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

The triglyceride-lowering effect of pitavastatin, a potent 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, was investigated in a rat model of postprandial lipemia. Plasma triglyceride levels started to increase 4 h after the fat load, reached the maximum at 6 h and then gradually decreased. A single dose of pitavastatin (1 mg/kg) significantly suppressed chylomicron-triglyceride secretion into the lymph by 40% and delayed the elevation of plasma triglyceride. Pitavastatin at 1 mg/kg decreased the 6-h plasma triglyceride levels by 53% and at 0.5 mg/kg decreased the 0-12 h area under the curve (AUC) of triglyceride levels by 56%. Atorvastatin also caused decreases, but to a lesser extent. Pitavastatin, and atorvastatin to a lesser extent, reduced the activity of the intestinal microsomal triglyceride transfer protein (MTP) at 6 h. These results suggested that a single dose of pitavastatin lowered postprandial triglyceride levels in rats by decreasing chylomicron-triglyceride secretion, probably through a reduction of intestinal MTP activity and triglyceride droplet formation in the endoplasmic reticulum.
 ...
PMID:Triglyceride-lowering effect of pitavastatin [corrected] in a rat model of postprandial lipemia. 1219 89

Nephrotic syndrome (NS) is characterized by the presence of proteinuria and hyperlipidemia. However, ingestion of soy protein has a hypolipidemic effect. The present study was designed to determine whether the ingestion of a 20% soy protein diet regulates the expression of hepatic sterol regulatory element binding protein (SREBP)-1, fatty acid synthase (FAS), malic enzyme, beta-hydroxy-beta-methylglutaryl-CoA (HMG-CoA) reductase (r) and synthase (s), and LDL receptor (r), and to assess whether soy protein improves lipid and renal abnormalities in rats with chronic NS. Male Wistar rats were injected with vehicle or with puromycin aminonucleoside to induce NS and were fed either 20% casein or soy protein diets for 64 d. NS rats fed 20% soy protein had improved creatinine clearance and reduced proteinuria, hypercholesterolemia, hypertriglyceridemia, as well as VLDL-triglycerides and LDL cholesterol compared with NS rats fed the 20% casein diet. In addition, the soy protein diet decreased the incidence of glomerular sclerosis, and proinflammatory cytokines in kidney. Ingestion of the soy protein diet by control rats reduced the gene expression of SREBP-1, malic enzyme, FAS and increased HMG-CoAr, HMG-CoAs and LDLr. However, NS rats fed either casein or soy protein diets had low insulin concentrations with reductions in SREBP-1, FAS and malic enzyme expression compared with control rats fed the casein diet. NS rats fed the soy diet also had lower HMG-CoAr and LDLr mRNA levels than NS rats fed casein. In conclusion, the beneficial effects of soy protein on lipid metabolism are modulated in part by SREBP-1. However, in NS rats, the benefit may be through a direct effect of this protein on kidney rather than mediated by changes in expression of hepatic lipid metabolism genes.
 ...
PMID:A soy protein diet alters hepatic lipid metabolism gene expression and reduces serum lipids and renal fibrogenic cytokines in rats with chronic nephrotic syndrome. 1222 Dec 9

Rhabdomyolysis is a known complication of hepatic 3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitor (statin) therapy for posttransplant hyperlipidemia, and thus monitoring for this effect is indicated. We report a case of an herbal preparation-induced rhabdomyolysis in a stable renal-transplant recipient, attributed to the presence of red yeast rice (Monascus purpureus) within the mixture. The condition resolved when consumption of the product ceased. Rice fermented with red yeast contains several types of mevinic acids, including monacolin K, which is identical to lovastatin. We postulate that the interaction of cyclosporine and these compounds through the cytochrome P450 system resulted in the adverse effect seen in this patient. Transplant recipients must be cautioned against using herbal preparations to lower their lipid levels to prevent such complications from occurring.
 ...
PMID:Rhabdomyolysis due to red yeast rice (Monascus purpureus) in a renal transplant recipient. 1243 74

High-sensitivity C-reactive protein (hs-CRP) is positively associated with the prevalence of coronary artery disease by epidemiologic data. Prospective studies indicate that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors reduced the plasma hs-CRP concentration and the risk of recurrent coronary events after myocardial infarction. Type 2 diabetes is associated with high mortality risk of coronary heart disease and this high risk may be involved in the inflammatory factors. We have therefore conducted a prospective study to assess whether simvastatin can rapidly reduce the plasma hs-CRP concentration in type 2 diabetic patients with hyperlipidemia. Seventeen type 2 diabetic patients with hyperlipidemia were enrolled in the study after 6 weeks on a lipid-lowering diet. Fourteen patients completed the study, taking simvastatin 20 mg daily for 8 weeks. Fasting blood samples were collected from each patient before and after 8-week administration of simvastatin. In response to 8-week administration of simvastatin, hs-CRP levels significantly decreased from 0.312+/-0.057 to 0.193+/-0.045 mg/dl (P<.01). Plasma LDL cholesterol also decreased significantly from 130+/-9 to 74+/-3 mg/dl (P=.001). This study shows that plasma hs-CRP concentration can be reduced by 8-week administration of simvastatin in type 2 diabetic patients with hyperlipidemia.
 ...
PMID:Simvastatin reduces plasma concentration of high-sensitivity C-reactive protein in type 2 diabetic patients with hyperlipidemia. 1247 21

We evaluated the economic efficiency as well as the clinical effectiveness on serum lipid levels of a change in drug therapy from bezafibrate or a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor to fenofibrate. Subjects were 26 outpatients suffering from type IIb or type IV hyperlipidemia who visited our hospital between October 2000 and January 2001. Medication doses, and serum lipid levels were recorded prior to the change to fenofibrate and at 6 months after the change. Medical costs were also calculated at the same time points. A significant reduction in medical costs of 14.9% was observed following the change to fenofibrate. Serum lipid levels were not significantly different, although an increase in low density lipoprotein-cholesterol (LDL-cholesterol) was observed in patients changing from the HMG-CoA reductase inhibitor. The actual drug costs were reduced by 21.8% in the bezafibrate to fenofibrate group and by 23.7% in the HMG-CoA reductase inhibitor to fenofibrate group. Although the drug costs of changing to fenofibrate decreased significantly, other costs remained almost unchanged.
 ...
PMID:Pharmacoeconomic evaluation of anti-hyperlipidemic agent fenofibrate. 1251 Mar 91

The great importance of HMGCoA reductase inhibitors (statins) in treatment of hyperlipidemia is well known, and accepted. Numerous multicenter trials have shown the effectiveness of statins in lowering cholesterol concentration, slowing down progression of atherosclerosis, and in decreasing number of cardio-vascular incidents. However, since the discovery of statins experiments have been carried out showing other mechanisms of action of these drugs. Many circumstances expose the antiproliferative, and antiinflammatory influence of HMGCoA reductase inhibitors. This paper presents a review of the studies on these mechanisms with a special emphasis on their nephroprotective role.
 ...
PMID:[Mechanisms of statin nephroprotective actions]. 1251 41

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are widely used antilipidemic agents that are also immunomodulatory. We evaluated possible effects of these agents after lung transplantation by comparing outcomes of 39 allograft recipients, who were prescribed statins for hyperlipidemia, with those of 161 contemporaneous control recipients who did not receive these drugs. Acute rejection (>or= Grade II) was less frequently found in the statin group (15.1 versus 25.6% of biopsies, p < 0.01). None of 15 recipients started on statins during postoperative Year 1 developed obliterative bronchiolitis, whereas the cumulative incidence of this complication among control subjects was 37% (p < 0.01). Total cellularity, as well as proportions of inflammatory neutrophils and lymphocytes, were significantly lower in bronchoalveolar lavages of statin recipients. Among double lung recipients, those taking statins had significantly better spirometry: FVC (80 +/- 2 versus 70 +/- 1%) and FEV1 (87 +/- 2 versus 70 +/- 1%), as percentages of predicted values, and absolute FEV1/FVC (83.4 +/- 1.2 versus 78.6 +/- 0.5) (all p < 0.01). The 6-year survival of recipients taking statins (91%) was much greater than that of control subjects (54%) (p < 0.01). These data suggest statin use may have substantial clinical benefits after pulmonary transplantation.
 ...
PMID:Statin use is associated with improved function and survival of lung allografts. 1261 29

Demonstration of the long-term efficacy of GH replacement in GH-deficient adults has depended on a combination of single-centre studies and data from large multinational databases, which, by virtue of their size, are likely to detect rare adverse events and also permit analysis of mortality rates. The Pharmacia International Metabolic Surveillance (KIMS) study (a pharmacoepidemiological survey of the safety and efficacy of GH replacement in adults, sponsored by Pharmacia) is currently the largest database, with information on over 8000 patients from a total of 27 countries. Abundant epidemiological evidence confirms that hypopituitarism is associated with premature mortality, with an increase in cardiovascular and cerebrovascular disease as a primary underlying cause. Central adiposity, hyperlipidaemia, insulin resistance, and diabetes mellitus are common in adults with hypopituitarism. GH replacement is associated with improvements in central fat mass and mean reductions in serum total and low-density lipoprotein cholesterol which may be additive to those achieved with hydroxymethylglutaryl-coenzyme A reductase inhibitors. These beneficial effects are maintained for at least 2 Years after initiation of therapy, as are reductions in central adiposity, with similar benefits seen in men and women when the GH dose is titrated to achieve a serum IGF-I between the median and the upper end of the age-related reference range. Fasting plasma glucose and glycated haemoglobin increase, usually within the reference range, during prolonged GH replacement, but do not tend to rise further above baseline in subjects with pre-existing impaired glucose tolerance. Bone remodelling increases during GH replacement therapy, but indices tend to return to baseline within 5 Years of commencing treatment. Bone mineral density increases in men whereas, in women, improvement is limited to stabilisation of bone density. Data from the KIMS study demonstrate that prolonged GH replacement is associated with a reduction in the number of patients requiring assistance with daily living and a significant reduction in sick leave and hospital admissions. GH replacement therapy improves psychological well-being, particularly in those patients with the greatest deficit prior to treatment, with improvement maintained beyond 6 Months of therapy and sustained during long-term follow-up. Data from the KIMS population show that there is no increase in the overall occurrence of de novo neoplasia or the rate of regrowth of primary pituitary tumours. There is an apparent increase in intracranial neoplasia, which may be an artefact of comparing a surveillance population with general population data. Unlike mortality in untreated hypopituitary GH-deficient patients, mortality in the KIMS study is currently similar to that predicted for the normal population.
 ...
PMID:Long-term experience with GH replacement therapy: efficacy and safety. 1267 Feb 95

The triglyceride (TG)-lowering effect of pitavastatin (CAS 147526-32-7), a potent 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, was investigated in a guinea pig model of post-prandial lipemia. Plasma TG levels started to rise 2 h after the fat load, reached the maximum at 8 h and then gradually decreased. A 14-day dose of pitavastatin at 3 mg/kg decreased the 8 h plasma TG levels by 59%, and the 0-12 h area under the curve (AUC) of TG levels above the initial levels, by 77%. This effect was also shown with 30 mg/kg of atorvastatin (CAS 134523-00-5), and the same dose of simvastatin (CAS 79902-63-9). The intensity of the action was equivalent for pitavastatin and atorvastatin, but weaker with simvastatin. In order to clarify the mechanism of this action, the effect of pitavastatin exerted on the activity of microsomal triglyceride transfer protein (MTP), which participates in the secretion to the lymph vessel of chyromicron (CM)-TG in the small intestine, and the activity of lipoprotein lipase (LPL), which is the hydrolysis enzyme of the very low density lipoprotein (VLDL)-TG and CM-TG, was examined. However, an influence on the activity of MTP or LPL by pitavastatin was not shown. These results suggested that pitavastatin lowered the postprandial TG levels in guinea pigs by accelerating the remnant clearance, probably through the enhancement of the low density lipoprotein (LDL) receptor. This effect is expected to improve postprandial lipemia.
 ...
PMID:Triglyceride-lowering effect of pitavastatin in a guinea pig model of postprandial lipemia. 1270 69

The observation that almost half of all myocardial infarctions and strokes occur in persons without elevated levels of low-density lipoprotein cholesterol has prompted the study of factors other than hyperlipidemia that contribute to the development of atherosclerosis. A growing body of evidence indicates that inflammation plays a substantial role in plaque progression and rupture. Research interest has increasingly focused on biomarkers of inflammation as a means of predicting more accurately which patients are at high risk for cardiovascular disease (CVD). Clinical studies indicate that C-reactive protein (CRP), a marker of systemic inflammation, independently predicts cardiovascular risk in healthy persons as well as in persons with established CVD and those with acute ischemia. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, have been shown to reduce levels of CRP through mechanisms independent of their effects on lipid levels. Initial clinical studies also suggest that CRP levels may have utility in the targeting of statin therapy, particularly in primary prevention. These results need direct testing in large, prospective clinical trials to determine whether statin therapy will benefit persons without overt hyperlipidemia but with evidence of systemic inflammation. Confirmation of these preliminary findings, if incorporated into evidence-based guidelines, may profoundly change the approach to diagnosis and treatment of CVD.
 ...
PMID:Connecting the role of C-reactive protein and statins in cardiovascular disease. 1270 38


<< Previous 1 2 3 4 5 6 7 8 9 10