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)

To investigate the efficacy of the intake of vinegar for prevention of hyperlipidaemia, we examined the effect of dietary acetic acid, the main component of vinegar, on serum lipid values in rats fed a diet containing 1 % (w/w) cholesterol. Animals were allowed free access to a diet containing no cholesterol, a diet containing 1 % cholesterol without acetic acid, or a diet containing 1 % cholesterol with 0.3 % (w/w) acetic acid for 19 d. Then, they were killed after food deprivation for 7 h. Cholesterol feeding increased serum total cholesterol and triacylglycerol levels. Compared with the cholesterol-fed group, the cholesterol and acetic acid-fed group had significantly lower values for serum total cholesterol and triacylglycerols, liver ATP citrate lyase (ATP-CL) activity, and liver 3-hydroxy-3-methylglutaryl-CoA content as well as liver mRNA levels of sterol regulatory element binding protein-1, ATP-CL and fatty acid synthase (P<0.05). Further, the serum secretin level, liver acyl-CoA oxidase expression, and faecal bile acid content were significantly higher in the cholesterol and acetic acid-fed group than in the cholesterol-fed group (P<0.05). However, acetic acid feeding affected neither the mRNA level nor activity of cholesterol 7alpha-hydroxylase. In conclusion, dietary acetic acid reduced serum total cholesterol and triacylglycerol: first due to the inhibition of lipogenesis in liver; second due to the increment in faecal bile acid excretion in rats fed a diet containing cholesterol.
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PMID:Dietary acetic acid reduces serum cholesterol and triacylglycerols in rats fed a cholesterol-rich diet. 1661 81

Hyperlipidemia can be effectively treated either with niacin or HMG-CoA reductase inhibitor (statin), or a combination of both. Few reports showed the effects of the combination regimen with niacin and statin on hemostatic functions. We conducted a single-center, double-blind, double-dummy, randomized, two-arm study to assess the effects of the niacin extended-release/lovastatin therapy in a fixed-dose formulation and of simvastatin on lipid lowering and two fibrinolytic parameters, fibrinogen and d-dimer. All patients were enrolled according to NCEP-ATP III guidelines and underwent a placebo run-in period of 4 weeks before being randomized to either niacin extended-release/lovastatin tablets (500/20 mg) once daily (n = 36) or simvastatin capsule (20 mg) once daily (n = 34). After 16 weeks of treatment, both groups of patients showed significantly reduced low-density lipoprotein cholesterol and total cholesterol (LDL-C, p < 0.001 and < 0.001, respectively, p = 0.159 between the groups; TC, p < 0.001 and < 0.001, respectively, p = 0.018 between the groups). Both drugs were well tolerated. Only in the group treated with niacin extended-release/lovastatin was fibrinogen concentration significantly reduced after treatment (2.48 +/- 0.65 to 1.99 +/- 0.62 g/L, p = 0.008). No difference was found with d-dimer in either group. This study shows that both niacin extended-release/lovastatin and simvastatin are effective and well-tolerated lipid-lowering drugs in Taiwanese patients with dyslipidemia. A combinational treatment with niacin extended-release/lovastatin may provide additional benefit in fibrinolysis.
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PMID:Randomized comparative study of the effects of treatment with once-daily, niacin extended-release/lovastatin and with simvastatin on lipid profile and fibrinolytic parameters in Taiwan. 1679 62

Metabolic syndrome (MS) is the term that encompasses metabolic risk factors that may lead to atherosclerotic cardiovascular disease. This study was undertaken to investigate the prevalence of MS in patients with ischemic cerebrovascular disease (CVD), according to National Cholesterol Education Program/Adult Treatment Panel III (ATP III) criteria. A total of 40 patients who were referred to the emergency department and given a diagnosis of CVD were included in this study. Detailed medical histories, physical examination findings, heights, weights, and waist circumferences of patients were recorded. Fasting blood glucose levels and lipid profiles of patients were evaluated. Those with hypertension, diabetes, or hyperlipidemia were regarded as meeting at least 1 of the ATP III criteria. Study results were compared, especially between females and males. In all, 55% of patients were female, and 70% were older than 65 y. Blood pressure over 130/85 mm Hg was assessed in 60% of patients. Among female patients, 81.8% had a waist circumference greater than 88 cm; 50% of male patients had a waist circumference over 102 cm. A fasting blood glucose level above 110 mg/dL was identified in 57.5% of patients. Serum triglyceride levels in 30% of patients were above 150 mg/L. It was noted that 33.3% of male patients had a high-density lipoprotein (HDL) level below 40 mg/L, and in 68.2% of female patients, an HDL level below 50 mg/dL was recorded. According to these findings, 14 of 22 female patients (64%) and 13 of 18 male patients (72%) were identified as having MS. High rates of stroke associated with MS reveal the importance of forthcoming preventive approaches.
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PMID:Metabolic syndrome and its association with ischemic cerebrovascular disease. 1691 32

Ligands for peroxisome proliferator-activated receptors alpha (PPARalpha) are clinically used for the treatment of patients with hyperlipidemia. As we have previously shown, a synthetic ligand of PPARalpha, fenofibrate, has a stimulatory effect on insulin secretion in clonal hamster insulinoma beta-cell line HIT-T15 cells. We have also demonstrated that fenofibrate directly inhibits ATP-sensitive potassium (K(ATP)) channels, an effect independent of PPARalpha. In this study, fenofibrate was shown to be able to reduce voltage-dependent K(+) (K(v)) channel currents in voltage-independent manner. Therefore, fenofibrate may modulate insulin secretion not only via inhibition of K(ATP) channels but also via reduction of the K(v) channel current.
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PMID:Effect of peroxisome proliferator-activated receptor alpha ligand fenofibrate on K(v) channels in the insulin-secreting cell line HIT-T15. 1735 36

The extracts from the roots of Salvia miltiorrhiza Bunge (Danshen) are widely and traditionally used in the treatment of angina pectoris, acute myocardial infarct, hyperlipidemia and stroke in China and other Asian countries. In this study, we have investigated the role of P-glycoprotein (P-gp) in the intestinal absorption of tanshinone IIA (TSA), a major active constituent of Danshen, using several in vitro and in vivo models. The oral bioavailability of TSA was about 2.9-3.4% in rats, with non-linear pharmacokinetics when its dosage increased. In a single pass rat intestinal perfusion model, the permeability coefficients (P(app)) based on TSA disappearance from the luminal perfusates (P(lumen)) were 6.2- to 7.2-fold higher (P < 0.01) than those based on drug appearance in mesenteric venous blood (P(blood)). The P(blood), but not P(lumen), was significantly increased when co-perfused with verapamil, or quinidine (both P-gp inhibitors). The uptake and efflux of TSA in confluent Caco-2 cells were significantly altered in the presence of verapamil, quinidine, MK-571, or probenecid. The transport of TSA across Caco-2 monolayers was pH-, temperature- and ATP-dependent. Furthermore, the transport from the apical (AP) to basolateral (BL) side of the Caco-2 monolayers was 3.3- to 8.5-fold lower than that from the BL to AP side, but such a polarized transport was attenuated by co-incubated verapamil or quinidine. A polarized transport was also observed in the control MDCKII cells and more apparent in MDR1-MDCKII monolayers, with the P(app) values of TSA in the BL-AP direction being 7- to 9-fold higher in MDR1-MDCKII monolayers than those in the control MDCKII cells. Moreover, TSA significantly inhibited P-gp-mediated transport of digoxin in P-gp-overexpressing membrane vesicles with an IC(50) of 2.6 microM, but stimulated vanadate-sensitive P-gp ATPase activity with estimated K(m) and V(max) values of 10.70 +/- 0.69 microM and 67.65 +/- 1.31 nmol/min/mg protein, respectively. TSA was extensively metabolized to tanshinone IIB (TSB), and two other oxidative metabolites in rat liver microsomes, but the formation rate of TSB in rat intestinal microsomes was only about 1/10 of that in liver microsomes. These findings indicate that TSA is a substrate and reversing agent for P-gp; and P-gp-mediated efflux of TSA into the gut lumen and the first-pass metabolism contribute to the low oral bioavailability. Further studies are needed to explore the role of other drug transporters and first-pass metabolism in the low bioavailability of TSA.
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PMID:Role of P-glycoprotein in the intestinal absorption of tanshinone IIA, a major active ingredient in the root of Salvia miltiorrhiza Bunge. 1750 22

Metabolic syndrome is a group of factors which increase the risk for development of diabetes, cardiovascular diseases and includes insulin resistance, abdominal adiposity, hyperlipidemia, hypertension and other disorders. Changes in prothrombotic and proinflammatory markers have been observed. Aim of this study was to asses the concentration of fibrinogen and other humoral markers of metabolic syndrome in type 2 diabetic patients. 77 patients both sexes, age 46-83 years have been included. Based on ATP III criteria patients were divided in two groups. Group I - diabetic patients with metabolic syndrome and Group II - diabetic patients without metabolic syndrome. Each group was divided in two subgroups, males and females. The plasma concentration of fibrinogen and humoral markers of metabolic syndrome (triglycerides, cholesterol and glucose) have been evaluated. There were 49.4% patients out of total who met the criteria for metabolic syndrome. Patients in Group I weight in average more then the patients in Group II. Average systolic and diastolic blood pressure values were in all groups and subgroups higher than recommended. Humoral markers of metabolic syndrome were significantly higher (p<0.05) in Group I (triglycerides 2.7+/-0,2 mmol/L, total cholesterol 6.0+/-0.2 mmol/L) compared to Group II (triglycerides up to 1,7 mmol/L, total cholesterol in serum up to 5,2 mmol/L ). Concentration of glucose in both groups was significantly higher compared to referral values. Average plasma fibrinogen concentration was 4.0+/-0.1 g/Lwithout significant differences between Group I and II. Females from Group I had significantly higher fibrinogen concentration (p=0.003) then the males from the same group (females 4.4+/-0.2 g/L vs. males 3.7+/-0.1 g/L). There was no difference in fibrinogen concentration between female and male patients in Group II. Fibrinogen plasma concentration is elevated in all type 2 diabetic patients without significant differences between subjects with or without metabolic syndrome.
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PMID:[Metabolic syndrome and plasma fibrinogen in type 2 diabetic patients]. 1758 66

The "metabolic syndrome" consists of some common risk factors for cardiovascular diseases: central obesity, diabetes mellitus, hyperlipidaemia and hypertension. The metabolic syndrome (MTS) leads to increased morbidity and mortality and to higher direct and indirect healthcare costs. The MTS can be diagnosed using the NCEP/ATP III criteria. The prevalence of the MTS in Germany is estimated at 23.8% and is expected to rise further, due to increasing obesity among children and adolescents. Studies have shown that the MTS leads to increased cardiovascular and total mortality and thus to a decreased life expectancy. Studies estimating the total costs of MTS are missing, but after addition of the costs for all the risk factors it is assumed that MTS costs amount to 5% of total healthcare costs. This is the result of the more frequent demand of health services and longer hospitalisation of patients with MTS. Even moderate weight loss can decrease the rates of morbidity and healthcare costs.
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PMID:[The metabolic syndrome]. 1791 84

Diabetes mellitus (DM) is an important cardiovascular risk factor and is associated with abnormalities in endothelial and vascular smooth muscle cell function, evoked by chronic hyperglycemia and hyperlipidemia. Chronic insulin deficiency or resistance is marked by decreases in the intensity of glucose transport, glucose phosphorylation, and glucose oxidation, plus decreases in ATP levels in cardiac myocytes. It is important to search for new agents that promote glucose consumption in the heart and partially inhibit extensive fatty acid beta-oxidation observed in diabetic, ischemia. When the oxygen supply for myocardium is decreased, the heart accumulates potentially toxic intermediates of fatty acid beta-oxidation, that is, long-chain acylcarnitine and long-chain acyl-CoA metabolites. Exogenous glucose and heart glycogen become an important compensatory source of energy. Therefore we studied the effect of the antidiabetic 1,4-dihydropyridine compound cerebrocrast at concentrations from 10(-10) M to 10(-7) M on isolated rat hearts using the method of Langendorff, on physiological parameters and energy metabolism. Cerebrocrast at concentrations from 10(-10) M to 10(-7) M has a negative inotropic effect on the rat heart. It inhibits L-type Ca(2+)channels thereby diminishing the cellular Ca(2+) supply, reducing contractile activity, and oxygen consumption, that normally favors enhanced glucose uptake, metabolism, and production of high-energy phosphates (ATP content) in myocardium. Cerebrocrast decreases heart rate and left ventricular (LV) systolic pressure; at concentrations of 10(-10) M and 10(-9) M it evokes short-term vasodilatation of coronary arteries. Increase of ATP content in the myocytes induced by cerebrocrast has a ubiquitous role. It can preserve the integrity of the cell plasma membranes, maintain normal cellular function, and inhibit release of lactate dehydrogenase (LDH) from cells that is associated with diabetes and heart ischemia. Administration of cerebrocrast together with insulin shows that both compounds only slightly enhance glucose uptake in myocardium, but significantly normalize the rate of contraction and relaxation ( +/- dp/dt). The effect of insulin on coronary flow is more pronounced by administration of insulin together with cerebrocrast at a concentration of 10(-7) M. Cerebrocrast may promote a shift of glucose consumption from aerobic to anerobic conditions (through the negative inotropic properties), and may be very significant in prevention of cardiac ischemic episodes.
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PMID:Acute effect of antidiabetic 1,4-dihydropyridine compound cerebrocrast on cardiac function and glucose metabolism in the isolated, perfused normal rat heart. 1799 Feb 88

Therapeutic strategies to protect the ischemic myocardium have been studied extensively. Reperfusion is the definitive treatment for acute coronary syndromes, especially acute myocardial infarction; however, reperfusion has the potential to exacerbate lethal tissue injury, a process termed "reperfusion injury." Ischemia/reperfusion injury may lead to myocardial infarction, cardiac arrhythmias, and contractile dysfunction. Ischemic preconditioning of myocardium is a well described adaptive response in which brief exposure to ischemia/reperfusion before sustained ischemia markedly enhances the ability of the heart to withstand a subsequent ischemic insult. Additionally, the application of brief repetitive episodes of ischemia/reperfusion at the immediate onset of reperfusion, which has been termed "postconditioning," reduces the extent of reperfusion injury. Ischemic pre- and postconditioning share some but not all parts of the proposed signal transduction cascade, including the activation of survival protein kinase pathways. Most experimental studies on cardioprotection have been undertaken in animal models, in which ischemia/reperfusion is imposed in the absence of other disease processes. However, ischemic heart disease in humans is a complex disorder caused by or associated with known cardiovascular risk factors including hypertension, hyperlipidemia, diabetes, insulin resistance, atherosclerosis, and heart failure; additionally, aging is an important modifying condition. In these diseases and aging, the pathological processes are associated with fundamental molecular alterations that can potentially affect the development of ischemia/reperfusion injury per se and responses to cardioprotective interventions. Among many other possible mechanisms, for example, in hyperlipidemia and diabetes, the pathological increase in reactive oxygen and nitrogen species and the use of the ATP-sensitive potassium channel inhibitor insulin secretagogue antidiabetic drugs and, in aging, the reduced expression of connexin-43 and signal transducer and activator of transcription 3 may disrupt major cytoprotective signaling pathways thereby significantly interfering with the cardioprotective effect of pre- and postconditioning. The aim of this review is to show the potential for developing cardioprotective drugs on the basis of endogenous cardioprotection by pre- and postconditioning (i.e., drug applied as trigger or to activate signaling pathways associated with endogenous cardioprotection) and to review the evidence that comorbidities and aging accompanying coronary disease modify responses to ischemia/reperfusion and the cardioprotection conferred by preconditioning and postconditioning. We emphasize the critical need for more detailed and mechanistic preclinical studies that examine car-dioprotection specifically in relation to complicating disease states. These are now essential to maximize the likelihood of successful development of rational approaches to therapeutic protection for the majority of patients with ischemic heart disease who are aged and/or have modifying comorbid conditions.
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PMID:Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and postconditioning. 1804 61

This retrospective cohort study conducted at the Durham Veterans Affairs Medical Center evaluated the effectiveness and safety of lipid-lowering therapy (LLT) in a HIV-infected population as compared with a general population with hyperlipidaemia. Fifty-three HIV-infected subjects who developed dyslipidaemia and 53 age-matched non-HIV-infected subjects receiving LLT were selected. Efficacy of LLT was assessed after three and six months. Non-HIV-infected subjects were more likely to achieve total cholesterol (TC) goals at three and six months (P = 0.045, P = 0.005) and triglyceride (TG) goals at six months (P = 0.017). Less than 45% of HIV-infected subjects met National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) goals at three or six months. While non-HIV-infected subjects were more likely to achieve TC and TG goals than HIV-infected subjects, overall achievement of NCEP III goals was poor. This result was likely due to treatment with inappropriately low doses of statins.
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PMID:A comparison of the effectiveness of lipid-lowering therapy between HIV- and non-HIV-infected subjects with hyperlipidaemia. 1807 21


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