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)

The effect of low molecular weight heparin (LMWH) on serum lipid profile in hemodialysis remains controversial and its effect on bone metabolism has not been studied. A crossover study was conducted in 40 patients on stable hemodialysis using unfractionated heparin (UFH) for more than 24 months. These patients were then treated with a LMWH (nadroparin-Ca) for 8 months during hemodialysis and subsequently switched back to UFH for 12 months. Serum lipid profile, biochemical markers for bone metabolism, and bone densitometry (BMD) were monitored at four-month intervals while all medications remained unchanged. Cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), lipoprotein(a) (Lp(a)), apolipoprotein B (Apo B) were raised in 35%, 29%, 12%, 24% and 24% of patients respectively. High-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 (Apo A-1) were reduced in 47% and 9% of patients. Bone-specific alkaline phosphatase (BALP) and intact osteocalcin (OSC), both reflecting osteoblastic activity, were raised in 65% and 94% of patients. Tartrate-resistant acid phosphatase (TRACP) reflecting osteoclastic activity and parathyroid hormone (PTH) were elevated in 35% and 88% of patients. Following LMWH treatment, TC, Tg, Lp(a) and Apo B were reduced by 7%, 30%, 21% and 10% respectively (p<0.05 or <0.01) while Apo A-1 were raised by 7% (p<0.01). Simultaneously, TRACP was reduced by 13% (p<0.05). These biochemical changes were detected soon after 4 months of LMWH administration. Although BMD values in our patients were lower than those of age-matched normal subjects, significant changes were not observed with LMWH treatment. After switching back to UFH for hemodialysis, these biochemical indices reverted to previous values during UFH treatment with a significant higher level in TC and Apo B while serum Apo A-1 remained elevated. Our study suggests LMWH may partially alleviate hyperlipidemia and, perhaps, osteoporosis associated with UFH administration in patients on maintenance hemodialysis.
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PMID:Effect of low molecular weight heparin on bone metabolism and hyperlipidemia in patients on maintenance hemodialysis. 1151 Sep 16

It is a known fact that ethanol increases lipid levels in humans and experimental animals. Reports show that the increased intake of polyunsaturated fatty acids (PUFAs) along with alcohol produces various pathological changes in liver resulting in hyperlipidemia. Heating of oil rich in PUFA produces various lipid peroxidative end products, which aggravate the pathological changes. In the present study, we have investigated the effect of curcumin (C) and photo-irradiated curcumin (IC) on alcohol- and PUFA-induced hyperlipidemia. Our results showed that the activities of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) in plasma and levels of cholesterol, triglycerides (TGs) and free fatty acids (FFAs) in tissues were increased significantly in both alcohol + raw as well as heated PUFA groups compared to normal, but decreased significantly on treatment with curcumin and IC. The IC treatment decreased the levels more significantly compared to curcumin. The phospholipids (PLs) were increased significantly in heart and intestine and decreased in liver and kidney in both alcohol + raw as well as heated PUFA groups. The levels were significantly decreased in liver and kidney and increased in intestine and heart in both curcumin- and IC-treated groups. But the effect of IC was more pronounced than curcumin. Histopathological observations were also in correlation with the biochemical parameters. Thus, photo-irradiated curcumin proves itself to be more effective than curcumin in treating the above pathological conditions.
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PMID:Comparative effects of curcumin and photo-irradiated curcumin on alcohol- and polyunsaturated fatty acid-induced hyperlipidemia. 1222 Sep 69

Fibric acid derivatives are a class of hypolipidaemic drugs used in the treatment of patients with hypertriglyceridaemia, mixed hyperlipidaemia and diabetic dyslipidaemia. Fibrate therapy results in a significant decrease in serum triglycerides and an increase in high-density lipoprotein (HDL) cholesterol levels. The latest drugs of this class are also effective in lowering low-density (LDL) cholesterol levels and can change the distribution of LDL towards higher and larger particles. The effects of fibrates on lipid metabolism are mostly mediated through the activation of peroxisome proliferator-activated receptors (PPARalpha). A number of angiographic and clinical trials have confirmed that fibrates can slow the progression of atherosclerotic disease and decrease cardiovascular morbidity and mortality. Recently published data suggest that the ability of fibrates to prevent atherosclerosis is not related only to their hypolipidaemic effects but also to other 'pleiotropic effects', such as their anti-inflammatory, antioxidant and antithrombotic effects, as well as their ability to improve endothelial function. Interestingly, fibrates may favourably influence the thrombotic/fibrinolytic system. In fact, most of these drugs can significantly decrease plasma fibrinogen levels and inhibit tissue factor expression and activity in human monocytes and macrophages. Some studies have shown that fibrates can improve carbohydrate metabolism in patients with dyslipidaemia, including diabetic patients. Among fibrates only fenofibrate can significantly decrease serum uric acid levels by increasing renal urate excretion. Fibrates, with the possible exception of gemfibrozil, can significantly increase serum creatinine and homocysteine levels. Finally, a reduction in serum alkaline phosphatase and gamma glutamyltranspeptidase (gammaGT) activity is a well-documented effect of therapy with fibrates. The fibrates are generally well-tolerated drugs with few side-effects. The most important side-effect is myositis, which is observed in patients with impaired renal function or when statins are given concomitantly.
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PMID:Effects of fibrates on serum metabolic parameters. 1274 Jan 59

Endogenous thyroid receptor hormones 3,5,3',5'-tetraiodo-l-thyronine (T(4), 1) and 3,5,3'-triiodo-l-thyronine (T(3), 2) exert a significant effects on growth, development, and homeostasis in mammals. They regulate important genes in intestinal, skeletal, and cardiac muscles, the liver, and the central nervous system, influence overall metabolic rate, cholesterol and triglyceride levels, and heart rate, and affect mood and overall sense of well being. The literature suggests many or most effects of thyroid hormones on the heart, in particular on the heart rate and rhythm, are mediated through the TRalpha(1) isoform, while most actions of the hormones on the liver and other tissues are mediated more through the TRbeta(1) isoform of the receptor. Some effects of thyroid hormones may be therapeutically useful in nonthyroid disorders if adverse effects can be minimized or eliminated. These potentially useful features include weight reduction for the treatment of obesity, cholesterol lowering for treating hyperlipidemia, amelioration of depression, and stimulation of bone formation in osteoporosis. Prior attempts to utilize thyroid hormones pharmacologically to treat these disorders have been limited by manifestations of hyperthyroidism and, in particular, cardiovascular toxicity. Consequently, development of thyroid hormone receptor agonists that are selective for the beta-isoform could lead to safe therapies for these common disorders while avoiding cardiotoxicity. We describe here the synthesis and evaluation of a series of novel TR ligands, which are selective for TRbeta(1) over TRalpha(1). These ligands could potentially be useful for treatment of various disorders as outlined above. From a series of homologous R(1)-substituted carboxylic acid derivatives, increasing chain length was found to have a profound effect on affinity and selectivity in a radioreceptor binding assay for the human thyroid hormone receptors alpha(1) and beta(1) (TRalpha(1) and TRbeta(2)) as well as a reporter cell assay employing CHOK1-cells (Chinese hamster ovary cells) stably transfected with hTRalpha(1) or hTRbeta(1) and an alkaline phosphatase reporter-gene downstream thyroid response element (TRAFalpha(1) and TRAFbeta(1)). Affinity increases in the order formic, acetic, and propionic acid, while beta-selectivity is highest when the R(1) position is substituted with acetic acid. Within this series 3,5-dibromo-4-[(4-hydroxy-3-isopropylphenoxy)phenyl]acetic acid (11a) and 3,5-dichloro-4-[(4-hydroxy-3-isopropylphenoxy)phenyl]acetic acid (15) were found to reveal the most promising in vitro data based on isoform selectivity and were selected for further in vivo studies. The effect of 2, 11a, and 15 in a cholesterol-fed rat model was monitored including potencies for heart rate (ED(15)), cholesterol (ED(50)), and TSH (ED(50)). Potency for tachycardia was significantly reduced for the TRbeta selective compounds 11a and 15 compared with 2, while both 11a and 15 retained the cholesterol-lowering potency of 2. This left an approximately 10-fold therapeutic window between heart rate and cholesterol, which is consistent with the action of ligands that are approximately 10-fold more selective for TRbeta(1). We also report the X-ray crystallographic structures of the ligand binding domains of TRalpha and TRbeta in complex with 15. These structures reveal that the single amino acid difference in the ligand binding pocket (Ser277 in TRalpha or Asn331 in TRbeta) results in a slightly different hydrogen bonding pattern that may explain the increased beta-selectivity of 15.
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PMID:Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1. 1269 76

Biological interactions between the bone and the blood vessels are gradually being clarified. To investigate the relationship between bone mineral density and atherosclerosis in hemodialysis patients, we examined the bone mineral density and the intima-media thickness of the carotid artery in 83 dialysis patients with non-diabetic nephropathy (44 men and 39 women) aged from 23 to 83 years. The duration of hemodialysis ranged from 2 to 344 months. The bone mineral density of the radius was measured by dual-energy X-ray adsorptiometry, and the ratio of this value to the standard value for the same age and gender was calculated ( Z-score). As an index of atherosclerosis, the intima-media thickness of the carotid artery was measured by high resolution B-mode ultrasonography. Then the relationship between the Z-score and various factors was examined using Spearman's rank correlation analysis and multiple regression analysis. The Z-score showed a negative correlation with the duration of hemodialysis, the carotid intima-media thickness, and the levels of alkaline phosphatase, intact parathyroid hormone, and low-density lipoprotein cholesterol by Spearman's rank correlation analysis. In addition, the Z-score showed a positive correlation with the lipoprotein (a) level and a negative correlation with the duration of hemodialysis, intima-media thickness, intact parathyroid hormone, and low-density lipoprotein cholesterol by multiple regression analysis. These findings suggest that the decrease of bone mineral density in hemodialysis patients is correlated with secondary hyperparathyroidism and hyperlipidemia, which are factors known to promote atherosclerosis, and thus bone density changes might be related to the progression of atherosclerosis, or vice versa.
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PMID:Bone mineral density may be related to atherosclerosis in hemodialysis patients. 1459 55

It is a known fact that ethanol increases lipid levels in humans and experimental animals. In this study, we have investigated the effect of dendrodoine analogue (DA), DA-[4-amino-5-benzoyl-2-(4-methoxyphenylamino)-thiazole], on alcohol- and thermally oxidized sunflower oil-induced hyperlipidemia. Ethanol was given to animals at a dose of 5 ml of 20% solution and thermally oxidized sunflower oil at a level of 15% (15 g oil/100 g feed). Our results showed increased activity of aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) and increased levels of cholesterol, triglycerides and phospholipids in the plasma of groups given alcohol, thermally oxidized oil and alcohol + thermally oxidized oil when compared with normal control group. The levels of tissue (liver and kidney) cholesterol and triglycerides were increased significantly in groups treated with alcohol, thermally oxidized oil and alcohol + thermally oxidized oil when compared with normal control rats. The levels were decreased when DA was given along with alcohol and thermally oxidized oil. The level of phospholipids decreased significantly in the liver and kidney of rats administered alcohol, thermally oxidized oil and alcohol + thermally oxidized oil when compared with normal control rats. The level increased when DA was administered along with alcohol and thermally oxidized oil. The activity of phospholipase A and C increased significantly in the liver of groups given alcohol, thermally oxidized oil and alcohol + thermally oxidized oil when compared with normal control rats, whereas the activity was decreased upon DA treatment. The obtained results indicate that DA can decrease the lipid levels in alcohol- and thermally oxidized oil-treated rats.
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PMID:Role of an aminothiazole derivative on ethanol- and thermally oxidized sunflower oil-induced toxicity. 1515 74

Artery calcification occurring in atherosclerosis is connected with a high risk of cardiovascular events. Quantitative calcification evaluation using electron beam tomography indicated a correlation between artery calcification and well-known cardiovascular risk factors, i.e. smoking, obesity, and hyperlipidemia. Elevated calcium scores are especially observed in diabetic patients, which may even explain the higher mortality in this group. Calcification leads to increased blood vessel rigidity and, consequently, elevated arterial vascular resistance and left ventricular hypertrophy. An increased risk of plaque rupture in relation to calcium-rich atherosclerotic lesions was not proved. Plaque rupture and thromboembolitic complications are probably higher in the case of lipid-rich lesions. Atherosclerotic calcification is an active process in which many cells (monocytes/macrophages, vascular smooth muscle cells, and endothelial cells) participate. Many substances and transcription factors normally participating in the bone remodeling process are found in calcified atherosclerotic lesions (e.g. Cbfa-1, osteocalcin, alkaline phosphatase, BMP-2, osteopontin, osteoprotegrin, and RANKL). On monocytes, cells playing an important role in atherosclerosis progression, the presence of a calcium-sensing receptor (CaR) has been demonstrated. Increase in monocyte chemotaxis and increased interleukin 6 secretion in response to extracellular calcium were observed. Monocytes also directly and indirectly enhance vascular calcification. Immune cells and cytokines participating in vascular calcification are connected in one pathogenetic mechanism, i.e. atherosclerosis as an inflammatory disease and calcification.
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PMID:[The role of calcium ions in the pathomechanism of the artery calcification accompanying atherosclerosis]. 1576 85

In this study, the effects of Melissa officinalis L. extract on hyperlipidemic rats were investigated, morphologically and biochemically. The animals were fed a lipogenic diet consisting of 2% cholesterol, 20% sunflower oil and 0.5% cholic acid added to normal chow and were given 3% ethanol for 42 days. The plant extract was given by gavage technique to rats to a dose of 2 g/kg every day for 28, 14 days after experimental animals done hyperlipidemia. The degenerative changes were observed in hyperlipidemic rats, light and electron microscopically. There was a significant increase in the levels of serum cholesterol, total lipid, alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), a significant decrease in the levels of liver tissue glutathione (GSH), a significant increase in the levels of tissue lipid peroxidation (LPO) in this group. On the other hand, the administration of Melissa officinalis L. extract reduced total cholesterol, total lipid, ALT, AST and ALP levels in serum, and LPO levels in liver tissue, moreover increased glutathione levels in the tissue. As a result, it was suggested that Melissa officinalis L. extract exerted an hypolipidemic effect and showed a protective effect on the liver of hyperlipidemic rats.
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PMID:Protective role of Melissa officinalis L. extract on liver of hyperlipidemic rats: a morphological and biochemical study. 1594 12

The Konelab 20XT (Thermo Electron Oy, Finland) is a clinical chemistry analyzer for colorimetric, immunoturbidimetric and ion-selective electrode measurements. The aim of our work was to evaluate the analytical performances of the Konelab 20XT according to the European Clinical Chemistry Laboratory Standards Guidelines. A total of 30 analytes including substrates, enzymes, electrolytes and specific proteins were tested. Investigation results showed low imprecision (within-run coefficient of variation was below 3.5% and between-day coefficient of variation was less than 2.5% for most analytes at all three levels studied) and acceptable accuracy of the analyzer. No significant sample- or reagent-related carry-over was found. It was demonstrated that the analytical system operates within the claimed linearity ranges. The results compared well with those obtained by instruments routinely used in our laboratory (Olympus AU2700, Behring Nephelometer II). In general, the data on interference by hemoglobin, hyperbilirubinemia and turbidity are in accordance with known facts. However, slight hemolysis was found to interfere with the alkaline phosphatase (ALP) assay and mild lipemia affected the glucose assay. The Konelab 20XT is an easy-to-use analyzer that is suitable for routine and emergency analyses in small laboratories.
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PMID:Evaluation of the Konelab 20XT clinical chemistry analyzer. 1600 62

Ethanol is one of the most widely used and abused drugs, increasing lipid levels in humans and experimental animals. Heating of oil rich in polyunsaturated fatty acids (PUFA) produces various lipid peroxidative end products that can aggravate the pathological changes produced by ethanol. In the present communication, the effect of Cuminum cyminum was investigated on alcohol and thermally oxidized oil induced hyperlipidaemia. The results showed increased activity of aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) and increased levels of cholesterol, triglycerides and phospholipids in the plasma of rats given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control group. The levels of tissue (liver and kidney) cholesterol and triglycerides were increased significantly in rats groups given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control rats. The levels were decreased when cumin was given along with alcohol and thermally oxidized oil. The level of phospholipids decreased significantly in the liver and kidney of groups given alcohol, thermally oxidized oil and alcohol+thermally oridized oil when compared with the normal control rats. The level increased when cumin was administered along with alcohol and thermally oxidized oil. The activity of phospholipase A and C increased significantly in the liver of groups given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control rats, whereas the activity was decreased with the cumin treatment. The results obtained indicate that cumin can decrease the lipid levels in alcohol and thermally oxidized oil induced hepatotoxicity.
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PMID:Therapeutic role of Cuminum cyminum on ethanol and thermally oxidized sunflower oil induced toxicity. 1610 95


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