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)

Chromium (Cr), an essential element, mainly affects saccharide (potentiated insulin action via interaction with insulin receptor on the cell surface) and lipid metabolism (inhibition of hydroxymethylglutaryl-CoA reductase with a hypolipidemic effect). The aim of the study was to describe Cr serum levels in different diseases (malignant, metabolic, renal) using an advanced analytical technique with correlation to other biochemical parameters. The concentration was measured using atomic absorption spectrometry with electrothermal atomization. The Cr levels were increased in hemodialysis patients-HD (3.67 +/- 0.35 micrograms/L) compared to controls-C (0.40 +/- 0.12 microgram/L), in significantly changed in diabetic patients-DM (0.29 +/- 0.08 microgram/L) and patients with lymphoproliferative disease-LP (0.24 +/- 0.07 microgram/L), and decreased in hyperlipidemic patients-HL (0.15 +/- 0.03 microgram/L). There were no differences in Cr concentration between DM treated by diet or peroral antidiabetic drugs; likewise hypolipidemic drugs in HL did not change the Cr concentration. The biochemical parameters-total protein, transferrin in LP group, glucose in DM group, total cholesterol, triacylglycerols, LDL-cholesterol, apolipoprotein B and A-I did not correlate with serum Cr concentration. However, the HDL-cholesterol concentration marginally significantly (p < 0.07) correlated with it. The role of Cr in humans has not yet been fully characterized. To prevent some complications in patients, it may be important to monitor the Cr levels. Chromium supplementation may be indicated in some diseases with no controversy concerning the importance of decreased serum and/or tissue levels and documented positive effects of Cr supplementation on the quality of life (e.g. hyperlipidemia).
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PMID:Chromium levels in patients with internal diseases. 980 4

Hyperlipidemia in the nephrotic syndrome results from increased synthesis and decreased catabolism of lipoproteins. The contribution of each to establishing blood lipid levels is unknown. Increased triglyceride rich lipoprotein concentration, very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) primarily results from decreased clearance. This defect is due in part to reduced lipoprotein lipase (LPL) on the vascular endothelium resulting either from decreased synthesis or inadequate binding of this enzyme to endothelial surfaces. In contrast, both low density lipoprotein (LDL) and lipoprotein(a) [Lp(a)] concentrations are increased. Unlike the case of albumin or transferrin, or apoA-I in the rat, LDL apoB 100 synthesis is not related to that of albumin, suggesting a different mechanism of regulation or a response to a stimulus that is not the same as that augmenting the synthesis of nonlipoproteins. Evidence is presented for synthesis of LDL through a mechanism that bypasses the normal delipidation pathway that requires a VLDL precursor for LDL formation. HDL concentration is normal but maturation is impaired leading to a shift from the larger HDL2 to the smaller HDL3, a variant that is less effective as a transporter of the LPL cofactor apolipoprotein C II.
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PMID:New insights into lipid metabolism in the nephrotic syndrome. 1041 29

Mortality is markedly elevated in patients with end-stage renal disease. The leading cause of death is cardiovascular disease. Lipoprotein levels are only slightly elevated in dialysis patients, and cardiovascular risk is inversely correlated with serum cholesterol, suggesting that a process other than hyperlipidemia plays a role in the incidence of cardiovascular disease. Hypoalbuminemia, ascribed to malnutrition, has been one of the most powerful risk factors that predict all-cause and cardiovascular mortality in dialysis patients. The presence of inflammation, as evidenced by increased levels of specific cytokines (interleukin-6 and tumor necrosis factor alpha) or acute-phase proteins (C-reactive protein and serum amyloid A), however, has been found to be associated with vascular disease in the general population as well as in dialysis patients. The process of inflammation, also called the acute-phase response, additionally causes loss of muscle mass and changes in plasma composition-decreases in serum albumin, prealbumin, and transferrin levels, also associated with malnutrition. Inflammation alters lipoprotein structure and function as well as endothelial structure and function to favor atherogenesis and increases the concentration of atherogenic proteins in serum, such as fibrinogen and lipoprotein (a). Inflammation in dialysis patients is episodic. The causes are likely to be multifactorial and include vascular access infection, less-than-sterile dialysate, dialysate back leak, and nonbiocompatible membranes in addition to clinically apparent infection. In addition, proinflammatory compounds, such as advanced glycation end products, accumulate in renal failure, and defense mechanisms against oxidative injury are reduced, contributing to inflammation and to its effect on the vascular endothelium.
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PMID:The microinflammatory state in uremia: causes and potential consequences. 1142 86

Clinical studies have recently suggested that statin treatment may beneficially elevate plasma concentrations of high density lipoprotein (HDL)-cholesterol in patients with hyperlipidemia. Here, we have investigated the effect of a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase on the synthesis and secretion of apolipoprotein AI (apoAI) in two model systems, HepG2 cells and primary hamster hepatocytes. Cultured cells were incubated with different doses of simvastatin (0.1-10 microM) for a period of 18 h. A dose-dependent increase in synthesis and secretion of apoAI was observed in both cell types. There was a significant increase in the synthesis of apoAI in HepG2 cells (44.3+/-12.1%), and hamster hepatocytes (212+/-2%) after treatment with 10 microM of the statin. The increase in apoAI synthesis appeared to result in a higher level of apoAI secreted into the culture media in both cell types (49.2+/-7.8% in HepG2, 197+/-0.2% in hamster hepatocytes). ApoAI mRNA levels were also significantly increased in both cell types in response to statin treatment. Control experiments with transferrin confirmed specificity of the effect on apoAI secretion. Analysis of a density fraction containing HDL particles in culture media revealed an increase in HDL-associated apoAI of 94.3+/-2.1% in HepG2 cells and 27.0+/-0.03% in hamster hepatocytes following 10 microM simvastatin-treatment. Comparative studies of simvastatin and lovastatin indicated a differential ability to induce apoAI synthesis and secretion, with simvastatin having a more significant effect. Thus, acute statin treatment of cultured hepatocytes (transformed as well as primary) resulted in a significant upregulation of apoAI mRNA and apoAI synthesis, causing oversecretion of apoAI and HDL extracellularly. The stimulatory effect on apoAI synthesis and secretion may thus explain the clinical observation of an elevated plasma HDL-cholesterol level in hyperlipidemic patients treated with certain statins.
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PMID:Simvastatin, an HMG-CoA reductase inhibitor, induces the synthesis and secretion of apolipoprotein AI in HepG2 cells and primary hamster hepatocytes. 1204 22

Chromium was known for many years to be an element causing allergic reactions and having neurotoxic and carcinogenic effects. These effects can be observed especially in the case of hexavalent chromium. Only a little more than four decades ago trivalent chromium has been known as an essential element with relation to glycide and lipid metabolism. And only during several last years this chromium function has been revealed on a molecular level. After absorption in the gastrointestinal tract, chromium is most likely transported to cells bound to the plasma protein transferrin. Insulin initiates chromium transport into the cells where it is bound to the oligopeptide apochromodulin. This oligopeptide combined with four chromium(III) atoms forms chromodulin, which is important for amplifying the insulin signalling effect. After binding to insulin-activated receptor, chromodulin increases tyrosine kinase activity by one order. This enzyme forms a part of intracellular portion of insulin receptor. Chromium supplementation in people with chromium deficiency can improve glucose tolerance and some lipid metabolism parameters. The supplementation is indicated in persons with impaired glucose tolerance both in preclinical and manifested stadium of type 2 diabetes mellitus where increased lost of chromium in urine was documented. In these patients, chromium deficiency can participate in insulin resistance and hyperlipidaemia. Chromium is usually applied in the form of organic compounds: yeast extract or chromium(III) picolinate. Cr(III) picolinate can be reduced to compounds of Cr(II) in the cells which can then produce free hydroxyl radical in the so called Fenton reaction.
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PMID:[Chromium as an essential element]. 1292 32

Cardiovacular disease is the main cause of morbidity and mortality in hemodialysis (HD) patients. However, there are no reliable data neither on the prevalence of cardiovacular disease nor its risk factors in Spain. The Morbidity and mortality Anemia Renal study (MAR) is a two-year multicenter, open-label, prospective cohorts study. Its main objective is to assess the general morbidity and mortality, particularly of a cardiovascular cause, and its relationship with the degree of anemia. Secondary objectives are: a/ the description of current clinical practices in anemia, dialysis, vascular access, and CV risk factor management; and b/ the description of hospitalization and mortality causes. This paper describes the prevalence of cardiovascular disease and risk factors of the HD population in Spain. A total of 1.710 patients were included (60% male, aged 64.4 years, 16.2 months on HD). The mean co-morbidity Charlson index was 6.5 +/- 2.3. Cardiovascular disease was the most prevalent comorbidity, 16.7% had a coronary disease, and 13.9% had different degrees of heart failure, while 11.6% had arrhythmia, 1.7% stroke and 5.5% peripheral artery disease. The prevalence of hypertension was 75.8%, 74.4% of patients received antihypertensive drugs, and still 40% of patients had an inadequate blood pressure control. The investigators considered as dyslipidemic 34.1% of patients, and prescribed treatment to 69.5% of them, while the remaining 30.5% (10.4% of the total) had hyperlipidemia with no drug therapy. Eleven percent was active smoker, and 26.6% former smoker. There was 47.4% of patients with a corporal mass index above 25. Secondary hyperparathyroidism with PTH above of 300 pg/ml was present in 22.2% of patients. Despite the EBPG and K-DOQI recommendations, only 68.8% of prevalent hemodialysis patients attained a hemoglobin (Hb) above 11 g/dl, 89.4% ferritin levels above 100 ng/ml, 66.5 degrees/a a transferrin saturation index (TSI) above 20%, and 61.1% met all three objectives. In summary, this first cross-sectional analysis has allowed us to know in detail the standard practice in multiple aspects of management of HD population in Spain. It has also established clear differences in the prevalence of cardiovascular disease and risk factors from the US registries. Last but not least we have identified therapeutic opportunities to improve the course and prognosis of our patients.
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PMID:[Cardiovascular risk in hemodialysis in Spain: prevalence, management and target results (MAR study)]. 1605 11

Efficient entry of synthetic polymers inside cells is a central issue in polymeric drug delivery. Though polymers are widely believed to interact nonspecifically with plasma membrane, we present unexpected evidence that amphiphilic block copolymers, depending on their aggregation state, can distinguish between caveolae- and clathrin-mediated endocytosis. A block copolymer of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), Pluronic P85 (P85), below critical micelle concentration (CMC) exists as single molecule coils (unimers) and above CMC forms 14.6 nm aggregated micelles with a hydrophobic PPO core and hydrophilic PEO shell. The internalization pathways of P85 in mammalian cells were elucidated using endocytosis inhibitors and colocalization with endocytosis markers (clathrin-specific antibodies and transferrin for clathrin and caveolin-1-specific antibodies and cholera toxin B for caveolae). Altogether, our results indicate that P85 unimers internalize through caveolae-mediated endocytosis, while P85 micelles internalize through clathrin-mediated endocytosis. Furthermore, at concentrations above 0.01% P85 inhibits caveolae-mediated endocytosis (cholera toxin B), while having little or no effect on the clathrin-mediated endocytosis (transferrin). Selective interaction of Pluronic with caveolae may explain its striking pharmacological activities including inhibition of drug efflux transport, activation of gene expression, and dose-dependent hyperlipidemia.
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PMID:Different internalization pathways of polymeric micelles and unimers and their effects on vesicular transport. 1872 94

Nonalcoholic steatohepatitis (NASH) was described by Ludwig mainly in obese, middle-aged women, often associated with diabetes mellitus and hyperlipidemia. In the recent years, NASH was found to be associated with male, nonobese, nondiabetic patients and with liver iron overload, which led to the hypothesis of iron playing a role in NASH pathogenesis. Increased ferritin with normal transferrin saturation is frequently found in fatty liver patients, but it reflects iron overload only in those patients in which it persists despite an appropriate diet. Insulin resistance hepatic iron overload (IR-HIO) is a new condition of hepatic iron overload, characterized by hyperferritinemia with normal or slightly increased transferrin saturation in the absence of hemochromatotic gene mutations. Although patients with IR-HIO have a high prevalence of insulin resistance-related metabolic disorders, the relationship of IR-HIO and NASH is unclear. Two characteristics allow differentiation of IR-HIO from genetic haemochromatosis: iron overload is heterogeneous from one hepatocyte to another in the periportal area, and sinusoidal iron is distributed throughout the lobule. In IR-HIO, fibrosis develops at a much lower hepatic iron burden than in genetic haemochromatosis, and sinusoidal iron, steatosis and inflammation could represent the histological mark of activity and progression of liver disease in IR-HIO.
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PMID:[Involvement and role of iron in nonalcoholic steatohepatitis]. 1929 96

Inflammation and oxidative stress are among the factors that have been implicated in the pathogenesis of hyperlipidemia. In metabolic syndrome and hyperlipidemic patients, peripheral polymorphonuclear leukocytes (PMNL) are primed and they release uncontrolled superoxide that contributes to oxidative stress and inflammation. Recent studies have demonstrated that the anti-hyperlipidemic drug, Atrovastatin effects improvement in endothelial function, exhibits anti-oxidative characteristics and reduces lipid markers of oxidation. To evaluate possible nontraditional effects of treatment with Atrovastatin on PMNL priming, oxidative stress and inflammation in hyperlipidemia, 50 non-smoking hyperlipidemic patients were treated for 6 months with Atrovastatin and compared to age and gender-matched healthy controls. PMNL priming was assessed by the rate of superoxide release from separated, phorbol ester-stimulated PMNL and by PMNL-CD11b levels. Inflammation was reflected by blood inflammatory markers including albumin, transferrin, C-reactive protein (CRP) and fibrinogen levels, white blood cells (WBC), PMNL counts and PMNL apoptosis. Atrovastatin treatment showed a reduction in PMNL priming, PMNL apoptosis, fibrinogen and CRP levels concomitant with decreased lipid levels. Atrovastatin may be preferred for hyperlipidemic patients owing to its combined anti-PMNL priming and anti-inflammatory effects in addition to its anti-atherogenic effects.
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PMID:Effects of statins on oxidative stress and primed polymorphonuclear leukocytes in hyperlipidemic patients. 2298 53

The nephrotic syndrome is characterized by the loss of many proteins, via the urinary system. It exceeds the bodies compensatory abilities and results in abnormalities in blood clotting system, particularly due to antithrombin deficiency. It significantly increases the risk of thromboembolic complications. A loss of erythropoietin and transferrin leads to anemia. Polycythemia is a rarely reported phenomenon. The case describes a 20-years old patient with massive nephrotic syndrome and polycythemia, complicated by a pulmonary embolism. The patient had a steroid-dependent submicroscopic glomerulonephritis with a severe episode of nephrotic syndrome associated with centralization of circulation, proteinuria 40.9 g/day, deep hypoproteinemia (albumin=1.2 g/dl), hyperlipidemia, hypercoagulable state (antithrombin activity 29%), polycythemia (Hb=21.1 g/dl, HTC=60%). Kidney function parameters were normal. We started the immunosupression (glycocorticosteroids i.v., continuated p.o. and cyclosporine A) and intensive symptomatic treatment. To reverse hypovolemia and polycythemia, 20% albumin solutions, intravenous infusions and diuretics were used. There was no effect. Due to intensive polycythemia the erythroapheresis procedure was performed. It resulted in normalization of the red blood cell count (Hb=13.4 g/dl, HCT=37%) and the improvement of blood circulation. To prevent the patient from thromboembolism, the prophylactic dose of low molecular weight heparin (LMWH) was administered (dalteparin 5000 IU subcutaneously, once a day). Despite the prophylaxis, an episode of dyspnea with tachycardia occured. It was connected with elevated Ddimer and troponin levels and a right ventricle overload in echocardiographic imaging. The pulmonary embolism was suspected. Perfusion lung scintigraphy confirmed this diagnosis. We supposed that the heparin was ineffective due to an antithrombin deficiency. Therefore, apart from a therapeutic dose of LMWH, intravenous antithrombin concentrate was given to the patient (1500 IU twice). The dyspnea resolving was observed. The D-dimer and troponin level reversion to normal was noticed. Heparin injections, connected with antithrombin infusion, was an effective treatment of the pulmonary embolism. Due to the lack of antithrombin in nephrotic syndrome, using only heparin may be insufficient. The erythroapheresis is an effective treatment of polycythemia.
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PMID:[Above-standard proceeding in nephrotic syndrome - case report]. 2708 3


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