Objective To assess the effectiveness and safety of nine lipid-lowing agents in the national essential drug list (2000) and provide evidence for the adjustment and selection of essential drugs. Methods Based on principles of health technology assessment (HTA) and evidence-based medicine, we searched for all published clinical studies about these drugs from the following databases: MEDLINE (1966-2002.8), The Cochrane Library, EMBASE (1974-2002), CBMdisk (1979-2002.8) and VIP (1989-2002.8), the database of National Center for Adverse Drug Reaction(ADR) Monitoring of China and the database of WHO Uppsala drug monitoring center. Included studies were appraised, analyzed and compared for the reduction of triglyceride (TC) or low density lipoprotein (LDL-C), the prevention for the coronary events and the incidence of ADR. Results The results from comparative trials for lipid-lowing agents showed that the equivalent dose of statins for 25% reduction of LDL-C was atorvastatin 10 mg/d, simvastatin 20 mg/d, pravastatin 40mg/d, lovastatin 40 mg/d, cerivastatin 0.3 mg/d and fluvastatin 80 mg/d. It was difficult to compare fenofibrate with gemfibrozil, acipimox with statins or fibrates based on available data. The study on the primary and secondary prevention of cardiovascular events showed that pravastatin and lovastatin were effective in primary prevention, and long-term use could reduce the incidence of cardiovascular disease.Gemfibrozil could reduce the mortality from coronary heart disease (CHD) but the overall mortality was not changed. Pravastatin, simvastatin, atorvastatin, fluvastatin, gemfibrozil and fenofibrate had a confirmed effect in secondary prevention. Data from large-scale clinical trials and the reports from ADR monitoring center of England, America, Canada and Australia suggested that the statins which had rare ADR were safe and tolerated. Rhabdomyolysis was rare but had a serious adverse reaction associated with statins. The rate of fatal rhabdomyolysis related to cerivastatin was the highest among 6 statins. The safety of simvastatin, lovastatin and atorvastatin was lower than cerivastatin but higher than simvastatin and atorvastatin. The number of ADR reports of fenofibrate was fewer than that of gemfibrozil. Conclusions At present, the best evidence focused on pravastatin, simvastatin and lovastatin are widely used and have a confirmed safety and efficacy. Atorvastatin, fluvastatin and fenofibrate still need more data to confirm their effects on coronary heart disease prevention. The drugs which were shown to be inferior or insufficient evidence are cerivastatin, gemfibrozil and acipimox.
Objective To study the effects of glucose and lipid metabolism on gallstone formation. Methods Twenty five patients with gallstones and 25 normal volunteer controls were studied from January to April in 1998. The patients were well matched the control with sex and age (1∶1). In the study, Body Mass Index (BMI) and Waist-to-Hip circumference ratio (W/H) were measured. Blood glucose, glucosylated hemoglobin (HbA1C), insulin, C peptide and all parameters of lipids were detected at fasting state. The glucose,insulin, C peptide were detected again at 2-hour after taking 75g glucose orally.Results The result showed there was no difference on BMI and W/H between the patients and controls. HbA1C、mean fasting and 2hour glucose concentration were not in significantly different between the two groups (Pgt;0.05, Pgt;0.2, Pgt;0.1 respectively). There were 10 patients with abnormal glucose metabolism (7 with NIDDM, 3 with IGT), but only 4 controls were abnoumal (one with NIDDM, three with IGT). The difference was significant (Plt;0.05). Furthermore, the mean fasting and 2hour insulin concentration of gallstone group was higher than that of the control (Plt;0.02, Plt;0.05). And the gallstone group had a higher fasting C peptide concentration than control (Plt;0.05). There was no statistical difference on the parameters of plasma lipid between the tow groups. Conclusion The study suggests that diabetes mellious and hyperinsulinemia acted as an important role on gallstone formation.
To elucidate the mechanism of renal injury following intestinal ischemia/reperfusion, reactive oxygen metabolites in kidney and plasma were examined in 20 rats following intestinal ischemia/reperfusion by measurement of lipid proxidation (LP).The plasma lipid peroxide concentration after reperfusion was higher than that of the contol group (Ｐ＜0.01),the LP in kidney homogenate was also significantly higher (Ｐ＜0.01) following intestinal ischemia/reperfusion.Our study suggests that reactive oxygen metabolites after intestinal ischemia/reperfusion plays an important role in kidney injury.
To investigate prospectively the short-term effect of different fat emulsions on plasma lipids and lipoproteins and to clarify the underlying mechanisms. Fifty six surgical patients were randomized to received intravenously either a 10%. Intralipid, a 20% Intralipid or no fat emulsions for 5 days postoperatively as part of a standard parenteral nutrition regimen. Serum lipids and lipoproteins were measured prior to and after the 5-day infusion period. Results: Intravenous administration of 10% Intralipid caused a marked increase of total cholesterol (Tcho), free cholesterol (Fcho), Low-density lipoprotein cholesterol (LDL-ch), phospholipid and lipoprotein X (LPX). Quantification of LPX revealed that its increase was proportionate to that of phospholipid and Tcho. Conclusion: Exogenous phospholipids when using fat emulsions with a high phospholipid/triglyceride (PL/TG) ratio play an impressive role in the formation of LPX and consequently are capable of inducing hypercholesterolemia after only a few days. Therefore, 20% Intralipid should be preferred to the corresponding 10% Intralipid for its low PL/TG ratio.
To study the lipid peroxidation injury and the protecting effect of vitamin E emulsion on liver function following acute cholangitis. During the operation and 24 hours after operation, vitamin E emulsion or placebo emulsion was infused via mesenteric vein in rats suffering acute cholangitis. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and adenosine triphosphate (ATP) in the liver tissue and serum were measured at 48hrs after operation. Results: As compared with the placebo emulsion group, MDA and mGOT contents in the liver tissue and serum decreased significantly, but SOD activity increased dramatically in the VE emulsion group. ATP content in the infected lobe was much higher than those in the placebo emulsion group. Conclusion: Intravenous infusion of large dose of vitamin E emulsion may reduce the lipid peroxidation reaction in acute cholangitis, and have protecting effect.
To investigate the mechanisms of hepatic injury after biliary obstruction. After a rat model of complete biliary obstruction(CBO) was induced, hepatocyte mitochondria was isolated and the calcium content of mitochondria, the contents of liver malondialdyhyde (MDA) and superoxide dismutase (SOD), the levels of serum T-Bil, ALT, ALP and GGT were measured in each group. Results: After CBO, mitochondrial calcium content, liver MDA and serum T-Bil, ALT, ALP, GGT became increased progressively, compared with control group (Ｐ＜0.05); the liver SOD was decreased markedly (Ｐ＜0.05). Mitochondrial calcium content was highly positively correlated with liver MDA content, serum ALT and ALP, r values were 0.967, 0.924 and 0.919 respectively (Ｐ＜0.01). The liver MDA content was highly positively correlated with serum ALT and ALP, r values were 0.949 and 0.843 respectively (Ｐ＜0.01). Conclusions: Mitochondrial calcium overload and liver lipid peroxidation may be the important mechanisms of hepatic injury induced by biliary obstruction.
The present study was designed to elucidate the role of apoE polymorphism in the lithogenesis of cholecystolithiasis and to explore the hereditary pathogenesis of the disease. Polymerase Chain Reaction (PRC) was used as researching apoE phenotypes and allele frequencies in patients with gallstones (n=87) and in controls (n=50), and the fasting serum lipids of subjects were also measured. The characteristics of lipid variants were analysed among the patients with different apoE phenotypes. The results showed that the levels of TG (1.43mmol/L), VLDL-C(0.68mmol/L) in E2/3 patients were greatly higher than those in E2/3 controls (1.06mmol/L, Ｐ＜0.05 and 0.48mmol/L, Ｐ＜0.05), and LDL-C (1.41mmol/L) was markably lower in E2/3 patients than that in controls (2.04mmol/L, Ｐ＜0.05). The levels of serum lipids decreased significantly in E3/3 patients with HDL-C (0.89mmol/L), HDL2-C (0.49mmol/L), HDL3-C (0.39mmol/L), and compared with those in E3/3 controls (1.28mmol/L Ｐ＜0.05, 0.73mmol/L Ｐ＜0.001 and 0.55mmol/L Ｐ＜0.001). In E3/4 patients there were only slight changes of VLDL-C, LDL-C level. The results suggest that the average level of serum lipids in the same apoE phenotype patients with gallstones is higher than that in controls, and the different apoE phenotypes patients with gallstones have different characteristics of dyslipidemia. ε2 allele is probably one of the dangerous factor in the lithogenesis of cholecystolithiasis.
The experimental models of chronic hepatic lesion of 40 rabbits were made by intra-abdominal injection of thioacetamide.The chronic hepatic lesion was confirmed by pathological examination and hepatectomies were performed in accordance with different measurements on each rabbit.The observations included indocyanine green retention rate,hepatic resection volume,and the outcomes of operations.The results showed that the mortality was correlative with the change of hepatic functions in the background of chronic hepatic lesion.The indocyanine green retention and the level of serum albumin are important parameters to indicate hepatic impairment.When the former was over 40% or the latter below 2.8g% the operative danger was high and the mortality was over 50%.In accordance with the classification of hepatic function,the preoperative functional state of liver were classified:grade A,B and C.the mortality of posthepatectomy were respectively 16.7%,3O%,and 72%.The multiple progressive regression equation is employed for calculating the postoperative outcome.The equation predicted the postoperative outcome with 88.9% accuracy.
The contents of lipid peroxides(LPO)and vitamin E(V.E)and some functional index and histologic changes in the lungs from the the rabbit models of acute cholangitis of severe type(ACST)were measured dynamically.The results revealed that the V.E content decreased strikingly from 6 hours and the LPO level increased progressivelg from 12 hours in the lungs.Simultanuosly,the congestion and neutrophil infiltreation in the lung mesenchyme,and the endothelial cell damage and thrombosis in the lung blood capillaries had been observed.These suggest that acute lung injury induced by ACST is referable to the lipid peroxidation damage to the lung blood capillaries which is due to increased LPO and decreased antioxidants including V.E.
The anti-oxidative ability of cirrhotic liver tissues was evalated in rat models of cirrhotic liver which were induced by injecting carbon tetrachloride subcutaneously. The superoxide dismutase (SOD), general anti-oxidative ability (GAOA) and malonyldiadehyde (MDA) levels were determined in cirrhotic and normal rats. It was found that SOD and GAOA leves decreased (Ｐ＜0.05, Ｐ＜0.01)respective and MDA level increased(Ｐ＜0.05) significantly in cirrhotic rat liver. The results suggest that cirrhotic livers hav little ability to eliminate the superoxide free radicals as compared with normals and are more sensitive to is chemic-reperfusion or other unjurie.