Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the enormous cardiovascular disease epidemic and poor survival among individuals with chronic kidney disease (CKD), traditional risk factors such as hypercholesterolemia, hypertension, and obesity appear not as relevant as was previously thought, nor would their management improve survival in patients with CKD who are undergoing dialysis. On the contrary, kidney disease wasting (KDW) (also known as the malnutrition-inflammation complex), renal anemia, and kidney bone disease (KBD) appear to be the 3 most important nontraditional risk factors associated with cardiovascular disease in CKD. KBD-associated hyperparathyroidism may contribute to worsening refractory anemia and KDW/inflammation. The main cause of secondary hyperparathyroidism is active vitamin D deficiency. Hence, treatment of patients with KBD with vitamin D analogs, especially those with lesser effects on calcium and phosphorus such as paricalcitol, may be the most promising option for improving CKD outcomes. By conducting survival analyses in a 2-year (7/2001 to 6/2003) cohort of 58,058 patients on hemodialysis, we recently found that associations between high serum parathyroid hormone and increased death risk were masked by the demographic and clinical characteristics of patients, and that alkaline phosphatase had an incremental association with mortality. Administration of paricalcitol was associated with improved survival in time-varying models. We now present additional subgroup analyses that show that administration of any dose of paricalcitol, when compared with no paricalcitol, is associated with better likelihood of survival in virtually all subgroups of patients on hemodialysis. Because these associations may be secondary to bias by indication, randomized clinical trials are necessary to verify the findings of this and similar observational studies.
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PMID:Impact of kidney bone disease and its management on survival of patients on dialysis. 1719 30

The monosex Nile tilapia, Oreochromis niloticus L., was exposed to subacute concentration (1.46 microg/l) of a pyrethroid insecticide, deltamethrin for 28 consecutive days. Behavioural, clinical, haematological, serum biochemical and histopathological consequences were assayed at a regular interval of 7 days. The abnormal behavioural responses and toxic symptoms were described. Exposure to deltamethrin not only significantly decreased lymphocyte and basophile percentages, total leucocytic and total erythrocytic counts, haemoglobin percentage and packed cell volume value, but also caused serious effects in the form of hypoproteinaemia, hypoalbuminaemia, hypercholesterolaemia, hyperglycaemia and significantly increased serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase activities. Moreover, the histopathological results indicated that the haemobiotic organs were affected by deltamethrin, primarily liver and gills. Our data suggest that subacute exposure to deltamethrin exerts a serious metabolic distress on the fish corresponding to the exposure period. In addition, the assayed parameters and histopathological findings can be as good biomarkers of pyrethroid ecosystem pollution.
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PMID:Subacute intoxication of a deltamethrin-based preparation (Butox) 5% EC) in monosex Nile tilapia, Oreochromis niloticus L. 1805 29

Osteoporosis has been linked with arteriosclerotic vascular diseases, suggesting that hypercholesterolemia or dyslipidemia may be a common pathogenetic factor underlying these diseases. However, little is known about the relationship between osteoporosis and hypercholesterolemia. The purpose of this study was, therefore, to investigate the effects of hypercholesterolemia upon bone metabolism, by measuring bone turnover markers in hypercholesterolemic patients. This study included 281 Japanese patients with hypercholesterolemia, and 267 control subjects. Serum bone-specific alkaline phosphatase (BAP) of the patients was significantly higher than that of the controls in women. Serum N-terminal telopeptide of type I collagen (NTx) of the patients was significantly higher than that of the controls in both men and women. In addition, both BAP and NTx in men showed a significantly negative correlation with high density lipoprotein cholesterol (HDL-C). On the other hand, in women, both BAP and NTx showed a significantly positive correlation with total cholesterol and low density lipoprotein cholesterol (LDL-C). These results indicate increased bone turnover in hypercholesterolemic or dyslipidemic patients regardless of gender, and suggest the importance of treating hypercholesterolemia or dyslipidemia in order to prevent not only arteriosclerotic complications but also osteoporotic bone loss and subsequent fractures.
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PMID:Increased bone turnover in patients with hypercholesterolemia. 1821 79

Statin treatment reduces hypercholesterolemia and may be anti-inflammatory. Case reports noted decreased alkaline phosphatase and histological improvement following statin treatment in primary biliary cirrhosis. The objective of this study was to assess the long-term effects of statin treatment in primary biliary cirrhosis. A retrospective analysis compared clinical and biochemical data from 15 hypercholesterolemic individuals with primary biliary cirrhosis who were treated long-term with atorvastatin with an age and gender matched, primary biliary cirrhosis control group. A significant decrease in total cholesterol and low-density lipoprotein (LDL)-cholesterol (p < or = 0.002) was observed throughout atorvastatin treatment (median time 2.5 years). LDL-cholesterol levels in the control group were not significantly changed after 2 years (p > 0.050). No significant changes were noted in alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin and Mayo Risk Score in either group (p > 0.05). Long-term atorvastatin treatment reduced LDL-cholesterol in primary biliary cirrhosis, but there was no evidence of any anti-inflammatory effect.
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PMID:Atorvastatin does not improve liver biochemistries or Mayo Risk Score in primary biliary cirrhosis. 1839 79

The association between hypercholesterolemia and kidney damage has been well known for last few decades. The oxidative stress and inflammatory responses are involved in renal injury, which is upregulated in hypercholesterolemic condition. The present study is aimed to evaluate the possible effect of lupeol and its ester derivative, lupeol linoleate in renal damage associated with hypercholesterolemic rats. Hypercholesterolemia was induced in male Wistar rats by feeding them with a high cholesterol diet (HCD) comprising normal rat chow supplemented with 4% cholesterol and 1% cholic acid for 30 days. Lupeol and lupeol linoleate were supplemented (50 mg/kg body wt/day) to HCD fed rats during the last 15 days. Increased levels of renal total cholesterol, triglycerides and phospholipids, along with altered serum biochemical parameters of tissue injury indices and elevated activities of renal marker enzymes (lactate dehydrogenase and alkaline phosphatase) were noted in HCD fed rats. Elevated lipid peroxidation levels coupled with decreased antioxidant status (enzymatic and non enzymatic antioxidants) were observed in hypercholesterolemic rats, which indicate the onset of oxidative changes in the renal tissue. Renal lysosomal acid hydrolase activities (ACP, beta-Glu, beta-Gal, NAG and Cat-D) and acute phase proteins like C-Reactive protein and fibrinogen were significantly increased in HCD fed rats, which further indicates the heightening of inflammation. In addition, histopathological findings also confirmed the renal damage in hypercholesterolemic condition. Lupeol and lupeol linoleate effectively reverted the above abnormalities and was comparable with that of the control. These observations highlight the protective effect of lupeol and its ester derivative in ameliorating the renal injury associated with hypercholesterolemia.
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PMID:Protective effect of lupeol and lupeol linoleate in hypercholesterolemia associated renal damage. 1856 36

Poloxamers are polyoxyethlyene, polyoxypropylene block polymers. The impurities of commercial grade Poloxamer 188, as an example, include low-molecular-weight substances (aldehydes and both formic and acetic acids), as well as 1,4-dioxane and residual ethylene oxide and propylene oxide. Most Poloxamers function in cosmetics as surfactants, emulsifying agents, cleansing agents, and/or solubilizing agents, and are used in 141 cosmetic products at concentrations from 0.005% to 20%. Poloxamers injected intravenously in animals are rapidly excreted in the urine, with some accumulation in lung, liver, brain, and kidney tissue. In humans, the plasma concentration of Poloxamer 188 (given intravenously) reached a maximum at 1 h, then reached a steady state. Poloxamers generally were ineffective in wound healing, but were effective in reducing postsurgical adhesions in several test systems. Poloxamers can cause hypercholesterolemia and hypertriglyceridemia in animals, but overall, they are relatively nontoxic to animals, with LD(50) values reported from 5 to 34.6 g/kg. Short-term intravenous doses up to 4 g/kg of Poloxamer 108 produced no change in body weights, but did result in diffuse hepatocellular vacuolization, renal tubular dilation in kidneys, and dose-dependent vacuolization of epithelial cells in the proximal convoluted tubules. A short-term inhalation toxicity study of Poloxamer 101 at 97 mg/m(3) identified slight alveolitis after 2 weeks of exposure, which subsided in the 2-week postexposure observation period. A short-term dermal toxicity study of Poloxamer 184 in rabbits at doses up to 1000 mg/kg produced slight erythema and slight intradermal inflammatory response on histological examination, but no dose-dependent body weight, hematology, blood chemistry, or organ weight changes. A 6-month feeding study in rats and dogs of Poloxamer 188 at exposures up to 5% in the diet produced no adverse effects. Likewise, Poloxamer 331 (tested up to 0.5 g/kg day(-1)), Poloxamer 235 (tested up to 1.0 g/kg day(-1)), and Poloxamer 338 (at 0.2 or 1.0 g/kg day(-1)) produced no adverse effects in dogs. Poloxamer 338 (at 5.0 g/kg day(-1)) produced slight transient diarrhea in dogs. Poloxamer 188 at levels up to 7.5% in diet given to rats in a 2-year feeding study produced diarrhea at 5% and 7.5% levels, a small decrease in growth at the 7.5% level, but no change in survival. Doses up to 0.5 mg/kg day(-1) for 2 years using rats produced yellow discoloration of the serum, high serum alkaline phosphatase activity, and elevated serum glutamicpyruvic transaminase and glutamic-oxalacetic transaminase activities. Poloxamers are minimal ocular irritants, but are not dermal irritants or sensitizers in animals. Data on reproductive and developmental toxicity of Poloxamers were not found. An Ames test did not identify any mutagenic activity of Poloxamer 407, with or without metabolic activation. Several studies have suggested anticarcinogenic effects of Poloxamers. Poloxamers appear to increase the sensitivity to anticancer drugs of multidrug-resistant cancer cells. In clinical testing, Poloxamer 188 increased the hydration of feces when used in combination with a bulk laxative treatment. Compared to controls, one study of angioplasty patients receiving Poloxamer 188 found a reduced myocardial infarct size and a reduced incidence of reinfarction, with no evidence of toxicity, but two other studies found no effect. Poloxamer 188 given to patients suffering from sickle cell disease had decreased pain and decreased hospitilization, compared to controls. Clinical tests of dermal irritation and sensitization were uniformly negative. The Cosmetic Ingredient Review (CIR) Expert Panel stressed that the cosmetic industry should continue to use the necessary purification procedures to keep the levels below established limits for ethylene oxide, propylene oxide, and 1,4-dioxane. The Panel did note the absence of reproductive and developmental toxicity data, but, based on molecular weight and solubility, there should be little skin penetration and any penetration of the skin should be slow. Also, the available data demonstrate that Poloxamers that are introduced into the body via routes other than dermal exposure have a rapid clearance from the body, suggesting that there would be no risk of reproductive and/or developmental toxicity. Overall, the available data do not suggest any concern about carcinogenesis. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used, and at what concentration, indicates a pattern of use. Based on these safety test data and the information that the manufacturing process can be controlled to limit unwanted impurities, the Panel concluded that these Poloxamers are safe as used.
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PMID:Safety assessment of poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate as used in cosmetics. 1883 Aug 66

Nonalcoholic steatohepatitis (NASH) comprises dysregulation of lipid metabolism and inflammation. Identification of the various genetic and environmental susceptibility factors for NASH may provide novel treatments to limit inflammation and fibrosis in patients. This study utilized a mouse model of hypercholesterolemia, low-density lipoprotein receptor knockout (LDLr(-/-)) mice fed a high-fat diet for 5 months, to test the hypothesis that farnesoid X receptor (FXR) deficiency contributed to NASH development. Either the high-fat diet or FXR deficiency increased serum alanine aminotransferase activity, whereas only FXR deficiency increased bile acid and alkaline phosphatase levels. FXR deficiency and high-fat feeding increased serum cholesterol and triglycerides. Although high fat led to macrosteatosis and hepatocyte ballooning in livers of mice regardless of genotype, no inflammatory infiltrate was observed in the livers of LDLr(-/-) mice. In contrast, in the livers of LDLr(-/-)/FXR(-/-) mice, foci of inflammatory cells were observed occasionally when fed the control diet and were greatly increased when fed the high-fat diet. Consistent with enhanced inflammatory cells, hepatic levels of tumor necrosis factor alpha and intercellular adhesion molecule-1 mRNA were increased by the high-fat diet in LDLr(-/-)/FXR(-/-) mice. In agreement with elevated levels of procollagen 1 alpha 1 and TGF-beta mRNA, type 1 collagen protein levels were increased in livers of LDLr(-/-)/FXR(-/-) mice fed a high-fat diet. In conclusion, FXR deficiency induces pathologic manifestations required for NASH diagnosis in a mouse model of hypercholesterolemia, including macrosteatosis, hepatocyte ballooning, and inflammation, which suggest a combination of FXR deficiency and high-fat diet is a risk factor for NASH development, and activation of FXR may be a therapeutic intervention in the treatment of NASH.
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PMID:Farnesoid X receptor deficiency induces nonalcoholic steatohepatitis in low-density lipoprotein receptor-knockout mice fed a high-fat diet. 1894 97

It is not known if vitamin E in hyperlipidemia and hypercholesterolemia of longer duration has any beneficial or adverse effects on electrolytes, and liver and kidney function. The objectives of this study are to determine (i) if long duration of mild hypercholesterolemia has any adverse effects on serum electrolytes, glucose and enzymes related to liver and kidney functions; (ii) if vitamin E has any effects on serum electrolytes, glucose and enzymes related to liver and kidney function in hypercholesterolemia. Blood samples were collected from the rabbits before and at various intervals during administration of a high cholesterol diet (0.25%) for 2 and 4 months, and while on a high cholesterol diet with vitamin E following a high cholesterol diet. Measurements of serum total cholesterol (TC), glucose, aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), albumin, creatinine, electrolytes [sodium (Na), potassium (K), chloride (Cl), and carbon dioxide (CO2)] were made. High cholesterol diet for 2 months produced hypercholesterolemia which was associated with reductions in serum glucose, unaltered serum electrolytes, ALT, ALP, GGT, albumin and creatinine, and increased levels of AST. Hypercholesterolemia for 4 months had effects similar to hypercholesterolemia for 2 months except it lowered serum ALP. Vitamin E did not affect any of the parameters except serum glucose and Cl, which decreased compared to the values at month 2. Hypercholesterolemia for short and long term does not have adverse effects on liver or kidney function, and serum electrolytes. Vitamin E during hypercholesterolemia does not affect serum electrolytes or liver and kidney function.
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PMID:Effects of vitamin E on serum enzymes and electrolytes in hypercholesterolemia. 1973 Sep 89

It has been reported that Ocimum sanctum L. (OS) leaves decrease serum lipid profile in normal and diabetic animals. No experimental evidences support the anti-hyperlipidemic and antioxidative actions against hypercholesterolemia. Moreover the identity of the specific chemical ingredients in OS leaves responsible for these pharmacological effects are unknown. Since OS leaves are rich in essential oil (EO). Therefore the present study was conducted to investigate the anti-hyperlipidemic and antioxidative activities of EO extracted from OS leaves in rats fed with high cholesterol (HC) diet. EO was extracted by the hydrodistillation method and the chemical constituents were then identified by Gas Chromatography-Mass Spectrometry. The experiment was performed in Male Wistar rats fed with 2.5 g%(w/w) of cholesterol diet for seven weeks. During the last 3 weeks, rats were daily fed with EO. The results showed that phenyl propanoid compounds including eugenol and methyl eugenol were the major constituents of EO. EO suppressed the high serum lipid profile and atherogenic index as well as serum lactate dehydrogenase and creatine kinase MB subunit without significant effect on high serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in rats fed with HC diet. In addition, EO was found to decrease the high levels of thiobarbituric acid reactive substances (TBARS), glutathione peroxidase (GPx) and superoxide dismutase (SOD) without impacting catalase (CAT) in the cardiac tissue while in the liver, it decreased high level of TBARS without significantly effecting GPx, SOD and CAT. Histopathological results confirmed that EO preserved the myocardial tissue. It can be concluded that EO extracted from OS leaves has lipid-lowering and antioxidative effects that protect the heart against hypercholesterolemia. Eugenol that is contained in EO likely contribute to these pharmacological effects.
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PMID:Antioxidant Activity and Lipid-Lowering Effect of Essential Oils Extracted from Ocimum sanctum L. Leaves in Rats Fed with a High Cholesterol Diet. 2010 65

Celery, chicory leaves, and barley grains are valuable in weight loss diets and regulate lipid metabolism. They may reduce risk of fatty liver. The present study aimed to investigate the effect of diet supplementation with celery, chicory, and barley powder on liver enzymes and blood lipids in rats fed with cholesterol-enriched diet. This study used four groups of rats fed with 3% cholesterol were supplemented diet to induce hypercholesterolemia and one group was fed on cholesterol-free basal diet. The dry powder of celery leaves, chicory leaves, and barley grains was separately added to the basal diet at 10% concentration or in combination of three plants at 15% for four weeks. Biochemical analyses of serum liver enzymes and blood lipids as well as histopathological examination of liver were performed. Feeding of diet supplemented with 10% of celery, 10% chicory, and 10% of barley lowered the elevated serum level of liver enzymes and blood lipids in rats. Feeding plant combination of celery, chicory, and barley at 15% concentration (5% from each) was more effective in decreasing the elevation of liver enzymes (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) and blood lipids. The histopathological lesions seen in the livers of hypercholesterolemic rats were ameliorated by feeding this plant mixture. This study recommends that dietary intake of plant mixture of celery; chicory, and barley at 15% (5% of each) concentration can be beneficial to patients suffering from hypercholesterolemia and liver diseases.
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PMID:Hepatoprotective effect of feeding celery leaves mixed with chicory leaves and barley grains to hypercholesterolemic rats. 2171 23


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