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Hydroxysafflor yellow A (HSYA) is one of the chemical component isolated from Chinese medicine Carthamus tinctorius L. Our preliminary study confirmed that HSYA attenuated bleomycin-induced pulmonary fibrosis in mice. In this study, we evaluated the effect of HSYA on TGF-β1-induced activation of human fetal lung fibroblasts (MRC-5) and explored the underlying mechanisms of its activity.
MRC-5 cells activated by TGF-β1 were incubated with HSYA and/or the TGF-β type I receptor inhibitor, SB431542. TGF-β1-induced cell proliferation, α-smooth muscle actin, collagen I alpha 1 and fibronectin expression, Smad, mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase/Akt signalling pathway activation were observed.
Hydroxysafflor yellow A significantly inhibited TGF-β1-induced cell proliferation and the expression, both mRNA and protein, of α-smooth muscle actin, collagen I alpha 1 and fibronectin. HSYA also suppressed TGF-β1 activation of Smad signal transduction via inhibition of Smad2 and Smad3 phosphorylation, their nuclear translocation and the binding activity of Smad3 to type I collagen promoter in MRC-5 cells. In addition, HSYA inhibited TGF-β1-induced phosphorylation of extracellular signal-regulated kinase (ERK). The inhibitory effects of HSYA were similar to SB431542.
These findings suggest that HSYA inhibits TGF-β1-induced activation of MRC-5 cells associated with TGF-β1/Smad and ERK/MAPK signalling pathways.
Carvedilol (CAR) is a poorly water-soluble beta-blocker. Its encapsulation within nanomicelles (NMs) could improve drug solubility and its oral bioavailability, allowing the development of a paediatric liquid CAR formulation with commercially available copolymers: D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly(vinyl caprolactam)-poly(vinyl acetate)-poly(ethylene glycol) (Soluplus®).
Drug-loaded NMs were prepared by copolymer and CAR dispersion in distilled water. Micellar size and morphology were characterized by dynamic light scattering and transmission electron microscopy, respectively. In-vitro drug permeation studies were evaluated by conventional gut sac method. In-vivo CAR oral bioavailability from NMs dispersions and drug control solution was evaluated in Wistar rats.
Carvedilol apparent aqueous solubility was increased (up to 60.4-folds) after its encapsulation within NMs. The micellar size was ranged between 10.9 and 81.9 nm with a monomodal size distribution. There was a significant enhancement of CAR relative oral bioavailability for both copolymers vs a micelle-free drug solution (P < 0.05). This improvement was higher for TPGS-based micelles (4.95-fold) in accordance with the in-vitro CAR permeation results.
The present investigation demonstrates the development of highly concentrated CAR liquid micellar formulation. The improvement on drug oral bioavailability contributes to the potential of this NMs formulation to enhance CAR paediatric treatment.
Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease, which affects synovial tissue in multiple joints. Although conventional treatments of RA commonly alleviate the symptoms, high incidence of adverse reactions leads to research tendency towards complementary and alternative medicine. As various medicinal plants are traditionally used for the management of symptomatologies associated with RA in Persian medicine, we reviewed medicinal literature to confirm their efficacy in the management of RA.
Scientific evidence revealed that traditional medicaments exert beneficial effects on RA through several cellular mechanisms including downregulation of pro-inflammatory cytokines such as TNF-α, IL-6 and NF-κB, suppression of oxidative stress, inhibition of cartilage degradation with destructive metalloproteinases and enhancement of antioxidant performance. Various active constituents from different chemical categories including flavonols, lignans, coumarins, terpenes, glycosylflavons, dihydroflavonols, phytoestrogens, sesquiterpene lactones, anthraquinones, alkaloids and thymoquinones have been isolated from the medicinal plants.
The pharmacological mechanisms of the medicinal plants traditionally used for RA in Persian medicine are discussed in the current review. Further investigations are mandatory to focus on bioefficacy of these phytochemicals for finding novel natural drugs.
Peristaltic pumps are increasingly employed during fill & finish operations of a biopharmaceutical drug, due to sensitivity of many biological products to rotary piston pump-related stresses. Yet, possibly also unit operations using peristaltic pumps may shed particulates into the final product due to abrasion from the employed tubing. It was the aim of this study to elucidate the potential influence of particles shed from peristaltic pump tubing on the stability of a drug product.
Spiking solutions containing shed silicone particles were prepared via peristaltic pumping of placebo under recirculating conditions and subsequently characterized. Two formulated antibodies were spiked with two realistic, but worst-case levels of particles and a 6-month accelerated stability study with storage at 2–8, 25 and 40°C were conducted.
Regarding the formation of aggregates and fragments, both mAbs degraded at their typically expected rates and no additional impact of spiked particles was observed. No changes were discerned however in turbidity, subvisible and visible particle assessments. Flow imaging data for one of the mAb formulations with spiked particles suggested limited colloidal stability of shed particles as indicated by a similar increase in spiked placebo.
Shed silicone particles from peristaltic pump tubing are assumed to not impair drug product stability.
The aim of this study was to determine the influence of non-ionisable excipients hydroxypropyl-β-cyclodextrin (HPβCD) and poloxamers 407 and 188 on the supersaturation and precipitation kinetics of ibuprofen, gliclazide, propranolol and atenolol induced through solution pH shifts using the CheqSol method.
The drug's kinetic and intrinsic aqueous solubilities were measured in the presence of increasing excipient concentrations using the CheqSol method. Experimental data rate of change of pH with time was also examined to determine excipient-induced parachute effects and influence on precipitation rates.
The measured kinetic and intrinsic solubilities provide a determination of the influence of each excipient on supersaturation index, and the area under the CheqSol curve can measure the parachute capability of excipients. The excipients influence on precipitation kinetics can be measured with novel parameters; for example, the precipitation pH or percentage ionised drug at the precipitation point, which provide further information on the excipient-induced changes in precipitation performance.
This method can therefore be employed to measure the influence of non-ionisable excipients on the kinetic solubility behaviour of supersaturated solutions of ionisable drugs and to provide data, which discriminates between excipient systems during precipitation.
Chlorogenic acid (CGA) is one of the most widely consumed polyphenols in diets and is recognized to be a natural hepatoprotective agent. Here, we evaluated the protective effect and the potential mechanism of CGA against ɑ-naphthylisothiocyanate (ANIT)-induced cholestasis and liver injury.
Twenty-five male 129/Sv mice were administered with CGA, and ANIT challenge was performed at 75 mg/kg on the 4th day. Blood was collected and subjected to biochemical analysis; the liver tissues were examined using histopathological analysis and signalling pathways.
Chlorogenic acid almost totally attenuated the ANIT-induced liver damage and cholestasis, compared with the ANIT group. Dose of 50 mg/kg of CGA significantly prevented ANIT-induced changes in serum levels of alanine aminotransferase, alkaline phosphatases, total bile acid, direct bilirubin, indirect bilirubin (5.3-, 6.3-, 18.8-, 158-, 41.4-fold, P<0.001) and aspartate aminotransferase (4.6-fold, P<0.01). Expressions of the altered bile acid metabolism and transport-related genes were normalized by cotreatment with CGA. The expressions of interleukin 6, tumour necrosis factor-α and suppressor of cytokine signalling 3 were found to be significantly decreased (1.2-fold, ns; 11.0-fold, P<0.01; 4.4-fold, P<0.05) in the CGA/ANIT group. Western blot revealed that CGA inhibited the activation and expression of signal transducer and activator of transcription 3 and NFκB.
These data suggest that CGA inhibits both ANIT-induced intrahepatic cholestasis and the liver injury. This protective effect involves down-regulation of STAT3 and NFκB signalling.
All-trans-retinoic acid (ATRA), a naturally occurring metabolite of vitamin A, has been shown to have great potential as an antitumorigenic drug to treat acute leukaemia by promoting cancer cell differentiation. Cytochrome P450 oxidoreductase (POR) is the only obligate electron donor for all of the microsomal cytochrome P450 enzymes including CYP26A1 which is highly specific for ATRA metabolism and efficacy in human myeloid leukaemia cells. In this study, we aimed to investigate the effect of POR on ATRA efficacy and CYP26A1 expression in human myeloid leukaemia HL-60 cells.
Stably expressed POR and POR-RNAi HL-60 cell lines were established by transfecting POR overexpression or RNAi (RNA interference) vectors mediated by lentivirus. The protein expression of POR and CYP26A1 was examined by Western blot. The potential roles of POR on ATRA efficacy in HL-60 cells were explored by cell viability assay, cell cycle distribution, cellular differentiation and apoptosis analysis.
All-trans-retinoic acid treatment caused the expression of POR upregulation and CYP26A1 downregulation in dose- and time-dependent manners. POR overexpression decreased CYP26A1 expression in HL-60 cells. When POR gene was interfered, the downregulation of CYP26A1 expression by ATRA was abolished. In addition, POR overexpression in HL-60 cells significantly compromised ATRA-induced cell proliferation inhibition, cell cycle arrest, differentiation and apoptosis, whereas downregulation of POR significantly potentiated ATRA effects.
Our study therefore suggested that POR played an important role in regulating ATRA efficacy and CYP26A1 expression in HL-60 cells.
This work aimed at preparing ginsenoside compound K (GCK)-loaded liposomes modified with TPGS (GCKT-liposomes) to enhance solubility and targeting capability of GCK, as well as inhibit the efflux of GCK from tumour cells.
GCKT-liposomes were prepared by the thin-film hydration method and characterized by particle size, polydispersity, zeta potential and drug encapsulation efficiency. A549 cells were used as antitumour cell model to access the cellular uptake of the GCK and perform its antitumour function. The enhancement of in vivo antitumour efficacy of GCKT-liposomes was evaluated by nude mice bearing tumour model.
The results showed that GCKT-liposomes achieved a comparatively high drug loading efficiency and reasonable particle size at the ratio of 7 : 3 (phospholipid: TPGS). The in vitro release demonstrated that the dissolution of GCK was remarkably improved by entrapping it into liposomes. In addition, GCKT-liposomes exhibited a great hypersensitizing effect on A549 cells, and the cellular uptake was enhanced. Compared with free GCK, the IC50 of GCKT-liposomes was significantly reduced (16.3 ± 0.8 vs 24.9 ± 1.0 μg/ml). In vivo antitumour assay also indicated that GCKT-liposomes achieved higher antitumour efficacy (67.5 ± 0.5 vs 40.8 ± 0.7%).
The novel GCKT-liposomes significantly improved the antitumour efficacy of GCK.
To propose approaches tailored to the specific needs of neonates, such as structured product development programmes, with the ultimate goal to improve the safe and effective use of analgosedatives in these fragile patients.
The feasibility and relevance of a structured product development programme in neonates (optimal study design based on preliminary data; model development; internal, external and prospective evaluation; an individualized dosing regimen; long-term safety; pharmacogenetics) are illustrated for the use of morphine. Based on changes in clinical practices, similar development plans are in progress for short-acting analgosedatives such as propofol, but are in need of tailored pharmacodynamic tools to assess and quantify effects. Furthermore, for drugs like paracetamol where there is already sufficient clinical pharmacology knowledge, attention needs to be given to long-term safety aspects. Finally, new covariates such as pharmacogenetics might further improve neonatal pain management, but clearly need to be integrated with other well-established covariates like age or weight.
Product development programmes for analgosedatives in neonates are needed. These programmes should be tailored to their specific needs (short-acting sedation, pain relief), should include long-term safety and should incorporate the exploration of newer covariates like pharmacogenetics.
The aim of this study was to investigate the possible protective effect of ellagic acid (EA) against gentamicin (GEN)-induced nephrotoxicity using biochemical, molecular and histopathological approaches.
Rats (n = 24) were divided into four groups: control, GEN (100 mg/kg, i.p.), EA (10 mg/kg, p.o.) and GEN plus EA. The regimes were administered for 10 successive days. 24 h after last treatment, kidney and blood samples were collected.
Ellagic acid treatment significantly reduced plasma creatinine and urea levels, which were initially increased due to GEN administration. Also, EA significantly ameliorated oxidative stress markers including lipid peroxidation, catalase (CAT) and superoxide dismutase (SOD) enzyme activity as well as glutathione (GSH) content in kidney tissue. Activation of caspase-3 and increase in the ratio of Bcl-2/Bax expression observed in GEN-treated group were significantly ameliorated by EA treatment. EA also protected GEN-induced mitochondrial damages as indicated by decreasing the mitochondrial ROS content, preventing of mitochondrial membrane potential (MMP) loss, reducing mitochondrial swelling and decreasing cytochrome c release. In addition, histopathological findings revealed that EA ameliorates GEN-induced kidney injury.
Our findings suggest that EA treatment attenuates GEN-induced nephrotoxicity, which may be ascribed to its antioxidant and anti-apoptotic properties.
Diabetes mellitus is characterised by progressive β-cell destruction and loss of function, or loss of ability of tissues to respond to insulin. Daily subcutaneous insulin injection is standard management for people with diabetes, although patient compliance is hard to achieve due to the inconvenience of injections, so other forms of delivery are being tested, including oral administration. This review summarises the developments in oral insulin administration.
The PubMed database was consulted to compile this review comparing conventional subcutaneous injection of insulin to the desired oral delivery.
Oral administration of insulin has potential benefits in reducing pain and chances of skin infection, improving the portal levels of insulin and avoiding side effects such as hyperinsulinemia, weight gain and hypoglycaemia. Although oral delivery of insulin is an ideal administration route for patients with diabetes, several physiological barriers have to be overcome. An expected low oral bioavailability can be attributed to its high molecular weight, susceptibility to enzymatic proteolysis and low diffusion rate across the mucin barrier.
Strategies for increasing the bioavailability of oral insulin include the use of enzyme inhibitors, absorption enhancers, mucoadhesive polymers and chemical modification for endogenous receptor-mediated absorption. These may help significantly increase patient compliance and disease management.
This study was designed to investigate pharmacological interaction between magnesium laxative and antacid in patients receiving opioid analgesic.
Data obtained from a total of 441 eligible patients receiving opioid analgesic for the first time were retrospectively analysed. The incidence of constipation, defined as stool-free interval of 3 days and more within the first week of opioid intake, was compared between patients who took laxative alone and those who received laxative in combination with antacid.
Laxatives were prescribed in 74% of patients, among them 61% received antacids such as proton pump inhibitor and H2 receptor blocker. Magnesia was the most commonly used laxative (89%). Constipation occurred in 21% and 55% of patients with and without laxatives, respectively. Antacids reversed the laxative action of lower doses (<2000 mg/day) but not higher doses (>2000 mg/day) of magnesia without affecting the effects of other laxatives. Therefore, it is suggested that both acid-dependent and acid-independent mechanisms may operate in the laxative action of magnesia, in which the former may be involved in the action of lower doses of magnesia.
Care should be taken to avoid the unfavourable pharmacological interaction between low doses of magnesia and antacid.
Carnitine/organic cation transporter 1 (OCTN1) is involved in gastrointestinal absorption and mitochondrial toxicity of biguanides in rodents, but its pharmacokinetic roles in humans are largely unknown. The purpose of this study was to clarify the transport activities of two major OCTN1 variants, L503F and I306T, for gabapentin and three biguanide drugs, metformin, buformin and phenformin.
HEK293 cells were transfected with OCTN1 gene, its variants, or vector alone, and the uptake and cytotoxicity of each drug were examined.
Buformin was identified to be an OCTN1 substrate. Uptake of biguanides, especially metformin, mediated by OCTN1 variant L503F, which is commonly found in Caucasians, was much higher than that by the wild-type transporter (WT-OCTN1). Cytotoxicity of metformin was also greater in HEK293 cells expressing the L503F variant, compared with WT-OCTN1. Uptake of gabapentin mediated by OCTN1 variant I306T, which is commonly found in both Asians and Caucasians, was lower than that by WT-OCTN1, although uptake of the typical OCTN1 substrate ergothioneine was similar.
Organic cation transporter 1 variant L503F transports biguanides, especially metformin, more efficiently than WT-OCTN1, whereas the I306T variant transports gabapentin less efficiently than WT-OCTN1, suggesting that the common OCTN1 variants may alter pharmacokinetics of these drugs.
Dispersible tablets are proposed by the World Health Organization as the preferred paediatric formulation. It was hypothesised that tablets made from a powdered milk-base that disperse in water to form suspensions resembling milk might be a useful platform to improve acceptability in children.
Milk-based dispersible tablets containing various types of powdered milk and infant formulae were formulated. The influence of milk type and content on placebo tablet properties was investigated using a design-of-experiments approach. Responses measured included friability, crushing strength and disintegration time. Additionally, the influence of compression force on the tablet properties of a model formulation was studied by compaction simulation.
Disintegration times increased as milk content increased. Compaction simulation studies showed that compression force influenced disintegration time. These results suggest that the milk content, rather than type, and compression force were the most important determinants of disintegration.
Up to 30% milk could be incorporated to produce 200 mg 10-mm flat-faced placebo tablets by direct compression disintegrating within 3 min in 5–10 ml of water, which is a realistic administration volume in children. The platform could accommodate 30% of a model active pharmaceutical ingredient (caffeine citrate).
Over-expressions of HMGA2, vimentin and MMP-9 and downregulation of E-cadherin occur on colorectal cancer cells followed by a reduction in let-7 as a regulatory factor. In this study, we first used carboxymethyl dextran (CMD)–chitosan nanoparticles (ChNPs) platform to encapsulate HMGA2 siRNA and doxorubicin (DOX), and then, we evaluated the efficacy of the simultaneous delivery of siRNA/drug on viability and gene expression of HT-29 cell lines.
ChNPs characteristics were determined by a dynamic light scattering and zeta sizer. Morphology of loaded ChNPs was assessed by scanning electron microscopy, and Fourier transform infrared spectroscopy was used to confirm the conjugation of ChNP/siRNA/DOX/CMD. Cell viability and relative mRNA expression were evaluated by MTT assay and real-time PCR, respectively.
The prepared ChNPs had high efficiency for siRNA and drug encapsulation (78% and 75%) and were stable against serum and heparin. ChNP/siRNA/DOX/CMD was more effective to induce tumour cell death and also could significantly reduce the expressions of HMGA2, vimentin as well as MMP-9 and increase E-cadherin expression.
In conclusion, our results revealed that dual delivery of a key gene siRNA and appropriate anticancer drug have great impact on the treatment of colorectal cancer.
The activation of the p53 pathway through the inhibition of MDM2 has been proposed as a novel therapeutic strategy against tumours. A series of cis-imidazoline analogues, termed nutlins, were reported to displace the recombinant p53 protein from its complex with MDM2 by binding to MDM2 in the p53 pocket, and exhibited an antitumour activity both in vitro and in vivo. Thus, the purpose of this study was to evaluate the antitumour properties of LQFM030 (2), a nutlin analogue created by employing the strategy of molecular simplification.
LQFM030 (2) cytotoxicity was evaluated in Ehrlich ascites tumour (EAT) cells, p53 wild type, by the trypan blue exclusion test, and the mechanisms involved in EAT cell death were investigated by light and fluorescence microscopy, flow cytometry, real-time PCR and Western blotting.
Our results demonstrate that LQFM030 has dose-dependent antiproliferative activity and cytotoxic activity on EAT cells, induces the accumulation of p53 protein and promotes cell cycle arrest and apoptosis. p53 gene transcription was unaffected by LQFM030 (2); however, MDM2 mRNA increased and MDM2 protein decreased.
These results suggest that the small-molecule p53 activator LQFM030 (2) has the potential for further development as a novel cancer therapeutic agent.
The aim of this study was to investigate the use of off-label (OL) and unlicensed (UL) medicines to hospitalised children in Norway, to add to the current knowledge on use of medicines in this vulnerable patient group.
The study was performed as a cross-sectional prospective study. Medication was classified as on- or off-label based on the comparison with the SmPC regarding age, indication, dosage, route of administration and handling of the product. UL products were classified as imported or pharmacy produced.
More than 90% of children receiving medicines in our study were given OL or UL medicines. More patients received OL (83%) than UL (59%). Route of administration was the most frequently observed OL category. The vast majority of the OL prescriptions were for 'off-patent' products. One-third of products prescribed were UL.
The study confirms that medicines to children in hospital to a significant degree are being used outside or without authorisation, in spite of recent paediatric regulatory initiatives. More data are still needed on efficacy and safety of medicines used in children, data to be incorporated in the SmPC. In addition, suitable formulations are needed to ensure optimal dosing and adherence without risky manipulations.
To evaluate safety, following introduction of standard concentrations of morphine infusions in paediatric critical care.
Implementation: A multidisciplinary team was convened, and several workstreams designated, including derivation of concentrations, manufacturing, supply, prescribing, administration using smart pump technology, training and evaluation.
Safety Evaluation: Retrieval of all existing data on medication errors linked to morphine use using our hospital incident reporting system and risk assessment of errors in relation to standard concentration implementation.
The pilot identified several areas for improvement, stock control, reasons for reverting from standard to variable concentrations and sources of error. Improvements included the following: refining morphine concentrations and weight limits for bands, pump reprogramming and education.
Long-term Safety: Over an 8-year period, 126 morphine-related incidents occurred (two-thirds in the 3 years around introduction). Of note, 67% (85/126) resulted in no patient harm; the remainder 33% resulted in low harm. Analysis of administration errors revealed that up to 70% could be eliminated by refining technology to include bar coding. These included the following: wrong syringe selection (24%), wrong pump mode (28%) and wrong patient weight inputted (18%).
Introduction of standard infusions is safe and effective. We are exploring ways to further refine safety and extending to other drugs.
To investigate the apoptosis-inducing effect and underlying mechanisms of luteolin in cholangiocarcinoma (CCA) cells.
Cell viability was determined by sulphorhodamine B. Apoptosis was detected using acridine orange/ethidium bromide dye staining and annexin V/PI staining followed by flow cytometry. The effect of luteolin on the oxidative status of CCA cells was evaluated by measuring intracellular reactive oxygen species (ROS) levels using the dihydroethidium method and quantifying glutathione levels. The mitochondria transmembrane potential (ΔΨm) was examined through JC-1 staining. The protein levels were determined by Western blot. Caspase activity was determined using specific fluorogenic substrates.
Luteolin decreased KKU-100 CCA cells' viability by induction of apoptosis. Luteolin treatment increased ROS production and decreased glutathione levels. These changes were associated with the decrease of Nrf2, γ-glutamylcysteine ligase and heme oxygenase-1 proteins. Moreover, luteolin induced mitochondrial depolarization, which was accompanied by the release of cytochrome c and a decrease of Bcl-2 and Bcl-XL proteins. Pretreatment with antioxidants, 4-hydroxy-TEMPO and N-acetyl-L-cysteine significantly prevented luteolin-induced CCA cell death and loss of ΔΨm. In addition, luteolin induced the activation of caspase-9 and caspase-3.
Luteolin exerts its pro-apoptotic action partly through generating intracellular ROS that then contributes to the activation of mitochondria-mediated apoptotic cell death.
The study aims to investigate the possible mechanism of the synergistic analgesic effect of propofol–alfentanil combination.
The synergistic analgesic effects of propofol–alfentanil combination in Sprague–Dawley (SD) rats were analysed through the von Frey test. Then, we examined the activity of phospholipase C (PLC) and the intracellular levels of Ca2+ and adenosine 3′, 5′cyclic monophosphate (cAMP) in primary neuronal cells of fetal SD rats. We detected the intracellular Ca2+ concentration by fluorescence and flow cytometry. The PLC activity of the primary neuronal cells was assayed using the EnzChek® Direct Phospholipase C Assay Kit. The cAMP content of the cells was assayed using the cAMP Direct Immunoassay Kit (Fluorometric).
Both propofol and alfentanil treatments depressed cAMP levels and PLC activity, but propofol–alfentanil combination decreased these parameters to a greater extent than alfentanil treatment alone. Propofol and alfentanil both inhibited Ca2+ channel, but propofol–alfentanil combination suppressed this channel to a greater extent than alfentanil treatment alone. Fluorescent image analysis revealed that both propofol and alfentanil reduced the intracellular levels of Ca2+, and propofol–alfentanil combination showed weaker signals than alfentanil alone. Propofol–alfentanil combination significantly reduced intracellular Ca2+ level, cAMP level and PLC activity.
Propofol and alfentanil exert synergistic analgesic effects through the adenylyl cyclase pathway.
Carvacrol, a monoterpene widely present in nature, is commonly used in the food industry and in cosmetics, besides to possess a plethora of pharmacological properties, among these also in vitro vasorelaxing effects and in vivo hypotensive responses. Although in rat aortic rings carvacrol evoked a vasodilatation both in the presence and in the absence of endothelium, in preparations with intact endothelial layer its vasoactive response markedly improved.
This study aimed at investigating the mechanism of action responsible for the endothelial component of the carvacrol-induced vasorelaxing response observed in rat isolated aortic rings.
Pharmacological characterization led us to exclude the involvement of NO pathway (neither L-NAME, NO biosynthesis inhibitor, nor ODQ, guanylate cyclase inhibitor, was able to modify the vascular effects of carvacrol) and of arachidonic acid cascade (no inhibitor intercepting the cascade influenced the endothelial-dependent vasodilatation of the monoterpene). Moreover, endothelial TRP channels were also not involved, as capsazepine did not antagonize vasorelaxing effect.
Finally, endothelial potassium channels were considered as possible targets of carvacrol; indeed, two voltage-operated potassium (Kv) channel blockers, 4-aminopyridine and quinine, significantly reduced carvacrol potency and efficacy indices.
Kv channels seem to be responsible for vascular effects of the monoterpene typical of Labiatae family.
Iron chelation in the transfusion-dependent anaemias management is essential to prevent end-organ damage and to improve survival. Deferasirox is a once-daily orally active tridentate selective iron chelator which pharmacokinetic disposition could influence treatment efficacy and toxicity. Therapeutic drug monitoring is an important tool for optimizing drug utilization and doses.
A fully validated chromatographic method was used to quantify deferasirox concentration in plasma collected from paediatric patients with β-thalassaemia. Samples obtained after 5 days of washout or in naïve patients before and after 2, 4, 6 and 24 h drug administration were evaluated.
Associations between variables were tested using the Pearson test. Twenty paediatric patients were enrolled; they were mainly men (13.65%), with median age of 6.35 years and body mass index of 15.45 kg/m2. Concerning pharmacokinetic parameters, a higher interindividual variability was shown. A positive, but not significant, correlation (r = 0.363; P = 0.115) was found between deferasirox area under the concentration curve over 24 h (AUC) and drug dose.
Monitoring plasma deferasirox concentrations appears beneficial for guiding appropriate patient treatment, enhancing effectiveness and minimizing toxicity.
The purpose of this article was to present an original standardized tool assessing the medicine's acceptability whichever their characteristics and the patient features.
An acceptability map was built with objective measures from medicine use assessments collected in real-life conditions. Multiple correspondence analysis (MCA) was used for the mapping process. Hierarchical classification on the principal components (HCPC) of the MCA was performed for the clustering process corresponding to distinct acceptability profiles.
The results presented here focus on 234 evaluations issued from the paediatric population and gathered in four clusters: 'well-accepted' (50%), 'accepted' (19%), 'poorly accepted' (25%) and 'not accepted' medicines (6%). The first one was characterized by a dose fully taken, in a short time, with a patient's positive reaction; the second by a longer administration time, a neutral reaction and the use of methods to achieve administration (reward, divided dose). Differentiation between the two last clusters was, respectively, originated by a required dose partially taken or not taken.
The acceptability profile of each medicine can be evaluated with the map position of the related patient's assessments barycentre. This tool should satisfy expectations in terms of methods for appropriate acceptability evaluation and standardized comparison among medicines.
Phyllanthus niruri is a traditional shrub of the genus Phyllanthaceae with long-standing Ayurvedic, Chinese and Malay ethnomedical records. Preliminary studies from cell and animal model have provided valuable scientific evidence for its use.
This review aims to summarize selected scientific evidence on the pharmacological properties of P. niruri over the past 35 years while identifying potential areas of further development of this herb as an economical adjunct.
The review covers literature pertaining to the evidence base therapeutic potential of P. niruri spanning from 1980 to 2015 available on PubMed.
Evidence suggests that the extracts of P. niruri possess hepatoprotective, antiviral, antibacterial, hypolipidaemic, hypoglycaemic, analgesic, anti-inflammatory, cardioprotective, anti-urolithiatic and antihyperuricaemic properties due its novel bioactive compounds.
Scientific evidence suggests that there is strong pharmacological potential in developing P. niruri as a drug to be used in liver disorders and in antiviral therapy. Despites this, large-scale heterogeneity in study protocol and unstandardized reporting standards limit the ability for valuable comparison and may mask the ability to replicate these studies. Thus interpretation of findings should be performed with caution and further studies should be performed in line with best practices. More cheminformatics, toxicological and mechanistic studies would aid the progress to clinical trial studies.
The purpose of this study was to investigate the pharmacokinetics of a single oral administration of metyrapone (MP) and metabolites produced from it in male Wistar rats, and the major tissues and enzymes involved in the production of the MP metabolites. Furthermore, the MP metabolism in human liver subcellular fractions was compared with that in rats.
High-performance liquid chromatography with ultraviolet detection (HPLC-UV) was used to determine the concentrations of MP and its metabolites in plasma and urine after administration, and the production activity of MP metabolites in subcellular fractions of various tissues.
Plasma concentration of MP was rapidly increased and decreased, and the primary metabolite, metyrapol (MPOL), was immediately produced. The production activity of MPOL was substantially inhibited by an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor in the rat and human liver microsomal and mitochondrial fractions. In the liver cytosolic fraction, the activity was inhibited by a carbonyl reductase inhibitor in the humans but not rats.
In this study, we elucidated the plasma pharmacokinetics of MP and its metabolites in male rats after an oral administration. MPOL is most likely to be produced by 11β-HSD1 in the male rats and humans.
We developed Cur nanosuspension (Cur-NS) with PVPK30 and SDS as stabilizers to improve poor water solubility and short biological half-time of Cur.
Physicochemical characterization of Cur-NS was characterized systematically. The in-vitro dissolution, cytotoxicity and in-vivo pharmacokinetic experiments of Cur-NS were also evaluated.
Scanning electron microscope indicated that the morphologies of Cur-NS were spherical or ellipsoidal in shape. X-ray diffraction verified that Cur was successfully developed as nanoparticles with an amorphous phase in Cur-NS. Fourier transform infrared spectroscopy suggested there was no degradation about Cur in the Cur-NS. Furthermore, the in-vitro study showed that the cumulative release of the Cur-NS was 82.16 ± 2.62% within 34 h and the cytotoxicity of the Cur-NS against HepG2 cells was much better than raw Cur. Besides, in-vivo pharmacokinetics in rats by intravenous injection displayed that the in-vivo process of Cur-NS pertained to two-compartment model. Meanwhile, the t1/2 and AUC0–t of Cur-NS were enhanced by 11.0-fold and 4.2-fold comparing to Cur solution.
The Cur-NS significantly increased the water solubility and half-time of Cur, suggesting its potential as a nanocarrier in the delivery of Cur for future clinical application.
The aims of the current research project were to investigate the efficiency of various polymers to enhance the solubility and increase the systemic absorption of piperine using hot melt extrusion technology.
Piperine 10–40% w/w and Eudragit® EPO/Kollidon® VA 64 or Soluplus® were mixed, and the resulting blends were extruded using a twin-screw extruder (Process 11, Thermo Fisher Scientific). Drug release profiles and piperine solubility studies of the extrudates were evaluated. A non-everted intestinal sac was employed for the most promising formulation, 10% w/w piperine/Soluplus®, and pure piperine to study the permeability characteristics.
Dissolution studies demonstrated enhancement in piperine per cent release of 10% and 20% w/w piperine/Soluplus® extrudates up to 95% and 74%, respectively. The solubility of 10% and 20% piperine/Soluplus® increased more than 160- and 45-fold in water, respectively. Furthermore, permeability studies demonstrated the enhancement in piperine absorption of 10% w/w piperine/Soluplus® extrudates up to 158.9 μg/5 ml compared with pure piperine at 1.3 μg/5 ml within 20 min.
These results demonstrated that increasing the bioavailability of piperine may be achieved as demonstrated by findings in this study.
New salicylic acid (SA)-loaded gels were developed using excipients made from renewable materials, and our goal was to improve drug permeation in the topical treatment of acne vulgaris.
We studied the preparation parameters to obtain suitable gel formulations. Only naturally occurring polymers were used as gelling agents. Two hydrogels and three lipogels were selected and characterized in terms of drug loading, pH, viability cells, rheology, mechanical properties and in vitro permeation; these hydrogels and lipogels were compared with the traditional ointment. We also evaluated skin parameters before and after gel application.
The formulations that we studied are non-Newtonian fluids; they have high drug loading and suitable mechanical properties. Lipogels exhibit a slower and more linear in vitro permeation profile compared with hydrogels. The different vehicles that we used affected drug permeation and improve patient compliance. Cytotoxicity studies suggest that all of the formulations are non-toxic.
Lipogels demonstrate appropriate technological features and improved performance compared with the traditional ointment with regard to their composition. Lipogels may represent a new bio-based topical system for SA delivery. The use of 'green' excipients leads to 'skin-friendly' formulations that are able to satisfy environmental safety.
Ocular diseases affecting retina, such as diabetic retinopathy (DR), age-related macular degeneration (AMD) and glaucoma are the major causes of blindness, and their treatment is still a challenge due to the special structure of the eye. The purpose of this study was to prepare a sustained release DEX conjugate formulation with enhanced ocular permeation using poly(amidoamine) (PAMAM) dendrimers and to evaluate the effects of conjugation on DEX release and ocular residence time.
PAMAM G3.5 and PAMAM G4.5 dendrimers were used to prepare DEX conjugates, and conjugation was confirmed using 1H-NMR. Formulations were evaluated in terms of drug release in the presence of ocular enzymes and cytotoxicity on ARPE19 cell lines. Fluorotron analysis was performed and ocular pharmacokinetic properties of DEX–PAMAM conjugates were studied in Sprague Dawley rats following intravitreal and subconjunctival applications.
The results indicated that DEX–PAMAM conjugates were able to enhance ocular permeability and ocular tissue levels of DEX following subconjunctival injection, and results were encouraging when compared to the literature that has reported DEX getting cleared from vitreous in 3 h.
Current studies are focused on formulation improvement to enhance hydrolysis and clearance time.
Neuregulin-1 (NRG1) has an important role in both the development and the plasticity of the brain as well as neuroprotective properties. In this study, we investigated the downstream pathways of NRG1 signalling and their role in the prevention of Aβ1–42-induced neurotoxicity.
Lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) generation, superoxide dismutase (SOD) activity and TUNEL staining were assayed to examine the neuroprotective properties in primary rat cortical neurons.
The inhibition of PI3K/Akt activation abolished the ability of NRG1 to prevent Aβ1–42-induced LDH release and increased TUNEL-positive cell count and reactive oxygen species accumulation in primary cortical neurons.
Our results demonstrate that NRG1 signalling exerts a neuroprotective effect against Aβ1–42-induced neurotoxicity via activation of the PI3K/Akt pathway. Furthermore, this suggests that NRG1 has neuroprotective potential for the treatment of AD.
A novel magnetic targeting anti-tumour drug delivery system (Fe3O4/KCTS-CHE) was designed using magnetic Fe3O4/chitosan alpha-ketoglutaric acid (Fe3O4/KCTS) as carrier and chelerythrine (CHE) as an anti-tumour drug model. Moreover, the anti-tumour activities and mechanisms of Fe3O4/KCTS-CHE were investigated.
The preparation conditions of Fe3O4/KCTS-CHE microspheres were optimized by response surface methodology (RSM). The CHE drug release kinetics was evaluated by fitting the experimental data to standard release equations. The inhibitive activities of Fe3O4/KCTS-CHE microspheres against the HepG2 cells were estimated using MTT assay in vitro, and the mechanisms were studied using Hoechst 33258 staining.
The optimum preparation conditions were 11.68 : 1 for Fe3O4/KCTS:CHE ratio, 4 : 1 for oil/water ratio and 50.03 min for the ultrasonic time. The drug loading content and entrapment efficiency under the optimal conditions were 23.3% and 50.9%. The best fit was Higuchi model for the microspheres. The inhibitive rate on HepG2 cells of Fe3O4/KCTS-CHE nanoparticles varied from 30.19 ± 2.64% to 70.46 ± 6.42% at different concentrations from 50 to 400 mg/l in 72 h.
Fe3O4/KCTS-CHE exhibited effective anti-tumour activities against the HepG2 cells and induced cell apoptosis in HepG2 cells. Fe3O4/KCTS-CHE possess a high drug loading efficiency and entrapment efficiency, which are a new matrix for controlling release of drugs and a promising candidate for targeted drug delivery.
To define likely targets (i.e. glia) and protocols (analgesic combinations) to improve postoperative pain outcomes and reduce chronic pain after surgery. Specifically, to assess the antihyperalgesic effects of the dexketoprofen : tramadol (DEX : TRM) combination, exploring the implication of glial activation.
In a mouse model of postincisional pain, we evaluated mechanical nociceptive thresholds (Von Frey) for 21 days postoperatively. We assessed DEX and TRM alone and combined (1 : 1 ratio) on postoperative hyperalgesia (POH, day 1) and delayed latent pain sensitisation (substantiated by a naloxone challenge; PS, day 21). The interactions were analysed using isobolograms, and concomitant changes in spinal glial cell activation were measured.
On day 1, DEX completely blocked POH, whereas TRM induced 32% inhibition. TRM, but not DEX, partially (47%) protected against PS, at 21 days. Co-administration of DEX : TRM (1 : 1 ratio) showed additivity for antihyperalgesia. Both drugs and their combination totally inhibited surgery-induced microglia activation on day 1, but had no effect on surgery-induced astrocyte activation (1 day) or re-activation after naloxone (21 days).
The DEX : TRM combination could have clinical advantages: a complete prevention of POH after surgery, together with a substantial (48%) inhibition of the development of PS by TRM. Microglia, but not astrocyte activation, could play a relevant role in the development of postoperative pain hypersensitivity.
This study evaluates the effect of isoflavone cladrin on high-fat diet (HFD)-induced bone loss and adipogenesis.
Thirty-two 4-week-old male C57BL/6J mice were divided into four groups: a standard diet group, a HFD group and HFD group with cladrin (5 and 10 mg/kg per day orally) for 12 weeks. The effect of cladrin on bone micro-architecture, bone marrow cell lineages and hyperlipidaemia were assessed. For assessing anti-adipogenic activity of cladrin, 3T3-L1 cells were used.
Cladrin attenuated HFD-induced hyperlipidaemia and bone loss by preserving bone micro-architecture and strength. Effect of cladrin was found at the level of bone marrow progenitor cells. Gene expression profile of cladrin-treated mice bone showed upregulation of osteoblast and downregulation of adipogenic transcription factors and increased OPG/RANKL ratio. Cladrin inhibited cellular lipid accumulation through downregulation of transcription factors such as PPAR-γ and C/EBP-α and modulated the expression of major adipokines involved behind obesity stimulation without eliciting cell cytotoxicity in 3T3-L1 adipocytes.
We conclude that cladrin may improve obesity-induced bone loss and hyperlipidaemia in mice fed HFD and adipogenesis in 3T3-L1 cells by modifying adipokines and could offer clinical benefits as a supplement to treat obesity-induced disorders.
Using an experimental model of allergic asthma, we evaluated the anti-asthmatic potential of polyphenol flavonol derivate morin after either acute or long-term treatment of male OVA-sensitised guinea pigs.
The following methods were used in experiments: the in-vitro tracheal smooth muscle contraction induced by histamine; the changes in specific airway resistance (sRaw) to histamine and the sensitivity of a chemically induced cough reflex both via an in-vivo method; the serum and BALF concentrations' analysis of the inflammatory cytokines interleukin IL-4, IL-5, IL-13; and lung tissue infiltration by eosinophils and mastocytes.
Our data show that acute morin (30 mg/kg) and chronic 21-day morin (30 mg/kg/day) administration had a comparable antitussive efficiency with opioid antitussive codeine. Acute morin bronchodilatory activity defined by in-vivo sRaw decline did not reach SABA salbutamol effect. However, bronchodilatory efficiency of morin after long-term administration was by 34% higher as effect of LABA salmeterol. The 21-day morin treatment of OVA-sensitised guinea pigs reduced the serum, BALF levels of IL-4 and IL-13, lung tissue eosinophil and mastocyte infiltration comparable with corticosteroid budesonide.
In summary, morin represents very rational target for additional studies as potential substance for control as well as prevention of asthma inflammation and symptoms.
Red propolis, an exclusive variety of propolis found in the northeast of Brazil has shown to present antitumour activity, among several other biological properties. This article aimed to help to evaluate the underlying molecular mechanisms of the potential anticancer effects of red propolis on tumour, Hep-2, and non-tumour cells, Hek-293.
Differentially expressed proteins in human cell lines were identified through label-free quantitative MS-based proteomic platform, and cells were stained with Giemsa to show morphological changes.
A total of 1336 and 773 proteins were identified for Hep-2 and Hek-293, respectively. Among the proteins here identified, 16 were regulated in the Hep-2 cell line and 04 proteins in the Hek-293 line. Over a total of 2000 proteins were identified under MS analysis, and approximately 1% presented differential expression patterns. The GO annotation using Protein Analysis THrough Evolutionary Relationships classification system revealed predominant molecular function of catalytic activity, and among the biological processes, the most prominent was associated to cell metabolism.
The proteomic profile here presented should help to elucidate further molecular mechanisms involved in inhibition of cancer cell proliferation by red propolis, which remain unclear to date.
(-)-Myrtenol is a natural fragrance monoterpenoid structurally related to α-pinene found in diverse plant essential oils. This study was aimed to assess the anti-ulcerogenic potential of (-)-myrtenol against ethanol-induced gastric lesions and to elucidate the underlying mechanism(s).
Gastroprotective activity of (-)-myrtenol was evaluated using the mouse model of ethanol-induced gastric damage. To elucidate the gastroprotective mechanism(s), the roles of GABA, prostaglandins, nitric oxide and KATP channels were assessed. Besides, the oxidative stress-related parameters and the mucus content in gastric tissues were analysed.
(-)-Myrtenol at oral doses of 25, 50 and 100 mg/kg significantly decreased the severity of ethanol-induced gastric lesions affording gastroprotection that was accompanied by a decrease in the activity of myeloperoxidase and malondialdehyde, an increase in GPx, SOD, and catalase activity in gastric tissues, and with well-maintained normal levels of nitrite/nitrate, gastric mucus and NP-SHs. Pretreatment with GABA-A receptor antagonist flumazenil, the COX inhibitor indomethacin, and NO synthesis inhibitor L-NAME but not with KATP channel blocker glibenclamide significantly blocked the (-)-myrtenol gastroprotection.
These results provide first-time evidence for the gastroprotective effect of (-)-myrtenol that could be related to GABAA-receptor activation and antioxidant activity.


text:
This question originally appeared on Quora. Answer by ...
"I enjoy getting out in front of the crowds every single night, I enjoy seeing their faces light up and having a good time out there and seeing the smiles on their faces. That's what gives me a thrill now, just getting up there for the live action and just performing."
Disturbing news for anyone averse to one-day-old, let alone 31-year-old, leftovers: a piece of wedding cake preserved from Princess Diana and Prince Charles's 1981 wedding is being auctioned off next month in Beverly Hills.
The allure and thrill of the unknown ending in an over-scripted world and the visceral encounter with the unaltered has left us drunk and horny on communal media peep shows. And to all that I ask, as hungrily and curiously as everyone, also with a lingering sense of unease -- what next?
When it came to my story about the seven years I spent as masseur and body-mind health-coach to Diana, Princess of Wales, I knew the book I wanted to write would come about in perfect timing
I waited outside, guarding the door, hoping these two women -- so hounded and so admired -- might find solace in each other's company.
As an Englishman, Diana meant many different things to me. But as a gay man she meant even more.
For the gay community (including me) there was much sympathy and empathy for Diana's personal life and her work. Back in the day when HIV/AIDS was considered very much a "gay disease," people identified not only with her but with her desire to help the cause.
What is it about icons like Diana that make them so unforgettable? And why do some stars fade away, while others continue to burn brightly long after they leave us?
A little more than 10 years ago I was having dinner with the Countess of Dundee in her Scottish castle, Birkhill, when her daughter Lavinia joined us and told us all about her afternoon. She had been to St. Andrews to visit her cousin, William. Just William. Yes, that William.
It seems like only yesterday we were stunned, sitting mouths agape as news of Diana's death dominated every hour, every second of the news. Cable outlets were still fairly new, and it was wall-to-wall. But even the three primetime networks abandoned all programming.
The deaths of Natalie Wood, Princess Diana and--but of course!--Marilyn Monroe--are once again the topic of gossip, rumor and perhaps even some poetry.
Once dubbed as "the maker of the most beautiful hats in the world" by Italian style icon and former Vogue editor Anna Piaggi, Stephen Jones has made...
A Conversation with Peter White Mike Ragogna: Peter, before we get into your new album Here We Go, let's start with your early days playing with Al...
None of the guests at the wedding party could have known that Charles and Diana's marriage was already beginning to unravel. The Queen couldn't avoid Diana's disquieting behavior. Nobody had ever flouted protocol as Diana did, or shown such disrespect to the Queen.
When a man is unfaithful, it's not as cut and dry as "I need a prettier woman in my life." He's usually fulfilling a deeper psychological desire.

subset: commoncrawl


text:
To try the thousands of add-ons available here, download Mozilla Firefox, a fast, free way to surf the Web!Close
Welcome to Firefox Add-ons.
Choose from thousands of extra features and styles to make Firefox your own.Close
About me
|Računalniški Operater
|User since
|April 15, 2010
|Number of add-ons developed
|0 add-ons
|Average rating of developer's add-ons
|Not yet rated
My Reviews
FT DeepDark
Beta works on Firefox Version 44 for x86 and x64 Rated 5 out of 5 stars
My first and primary theme from first version :D I know is awesome theme for Firefox . My Firefox with All in One Sidebar , Classic Theme Restorer + Multi-Row and a few others addons all 10 and is perfect browser and theme works OK. I love developers they do great work.
With your teme my Firefox looks awesome and perfect! Thanks please keep up to date.
FT DeepDark 14 Beta 7
Tested on:
Firefox 44.0 x86-32bit and x64-64bit - Without any errors etc. theme works perfect.
HTTPS Everywhere
I recommend Rated 5 out of 5 stars
I am using this Apps and I never had any problems, Really awesome apps. Tor example: Adblock Plus settings are perfect automatic updates... Easy to use and user who know the site he create filter for that. Is very good feature I reali like it.
I don't know but on this app is a little more complicated.... Could you please add button "Disable for this site"....
Tab Utilities Fixed
Signing your add-on - Firefox 43 Rated 5 out of 5 stars
Starting with Firefox 43, there are some restrictions in place for add-on distribution.
If is possible please fix this.... Thanks
InstantFox Quick Search
Perfect Rated 5 out of 5 stars
The best addon!!This review is for a previous version of the add-on (3.0.2). This user has other reviews of this add-on.
Speed Dial
Addon for Chrome Rated 5 out of 5 stars
I don`t like Chrome because doesn`t have good addons and is not customizabled. I use it only few times per month but I can`t use it without your Speed Dial :) so could you do the same add-on for Chrome to? I search and all Speed Dials for Chrome are to complicated and have a lot of useless things. I need simple and only Speed Dial. If you had time made same import/export file as Firefox have it... because I have more than 100 pages added in groups.
Your Speed Dial is not only Awesome but Perfect :) I really like it because works perfect and is simple Speed Dial.
InstantFox Quick Search
Rated 5 out of 5 stars
I like it first because I can add sites my self, and of course shortcuts to. Very easy to use and search that for sure :)
Anyway I only "hate" import/export it will be alot better if it was import/export from/is file and not from clipboard. If you made now update please fix this and make import/export to/from File.
Perfect Addon now I can search alot faster and alot easy with this addon. What me do without you guys Addon Developers :) I will tell you the truth I can`t use my browser without addons is impossible realy impossible. Addons make Browser alot better and for sure alot easy to use it!!
Please keep up to date :)
Tab Utilities Phoenix
Rated 2 out of 5 stars
For now best same addon is:
Works perfect on latest version 39.0 !
Customizable Shortcuts
Added by default Rated 5 out of 5 stars
@Stian = I agree with you this most be by default almost all softwares have it why not Firefox? More addons is worse not better then new updates, problems with other addons etc.
Works ok on Version 39 and with other addons
Quick Translator
Rated 5 out of 5 stars
Very good works perfect I really like it :) Thanks
Firefox Version:
Windows 8.1
Tab Utilities
Rated 5 out of 5 stars
Sure this addon is awesome I`m using it for long long time but one problem no updates :( Please fix save file problem this is almost only reason I can`t using it.... :( I will give you 5 Stars.This user has 2 previous reviews of this add-on.
Tab Scope
Rated 5 out of 5 stars
Thanks I`m using it for long long time and works perfect. I know is only a few settings... but if you have time or... please add inside option for Backup Settings (Export/Import). I always like it easy and fast with same settings.
Rated 5 out of 5 stars
Very good addon! For now works perfect but i`m using it for about a day. Thanks we need good addons for best Browser!! :)This review is for a previous version of the add-on (5.1.0).
Tab Utilities Fixed
We need MORE developers like YOU Rated 5 out of 5 stars
Thanks for fix! I realy like this addon is all in one :) I always hate when best addons doesn`t work and no more updates :S I always hate this so really thanks for Fix!This review is for a previous version of the add-on (1.5.2015.04.05).
Add-on Compatibility Reporter
Very good Addon Rated 5 out of 5 stars
Works perfect on Firefox version 37.0.2.
It will be good if page show which addons was checked with this addon or any other default addon or function checker !
I mean for every addon which has been checked will be showed below users reviews on the right side!
This will be very helpful for other users. Firefox have alot addons which is very good and I am also very satisfied. Every user use own addon he like.... but problem is that some addons doesn`t work or they not working correct. If page show which addons work perfect will be very helpful....
All-in-One Sidebar
Best of the Best Rated 5 out of 5 stars
Best addon for Firefox !! I realy don`t know what I do without this addon!! I use this addon from first version :D
I realy hate that only Firefox have this addon all other browsers doesn`t have sidebar is realy stupid because for Favorites, Download, History I need to search in options LOL !! With this addon I can open Favorites, Download, History with only one click and History or Favorites will be open, and I can click any page without close it!
For example, in Chrome I need 2 clicks for opening Downloads, Favorites and what is more stupid who need the entire tab for Download, Histrory and Favorites LOL !
With this addon I could have open Download, History, Favorites and I still could searching on sites etc. without closing it! On Chrome you can`t because for Downloads, History, Favorites use entire tab is realy annoying !
This addon works perfect even on Firefox Nightly !!
Please keep up to date :)
Classic Theme Restorer
Rated 5 out of 5 stars
What would we do without this addon!!! I hate Australis I hate what they do with Firefox they remove everything....
Thanks for this addon please keep up to date please!
MaskMe: Online Privacy Protection
Rated 5 out of 5 stars
Is a new addon Blur is a new MaskMe !
All in One
FT DeepDark
Rated 5 out of 5 stars
Best Theme for Firefox works perfect even with All In One Sidebar !!!
Thanks for awesome Theme !
Anyway it doesn`t work for x64 (39.0a1) can you fix this?
Classic Theme Restorer
Best Addon ever made for Firefox - I hate Australis !! Rated 5 out of 5 stars
Best addon I hate Firefox Australis is the worst Firefox ever made with this addon I made perfect Firefox!!! Movable buttons etc. perfect!!!
All-in-One Sidebar
BEST ADDON 100 Stars Rated 5 out of 5 stars
Best addon!! Without this addon I can`t use Firefox! Please keep Up to Date :) I use it from the first version. First I was using Opera but then I found this addon and is Amesome!
If this addon would not exist I would be now on Opera 12! Really I do not lie!
5 Stars for this addon is not enough! This addon deserves a minimum 100 stars!!
Please keep Up to Date :)
Anyway only one SMALL problem - First this addon had buttons on Download page but now doesn`t have I miss these buttons - Delete, Open etc.
To create your own collections, you must have a Mozilla Add-ons account.


text:
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Let $L^{p}(\mathbb{R}^d)$ be the linear space consists of $L^p$-integrable functions on $\mathbb{R}^d$ for $1\le p \le \infty$. Are there any relation among these spaces?
A simple observation, which apparently was not mentioned in either of the aforementioned threads.
If $p\le q\le r$, then $L^p\cap L^r\subset L^q\subset L^p+L^r$. This holds on any measure space, including $\mathbb R^d$.
Proof is based on the decomposition $f=f_S+f_L$ where $f_S=f\chi_{\{|f|\le 1\}}$ and $f_L=f\chi_{\{|f|>1\}}$. Indeed, $|f_S|^r\le |f_S|^q\le |f_S|^p$ and $|f_L|^p\le |f_L|^q\le |f_L|^r$ pointwise. Therefore, $f\in L^q$ implies that $f_S\in L^r$ and $f_L\in L^p$, proving the second inclusion. Proof of the first inclusion is left as an exercise.


text:
Book your room at La Quinta Inn & Suites Jacksonville Butler Blvd
Get an overview of this hotelJacksonville hotel in Southpoint with free breakfast and outdoor pool
Located in Southpoint, this hotel is within 6 mi (10 km) of Saint Vincent's Medical Center Southside, St. Johns Town Center, and The Avenues. Dog Wood Park of Jacksonville and Crabtree Park are also within 6 mi (10 km).
Hotel Features
An outdoor pool, a fitness center, and a spa tub are available at this smoke-free hotel. Free continental breakfast, free WiFi in public areas, and free self parking are also provided. Additionally, coffee/tea in a common area, a business center, and a meeting room are onsite.
Room Amenities
All 131 rooms offer free WiFi, pillowtop beds, and flat-screen TVs with cable channels. Guests will also find coffee makers, free local calls, and hair dryers.Would you like to give us feedback? Share it! Opens in a new window
La Quinta Inn & Suites Jacksonville Butler Blvd4686 Lenoir Ave S Jacksonville FL 32216
Hotel Amenities
Hotel Amenities
In addition to an outdoor pool, La Quinta Inn & Suites Jacksonville Butler Blvd provides a spa tub and a fitness center. High-speed wireless Internet access is complimentary. This hotel offers access to a business center and a meeting room. A complimentary breakfast is offered. This Jacksonville hotel also offers multilingual staff, coffee/tea in a common area, and an elevator (lift). Complimentary self parking is available on site.
La Quinta Inn & Suites Jacksonville Butler Blvd is a smoke-free property.
- 24-hour front desk
- Business center
- Coffee/tea in common areas
- Elevator/lift
- Fitness facilities
- Free breakfast
- Free self parking
- Free WiFi
- Multilingual staff
- Number of floors - 6
- One meeting room
- Outdoor pool
- Smoke-free property
- Spa tub
- Total number of rooms - 131
Family Friendly Amenities
- Cribs/infant beds (complimentary)
- Free Wi-Fi
- Outdoor pool
Available in all rooms: Free WiFi
Available in some public areas: Free WiFi
Free self parking
Room Amenities
- Air conditioning
- Cable TV service
- Coffee/tea maker
- Free toiletries
- Free cribs/infant beds
- Daily housekeeping
- Desk
- Flat-panel TV
- Free local calls
- Free WiFi
- Hair dryer
- Iron/ironing board
- Phone
- Pillowtop mattress
- Premium TV channels
- Private bathroom
- Shower/tub combination
Where to Eat
Guests are offered a complimentary continental breakfast.
Nearby Things to Do
An outdoor pool and a spa tub are on site. Other recreational amenities include a fitness center.
To make requests for specific accessibility needs, complete the "Special or Accessibility Requests" section of "Trip Preferences" when you book your hotel.
- Accessible bathroom
Hotel Policies
Check-in time ends at Midnight
Check-in time starts at 3 PM
Minimum check-in age is 21
Check-out time is Noon
Payment types
- Pets stay free
You need to know
Extra-person charges may apply and vary depending on hotel policy.
Government-issued photo identification and a credit card are required at check-in for incidental charges.
Special requests are subject to availability upon check-in and may incur additional charges. Special requests cannot be guaranteed.
- The name on the credit card used at check-in to pay for incidentals must be the primary name on the guestroom reservation.
No rollaway/extra beds available
Pets allowed (no fees)
Hotel Name
- Butler Boulevard
- Butler Boulevard Jacksonville
- Butler Jacksonville
- La Quinta Butler Boulevard
- La Quinta Inn Butler Boulevard
- La Quinta Inn Jacksonville Butler Boulevard
- La Quinta Jacksonville Butler Boulevard
- Quinta Inn Jacksonville Butler Boulevard
- Quinta Inn Butler Boulevard
- Quinta Jacksonville Butler Boulevard
- Quinta Butler Boulevard
- Quinta Inn Jacksonville Butler Blvd
- Quinta Inn Butler Blvd
- Quinta Jacksonville Butler Blvd
- Quinta Butler Blvd
- La Quinta Inn And Suites Jacksonville Butler Boulevard
- Jacksonville La Quinta
- La Quinta Inn & Suites Jacksonville Butler Boulevard Hotel
- La Quinta Inn Suites Jacksonville Butler Boulevard
We should mention
Children 18 years old and younger stay free when occupying the parent or guardian's room, using existing bedding.


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AIG Was Cut Out of Wall Street 2 for Being 'Too Complex'
Former chairman's film debut ends up on the cutting room floor.
"We did have scenes with AIG, by the way," Mr. Stone said. "We had the chairman, [Maurice] Greenberg, but I ended up cutting it out because, frankly, it was too complex for the average viewer." (Don't be sad, Hank. The same thing happened to Kevin Costner in The Big Chill and things turned out pretty well for him.) [NYO]


text:
Cost almost £800 altogether from Audi.
Will fit all pre-facelift A5s / S5s or RS5s.
Just a few months old.
Comes with the number plate plinth,...
Cheers! Yes, Reinis is an artist with a camera!
I looked for a long time to find this car as it has all the extras and the spec that I wanted but need a 4 door car now so it's time to sell...
No the belt was got by the fitter who is trying to pass the buck on to the supplier (motor factor) for supplying the wrong belt.
Hi guys.
Just wanted to pick your brains here.
A family member who lives in London had a timing belt replaced recently that led to a failure....
Found out myself (finally).
It's: 8K0805163A just in case anyone ever needs them!
Hi guys.
Does anyone know what the Audi part number for these undertray clips is?
It's a 2009 2.0TDi coupe.
There are 11 altogether that...
I have an S Line with 20" wheels AND Eibach Sportline springs.
Ironically it's very comfortable!
Are there better aftermarket grilles than others?
I can get a genuine RS5 grille for a bit over £500.
Just wondering if it's worth the extra money.
The only cosmetic thing I'd change on my pre-facelift 2009 A5 Quattro S-Line coupe would be the rather bland looking grille.
Question is; what...
You might want to get the MAF sensor values checked and also check for boost leaks.
I'd recommend adding a bottle of Wynn's diesel clean 3 to half...
Averaging 40-45 MPG on my quattro 2.0TDi coupe.
Get 50+ on a longer journey (30 miles +)
Have the Revo stage 1 on my CR 170 2.0TDi Quattro and it's great.
Smoother and a lot more power.
Ok chaps.
Fitted a set of Eibach pro kit springs yesterday.
The springs may need to settle a bit but the front end is too high compared to the...
Thanks for the reply Damian.
Does the S line share the same shocks as the sport and SE?
IE, are the springs the only difference?
I'd like to drop my S line 2009 A5 slightly but am not sure which springs to go for.
It sits up at the front more so ideally I'd like a drop of...


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[CSip] Froyo theme
Froyo (android 2.2) theme for CSipSimple application. !!! YOU NEED CSIPSIMPLE INSTALLED TO HAVE
Free • 257
All Android applications categories
All Android games categories
Froyo (android 2.2) theme for CSipSimple application. !!! YOU NEED CSIPSIMPLE INSTALLED TO HAVE
Free • 257
.9.12 - Supports 2.2 Froyo
Free • 12.4K
: - Android OS 2.2 (Froyo) or up. - ssLauncher Original app installed. 2. Applying Theme : - In ss
$1.99 Free • 91
: - Android OS 2.2 (Froyo) or up. - ssLauncher Original app installed. 2. Applying Theme : - In ss
$0.99 Free • 203
: ------------------------ Android 2.2 (Froyo) to Android 4.x Ice Cream Sandwich and Jellybean. Disclaimer
Free • 253
dark action bar) themes in mind, but it will also work on any Android 2.2+ cellphone or tablet
Free • 809
★ Top Developer (awarded 2013 / 2015) ★ Chess Free is the best free Chess game on Android and is currently the highest ranked (at time of writing) from the 120+ free chess programs listed! Its first class tutor makes it great for both developing Chess Strategy and improving your chess skills. Completely free! This is not a demo, and has no locked…
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Remember me: "Learning By Heart"
by Ana Gracia
THE VERDICT Remember Me is a language learning application that tries to make sure that you actually learn foreign vocabulary. Often, when reading a text in another language, we come across some words that we don't know what they mean. After lo…
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Published: Sunday, May 30, 2004 at 4:30 a.m.
Last Modified: Sunday, May 30, 2004 at 12:00 a.m.
COLUMBUS -- Standing beside a partially completed fountain, three veterans reminisced about the trials and triumphs involved in the city's new veterans park.
Scott Camp, Garry Fisher and William Hampton have been involved in the project since its beginnings in 1994 and all served their country in the military.
Camp, 75, served in the Merchant Marines in World War II. Fisher, 55, joined the Army at the age of 17 and was sent to Korea. He later served in Vietnam. Hampton, 72, skipped his high school graduation to go into the Navy in 1951. He served as an electrician's mate on the USS Gainard toward the end of the Korean War.
For the trio of veterans, the goal was to create a memorial to mountain veterans so that the sacrifices they made for America "should never end in our memories," they said.
"The men who died should be remembered for giving their lives for what they believed in," Camp said.
The late Jim McCain, chaplain of the Veterans of Foreign Wars Post 9116 in Columbus, came up with the idea for the memorial. McCain served as a Navy chaplain for 32 years.
"He served his country, served his God and served his county," Fisher said.
The project ran into various setbacks, the biggest being procuring land for the park. That problem was solved with an anonymous donation of land near the Polk County Courthouse.
Not forgotten
Construction began on the park three months ago.
It was expected to be completed by Memorial Day, but it will probably not be finished for another six weeks because of the weather, Camp said.
When finished, it will feature a fountain with engraved bricks along the edge. The bricks, which were sold for $25 each, will have the names and ranks of veterans.
Not all of the bricks belong to deceased veterans. Some were purchased by living veterans. The memorial will include more than 1,000 engraved bricks. Proceeds from sales of the bricks generated $20,000 for scholarships for the children of veterans.
Seven flags will also be flown over the park -- the American flag and one for each branch of the military, including the Coast Guard and the Merchant Marines.
The park will also feature a 30-foot-by-16-foot concrete stage that will be used for events such as the city's Fourth of July celebration.
Town administrator Glenn Rhodes secured most of the $170,000 needed to build the park. A $137,000 grant from the N.C. Department of Parks and Recreation paid for a large portion of the park's construction.
Although the park will commemorate the dead, Fisher, Camp and Hampton say it as a place "more for the living."
With Memorial Day on Monday, more people will take time to remember the men and women who served America. Reflecting on the importance of veterans memorials, Janice Holm, president of the Ladies Auxiliary of VFW Post 4309, said, "What it means is that there were citizens of our country who made the ultimate sacrifice for my freedom."
Forest Lawn memorial
Forest Lawn Memorial Park off Tracy Grove Road honors the veterans buried beneath its manicured turf.
A granite memorial wall with the names of 419 veterans inscribed upon it was dedicated Memorial Day 1985. Not all of the 832 veterans buried at the cemetery have had their names inscribed yet. Their names will appear on one of two other tablets that will be placed at the cemetery. The cemetery will place the second tablet by Veterans Day, Nov. 11. They expect to place the third by Memorial Day 2005.
Forest Lawn set aside three sections of the cemetery for veterans' and their immediate families' burial plots. Two of the sections -- the Veterans Garden of Taps and the Veterans Garden of Honor -- have flat markers on the ground.
The other section is for those with upright headstones marking their graves. Altogether, there are 3,000 plots for local veterans and their families.
On Memorial Day, Forest Lawn hosts a service honoring the veterans.
Shuford Edmisten, a Vietnam veteran and past state commander of the American Legion, takes pride in hosting the Memorial Day service.
"There's so much history buried out here," he said.
Other memorials
Originally placed at the intersection of Main Street and First Avenue, it was moved to its current location in 1925. It had become a traffic hazard.
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Poll: In my story Seme and Slave, should Sasuke and Itachi ever find out that they're brothers? Vote Now!
Author has written 3 stories for Naruto.
Hello, peoples of FanFiction! My name's Crimson, and I like to obsess over fandoms. Oh, and Yaoi. I LOVE YAOI!!! Especially Naruto yaoi, but any yaoi is fantastic. I also watch Doctor Who and I like the Eragon books. I'm really not that interesting... most of my stories will be yaoi and will contain lemons, and they will be boy-boy, so if you don't like then don't read, and please don't flame. Thanks :) Oh, and PS... I'm a bit of a pervert. Just warning you, in case you hadn't figured that out already. If you like you can request a lemon yaoi pairing and I might write a oneshot for you, depending on if I like the pairing. If I'm gonna publish a story that's curse and lemon-free I'll state it in the summary.
I am a huge pervert. I am also a huge fan of uke Sasuke. Especially slave BDSM uke Sasuke... so I would be eternally grateful to anyone who knows of a good story like that and told me about it. I don't even care who the seme is (although I do enjoy Itachi and Naruto as seme), as long as Sasuke is uke... and him being a slave is just a bonus. So yeah, drop me a line if you know of any good ones, I'll love you forever :) If I don't want any more I'll delete this note, so if it's still up then please, do tell. I've been tearing FF apart recently for good, slave Sasuke fics and I'm running extremely low :( help, anyone?
Also something you should know: I am Bi. It's been an interesting process, accepting that about myself. But I've begun to realize that sexual orientation isn't all there is to a person, even though when my parents found out they sent me to the loony bin to try and fix the 'problem'. Damn bastards. I have attempted to tell them that simply because they don't believe in being bisexual or gay doesn't mean it is wrong, and that I DON'T need to see therapists because I am 'confused', but to no avail. I'M NOT INSANE BECAUSE I'M BISEXUAL. It pisses me off and makes me sad :( Ahem, anyways... didn't come here to read my sob story, did you? So, moving on.
Stories I'm working on:
Seme and Slave (Naruto, ItaSasu, yaoi lemons, in progress) Next chapter's in progress. I thought I should warn you guys in advance this time, it's looking to be a long wait this time around. I'm so sorry but the motivation is eluding me... I'm still hacking away at it but every sentence feels choppy and forced and downright painful. So. My apologies but it's probably gonna be a while :(
Love like This (Naruto, Oneshot, SasuGaara, yaoi lemon) quite possibly the worst piece I've ever written, my first lemon ever and god is it bad. I should really delete the horrendous thing off the internet but I haven't gotten around to it yet.
Three's a Party (Naruto, ItaNaruSasu, yaoi lemons, in progress) As of right now I'm focusing mainly on Seme and Slave, and once that's finished I'll give this one some love. I do fully intend to get back to it though, just not soon. When I do though, I think it's gonna be good :) lots of pervertedness and ItaNaruSasu lemony fun.
I should introduce you to Neko-san, if you don't know him already - he's my mascot. Neko-san's at the end of every chapter along with my author's note. He is also sometimes known as Hypno-kitty.
On a happier note - my favorite people in the world are my reviewers. Seriously, with my family trying to counsel the bi-ness out of me, my readers are some of the only people who seem to care and accept me. And even more than the feedback (which is also brilliant), I love you guys for that. Wouldn't be where I am not if it weren't for you.
Alright, enough of that... here's some random info on me, which none of you are probably interested in, but I thought I'd put it here anyway. These are common misconceptions people like to make about me and everybody else.
I'm SKINNY, so I MUST be anorexic. (Lie. I'm tall, it's an optical illusion that I'm skinny. I'm average.)
I'm CONSERVATIVE, so I MUST be against Abortion (True, I am against abortion)
Okay, that's over and done with. I'm high on sugar right now so I'm just gonna go rambling on, I know most of you probably won't read this, it's okay, don't bother, there's nothing important or useful here anyway.
Also, I met an Itachi cosplayer. I glomped him with love and chased him around for the next three hours, it was hilarious. I'm not usually that weird. But then again, this sugar high has been going on for a very long time, and sugar makes me do weird things.
Did you know that I sing? I do. I like to sing. My mom is better than me though, she makes me feel small :( she's so pretty and cool and kind to everybody but scary when she's mad she's just, oh I love my mom. Except when she's being a bitch about me being bi, then she's evil and I'm sad that she doesn't understand that being bi isn't all I am.
I took the Seme and Uke quiz, I got the Chibi Seme, just like the first time I took it three years ago... I guess I haven't changed much :P
I don't know why any of you would care to know any of this. Sugar is like alcohol to me, I'm probably gonna freak out and delete this in the morning... hehehe...
Ok. I'm tired now. Need to go work on SAS... will see you peoples latur :)
Mah life hates meh! I stare for hours on end at the computer screen trying for the life of me to WRITE SOMETHING but I can't... waaahh... *dissolves into writer's-block-induced depression* STUPID SASUKE BEING SO CUTE I CAN'T WRITE YOU ANYMORE!


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News from Upstate
May 23, 2013
Darryl Geddes 315 464-4828
Darryl Geddes 315 464-4828
New York Gov. Andrew Cuomo visits Upstate campus 2013
New York Gov. Andrew Cuomo talks to media following his announcement of a program that would incentivize new business to set up shop near SUNY campuses.
Search Upstate News
Upstate in the News
- How 'Determined Danielle' became president of Upstate Medical University
Syracuse Post Standard
- BRCA Gene Mutations May Influence Prostate Cancer Risk
Renal and Urology News
- Upstate Medical to use nearly $200,000 in NSF funding to fight Zika virus
Central New York Business Journal
- Exposure to music can help your baby learn important skills
WTVH CBS5 Syracuse
- White coats and a white picket fence for couple matched together
WSYR TV9 Syracuse
- Upstate med students celebrate 'Shut Up and Match' day (Video)
Syracuse Post Standard


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Check Availability(781) 494-9124(877) 248-7058(781) 296-8721
Waltham Overlook
$1937 - $24455 units available now — Updated 15 hours ago
15 Dolores Avenue, Waltham, MA 02452
- Lifestyles:
- Luxury Community
Floor Plans & Pricing
Prices and availability subject to change without notice.
Apartment Features
- Air Conditioning
- Cable Ready
- Dishwasher
- New/Renovated Interior
- Some Paid Utilities
- Stainless Steel Appliances
- Deck
- Garbage Disposal
- Patio
Special Features
- Pets
- Short Term Available
- No aggressive breeds Dogs Allowed
- Cats Allowed
- Pets Accepted
Community Features
- Accepts Electronic Payments
- Emergency Maintenance
- Extra Storage
- Fitness Center
- Laundry Facility
- Public Transportation
- Swimming Pool
- On Site Maintenance
- On Site Management
- Pet Friendly
- Luxury Community
Additional Features
- Barbecue Grills
- Beautifully Landscaped
- Classic One and Two Bedroom Floor Plans
- Courtyard
- Free Weights
- Fully Equipped Fitness Center
- Just minutes from I-95/128, Route 2 and Mass Pike
- Microwave
- Private Patios and Balconies
- Public Transportation
- Seasonal Pool
Ratings & Reviews
2 Reviews for Waltham Overlook
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Keep things the way they are. It works great. If something is changed for the better they do it.
The yearly rent increase is a bit much
What is a Certified Resident?
A resident who lives at the property and has completed a resident satisfaction survey.
Advertising properties provide a list of email addresses of its residents to Kingsley Associates, a third party market research firm, who then sends out the satisfaction survey to the residents. Properties may also conduct satisfaction surveys of its residents through other third party market research firms. In those cases, we will publish those survey responses as long as the questions conform to our standard survey format.
Because reviews are from Certified Residents, and are managed by a third party, you can feel confident that the feedback provided is accurate and trustworthy.
General Directions
From 128, take exit 28 (Trapelo Rd. toward Belmont) Continue on Trapelo Rd. for about a mile. At the intersection of Lexington St and Trapelo Road, take a right. At your second set of lights, take a left on Lionel Road. Take your first left on Jacqueline Road. You will then see signs that will direct you toward the leasing office which is located on 15 Dolores Avenue.


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The son of a preacher, longtime Oakcrest High School vocal/music teacher Charlie Bass grew up in the pews of his father's church. It was there, at age 5, that he met the love of his life, Renee, whom he married in 1978, and it was there he discovered his professional love.
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- SHOPPINGCHAT.COM ONLINE SHOPPING CHAT MAKEUP SHOPPINGCHAT BestMakeup:
BestMakeup and ShoppingChat are networking together. Shopping Chat & Best Makeup are blogging online about Makeup.
SHOPPINGCHAT.COM is looking to build out great new features.
We at BEST MAKEUP are networking with other Cosmetic Sites — and those selling cosmetics online.
BEST MAKEUP ONLINE BLOG with us at BestMakeup.
SHOPPINGCHAT.COM is networking with shopping sites. ONLINE SHOPPING CHAT MAKEUP & ONLINE SHOPPING BLOG with us at SHOPPINGCHAT.
BestMakeup and ShoppingChat are networking with social media companies.
Best Makeup is networking with cosmetic companies. BestMakeup.com is networking with bloggers in the makeup space. BestMakeup is looking to bring innovation.


text:
In common with other publishing sectors, most print magazines lost sales in the first half of this year.
But print sales are being offset in some cases by digital edition growth. And these figures do not include the contribution made to readership, advertising and subscription revenue by websites and apps.
Even just focusing on print, many titles continue to hold their ground (such as The Economist and Private Eye) or even grow their print sales (MoneyWeek, Women's Health and The Oldie for instance).
Here is a round-up of Press Gazette's coverage of the consumer magazine industry ABC figures for the first half of 2013:
Full magazine circulation round-up for the first half of 2013 (every title listed)
Women's weeklies: every title down year on year
Under press lads' mags see big circulation declines
Digital edition sales nearly double year on year
Music magazine sales hit bum note across the board
Cosmo, Glamour and Grazia among the big fallers in women's lifestyle sector
Private Eye still leads print sales in robust current affairs sector
Digital editions cancelling out print sales decline for some magazine titles
TV Choice stays top of the pile as rival listings titles lose sales


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`India`s next venture is Mars orbiter mission`
Bhubaneswar: Describing prospects of India`s space programme as exciting and challenging, ISRO Chairman Dr K Radhakrishnan today said the country`s next venture would be the Mars orbiter mission while the first navigation satellite is slated to be launched by June this year.
Mars has played a major role in evolution of life on earth and the next mission is the Mars orbiter mission, Radhakrishnan said during an interaction with students of KIIT University here.
"The first navigation satellite is slated to be launched by June this year. Chandrayan-I is a major step towards lunar and planetary exploration," Radhakrishnan, also Chairman of Space Commission and Secretary, Department of Space, said.
"The next major objective of ISRO is to have a GSLV rocket, which is scheduled to be launched by May," he said.
Stating that the Indian Space Research organisation (ISRO) was now focussing on satellites and launch vehicles, he said prospects and the way forward for India`s space programme "is exciting and challenging".
"India is planning to have a navigation satellite system, called Indian Regional Navigation Satellite, planned in 2013," he said, adding that six more such satellites would be launched in eighteen months.
Radhakrishnan said while most scientific organizations were researching about life and evolution, ISRO put importance on the study of the Moon, Mars and the Sun.
He said the environment of Moon and planets including Mars were missions of the future. "It is projected that by 2030 or 2040 Moon will be an intermediate station for moving to Mars."
On space enterprise, he said several satellites were carrying out important functions in communication, medication and global processing system, according to a release from KIIT university.
The turnover of space enterprises in the world was about USD 177 billion in 2012-13.
US, Russia, China and others were into high technology, including putting human beings in space, while India`s focus for last 50 years was essential application oriented programmes, in which it had become a role model, he said, adding India was among top six space-faring countries.
On academic research, the ISRO chief said many institutes had joined it for development of multi-disciplinary technology.
Academic institutions would continue to play an even greater role in the future.
"Launch of a satellite is a team work involving more than 2,000 (persons)," he said.
More from India
More from World
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- FBI probes Democratic email hack, but is Russia to blame?
- Florida shooting: Three taken into custody, more suspects sought


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Little Azio
This speedy pizza-and-pasta joint, particularly the Midtown location, is a good choice when you're hungry before a show and don't have time for a lengthy meal. Order at the counter from the mix-and-match menu (angel hair, rigatoni, pesto, marinara -- the standard suspects) and your pasta will be out in minutes. We're stuck on the bowtie-shaped farfalle paired with the Rustica, a feisty combination of sausage and peppers. 903-B Peachtree St., 404-876-7711; 749 Moreland Ave., 404-624-0440. www.littleazio.com.
)steria 832
If you order the pasta at Osteria 832, be prepared for two things: your plate arriving five minutes after the pizzas, and other people's forks prodding out your pasta goodies. The Bolognese, a classic tomato and meat sauce served with ribbed rigatoni, whistles with a syrupy red wine note behind each gulp of dark meatiness. The boscaiola is downright celebratory; bulbous shells hide plump English peas, niblets of pancetta and cremini mushrooms all melding together in a swirl of spunky cream. 832 N. Highland Ave. 404-897-1414. www.osteria832.com.
Pasta da Pulcinella
We're old-school customers of this Midtown restaurant, and still miss its original location in the now dilapidated strip of businesses across from the Federal Reserve Building. We also remember when the Pizzoccheri coi Rapini, a dish that inspires fierce loyalty among its fans, cost $6.95. Other old-time winners, as sterling as ever, include the Tortelli di Mele with apple and sausage, and the classic, meaty tagliatelle Bolognese. 1123 Peachtree Walk. 404-876-1114.
Sotto Sotto
Oh my. Where to begin? With the silky, Bechamel-based lasagnette? The rich, sensual Tortelli di Michelangelo? Impressively affordable and still vibrantly hip, this is simply the finest Italian restaurant we have, and the pasta selection is the foundation of its excellence. 'Nough said. 313 N. Highland Ave. 404-523-6678. www.sottosottorestaurant.com.
Frederic Castellucci is the ringleader of this family-oriented spot that specializes in the art of charming overkill. The list of ingredients in each dish astounds. The size of the portions stupefies. If you don't know where to jump in, start with the Pasta Duetto, which features two baseball-sized sausage meatballs. Vegetarians will dig Dorothea's garden parpardelle. 408 S. Atlanta St., Roswell. 770-641-9131. www.sugorestaurant.com.
Boo! My family and I used to eat Sunday brunch there. I remember when it…
Omg, glad to find this thread. I was a waiter for 12 years and have…
You should try a glazed donut from the original Sarah donuts (Sara donuts) on Satallite…
One doughnut from each shop is definitely a weird way to do this Smackdown. It…
"vegan goodness" -- oxymoron of the day.


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Texas Man On Death Row Gets August Execution DateA 33-year-old man on death row for the fatal shooting of an 18-year-old Texas woman whose remains weren't found until two years after she vanished has received an execution date.
High Court Weighs Whether To Spare Texas Man From ExecutionThe U.S. Supreme Court was considering whether a Texas man who killed a city worker in 2005 should be spared from a lethal injection, as his lawyers argue that a ban on executing mentally impaired prisoners should be extended to him.
Texas Inmate Set To Die For 1997 Rampage That Killed 5Texas prisoner Coy Wesbrook is realistic about the likelihood he'll be executed Wednesday for a shooting rampage more than 18 years ago that left five people dead.
Texas Inmate Set To Die Tuesday For Dallas-Area Store HoldupA Collin County convenience store clerk was on the phone with his girlfriend when two people, one of them carrying a sawed-off shotgun, walked in. Gregory Martin told her he believed he was about to be robbed and to call police.
Bid To Ensure Transparency Of Execution Drugs Hits RoadblockOne lawmaker is joining a chorus of voices across numerous states pushing officials to reveal the source of drugs used in lethal-injection executions.
No Appeals Planned For Man Set To Die For Texas Officer's DeathNo late appeals are expected for a man who is set to be executed for a Texas game warden's death during a 2007 shootout. James Freeman's scheduled lethal injection would be the second in as many weeks in Texas.
Convicted Texas Killer Who Says Death Was Accident To Be ExecutedThe U.S. Supreme Court is considering multiple appeals from lawyers trying to keep a Texas inmate from execution Wednesday evening for a slaying 15 years ago that the man claims was accidental.
Texas Set To Execute Convicted Killer Of Female ImpersonatorA Texas inmate scheduled to be executed this week for strangling a female impersonator 15 years ago insists the death was an accident during sex and has made multiple appeals to the U.S. Supreme Court.
Cardinal: Pope's Following Looming Execution Case In TexasVienna's cardinal says he is in touch with a man condemned to die in Texas, and that Pope Francis is following the case, too.
Execution Scheduled For Texas Man Who Set Fire That Killed 3 ChildrenA Texas inmate was set to be executed Wednesday evening for setting a fire that killed his 18-month-old daughter and her two young half-sisters at an East Texas home 15 years ago.
Texas Man Set To Die For Fire That Killed Wife's 3 ChildrenCondemned Texas inmate Raphael Holiday says he loved his kids and has no idea how the East Texas log cabin where they lived with their mother caught fire 15 years ago.
Inmate Convicted Of Killing 89-Year-Old Fort Worth Man Loses AppealA Fort Worth man sent to death row for smothering an 89-year-old man and robbing him of about $6,000 has lost a federal court appeal.


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What is optionally renewable?
The Bankrate.com financial term of the day is: "optionally renewable."
Optionally renewable is a term that refers to health insurance, and it means that your health plan can't drop you whenever it feels like it. Instead, the insurer may cancel you only at specific times, such as on your policy's anniversary date, or when your next premium is due.
If you have optionally renewable health insurance, you can't lose your coverage at the insurance company's whim. There are restrictions on when you can be canceled.
To get an insurance quote, visit the Insurance section at Bankrate.com.
Are you reluctant to negotiate a medical bill? Here are some tips to help you slash those costs.
Not sure if you should file a claim? Jean Chatzky shares insight to help you decide.
Jean Chatzky shares tips on how to stop paying too much for your auto insurance.
All it takes is one serious accident to understand why it's important to have umbrella insurance.
Find out the different factors that go into determining the rate you'll pay for life insurance.
How to make your home look like a million dollars by changing the front door.
How to make your home look like a million dollars by reupholstering old furniture.
How to use lamps to make your house look like a million dollars.
How to make your home smell like a million dollars.
How to make your home look like a million dollars with a little paint.
Bankrate wants to hear from you and encourages thoughtful and constructive comments. We ask that you stay focused on the story topic, respect other people's opinions, and avoid profanity, offensive statements, illegal contents and advertisement posts. Comments are not reviewed before they are posted. Bankrate reserves the right (but is not obligated) to edit or delete your comments. Please avoid posting private or confidential information, and also keep in mind that anything you post may be disclosed, published, transmitted or reused. We do not permit the inclusion of hyperlinks in comments and may remove any comment that includes a hyperlink.
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Tesla's CEO outlines plan to build more car models, be a player in public transportation and continue developing its Autopilot technology to a future of fully autonomous cars.
... Read more


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Darcy M Lake
Main Address:
Marina, CA 93933
Darcy Milligan is a PGA Professional in Marina, CA. The PGA of America comprises 27,000 men and women professionals with one singular goal in mind - to make the game of golf more enjoyable for you.
Services Offered:
- Instruction
Professional has not entered award information.
Home » Golf Courses » California » Marina » Darcy M Lake
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