Drug-associated reward memories are conducive to intense craving and often trigger relapse. Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive. Here, we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm. We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference (CPP) without affecting CPP acquisition. Specifically, only simvastatin administered during extinction prevented cocaine-primed reinstatement. Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin. The metabolism of fatty-acids, phospholipids, and triacylglycerol was profoundly affected. Simvastatin reversed most of the effects on phospholipids induced by cocaine. The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions. Furthermore, simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine. In summary, pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.
Animals ; Brain ; Cocaine ; Conditioning, Operant ; Extinction, Psychological ; Lipidomics ; Male ; Mice ; Simvastatin/therapeutic use*

OBJECTIVETo compare the lipid lowering effects of Zhikang Granule (ZKG) and simvastatin.

METHODSForty-five out-patients with hyperlipemia who met the entry criteria were enrolled and randomized into two groups in the ratio of 2: 1, 30 patients in the ZKG group and 15 patients in the simvastatin group. The lipid lowering effects and safety of treatment during the 24-week therapeutic period, as well as the influence of treatment on plasma high sensitivity C reactive protein (hs-CRP) level in patients were observed.

RESULTSNo significant difference between the two groups was observed in serum levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) at the 4th, 8th, 12th and 24th week (P > 0.05). However, as compared with baseline, significant reduction of TC and LDL-C in both groups was shown at all the observing time points (P < 0.01), while the changes in TG and HDL-C were insignificant (P > 0.05). The control rates of LDL-C and TC in the ZKG group and the simvastatin group were 86.7% (26/30) versus 100% (15/15) at the 4th week, 80.0% (24/30) versus 100% (15/15) at the 8th week, 53.3% (16/30) versus 60.0% (9/15) at the 12th week, and 90.0% (27/30) versus 93.3% (14/15) at the 24th week, respectively, all showed insignificant difference between groups. No statistical differences were found between groups in levels of plasma transaminase, creatinine, uric acid and hs-CRP (P > 0.05).

CONCLUSIONZKG has a definite effect in lowering LDL-C and TC, and it is safe in long-term administration.

Aged ; C-Reactive Protein ; analysis ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Hyperlipidemias ; drug therapy ; Hypolipidemic Agents ; therapeutic use ; Lipids ; blood ; Male ; Middle Aged ; Phytotherapy ; Simvastatin ; therapeutic use

BACKGROUNDResearches in arterial elasticity have increased over the past few years. We investigated the effects of simvastatin on vascular stiffness in fat fed rabbits by ultrasonography.

METHODSThirty rabbits were assigned randomly to 3 groups: normal control group (A), the cholesterol group (B), simvastatin group (C: high fat diet for 4 weeks and high fat diet + simvastatin for further 4 weeks). Stiffness coefficient, pressure strain elastic modulus and velocity of pulse waves in abdominal aorta and femoral artery were measured by ultrasonographic echo tracking at the end of the 4th and the 8th weeks.

RESULTSAt the end of the 4th week, stiffness coefficient, pressure strain elastic modulus and pulse wave velocity of femoral artery were significantly increased in group B compared with those in group A. Similarly, at the end of the 8th week, the same parameters of abdominal aorta were significantly increased in group B compared with those in group A. In contrast, stiffness coefficient, pressure strain elastic modulus and pulse wave velocity of femoral artery were significantly decreased in group C compared with those in group B, however, there was no significant difference in parameters of abdominal aorta between groups B and C.

CONCLUSIONShort term administration of simvastatin can improve the elasticity of femoral artery but not abdominal aorta.

Animals ; Anticholesteremic Agents ; therapeutic use ; Aorta, Abdominal ; drug effects ; Blood Flow Velocity ; drug effects ; Dietary Fats ; adverse effects ; Femoral Artery ; drug effects ; Rabbits ; Random Allocation ; Simvastatin ; therapeutic use

OBJECTIVETo investigate whether patients, who are at risk of major acute coronary events, are safe to undergo and benefit from early intervention after using simvastatin.

METHODSThe study was a randomized, open, two-dosage-controlled trial to evaluate the safety and benefits of simvastatin administered to 197 patients (10 mg group, n = 98 and 20 mg group, n = 99), within 48 hours of hospitalization for a diagnosis of unstable angina or acute myocardial infarction (MI), with total cholesterol (TC) >/= 180 mg/dL or low-density lipoprotein cholesterol (LDL-C) >/= 100 mg/dL. Lipid levels were measured immediately, followed by the 3rd, 6th and 12th month after admission and all adverse events were recorded during follow-up.

RESULTSTC levels fell by 10.15% and 14.52% in the 10 mg and 20 mg groups (P < 0.05), and LDL-C levels fell 13.87% and 19.38% in the 10 mg and 20 mg groups, respectively (P < 0.01), 12 months after using simvastatin. The rates of achieving target TC reached 26.3% and 36.5% in the 10 mg and 20 mg groups (P < 0.01), and that of LDL-C reached 28.2% and 40.3% in the 10 mg and 20 mg groups, respectively (P < 0.01). There were higher rates of MI and re-hospitalization resulting from angina pectoris and revascularization in the 10 mg group compared with the 20 mg group.

CONCLUSIONSThe results suggest that early intervention with the HMG-CoA reductase inhibitor, simvastatin, in acute coronary syndromes is possible and safe. It also indicates that the clinical dosage of simvastatin are relatively smaller than that for satisfactory lipid control in patients with acute coronary syndromes.

Acute Disease ; Aged ; Cholesterol ; blood ; Cholesterol, LDL ; blood ; Coronary Disease ; blood ; drug therapy ; Female ; Follow-Up Studies ; Humans ; Hypolipidemic Agents ; therapeutic use ; Male ; Middle Aged ; Simvastatin ; therapeutic use

OBJECTIVETo evaluate the role of Jiangzhi Xiaoban Tablet (JXT) in improving heartfunction of coronary heart disease (CHD) patients by tissue Doppler imaging (TDI) and speckle trackingimaging (STI) technology.

METHODSRecruited were 60 inpatients with confirmed CHD by coronary angiography at First Affiliated Hospital, Hunan University of Traditional Chinese Medicine from October 2013to November 2014. They were assigned to the treatment group (group A) and the control group (groupB) according to random digit table, 30 cases in each group. Patients in group A took JXT, 0.45 g/tablet,4 tablets each time, 3 times per day, while those in group B took Simvastatin Tablet, 20 mg/tablet, 1 tablet each time, once per evening. The therapeutic course for all was 8 weeks. The long axis view of theheart of 18 segments STI Peak strain LS and TDI peak systolic Sa parameters were performed in all patients before and after treatment.

RESULTSBefore treatment segments of STI strain LS and TDI longitudinal peak systolic peak Sa were not statistically different between the two groups (P > 0.05). Each segment of STI peak longitudinal strain LS and TDI peak systolic Sa in the two groups were higher after treatment than before treatment (P < 0.05). After treatment each segment of STI parameters of LS and eachTDI segment parameters of Sa were significantly lower in group B than in group A (P < 0.01).

CONCLUSIONJXT could improve heart function of CHD patients to different degrees, and its curative effect was betterthan that of routine Western medicine (Simvastatin Tablets) treatment.

Coronary Artery Disease ; drug therapy ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Echocardiography, Doppler ; Heart ; drug effects ; Humans ; Simvastatin ; therapeutic use ; Tablets

Cholesterol, LDL ; blood ; Diabetes Mellitus, Type 2 ; complications ; Humans ; Hyperlipidemias ; blood ; drug therapy ; etiology ; Hypolipidemic Agents ; therapeutic use ; Simvastatin ; therapeutic use ; Triglycerides ; blood

Aspirin ; therapeutic use ; Bisoprolol ; therapeutic use ; Cardiomyopathies ; chemically induced ; etiology ; Cardiotonic Agents ; adverse effects ; Chest Pain ; diagnostic imaging ; Dobutamine ; adverse effects ; Echocardiography, Stress ; adverse effects ; Enalapril ; therapeutic use ; Humans ; Male ; Middle Aged ; Simvastatin ; therapeutic use

OBJECTIVE: To explore the effect of simvastatin on myocardiac fibrosis in patients with essential hypertension (EH). METHODS: Sixty EH patients were randomly assigned into 2 groups: Benazepril (10 mg/d) group (n = 28) and simvastatin (20 mg/d) + benazepril (10 mg/d) group. Procollagen type III aminoterminal peptide (PIIIP), and procollagen type IV aminoterminal peptide (PIVP) levels in serum as well as transforming growth factor beta 1 (TGFbeta1) level in plasma were measured by radioimmunoassay (RIA) before and 6 months after the treatment. Doppler ultrasound recordings were obtained from all patients before and 6 months after the treatment to determine several parameters related to the left ventricular anatomy and function. RESULTS: After 6 month of treatment, the mean blood pressure (MBP), PIIIP, PIVP, TGFbeta1, left ventricular mass index (LVMI), interventricular spectum dimension (IVSD), and left ventricular posterio wall dimension (LPWD) in the 2 groups were significantly lower than those before the treatment. TGFbeta1 decreased in the simvastatin and benazepril group compared with the benazepril group (P < 0.01). The ratio of early diastolic blood flow velocity of mitral valve (VE) and blood flow velocity of atrium systolic period (VA) in the 2 groups significantly increased after 6 months of treatment, and the ratio in the simvastatin and benazepril group was significantly higher than that in the enazepril group (P < 0.05). CONCLUSION Angiotension converting enzyme inhibitor combined with simvastatin is helpful to reduce the myocardial fibrosis and to improve the left ventricular hypertrophy and diastolic function in EH patients.
Adult ; Aged ; Aged, 80 and over ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Antihypertensive Agents ; therapeutic use ; Benzazepines ; therapeutic use ; Drug Therapy, Combination ; Female ; Fibrosis ; etiology ; prevention & control ; Humans ; Hypertension ; complications ; drug therapy ; Male ; Middle Aged ; Myocardium ; pathology ; Simvastatin ; therapeutic use

OBJECTIVETo observe the association between plasma endothelin (ET) concentration and blood pressure level in essential hypertensive (EH) patients with or without complications and possible impact of statins on ET concentration.

METHODSFrom Sep 2007 to Mar 2009, 149 patients with EH were analyzed [44 EH, 40 EH complicated by left ventricular hypertrophy (EH-LVH), 36 EH complicated by atrial fibrillation (EH-AF), and 29 EH complicated by lacunar infarction (EH-LI)], 30 healthy persons were selected as controls. EH patients were randomly divided into routine treatment group (calcium antagonists, ACEI, diuretics, beta-receptor blocker for 8 weeks) and simvastatin intervention group (routine treatment + simvastatin 40 mg/d for 8 weeks), plasma ET concentrations before and after drug intervention were measured.

RESULTS(1) ET concentration was higher in EH group than that in control group [(71.42 +/- 6.62) pg/ml vs. (45.52 +/- 8.28) pg/ml, P < 0.01]. ET concentration was higher in EH-LVH group, EH-AF group and EH-LI group than that in EH group [(97.67 +/- 10.53) pg/ml, (102.15 +/- 12.96) pg/ml, (103.49 +/- 9.91) pg/ml vs. (71.42 +/- 6.62) pg/ml, P <0.01]. The degrees of elevated blood pressure was positively correlated with ET concentrations(all P < 0.001). (2) The left atrial diameters of EH-AF group were positively correlated with ET concentration (r = 0.684, P < 0.001). The left ventricular mass index of EH-LVH group were positively correlated with ET concentration (r = 0.545, P < 0.001). (3) The percentages of class 3 hypertension in EH-LVH group, EH-AF group and EH-LI group were higher than that in EH group (57.5%, 50.0%, 62.1% vs. 25.0%, all P < 0.05). (4) Blood pressure in class 3 hypertension patient treated with simvastatin decreased more significantly than that in routine treatment group (P < 0.05). (5) ET concentration of class 2 hypertension patient treated with simvastatin decreased significantly than that in routine treatment group (P < 0.05). ET concentrations of class 3 hypertension patient treated with simvastatin and routine treatment patient decreased significantly after treatment (P < 0.05), and the former was lower (P < 0.05).

CONCLUSIONThe level of ET were positively correlated with the severity of EH. Simvastatin could decrease the ET levels of patients with EH and blood pressure levels of patients with class 3 hypertension. It suggested that therapeutic alliance of antihypertensive drugs and statins could be benefit to patients with EH.

Aged ; Aged, 80 and over ; Antihypertensive Agents ; therapeutic use ; Blood Pressure ; Endothelins ; blood ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Hypertension ; blood ; complications ; drug therapy ; Male ; Middle Aged ; Simvastatin ; therapeutic use

OBJECTIVEThe aim of this study was to evaluate the efficacy and safety of combination therapy with simvastatin and fenofibrate in patients with combined hyperlipidemia.

METHODSA total of 221 patients with combined hyperlipidemia were randomly assigned to receive 10 mg simvastatin (n = 72) or 200 mg fenofibrate (n = 68), or a combination of 10 mg simvastatin + 200 mg fenofibrate (n = 81) for 6 months. Lipid profiles, physical and laboratory investigations for adverse effects were assessed.

RESULTS(1) Combination treatment were more effective in normalizing lipid profile than any monotherapy. Serum TC, LDL-C, and TG were reduced by 30%, 37% and 56% respectively, whilst HDL-C significantly increased by 24% (all P < 0.01). The improvement in TG and HDL-C achieved by combination treatment was superior to fenofibrate or simvastatin alone. (2) The success rate of TC, LDL-C and TG control in the combination therapy group were 51%, 55% and 61% respectively, with an overall success rate (all three together) of 45%, which was superior to either drug given as monotherapy. (3) All treatments were well tolerated with no increase in adverse events for combination therapy versus monotherapy.

CONCLUSIONThe results of this study demonstrated that combination therapy with fenofibrate (200 mg/day) and low-dose simvastatin (10 mg/day) is more effective than monotherapy in patients with combined hyperlipidemia, and is generally safe and well tolerated.

Drug Therapy, Combination ; Female ; Fenofibrate ; administration & dosage ; adverse effects ; therapeutic use ; Humans ; Hyperlipoproteinemia Type V ; drug therapy ; Hypolipidemic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Simvastatin ; administration & dosage ; adverse effects ; therapeutic use