OBJECTIVE This study tested the hypothesis that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor affects T cell-mediated autoimmunity through inhibition of nuclear factor-kappaB (NFkappaB) and reduces the severity of experimental autoimmune myocarditis (EAM). METHODS EAM was induced in Lewis rats by immunization with myosin. High-dose or low-dose fluvastatin or vehicle was...

Hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins are well tolerated, but associated with various statin-associated symptoms (SAS), including statin-associated muscle symptoms (SAMS), diabetes mellitus (DM), and central nervous system complaints. These are "statin-associated symptoms" because they are rare in clinical trials, making their causative relationship to sta...

The visible wavelength excited fluorophore 3,3'-dioctadecylindocarbocyanine iodide (Dil[3]) was incorporated into human low density lipoprotein (LDL) to form the highly fluorescent LDL derivative dil(3)-LDL. Dil(3)-LDL binds to normal human fibroblasts and to human fibroblasts defective in LDL receptor internalization but does not bind to LDL receptor-negative human fibroblasts at 4 degrees C o...

M any people have high blood cholesterol that may lead to coronary heart disease (CHD). A multifaceted approach consisting of diet, exercise, and pharmacological management is recommended to lower the risk of CHD.1 Elevated low-density lipoprotein-cholesterol (LDL-C) has been established as a major cause of CHD.1 The group of cholesterol-lowering drugs known as statins (3-hydroxy3-methylglutary...

Daptomycin is a novel bactericidal antibiotic with excellent activity against gram-positive organisms. It is a large cyclic lipopeptide with a unique mechanism of action. Daptomycin is given once a day and is renally cleared, requiring dose adjustment in patients with impaired renal function. Unfortunately, there have been case reports of resistant gram-positive organisms. Daptomycin is general...

A method for solubilizing HMG-CoA reductase is described that reproducibly yielded approximately 190% of the activity assayed in rat liver microsomes. Optimal solubilization occurred when microsomal membranes were frozen at a fixed concentration, thawed, homogenized in a buffer containing 50% glycerol, and incubated at 37 degrees C for 60 minutes. A rapid spectrophotometric assay of the reducta...

The two yeast genes for 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, HMG1 and HMG2, each encode a functional isozyme. Although cells bearing null mutations in both genes are inviable, cells bearing a null mutation in either gene are viable. This paper describes a method of screening for recessive mutations in the HMG1 gene, the gene encoding the majority of HMG-CoA reductase activ...

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, are the most potent pharmacologic agents for lowering total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). They have become an accepted standard of care in the treatment of patients with known atherosclerotic cardiovascular disease (secondary prevention) and also those at increased risk of cardiovascular ...

Lipid lowering 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors--statins--significantly diminish the risk of cardiovascular morbidity and mortality in patients with cardiovascular diseases. Moreover, some clinical trials results indicate that this group of drugs reduces blood pressure, especially in patients with hypertension. In the article pleiotropic effects of statins th...

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMG-R) is the major rate-limiting enzyme of the mevalonate pathway in many organisms, including yeasts. In the yeast Saccharomyces cerevisiae, there are two isoenzymes of HMG-R (Hmg1p and Hmg2p). Both consist of an anchoring transmembrane domain and a catalytic domain. We have removed the known controlling features of HMG-R b...