Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of 5-methyl-7-diethylamino-s-triazolo-1, 5-a) pyrimidine (trapidil, Rocornal), a therapeutic agent for ischemic heart disease, on various types of experimental hyperlipemias were studied. With administration of trapidil, elevation of serum high density lipoprotein cholesterol (HDL-C) levels and reduction in serum total cholesterol (TC), low density lipoprotein and very low density lipoprotein cholesterol (LDL-C) and the ratio of HDL-C to LDL-C (LDL-C/HDL-c) were observed in most disease models. Changes in HDL-C levels and LDL-C/HDL-C in the hyperlipemia induced by lipid-enriched diet in mice and in the hyperlipemia induced by high cholesterol diet in Japanese quails were of statistical significance. Also, amelioration of reduction in HDL-C induced by high fat emulsion plus 6-n-propyl-2-thiouracil in rats was observed to be significant. Moreover, trapidil significantly reduced TC, LDL-C levels and LDL-C/HDL-C in the hyperlipemia in hamsters. To investigate possible mechanisms of therapeutic effects of trapidil, blood enzyme activities in Japanese quails with hyperlipemia were assayed. Trapidil showed increases in plasma lipoprotein lipase and serum lecithin-cholesterol acyltransferase activities. These results suggest that trapidil may be an effective chemotherapeutic agent for treating ischemic heart disease.
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PMID:[Effects of 5-methyl-7-diethylamino-s-triazolo-(1, 5-a) pyrimidine (trapidil) on various experimental hyperlipemias (author's transl)]. 720 81

Cyclosporine is a potent tool in the immunosuppressive armamentarium. It provides relatively selective inhibition of T-cell responses without dampening nonspecific resistance. However, its use is confounded by a pleiotropic array of side effects, the most important of which is renal dysfunction with the not uncommon sequelae of hypertension, hyperuricemia, and hyperkalemia. The hepatic injury associated with CyA administration, which is characterized by a chronic elevation of serum transaminase values, is potentiated by azathioprine or recrudescent or de novo viral infections. Finally, the proclivity of the drug to produce hyperlipidemia may jeopardize long-term survival; patients not infrequently require gemfibrizol and/or pravastatin therapy to control triglyceride and/or cholesterol levels, respectively. Two strategies appear to be useful. Our concentration-control strategy assesses CyA exposure by analyzing serial pharmacokinetic profiles, titering drug doses to achieve initial steady state concentrations of 400 ng/mL during continuous i.v. infusion, and to achieve average concentrations, namely AUC divided by dosing interval (in hours), of 550 ng/mL initially with trough levels of 200 ng/mL or above. Pretransplant pharmacokinetic profiling permits prediction of the appropriate initial i.v. dose in 73% of patients, and in combination with a posttransplant profile of the oral dose in about 60% of patients. The target oral concentrations are progressively reduced, thereby permitting prospective CyA control and minimizing adverse effects. The second synergistic drug strategy uses the median effect mathematical model to identify new drug combinations. The combination of CyA with RAPA, a macrolide which inhibits lymphokine signal transduction, and with BQR, a difluoro quinoline carboxylic acid analog that inhibits pyrimidine biosynthesis, permits at least a 20-fold reduction of the CyA dose in rat allograft models as well as prevents the activation of some CyA-resistant rejection pathways. Future investigations of pharmacologic strategies are undoubtedly likely to re-enforce the efficacy and safety of CyA administration for a range of immunologic disorders.
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PMID:Optimization of cyclosporine therapy. 835 18

Rhizoma Alismatis (RA), a diuretic in Asia and Europe, was found to possess anti-hyperlipidemic activity. Since the biomarkers and mechanisms of RA in the treatment of hyperlipidemia are inadequate, ultra-performance liquid chromatography coupled with quadrupole time-of-flight synapt high-definition mass spectrometry and multivariate data analysis were employed to investigate the urinary metabolomics of RA on hyperlipidemic rats induced by high-fat diet. The metabolic profile of RA-treated hyperlipidemic group located between control and diet-induced hyperlipidemic groups. Nineteen metabolites with significant fluctuations were identified as potential biomarkers related to the hyperlipidemia and anti-hyperlipidemia of RA using partial least-squares-discriminate analysis, heatmap analysis and correlation coefficient analysis. The fluctuations of these biomarkers represented disturbances in amino acid metabolism, purine metabolism, pyrimidine metabolism and energy metabolism. After RA treatment, these perturbed metabolites were restored to normal or nearly normal levels. RA can alleviate high-fat diet-induced dysfunctions in these metabolic pathways.
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PMID:Urinary biomarker and treatment mechanism of Rhizoma Alismatis on hyperlipidemia. 2757 31

The main objective of this study was to investigate the ameliorative effects of aspirin eugenol ester (AEE) in hyperlipidemic rat. After five-week oral administration of AEE in high fat diet (HFD)-induced hyperlipidemic rats, the impact of AEE on plasma and urine metabonomics was investigated to explore the underlying mechanism by UPLC-Q-TOF/MS analysis. Blood lipid levels and histopathological changes of liver, stomach and duodenum were also evaluated after AEE treatment. Without obvious gastrointestinal (GI) side effects, AEE significantly relieved fatty degeneration of liver and reduced triglyceride (TG), low density lipoprotein (LDL) and total cholesterol (TCH) (P<0.01). Clear separations of metabolic profiles were observed among control, model and AEE groups by using principal component analysis (PCA) and orthogonal partial least-squares-discriminate analysis (OPLS-DA). 16 endogenous metabolites in plasma and 18 endogenous metabolites in urine involved in glycerophospholipid metabolism, fatty acid metabolism, fatty acid beta-oxidation, amino acid metabolism, TCA cycle, sphingolipid metabolism, gut microflora and pyrimidine metabolism were considered as potential biomarkers of hyperlipidemia and be regulated by AEE administration. It might be concluded that AEE was a promising drug candidate for hyperlipidemia treatment. These findings could contribute to the understanding of action mechanisms of AEE and provide evidence for further studies.
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PMID:UPLC-Q-TOF/MS-based urine and plasma metabonomics study on the ameliorative effects of aspirin eugenol ester in hyperlipidemia rats. 2873 7