interacts_with DB06695?
Interpretation of point-of-care INR results in patients treated with dabigatran . BACKGROUND : Point-of-care devices for measurement of the international normalized ratio ( INR ) are commonly used to monitor therapy and maintain therapeutic levels of anticoagulation in patients treated with vitamin K antagonists . DB06695 , a new oral , reversible direct thrombin inhibitor approved for stroke prevention in patients with atrial fibrillation does not require routine coagulation monitoring . However , case reports have identified falsely elevated point-of-care INR levels in patients treated with dabigatran using one of these devices ( Hemochron ) . This in vitro study was designed to verify this issue . METHODS : We compared INR levels in whole blood and plasma using a Hemochron Jr . Signature+ point-of-care device ( International Technidyne Corporation , Edison , NJ ) with routine laboratory monitoring , using blood from healthy volunteers that was spiked with increasing concentrations of dabigatran . RESULTS : P00734 time and INR levels were increased about 2- to 4-fold with the point-of-care device compared with laboratory measures across the plasma dabigatran concentration range 50-1400 ng/mL . At plasma concentrations of dabigatran likely to be observed in patients , at a dose of 150 mg twice daily ( 60-275 ng/mL ) , whole blood point-of-care INR values increased from 1.7 to 4.0 , versus 1.1 to 1.5 measured with the laboratory coagulometer . Similar differences in prothrombin time were observed in plasma samples . CONCLUSIONS : INR levels in patients taking dabigatran are substantially higher using a Hemochron Jr. point-of-care device compared with laboratory values . We discourage the use of these devices specifically , as well as the use of the INR in general , for measuring the anticoagulant effect of dabigatran . Genetic factors influencing outcome from neurotrauma . PURPOSE OF REVIEW : Clinical outcome after neurotrauma is considerably variable and can only partly be explained by known prognostic factors . There is converging evidence from genetic research that a number of genetic variants may contribute to this variability . This review provides recent data from human studies , published in the previous year , on genetic factors influencing outcome after neurotrauma . The bibliographic databases MEDLINE , EMBASE and PsycINFO were searched to identify relevant studies . RECENT FINDINGS : Genetic susceptibility to various aspects of clinical outcome after neurotrauma was reported in recent clinical studies . Genetic loci investigated include polymorphisms in P02649 , P21397 , P23560 , NOS3 , P05231 , P12036 , P31645 , P21964 , P48454 and Q8IX03 genes . The importance of these findings and future directions are discussed . SUMMARY : Recent genetic studies have revealed emerging aspects and extended the existing knowledge regarding the pathogenesis of neurotrauma and the genetic influence on phenotypic diversity . A better understanding of the underlying biological pathways and molecular mechanisms of an individual 's response to neurotrauma may hold the promise of novel treatment strategies and improved clinical outcome . Therapy with a synthetic retinoid -- ( Ro 10-1670 ) etretin -- increases the cellular retinoic acid-binding protein in nonlesional psoriatic skin . Cellular retinol ( P09455 ) -and retinoic acid ( CRABP ) -binding proteins were determined in samples of lesional and nonlesional skin of psoriatic patients , before and during oral administration of a synthetic retinoid , DB00459 ( Ro 10-1670 ) . A 200 % increase in CRABP levels , measured by the ability of the protein to bind retinoic acid , was observed in the normal skin during treatment . The P09455 levels were not altered during therapy . The results show that P09455 and CRABP are independently regulated in human skin and suggest that synthetic retinoids may exert their pharmacologic effects by interfering with the regulation of natural retinoic acid receptors . [ DB00707 sodium ( Photofrin-II ) ] . DB00707 sodium ( DB00707 ) is a photosensitizer which distributes selectively to tumor tissues , and causes tumor cell death by combination with light irradiation . Photodynamic therapy ( PDT ) by combination of porfimer sodium and laser was developed as a new cancer therapy . Tumor selectivity of porfimer sodium are based on the following reasons ; 1 ) high affinity for lipoprotein , especially , low density lipoprotein ( LDL ) , 2 ) elevation of P01130 activity in cancer tissue , and 3 ) lack or imcompleteness of lymphatic system in cancer tissue . DB00707 sodium is activated by laser irradiation at 630 nm , which can reacts with tissue oxygen to produce highly reactive excited siglet oxygen ( 1O2 ) . This highly reactive molecule is subsequently capable of killing tumor cells through oxidation of cellular component like mitochondrial enzymes . In addition , this highly reactive intermediate causes destruction of the tumor capillaries , which accelerates tumor cell death . The growth suppression or lethal damage to tumor cells by PDT of porfimer sodium and excimer dye laser were observed in experimental tumor models . In human clinical trials , the rates of complete response ( CR ) for roentgenographically occult lung cancer , stage I lung cancer , superficial esophageal cancer , superficial gastric cancer and carcinoma in situ or dysplasia of the cervix were 84.8 % , 50.0 % , 90.0 % , 87.5 % and 94.4 % , respectively . The major side effects were cutaneous symptoms e.g. photosensitivity , pigmentation , increasing GOT , GPT but these symptoms were not severe . PDT using porfimer sodium and excimer dye laser must be clinically useful for the treatment of inoperable early cancer or conservation of organ functions . Is phentermine an inhibitor of monoamine oxidase ? A critical appraisal . DB00191 produces a spectrum of concentration-dependent biochemical effects . It interacts with NE transporters at 0.1 microM , DA transporters at about 1 microM , 5-HT transporters at 15 microM and P21397 at about 100 microM . When administered at typical anorectic doses , phentermine primarily interacts with DA and NE transporters and does not produce biochemical or neurochemical effects which would occur if it were inhibiting P21397 . Some other explanation other than MAO inhibition must be sought to explain how oral phentermine increases platelet 5-HT , since platelet P27338 does not metabolize platelet 5-HT , and since amphetamine-type drugs are even weaker inhibitors of P27338 than P21397 . Clinical studies in humans have shown that amphetamine , which is a more potent inhibitor of P21397 than phentermine , does not inhibit P21397 at therapeutic doses . Neither phentermine alone , fluoxetine alone or their combined use have been associated with cardiac valvulopathy , and clinical experience has shown their combined use to be free of significant adverse effects . Viewed collectively , there appears to be no data to support the hypothesis that phentermine inhibits MAO at typical therapeutic doses . Glioma cell activation by Alzheimer 's peptide Abeta1-42 , alpha1-antichymotrypsin , and their mixture . We compared the effects ofAlzheimer 's peptide ( Abeta1-42 ) , a,-antichymotrypsin ( ACT ) and an ACT/Abeta1-42 mixture on human glioma DK-MG cells . The solution of Abeta ( 5 microM ) formed by 2-h incubation at room temperature induced tumour necrosis factor-alpha ( P01375 ) and interleukin ( IL ) -6 levels by 55 and 45 % , respectively , and increased gelatinase B activity by 67 % , while exposure of cells to the ACT/Abeta1-42 mixture ( 1:10 molar ratio ACT : Abeta1-42 ) under the same experimental conditions showed no effect on P05231 levels or gelatinase B activity , but strongly induced P01375 ( by 190 % ) , compared to the controls . Stimulation of the cells with Abeta1-42 alone , but not with ACT , increased by about 20 % low-density lipoprotein ( LDL ) uptake and mRNA levels for P01130 and P04035 , while the ACT/Abeta1-42 mixture significantly increased LDL uptake ( by 50 % ) , up-regulated mRNA levels for P01130 and P04035 by 48 and 63 % , respectively , and increased lipid accumulation by about 20-fold . These data suggest a possible new role for Abeta in Alzheimer 's disease through its interaction with the inflammatory reactant , ACT . Osteoclast size heterogeneity in rat long bones is associated with differences in adhesive ligand specificity . P00734 ( PT ) is an RGD-containing bone-residing precursor to the serine protease thrombin ( TH ) , which acts as an agonist for a variety of cellular responses in osteoblasts and osteoclasts . We show here that PT , TH , osteopontin ( P10451 ) and fibronectin ( FN ) promoted adhesion of isolated neonatal rat long bone osteoclasts . However , the cells that adhered to PT and TH were smaller in size , rounded and contained 3-4 nuclei , in comparison to the cells adhering to P10451 and FN , which were larger with extended cytoplasmic processes and 6-7 nuclei . Attachment of the larger osteoclasts to P10451 and FN was inhibited by antibodies towards beta 3 and beta 1 integrin subunits , respectively . Whereas an RGD-containing peptide inhibited adhesion of the smaller osteoclasts to PT and TH , this was not seen with the beta 3 or beta 1 antibodies . In contrast , the beta 1 antibody augmented osteoclast adhesion to PT and TH in an RGD-dependent manner . Small osteoclasts were less efficient in resorbing mineralized bovine bone slices , as well as expressed lower mRNA levels of P14780 and the cathepsins K and L compared to large osteoclasts . The small osteoclast adhering to PT and TH may represent either an immature , less functional precursor to the large osteoclast or alternatively constitute a distinct osteoclast population with a specific role in bone . Favorable coagulation profile with fondaparinux after hip surgery in elderly patients . Twenty-three patients with fondaparinux prophylaxis over 75 years of age who underwent hip fracture surgery were enrolled in the study . DB00569 ( 2.5 mg ) was administered subcutaneously 6 h postoperatively and then every 24 h for 28 days . Coagulation and inflammatory parameters were measured preoperatively , then 10 h , 2 , 7 , and 28 days postoperatively . Increased D-dimers , positive acute phase proteins , and P05231 , and decreased negative acute phase proteins were observed preoperatively ( P < 0.05 ) . Maximum values were reached 10 h postoperatively for P05231 and D-dimer , and on postoperative days 2 and 7 for positive acute phase proteins ( P < 0.05 ) . P02787 , prealbumin and antithrombin levels were lowest 10 h postoperatively and on postoperative day 2 ( P < 0.05 ) . Increased D-dimers , P05231 , and positive acute phase proteins , and decreased negative acute phase proteins persisted until postoperative day 28 ( P < 0.05 ) . P00734 fragments ( F1 + 2 ) reached peak levels preoperatively and decreased gradually until postoperative day 28 . Fondaparinux promoted the inhibition of thrombin generation , as documented by negative correlation between F1 + 2 and FXa inhibition ( r = -0.46 ; P < 0.001 ) . Fondaparinux-induced FXa inhibition increased gradually until postoperative day 28 . This increase correlated positively with antithrombin activity ( r = 0.4 ; P < 0.05 ) . Fondaparinux prophylaxis counteracted pro-thrombogenic effect associated with hip fracture and subsequent surgery without severe bleeding complications . Combined thrombophilic polymorphisms in women with idiopathic recurrent miscarriage . OBJECTIVE : To identify associations or interrelations between carriage of the methylenetetrahydrofolate reductase ( P42898 ) C677T , the P42898 A1298C , the factor V Leiden G1691A , the factor II prothrombin G20210A , the human platelet antigen ( Q9Y251 ) 1 C12548T , and the apolipoprotein ( APO ) B R3500Q polymorphisms and idiopathic recurrent miscarriage ( IRM ) . DESIGN : Prospective case control study . SETTING : Academic research institution . PATIENT(S) : One hundred forty-five women with a history of three or more consecutive pregnancy losses before 20 weeks gestation and 101 healthy postmenopausal women with at least two live births and no history of pregnancy loss . INTERVENTION(S) : Peripheral venous punctures . MAIN OUTCOME MEASURE(S) : Multiplex polymerase chain reaction was performed to identify the different alleles of six candidate genetic risk factors for IRM ( P42898 C677T , P42898 A1298C , factor V Leiden G1691A , factor II prothrombin G20210A , Q9Y251 1 C12548T , and the APO B R3500Q ) . RESULT(S) : Allele and genotype frequencies of all polymorphisms were not significantly different between the study and the control groups . Also , no significant associations occurred between combinations of polymorphisms and the occurrence of IRM . CONCLUSION(S) : Our data fall short of showing any significant association between single polymorphisms of the P42898 , the Factor V Leiden , the Factor II P00734 , the Q9Y251 1 and APO B genes or combinations of these polymorphisms and the occurrence of IRM . Retinoids induce P14780 expression through RARalpha during mammary gland remodeling . Retinoic acid ( RA ) is a signaling molecule in the morphogenesis of the mammary gland , modulating the expression of matrix metalloproteinases ( MMPs ) . The aim of this paper was to study the role of RA during weaning , which consists of three events : apoptosis of the secretory cells , degradation of the extracellular matrix , and adipogenesis . CRABP II and P09455 -1 carrier proteins increased significantly during weaning compared with lactating glands but reverted to control values after the litter resuckled . The effects of RA are mediated by the nuclear receptors RARalpha , RARbeta , RARgamma , and RXRalpha , which underwent an increase in protein levels during weaning . In an attempt to elucidate the RARalpha-dependent signaling pathway , ChIP assays were performed . The results showed the binding of RARalpha to the P14780 promoter after 24- and 72-h weaning together with its coactivator p300 ; this fact could be responsible for the increase found in P14780 mRNA and protein levels in these conditions . Expression of related MMPs ( P08253 and P08254 ) was also increased during weaning . Using gelatine zymography , we observed a time-dependent increase in active forms of P14780 and P08253 . On the other hand , the inhibitor of MMPs , P01033 , was almost undetectable at 24- and 72-h weaning by Western blot . The role of retinoids in matrix remodeling is reinforced by the fact that administration of an acute dose of retinol palmitate to control lactating rats also induces P14780 expression . This emphasizes the importance of retinoids in vivo to regulate mammary gland involution . Nongenomic , glucocorticoid receptor-mediated regulation of serotonin transporter cell surface expression in embryonic stem cell derived serotonergic neurons . Depressive disorders have been linked to the combined dysregulation of the hypothalamus-pituitary-adrenal ( Q9Y251 ) -axis and the serotonergic system . The Q9Y251 -axis and serotonergic ( 5-HT ) neurons exert reciprocal regulatory actions . It has been reported that glucocorticoid-glucocorticoid receptor ( GR ) signaling influences serotonin transporter ( 5-HTT ) transcription but data also points to the fact that 5-HTT expression is regulated nongenomically via redistribution of 5-HTT from the cell surface into intracellular compartments . In order to analyze the acute effects of glucocorticoids on 5-HTT cell surface localization we differentiated serotonergic neurons from mouse embryonic stem ( ES ) cells derived from the C57BL/6N blastocysts . These postmitotic 5-HT neurons express all relevant serotonergic markers following the application of a growth factor-based differentiation protocol . Increasing concentrations of the GR agonist dexamethasone ( DB00514 ) resulted in enhanced , dose-dependent 5-HTT cell surface localization in the presence of the protein synthesis inhibitor cycloheximide already 1h after incubation . Inhibition of GR function by the specific GR-antagonist mifepristone abolished the increase in 5-HTT cell surface localization . Hence , our data account for a nongenomic upregulation of 5-HTT cell surface expression by glucocorticoid-GR interaction which likely constitutes a rapid physiological response to increased levels of glucocorticoids as seen during stress . Taken together , we provide a cellular model to analyze and dissect glucocorticoid- P31645 interactions on a molecular level that corresponds to in vivo animal models using C57BL/6N mice . Rationalizing cyclooxygenase ( P36551 ) inhibition for maximal efficacy and minimal adverse events . New information indicates that cyclooxygenase-2 ( P35354 ) is constitutively expressed in several tissues , including brain , lung , pancreas , kidney , and ovary , and plays an important role in renal and gastrointestinal function . Selective P35354 inhibition has been associated in animal studies with impairment of ulcer healing and renal function and inhibition of prostacyclin , an effect that inhibits vasodilation without inhibiting platelet aggregation . The clinical consequences , if any , of these effects remain to be determined in long-term studies in humans . The premise that selective P35354 inhibitors will cause less gastrointestinal toxicity than nonsteroidal antiinflammatory drugs that inhibit both P36551 isoforms needs to take into account the low toxicity of nabumetone . The gastrointestinal safety profile of this nonacidic , dual P36551 inhibitor that does not undergo enterohepatic circulation has been evaluated in extensive clinical trials . The data submitted to the US Food and Drug Administration in the New Drug Application for nabumetone ( DB00461 ) , the comparative trials subsequently completed , the published databases of the comparative gastrointestinal toxicity of various nonsteroidal anti-inflammatory drugs ( NSAIDs ) , and the meta-analysis published in this issue of The American Journal of Medicine ( Schoenfeld , page 48S ) indicate that nabumetone has the lowest incidence of gastrointestinal toxicity among the extensively studied NSAIDs . Overall , the incidence is approximately 10-fold less than with comparator drugs . This rate is an appropriate current reference against which the gastrointestinal toxicity of P35354 inhibitors can be compared . P00734 kringle-2 induces death of mesencephalic dopaminergic neurons in vivo and in vitro via microglial activation . We have shown that prothrombin kringle-2 ( pKr-2 ) , a domain of human prothrombin distinct from thrombin could activate cultured rat brain microglia in vitro . However , little is known whether pKr-2-induced microglial activation could cause neurotoxicity on dopaminergic ( DA ) neurons in vivo . To address this question , pKr-2 was injected into the rat substantia nigra ( SN ) . Tyrosine hydroxylase ( TH ) immunohistochemistry experiments demonstrate significant loss of DA neurons seven days after injection of pKr-2 . In parallel , pKr-2-activated microglia were detected in the SN with OX-42 and OX-6 immunohistochemistry . Reverse transcription PCR and double-label immunohistochemistry revealed that activated microglia in vivo exhibit early and transient expression of inducible nitric oxide synthase ( P35228 ) , cyclooxygenase-2 ( P35354 ) and several proinflammatory cytokines . The pKr-2-induced loss of SN DA neurons was partially inhibited by the NOS inhibitor N(G)-nitro-L-arginine methyl ester hydrochloride , and the P35354 inhibitor DuP-697 . P27361 /2 , c-Jun N-terminal kinase and p38 mitogen-activated protein kinase were activated in the SN as early as 1 hr after pKr-2 injection , and localized within microglia . Inhibition of these kinases led to attenuation of mRNA expression of P35228 , P35354 and several proinflammatory cytokines , and rescue of DA neurons in the SN . Intriguingly , following treatment with pKr-2 in vitro , neurotoxicity was detected exclusively in co-cultures of mesencephalic neurons and microglia , but not microglia-free neuron-enriched mesencephalic cultures , indicating that microglia are required for pKr-2 neurotoxicity . Our results strongly suggest that microglia activated by endogenous compound(s) , such as pKr-2 , are implicated in the DA neuronal cell death in the SN . DB01197 reduced plasminogen activator inhibitor activity in patients with acute myocardial infarction . Recent clinical trials have demonstrated that the administration of angiotensin-converting enzyme ( P12821 ) inhibitors to patients with myocardial infarction reduces the incidence of recurrent myocardial infarction . It has also been reported that an elevated level of plasminogen activator inhibitor ( P05121 ) appears to constitute a marker of the risk of recurrent coronary thrombosis . To determine whether the P12821 inhibitor captopril reduces plasma P05121 inhibitor activity , we measured changes in plasma P05121 activity ( IU/ml ) , tissue plasminogen activator ( t-PA ) antigen ( ng/ml ) , and serum P12821 activity ( IU/L ) in 14 survivors of myocardial infarction receiving captopril therapy ( 37.5 mg daily ) and compared them with the values in 15 placebo-treated patients chosen at random . Blood sampling was performed at 07.00 h . In the captopril-treated group , serum P12821 activity decreased significantly , from 14.0 +/- 0.8 to 11.5 +/- 1.2 IU/L 24 h after captopril therapy ( p < 0.01 ) , and those of P05121 activity and t-PA antigen also decreased significantly-from 11.9 +/- 2.8 to 5.5 +/- 2.2 IU/ml ( p < 0.02 ) and from 9.9 +/- 1.0 to 7.5 +/- 0.9 ng/ml ( p < 0.05 ) , respectively 48 h after captopril therapy . However , the levels of P12821 activity , P05121 activity , and t-PA antigen remained unchanged during the study period in the placebo group . Thus , our data indicate that the administration of captopril to patients with acute myocardial infarction may result in a reduced frequency of recurrent coronary thrombosis by increasing fibrinolytic capacity . Increase in proinflammatory cytokines in peripheral blood without haemostatic changes after LPS inhalation . INTRODUCTION : Bronchoalveolar fibrin deposition is a characteristic of various lung disorders including acute lung injury , acute respiratory distress syndrome and sepsis . It is secondary to the activation of coagulation and inhibition of fibrinolysis in the alveolar space , and can be stimulated by lipopolysaccharide ( LPS ) inhalation . The aim of this study was to determine the relation between compartmental stress in the lung and systemic response after LPS inhalation by measuring haemostatic parameters . PATIENTS AND METHODS : 12 healthy subjects underwent a bronchial challenge test with LPS ; sequential dosages were performed for 5 biological markers ( P05231 ( P05231 ) , C-Reactive Protein ( CRP ) , P00734 Fragments 1 and 2 ( F 1+2 ) , cortisol and P00747 Activator Inhibitor 1 ( P05121 ) before endotoxin inhalation and 2 , 4 , 6 , 8 and 24 hours afterwards . RESULTS : P05231 and CRP levels in the peripheral blood were higher after LPS inhalation ; there was no activation of coagulation and no increase in P05121 level . CONCLUSION : This study confirms that despite systemic release of proinflammatory cytokines , LPS inhalation does not induce systemic haemostatic response to LPS challenge . Microvascular injury and blood-brain barrier leakage in Alzheimer 's disease . Thinning and discontinuities within the vascular basement membrane ( VBM ) are associated with leakage of the plasma protein prothrombin across the blood-brain barrier ( BBB ) in Alzheimer 's disease ( AD ) . P00734 immunohistochemistry and ELISA assays were performed on prefrontal cortex . In severe AD , prothrombin was localized within the wall and neuropil surrounding microvessels . Factor VIII staining in severe AD patients indicated that prothrombin leakage was associated with shrinkage of endothelial cells . ELISA revealed elevated prothrombin levels in prefrontal cortex AD cases that increased with the Braak stage ( Control=1.39 , I-II=1.76 , III-IV=2.28 , and V-VI=3.11 ng prothrombin/mg total protein ) . Comparing these four groups , there was a significant difference between control and Braak V-VI ( p=0.0095 ) and also between Braak stages I-II and V-VI ( p=0.0048 ) . There was no significant difference in mean prothrombin levels when cases with versus without cerebral amyloid angiopathy ( CAA ) were compared ( p-value=0.3627 ) . When comparing AD patients by P02649 genotype ( ApoE3,3=2.00 , ApoE3,4=2.49 , and ApoE4,4=2.96 ng prothrombin/mg total protein ) an analysis of variance indicated a difference between genotypes at the 10 % significance level ( p=0.0705 ) . Tukey 's test indicated a difference between the 3,3 and 4,4 groups ( p=0.0607 ) . These studies provide evidence that in advanced AD ( Braak stage V-VI ) , plasma proteins like prothrombin can be found within the microvessel wall and surrounding neuropil , and that leakage of the blood-brain barrier may be more common in patients with at least one APOE4 allele . DB00741 is a suppressor of apoptosis in bovine corpus luteum . Glucocorticoid ( GC ) acts as a modulator of physiological functions in several organs . In the present study , we examined whether GC suppresses luteolysis in bovine corpus luteum ( CL ) . DB00741 ( an active GC ) reduced the mRNA expression of caspase 8 ( Q14790 ) and caspase 3 ( P42574 ) and reduced the enzymatic activity of P42574 and cell death induced by tumor necrosis factor ( P01375 ) and interferon gamma ( P01579 ) in cultured bovine luteal cells . mRNAs and proteins of GC receptor ( P04150 ) , 11beta-hydroxysteroid dehydrogenase type 1 ( P28845 ) , and P80365 were expressed in CL throughout the estrous cycle . Moreover , the protein expression and the enzymatic activity of P28845 were high at the early and the midluteal stages compared to the regressed luteal stage . These results suggest that cortisol suppresses P01375 - P01579 -induced apoptosis in vitro by reducing apoptosis signals via Q14790 and P42574 in bovine CL and that the local increase in cortisol production resulting from increased P28845 at the early and midluteal stages helps to maintain CL function by suppressing apoptosis of luteal cells . DB01095 inhibits growth and alters the malignant phenotype of the P13671 glioma cell line . BACKGROUND : DB01095 is a member of the family of P04035 inhibitors ( statins ) extensively used in medical practice . Increasing evidence suggests that fluvastatin may be implicated in suppression of cancer growth and development . The aim of the present study was to investigate the anti-cancer potential of fluvastatin in P13671 rat malignant glioma cells . METHODS : First , the effects of fluvastatin on cell viability ( MTT assay ) , proliferation ( BrdU assay ) , cell morphology , and cytoskeleton were examined . Subsequently , its effect on extracellular signal regulated kinase 1 and 2 ( P27361 /2 ) and P45983 and 2 ( JNK 1/2 ) expression was estimated by Western blot . Finally , the influence of fluvastatin on cell migration and production of P14780 and P15692 was determined using a wound-healing assay and ELISA test , respectively . RESULTS : The results obtained showed that fluvastatin had a remarkable inhibitory and cytotoxic effect on tumor P13671 cells ( IC(50) = 8.6 μM , 48 h ) , but did not inhibit the growth of normal neuronal cells . The concentrations from 1 to 10 μM induced marked morphologic alterations typical for apoptosis including shrinkage of cytoplasm , chromatin condensation , and nucleus breakdown . CONCLUSION : The inhibitory effects of fluvastatin on cell proliferation seemed to be associated with decreased p- P27361 /2 expression , upregulation of p- P45983 /2 , and reduction in the P14780 and P15692 concentrations in culture media . The high anticancer ( antiproliferative , proapoptotic , antiinvasive ) activity of fluvastatin and lack of its toxicity against normal cells indicate a potential use of this statin in the treatment of malignant glioma . Retinal gene expression and Müller cell responses after branch retinal vein occlusion in the rat . PURPOSE : In a rat model of branch retinal vein occlusion ( BRVO ) , changes in gene expression of factors implicated in the development of retinal edema and alterations in the properties of Müller cells were determined . METHODS : In adult Long-Evans rats , BRVO was induced by laser photocoagulation of retinal veins ; untreated eyes served as controls . The mRNA levels of after factors were determined with real-time RT-PCR in the neural retina and retinal pigment epithelium after 1 and 3 days of BRVO : P15692 , pigment epithelium-derived factor ( P36955 ) , tissue factor , prothrombin , the potassium channel Kir4.1 , and aquaporins 1 and 4 . DB01345 currents were recorded in isolated Müller cells , and cellular swelling was assessed in retinal slices . RESULTS : In the neural retina , the expression of P15692 was upregulated within 1 day of BRVO and returned to the control level after 3 days . P36955 was upregulated in the neuroretina and retinal pigment epithelium after 3 days of BRVO . P00734 , Kir4.1 , and both aquaporins were downregulated in the neuroretina . After BRVO , Müller cells displayed a decrease in their potassium currents and an altered distribution of Kir4.1 protein , an increase in the size of their somata , and cellular swelling under hypoosmotic stress that was not observed in control tissues . CONCLUSIONS : BRVO results in a rapid transient increase in the expression of P15692 and a delayed increase in the expression of P36955 . The downregulation of Kir4.1 and aquaporins , the mislocation of Kir4.1 protein , and the osmotic swelling of Müller cells may contribute to the development of edema and neuronal degeneration . Inhibition of prothrombin kringle-2-induced inflammation by minocycline protects dopaminergic neurons in the substantia nigra in vivo . P00734 kringle-2 ( pKr-2 ) , a domain of prothrombin , can cause the degeneration of mesencephalic dopaminergic neurons through microglial activation . However , the chemical products that inhibit pKr-2-induced inflammatory activities in the brain are still not well known . The present study investigated whether minocycline , a semisynthetic tetracycline derivative , could inhibit pKr-2-induced microglial activation and prevent the loss of nigral dopaminergic ( DA ) neurons in vivo . To address this question , rats were administered a unilateral injection of pKr-2 in the substantia nigra in the presence or absence of minocycline . Our results show that pKr-2 induces the production of proinflammatory cytokines , such as tumor necrosis factor-α ( P01375 -α ) and interleukin-1β ( IL-1β ) , and inducible nitric oxide synthase from the activated microglia . In parallel , 7 days after pKr-2 injection , tyrosine hydroxylase immunocytochemical analysis and western blot analysis showed a significant loss of nigral DA neurons . This neurotoxicity was antagonized by minocycline and the observed neuroprotective effects were associated with the ability of minocycline to suppress the expression of tumor necrosis factor-α , interleukin-1β , and nitric oxide synthase . These results suggest that minocycline may be promising as a potential therapeutic agent for the prevention of DA neuronal degeneration associated with pKr-2-induced microglial activation .