This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid β oxidation in the liver.
Rats ; Male ; Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Sterol Regulatory Element Binding Protein 1/metabolism* ; Diet, High-Fat/adverse effects* ; Diosgenin/metabolism* ; Chaperonin 60/therapeutic use* ; Rats, Sprague-Dawley ; Liver ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Triglycerides ; RNA, Messenger/metabolism* ; Simvastatin/therapeutic use* ; Body Weight ; Lipid Metabolism ; Mammals/metabolism*

Statins are a kind of prescription drug that is widely used to treat hyperlipidemia, coronary artery disease, and other atherosclerotic diseases. A common side effect of statin use is a mild rise in liver aminotransferases, which occurs in less than 3% of patients. Statin-related liver injury is most commonly caused by atorvastatin and simvastatin, but severe liver injury is uncommon. Therefore, understanding and evaluating hepatotoxicity and weighing the benefits and risks is of great significance to better realize the protective effect of statins.
Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects* ; Atorvastatin/adverse effects* ; Simvastatin/adverse effects* ; Chemical and Drug Induced Liver Injury/drug therapy* ; Drug-Related Side Effects and Adverse Reactions/drug therapy*

OBJECTIVE: To observe the role of aminophylline and simvastatin in preventing and curing chronic obstructive pulmonary disease (COPD), and to explore the underlying mechanisms based on airway inflammation and mucus hypersecretion.
 METHODS: The rat model of COPD was established by combination of cigarette smoking with intratracheal lipopolysaccharide (LPS) injection. Male SD rats were randomly divided into 4 groups (n=10 per group): a control group, a COPD group, an aminophylline group and a simvastatin group. The rats in the control group and the COPD group were treated with normal saline once a day via intragastric administration, while the rats in the aminophylline group and the simvastatin group were treated with aminophylline (5 g/L) and simvastatin (0.5 g/L) 1 mL/100 g once a day via intragastric administration, respectively. Pulmonary function and pathological changes in bronchus and lung were observed. The levels of IL-8, IL-17, and TNF-α in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expressions of TLR4 and mucin 5AC (MUC5AC) in bronchi and lung tissues were detected by real-time PCR and Western blot, respectively.
 RESULTS: Pulmonary function and the pathophysiologic changes in bronchi and lung tissues in the COPD rats were consistent with typical phenotype of COPD. Compared with the control group, lung function indexes were significantly attenuated in the COPD group, while the levels of IL-8, IL-17, and TNF-α in BALF as well as the mRNA and protein levels of MUC5AC and TLR4 were significantly increased. Compared with the COPD group, lung function indexes were significantly increased in the aminophylline group and simvastatin group (P<0.01), while pulmonary pathological damages, the levels of IL-8, IL-17, and TNF-α in BALF as well as the mRNA and protein levels of MUC5AC and TLR4 were significantly decreased (P<0.01). Compared with the aminophylline group, the peak expiratory flow as well as the levels of IL-8, IL-17, and TNF-α in the simvastatin group were elevated (P<0.05). There are no significant difference in the mRNA and protein levels of MUC5AC and TLR4 between the 2 groups (P﹥0.05).
 CONCLUSION Aminophylline and simvastatin can decrease IL-8, IL-17, and TNF-α levels in BALF and inhibit the expression of MUC5AC and TLR4 in airway and lung tissues in COPD rats, suggesting that they may have a preventive and therapeutic effect on COPD through reducing the airway inflammation and mucus hypersecretion.
Aminophylline ; pharmacology ; Animals ; Bronchi ; metabolism ; Bronchoalveolar Lavage Fluid ; chemistry ; Cytokines ; chemistry ; Inflammation ; drug therapy ; Lipopolysaccharides ; Lung ; metabolism ; physiopathology ; Male ; Mucin 5AC ; metabolism ; Mucus ; metabolism ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Simvastatin ; pharmacology ; Smoke ; adverse effects ; Smoking ; adverse effects ; Toll-Like Receptor 4 ; metabolism

Dental surgery is very common, and it is important for our dental colleagues to understand the medical history and chronic medications of our co-managed patients. Antibiotic prophylaxis is currently recommended only for patients at high risk for infective endocarditis when undergoing high-risk dental procedures. Good dental hygiene can prevent more infective endocarditis than prophylactic antibiotic therapy, as transient bacteraemia is common in daily activities such as the brushing and flossing of teeth. Most dental surgeries can generally be performed on patients taking a daily dose of aspirin, but the dentist must be able to assess the risk-benefit ratio of employing local measures of haemostasis versus stopping the antiplatelet therapy. Patients on antiplatelet with recent coronary artery stenting should be referred to their primary cardiologist regarding the cessation of these agents before any surgery.
Angioplasty ; Antibiotic Prophylaxis ; methods ; Aspirin ; therapeutic use ; Dental Care for Chronically Ill ; methods ; Dentists ; Drug Interactions ; Endocarditis ; prevention & control ; Humans ; Hyperlipidemias ; complications ; Macrolides ; adverse effects ; Male ; Mitral Valve Prolapse ; complications ; Myocardial Ischemia ; complications ; Platelet Aggregation Inhibitors ; adverse effects ; Simvastatin ; adverse effects ; Streptococcal Infections ; prevention & control ; Tooth Extraction ; methods ; Viridans Streptococci ; metabolism

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

OBJECTIVETo investigate the clinical features and prognosis of rhabdomyolysis related to seizure attacks and use of statin.

METHODSThe medical records of 3 patients with established diagnosis of rhabdomyolysis were analyzed and the related literatures were reviewed.

RESULTSAll the 3 patients had seizure attacks and/or used statin before the onset of rhabdomyolysis. Two of the patients complained of back pain, and all the 3 patients had dark-colored urine. Serum levels of creatine kinase (CK) were markedly increased by over 50 times above the normal upper limit. CK level kept increasing even after proper interventions, till reaching the peak level about 3 days later. The patients improved rapidly with full recovery thereafter, and CK became normal in 2 weeks. None of the patients had renal failure.

CONCLUSIONSeizure attacks and use of statin are common risk factors for non-traumatic rhabdomyolysis. Caution needs to be taken when prescribing statin to patients with recent seizure attacks. Special attention should be given to such early symptoms as muscle pain, weakness and dark-colored urine, and CK level monitoring is advisable in such cases.

Cerebral Infarction ; drug therapy ; Creatine Kinase ; blood ; Epilepsy ; complications ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; adverse effects ; therapeutic use ; Lovastatin ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Rhabdomyolysis ; chemically induced ; enzymology ; etiology ; Simvastatin ; adverse effects ; therapeutic use

HMG-CoA reductase inhibitors (statins) are widely used to treat hypercholesterolemia. Among the adverse effects associated with these drugs are statin-associated myopathies, ranging from asymptomatic elevation of serum creatine kinase to fatal rhabdomyolysis. Fluvastatin-induced fatal rhabdomyolysis has not been previously reported. We describe here a patient with liver cirrhosis who experienced fluvastatin-induced fatal rhabdomyolysis. This patient had been treated with simvastatin (20 mg/day) for coronary artery disease and was switched to fluvastatin (20 mg/day) 10 days before admission. He was also taking aspirin, betaxolol, candesartan, lactulose, and entecavir. Rhabdomyolysis was complicated and continued to progress. He was treated with massive hydration, urine alkalization, intravenous furosemide, and continuous renal replacement therapy for acute renal failure, but eventually died due to rhabdomyolysis complicated by hepatic failure. In conclusion, fluvastatin should be used with caution in patients with liver cirrhosis, especially with other medications metabolized with CYP2C9.
Coronary Artery Disease/complications/*drug therapy ; Fatal Outcome ; Fatty Acids, Monounsaturated/administration & dosage/*adverse effects/therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage/*adverse effects/therapeutic use ; Indoles/administration & dosage/*adverse effects/therapeutic use ; Liver Cirrhosis/*complications ; Male ; Middle Aged ; Rhabdomyolysis/*chemically induced ; Simvastatin/administration & dosage/therapeutic use

The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of ezetimibe/simvastatin (E/S) after drug-eluting stent (DES) implantation in a porcine coronary restenosis model. Pigs were randomized into two groups in which the coronary arteries (23 pigs) had DES. Stents were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries. Fifteen pigs were taken 10/20 mg of E/S and eight pigs were not taken E/S. Histopathologic analysis was assessed at 28 days after stenting. In neointima, most inflammatory cells were lymphohistiocytes. Lymphohistiocyte count was not different between two groups (337+/-227 vs. 443+/-366 cells, P=0.292), but neointima area was significantly smaller (1.00+/-0.49 mm2 vs. 1.69+/-0.98 mm2, P=0.021) and percent area stenosis was significantly lower (23.3+/-10% vs. 39+/-19%, P=0.007) in E/S group compared with control group. There were no significant differences in fibrin score (1.99+/-0.79 vs. 1.81+/-0.88, P=0.49), endothelial score (1.75+/-0.66 vs. 1.80+/-0.59, P=0.79), and the percent of endothelium covered lumen (43+/-21% vs. 45+/-21%, P=0.84) between E/S group and control group. Combined therapy with ezetimibe and simvastatin inhibits neointimal hyperplasia, but does not inhibit inflammatory infiltration and arterial healing after DES implantation in a porcine coronary restenosis model.
Animals ; Anticholesteremic Agents/administration & dosage ; Azetidines/*administration & dosage ; Coronary Restenosis/diagnosis/drug therapy/*etiology ; *Disease Models, Animal ; Drug Combinations ; Drug Implants/administration & dosage ; Drug-Eluting Stents/*adverse effects ; Female ; Graft Occlusion, Vascular/diagnosis/*drug therapy/*etiology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage ; Simvastatin/*administration & dosage ; Swine ; Treatment Outcome

BACKGROUND/AIMS: The efficacy and safety of a combination of ezetimibe and low-dose statin as primary treatment for dyslipidemia in renal transplant patients were evaluated prospectively. METHODS: The study enrolled 77 renal transplant recipients with dyslipidemia. They were given ezetimibe (10 mg) and simvastatin (10 mg) for 6 months as the initial treatment for dyslipidemia. Efficacy and safety were evaluated using lipid profiles, trough calcineurin inhibitor levels, allograft function, and adverse effects. The effects on proteinuria and high sensitivity C-reactive protein (hsCRP) levels were also evaluated. RESULTS: Ezetimibe and low-dose simvastatin significantly decreased the levels of total cholesterol (34.6%), triglyceride (16.0%), and low-density lipoprotein cholesterol (LDL-C) (47.6%), and 82.5% of the patients reached the target LDL-C level of <100 mg/dL. No significant change in the trough calcineurin inhibitor levels or allograft function occurred, and no serious adverse effects were observed. Fourteen patients (18.2%) discontinued treatment; eight patients (11.7%) developed muscle pain or weakness without an increase in creatinine kinase levels, and two patients (2.6%) developed elevated liver transaminase levels. The proteinuria and hsCRP levels did not change significantly. CONCLUSIONS: Ezetimibe and low-dose statin treatment is safe and effective as a primary treatment for dyslipidemia in renal transplant patients.
Adult ; Azetidines/*administration & dosage/adverse effects ; C-Reactive Protein/analysis ; Cholesterol, LDL/blood ; Dyslipidemias/blood/*drug therapy ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & dosage ; *Kidney Transplantation ; Male ; Middle Aged ; Prospective Studies ; Simvastatin/*administration & dosage/adverse effects

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