Hyperlipidemia treatment studies

Unlike the previously discussed compounds, which inhibit MTP in both liver and intestine, an intestine-selective orally-active MTP inhibitor JTT-130 (structure not yet disclosed) has been reported to decrease plasma cholesterol and TG in guinea pigs with no hepatic lipid accumulation [16]. Although further studies in human are needed, inhibitors that selectively target intestinal MTP might be a safer alternative as a treatment for hyperlipidemia than the liver-targeting MTP inhibitors. 

The incidence of acute pancreatitis as a suspected complication of finasteride treatment has been examined in a case-control study in a Danish regional population of 490 000 over 7 years. Of 302 men aged 60 and older with incident acute pancreatitis, three had been exposed to finasteride of 2994 controls 37 had been exposed to finasteride. After adjustment for alcohol-related diseases, gallstone disease, hyperlipidemia, hypercalcemia, and hyperparathyroidism, the authors found no evidence of an increased risk of acute pancreatitis in users of finasteride (48). 

Two studies evaluated the effects of lipid-lowering therapy on clinical endpoints in the leg. The Program on the Surgical Control of the Hyperlipidemias was a randomized trial of partial ileal-bypass surgery for the treatment of hyperlipidemia in 838 patients (9). After five years, the relative risk (RR) of an abnormal ankle-brachial index value (ABI) was 0.6 (95% Cl, 0.4 to 0.9, absolute risk reduction, 15% points, p < 0.01), and the RR of claudication or limb-threatening ischemia was 0.7 (95% Cl, 0.2 to 0.9, absolute risk reduction, 7% points, p < 0.01), as compared with the control group. 

The promising second oral therapy is Temsirolimus (Wyeth Pharm). Temsirolimus is believed to block the proliferation of immune T cells activated by interleukin, IL-2. The phase It clinical trial of Temsirolimus was also an international double blind placebo controlled trial. The trial involved 296 patients with either RR MS or SP MS with relapses. Participants received one of three doses of oral temsirolimus or placebo daily for 9 months. The primary outcome measure was the number of enhancing lesions after 9 months in study. By 32 w eeks into the study, those in the highest treatment dose had 47.8% fewer new enhancing lesions compared to those on placebo. The high dose group also had 51 % fev er relapses than the placebo group. Side effects included mouth ulceration or inflammation, menstrual dysfunction, hyperlipidemia and rashes. 

Pharmacogenomic studies have been performed on a range of different cultured cells that participate in the formation of atherosclerotic lesion including ECs, SMCs, monocytes, and macrophages [144], as well as animal models [145], atherosclerotic lesion samples and blood-derived cells from patients with hyperlipidemia or coronary artery disease [144], Representative examples of such studies and their contribution towards improving atheroprotective treatments are presented in the following sections. 

Introduction - This review will present recent developments on the etiology and treatment of atherosclerosis, hyperlipidemia and cholelithiasis. The other major lipid disorder, obesity, has recently been reviewed as to pathogenesis and treatment,1 new efficacy trials and mechanism of action studies on anorectic agents,2 5 and appetite regulation in normal and abnormal states.3 6... 

Current guidelines do not advocate carnitine administration for the treatment of hypertriglyceridemia. Studies of carnitine for this indication have varied widely in duration and have used both oral and intravenous administration in varying doses (1 mg/kg to 2 g/day intravenously, 10 mg/kg per day to 3 g/day orally). Patients receiving longterm dialysis treatment also have been shown to accumulate renmants of triglyceride-rich lipoproteins. This hpoprotein abnormahty can result in type III hyperlipidemia with increased intermediate-density lipoprotein. 

The first study with retinoic acid on humans, however, failed to show any positive effects on the emphysema, but it did show mild negative side effects (including skin changes, transient headache, hyperlipidemia, transaminitis, and musculoskeletal pains) [91]. To evaluate the feasibility of ATRA as a clinical therapy, 20 patients with severe emphysema were enrolled into a randomized, double-blind, placebo-controlled pilot study. In general, treatment was well tolerated and associated with only mild side effects including skin changes, transient headache, hyperlipidemia, transaminitis, and musculoskeletal pains. 

Knopp, R.H., Retzlaff, B.M., Fish, B., Dowdy, A., Twaddell, B., Nguyen, T., and Paramsothy, P., 2009. The SLIM study Slo-Niacin(r) and atorvastatin treatment of lipoproteins and inflammatory markers in combined hyperlipidemia. Journal of Clinical Lipidology. 3 167-178. 

In compensation for this abnormal situation, fat is preferentially used as a sole energy source in the body. The metabolic shift to lipid utilization leads to hypertriglyceridemia accompanied by elevation of free fatty acid in blood and, in very advanced stages by elevation of ketone bodies including acetoacetate and 3-hydroxy-butyrate in blood. Increased level of CoA and acyl CoA in the diabetic rat liver was reported by Smith et al. [1]. This seems to be a metabolic response to increased utilization of fatty acid in diabetic state and suggests increased requirement for CoA in diabetic tissues. It is, therefore, interesting to study the effect of some precursors of CoA on diabetic hyperlipidemia. The present paper deals with a favorable effect of pantethine on lipid metabolism in streptozotocin diabetic rats. Pantethine treatment has been found to reduce increased levels of serum triglycerides,... 

The present study revealed that pantethine treatment effectively reduced serum triglyceride, -hydroxybutyrate and free fatty acid in diabetic hyperlipidemia of the rats. As reported by Smith et al. 

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