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To evaluate the combination of several statins (atorvastatin, fluvastatin and simvastatin) and azoles (voriconazole, posaconazole and itraconazole) against Acanthamoeba spp. Methods: The efficiency of the different drug combinations against the trophozoite stage of different Acanthamoeba strains were evaluated by Alamar Blue assay. Effect on the cyst stage was observed by inverted microscope. Cytotoxicity of combinations of azoles and statins was evaluated by measuring the release of lactate dehydrogenase from a murine macrophage cell line. Results: Combinations of any of the tested statins and voriconazole or posaconazole were more efficient in inhibiting Acanthamoeba compared to statins or azoles individually. The drug combinations at the combined inhibitory concentrations 50% showed lower toxicity compared to that of the compounds alone. Conclusions: The combinations of statins together with voriconazole and posaconazole are more efficient than these drugs alone, and these combinations have lower cytotoxicity in mammalian cell lines.
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To evaluate the combination of several statins (atorvastatin, fluvastatin and simvastatin) and azoles (voriconazole, posaconazole and itraconazole) against Acanthamoeba spp. Methods: The efficiency of the different drug combinations against the trophozoite stage of different Acanthamoeba strains were evaluated by Alamar Blue assay. Effect on the cyst stage was observed by inverted microscope. Cytotoxicity of combinations of azoles and statins was evaluated by measuring the release of lactate dehydrogenase from a murine macrophage cell line. Results: Combinations of any of the tested statins and voriconazole or posaconazole were more efficient in inhibiting Acanthamoeba compared to statins or azoles individually. The drug combinations at the combined inhibitory concentrations 50% showed lower toxicity compared to that of the compounds alone. Conclusions: The combinations of statins together with voriconazole and posaconazole are more efficient than these drugs alone, and these combinations have lower cytotoxicity in mammalian cell lines.
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OBJECTIVE The purpose of the present study was to investigate the impact of fluvas-tatin formulation on the pharmacokinetics-genetic polymorphis relationship. METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release (ER) 80 mg tablet and an immediate-release(IR)40 mg capsule in terms of drug metabolism enzyme and transporter ge-netic polymorphisms. In this open-label, randomized, two-period, two-treatment, crossover study, ef-fects of BCRP, SLCO1B1, MDR1, CYP2C9, and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using high-performance liquid chromatography-tandem mass spectrometry. RESULTS The SLCO1B1 T521C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1B1 T521C genotype correlated with the AUC0-24of repeat doses (P=0.01). The CYP2C9*3 genotype correlated with the AUC0- 24after the first dose IR 40 mg capsule (P<0.05); however, the difference between CYP2C9*1/*1 and CYP2C9*1/*3 was not statistically significant after repeated doses. CONCLUSION The effect of SLCO1B1 T521C on fluvas-tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.
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Objective: To study therapeutic effect and influence of fluvastatin combined arotinolol on serum levels of growth differentiation factor 15 (GDF-15) and neutrophil gelatinase associated lipocalin (NGAL) in patients with coronary heart disease (CHD) complicated heart failure (HF). Methods: A total of 140 CHD + HF patients, who were treated in our department of cardiology from May 2013 to May 2015, were selected. According to random number table, patients were randomly and equally divided into arotinolol group and combined treatment group (received fluvastatin based on arotinolol group), both groups were treated for three months. Therapeutic effect, left ventricular end-diastolic dimension (LVEDd), end-diastolic interventricular septal thickness (IVSTd), left ventricular ejection fraction (LVEF), mean arterial pressure (MAP), cardiac index (CI), stroke index (SI), stroke volume (SV), serum levels of GDF-15 and NGAL before and after treatment were compared between two groups. Results: Compared with arotinolol group after treatment, there were significant rise in LVEF [(45. 31±6. 73) ％ vs. (72. 64±7. 29) ％], MAP [(59. 34±6. 93) mmHg vs. (75. 61±7. 24) mmHg], CI [(2. 66±1. 31) L/min2 vs. (3. 12± 1. 37) L/min2], SI [(27. 15±4. 37) ml/m2 vs. (49. 81±5. 79) ml/m2]and SV [(60. 99±5. 13) ml vs. (71. 24± 5. 94) ml], and significant reductions in IVSTd [(13. 51±3. 17) mm vs. (11. 27±7. 26) mm], serum levels of GDF-15 [(1153. 4±153. 7) ng/L vs. (923. 8±81. 4) ng/L]and NGAL [(112. 52±61. 49) μg/L vs. (78. 14± 35. 74) μg/L]in combined treatment group (P＜0. 05 or＜0. 01). Total effective rate of combined treatment group was significantly higher than that of arotinolol group (87. 14％ vs. 74. 29％), P=0. 007. Conclusion: Fluvastatin combined arotinolol can effectively improve heart function, significantly reduce serum GDF-15 and NGAL levels, and improve prognosis in CHD + HF patients, which is worth extending.
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Connective tissue growth factor (CTGF) is a novel fibrotic mediator, which is considered to mediate fibrosis through extracellular matrix (ECM) synthesis in diabetic cardiovascular complications. Statins have significant immunomodulatory effects and reduce vascular injury. We therefore examined whether fluvastatin has anti-fibrotic effects in vascular smooth muscle cells (VSMCs) and elucidated its putative transduction signals. We show that advanced glycation end products (AGEs) stimulated CTGF mRNA and protein expression in a time-dependent manner. AGE-induced CTGF expression was mediated via ERK1/2, JNK, and Egr-1 pathways, but not p38; consequently, cell proliferation and migration and ECM accumulation were regulated by CTGF signaling pathway. AGE-stimulated VSMC proliferation, migration, and ECM accumulation were blocked by fluvastatin. However, the inhibitory effect of fluvastatin was restored by administration of CTGF recombinant protein. AGE-induced VSMC proliferation was dependent on cell cycle arrest, thereby increasing G1/G0 phase. Fluvastatin repressed cell cycle regulatory genes cyclin D1 and Cdk4 and augmented cyclin-dependent kinase inhibitors p27 and p21 in AGE-induced VSMCs. Taken together, fluvastatin suppressed AGE-induced VSMC proliferation, migration, and ECM accumulation by targeting CTGF signaling mechanism. These findings might be evidence for CTGF as a potential therapeutic target in diabetic vasculature complication.
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Cell Cycle , Cell Cycle Checkpoints , Cell Proliferation , Connective Tissue Growth Factor , Connective Tissue , Cyclin D1 , Extracellular Matrix , Fibrosis , Genes, Regulator , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Muscle, Smooth, Vascular , Phosphotransferases , RNA, Messenger , Vascular System InjuriesABSTRACT
Objective To investigate the effect of fluvastatin on ventricular remodeling and serum tumor necrosis factor alpha(TNF-α)level in elderly patients with acute myocardial infarction.Methods 87 elderly patients with acute myocardial infarction were chosen in Jiande Hospital of Integrated Traditional Chinese and Western Medicine from October 2014 to October 2016,were randomly divided into control group(42 cases)and observation group(45 cases),the control group received aspirin,PI Gray chlorine and other conventional treatment,the observation group were given fluvastatinon the basis of the control group treatment.The changes of cardiac function and serum inflammatory factor TNF-α levels were observed before and after treatment.Results After the treatment,left ventricular weight index such asleft ventricular systolic volume index,left ventricular diastolic membrane membrane volume index,left ventricular ejection fraction in the two groups were improved in different degree,but the observation group improved significantly(P<0.05).In the control group,there was no significant improvement; and after treatment,the indexes of the observation group were significantly better than those of the control group(P<0.05).The effective rate in the observation groupwas 93.33％,was significantly higher than the control group(P<0.05).After treatment,the levels of serum TNF-α were significantly improved in the observation group,and the level of serum was significantly decreased compared with before treatment(P<0.05),and the observation group after the treatment was obviously lower than the control group(P<0.05).Conclusion For elderly patients with acute myocardial infarction with fluvastatin can better improve the patient's heart function,improve the body's inflammatory level,effectively improve the treatment effect,inhibit ventricular remodeling.
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Objective To investigate the effect of Hedan tablet combined with fluvastatin on serum LDL and heart rate variability in patients with coronary atherosclerotic heart disease (CHD).Methods 110 patients with coronary heart disease who were treated from March 2015 to June 2016 in our hospital were selected and randomly divided into observation group and control group, with 55 cases in each group.The patients in the observation group were treated with Hedan tablet combined with fluvastatin, and the control group was treated with fluvastatin.The changes of heart rate variability, blood lipids and inflammatory factors were compared before and after treatment, and the clinical curative effect was observed.Results After treatment, the total effective rate of the observation group was 96.4%, significantly higher than the control group 85.5%, the difference was statistically significant (P<0.05).The SDNN of the observation group was (85.42 ±9.11) ms and the SDANN was (49.11 ±5.13) ms, was significantly higher than those in the control group (76.87 ±8.12) ms, (44.16 ±4.76) ms.In the observation group, TC was (4.14 ±0.45) mmol/L, TG was (1.26 ±0.16) mmol/L, LDL was (2.08 ±0.31) mmol/L, significantly lower than the control group (4.78 ±0.51) mmol/L, (1.42 ±0.18) mmol/L, (2.43 ± 0.27) mmol/L, and HDL levels was (1.51 ±0.18) mmol/L, significantly higher than those in the control group (1.35 ±0.15) mmol/L, the difference was statistically significant (P<0.05), and the levels of inflammatory factors in the observation group were significantly lower than those in the control group, the difference was statistically significant (P<0.05).Conclusion Hedan tablets combined with fluvastatin in treating coronary atherosclerotic heart disease can effectively reduce serum LDL levels, improve heart rate variability, significantly improve the treatment effect.
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OBJECTIVE:To investigate the effects of fluvastatin combined with aspirin on the related indicators of patients with diabetic lower extremity arteriosclerosis occlusive desease(LEAOD). METHODS:80 patients with diabetic LEAOD were ran-domly divided into control group(40 cases)and observation group(40 cases). Based on convertional treatment,control group was given Rosuvastatin calcium tablet 5 mg+Aspirin enteric-coated tablet 100 mg every evening;observation group was given Fluvas-tatin sodium capsule 40 mg+Aspirin enteric-coated tablet 100 mg. They were treated for 3 months. Fibrinogen,plasma D-dimer, blood viscosity, cholesterol (TC), triglyceride (TG), glycosylated hemoglobin (HbAlc), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), carotid intima-media thickness, compliance situation of TC, TG, HbAlc,LDL-C and HDL-C,cases of carotid intima thickening,plaque formation,stenosis and occlusion before and after treat-ment were observed,and the incidence of adverse reactions was recorded. RESULTS:After treatment,fibrinogen,plasma D-di-mer,blood viscosity,TC,TG,HbAlc,LDL-C and carotid intima-media thickness in 2 groups were significantly lower than before treatment,and observation group was significantly lower than control group;HDL-C in 2 groups was significantly higher than be-fore,and observation group was significantly higher than control group,with statistical significance (P0.05). CONCLUSIONS:Fluvastatin combined with aspirin can significantly improve the pa-tients 'blood viscosity,blood lipid,vascular endothelial function in the treatment of diabetic LEAOD,it can reduce the thrombotic disease risk,and does not increase the incidence of adverse reactions.
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Objective To comprehensively evaluate the clinical efficacy,safety and economic benefits of atorvastatin and fluvastatin in regulating dyslipidemia.Methods The clinical randomized controlled trials (RCTs) for comparing clinical efficacy of atorvastatin and fluvastatin on regulating dyslipidemia were retrieved from databases,including Cochrane Library,PubMed,Medline,Embase,Wiley,Springer,CNKI,Wanfang and VIP,till June 2016.Data were evaluated by two reviewers independently according to the Jadad standard.The changes of low density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C),total cholesterol (TC) and triglyceride (TG) before and after treatment were extracted to perform Meta-analysis by using RevMan5.0 software.The economic evaluation was carried out,as well.Results A total of 7 RCTs were included,including 684 cases of patients treated with fluvastatin and 2 208 cases of patients treated with atorvastatin.The patients were spitted into two subgroups according to the same or different maximum dose of atorvastatin and fluvastatin.The results indicated that the effects of atorvastatin on down-regulating LDL-C,TC and TG levels were significantly better than those of fluvastatin,the differences were statistically significant (Z=23.63、23.32、5.50,P＜0.000 01).No significant difference was found in regulating HDL-C level between atorvastatin and fluvastatin.Conclusion Compared with fluvastatin,atorvastatin is more effective to regulate levels of LDL-C,TC and TG,but there is no significant difference in up-regulating HDL-C level.Additionally,application of atorvastatin is more economicallv effective.
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Objective To comprehensively evaluate the clinical efficacy,safety and economic benefits of atorvastatin and fluvastatin in regulating dyslipidemia.Methods The clinical randomized controlled trials (RCTs) for comparing clinical efficacy of atorvastatin and fluvastatin on regulating dyslipidemia were retrieved from databases,including Cochrane Library,PubMed,Medline,Embase,Wiley,Springer,CNKI,Wanfang and VIP,till June 2016.Data were evaluated by two reviewers independently according to the Jadad standard.The changes of low density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C),total cholesterol (TC) and triglyceride (TG) before and after treatment were extracted to perform Meta-analysis by using RevMan5.0 software.The economic evaluation was carried out,as well.Results A total of 7 RCTs were included,including 684 cases of patients treated with fluvastatin and 2 208 cases of patients treated with atorvastatin.The patients were spitted into two subgroups according to the same or different maximum dose of atorvastatin and fluvastatin.The results indicated that the effects of atorvastatin on down-regulating LDL-C,TC and TG levels were significantly better than those of fluvastatin,the differences were statistically significant (Z=23.63、23.32、5.50,P＜0.000 01).No significant difference was found in regulating HDL-C level between atorvastatin and fluvastatin.Conclusion Compared with fluvastatin,atorvastatin is more effective to regulate levels of LDL-C,TC and TG,but there is no significant difference in up-regulating HDL-C level.Additionally,application of atorvastatin is more economicallv effective.
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Objective To investigate the effect of fluvastatin sodium on the risk factors of atherosclerosis in patients with previous coronary heart disease.Methods 58 cases meeting the inclusion criteria and diagnosed coronary heart disease history of chlamydial infection were selected and randomly divided into study group and control group, 29 cases in each group, the control group were given routine treatment, study group on the basis of conventional treatment of fluvastatin sodium(20 mg pertime, once daily) treatment.A total of 4 weeks treatment for a course, the blood lipid and vascular endothelial function, matrix metalloproteinases and inflammatory factor levels were determined before and after treatment, and adverse reactions were recorded between the two groups.Results Compared with the control group, the total cholesterol ( TC ) , triglyceride ( TG ) , low density lipoprotein cholesterol(LDL-C) and lipid comprehensive index(LCI) in study group after treatment were lower, the high density lipid-cholesterol(HDL-C) was higher, the soluble intercellular adhesion molecule-1(sI-CAM-1) and endothelin-1(ET-1) were lower, the NO was higher, matrix metalloproteinase-1 (MMP-1), MMP-9 and tissue inhibitor of metalloproteinase-1(TIMP-1) were lower, and tumor necrosis factor-α(TNF-α), interleukin 1 beta(IL-1β), high-sensitivity c-reactive protein( Hs-CRP ) and IL-6 were lower ( all P <0.05 ).All patients were followed up, only slight gastrointestinal adverse reaction, there was no significant difference in adverse reactions between the two groups.Conclusion The fluvastatin sodium can reduce the blood lipid, the level of matrix metalloproteinases, improve vascular endothelial function and inflammatory state, with high safety.
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Objective:To observe the effects of fluvastatin adjuvant therapy on plasma connective tissue growth factor ( CTGF) and brain natriuretic peptide (BNP) in chronic heart failure (CHF) patients.Methods:Totally 112 cases of chronic heart failure patients were randomly divided into two groups ,and 56 patients in the control group were treated with the conventional method , while 56 cases in the treatment group were given fluvastatin additionally .The course of treatment was 6 months.The clinical effect,and CTGF and BNP levels of the two groups were compared .Results: The efficiency rate of the treatment group was significantly higher than that of the control group with statistical significance (P0.05).After the treatment, the cardiac function indices (LVEF and FS) and lipid level (HDL-C) in the treat-ment group were increased obviously , which were higher than those in the control group; the cardiac function indices ( LVDD and LVSD) and lipid levels ( TC, TG and LDL-C) in the treatment group were decreased obviously , which were lower than those in the control group, and all the differences had statistical significance (P0.05).Conclusion: The conventional treatment combined with fluvastatin is effective in the patients with CHF, which can significantly reduce plasma BNP level and CTGF level .
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Objective:To investigate the effect of fluvastatin sodium (FS ) on MMP-9 expression in tongue squamous carcinoma Tca81 1 3 cells.Methods:Immunofluorescence method and Western blot were used to detect the level of MMP-9 expression in Tca81 1 3 cells treated by different concentration of FS for 24 h,the data were statistically analyzed.Results:MMP-9 expression in FS treated cells was significantly reduced(P<0.05)compared with control cells.With FS concentration increase the protein expression decreased in a dose-dependant manner detected by the 2 mothods.Conclusion:Fluvastatin Sodium can dose-dependantly inhibit the expression level of MMP-9 in Tca81 1 3 cells.
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Objective To investigate clinical effect of fluvastatin in the treatment of early diabetic nephropa-thy,to provide a reference for clinical treatment.Methods 90 patients with diabetic nephropathy were selected,the patients were divided into observation group(50 cases)and control group(40 cases).Conventional hypoglycemic ther-apy used in the control group,and valsartan treatment also used.The observation group received fluvastatin on the basis of treatment of control group.The efficacy,urinary albumin excretion rate,inflammatory markers,serum creatinine and other indicators and adverse reactions were compared.Results The effective rate of the observation group was 90.00%,which was significantly higher than 75.00% of the control group,the difference was statistically significant (χ2 =4.325,P <0.05).After treatment,the BUN,UAER,TC,TG,LDL of the observation group were (6.54 ± 1.24)mmol/L,(40.43 ±4.21)μg/min,(3.81 ±0.47)mmol/L,(2.51 ±0.34)mmol/L,(2.41 ±0.64)mmol/L, the improvement was better than the control group,the differences were statistically significant (t =5.547,5.225, 5.457,4.957,5.339,all P <0.05).After treatment,the CRP,IL -6,IL -18,TNF -αin the observation group and control group were significantly improved compared with before treatment,the differences were statistically significant (P <0.05 ).After treatment,the CRP,IL -6,IL -18,TNF -αlevels of the observation group were (4.14 ± 0.87)mg/L,(88.17 ±8.54)pg/mL,(139.64 ±9.48)ng/L,(40.17 ±5.22)ng/L,the improvement was better than the control group,the differences were statistically significant (t =6.914,6.357,5.847,7.054,all P <0.05 ). Conclusion Fluvastatin in the treatment of early diabetic nephropathy has good effect,which will help to improve inflammatory cytokines and proteinuria and protect renal function,it is worthy of clinical application.
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Objective To explore effects of different doses of fluvastatin on serum hs -CRP,NT -proBNP in patients with coronary heart disease (CHD)and chronic heart failure (CHF)and its clinical efficacy.Methods 120 CHD patients with CHF were randomly divided into three groups,each group included 50 cases.Each group received the therapy of 20mg/d(20mg group),40mg/d(40mg group),and 80mg/d(80mg group),respectively,three groups were treated for 12 weeks.The related indicators were compared among the three groups before and after treat-ment,and the incidence of major cardiovascular events (MACE )and adverse reactions were recorded.Results There was no statistically significant difference between groups before treatment (P >0.05).The serum hs -CRP and BNP of three groups were significantly different after treatment(F =185.956,16.824,all P 0.05).The incidence of MACE in 80mg group was lower than that in 20mg group and 40mg group.However,the incidence of three groups had no significant difference after treatment (P >0.05 ). Conclusion The treatment of high -dose fluvastatin can significantly decrease inflammatory of CHD patients with CHF,and also decreases the NT -proBNP level,effectively control lipid levels,the treatment is safe and worthy of clinical recommendations.
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Objective:To investigate the effects of fluvastatin on high-sensitivity c-reactive protein( hs-CRP) , tumor necrosis fac-tor-α(TNF-α), urine albumer excretion rate (UAER)and serum creatinine (Cr) in the patients with early diabetic nephropathy. Methods:Totally 69 patients with early diabetic nephropathy were randomly divided into the observation group with 34 cases and the control group with 35 cases. The observation group was treated by low-protein diet plus fluvastatin, and the control group was treated by low-protein diet only. The course of treatment was 8 weeks. Totally 65 nondiabetic persons were selected as the normal group, and the levels of TNF-α, hs-CRP, UAER, ALT and Cr were detected before and after the treatment. Results:The levels of TNF-α, hs-CRP and UAER in the observation group and the control group were significantly higher than those in the normal group(P0. 05). Compared with that before the treatment, the level of UAER was de-creased significantly in the control group after the treatment (P0. 05). In the observation group, the levels of TNF-α, hs-CRP and UAER were all decreased sig-nificantly after the treatment (P<0. 05). Conclusion:UAER, hs-CRP and TNF-α are closely connected with diabetic nephropathy. Fluvastatin can decrease the levels of TNF-α, hs-CRP and UAER. Low-protein diet plus fluvastatin is effective and safe in the treat-ment of early diabetic nephropathy, and the efficacy is superior to that of low-protein diet only.
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OBJECTIVE: To study the effect of fluvastatin on plasma von willebrand factor (vWF),D-dimer(D-D)level and heart function in patients with chronic heart failure(CHF). METHODS: 78 patients with CHF were randomly divided into control group and test group. Control group was given conventional treatment,including cardiac glycoside drugs,diuretics,angiotensin converting enzyme inhibitors or angiotensin receptor blockers andβ-receptor blockers,etc. On this basis,test group was given Fluv-astatin capsules 40 mg,administrated at draught after dinner. The course for both was 28 d. The clinic data was observed,includ-ing left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),vWF,D-D levels before and after treatment and incidence of adverse reactions. RESULTS:After treatment,the LVEF level in 2 groups was significantly higher than before,and test group was higher than control group;LVEDD,vWF and D-D level were significantly lower than before,and test group was lower than control group,with significant differences(P<0.05). There were no obvious adverse reactions during treat-ment. CONCLUSIONS: Based on the conventional treatment,fluvastatin can significantly improve the coagulation function in pa-tients with CHF,with good safety.
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Objective To explore the efficacy and safety of the treatment of Xuezhikang and fluvastatin in elderly angina patients with mildly abnormal liver function .Methods 84 cases of ALT in 40-80u/L very elderly patients with coronary heart disease were randomly selected and divided into the two groups , the Xuezhikang group received Xuezhikang (0.6g,bid,orally),the fluvastatin group received fluvastatin (40mg,1time/night,oral),the total course was 12weeks,the TC,TG,LDL-C,HDL -C were measured before and after treatment ,liver function was measured once 2 -4times.If ALT was 3 times higher than before , Xuezhikang was instead of statins , if ALT was 5 times higher than before ,both of the two drags were withdrawaled .Results The TC,LDL,TG,HDL-C and ALT of the two groups were no significant difference before treatment (P >0.05),the TC,LDL,TG were decreased after treatment in the both group .There was no case of increased of ALT to three times in Xuezhikang group ,however ,ALT of 6 patients were increased more than three times in fluvastatin group ,four weeks after exchange of Xuezhikang ,the ALT were not continued to rise .Conclusion Both the two medicine can significantly lowered the cholesterol in very elderly patients with angina ,but the Xuezhikang were more safety in the patient with mild increased of liver function .
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Background & objectives: To study effects of drugs against rheumatoid arthritis (RA) synoviocytes or fibroblast like synoviocytes (FLS) are used. To overcome the drawbacks of using FLS, this study was conducted to show the validity of SW982 synovial cell line in RA study. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Annexin V propidium iodide (PI) staining, mitochondrial membrane potential assay, Triton X-114 Phase partitioning, and immunolot for apoptosis signaling in SW982 human synovial cell line were performed. Results: Fluvastatin induced apoptosis in a dose- and time-dependent manner in TNFα -stimulated SW982 human synovial cells. A geranylgeranylpyrophosphate (GGPP) inhibitor, but not a farnesylpyrophosphate (FPP) inhibitor, induced apoptosis, and fluvastatin-induced apoptosis was associated with the translocation of isoprenylated RhoA and Rac1 proteins from the cell membrane to the cytosol. Fluvastatin-induced downstream apoptotic signals were associated with inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Accordingly, 89 kDa apoptotic cleavage fragment of poly (ADP-ribose) polymerase (PARP) was detected. Interpretation & conclusions: Collectively, our data indicate that fluvastatin induces apoptotic cell death in TNFα-stimulated SW982 human synovial cells through the inactivation of the geranylgerenylated membrane fraction of RhoA and Rac1 proteins and the subsequent inhibition of the PI3K/Akt signaling pathway. This finding shows the validity of SW982 cell line for RA study.
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Objective To assess the efficacy and safety of fluvastatin sodium extended-release tablets (fluvastatin XL) 80 mg once daily compared to fluvastatin sodium immediate-release capsules (fluvastatin IR) 40 mg twice daily in Chinese hyperlipidemic patients with moderate or high cardiovascular risk.Methods In this multi-center,randomized,double-blind,double-dummy,active-controlled,parallel-group study,after 6-week open-label treatment with fluvastatin IR 40 mg once daily,patients who did not reach their lipid goals were randomized to 12-week double-blind treatment with fluvastatin XL 80 mg once daily or fluvastatin IR 40 mg twice daily.Results (1) There were 218 patients enrolled in each group.At the study endpoint,no statistical difference was found in the mean percent change from baseline for LDL-C with-8.69％ [from (3.504 ±0.060) mmol/L to (3.153 ±0.065) mmol/L] in the fluvastatin XL group and-7.89％ [from (3.491 ±0.050) mmol/L to (3.181 ±0.060) mmol/L] in the fluvastatin IR group (P ＞ 0.05).The 95％ CI for difference between the two groups in adjusted mean percent change from baseline was (-4.70％-3.09％),which was within the pre-specified non-inferiority margin.In the fluvastatin XL group,the proportion of patients with moderate cardiovascular(CV) risk and high CV risk achieving their LDL-C treatment goals at endpoint was 50.0％ and 31.5％ respectively,while the proportion was 42.5％ and 24.5％ respectively in the fluvastatin IR group.No significant difference was found between the two groups in the proportion of patients who reached their lipid goals and the changes from baseline with other lipid parameters.(2)Similar safety profiles were observed in the two treatment groups,with 21.1％ adverse event (AE) (8.3％ study-drug related AE) in the fluvastatin XL group and 17.0％ AE (6.3％ study-drug related AE) in the fluvastatin IR group.Conclusion The efficacy of fluvastatin XL 80 mg once daily is comparable to fluvastatin IR 40 mg twice daily in Chinese hyperlipidemic patients with moderate or high cardiovascular risk and both treatments are safe and well-tolerated.