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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effects of chronic treatment with cromakalim (75 ug kg(-1) per day) and glibenclamide (20 mg kg(-1) per day) in alloxan-induced diabetic rats. Injection of alloxan (60 mg kg(-1)/i.v., single dose) produced a significant increase in the blood pressure, bradycardia, hyperglycemia, hypoinsulinemia, hyperlipidemia, hypothyroidism and depression in left ventricular developed pressure (LVDP). While glibenclamide significantly prevented alloxan-induced hyperglycemia and hypoinsulinaemia, it failed to alter hypertension, bradycardia, hypertriglyceridaemia and hypercholesterolemia. Treatment with cromakalim-prevented hypertension and bradycardia, but not the hyperglycemia or hypoinsulinaemia. Co-administration of cromakalim with glibenclamide antagonized the effect of glibenclamide on these parameters. Cromakalim treatment also prevented alloxan-induced hypercholesterolemia and hypertriglyceridaemia. It also produced a significant increase in serum T(3) and T(4) levels. Glibenclamide did not significantly alter alloxan-induced hypothyroidism. In conclusion our data suggest that cromakalim and glibenclamide produce some metabolic effects that are either not related to K(ATP) channel modulation or may involve different sub-types of potassium channels. Further glibenclamide when combined with cromakalim may not be beneficial in a condition when diabetes mellitus and hypertension co-exits.
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PMID:Effects of chronic treatment with cromakalim and glibenclamide in alloxan-induced diabetic rats. 1222 Sep 47

11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) regenerates cortisol from inactive cortisone in liver and adipose tissue. Inhibition of 11 beta-HSD1 offers a novel potential therapy to lower intracellular cortisol concentrations and thereby enhance insulin sensitivity and hepatic lipid catabolism in type 2 diabetes, obesity, and hyperlipidemia. We evaluated this approach using the nonselective 11 beta-HSD inhibitor, carbenoxolone, in healthy men and lean male patients with type 2 diabetes. Six diet-controlled nonobese diabetic patients with hemoglobin A(1c) less than 8%, and six matched controls participated in a double-blind, cross-over comparison of carbenoxolone (100 mg every 8 h, orally, for 7 d) and placebo. They were admitted overnight for infusions of insulin (as required to maintain arterialized plasma glucose of 5.0 mM) and [13C6]glucose. Glucose kinetics were measured in the fasted state from 0700-0730 h, during a 3-h euglycemic hyperinsulinemic clamp (including somatostatin infusion and replacement of physiological GH and glucagon levels), and during a 2-h euglycemic hyperinsulinemic clamp with a 4-fold increase in glucagon levels. Data are the mean +/- SEM. Carbenoxolone had the expected effects of raising blood pressure and lowering plasma potassium. Carbenoxolone reduced total cholesterol in healthy subjects (5.25 +/- 0.34 vs. 4.78 +/- 0.40 mM; P < 0.01), but had no effect on other serum lipids or on cholesterol in diabetic patients. Carbenoxolone did not affect the rate of glucose disposal or the suppression of free fatty acids during hyperinsulinemia. However, carbenoxolone reduced the glucose production rate during hyperglucagonemia in diabetic patients (1.90 +/- 0.2 vs. 1.53 +/- 0.3 mg/kg x min; P < 0.05). This was attributable to reduced glycogenolysis (1.31 +/- 0.2 vs. 1.01 +/- 0.2 mg/kg x min; P < 0.005) rather than altered gluconeogenesis. These observations reinforce the potential metabolic benefits of inhibiting 11 beta-HSD1 in the liver of patients with type 2 diabetes. Further studies in obesity and hyperlipidemia are now warranted. However, clinically useful therapeutic effects will probably require selective 11 beta-HSD1 inhibitors that lower intraadipose cortisol levels and enhance peripheral glucose uptake.
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PMID:Effects of the 11 beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone on insulin sensitivity in men with type 2 diabetes. 1251 67

The endothelial cell layer displays the features of a distributed organ and has a variety of biological functions such as keeping the balance between coagulation and fibrinolysis, expression of adhesion molecules for cells in the immune system, metabolism of noradrenaline and 5-hydroxytryptamine, and conversion of angiotensin I and bradykinin. The endothelium also regulates the underlying smooth muscle layer and vascular tone by release of endothelium-derived relaxing factors such as nitric oxide (NO), prostaglandins, and endothelium-derived hyperpolarizing factor (EDHF) as well as vasoconstricting factors such as endothelin, superoxide (O(2)(-)), and thromboxane. We have reviewed the nature, mechanisms of action, and role of these factors in regulation of vascular tone, with special emphasis on NO. By a process catalyzed by NO synthase, NO and citrulline is formed from the substrates molecular O(2) and L-arginine. The main receptor for NO is guanylyl cyclase leading to formation of smooth muscle cyclic guanosinmonophosphate and relaxation. EDHF is an endothelium-derived factor causing vasorelaxation of the underlying smooth muscle layer by hyperpolarization. The nature of EDHF is still unknown, but several candidates for EDHF have been proposed such as potassium ions, hydrogen peroxide, and epoxyeicosatrienoic acids. Prostaglandins such as prostacyclin and prostaglandin E2 binds to specific receptors followed by increases in cyclic adenosinmonophosphate and vasorelaxation, while contractile prostaglandins constrict vessels by activation of thromboxane and endoperoxidase receptors. Superoxide anions induce contraction of vascular smooth muscles cells by scavenging NO. Endothelin is a potent endothelium-derived contractile factor. The synthesis of endothelin-1 is induced by hypoxia, thrombin, interleukin-1, transforming growth factor-beta1, vasopressin, and catecholamines. Cardiovascular risk factors like age, hypertension, and hyperlipidemia are associated with impaired endothelium-dependent vasodilation either as a consequence of increased inactivation of endothelium-derived vasodilators or increased formation of endothelium-derived contracting factors. This imbalance of endothelium-derived factors plays a role for development of atheroslerosis and ischemic vascular diseases.
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PMID:[Role of nitric oxide and other endothelium-derived factors]. 1273 1

Early optimalization of the treatment of patients with chronic renal insufficiency can reduce morbidity and deaths. For each patient with a raised serum creatinine concentration, the creatinine clearance should be measured or calculated. When this is abnormal, the cause thereof should be investigated. Chronic renal insufficiency is often progressive, even when the initiating factors are no longer present. Progression can be delayed by treating the high blood pressure, proteinuria and hyperlipidemia by means of a restricted protein diet and advice not to smoke. Acute deterioration of an existing chronic renal dysfunction through dehydration and underfill or through the use of certain medications or toxic substances such as radio-opaque media should be avoided. In patients with chronic renal insufficiency specific attention should be paid not only to hypertension, lipid disturbances, smoking and weight, but also to the calcium-phosphate balance, anaemia and homocysteine levels. The blood pressure, oedema and weight of patients with a clearance between 30-59 ml/min should be checked 2-3 times a year, in addition to laboratory tests for Hb, Ht, creatinine, urea, potassium, calcium, phosphate, pH, bicarbonate and lipid spectrum. It is recommended that when creatinine clearance (< 50 ml/min) falls a nephrologist should be consulted at least once with respect to the strategy to be followed. Symptoms of chronic renal insufficiency can occur when the creatinine clearance is < 30 ml/min. This relates to: sodium retention, imbalances in the calcium and phosphate levels, anaemia, uraemia, water retention, potassium retention and metabolic acidosis. Referral should take place at a creatinine clearance of < or = 30 ml/min.
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PMID:[Treatment of patients with chronic renal insufficiency; a guideline for internists]. 1511 99

The understanding of the involvement of the gap junctions (GJ) in the vascular reactivity is an ongoing effort. In this study we questioned on impact of pathologies such as diabetes, hyperlipemia, and simultaneous hyperlipemia-diabetes on GJ involvement in the contractile/relaxant response of the mesenteric resistance arteries. To this purpose, four groups of Golden Syrian hamsters were used: (i) diabetics (D), injected by streptozotocin, (ii) hyperlipemics (H), fed the standard chow of the species supplemented with 3% cholesterol and 15% butter, (iii) simultaneously hyperlipemic-diabetics (HD), and (iv) controls (C), age-matched normal healthy animals. At 24 weeks after the beginning of the experiment, the vascular reactivity of the resistance arteries was measured by the myograph technique in the presence/absence of 1 mM Heptanol (Hep) and of vasoconstrictors and vasodilators. The results showed that: (i) in pathological conditions 1 mM Hep significantly impaired the constrictor response of the hamster resistance arteries to both 10(-5) M NA (noradrenaline, agonist of alpha(1)-adrenoceptors) and 64.1 mM K+ (potassium ion, the major intracellular cation). The impairment occur in the group range: HD < H < D < C being the highest at the simultaneous insult of hyperlipemia and diabetes; (ii) independently of the pathological condition, 1 mM Hep abolishes both endothelium-dependent and independent relaxation of the hamster resistance arteries. At 1 mM Hep we noticed a reversible effect on endothelium-dependent relaxation that may be partially restored (in normal) in the presence of L-arginine. It is hoped that these results may contribute to understanding of the involvement of GJ in vascular pathology/dysfunction.
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PMID:Effect of gap junction uncoupler heptanol on resistance arteries reactivity in experimental models of diabetes, hyperlipemia and hyperlipemia-diabetes. 1665 Oct 32

Diabetes-induced hyperlipidemia, oxidative stress and protein glycation impair cellular calcium and sodium homeostasis associated with abnormal membrane-bound enzyme activities resulting in cardiac dysfunction in diabetes. To explore the cardioprotective mechanism of green tea in diabetes, we measured the changes in the levels of calcium, sodium, potassium and the activities of Na+/K+ -ATPase and Ca2+ -ATPase in green tea treated diabetic rat hearts. The effect of green tea on triglycerides, lipid peroxidation and protein glycation in diabetic heart were also measured to elucidate the underlying mechanisms. Diabetes was induced by streptozotocin (STZ, 60 mg/kg i.p.). Six weeks after the induction of diabetes, some of the diabetic rats were treated orally with green tea extract (GTE) (300 mg/kg/day) for 4 weeks. GTE produced reduction in blood glucose and lowered the levels of lipid peroxides, triglycerides and extent of protein glycation in the heart of diabetic rats. GTE blunted the rise in cardiac [Ca2+] and [Na+] whereas increased the activities of Ca2+ -ATPase and Na+/K+ -ATPase in diabetic rats. In conclusion, the data provide support to the therapeutic effect of GTE and suggest that a possible mechanism of action may be associated with the attenuation of the rise in [Ca2+] and [Na+] by ameliorating Ca2+ -ATPase and Na+/K+ -ATPase activities.
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PMID:Green tea impedes dyslipidemia, lipid peroxidation, protein glycation and ameliorates Ca2+ -ATPase and Na+/K+ -ATPase activity in the heart of streptozotocin-diabetic rats. 1684 94

The influence of interference by hemolysis, icterus and lipemia on the results of routine chemistries may lead to wrong interpretations. On Synchron LX-20 instruments (Beckman Coulter) serum or plasma indices can be used as reliable semi-quantitative measures of the magnitude of such interference. In an article recently published in this journal, we presented the results of a multicenter study carried out in Dutch hospitals in which we determined cutoff indices for analytes above which analytically significant interference exists. Clinically significant interference cutoff indices were also derived for these analytes. In this article, we describe the handling of patient samples with clinically significant interference by hemolysis, icterus or lipemia. We investigated several possible approaches for correction of the result: dilution of the interference; mathematical correction in the case of hemolysis; treatment with ferrocyanide to destroy bilirubin; and removal of lipids in lipemic patient samples. We concluded, that mathematical correction of potassium or lactate dehydrogenase results in hemolytic samples can only be carried out if intravascular hemolysis is ruled out. Hemoglobin quantification in serial patient samples, combined with measurement of haptoglobin, represents a useful tool to rule out in vivo hemolysis. We derived an algorithm for this situation. We do not simply recommend mathematical correction, unless it is clinically acceptable. We present formulas for potassium and lactate dehydrogenase: corrected potassium=measured potassium-(hemolytic index increment x 0.14); corrected lactate dehydrogenase=measured lactate dehydrogenase-(hemolytic index increment x 75). The dilution studies indicated that dilution is only applicable for bilirubin, C-reactive protein and iron. The results of treatment with ferrocyanide were poor, and we do not recommend this method. Removal of lipids using high-speed centrifugation or LipoClear (StatSpin Inc.), a non-toxic and non-ionic polymer, is a very effective approach, although C-reactive protein, creatine kinase-MB (CK-MB) and cholesterol cannot be removed using LipoClear. For all interferants (hemoglobin, bilirubin, lipids), relatively simple algorithms are derived that can easily be implemented in the clinical laboratory.
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PMID:Correction of patient results for Beckman Coulter LX-20 assays affected by interference due to hemoglobin, bilirubin or lipids: a practical approach. 1724 28

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

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

The coconut water presents a series of nutritional and therapeutic properties, being a natural, acid and sterile solution, which contains several biologically active components, l-arginine, ascorbic acid, minerals such as calcium, magnesium and potassium, which have beneficial effects on lipid levels. Recent studies in our laboratory showed that both tender and mature coconut water feeding significantly (P<0.05) reduced hyperlipidemia in cholesterol fed rats [Sandhya, V.G., Rajamohan, T., 2006. Beneficial effects of coconut water feeding on lipid metabolism in cholesterol fed rats. J. Med. Food 9, 400-407]. The current study evaluated the hypolipidemic effect of coconut water (4ml/100g body weight) with a lipid lowering drug, lovastatin (0.1/100g diet) in rats fed fat-cholesterol enriched diet ad libitum for 45 days. Coconut water or lovastatin supplementation lowered the levels of serum total cholesterol, VLDL+LDL cholesterol, triglycerides and increased HDL cholesterol in experimental rats (P<0.05). Coconut water feeding decreased activities of hepatic lipogenic enzymes and increased HMG CoA reductase and lipoprotein lipase activity (P<0.05). Incorporation of radioactive acetate into free and ester cholesterol in the liver were higher in coconut water treated rats. Coconut water supplementation increased hepatic bile acid and fecal bile acids and neutral sterols (P<0.05). Coconut water has lipid lowering effect similar to the drug lovastatin in rats fed fat-cholesterol enriched diet.
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PMID:Comparative evaluation of the hypolipidemic effects of coconut water and lovastatin in rats fed fat-cholesterol enriched diet. 1880 54


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