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)

A case is presented to illustrate the need for technical care when handling blood gas samples. The physics of solubility are used to show hour samples changed their oxygen tension (pO2) during handling, while investigating a clinical case to show the effect of hyperlipidemia on blood gases. It appeared that inadvertent access to air allowed atmospheric oxygen to equilibrate with the sample. The physical laws predicting the effect of partial pressure and temperature on gas solubility in a liquid are illustrated by the pO2 levels measured in this case. Effects due to hyperlipidemia were not observed. The calculations are described in detail. Brief suggestions for sample handling to avoid misleading results from such cases are discussed.
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PMID:The effect of solubility and hyperlipidemia on perioperative arterial blood gas tensions. 919 59

Carvedilol is a novel, multiple-action cardiovascular drug that is currently approved in many countries for the treatment of hypertension. The reduction in blood pressure produced by carvedilol results primarily from beta-adrenoceptor blockade and vasodilation, the latter resulting from alpha 1-adrenoceptor blockade. These actions, as well as several of the other activities of carvedilol, are associated with cardioprotection in animal models that occurs to a degree that is greater than that observed with other drugs. The multiple actions of carvedilol may also provide the underlying rationale for the use of the drug in the treatment of coronary artery disease and congestive heart failure. By virtue of being both a beta-blocker and a vasodilator, carvedilol significantly decreases myocardial work by reducing all three components of myocardial oxygen demand, namely, heart rate, contractility, and wall tension. The vasodilatory effects of carvedilol reduce afterload, and the resulting decrease in impedance to left ventricular ejection offsets the negative inotropic effect that would normally result from beta-blockade. As a consequence, stroke volume and cardiac output are maintained or even increased in animals and in patients with congestive heart failure who are treated with carvedilol. Carvedilol and several of its metabolites are potent antioxidants, and this activity may account, in part, for the cardioprotective effects of the drug observed in animal models of acute myocardial ischemia and, in theory, could also serve to protect the myocardium of patients with hypertension, coronary artery disease, and congestive heart failure, in which oxidative stress is now recognized to occur. The antioxidant effects of carvedilol may both inhibit the direct cytotoxic actions of reactive oxygen radicals and prevent oxygen-radical induced activation of transcription factors and genes associated with inflammatory and remodeling processes. Accordingly, carvedilol inhibits the gene expression of the intracellular adhesion molecule-1 (ICAM-1), an adhesion molecule for polymorphonuclear leukocytes, which typically infiltrate the myocardium under conditions of ischemia and may exacerbate ischemic injury. The antioxidant activity of carvedilol has been shown to inhibit the oxidation of low density lipoprotein (LDL) in vitro, thereby preventing the formation of this cytotoxic and atherogenic form of LDL. It follows, therefore, that in animal models of hyperlipidemia, carvedilol attenuates aortic lipid accumulation and decreases the aortic content of monocytes and foam cells, and at the same time it has been shown to preserve endothelial integrity and function. These actions of carvedilol are not shared by other beta-blockers or by other drugs currently used in the management of hypertension, coronary artery disease, or congestive heart failure. The multiple actions of carvedilol may provide the underlying pharmacologic rationale for the use of this drug in the treatment of patients with coronary artery disease or congestive heart failure, and these actions may account, at least in part, for the reduction in mortality produced by carvedilol in clinical trials involving patients with congestive heart failure. Likewise, these actions of carvedilol may also provide protection, beyond that afforded from reduction in blood pressure, against secondary organ damage in hypertensive patients treated with the drug.
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PMID:Pharmacology of carvedilol: rationale for use in hypertension, coronary artery disease, and congestive heart failure. 921 Oct 17

Polymerized hemoglobin solutions (Hb-based oxygen carriers; HBOCs) and a second-generation perfluorocarbon (PFC) emulsion (Perflubron) are in clinical trials as temporary oxygen carriers ("blood substitutes"). Plasma and serum samples from patients receiving HBOCs look markedly red, whereas those from patients receiving PFC appear to be lipemic. Because hemolysis and lipemia are well-known interferents in many assays, we examined the effects of these substances on clinical chemistry, immunoassay, therapeutic drug, and coagulation tests. HBOC concentrations up to 50 g/L caused essentially no interference for Na, K, Cl, urea, total CO2, P, uric acid, Mg, creatinine, and glucose values determined by the Hitachi 747 or Vitros 750 analyzers (or both) or for immunoassays of lidocaine, N-acetylprocainamide, procainamide, digoxin, phenytoin, quinidine, or theophylline performed on the Abbott AxSym or TDx. Gentamycin and vancomycin assays on the AxSym exhibited a significant positive and negative interference, respectively. Immunoassays for TSH on the Abbott IMx and for troponin I on the Dade Stratus were unaffected by HBOC at this concentration. Tests for total protein, albumin, LDH, AST, ALT, GGT, amylase, lipase, and cholesterol were significantly affected to various extents at different HBOC concentrations on the Hitachi 747 and Vitros 750. The CK-MB assay on the Stratus exhibited a negative interference at 5 g/L HBOC. HBOC interference in coagulation tests was method-dependent-fibrometer-based methods on the BBL Fibro System were free from interference, but optical-based methods on the MLA 1000C exhibited interferences at 20 g/L HBOC. A 1:20 dilution of the PFC-based oxygen carrier (600 g/L) caused no interference on any of these chemistry or immunoassay tests except for amylase and ammonia on the Vitros 750 and plasma iron on the Hitachi 747.
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PMID:Effect of hemoglobin- and Perflubron-based oxygen carriers on common clinical laboratory tests. 929 68

Two series of studies were made to assess probucol medicines (lipomal, "Alkaloid"; fenbutol "Akrikhin") effect on clinical symptoms, lipid metabolism, primary and secondary products of lipid peroxidation, activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase) in atherosclerotic patients with hyperlipidemia type IIA and IIB. In both series probucol reduced frequency of anginal attacks, content of total cholesterol and LDL cholesterol. HDL cholesterol remained unchanged or reduced insignificantly. Lipoperoxides and malonic dialdehyde levels in plasma progressively lowered against activation of antioxidant enzymes. These biochemical parameters returned to initial values within 3 months since the drug discontinuation. It is evident that antiatherogenic effect of probucol is due to indirect activation of natural defense systems responsible for enzymic detoxication of active oxygen forms and lipoperoxides rather than to direct interaction of this synthetic antioxidant with lipid radicals.
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PMID:[The antioxidant probucol as a regulator of the intensity of free-radical lipid peroxidation processes in the blood of patients with coronary atherosclerosis]. 941 23

The generation of nitric oxide by the vascular endothelium maintains a continuous vasodilator tone that is essential for the regulation of blood flow and blood pressure. Nitric oxide also contributes to the control of platelet aggregation and has important antiatherogenic effects. These properties are mediated by the action of constitutive nitric oxide synthase and subsequent activation by nitric oxide of soluble guanylate cyclase. Impaired release of nitric oxide occurs in most animal and human models of hypertension, contributing to the increased peripheral resistance and most likely to the development of cardiovascular complications. Antihypertensive medications (angiotensin-converting enzyme [ACE] inhibitors and calcium channel blockers) appear to prevent the impairment of nitric oxide-mediated vasodilation in experimental hypertension, though in humans the data are not as clear. Reduced nitric oxide release appears therefore to be a consequence rather than a cause of high blood pressure, and the reduction in blood pressure per se is most important. In hyperlipidaemia, endothelium-dependent relaxations are reduced probably due to the inhibitory action of oxidized low-density lipoproteins on endothelium-dependent relaxations. Lipid-lowering strategies and, more recently, ACE inhibition have been demonstrated to improve nitric oxide dependent coronary vasodilation in hypercholesterolaemic patients with and without atheromatous coronary disease. Nitric oxide dependent vasodilation is also impaired in insulin- and non-insulin-dependent diabetes as well as in healthy aging. Endothelial dysfunction may be improved in non-insulin-dependent diabetes by administration of the antioxidants, supporting the hypothesis that nitric oxide inactivation by oxygen-derived free radicals contributes to abnormal vascular reactivity in diabetes.
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PMID:Impairment and restoration of nitric oxide-dependent vasodilation in cardiovascular disease. 948 1

Hyperlipidemia is frequently associated with hyperinsulinemia, but because the effects of fatty acids on insulin secretion in in vitro studies using isolated perifused islets have mostly been described with supraphysiological concentrations of fatty acids, it has remained uncertain whether elevated lipid levels contribute to hyperinsulinemia by their direct stimulation of insulin secretion. In the present study, we have identified reoxygenation injury in isolated islet function as a contributing factor in the failure of physiological concentrations of free fatty acids to stimulate insulin secretion in isolated perifused islets. Reoxygenation of isolated islets is associated with the production of reactive oxygen species, which impair islet function. We have found that pretreatment of freshly isolated islets with the antioxidant glutathione (GSH), as well as a 24-hour preculture of isolated islets under appropriate conditions, enhanced their sensitivity to fatty acid stimulation.
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PMID:Reoxygenation injury affects isolated islet response to fatty acid stimulation. 966 26

Alcoholic fatty liver and hyperlipemia result from the interaction of ethanol and its oxidation products with hepatic lipid metabolism. An early target of ethanol toxicity is mitochondrial fatty acid oxidation. Acetaldehyde and reactive oxygen species have been incriminated in the pathogenesis of the mitochondrial injury. Microsomal changes offset deleterious accumulation of fatty acids, leading to enhanced formation of triacylglycerols, which are partly secreted into the plasma and partly accumulate in the liver. However, this compensatory mechanism fades with progression of the liver injury, whereas the production of toxic metabolites increases, exacerbating the lesions and promoting fibrogenesis. The early presence of these changes confers to the fatty liver a worse prognosis than previously thought. Alcoholic hyperlipemia results primarily from increased hepatic secretion of very-low-density lipoprotein and secondarily from impairment in the removal of triacylglycerol-rich lipoproteins from the plasma. Hyperlipemia tends to disappear because of enhanced lipolytic activity and aggravation of the liver injury. With moderate alcohol consumption, the increase in high-density lipoprotein becomes the predominant feature. Its mechanism is multifactorial (increased hepatic secretion and increased extrahepatic formation as well as decreased removal) and explains part of the enhanced cholesterol transport from tissues to bile. These changes contribute to, but do not fully account for, the effects on atherosclerosis and/or coronary heart disease attributed to moderate drinking.
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PMID:Alcohol and lipids. 975 44

Eighteen children with steroid-sensitive nephrotic syndrome (SSNS) were studied. The control group comprised 20 healthy children. The following indirect parameters of reactive oxygen species activity were determined in nephrotic patients during four stages of the disease (full relapse before prednisone administration, disappearance of proteinuria, prednisone cessation, unmaintained remission): plasma malondialdehyde (MDA) levels, copper/zinc superoxide dismutase (CuZn SOD) activity and glutathione peroxidase (GPX) activity in erythrocytes, reduced glutathione (GSH) and vitamin C levels in whole blood, and vitamin E level in serum. Increased MDA levels, reduced vitamin C levels, and enhanced CuZn SOD activity were found in relapse. GSH concentration was high during all four stages. Vitamin E level was also increased, parallel to the pattern of serum lipids. GPX activity remained low during the proteinuria stage and in remission. We conclude that the majority of abnormal findings can be attributed to the hyperlipidemia of NS. Low GPX activity may be a factor limiting the antioxidant capacity in NS. The present study is inconclusive regarding the role of free radicals in the proteinuria of NS.
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PMID:Antioxidant status of children with steroid-sensitive nephrotic syndrome. 987 20

We found previously that human bone alkaline phosphatase (AP) was glycated by aseptic incubation with glucose, and partially broken down by reactive oxygen species. In this study, we examined whether selective in vivo glycation of AP molecules occurred in bone tissue, using experimental diabetic rats induced by streptozotocin and spontaneously diabetic rats. Additionally, the effects of hyperlipidemia on bone AP activity were examined. Serum AP activity was significantly elevated after incipient onset of diabetes, and the increased activity originated from the intestinal isozyme. High levels of intestinal AP activity were also observed in rats with hyperlipidemia induced by feeding high-fat or high-fructose chow, but the AP activity in bone tissues was maintained at a constant level. AP activity in bone was reduced after the onset of diabetes. The resulting bone AP molecule bound to an aminophenylboronic acid column, which had affinity for glycated proteins, and contained smaller molecular sizes than the native bone AP. These results suggest that elevated levels of serum AP activity originated from the intestinal isozyme accompanied with hyperlipidemia induced by diabetes. In contrast, the reduced serum levels of AP activity in diabetic rats might be dependent on inactivation of bone AP, which was glycated, followed by partial breakdown of bone AP molecules, possibly due to reactive oxygen species.
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PMID:Reduced alkaline phosphatase activity in diabetic rat bone: a re-evaluation. 997 13

1. Insulin resistance has been highlighted as a common causal factor for hypertension, hyperlipidaemia, diabetes mellitus and obesity, all of which are recognized to occur simultaneously, and a distinct clinical entity is defined as 'multiple risk factor syndrome'. 2. Recently, a new class of antidiabetic agents, thiazolidinediones (TZD) has been developed and has been shown to improve insulin resistance by binding and activating a nuclear receptor, peroxisome proliferator-activated receptor (PPAR) gamma. 3. cDNA of rat PPAR gamma 1 and gamma 2 were cloned and gene regulation of PPAR gamma in rat mature adipocytes was examined. Hydrogen peroxide, an oxygen radical, which is recognized to be the common intracellular signal for multiple risk factors, potently down-regulated PPAR gamma mRNA expression in rat mature adipocytes. 4. Tumour necrosis factor (TNF)-alpha, which is considered to play a role in obesity-induced non-insulin-dependent diabetes mellitus and to augment oxidative stress, also suppressed PPAR gamma expression. 5. Thiazolidinediones dose-dependently recovered TNF-alpha-induced down-regulation of PPAR gamma mRNA expression. 6. The modulation of PPAR gamma expression by TZD can be one mechanism for the improvement of insulin resistance by TZD. 7. Vascular tone and remodelling are controlled by several vasoactive autocrine/paracrine factors produced by endothelial cells in response to several vascular injury stimuli, including hypertension. The PPAR gamma gene transcript was detected in cultured endothelial cells. 8. The administration of TZD stimulated the endothelial secretion of type-C natriuretic peptide, which is one of the natriuretic peptide family and is demonstrated by us to act as a novel endothelium-derived relaxing peptide. 9. Concomitantly, TZD significantly suppressed the secretion of endothelin, a potent endothelium-derived vasoconstricting peptide. 10. Thiazolidinediones can affect vascular tone and growth by modulating the production of endothelium-derived vasoactive substances to influence occurrence and progression of hypertension and atherosclerosis.
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PMID:Hypertension and insulin resistance: role of peroxisome proliferator-activated receptor gamma. 1040 88


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