on Melanin Synthesis via Repression of Tyrosinase Expression.
Park, Hwayong; Song, Kwang Hoon; Jung, Pil Mun; Kim, Ji-Eun; Ro, Hyunju; Kim, Mi Yoon; Ma, Jin Yeul
To identify the active compound arctigenin in Fructus Arctii (dried seed of medicinal plant Arctium lappa) and to elucidate the inhibitory mechanism in melanogenesis, we analyzed melanin content and tyrosinase activity on B16BL6 murine melanoma and melan-A cell cultures. Water extracts of Fructus Arctii were shown to inhibit tyrosinase activity in vitro and melanin content in ? -melanocyte stimulating hormone-stimulated cells to similar levels as the well-known kojic acid and arbutin, respectively. The active compound arctigenin of Fructus Arctii displayed little or no cytotoxicity at all concentrations examined and decreased the relative melanin content and tyrosinase activity in a dose-dependent manner. Melanogenic inhibitory activity was also identified in vivo with zebrafish embryo. To determine the mechanism of inhibition, the effects of arctigenin on tyrosinase gene expression and tyrosinase promoter activity were examined. Also in addition, in the signaling cascade, arctigenin dose dependently decreased the cAMP level and promoted the phosphorylation of extracellular signal-regulated kinase. This result suggests that arctigenin downregulates cAMP and the tyrosinase enzyme through its gene promoter and subsequently upregulates extracellular signal-regulated kinase activity by increasing phosphorylation in the melanogenesis signaling pathway, which leads to a lower melanin content. PMID:23781272
An analysis of inhibitory junction potentials in the guinea-pig proximal colon
Hirst, GDS; Bywater, RAR; Teramoto, N; Edwards, FR
Intracellular recordings were made from either sheets or isolated bundles of the circular muscle layer of guinea-pig proximal colon and the responses evoked by stimulating inhibitory nerve fibres were analysed. Inhibitory junction potentials (IJPs), evoked by single stimuli, had two components which could be separated on their pharmacological and temporal characteristics and their voltage sensitivities. The initial component, which was abolished by apamin and reduced in amplitude by pyridoxalphosphate-6-azophenyl-2?,4?-disulphonic acid (PPADS), had a brief time course: its amplitude was changed when the external concentration of potassium ions ([K+]o) was changed. The second component of the IJP had a slower onset than the first component, was abolished by l-nitroarginine (NOLA) and oxadiazolo quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase: its amplitude was little affected by changing [K+]o and was increased when the membrane potential of the circular layer was hyperpolarized. The observations suggest that the initial component of the IJP results from the release of ATP which triggers an increase in membrane conductance to K+ and that the second component results from the release of nitric oxide which suppresses a background inward current. PMID:15194738
Minimum rock bolt force and minimum static acceleration in tetrahedral wedge stability: A probabilistic study
Pinnaduwa H. S. W. Kulatilake
An investigation of effect of variability of strength and orientation on stability of tetrahedral wedges with two free surfaces is presented. Study was limited to potential sliding along the line of intersection of the two joint planes. Minimum rock bolt force and minimum static acceleration were considered as output stability parameters in this study. An analytical procedure which combines a
State Minimum Competency Testing Programs: Resource Guide. Legislation and State Policy Authorizing Minimum Competency Testing.
ERIC Educational Resources Information Center
Pipho, Chris
This guide to legislation and state board of education policy on minimum competency testing is designed to explain the legal basis for minimum competency testing mandates in the various states. Specifically, it explores: the differences between board mandates and state legislation; details of the requirements--subject areas, grade promotion and…
Optimized laser turrets for minimum phase distortion
NASA Technical Reports Server (NTRS)
Vanderplaats, G. N.; Fuhs, A. E.; Blaisdell, G. A.
An analysis and computer program which optimizes laser turret geometry to obtain minimum phase distortion is described. Phase distortion due to compressible, inviscid flow over small perturbation laser turrets in subsonic or supersonic flow is calculated. The turret shape is determined by a two dimensional Fourier series; in a similar manner, the flow properties are given by a Fourier series. Phase distortion is calcualted for propagation at serveral combinations of elevation and azimuth angles. A sum is formed from the set of values, and this sum becomes the objective function for an optimization computer program. The shape of the turret is varied to provide minimum phase distortion.
Optimized laser turrets for minimum phase distortion
NASA Astrophysics Data System (ADS)
Vanderplaats, G. N.; Fuhs, A. E.; Blaisdell, G. A.
An analysis and computer program which optimizes laser turret geometry to obtain minimum phase distortion is described. Phase distortion due to compressible, inviscid flow over small perturbation laser turrets in subsonic or supersonic flow is calculated. The turret shape is determined by a two dimensional Fourier series; in a similar manner, the flow properties are given by a Fourier series. Phase distortion is calcualted for propagation at serveral combinations of elevation and azimuth angles. A sum is formed from the set of values, and this sum becomes the objective function for an optimization computer program. The shape of the turret is varied to provide minimum phase distortion.
Image Data Compression Having Minimum Perceptual Error
NASA Technical Reports Server (NTRS)
Watson, Andrew B. (Inventor)
A method is presented for performing color or grayscale image compression that eliminates redundant and invisible image components. The image compression uses a Discrete Cosine Transform (DCT) and each DCT coefficient yielded by the transform is quantized by an entry in a quantization matrix which determines the perceived image quality and the bit rate of the image being compressed. The quantization matrix comprises visual masking by luminance and contrast technique all resulting in a minimum perceptual error for any given bit rate, or minimum bit rate for a given perceptual error.
Image data compression having minimum perceptual error
NASA Technical Reports Server (NTRS)
Watson, Andrew B. (inventor)
A method for performing image compression that eliminates redundant and invisible image components is described. The image compression uses a Discrete Cosine Transform (DCT) and each DCT coefficient yielded by the transform is quantized by an entry in a quantization matrix which determines the perceived image quality and the bit rate of the image being compressed. The present invention adapts or customizes the quantization matrix to the image being compressed. The quantization matrix comprises visual masking by luminance and contrast techniques and by an error pooling technique all resulting in a minimum perceptual error for any given bit rate, or minimum bit rate for a given perceptual error.
Deep solar minimum and global Climate Changes
NASA Astrophysics Data System (ADS)
Abdel Hady, Ahmed
This paper examines the deep minimum of solar cycle 23 and its likely impact on climate change. In addition, a source region of the solar winds at solar activity minimum, especially in the solar cycle 23, the deepest during the last 100 years, has been studied. Solar activities have had notable effect on palaeoclimatic changes. Contemporary solar activities are so weak and hence expected to cause global cooling. Prevalent global warming, caused by building-up of green-house gases in the troposphere, seems to exceed this solar effect. This paper discusses this issue.
Deep solar minimum and global climate changes
NASA Astrophysics Data System (ADS)
Hady, Ahmed A.
This paper examines the deep minimum of solar cycle 23 and its potential impact on climate change. In addition, a source region of the solar winds at solar activity minimum, especially in the solar cycle 23, the deepest during the last 500 years, has been studied. Solar activities have had notable effect on palaeoclimatic changes. Contemporary solar activity are so weak and hence expected to cause global cooling. Prevalent global warming, caused by building-up of green-house gases in the troposphere, seems to exceed this solar effect. This paper discusses this issue.
Deep solar minimum and global climate changes.
Hady, Ahmed A
This paper examines the deep minimum of solar cycle 23 and its potential impact on climate change. In addition, a source region of the solar winds at solar activity minimum, especially in the solar cycle 23, the deepest during the last 500 years, has been studied. Solar activities have had notable effect on palaeoclimatic changes. Contemporary solar activity are so weak and hence expected to cause global cooling. Prevalent global warming, caused by building-up of green-house gases in the troposphere, seems to exceed this solar effect. This paper discusses this issue. PMID:25685420
The minimum distance approach to classification
NASA Technical Reports Server (NTRS)
Wacker, A. G.; Landgrebe, D. A.
The work to advance the state-of-the-art of miminum distance classification is reportd. This is accomplished through a combination of theoretical and comprehensive experimental investigations based on multispectral scanner data. A survey of the literature for suitable distance measures was conducted and the results of this survey are presented. It is shown that minimum distance classification, using density estimators and Kullback-Leibler numbers as the distance measure, is equivalent to a form of maximum likelihood sample classification. It is also shown that for the parametric case, minimum distance classification is equivalent to nearest neighbor classification in the parameter space.
Eustice, Ryan
BME ERGONOMICS AND REHABILITATION ENGINEERING CONCENTRATION1 F10 MS: 30 total credit hours minimum Advisor: Thomas J. Armstrong, Ph.D. (email@example.com) Ergonomics /Rehabilitation Engineering: IOE 463 Measurement and Design of Work (3) (I, II) (Prerequisite: IOE 333 Ergonomics) BIOMED E 534
Linking Impulsivity and Inhibitory Control Using Manual and Oculomotor Response Inhibition Tasks
Roberts, Walter; Fillmore, Mark T.; Milich, Richard
Separate cognitive processes govern the inhibitory control of manual and oculomotor movements. Despite this fundamental distinction, little is known about how these inhibitory control processes relate to more complex domains of behavioral functioning. This study sought to determine how these inhibitory control mechanisms relate to broadly defined domains of impulsive behavior. Thirty adults with attention-deficit/hyperactivity disorder (ADHD) and 28 comparison adults performed behavioral measures of inhibitory control and completed impulsivity inventories. Results suggest that oculomotor inhibitory control, but not manual inhibitory control, is related to specific domains of self-reported impulsivity. This finding was limited to the ADHD group; no significant relations between inhibitory control and impulsivity were found in comparison adults. These results highlight the heterogeneity of inhibitory control processes and their differential relations to different facets of impulsivity. PMID:21982865
Synthesis and inhibitory activity of thymidine analogues targeting Mycobacterium tuberculosis thymidine monophosphate kinase
Sara Van Poecke; Hélčne Munier-Lehmann; Olivier Helynck; Matheus Froeyen; Serge Van Calenbergh
We report on Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) inhibitory activities of a series of new 3?- and 5?-modified thymidine analogues including ?- and ?-derivatives. In addition, several analogues were synthesized in which the 4-oxygen was replaced by a more lipophilic sulfur atom to probe the influence of this modification on TMPKmt inhibitory activity. Several compounds showed an inhibitory potency
Dynamical Neural Network Model of Hippocampus with Excitatory and Inhibitory Neurons
NASA Astrophysics Data System (ADS)
Omori, Toshiaki; Horiguchi, Tsuyoshi
We propose a dynamical neural network model with excitatory neurons and inhibitory neurons for memory function in hippocampus and investigate the effect of inhibitory neurons on memory recall. The results by numerical simulations show that the introduction of inhibitory neurons improves the stability of the memory recall in the proposed model by suppressing the bursting of neurons.
Minimum Competency Testing--Grading or Evaluation?
ERIC Educational Resources Information Center
Prakash, Madhu Suri
The consequences of the minimum competency testing movement may bring into question the basic assumptions, goals, and expectations of our school system. The intended use of these tests is the assessment of students; the unintended consequence may be the assessment of the school system. There are two ways in which schools may fail in the context of…
Minimum Energy Pulse Synthesis Inverse Scattering Transform
Minimum Energy Pulse Synthesis via the Inverse Scattering Transform Charles L. Epstein LSNI profile and certain auxiliary parameters used in the inverse scattering transform (IST) approach to RF-pulse of nuclear magnetic resonance. The oldest method of pulse synthesis is the Fourier transform method
Maximizing the Minimum Load for Selfish Agents
Leah Epstein; Rob Van Stee
We consider the problem of maximizing the minimum load for machines that are controlled by selfish agents, who are only interested in maximizing their o wn profit. Unlike the regular load balancing problem, this problem has not been considered in this context before. For a constant number of machines, m, we show a monotone polynomial time approximation scheme (PTAS) with
Maximizing the minimum load for selfish agents
Leah Epstein; Rob Van Stee
We consider the problem of maximizing the minimum load (completion time) for machines that are controlled by selfish agents, who are only interested in maximizing their own profit. Unlike the classical load balancing problem, this problem has not been considered for selfish agents until now. The goal is to design a truthful mechanism, i.e., one in which all users have
Minimum Competency Testing: A Curricular Debate.
ERIC Educational Resources Information Center
Page, Reba Neukom
The symbolic function of curricular debate, as it is manifested in the minimum competency testing movement (MCT), is investigated. Curricular debate necessarily reflects the demands of the society in which it arises. The topics that are addressed spring from this milieu and the language in which issues are couched must be appropriate to it.…
Aurora borealis lag during the Maunder minimum
Ludwig Schlamminger
Observations of 121 occurrences of the aurora borealis recorded in Central Europe from 1645 to 1712 C.E. are compared with known phase relationships between auroral activity and sunspot cycles in modern times. A remarkable analogy of the aurora borealis cycles during the Maunder minimum is found, both with respect to phase-dependent frequency and to delayed maxima, with aurorae during the
University Scholarships Minimum Credit Hour Contract
Olsen Jr., Dan R.
University Scholarships Minimum Credit Hour Contract · If you are a recipient of a university for either the 28-Credit Hour Alternative OR the Credit Hour Reduction for Final Enrollment. 28-Credit Hour Alternative Once you have been notified of a scholarship, you may contract to complete 28 credit hours during
Minimum Standards for Tribal Child Care Centers.
ERIC Educational Resources Information Center
Administration on Children, Youth, and Families (DHHS), Washington, DC. Child Care Bureau.
These minimum standards for tribal child care centers are being issued as guidance. An interim period of at least 1 year will allow tribal agencies to identify implementation issues, ensure that the standards reflect tribal needs, and guarantee that the standards provide adequate protection for children. The standards will be issued as regulations…
Testing Beyond Minimums. Occasional Paper #5.
ERIC Educational Resources Information Center
Rudman, Herbert C.
This paper considers three areas related to the testing of minimum knowledge and skills: public policy, the nature of higher-order thinking and selected aspects of educational measurement. The discussion of public policy issues centers around an apparent dichotomy of egalitarianism and elitism in public education, schooling and the public economy,…
Minimum required signal for LIMARS experiments
Lawrence E. Myers
This report determines the minimum detectable signal required to perform the Laser Imaging and Ranging System experiment. LIMARS is a direct detection laser radar using a novel receiver scheme to produce a pixel-registered range image without scanning. This work was motivated by the need to size the transmitter laser which, for this experimental system, is a Nd:YAG laser operation at
A Laser Range Scanner Designed for Minimum
Stanford University
and Modeling3D Digital Imaging and Modeling 3DIM 20013DIM 2001 #12;2 Scanner Designs #12;3 Scanner DesignA Laser Range Scanner Designed for Minimum Calibration Complexity James Davis,James Davis, XingXing ChenChen Stanford Computer Graphics LaboratoryStanford Computer Graphics Laboratory 3D Digital Imaging
Solar Radius at Minimum of Cycle 23
NASA Astrophysics Data System (ADS)
Sigismondi, Costantino
Observations of Baily beads in French Guyana, during 2006 September 22 annular eclipse, have been made to measure solar radius around solar minimum activity of cycle 23. The correction to standard solar radius at unit distance (1 AU) 959.63" to fit observations is ?R? = -0.01" ± 0.17". Sources of errors are outlined in view of relativistic accuracies.
Minimum Standards for Day Care Centers.
ERIC Educational Resources Information Center
Texas State Dept. of Public Welfare, Austin.
This document describes the minimum standards that must be met and maintained by day care centers in the state of Texas. These standards were drawn up by the State Department of Public Welfare and are applicable to both non-profit and proprietary day care centers. The areas covered by the standards include: (1) organization and general…
State Minimum Competency Testing: A Survey.
ERIC Educational Resources Information Center
Simmons, Robert M.
Information regarding state minimum competency testing programs was requested from the 50 state departments of education in the United States in the spring of 1979. The following questions were asked: (1) Do you have a testing program? (2) If you do, what tests are being used? (3) Do you have a testing program in the planning stages? (4) Are there…
Minimum ignition energy of nylon fibres
L. Marmo; D. Cavallero
The aim of this paper is to provide new experimental data on the minimum ignition energy (MIE) of clouds of fibres dispersed in the air. Nylon fibres from an Italian flock manufacturer (diameter between 10 and 27.4?m, length between 600 and 1800?m) were collected and tested in a modified Hartmann tube in order to measure the MIE. The instrument is
Solving the Minimum Weighted Integer Coloring Problem
Jue Xue
In this paper, we present, as we are aware of, the first combinatorialalgorithm specifically designed for the minimum weighted integercoloring problem (MWIP). We test the algorithm on randomly generated graphs with integer weights uniformly drawn from intervals [1, 1], [1, 2], [1, 5], [1, 10], [1, 15], and [1, 20]. We also use theproposed algorithm to test the quality of
7 CFR 33.10 - Minimum requirements.
Code of Federal Regulations, 2010 CFR
...REGULATIONS ISSUED UNDER AUTHORITY OF THE EXPORT APPLE ACT Regulations § 33.10 Minimum requirements...receive for transportation, any shipment of apples to any foreign destination unless: (a) Apples grade at least U.S. No. 1 or U.S....
7 CFR 33.10 - Minimum requirements.
Code of Federal Regulations, 2012 CFR
...REGULATIONS ISSUED UNDER AUTHORITY OF THE EXPORT APPLE ACT Regulations § 33.10 Minimum requirements...receive for transportation, any shipment of apples to any foreign destination unless: (a) Apples grade at least U.S. No. 1 or U.S....
7 CFR 33.10 - Minimum requirements.
Code of Federal Regulations, 2013 CFR
...REGULATIONS ISSUED UNDER AUTHORITY OF THE EXPORT APPLE ACT Regulations § 33.10 Minimum requirements...receive for transportation, any shipment of apples to any foreign destination unless: (a) Apples grade at least U.S. No. 1 or U.S....
7 CFR 33.10 - Minimum requirements.
Code of Federal Regulations, 2014 CFR
...REGULATIONS ISSUED UNDER AUTHORITY OF THE EXPORT APPLE ACT Regulations § 33.10 Minimum requirements...receive for transportation, any shipment of apples to any foreign destination unless: (a) Apples grade at least U.S. No. 1 or U.S....
7 CFR 33.10 - Minimum requirements.
Code of Federal Regulations, 2011 CFR
...REGULATIONS ISSUED UNDER AUTHORITY OF THE EXPORT APPLE ACT Regulations § 33.10 Minimum requirements...receive for transportation, any shipment of apples to any foreign destination unless: (a) Apples grade at least U.S. No. 1 or U.S....
Optimum minimum variance fixed interval smoothing
Garry A. Einicke
The paper describes an optimal minimum-variance fixed-interval smoother. The optimal solution involves a cascade of a Kalman predictor and an adjoint Kalman predictor. Speech enhancement and nonlinear demodulation examples are presented which demonstrate that optimal and extended Kalman smoothers can provide performance benefits.
Inhibitory Activity of Eleven Artemisia Species from Iran against Leishmania Major Parasites
Emami, Seyed Ahmad; Zamanai Taghizadeh Rabe, Shahrzad; Ahi, Ali; Mahmoudi, Mahmoud
Objective(s) Annual incidence of cutaneous leishmaniasis is increasingly growing and development of the alternative drugs against it is a major concern. Artemisia genus is a traditional medicinal plant in Iran. The aim of this study was to examine the leishmanicidal activity of various Iranian Artemisia species extracts. Materials and Methods Different extracts were gathered from eleven Iranian Artemisia species. Their leishmanicidal activities against the growth of Leishmania major (L. major) promastigotes were examined as the half maximal inhibitory concentration (IC50) using MTT assay. Results Obtained results showed that ethanol extracts especially those taken from A. ciniformis, A. santolina and A. kulbadica have the strongest effects. Conclusion Looking for the effective leishmanicidal agents from natural resources in Iran, we found that the ethanol extract of collected Artemisia species had significant effect on in vitro leishmanicidal activity and may be suitable candidates in the treatment of leishmaniasis. PMID:23493354
Postsynaptic distribution of IRSp53 in spiny excitatory and inhibitory neurons
Burette, Alain C.; Park, Haram; Weinberg, Richard J.
The 53 kDa insulin receptor substrate protein (IRSp53) is highly enriched in the brain. Despite evidence that links mutations of IRSp53 with autism and other neuropsychiatric problems, the functional significance of this protein remains unclear. We here use light and electron microscopic immunohistochemistry to demonstrate that IRSp53 is expressed throughout the adult rat brain. Labeling concentrated selectively in dendritic spines, where it was associated with the postsynaptic density. Surprisingly, its organization within the PSD of spiny excitatory neurons of neocortex and hippocampus differed from that within spiny inhibitory neurons of neostriatum and cerebellar cortex. The present data support previous suggestions that IRSp53 is involved in postsynaptic signaling, while hinting that its signaling role may differ in different types of neurons. PMID:24639075
"Brain MR spectroscopy in autism spectrum disorder—the GABA excitatory/inhibitory imbalance theory revisited"
Brix, Maiken K.; Ersland, Lars; Hugdahl, Kenneth; Grüner, Renate; Posserud, Maj-Britt; Hammar, Ĺsa; Craven, Alexander R.; Noeske, Ralph; Evans, C. John; Walker, Hanne B.; Midtvedt, Tore; Beyer, Mona K.
Magnetic resonance spectroscopy (MRS) from voxels placed in the left anterior cingulate cortex (ACC) was measured from 14 boys with Autism Spectrum Disorder (ASD) and 24 gender and age-matched typically developing (TD) control group. Our main aims were to compare the concentration of ?-aminobutyric acid (GABA) between the two groups, and to investigate the relationship between brain metabolites and autism symptom severity in the ASD group. We did find a significant negative correlation in the ASD group between Autism Spectrum Screening Questionnaire (ASSQ) and GABA+/Cr, which may imply that severity of symptoms in ASD is associated with differences in the level of GABA in the brain, supporting the excitatory/inhibitory (E/I) imbalance theory. However we did not find a significant difference between the two groups in GABA levels. PMID:26157380
Modeling and simulation of mixed-culture interactions in anaerobiosis of inhibitory substrate
Chua, H. [Hong Kong Polytechnic Univ., Kowloon (Hong Kong); Yap, M.G.S.; Ng, N.J. [National Univ. of Singapore, Kent Ridge (Singapore)
The model describes the anaerobiosis of 2-ethylhexanoic acid (2-EHA), which is a persistent and inhibitory organic waste. Model development was based on a biphasic degradation pathway mediated by three groups of bacteria. The model comprises seven equations with 13 constant parameters. The distinctive features include: (1) Grouping of anaerobic bacteria according to the metabolic functions; (2) Description of all essential reactions and mixed-culture interactions, namely interspecies H{sub 2} and volatile fatty acid transfers; and (3) Correlation of 2-EHA inhibition with the concentration of unionized 2-EHA. The validated and fine-tuned model was applied to simulate substrate utilization, intermediate and product formations, and bacterial cell synthesis.
Inhibitory effect of gymnemic acid on intestinal absorption of oleic acid in rats.
Wang, L F; Luo, H; Miyoshi, M; Imoto, T; Hiji, Y; Sasaki, T
Gymnemic acid, a mixture of triterpene glycosides extracted from the leaves of Gymnema sylvestre, is known to inhibit the intestinal absorption of glucose in human and rats. This work examined the effect of gymnemic acid on oleic acid absorption by the method of intestinal perfusion in rats. The results showed the following. (i) Gymnemic acid potently inhibited the absorption of oleic acid in intestine. (ii) This inhibition was dose dependent and reversible. (iii) The extent of inhibition and the recovery progress were extremely similar to that of glucose absorption. (iv) Taurocholate did not affect the inhibitory effect of gymnemic acid on oleic acid absorption, but lowering its concentration facilitated the recovery from the inhibition. (v) The absorption of oleic acid was not affected by other glycosides such as phloridzin, stevioside, and glycyrrhizin. These new findings are important for understanding the roles of gymnemic acid in therapy of diabetes mellitus and obesity. PMID:10100884
Minimum Wage Laws and the Distribution of Employment.
ERIC Educational Resources Information Center
Lang, Kevin
The desirability of raising the minimum wage long revolved around just one question: the effect of higher minimum wages on the overall level of employment. An even more critical effect of the minimum wage rests on the composition of employment--who gets the minimum wage job. An examination of employment in eating and drinking establishments…
Minimum Encoding Approaches for Predictive Modeling Peter Grunwald
Myllymäki, Petri
inference and model selection: the Minimum Description Length (MDL) principle, and the Minimum Message selection are the Minimum Descrip tion Length (MDL) principle (Rissanen, 1978, 1987, 1996), and the Minimum Length (MML) principle. Based on this analysis, we present two revised versions of MML: a pointwise
Identification of Michael Acceptor-Centric Pharmacophores with Substituents That Yield Strong Thioredoxin Reductase Inhibitory Character Correlated to Antiproliferative Activity
Gan, Fei-Fei; Kaminska, Kamila K.; Yang, Hong; Liew, Chin-Yee; Leow, Pay-Chin; So, Choon-Leng; Tu, Lan N.L.; Roy, Amrita; Yap, Chun-Wei; Kang, Tse-Siang; Chui, Wai-Keung
Abstract Aims: The role of thioredoxin reductase (TrxR) in tumorigenesis has made it an attractive anticancer target. A systematic approach for development of novel compounds as TrxR inhibitors is currently lacking. Structurally diversified TrxR inhibitors share in common electrophilic propensities for the sulfhydryl groups, among which include the Michael reaction acceptors containing an ?,?-unsaturated carbonyl moiety. We aimed to identify features among structurally diversified Michael acceptor-based compounds that would yield a strong TrxR inhibitory character. Results: Structurally dissimilar Michael acceptor-based natural compounds such as isobutylamides, zerumbone, and shogaols (SGs) were found to possess a poor TrxR inhibitory activity, indicating that a sole Michael acceptor moiety was insufficient to produce TrxR inhibition. The 1,7-diphenyl-hept-3-en-5-one pharmacophore in 3-phenyl-3-SG, a novel SG analog that possessed comparable TrxR inhibitory and antiproliferative potencies as 6-SG, was modified to yield 1,5-diphenyl-pent-1-en-3-one (DPPen) and 1,3-diphenyl-pro-1-en-3-one (DPPro, also known as chalcone) pharmacophores. These Michael acceptor-centric pharmacophores, when substituted with the hydroxyl and fluorine groups, gave rise to analogs displaying a TrxR inhibitory character positively correlated to their antiproliferative potencies. Lead analogs 2,2?-diOH-5,5?-diF-DPPen and 2-OH-5-F-DPPro yielded a half-maximal TrxR inhibitory concentration of 9.1 and 10.5??M, respectively, after 1-h incubation with recombinant rat TrxR, with the C-terminal selenocysteine residue found to be targeted. Innovation: Identification of Michael acceptor-centric pharmacophores among diversified compounds demonstrates that a systematic approach to discover and develop Michael acceptor-based TrxR inhibitors is feasible. Conclusion: A strong TrxR inhibitory character correlated to the antiproliferative potency is attributed to structural features that include an ?,?-unsaturated carbonyl moiety centered in a DPPen or DPPro pharmacophore bearing hydroxyl and fluorine substitutions. Antioxid. Redox Signal. 19, 1149–1165. PMID:23311917
Concentration of vanadium in soil water and its effect on growth and metabolism of rye and wheat plants
Minobu Kasai; Junichi Yamazaki; Miho Kikuchi; Miyuki Iwaya; Shinichi Sawada
Because the vanadium (V) chemistry provides that a significant amount of V in soil water can exist as vanadate which has been shown to have inhibitory effects on plant some enzymes, we analyzed the concentration of V in soil water, and examined the effect of such concentrations of vanadate on plant growth and metabolism. Concentration of V in water of
Flavonoids from Salvia chloroleuca with ?-Amylsae and ?-Glucosidase Inhibitory Effect.
Asghari, Behvar; Salehi, Peyman; Sonboli, Ali; Nejad Ebrahimi, Samad
It is believed that the inhibition of carbohydrate hydrolyzing enzymes including ?-amylase and ?-glucosidase is one of the therapeutic approaches to decrease the postprandial glucose level after a meal, especially in the people with type 2 diabetes. Medicinal plants and their extracts are one of the main sources to find new inhibitors to the enzymes. In our study four flavonoids, namely luteolin 7-O-glucoside (1), luteolin 7-O-glucuronide (2), diosmetin 7-O-glucuronide (3) and salvigenin (4) were isolated from aerial parts of Salvia chloroleuca. The inhibitory activity of these compounds against ?-amylase and ?-glucosidase were evaluated. Compounds 1, 2 and 3 showed potent ?-glucosidase inhibitory effect with IC50 values of 18.3, 14.7, and 17.1 µM, respectively. Also these compounds exhibited moderate ?-amylase activity with IC50 values 81.7, 61.5, and 76.3 µM, respectively. PMID:25901170
Lipoxygenase inhibitory activity of Cuspidaria pulchra and isolated compounds.
Alvarenga, Tavane A; Bertanha, Camila S; de Oliveira, Pollyanna F; Tavares, Denise C; Gimenez, Valéria M M; Silva, Márcio L A; Cunha, Wilson R; Januário, Ana H; Pauletti, Patrícia M
This work evaluated the in vitro inhibitory activity of the crude ethanolic extract from the aerial parts of Cuspidaria pulchra (Cham.) L.G. Lohmann against 15-lipoxygenase (15-LOX). The bioassay-guided fractionation of the n-butanol fraction, which displayed the highest activity, led to the isolation of three compounds: caffeoylcalleryanin (1), verbascoside (2) and 6-hydroxyluteolin-7-O-?-glucoside (3). Assessment of the ability of the isolated compounds to inhibit 15-LOX revealed that compounds 1, 2 and 3 exerted strong 15-LOX inhibitory activity; IC50 values were 1.59, 1.76 and 2.35 ?M respectively. The XTT assay showed that none of the isolated compounds seemed to be significantly toxic. PMID:25428032
Spikes matter for phase-locked bursting in inhibitory neurons
NASA Astrophysics Data System (ADS)
Jalil, Sajiya; Belykh, Igor; Shilnikov, Andrey
We show that inhibitory networks composed of two endogenously bursting neurons can robustly display several coexistent phase-locked states in addition to stable antiphase and in-phase bursting. This work complements and enhances our recent result [Jalil, Belykh, and Shilnikov, Phys. Rev. EPLEEE81539-375510.1103/PhysRevE.81.045201 81, 045201(R) (2010)] that fast reciprocal inhibition can synchronize bursting neurons due to spike interactions. We reveal the role of spikes in generating multiple phase-locked states and demonstrate that this multistability is generic by analyzing diverse models of bursting networks with various fast inhibitory synapses; the individual cell models include the reduced leech heart interneuron, the Sherman model for pancreatic beta cells, and the Purkinje neuron model.
Flavonoids from Salvia chloroleuca with ?-Amylsae and ?-Glucosidase Inhibitory Effect
Asghari, Behvar; Salehi, Peyman; Sonboli, Ali; Nejad Ebrahimi, Samad
It is believed that the inhibition of carbohydrate hydrolyzing enzymes including ?-amylase and ?-glucosidase is one of the therapeutic approaches to decrease the postprandial glucose level after a meal, especially in the people with type 2 diabetes. Medicinal plants and their extracts are one of the main sources to find new inhibitors to the enzymes. In our study four flavonoids, namely luteolin 7-O-glucoside (1), luteolin 7-O-glucuronide (2), diosmetin 7-O-glucuronide (3) and salvigenin (4) were isolated from aerial parts of Salvia chloroleuca. The inhibitory activity of these compounds against ?-amylase and ?-glucosidase were evaluated. Compounds 1, 2 and 3 showed potent ?-glucosidase inhibitory effect with IC50 values of 18.3, 14.7, and 17.1 µM, respectively. Also these compounds exhibited moderate ?-amylase activity with IC50 values 81.7, 61.5, and 76.3 µM, respectively. PMID:25901170
Evidence for the putative cannabinoid receptor, GPR55, mediated inhibitory effects on intestinal contractility in mice
Ross, Gracious R; Lichtman, Aron; Dewey, William L; Akbarali, Hamid I
Background Cannabinoids inhibit intestinal motility via presynaptic cannabinoid receptor type I(CB1) in enteric neurons while cannabinoid receptor type II (CB2) receptors are located mainly in immune cells. The recently deorphanized G-protein-coupled receptor, GPR55, has been proposed to be the "third" cannabinoid receptor. Although gene expression of GPR55 is evident in the gut, functional evidence for GPR55 in the gut is unknown. In this study, we tested the hypothesis that GPR55 activation inhibits neurogenic contractions in the gut. Methods We assessed the inhibitory effect of the atypical cannabinoid O-1602, a GPR55 agonist, in mouse colon. Isometric tension recordings in colonic tissue strips were used from either wild type, GPR55?/? or CB1?/?/CB2?/?knock-out mice. Results O-1602 inhibited the electrical field-induced contractions in the colon strips from wild type and CB1?/?/CB2?/? in a concentration–dependent manner, suggesting a non-CB1/CB2-receptor mediated prejunctional effect. The concentration–dependent response of O-1602 was significantly inhibited in GPR55?/? mice. O-1602 did not relax colonic strips pre-contracted with high K+ (80 mmol/l), indicating no involvement of Ca2+ channel blockade in O-1602–induced relaxation. However, 10 ?mol/l O-1602 partially inhibited the exogenous acetylcholine (10 ?mol/l) –induced contractions. Moreover, we also assessed the inhibitory effects of JWH 015, a CB2/GPR55 agonist on neurogenic contractions of mouse ileum. Surprisingly, the effects of JWH015 were independent of the known cannabinoid receptors. Conclusion These findings taken together suggest that activation of GPR55 leads to inhibition of neurogenic contractions in the gut, and are predominantly prejunctional. PMID:22759743
Inhibitory effect of selenium against Penicillium expansum and its possible mechanisms of action.
Wu, Zhi-Lin; Yin, Xue-Bin; Lin, Zhi-Qing; Bańuelos, Gary S; Yuan, Lin-Xi; Liu, Ying; Li, Miao
Some organic and inorganic salts could inhibit the growth of many pathogens. Selenium (Se), as an essential micronutrient, was effective in improving the plant resistance and antioxidant capacity at a low concentration. Penicillium expansum is one of the most important postharvest fungal pathogens, which can cause blue mold rot in various fruits and vegetables. In this study, the inhibitory effect of Se against P. expansum was evaluated. The result showed that Se strongly inhibited spore germination, germ tube elongation, and mycelial spread of P. expansum in the culture medium. The inhibitory effect was positively related to the concentration of Se used. Fluorescence microscopy observation of P. expansum conidia stained with propidium iodide (PI) indicated that the membrane integrity decreased to 37 % after the conidia were treated with Se (20 mg/l) for 9 h. With the use of an oxidant-sensitive probe 2,7-dichlorofluorescin (DCHF-DA), we found that Se at 15 mg/l could induce the generation of intracellular reactive oxygen species (ROS). Furthermore, methane dicarboxylic aldehyde (MDA) content, hydrogen peroxide (H2O2), and superoxide anion (O2 (-)) production rate in P. expansum spores exposed to Se increased markedly. Compared with the control, the activities of superoxide dismutase (SOD) and the content of glutathione (GSH) were reduced, confirming that damage of Se to cellular oxygen-eliminating system is the main reason. These results suggest that Se might serve as a potential alternative to synthetic fungicides for the control of the postharvest disease of fruit and vegetables caused by P. expansum. PMID:24682262
Sub-Inhibitory Fosmidomycin Exposures Elicits Oxidative Stress in Salmonella enterica Serovar typhimurium LT2
Fox, David T.; Schmidt, Emily N.; Tian, Hongzhao; Dhungana, Suraj; Valentine, Michael C.; Warrington, Nicole V.; Phillips, Paul D.; Finney, Kellan B.; Cope, Emily K.; Leid, Jeff G.; Testa, Charles A.; Koppisch, Andrew T.
Fosmidomycin is a time-dependent nanomolar inhibitor of methylerythritol phosphate (MEP) synthase, which is the enzyme that catalyzes the first committed step in the MEP pathway to isoprenoids. Importantly, fosmidomycin is one of only a few MEP pathway-specific inhibitors that exhibits antimicrobial activity. Most inhibitors identified to date only exhibit activity against isolated pathway enzymes. The MEP pathway is the sole route to isoprenoids in many bacteria, yet has no human homologs. The development of inhibitors of this pathway holds promise as novel antimicrobial agents. Similarly, analyses of the bacterial response toward MEP pathway inhibitors provides valuable information toward the understanding of how emergent resistance may ultimately develop to this class of antibiotics. We have examined the transcriptional response of Salmonella enterica serovar typhimurium LT2 to sub-inhibitory concentrations of fosmidomycin via cDNA microarray and RT-PCR. Within the regulated genes identified by microarray were a number of genes encoding enzymes associated with the mediation of reactive oxygen species (ROS). Regulation of a panel of genes implicated in the response of cells to oxidative stress (including genes for catalases, superoxide dismutases, and alkylhydrogen peroxide reductases) was investigated and mild upregulation in some members was observed as a function of fosmidomycin exposure over time. The extent of regulation of these genes was similar to that observed for comparable exposures to kanamycin, but differed significantly from tetracycline. Furthermore, S. typhimurium exposed to sub-inhibitory concentrations of fosmidomycin displayed an increased sensitivity to exogenous H2O2 relative to either untreated controls or kanamycin-treated cells. Our results suggest that endogenous oxidative stress is one consequence of exposures to fosmidomycin, likely through the temporal depletion of intracellular isoprenoids themselves, rather than other mechanisms that have been proposed to facilitate ROS accumulation in bacteria (e.g. cell death processes or the ability of the antibiotic to redox cycle). PMID:24751777
Synthesis and evaluation of c-Src kinase inhibitory activity of pyridin-2(1H)-one derivatives.
Chand, Karam; Prasad, Suchita; Tiwari, Rakesh K; Shirazi, Amir N; Kumar, Sumit; Parang, Keykavous; Sharma, Sunil K
Src kinase, a prototype member of the Src family of kinases (SFKs), is over-expressed in various human tumors, and has become a target for anticancer drug design. In this perspective, a series of eighteen 2-pyridone derivatives were synthesized and evaluated for their c-Src kinase inhibitory activity. Among them, eight compounds exhibited c-Src kinase inhibitory activity with IC50 value of less than 25?M. Compound 1-[2-(dimethylamino)ethyl]-5-(2-hydroxy-4-methoxybenzoyl)pyridin-2(1H)-one (36) exhibited the highest c-Src kinase inhibition with an IC50 value of 12.5?M. Furthermore, the kinase inhibitory activity of compound 36 was studied against EGFR, MAPK and PDK, however no significant activity was observed at the highest tested concentration (300?M). These results provide insights for further optimization of this scaffold for designing the next generation of 2-pyridone derivatives as candidate Src kinase inhibitors. PMID:24632506
Blood Pressure-Lowering Peptides from Neo-Fermented Buckwheat Sprouts: A New Approach to Estimating ACE-Inhibitory Activity
Koyama, Masahiro; Hattori, Seiji; Amano, Yoshihiko; Watanabe, Masanori; Nakamura, Kozo
Neo-fermented buckwheat sprouts (neo-FBS) contain angiotensin-converting enzyme (ACE) inhibitors and vasodilators with blood pressure-lowering (BPL) properties in spontaneously hypertensive rats (SHRs). In this study, we investigated antihypertensive mechanisms of six BPL peptides isolated from neo-FBS (FBPs) by a vasorelaxation assay and conventional in vitro, in vivo, and a new ex vivo ACE inhibitory assays. Some FBPs demonstrated moderate endothelium-dependent vasorelaxation in SHR thoracic aorta and all FBPs mildly inhibited ACE in vitro. Orally administered FBPs strongly inhibited ACE in SHR tissues. To investigate detailed ACE-inhibitory mechanism of FBPs in living body tissues, we performed the ex vivo assay by using endothelium-denuded thoracic aorta rings isolated from SHRs, which demonstrated that FBPs at low concentration effectively inhibited ACE in thoracic aorta tissue and suppressed angiotensin II-mediated vasoconstriction directly associated with BPL. These results indicate that the main BPL mechanism of FBP was ACE inhibition in living body tissues, suggesting that high FBP's bioavailability including absorption, tissue affinity, and tissue accumulation was responsible for the superior ACE inhibition in vivo. We propose that our ex vivo assay is an efficient and reliable method for evaluating ACE-inhibitory mechanism responsible for BPL activity in vivo. PMID:25222748
New dammarane-type triterpenoids from the leaves of Panax notoginseng and their protein tyrosine phosphatase 1B inhibitory activity
Li, Dawei; Cao, Jiaqing; Bi, Xiuli; Xia, Xichun; Li, Wei; Zhao, Yuqing
Background Panax notoginseng has been used as a general tonic agent to invigorate human body for millennia in China and continued to be used until present. Methods Some chromatographic methods were performed to isolate pure triterpenoids, and their structures were determined by nuclear magnetic resonance (NMR) experiments. Anti-diabetes activities of isolated compounds were evaluated through their inhibitory activity of protein tyrosine phosphatase 1B (PTP1B) enzyme. Results and Conclusion Three new dammarane-type triterpenoids, notoginsenoside-LX (1), notoginsenoside-LY (2), and notoginsenoside-FZ (3) together with eighteen known compounds were isolated from the Panax notoginseng leaves. The structure-activity relationship of the compounds with dammarane-type triterpenoids and their PTP1B inhibitory activity were also reported. Results showed that compounds 2, 15, 20, and 21 can significantly inhibit the enzyme activity of PTP1B in a dose-dependent manner, with inhibitory concentration 50 (IC50) values of 29.08 ?M, 21.27 ?M, 28.12 ?M, and 26.59 ?M, respectively. The results suggested that Panax notoginseng leaves might have potential as a new therapeutic agent for the treatment of diabetes. PMID:24558307
Inhibitory effect of selective cyclooxygenase-2 inhibitor etoricoxib on human organic anion transporter 3 (hOAT3).
Honjo, Hiroaki; Uwai, Yuichi; Iwamoto, Kikuo
It is well known that nonsteroidal anti-inflammatory drugs (NSAIDs) delay the elimination of methotrexate. One of the mechanisms is thought to be inhibition of methotrexate uptake via human organic anion transporter 3 (hOAT3, SLC22A8) in the renal proximal tubule by NSAIDs. In this study, we evaluated the inhibitory effects of selective cyclooxygenase-2 inhibitor etoricoxib on hOAT3 by uptake experiments using Xenopus laevis oocytes. The injection of hOAT3 cRNA stimulated the uptake of methotrexate into the oocytes, and its transport was inhibited by etoricoxib. Etoricoxib inhibited estrone sulfate uptake by hOAT3 dose dependently, and the 50% inhibitory concentration was estimated to be 9.8 µM. Eadie-Hofstee plot analysis showed that etoricoxib inhibited hOAT3 in a competitive manner. These findings show that etoricoxib has inhibitory effect on hOAT3, and that the potential is comparable to that of traditional NSAIDs. PMID:21457143
Chemical characterization, antioxidant and inhibitory effects of some marine sponges against carbohydrate metabolizing enzymes
Background More than 15,000 marine products have been described up to now; Sponges are champion producers, concerning the diversity of products that have been found. Most bioactive compounds from sponges were classified into anti-inflammatory, antitumor, immuno- or neurosurpressive, antiviral, antimalarial, antibiotic, or antifouling. Evaluation of in vitro inhibitory effects of different extracts from four marine sponges versus some antioxidants indices and carbohydrate hydrolyzing enzymes concerned with diabetes mellitus was studied. The chemical characterizations for the extracts of the predominating sponges; SP1 and SP3 were discussed. Methods All chemicals served in the biological study were of analytical grade and purchased from Sigma, Merck and Aldrich. All kits were the products of Biosystems (Spain), Sigma Chemical Company (USA), Biodiagnostic (Egypt). Carbohydrate metabolizing enzymes; α-amylase, α-glucosidase, and β-galactosidase (EC184.108.40.206, EC184.108.40.206, and EC126.96.36.199, respectively) were obtained from Sigma Chemical Company (USA). Results Four marine sponges; Smenospongia (SP1), Callyspongia (SP2), Niphates (SP3), and Stylissa (SP4), were collected from the Red Sea at Egyptian coasts, and taxonomically characterized. The sponges' extracts exhibited diverse inhibitory effects on oxidative stress indices and carbohydrate hydrolyzing enzymes in linear relationships to some extent with concentration of inhibitors (dose dependant). The extracts of sponges (3, 1, and 2) showed, respectively, potent-reducing power. Purification and Chemical characterization of sponge 1 using NMR and mass spectroscopy, recognized the existence of di-isobutyl phthalate (1), di-n-butyl phthalate (2), linoleic acid (3), ?-sitosterol (4), and cholesterol (5). Sponge 3 produced bis-[2-ethyl]-hexyl-phthylester (6) and triglyceride fatty acid ester (7). Conclusion Marine sponges are promising sources for delivering of bioactive compounds. Four marine sponges, collected from Red Sea at Egyptian coasts, were identified as Smenospongia (SP1), Callyspongia (SP2), Niphates (SP3), and Stylissa (SP4). The results demonstrated that different sponges extracts exhibited inhibitory effects on oxidative stress indices and carbohydrate hydrolyzing enzymes in linear relationships to some extent with concentration of inhibitors (dose dependant). The extracts of sponges (3, 1, and 2) showed, respectively, potent-reducing power. Chemical characterizations of sponges SP1 and SP3 were discussed. Based on this study, marine sponges are considered as talented sources for production of diverse and multiple biologically active compounds. PMID:22898269
Guanine modification of inhibitory oligonucleotides potentiates their suppressive function.
Römmler, Franziska; Jurk, Marion; Uhlmann, Eugen; Hammel, Monika; Waldhuber, Anna; Pfeiffer, Lavinia; Wagner, Hermann; Vollmer, Jörg; Miethke, Thomas
Inhibitory TLR7 and/or TLR9 oligonucleotides (inhibitory oligonucleotide [INH-ODN]) are characterized by a phosphorothioate backbone and a CC(T)XXX???GGG motif, respectively. INH-ODN 2088 is a prototypic member of this class of INH-ODN and acts as a TLR7 and TLR9 antagonist. It contains a G quadruple that leads to higher order structures by the formation of G tetrads. These structures are unfavorable for the prediction of their pharmacological and immunological behavior. We show in this study that modification of Gs within the G quadruple by 7-deaza-guanine or 7-deaza-2'-O-methyl-guanine avoids higher order structures and improves their inhibitory potential. Whereas TLR9-induced TNF-? secretion of bone marrow-derived macrophages and conventional dendritic cells was equally inhibited by INH-ODN 2088 and G-modified INH-ODNs such as INH-ODN 24888, TLR7-induced TNF-? release and TLR7- and TLR9-induced IL-12p40 release were significantly more impaired by G-modified INH-ODNs. Similarly, the IL-6 release of B cells from wild-type and autoimmune MRL/Mp-lpr/lpr mice was more efficiently impaired by G-modified INH-ODNs. Surprisingly, INH-ODN 2088 stimulated B cells to proliferate when used in higher doses. Finally, in vivo, in wild-type and autoimmune MRL/Mp-lpr/lpr mice, G-modified INH-ODN 24888 was significantly more efficient than unmodified INH-ODN 2088. In summary, G modification allows the development of INH-ODNs with superior inhibitory potency for inflammatory diseases with high medical need such as systemic lupus erythematosus. PMID:23966630
ACE-inhibitory activity of tilapia protein hydrolysates
Sivakumar Raghavan; Hordur G. Kristinsson
Fish processing wastes can be used for preparing bioactive peptides with various functionalities. Our objective was to evaluate the in vitro angiotensin converting enzyme (ACE) inhibitory activity of tilapia protein hydrolysates and its corresponding fractionates. Tilapia protein was alkali-solubilised at pH 11.0 and recovered at pH 5.5 to obtain a stable substrate. This substrate was hydrolysed using two enzymes, Cryotin-F
PD1: an inhibitory immunoreceptor involved in peripheral tolerance
Hiroyuki Nishimura; Tasuku Honjo
PD-1 deficiency causes a variety of autoimmune diseases. Inhibitory signaling through the PD-1 receptor might therefore be involved in the regulation of peripheral tolerance. The constitutive expression of PD-1 ligands (PD-L1 and PD-L2) on parenchymal cells of heart, lung and kidney suggests that the PD-1–PD-L system could provide unique negative signaling to help prevent autoimmune diseases.
Acetylcholinesterase inhibitory-active components of Rhodiola rosea L
Hua Wang; Gaochao Zhou; Xiangdong Gao; Yidan Wang; Wenbing Yao
An activity-directed fractionation and purification process was used to identify the acetylcholinesterase inhibitory-active components of Rhodiola rosea L. (RR). Dried rhizome of RR was extracted with boiled ethanol. After removal of tannins, the extract was separated into chloroform, ethyl acetate, n-butanol and water fractions. Among these, chloroform and n-butanol fractions showed stronger activity by bioassay for anti-cholinesterase activity than did
Inhibitory effect of artocarpanone from Artocarpus heterophyllus on melanin biosynthesis.
Arung, Enos Tangke; Shimizu, Kuniyoshi; Kondo, Ryuichiro
In our previous efforts to find new tyrosinase inhibitory materials, we investigated 44 Indonesian medicinal plants belonging to 24 families. Among those plants, the extract of Artocarpus heterophyllus was one of the strongest inhibitors of tyrosinase activity. By activity-guided fractionation of A. heterophyllus wood extract, we isolated artocarpanone, which inhibited both mushroom tyrosinase activity and melanin production in B16 melanoma cells. This compound is a strong candidate as a remedy for hyperpigmentation in human skin. PMID:16946519
Triterpenoids and ?-glucosidase inhibitory constituents from Salacia hainanensis.
Yu, Mei-Hua; Shi, Zheng-Feng; Yu, Bang-Wei; Pi, En-Hao; Wang, He-Yao; Hou, Ai-Jun; Lei, Chun
Thirteen triterpenoids (1-13), including two new lupane triterpenoids, salacinins A and B (1 and 2), as well as one new friedelane triterpenoid, salacinin C (3), were isolated from the roots and stems of Salacia hainanensis. The structures of new compounds were elucidated by extensive spectroscopic analysis including 1D and 2D NMR, and MS experiments. Compound 1 possesses rare 2,3-seco-lupane skeleton. Compounds 4, 6 and 7 showed inhibitory effects on ?-glucosidase in vitro. PMID:25073097
Individual Differences in Inhibitory Control and Children's Theory of Mind
Stephanie M. Carlson; Louis J. Moses
This research examined the relation between individual differences in inhibitory control (IC; a central compo- nent of executive functioning) and theory-of-mind (ToM) performance in preschool-age children. Across two sessions, 3- and 4-year-old children ( N ? 107) were given multitask batteries measuring IC and ToM. Inhibi- tory control was strongly related to ToM, r ? .66, p ? .001. This
Screening of Korean medicinal plants for lipase inhibitory activity.
Kim, Hye Young; Kang, Mun Hui
The pancreatic lipase inhibitory activity of the aqueous ethanol extracts obtained from 19 medicinal plants was evaluated in vitro by a continuous-monitoring pH-Stat technique using tributyrin as a substrate. Of the extracts tested, those of Juniperus communis (bark) and Illicium religiosum (wood) exhibited the strongest activity with an IC50 value of 20.4 and 21.9 microg/mL, respectively. PMID:16041737
Plants from Brazilian Cerrado with Potent Tyrosinase Inhibitory Activity
Souza, Paula Monteiro; Elias, Silvia Taveira; Simeoni, Luiz Alberto; de Paula, José Elias; Gomes, Sueli Maria; Guerra, Eliete Neves Silva; Fonseca, Yris Maria; Silva, Elton Clementino; Silveira, Dâmaris; Magalhăes, Pérola Oliveira
The increased amount of melanin leads to skin disorders such as age spots, freckles, melasma and malignant melanoma. Tyrosinase is known to be the key enzyme in melanin production. Plants and their extracts are inexpensive and rich resources of active compounds that can be utilized to inhibit tyrosinase as well as can be used for the treatment of dermatological disorders associated with melanin hyperpigmentation. Using in vitro tyrosinase inhibitory activity assay, extracts from 13 plant species from Brazilian Cerrado were evaluated. The results showed that Pouteria torta and Eugenia dysenterica extracts presented potent in vitro tyrosinase inhibition compared to positive control kojic acid. Ethanol extract of Eugenia dysenterica leaves showed significant (p<0.05) tyrosinase inhibitory activity exhibiting the IC50 value of 11.88 µg/mL, compared to kojic acid (IC50 value of 13.14 µg/mL). Pouteria torta aqueous extract leaves also showed significant inhibitory activity with IC50 value of 30.01 µg/mL. These results indicate that Pouteria torta and Eugenia dysenterica extracts and their isolated constituents are promising agents for skin-whitening or antimelanogenesis formulations. PMID:23173036
Inhibitory control deficits in rats with ventral hippocampal lesions.
Abela, Andrew R; Dougherty, Stephen D; Fagen, Erin D; Hill, Carolyn J R; Chudasama, Y
Two experiments are reported in which rats with selective hippocampal lesions were tested on 2 prefrontal-dependent tasks. In Experiment 1, we compared the effects of lesions of the ventral hippocampus (vHC), dorsal hippocampus (dHC), and sham control surgery on the 5-choice reaction time task. Whereas rats with lesions of the dHC were indistinguishable from sham controls, those with vHC lesions showed increased premature responses and reduced accuracy throughout the experiment. The subsequent administration of systemic escitalopram (5 mg/kg), a selective serotonin reuptake inhibitor, reduced the number of premature responses in the vHC animals to control levels. In contrast, systemic injections of GBR 12909, a dopamine reuptake inhibitor, failed to ameliorate the impulsive deficit in the vHC group and, in addition, elevated perseverative responding in the vHC group only. In Experiment 2, we tested a separate group of rats with vHC lesions on a touchscreen visual discrimination and reversal learning task. Rats with vHC lesions acquired the visual discrimination as well as sham controls and showed normal inhibitory control of a previously reinforced response during reversal learning. These data support a role for the vHC in inhibitory control functions, especially in the inhibitory control of impulsive actions. PMID:22615141
Alcohol and lateral inhibitory interactions in human vision.
Johnston, Kevin; Timney, Brian
Acute alcohol consumption detrimentally affects many aspects of visual function, but few studies have addressed the neural mechanisms underlying such changes. One candidate mechanism that may be responsible for some alcohol-induced changes in visual function is lateral inhibition. Alcohol has been shown to abolish lateral inhibitory interactions in experimental preparations in which it is applied directly to the retina, but few studies have attempted to link alcohol-induced reductions in lateral inhibitory interactions with psychophysical performance in assessments of visual function dependent on this mechanism. In the present series of studies we addressed this by investigating the effects of alcohol consumption on a perceptual phenomenon mediated in part by lateral inhibition, the Hermann grid illusion. Participants estimated the contrast of the illusory blobs present at the grid intersections using a matching procedure after consumption of a drink containing alcohol or a nonalcoholic drink. The magnitude of the illusion was diminished in the alcohol condition, and this effect was consistent when we parametrically varied the contrast of the grid squares and widths of the grid bars. These data suggest that alcohol reduces lateral inhibitory interactions in human vision. PMID:24649633
Defining inhibitory neurone function in respiratory circuits: opportunities with optogenetics?
Abdala, Ana Paula; Paton, Julian F R; Smith, Jeffrey C
Pharmacological and mathematical modelling studies support the view that synaptic inhibition in mammalian brainstem respiratory circuits is essential for generating normal and stable breathing movements. GABAergic and glycinergic neurones are known components of these circuits but their precise functional roles have not been established, especially within key microcircuits of the respiratory pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes involved in phasic control of respiratory pump and airway muscles. Here, we review briefly current concepts of relevant complexities of inhibitory synapses and the importance of synaptic inhibition in the operation of these microcircuits. We highlight results and limitations of classical pharmacological studies that have suggested critical functions of synaptic inhibition. We then explore the potential opportunities for optogenetic strategies that represent a promising new approach for interrogating function of inhibitory circuits, including a hypothetical wish list for optogenetic approaches to allow expedient application of this technology. We conclude that recent technical advances in optogenetics should provide a means to understand the role of functionally select and regionally confined subsets of inhibitory neurones in key respiratory circuits such as those in the pre-BötC and BötC. PMID:25384785
Energy coding in neural network with inhibitory neurons.
Wang, Ziyin; Wang, Rubin; Fang, Ruiyan
This paper aimed at assessing and comparing the effects of the inhibitory neurons in the neural network on the neural energy distribution, and the network activities in the absence of the inhibitory neurons to understand the nature of neural energy distribution and neural energy coding. Stimulus, synchronous oscillation has significant difference between neural networks with and without inhibitory neurons, and this difference can be quantitatively evaluated by the characteristic energy distribution. In addition, the synchronous oscillation difference of the neural activity can be quantitatively described by change of the energy distribution if the network parameters are gradually adjusted. Compared with traditional method of correlation coefficient analysis, the quantitative indicators based on nervous energy distribution characteristics are more effective in reflecting the dynamic features of the neural network activities. Meanwhile, this neural coding method from a global perspective of neural activity effectively avoids the current defects of neural encoding and decoding theory and enormous difficulties encountered. Our studies have shown that neural energy coding is a new coding theory with high efficiency and great potential. PMID:25806094
Reward, Interrupted: Inhibitory Control and Its Relevance to Addictions
Jentsch, James David; Pennington, Zachary T.
There are broad individual differences in the ability to voluntarily and effortfully suppress motivated, reward-seeking behaviors, and this review presents the hypothesis that these individual differences are relevant to addictive disorders. On one hand, cumulative experience with drug abuse appears to alter the molecular, cellular and circuit mechanisms that mediate inhibitory abilities, leading to increasingly uncontrolled patterns of drug-seeking and –taking. On the other, native inter-individual differences in inhibitory control are apparently a risk factor for aspects of drug-reinforced responding and substance use disorders. In both cases, the behavioral manifestation of poor inhibitory abilities is linked to relatively low striatal dopamine D2-like receptor availability, and evidence is accumulating for a more direct contribution of striatopallidal neurons to cognitive control processes. Mechanistic research is now identifying genes upstream of dopamine transmission that mediate these relationships, as well as the involvement of other neurotransmitter systems, acting alone and in concert with dopamine. The reviewed research stands poised to identify new mechanisms that can be targeted by pharmacotherapies and/or by behavioral interventions that are designed to prevent or treat addictive behaviors and associated behavioral pathology. PMID:23748054
Role of inhibitory feedback for information processing in thalamocortical circuits
Mayer, Joerg; Schuster, Heinz Georg; Claussen, Jens Christian [Institut fuer Theoretische Physik und Astrophysik, Christian-Albrechts Universitaet, Olshausenstrasse 40, 24098 Kiel (Germany)
The information transfer in the thalamus is blocked dynamically during sleep, in conjunction with the occurrence of spindle waves. In order to describe the dynamic mechanisms which control the sensory transfer of information, it is necessary to have a qualitative model for the response properties of thalamic neurons. As the theoretical understanding of the mechanism remains incomplete, we analyze two modeling approaches for a recent experiment by Le Masson et al. [Nature (London) 417, 854 (2002)] on the thalamocortical loop. We use a conductance based model in order to motivate an extension of the Hindmarsh-Rose model, which mimics experimental observations of Le Masson et al. Typically, thalamic neurons posses two different firing modes, depending on their membrane potential. At depolarized potentials, the cells fire in a single spike mode and relay synaptic inputs in a one-to-one manner to the cortex. If the cell gets hyperpolarized, T-type calcium currents generate burst-mode firing which leads to a decrease in the spike transfer. In thalamocortical circuits, the cell membrane gets hyperpolarized by recurrent inhibitory feedback loops. In the case of reciprocally coupled excitatory and inhibitory neurons, inhibitory feedback leads to metastable self-sustained oscillations, which mask the incoming input, and thereby reduce the information transfer significantly.
Inhibitory glutamatergic regulation of evoked dopamine release in striatum.
Wu, Y; Pearl, S M; Zigmond, M J; Michael, A C
Certain aspects of schizophrenia and Parkinson's disease suggest that glutamate might have an inhibitory effect on dopamine release. Several studies have reported that the excitatory actions of ionotropic glutamate agonists on extracellular dopamine levels in striatum are resistant to tetrodotoxin, which suggests that glutamate excites an impulse-independent mechanism of dopamine release. We tested the hypothesis that an inhibitory action of glutamate on dopamine terminals in the striatum specifically involves an impulse-dependent mechanism of dopamine release. We used voltammetry to monitor electrically-evoked dopamine release in striatal slices, which is completely tetrodotoxin- and Ca(2+)-sensitive and so provides a model of impulse-dependent dopamine release. Agonists of the ionotropic glutamate receptors significantly decreased the amplitude of the response, while antagonists significantly increased the amplitude of the response, by as much as approximately 60% in the case of kynurenic acid. These results support the hypothesis that ionotropic glutamate receptors can inhibit impulse-dependent dopamine release by a mechanism that acts locally within the striatum. This finding contrasts with previous reports that glutamate can excite impulse-independent dopamine release. This extends earlier findings that glutamate may both excite and inhibit subcortical dopamine systems by suggesting that the excitatory and inhibitory actions of striatal ionotropic glutamate receptors are specifically associated with impulse-independent and impulse-dependent dopamine release, respectively. PMID:10683411
Wavelet minimum description length detrending for near-infrared spectroscopy
NASA Astrophysics Data System (ADS)
Jang, Kwang Eun; Tak, Sungho; Jung, Jinwook; Jang, Jaeduck; Jeong, Yong; Ye, Jong Chul
Near-infrared spectroscopy (NIRS) can be employed to investigate brain activities associated with regional changes of the oxy- and deoxyhemoglobin concentration by measuring the absorption of near-infrared light through the intact skull. NIRS is regarded as a promising neuroimaging modality thanks to its excellent temporal resolution and flexibility for routine monitoring. Recently, the general linear model (GLM), which is a standard method for functional MRI (fMRI) analysis, has been employed for quantitative analysis of NIRS data. However, the GLM often fails in NIRS when there exists an unknown global trend due to breathing, cardiac, vasomotion, or other experimental errors. We propose a wavelet minimum description length (Wavelet-MDL) detrending algorithm to overcome this problem. Specifically, the wavelet transform is applied to decompose NIRS measurements into global trends, hemodynamic signals, and uncorrelated noise components at distinct scales. The minimum description length (MDL) principle plays an important role in preventing over- or underfitting and facilitates optimal model order selection for the global trend estimate. Experimental results demonstrate that the new detrending algorithm outperforms the conventional approaches.
Wavelet minimum description length detrending for near-infrared spectroscopy.
Jang, Kwang Eun; Tak, Sungho; Jung, Jinwook; Jang, Jaeduck; Jeong, Yong; Ye, Jong Chul
Near-infrared spectroscopy (NIRS) can be employed to investigate brain activities associated with regional changes of the oxy- and deoxyhemoglobin concentration by measuring the absorption of near-infrared light through the intact skull. NIRS is regarded as a promising neuroimaging modality thanks to its excellent temporal resolution and flexibility for routine monitoring. Recently, the general linear model (GLM), which is a standard method for functional MRI (fMRI) analysis, has been employed for quantitative analysis of NIRS data. However, the GLM often fails in NIRS when there exists an unknown global trend due to breathing, cardiac, vasomotion, or other experimental errors. We propose a wavelet minimum description length (Wavelet-MDL) detrending algorithm to overcome this problem. Specifically, the wavelet transform is applied to decompose NIRS measurements into global trends, hemodynamic signals, and uncorrelated noise components at distinct scales. The minimum description length (MDL) principle plays an important role in preventing over- or underfitting and facilitates optimal model order selection for the global trend estimate. Experimental results demonstrate that the new detrending algorithm outperforms the conventional approaches. PMID:19566297
Presynaptic regulation of the inhibitory transmission by GluR5-containing kainate receptors in spinal substantia gelatinosa
Xu, Hui; Wu, Long-Jun; Zhao, Ming-Gao; Toyoda, Hiroki; Vadakkan, Kunjumon I; Jia, Yongheng; Pinaud, Raphael; Zhuo, Min
GluR5-containing kainate receptors (KARs) are known to be involved in nociceptive transmission. Our previous work has shown that the activation of presynaptic KARs regulates GABAergic and glycinergic synaptic transmission in cultured dorsal horn neurons. However, the role of GluR5-containing KARs in the modulation of inhibitory transmission in the spinal substantia gelatinosa (SG) in slices remains unknown. In the present study, pharmacological, electrophysiological and genetic methods were used to show that presynaptic GluR5 KARs are involved in the modulation of inhibitory transmission in the SG of spinal slices in vitro. The GluR5 selective agonist, ATPA, facilitated the frequency but not amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) in SG neurons. ATPA increased sIPSC frequency in all neurons with different firing patterns as delayed, tonic, initial and single spike patterns. The frequency of either GABAergic or glycinergic sIPSCs was significantly increased by ATPA. ATPA could also induce inward currents in all SG neurons recorded. The frequency, but not amplitude, of action potential-independent miniature IPSCs (mIPSCs) was also facilitated by ATPA in a concentration-dependent manner. However, the effect of ATPA on the frequency of either sIPSCs or mIPSCs was abolished in GluR5-/- mice. Deletion of the GluR5 subunit gene had no effect on the frequency or amplitude of mIPSCs in SG neurons. However, GluR5 antagonist LY293558 reversibly inhibited sIPSC and mIPSC frequencies in spinal SG neurons. Taken together, these results suggest that GluR5 KARs, which may be located at presynaptic terminals, contribute to the modulation of inhibitory transmission in the SG. GluR5-containing KARs are thus important for spinal sensory transmission/modulation in the spinal cord. PMID:16948848
Ion composition of the topside equatorial ionosphere during solar minimum
NASA Technical Reports Server (NTRS)
Gonzalez, S. A.; Fejer, B. G.; Heels, R. A.; Hanson, W. B.
Observations from both the Bennett ion mass spectrometer and the retarding potential analyzer on board the Atmosphere Explorer E satellite were used to study the longitudinally averaged O(+), H(+), and He(+) concentrations from 150 to 1100 km in the equatorial ionosphere during the 1975-1976 solar minimum. The results suggest that the ion mass spectrometer measurements need to be increased by a factor of 2.15 to agree with the densities from the retarding potential analyzer and with ground-based measurements. The peak H(+) concentrations are about 2.5 x 10 exp 4/cu cm during the day and 10 exp 4/cu cm at night and vary little with season. The O(+)/H(+) transition altitude lies between 750 and 825 km during the day and between 550 and 600 km at night. He(+) is a minor species at all altitudes; its concentration is highly variable with a maximum value of about 10 exp 3/cu cm during equinox daytime.
Regional climate impacts of a possible future grand solar minimum.
Ineson, Sarah; Maycock, Amanda C; Gray, Lesley J; Scaife, Adam A; Dunstone, Nick J; Harder, Jerald W; Knight, Jeff R; Lockwood, Mike; Manners, James C; Wood, Richard A
Any reduction in global mean near-surface temperature due to a future decline in solar activity is likely to be a small fraction of projected anthropogenic warming. However, variability in ultraviolet solar irradiance is linked to modulation of the Arctic and North Atlantic Oscillations, suggesting the potential for larger regional surface climate effects. Here, we explore possible impacts through two experiments designed to bracket uncertainty in ultraviolet irradiance in a scenario in which future solar activity decreases to Maunder Minimum-like conditions by 2050. Both experiments show regional structure in the wintertime response, resembling the North Atlantic Oscillation, with enhanced relative cooling over northern Eurasia and the eastern United States. For a high-end decline in solar ultraviolet irradiance, the impact on winter northern European surface temperatures over the late twenty-first century could be a significant fraction of the difference in climate change between plausible AR5 scenarios of greenhouse gas concentrations. PMID:26102364
Antifeedant, larvicidal and growth inhibitory effects of ononitol monohydrate isolated from Cassia tora L. against Helicoverpa armigera (Hub.) and Spodoptera litura (Fab.) (Lepidoptera: Noctuidae).
Baskar, Kathirvelu; Ignacimuthu, Savarimuthu
Ononitol monohydrate isolated from the ethyl acetate extract of Cassia tora L. using column chromatography was evaluated for its antifeedant, larvicidal and growth inhibitory activities against Helicoverpa armigera and Spodoptera litura at different concentrations of 125, 250, 500 and 1000 ppm. Leaf disc no-choice method was used for the bioassay. The compound showed significant antifeedant, larvicidal and pupicidal activities against H. armigera and S. litura. The compound also prolonged the larval-pupal duration of the insect at all the tested concentrations. The activities were concentration dependent for both the insects. Ononitol could be used as an agent to prepare botanical new pesticidal formulations. PMID:22436590
Minimum Time/Minimum Fuel Control of an Axisymmetric Rigid Body
Torres, Jonathan Farina
MINIMUM TIME/MINIMUM FUEL CONTROL OF AN AXISYMMETRIC RIGID BODY A Thesis by JONATHAN FARINA TORRES Submitted to the Office of Graduate and Professional Studies of Texas A&M University in partial fulfillment of the requirements for the degree... of MASTER OF SCIENCE Chair of Committee, Shankar P. Bhattcharyya Co-Chair of Committee, John Hurtado Committee Members, Aniruddha Datta Le Xie Head of Department, Chanan Singh August 2014 Major Subject: Electrical Engineering Copyright 2014 Jonathan Farina...
Minimum Breakdown Voltage in Cylindrical Diode
NASA Astrophysics Data System (ADS)
Uhm, Han S.
The discharge plasma is generated by the electrical breakdown. Reduction of the discharge voltage is therefore the key element in enhancing the electrical efficiency for plasma generation. The electrical efficiency enhancement of plasma generation also prolongs system's lifetime, eliminating unnecessary heat and stress generations in the system. Properties of electrical breakdown in cylindrical diode are investigated by making use of Paschen's law. The sparking criterion indicates that discharge properties are insensitive to the electrical field polarity inside cylindrical diode, if the second ionization-coefficient is constant. Due to the curvature effects, the minimum breakdown-voltage in cylindrical geometry increases significantly from its planar value for a large aspect ratio of b/a, where a and b are radii of the inner and outer conductors, respectively. However, the optimum pressure parameter for minimum breakdown-voltage in cylindrical geometry is identical to that in planar electrodes.
On the Minimum Induced Drag of Wings
NASA Technical Reports Server (NTRS)
Bowers, Albion H.
Birds do not require the use of vertical tails. They do not appear to have any mechanism by which to control their yaw. As an example the albatross is notable in this regard. The authors believe this is possible because of a unique adaptation by which there exists a triple-optimal solution that provides the maximum aerodynamic efficiency, the minimum structural weight, and it provides for coordination of control in roll and yaw. Until now, this solution has eluded researchers, and remained unknown. Here it is shown that the correct specification of spanload provides for all three solutions at once, maximum aerodynamic efficiency, minimum structural weight, and coordinated control. The implications of this result has far reaching effects on the design of aircraft, as well as dramatic efficiency improvement.
On finding minimum-diameter clique trees
Blair, J.R.S. (Tennessee Univ., Knoxville, TN (United States). Dept. of Computer Science); Peyton, B.W. (Oak Ridge National Lab., TN (United States))
It is well-known that any chordal graph can be represented as a clique tree (acyclic hypergraph, join tree). Since some chordal graphs have many distinct clique tree representations, it is interesting to consider which one is most desirable under various circumstances. A clique tree of minimum diameter (or height) is sometimes a natural candidate when choosing clique trees to be processed in a parallel computing environment. This paper introduces a linear time algorithm for computing a minimum-diameter clique tree. The new algorithm is an analogue of the natural greedy algorithm for rooting an ordinary tree in order to minimize its height. It has potential application in the development of parallel algorithms for both knowledge-based systems and the solution of sparse linear systems of equations. 31 refs., 7 figs.
Minimum weight aerospace structural synthesis program
Walker, John Michael
(in) maximum height (in) moment of inertia (in ) 4 1 + y+ EXC(n -1) c EXC I 2 1 + y+ EXC(n -2) c EXC J 0 J2 dc' N E xyw w 3/7 n (. 577 a' ) w J3 n -1 n + J2&7 w w 2 w J4 1 + J u w n -1 2 w K s k e buckling coefficient thin walled.... i c i~i 7/ E ( d. g. a, i C M. + p Y. g. d. i m2E g 2 r 1 1. 1 ct ? 1 1+et + d i i w i 0E(N. (52) Differentiating to find a dw. i minimum ? = 0 da. i 2 C (1+y) p r r OPT n y Pc 1+y 1 (0E () 3y+2 E d r (53) To find the minimum weight...
Autocorrelation of rainfall and streamflow minimums
Matalas, N.C.
Hydrologic time series of annual minimum mean monthly rainfall and annual minimum 1-day and 7-day discharge, considered as drought indices, were used to study the distribution of droughts with respect to time. The rainfall data were found to be nearly random. The discharge data, however, were found to be nonrandomly distributed in time and generated by a first-order Markov process. The expected value of the variance for a time series generated by a first-order Markov process was compared with the expected value of the variance for a random time series. This comparison showed that the expected value of the variance for a nonrandom time series converged to the population variance with an increase in sample size at a slower rate than for a random time series.
On robustified adaptive minimum-variance controller
An adaptive regulator of the minimum-variance type in the presence of disturbance uncertainly is considered in the paper. Supposing a linear ARMAX model of the single input-single output system, a robustified direct adaptive control algorithm is derived using the robust statistical approach named M-estimation. The derived algorithm differs from the conventional linear algorithms by the insertion of a suitably chosen
Two variants of minimum discarded fill ordering
D'Azevedo, E.F. (Oak Ridge National Lab., TN (USA)); Forsyth, P.A.; Tang, Wei-Pai (Waterloo Univ., ON (Canada). Dept. of Computer Science)
It is well known that the ordering of the unknowns can have a significant effect on the convergence of Preconditioned Conjugate Gradient (PCG) methods. There has been considerable experimental work on the effects of ordering for regular finite difference problems. In many cases, good results have been obtained with preconditioners based on diagonal, spiral or natural row orderings. However, for finite element problems having unstructured grids or grids generated by a local refinement approach, it is difficult to define many of the orderings for more regular problems. A recently proposed Minimum Discarded Fill (MDF) ordering technique is effective in finding high quality Incomplete LU (ILU) preconditioners, especially for problems arising from unstructured finite element grids. Testing indicates this algorithm can identify a rather complicated physical structure in an anisotropic problem and orders the unknowns in the preferred'' direction. The MDF technique may be viewed as the numerical analogue of the minimum deficiency algorithm in sparse matrix technology. At any stage of the partial elimination, the MDF technique chooses the next pivot node so as to minimize the amount of discarded fill. In this work, two efficient variants of the MDF technique are explored to produce cost-effective high-order ILU preconditioners. The Threshold MDF orderings combine MDF ideas with drop tolerance techniques to identify the sparsity pattern in the ILU preconditioners. These techniques identify an ordering that encourages fast decay of the entries in the ILU factorization. The Minimum Update Matrix (MUM) ordering technique is a simplification of the MDF ordering and is closely related to the minimum degree algorithm. The MUM ordering is especially for large problems arising from Navier-Stokes problems. Some interesting pictures of the orderings are presented using a visualization tool. 22 refs., 4 figs., 7 tabs.
Minimum ignition energy for laser spark ignition
Donald H. McNeill
Combustion ignition by electrical sparks and nonresonant laser sparks is preceded by breakdown, electron heating, relaxation of internal plasma energy, shock wave generation and propagation, and subsonic flows. Measurements and model calculations of these processes (which occur over times of 10?12–10?1s) in laser sparks show that the minimum ignition energy (MIE) for laser sparks is higher than for electrical sparks,
Minimum Model Error Approach for Attitude Estimation
John L. Crassidis; F. Landis Markley
In this paper, an optimal batch estimator and smoother based on the Minimum Model Error (MME) approach is developed for three-axis stabilized spacecraft. The formulation described in this paper is shown using only attitude sensors (e.g., three-axis magnetometers, sun sensors, star trackers, etc). This algorithm accurately estimates the attitude of a spacecraft, and substantially smoothes noise associated with attitude sensor
Design for minimum energy in interstellar communication
NASA Astrophysics Data System (ADS)
Messerschmitt, David G.
Microwave digital communication at interstellar distances is the foundation of extraterrestrial civilization (SETI and METI) communication of information-bearing signals. Large distances demand large transmitted power and/or large antennas, while the propagation is transparent over a wide bandwidth. Recognizing a fundamental tradeoff, reduced energy delivered to the receiver at the expense of wide bandwidth (the opposite of terrestrial objectives) is advantageous. Wide bandwidth also results in simpler design and implementation, allowing circumvention of dispersion and scattering arising in the interstellar medium and motion effects and obviating any related processing. The minimum energy delivered to the receiver per bit of information is determined by cosmic microwave background alone. By mapping a single bit onto a carrier burst, the Morse code invented for the telegraph in 1836 comes closer to this minimum energy than approaches used in modern terrestrial radio. Rather than the terrestrial approach of adding phases and amplitudes increases information capacity while minimizing bandwidth, adding multiple time-frequency locations for carrier bursts increases capacity while minimizing energy per information bit. The resulting location code is simple and yet can approach the minimum energy as bandwidth is expanded. It is consistent with easy discovery, since carrier bursts are energetic and straightforward modifications to post-detection pattern recognition can identify burst patterns. Time and frequency coherence constraints leading to simple signal discovery are addressed, and observations of the interstellar medium by transmitter and receiver constrain the burst parameters and limit the search scope.
Computing Minimum Spanning Trees with Uncertainty
Erlebach, Thomas; Krizanc, Danny; Mihal'ák, Matús; Raman, Rajeev
We consider the minimum spanning tree problem in a setting where information about the edge weights of the given graph is uncertain. Initially, for each edge $e$ of the graph only a set $A_e$, called an uncertainty area, that contains the actual edge weight $w_e$ is known. The algorithm can `update' $e$ to obtain the edge weight $w_e \\in A_e$. The task is to output the edge set of a minimum spanning tree after a minimum number of updates. An algorithm is $k$-update competitive if it makes at most $k$ times as many updates as the optimum. We present a 2-update competitive algorithm if all areas $A_e$ are open or trivial, which is the best possible among deterministic algorithms. The condition on the areas $A_e$ is to exclude degenerate inputs for which no constant update competitive algorithm can exist. Next, we consider a setting where the vertices of the graph correspond to points in Euclidean space and the weight of an edge is equal to the distance of its endpoints. The location of each point is initially g...
Minimum Contradiction Matrices in Whole Genome Phylogenies
Thuillard, Marc
Minimum contradiction matrices are a useful complement to distance-based phylogenies. A minimum contradiction matrix represents phylogenetic information under the form of an ordered distance matrix Yi, jn. A matrix element corresponds to the distance from a reference vertex n to the path (i, j). For an X-tree or a split network, the minimum contradiction matrix is a Robinson matrix. It therefore fulfills all the inequalities defining perfect order: Yi, jn ? Yi,kn, Yk jn ? Yk, In, i ? j ? k < n. In real phylogenetic data, some taxa may contradict the inequalities for perfect order. Contradictions to perfect order correspond to deviations from a tree or from a split network topology. Efficient algorithms that search for the best order are presented and tested on whole genome phylogenies with 184 taxa including many Bacteria, Archaea and Eukaryota. After optimization, taxa are classified in their correct domain and phyla. Several significant deviations from perfect order correspond to well-documented evolutionary events. PMID:19204821
Laplacian filtered minimum shift keying modulation
NASA Astrophysics Data System (ADS)
Abu-Isbeih, Ibrahim N.; Maqusi, Mohammad
Gaussian minimum shift keying (GMSK) is a continuous-phase frequency-shift keying modulation scheme. It is similar to standard minimum-shift keying (MSK); however the digital data stream is first shaped with a Gaussian filter before being applied to a frequency modulator. This has the advantage of reducing sideband power, which in turn reduces out-of- band interference between signal carriers in adjacent frequency channels. In this paper a new method of premodulation filtered MSK called Laplacian minimum shift keying (LMSK) is proposed. LMSK is proposed as a method for achieving good spectral efficiency over regular MSK, and it turns out to achieve improvement in error rate performance over the known GMSK. To compare the behavior of the system under the proposed method, bandwidth efficiency (i.e., bps/Hz), fractional out-of-band power and error rate performance in such systems are used. Results show that the proposed LMSK attains good improvement in spectral efficiency over MSK; and in using LMSK we have also good improvement in power efficiency over GMSK.
Inhibitory effects of organochlorine pesticides on intercellular transfer of Lucifer Yellow in cultured bovine oviductal cells.
Tiemann, U; Pöhland, R
The present study investigated the effects of dichlorodiphenyltrichloroethane (DDT), methoxychlor (MXC), and gamma-hexachlorocyclohexane (gammaHCH, lindane) on gap junctional intercellular communication (GJIC) in cultured bovine oviductal cells. GJIC was evaluated by microinjecting fluorescent dye Lucifer Yellow and observing the inhibition of the spreading of dye into adjacent cells. After incubation for 1 h at 37 degrees C, a dose-dependent inhibition of GJIC was observed over a concentration range of 16 to 128 microM DDT, MXC, or gammaHCH compared with nonexposed controls. A significant inhibition began at 32 microM DDT, MXC, or gammaHCH. After incubation for 5 h, a dose-dependent inhibition of GJIC was obtained in the concentration range from 8 to 64 microM of the pesticides. The first significant inhibitory effect on GJIC was caused by 8 microM DDT, 16 microM MXC, and 32 microM gammaHCH. The 128 microM concentration of the pesticides was toxic. At pesticide concentration of 64 microM, the decrease in dye-coupling observed was not due to lethal cell injury, as is indicated by the use of trypan blue dye exclusion. After removal of 64 microM DDT from the culture medium, intercellular communication was reestablished within 3 h. Measurement of cytosolic free Ca2+ concentration [Ca2+]i in fura-2/AM-loaded oviductal cells showed that the inhibition of GJIC by addition of DDT, MXC, or gammaHCH was not associated with a detectable increase in [Ca2+]i. Coincubation of the DDT with dibutyryl-cAMP prevented the 64 microM DDT-induced inhibition of intercellular communication in adherent oviduct cells. It is suggested that organochlorine pesticides can influence cells responsible for reproduction. PMID:10213519
Inhibitory effects of the essential oil of chamomile ( Matricaria recutita L.) and its major constituents on human cytochrome P450 enzymes
M. Ganzera; P. Schneider; H. Stuppner
Chamomile extracts and tea are widely used herbal preparations for the treatment of minor illnesses (e.g. indigestion, inflammation). In this study the inhibitory effect of chamomile essential oil and its major constituents on four selected human cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP2D6 and CYP3A4) was investigated. Increasing concentrations of the test compounds were incubated with individual, recombinant CYP isoforms and
Association of macrophage inhibitory cytokine-1 with nutritional status, body composition and bone mineral density in patients with anorexia nervosa: the influence of partial realimentation
Ivana Dostálová; Petra Kaválková; Hana Papežová; Daniela Domluvilová; Vít Zikán; Martin Haluzík
BACKGROUND: Macrophage inhibitory cytokine-1 (MIC-1) is a key inducer of cancer-related anorexia and weight loss. However, its possible role in the etiopathogenesis of nutritional disorders of other etiology such as anorexia nervosa (AN) is currently unknown. METHODS: We measured fasting serum concentrations of MIC-1 in patients with AN before and after 2-month nutritional treatment and explored its relationship with nutritional
Inhibitory effects of the herbal medicine Sho-saiko-to (TJ-9) on cell proliferation and procollagen gene expressions in cultured rat hepatic stellate cells
Kozo Kayano; Isao Sakaida; Koichi Uchida; Kiwamu Okita
Background\\/Aims: It is of extreme importance to prevent liver fibrosis and subsequent progression to liver cirrhosis. The aim of our study was to elucidate in vitro whether Sho-saiko-to exerted inhibitory effects on hepatic stellate cells.Methods: Hepatic stellate cells were isolated from male Wistar rats. Water-soluble ingredients of Sho-saiko-to were obtained at concentrations of 10, 100, 250, 500 and 1000 ?g\\/ml.
[Inhibitory effect of macrolide antibiotics on biofilm formation by Pseudomonas aeruginosa].
Kondoh, K; Hashiba, M
In recent years, various medical indwelling devices have been developed and used. Bacteria adhering to these devices often cause refractory infection. In the field of otolaryngology, refractory infection accompanying these medical indwelling devices such as middle ear ventilation tubes and artificial auditory ossicles has been reported. The concept of bacterial biofilm infection has been suggested as an explanation for the refractory infection. Furthermore it has been reported that a bacterial biofilm is involved in refractory infection unrelated to medical indwelling devices. Topical biofilm formation was detected in patients with chronic sinusitis, chronic purulent otitis media or habitual tonsillitis. In this study, we morphologically and quantitatively examined the biofilm-forming capacity of a clinically isolated strain of mucoid type Psecudomonas aeruginosa on Teflon to investigate the effects of macrolide antibiotics on bacterial biofilm formation. In the morphological examination, P.aeruginosa was cultured together with a Teflon sheet in minimal medium containing various concentrations of the macrolide antibiotics clarithromycin (CAM), erythromycin (EM) and midecamycin (MDM), at 37 degrees C for 7 days. The surfaces of the Teflon sheets were examined by electron microscopy. The adherent bacteria and biofilm formation on Teflon sheets soaked in minimal medium containing CAM or EM were found to be decreased in a dose-dependent manner. However, in the Teflon sheets soaked in minimal medium containing MDM, there was no decrease in biofilm formation regardless of the MDM concentration. In the quantitative examination, P. aeruginosa was cultured in minimal medium containing various concentrations of the macrolide antibiotics at 37 degrees C for 7 days together with Teflon beads. The levels of hexose, protein and alginate adhering to the Telfon beads were quantified as an estimation of biofilm formation. On Teflon beads treated with CAM or EM, there were dose-dependent decreases in hexose, protein and alginate levels. In particular, marked decreases were noted when CAM and EM concentrations were 10 micrograms/ml or more. Furthermore, there was no significant difference between CAM and EM. However, in the presence of MDM, there was no decrease in hexose, protein or alginate levels regardless of the MDM concentration. The minimal inhibitory concentration (MIC100) of each macrolide against P. aeruginosa used in this experiment was 100 micrograms/ml or more. There may be no bactericidal effect on this strain at the macrolide concentrations used in this experiment. However, this experiment used 7-day treatment. The long-term bactericidal activity of macrolides was examined. In the presence of CAM or MDM, bacterial levels after culture were similar to preculture levels or slightly lower than the preculture levels. In the presence of EM, bacterial levels were similar to the preculture levels. These results demonstrated that CAM and EM, which are 14-membered macrolides inhibited biofilm formation, while MDM which is 16-membered macrolide, did not. These inhibitory effects of CAM and EM may be related to actions other than bactericidal activity. In our experiment, CAM and EM inhibited biofilm formation at 10 micrograms/ml or more. This concentration corresponded to 1/20 x MIC. This concentration can be achieved in tissues, nasal discharge and sputum with actual clinical doses. Therefore, these agents may be effective against biofilm disease caused by P. aeruginosa in the field of otolaryngology. PMID:9493436
Enhanced Detection of Vibrio Cholerae in Oyster Homogenate Based on Centrifugal Removal of Inhibitory Agents
NASA Technical Reports Server (NTRS)
Alexander, Donita; DePaola, Angelo; Young, Ronald B.
The disease cholera, caused by Vibrio cholerae, has been associated with consumption of contaminated seafood, including raw oysters. Detection of V. cholerae in foods typically involves blending the oysters, diluting the homogenate in alkaline peptone water (APW), overnight enrichment, and isolation on selective agar. Unfortunately, the oyster homogenate must be diluted to large volumes because lower dilutions inhibit the growth of V. cholerae. The goals of this study were to develop an alternative to large dilutions and to evaluate the basis for the inhibition observed in lower dilutions of oyster homogenates. Centrifugation of oyster homogenates at 10,000 x g for 15 min, followed by enrichment of the resulting pellet in APW, was found to eliminate the inhibition of V. cholerae growth. Inhibition appears not to be due to competing microflora but to a component(s) released when V. cholerae grows in the presence of oyster homogenate. The inhibitory component(s) kills the V. cholerae after the cell concentration reaches > 10(exp 8) cells/mL, rather than initially preventing their growth. The pH also declines from 8.0 to 5.5 during this period; however, the pH decline by itself appears not to cause V. cholerae death. Seven strains of V. cholerae (01 and non-01) and two strains of V. vulnificus were susceptible to the inhibitory agent(s). However, other Vibrio and non-Vibrio species tested were not inhibited by the oyster homogenates. Based on digestion of oyster homogenates with pronase, trypsin and lipase, the inhibitory reaction involves a protein(s). In a preliminary trial with oyster homogenate seeded with 1 cfu/g of V. cholerae, the modified centrifugation technique detected a slightly higher percentage of samples at a 1:10 dilution than the standard FDA Bacteriological Analytical Method (BAM) detected in uncentrifuged oyster homogenate at a 1:100 dilution. V. cholerae in seeded samples could also be detected more frequently by the modified centrifugation method than by PCR at a 1:10 dilution.
Hydrogen Sulfide Plays a Key Role in the Inhibitory Neurotransmission to the Pig Intravesical Ureter
Fernandes, Vítor S.; Ribeiro, Ana S. F.; Martínez, Pilar; López-Oliva, María Elvira; Barahona, María Victoria; Orensanz, Luis M.; Martínez-Sáenz, Ana; Recio, Paz; Benedito, Sara; Bustamante, Salvador; García-Sacristán, Albino; Prieto, Dolores; Hernández, Medardo
According to previous observations nitric oxide (NO), as well as an unknown nature mediator are involved in the inhibitory neurotransmission to the intravesical ureter. This study investigates the hydrogen sulfide (H2S) role in the neurogenic relaxation of the pig intravesical ureter. We have performed western blot and immunohistochemistry to study the expression of the H2S synthesis enzymes cystathionine ?-lyase (CSE) and cystathionine ?-synthase (CBS), measurement of enzymatic production of H2S and myographic studies for isometric force recording. Immunohistochemical assays showed a high CSE expression in the intravesical ureter muscular layer, as well as a strong CSE-immunoreactivity within nerve fibres distributed along smooth muscle bundles. CBS expression, however, was not consistently observed. On ureteral strips precontracted with thromboxane A2 analogue U46619, electrical field stimulation (EFS) and the H2S donor P-(4-methoxyphenyl)-P-4-morpholinylphosphinodithioic acid (GYY4137) evoked frequency- and concentration-dependent relaxations. CSE inhibition with DL-propargylglycine (PPG) reduced EFS-elicited responses and a combined blockade of both CSE and NO synthase (NOS) with, respectively, PPG and NG-nitro-L-arginine (L-NOARG), greatly reduced such relaxations. Endogenous H2S production rate was reduced by PPG, rescued by addition of GYY4137 and was not changed by L-NOARG. EFS and GYY4137 relaxations were also reduced by capsaicin-sensitive primary afferents (CSPA) desensitization with capsaicin and blockade of ATP-dependent K+ (KATP) channels, transient receptor potential A1 (TRPA1), transient receptor potential vanilloid 1 (TRPV1), vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide (VIP/PACAP) and calcitonin gene-related peptide (CGRP) receptors with glibenclamide, HC030031, AMG9810, PACAP6–38 and CGRP8–37, respectively. These results suggest that H2S, synthesized by CSE, is involved in the inhibitory neurotransmission to the pig intravesical ureter, through an NO-independent pathway, producing smooth muscle relaxation via KATP channel activation. H2S also promotes the release of inhibitory neuropeptides, as PACAP 38 and/or CGRP from CSPA through TRPA1, TRPV1 and related ion channel activation. PMID:25415381
Evidence for inhibitory deficits in the prefrontal cortex in schizophrenia.
Radhu, Natasha; Garcia Dominguez, Luis; Farzan, Faranak; Richter, Margaret A; Semeralul, Mawahib O; Chen, Robert; Fitzgerald, Paul B; Daskalakis, Zafiris J
Abnormal gamma-aminobutyric acid inhibitory neurotransmission is a key pathophysiological mechanism underlying schizophrenia. Transcranial magnetic stimulation can be combined with electroencephalography to index long-interval cortical inhibition, a measure of GABAergic receptor-mediated inhibitory neurotransmission from the frontal and motor cortex. In previous studies we have reported that schizophrenia is associated with inhibitory deficits in the dorsolateral prefrontal cortex compared to healthy subjects and patients with bipolar disorder. The main objective of the current study was to replicate and extend these initial findings by evaluating long-interval cortical inhibition from the dorsolateral prefrontal cortex in patients with schizophrenia compared to patients with obsessive-compulsive disorder. A total of 111 participants were assessed: 38 patients with schizophrenia (average age: 35.71 years, 25 males, 13 females), 27 patients with obsessive-compulsive disorder (average age: 36.15 years, 11 males, 16 females) and 46 healthy subjects (average age: 33.63 years, 23 females, 23 males). Long-interval cortical inhibition was measured from the dorsolateral prefrontal cortex and motor cortex through combined transcranial magnetic stimulation and electroencephalography. In the dorsolateral prefrontal cortex, long-interval cortical inhibition was significantly reduced in patients with schizophrenia compared to healthy subjects (P = 0.004) and not significantly different between patients with obsessive-compulsive disorder and healthy subjects (P = 0.5445). Long-interval cortical inhibition deficits in the dorsolateral prefrontal cortex were also significantly greater in patients with schizophrenia compared to patients with obsessive-compulsive disorder (P = 0.0465). There were no significant differences in long-interval cortical inhibition across all three groups in the motor cortex. These results demonstrate that long-interval cortical inhibition deficits in the dorsolateral prefrontal cortex are specific to patients with schizophrenia and are not a generalized deficit that is shared by disorders of severe psychopathology. PMID:25524710
Benzisothiazolones as modulators of macrophage migration inhibitory factor
Jorgensen, William L.; Trofimov, Alexander; Du, Xin; Hare, Alissa A.; Leng, Lin; Bucala, Richard
Substituted N-phenylbenzisothiazolones have been investigated as inhibitors of the tautomerase activity of the proinflammatory cytokine MIF (macrophage migration inhibitory factor). Numerous compounds were found to possess antagonist activity in the low micromolar range with the most potent being the 6-hydroxy analog 1w. 1w and the p-cyano analog 1c were also shown to exhibit significant inhibition of the binding of MIF to its transmembrane receptor CD74. Consistently, both compounds were also found to retard the MIF-dependent phosphorylation of ERK1/2 in human synovial fibroblasts. PMID:21719283
Benzisothiazolones as modulators of macrophage migration inhibitory factor.
Jorgensen, William L; Trofimov, Alexander; Du, Xin; Hare, Alissa A; Leng, Lin; Bucala, Richard
Substituted N-phenylbenzisothiazolones have been investigated as inhibitors of the tautomerase activity of the proinflammatory cytokine MIF (macrophage migration inhibitory factor). Numerous compounds were found to possess antagonist activity in the low micromolar range with the most potent being the 6-hydroxy analog 1w. Compound 1w and the p-cyano analog 1c were also shown to exhibit significant inhibition of the binding of MIF to its transmembrane receptor CD74. Consistently, both compounds were also found to retard the MIF-dependent phosphorylation of ERK1/2 in human synovial fibroblasts. PMID:21719283
Characterizing the neurite outgrowth inhibitory effect of Mani.
Mishra, Manisha; Lee, Sachiko; Lin, Michelle K; Yamashita, Toshihide; Heese, Klaus
Mani (myelin-associated neurite-outgrowth inhibitor) protein is implicated in both axonal guidance and axonal regeneration after central nervous system (CNS) injury. Here, we applied a neurite outgrowth assay, coupled with a siRNA-driven investigation and immunocytochemistry, to unveil Mani's axonal outgrowth inhibitory effect in embryonic rat cortical primary neurons in vitro. We further demonstrate Mani's neuronal localization in comparison with a principal subunit, Cdc27, of the anaphase promoting complex (APC). Considering the protein structure of Mani obtained via a series of bio-computational studies, we propose a Cdc27-Mani-APC-related signalling pathway may be involved in CNS axon regeneration. PMID:22771904
Antimutagenic and ?-glucosidase inhibitory effects of constituents from Kaempferia parviflora
Toshiaki Azuma; Shin-ichi Kayano; Yoko Matsumura; Yotaro Konishi; Yasuo Tanaka; Hiroe Kikuzaki
The dichloromethane extract and ethyl acetate soluble fraction of Kaempferia parviflora showed antimutagenicity and ?-glucosidase inhibitory activity. 7-Methoxyflavones were the major constituents of both extracts and demonstrated antimutagenic activity. In particular, 5,7-dimethoxyflavone (IC50=0.40nmol\\/plate), 5,3?-dihydroxy-3,7,4?-trimethoxyflavone (0.40nmol\\/plate), 3,5,7-trimethoxyflavone (0.42nmol\\/plate) and 5-hydroxy-7-methoxyflavone (0.47nmol\\/plate) showed potent antimutagenic activity. The results of structure–activity relationship studies suggest that methylation of the 5-hydroxy group enhanced activity. On
Screening the methanol extracts of some Iranian plants for acetylcholinesterase inhibitory activity
Gholamhoseinian, A.; Moradi, M.N.; Sharifi-far, F.
Acetylcholinesterase (AChE) is the main enzyme for the breakdown of acetylcholine. Nowadays, usage of the inhibitors of this enzyme is one of the most important types of treatment of mild to moderate neurodegenerative diseases such as Alzheimer's disease. Herbal medicines can be a new source of inhibitors of this enzyme. In this study we examined around 100 different plants to evaluate their inhibitory properties for AChE enzyme. Plants were scientifically identified and their extracts were prepared by methanol percolation. Acetylcholinesterase activity was measured using a colorimetric method in the presence or absence of the extracts. Eserine was used as a positive control. Methanol extracts of the Levisticum officinale, Bergeris integrima and Rheum ribes showed more than 50% AChE inhibitory activity. The inhibition kinetics were studied in the presence of the most effective extracts. L. officinale and B. integrima inhibited AChE activity in a non-competitive manner, while R. ribes competitively inhibitied the enzyme as revealed by double-reciprocal Linweaver-Burk plot analysis. Under controlled condition, Km and Vmax values of the enzyme were found to be 9.4 mM and 0.238 mM/min, respectively. However, in the presence of L. officinale, B. integrima, and R. ribes extracts, Vmax values were 0.192, 0.074 and 0.238 mM/min, respectively. Due to the competitive inhibition of the enzyme by R. ribes extract, the Km value of 21.2 mM was obtained. The concentration required for 50% enzyme inhibition (IC50 value) was 0.5, 0.9, and 0.95 mg/ml for the L. officinale, B. integrima and R. ribes extracts, respectively. The IC50 of the eserine was determined to be 0.8 mg/ml. PMID:21589805
Inhibitory activity of carbonyl compounds on alcoholic fermentation by Saccharomyces cerevisiae.
Cao, Dongxu; Tu, Maobing; Xie, Rui; Li, Jing; Wu, Yonnie; Adhikari, Sushil
Aldehydes and acids play important roles in the fermentation inhibition of biomass hydrolysates. A series of carbonyl compounds (vanillin, syringaldehyde, 4-hydroxybenzaldehyde, pyrogallol aldehyde, and o-phthalaldehyde) were used to examine the quantitative structure-inhibitory activity relationship of carbonyl compounds on alcoholic fermentation, based on the glucose consumption rate and the final ethanol yield. It was observed that pyrogallol aldehyde and o-phthalaldehyde (5.0 mM) reduced the initial glucose consumption rate by 60 and 89%, respectively, and also decreased the final ethanol yield by 60 and 99%, respectively. Correlating the molecular descriptors to inhibition efficiency in yeast fermentation revealed a strong relationship between the energy of the lowest unoccupied molecular orbital (ELUMO) of aldehydes and their inhibitory efficiency in fermentation. On the other hand, vanillin, syringaldehyde, and 4-hydroxybenzaldehyde (5.0 mM) increased the final ethanol yields by 11, 4, and 1%, respectively. Addition of vanillin appeared to favor ethanol formation over glycerol formation and decreased the glycerol yield in yeast fermentation. Furthermore, alcohol dehydrogenase (ADH) activity dropped significantly from 3.85 to 2.72, 1.83, 0.46, and 0.11 U/mg at 6 h of fermentation at vanillin concentrations of 0, 2.5, 5.0, 10.0, and 25.0 mM correspondingly. In addition, fermentation inhibition by acetic acid and benzoic acid was pH-dependent. Addition of acetate, benzoate, and potassium chloride increased the glucose consumption rate, likely because the salts enhanced membrane permeability, thus increasing glucose consumption. PMID:24401115
The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice
Ogawa, Eiichi [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan)] [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Hosokawa, Masaya [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan) [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Faculty of Human Sciences, Tezukayama Gakuin University, Osaka (Japan); Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan)] [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Tsukiyama, Katsushi; Yamada, Yuichiro [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan) [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Department of Internal Medicine, Division of Endocrinology, Diabetes and Geriatric Medicine, Akita University School of Medicine, Akita (Japan); Seino, Yutaka [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan) [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Kansai Electric Power Hospital, Osaka (Japan); Inagaki, Nobuya, E-mail: email@example.com [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan) [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); CREST of Japan Science and Technology Cooperation (JST), Kyoto (Japan)
Research highlights: {yields} Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. {yields} Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. {yields} The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic {beta} cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [{sup 14}C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [{sup 14}C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin-mediated pathway rather than through a GLP-1-mediated pathway.
Ophiobolin A, a sesterterpenoid fungal phytotoxin, displays higher in vitro growth-inhibitory effects in mammalian than in plant cells and displays in vivo antitumor activity.
Bury, Marina; Novo-Uzal, Esther; Andolfi, Anna; Cimini, Sara; Wauthoz, Nathalie; Heffeter, Petra; Lallemand, Benjamin; Avolio, Fabiana; Delporte, Cédric; Cimmino, Alessio; Dubois, Jacques; Van Antwerpen, Pierre; Zonno, Maria Chiara; Vurro, Maurizio; Poumay, Yves; Berger, Walter; Evidente, Antonio; De Gara, Laura; Kiss, Robert; Locato, Vittoria
Ophiobolin A, a sesterterpenoid produced by plant pathogenic fungi, was purified from the culture extract of Drechslera gigantea and tested for its growth-inhibitory activity in both plant and mammalian cells. Ophiobolin A induced cell death in Nicotiana tabacum L. cv. Bright Yellow 2 (TBY-2) cells at concentrations ?10 µM, with the TBY-2 cells showing typical features of apoptosis-like cell death. At a concentration of 5 µM, ophiobolin A did not affect plant cell viability but prevented cell proliferation. When tested on eight cancer cell lines, concentrations <1 µM of ophiobolin A inhibited growth by 50% after 3 days of culture irrespective of their multidrug resistance (MDR) phenotypes and their resistance levels to pro-apoptotic stimuli. It is, thus, unlikely that ophiobolin A exerts these in vitro growth-inhibitory effects in cancer cells by activating pro-apoptotic processes. Highly proliferative human keratinocytes appeared more sensitive to the growth-inhibitory effects of ophiobolin A than slowly proliferating ones. Ophiobolin A also displayed significant antitumor activity at the level of mouse survival when assayed at 10 mg/kg in the B16F10 mouse melanoma model with lung pseudometastases. Ophiobolin A could, thus, represent a novel scaffold to combat cancer types that display various levels of resistance to pro-apoptotic stimuli and/or various MDR phenotypes. PMID:23754298
Model Selection Based on Minimum Description Length.
We introduce the minimum description length (MDL) principle, a general principle for inductive inference based on the idea that regularities (laws) underlying data can always be used to compress data. We introduce the fundamental concept of MDL, called the stochastic complexity, and we show how it can be used for model selection. We briefly compare MDL-based model selection to other approaches and we informally explain why we may expect MDL to give good results in practical applications. Copyright 2000 Academic Press. PMID:10733861
Minimum energy information fusion in sensor networks
Chapline, G
In this paper we consider how to organize the sharing of information in a distributed network of sensors and data processors so as to provide explanations for sensor readings with minimal expenditure of energy. We point out that the Minimum Description Length principle provides an approach to information fusion that is more naturally suited to energy minimization than traditional Bayesian approaches. In addition we show that for networks consisting of a large number of identical sensors Kohonen self-organization provides an exact solution to the problem of combing the sensor outputs into minimal description length explanations.
Implementation of automated minimum resolvable temperature testing
NASA Astrophysics Data System (ADS)
Orlando, Harold; Nelson, Neil; Pappas, Mike; Scherr, Larry
Minimum resolvable temperature (MRT) is a subjective test technique used to demonstrate the performance of thermal imaging sensors with human observers. To measure MRT, an automated test method that is closely related to the traditional MRT was developed. Results of automated MRT testing in the consolidated automated support system (CASS) electrooptical subsystem are presented. The paper compares the automated MRT to traditional MRT data from the same thermal imaging sensor, and the theory of MRT is described as it relates to automated testing. The reasons for developing automated MRT testing are explored as is the motivation for promoting acceptance of this kind of testing.
An introduction to minimum intervention dentistry.
Mickenautsch, Steffen
Minimum intervention dentistry (MI) can be defined as a philosophy of professional care concerned with the first occurrence, early detection, and earliest possible cure of disease on micro levels, followed by minimally invasive, patient-friendly treatment to repair irreversible damage caused by such disease. The benefit for patients from MI lies in better oral health through disease healing and not merely on symptom relief. Furthermore, minimally invasive treatment assists in reducing widespread patient dental anxieties. MI has the potential for dentists to apply a more conservative approach to caries treatment and simultaneously offer patients less invasive, health-oriented treatment options. PMID:16438261
29 CFR 541.604 - Minimum guarantee plus extras.
Code of Federal Regulations, 2013 CFR
...2013-07-01 2013-07-01 false Minimum guarantee plus extras. 541.604 Section 541.604 Labor Regulations...EMPLOYEES Salary Requirements § 541.604 Minimum guarantee plus extras. (a) An employer may provide an...
29 CFR 541.604 - Minimum guarantee plus extras.
Code of Federal Regulations, 2014 CFR
...2014-07-01 2014-07-01 false Minimum guarantee plus extras. 541.604 Section 541.604 Labor Regulations...EMPLOYEES Salary Requirements § 541.604 Minimum guarantee plus extras. (a) An employer may provide an...
29 CFR 541.604 - Minimum guarantee plus extras.
Code of Federal Regulations, 2011 CFR
...2011-07-01 2011-07-01 false Minimum guarantee plus extras. 541.604 Section 541.604 Labor Regulations...EMPLOYEES Salary Requirements § 541.604 Minimum guarantee plus extras. (a) An employer may provide an...
29 CFR 541.604 - Minimum guarantee plus extras.
Code of Federal Regulations, 2010 CFR
...2010-07-01 2010-07-01 false Minimum guarantee plus extras. 541.604 Section 541.604 Labor Regulations...EMPLOYEES Salary Requirements § 541.604 Minimum guarantee plus extras. (a) An employer may provide an...
29 CFR 541.604 - Minimum guarantee plus extras.
Code of Federal Regulations, 2012 CFR
...2012-07-01 2012-07-01 false Minimum guarantee plus extras. 541.604 Section 541.604 Labor Regulations...EMPLOYEES Salary Requirements § 541.604 Minimum guarantee plus extras. (a) An employer may provide an...
36 CFR 223.221 - Establishing minimum rates.
Code of Federal Regulations, 2013 CFR
...be sold for appraised value or minimum rates, whichever is higher. No products may be sold or harvested for less than minimum rates except to provide for the removal of insect infested, diseased, dead or distressed...
42 CFR 84.115 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2013 CFR
...2013-10-01 2013-10-01 false Breathing tubes; minimum requirements. 84.115 Section...DEVICES Gas Masks § 84.115 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with gas masks shall...
42 CFR 84.72 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2013 CFR
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42 CFR 84.72 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2014 CFR
...2014-10-01 2014-10-01 false Breathing tubes; minimum requirements. 84.72 Section...Breathing Apparatus § 84.72 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with breathing...
42 CFR 84.172 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2012 CFR
...2012-10-01 2012-10-01 false Breathing tubes; minimum requirements. 84.172 Section...Particulate Respirators § 84.172 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with respirators...
42 CFR 84.172 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2011 CFR
...2011-10-01 2011-10-01 false Breathing tubes; minimum requirements. 84.172 Section...Particulate Respirators § 84.172 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with respirators...
42 CFR 84.195 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2012 CFR
...2012-10-01 2012-10-01 false Breathing tubes; minimum requirements. 84.195 Section...Cartridge Respirators § 84.195 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with respirators...
42 CFR 84.195 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2013 CFR
...2013-10-01 2013-10-01 false Breathing tubes; minimum requirements. 84.195 Section...Cartridge Respirators § 84.195 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with respirators...
42 CFR 84.1132 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2012 CFR
...2012-10-01 2012-10-01 false Breathing tubes; minimum requirements. 84.1132 Section...Combination Gas Masks § 84.1132 Breathing tubes; minimum requirements. (a) Flexible breathing tubes used in conjunction with respirators...
42 CFR 84.115 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2012 CFR
...2012-10-01 2012-10-01 false Breathing tubes; minimum requirements. 84.115 Section...DEVICES Gas Masks § 84.115 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with gas masks shall...
42 CFR 84.1132 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2014 CFR
...2014-10-01 2014-10-01 false Breathing tubes; minimum requirements. 84.1132 Section...Combination Gas Masks § 84.1132 Breathing tubes; minimum requirements. (a) Flexible breathing tubes used in conjunction with respirators...
42 CFR 84.172 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2013 CFR
...2013-10-01 2013-10-01 false Breathing tubes; minimum requirements. 84.172 Section...Particulate Respirators § 84.172 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with respirators...
42 CFR 84.132 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2012 CFR
...2012-10-01 2012-10-01 false Breathing tubes; minimum requirements. 84.132 Section...Supplied-Air Respirators § 84.132 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with supplied-air...
42 CFR 84.132 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2013 CFR
...2013-10-01 2013-10-01 false Breathing tubes; minimum requirements. 84.132 Section...Supplied-Air Respirators § 84.132 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with supplied-air...
42 CFR 84.115 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2011 CFR
...2011-10-01 2011-10-01 false Breathing tubes; minimum requirements. 84.115 Section...DEVICES Gas Masks § 84.115 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with gas masks shall...
42 CFR 84.172 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2014 CFR
...2014-10-01 2014-10-01 false Breathing tubes; minimum requirements. 84.172 Section...Particulate Respirators § 84.172 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with respirators...
42 CFR 84.1132 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2013 CFR
...2013-10-01 2013-10-01 false Breathing tubes; minimum requirements. 84.1132 Section...Combination Gas Masks § 84.1132 Breathing tubes; minimum requirements. (a) Flexible breathing tubes used in conjunction with respirators...
42 CFR 84.132 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2011 CFR
...2011-10-01 2011-10-01 false Breathing tubes; minimum requirements. 84.132 Section...Supplied-Air Respirators § 84.132 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with supplied-air...
42 CFR 84.132 - Breathing tubes; minimum requirements.
Code of Federal Regulations, 2014 CFR
...2014-10-01 2014-10-01 false Breathing tubes; minimum requirements. 84.132 Section...Supplied-Air Respirators § 84.132 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with supplied-air...