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)

Primary biliary cirrhosis (PBC) is a chronic nonsuppurative, destructive cholangitis, whose etiology is unknown. Morbidity arises early from pruritus and later from hypercholesterolemia with xanthoma formation. Therapy is supportive and directed at the complications of cholestasis. Plasmapheresis has been reported to benefit patients with hyperlipidemia and PBC; thus a pilot study of plasmapheresis utilizing the Haemonetics Model 30 with replacement by albumin and saline was conducted. Five patients (four female and one male) with a mean age of 43 (range 29-58) and a mean duration of illness of 9.5 years (range 6-21) with marked jaundice, xanthomas, xanthelasma, hepatomegaly, fatigability, anorexia, and pruritus, as well as mild nausea were studied. Peripheral neuropathy was present in two patients. Two patients had splenomegaly. Two patients had an associated Sjogren syndrome. All patients had high serum bilirubin, alkaline phosphatase, and cholesterol levels and mild elevations in aspartate amino transferase and alanine amino transferase activities. Immune complexes measured in four patients were present. Antimitochondrial antibody titers were significant in all patients. Patients underwent a mean of 63 plasmapheresis procedures over a mean of 112 weeks removing a mean of 94.7 liters of plasma. No serious toxicity was seen. All patients showed a reduction in pruritus, xanthomas, xanthelasmas, and serum cholesterol values. The two patients who had evidence of Sjogren syndrome noted subjective improvement. All patients who had fatigue, anorexia and nausea also noted moderate improvement. There was no change in hepatomegaly or splenomegaly in patients demonstrating such organomegaly. Liver function did not change significantly. Overall, four patients had improvement in their condition and one patient achieved stability.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The clinical effectiveness and safety of chronic plasmapheresis in patients with primary biliary cirrhosis. 403 Jul 9

Naturally-occurring hyperadrenocorticism was diagnosed in an 11-year-old female Dachshund with signs of polydipsia, polyuria, pendulous abdomen, weakness, depression and lethargy, and laboratory test abnormalities comprising lymphocytopaenia, eosinopaenia, hypercholesterolaemia and increased plasma alkaline phosphatase concentration. While awaiting hormonal test results, an adrenocorticolytic drug (o,p'-DDD) was administered for 14 days, during which the patient deteriorated. Hormonal assays suggested a functioning adrenocortical tumour, but the poor condition of the patient precluded adrenalectomy. An adrenocortical carcinoma with hepatic metastases was found at necropsy.
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PMID:Functioning adrenocortical tumour in a dog. 628 91

Twenty-seven patients with primary hypothyroidism were studied to evaluate the relationship between hepatic function and thyroid hormone deficiency in this disorder. In hypothyroidism, hypergammaglobulinemia was found in 71%, elevated glutamic oxaloacetic transaminase (GOT) in 48%, high lactic dehydrogenase (LDH) in 58%, hypercholesteremia in 52% and low elimination rate constant of indocyanin green (KICG) in 44%. In each criterion of liver function, these patients were divided into two groups, normal level and abnormal level group, respectively. T3 and T4 in patients with abnormal levels of GOT, glutamic pyruvic transaminase (GPT), gamma-glutamyl transpeptidase (gamma-GTP), leucine aminopeptidase (LAP), alkaline phosphatase (ALP) and 45 minutes retention rate of bromsulphalein (BSP) were not different from those in the normal level group. However, T3 and T4 in patients with abnormal levels of LDH, cholesterol, cholinesterase (ChE) and KICG were lower than those in the normal level group. The abnormal KICG group had a statistically higher cardio-thoracic ratio (CTR) than the normal group (65.7 +/- 18.8% vs 50.4 +/- 8.3%, p less than 0.05). In patients with pericardial effusion, CTR was 65.9 +/- 14.6%, while that in patients without pericardial effusion was 49.9 +/- 7.5% (p less than 0.05). These abnormalities of liver function were normalized in all cases after hormone replacement therapy. Liver biopsy in three cases disclosed normal liver in two cases and mild infiltration of monocyte into Glisson's capsule in one case.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic dysfunction in primary hypothyroidism. 673 26

The benefits of using cyclosporin in organ transplantation to prevent graft rejection outweigh its potential disadvantages, but with the use of low-dose cyclosporin in relatively healthy individuals, such as those with psoriasis, the risk:benefit ratio is altered. The effects of low-dose cyclosporin (< 5 mg/kg body weight) on liver function and serum lipids and lipoproteins were examined in 40 normolipidaemic, normotensive psoriasis patients with normal renal function. After 3 months of treatment, serum cholesterol and bilirubin concentrations and alkaline phosphatase activity increased significantly (p = 0.001), and glomerular filtration rate (GFR) declined from 107 to 96 ml/min/1.73 m2 (p = 0.05). All these values returned to pretreatment levels 3 months after cessation of cyclosporin. In 15 patients in whom lipoproteins were isolated by ultracentrifugation, there was an increase in plasma low-density lipoprotein (LDL) cholesterol (p = 0.05), but very-low-density lipoprotein cholesterol, high-density lipoprotein (HDL) and HDL2 and HDL3 cholesterol concentrations did not change. The increases in serum bilirubin, alkaline phosphatase activity and LDL cholesterol, seen in individuals with normal baseline liver and renal function, which reverted to baseline following cessation of cyclosporin, suggest that cyclosporin-induced hypercholesterolaemia may be due to either decreased biliary excretion of cholesterol or impaired catabolism of LDL.
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PMID:Effect of low-dose cyclosporin on plasma lipoproteins and markers of cholestasis in patients with psoriasis. 770 61

When used as treatment for hypercholesterolemia HMG-CoA reductase inhibitors will first pass through and act upon the gut mucosa. Although cholesterol availability is essential for cell growth of the intestinal mucosa adverse intestinal events are rare which is possibly due to hitherto undefined compensatory mechanisms. In the present work we therefore studied the long-term influence of mevinolin on proliferation and differentiation of CaCo-2 cells as an enterocyte model and their response upon the cholesterol supply of different origin. Mevinolin caused a marked and dose-dependent inhibition of cell proliferation, microvilli length and alkaline phosphatase. This parallel suppression was reversed by the addition of either exogenous free cholesterol, endogenous cholesterol from mevalonolactone or LDL but not HDL3. Surprisingly, sucrase activity reacted in an inverse fashion to alkaline phosphatase activity. Mevinolin induced enzyme activity and this was further enhanced by mevalonolactone supply, while cholesterol and LDL normalized sucrase to controls. In conclusion, the presence of luminal cholesterol as well as plasma LDL as the cholesterol source for the enterocyte may prevent mevinolin toxicity.
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PMID:Influence of cholesterol supply on cell growth and differentiation in cultured enterocytes (CaCo-2). 789 34

Risk factors for primary cerebral hemorrhage remain uncertain. The population-based Stroke Registry of Dijon provides data on the risk factors. Among residents of Dijon (France), 130 cases of primary cerebral hemorrhage hospitalized from 1985 to 1992 were matched with 130 controls by age and sex. The following data were collected: history of hypertension, alcohol consumption, tobacco consumption, history of coagulation disorder, diabetes mellitus, dyslipidemia, and infectious disease in the 7 days before admission. The following parameters were measured on admission: blood pressure, blood glucose, cholesterol, triglycerides, hematocrit, fibrinogen, prothrombin levels, platelet counts, prothrombin time, bilirubin, transaminases, gamma-glutamyltransferase, and alkaline phosphatase. Electrocardiogram and Doppler ultrasound examination of cervical arteries were performed. Statistical analysis was performed by means of relative risk ratio for paired samples when dealing with proportions, and Student's t test for quantitative variables. A stepwise discriminant analysis was carried out to establish the relative weight of the different risk factors and their discriminant values. Among the qualitative data, the significant factors were history of hypertension, alcohol consumption, cardiac arrhythmia, atherosclerosis of carotid arteries and a previous infectious disease in the 7 days before admission. Among the quantitative data, the significant factors were early hypertension, high blood glucose levels, high hematocrit, and low cholesterol levels, in the acute stage of the stroke. After multifactorial analysis, only two factors were significant: hypertension and low cholesterol levels. Our population-based case-control study showed that hypertension and low cholesterol levels are the two discriminant risk factors for both lobar and basal ganglia primary cerebral hemorrhage. Therefore, treatment of hypercholesterolemia may increase risk of cerebral hemorrhage.
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PMID:Risk factors for primary cerebral hemorrhage: a population-based study--the Stroke Registry of Dijon. 789 3

We describe a 33-yr-old pregnant woman in whom a primary biliary cirrhosis-like syndrome developed after 2 wk of chlorpromazine therapy. The clinical course was characterized by severe jaundice lasting 22 mo, intense pruritus, fever, steatorrhea, high alkaline phosphatase levels and hypercholesterolemia. Jaundice resolved with initiation of ursodeoxycholic acid therapy, but subclinical cholestasis and low-level inflammatory activity persisted and ultimately evolved into biliary cirrhosis. The pathological substrate of this severe and prolonged cholestatic reaction was found to be the vanishing bile duct syndrome with a marked transient pseudoxanthomatosis.
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PMID:Chlorpromazine-induced vanishing bile duct syndrome leading to biliary cirrhosis. 798 42

A total of 123 patients with primary hypercholesterolemia were randomized on a 2:1 ratio to receive either fluvastatin at 20 mg once daily at night (n = 82) or gemfibrozil at 600 mg twice daily (n = 41) in a double-blind, double-dummy comparison of the effects on plasma lipid parameters and tolerability over 8 weeks. All patients had either low-density lipoprotein cholesterol (LDL-C) concentrations > or = 160 mg/dL (4.1 mmol/L) in association with definite coronary artery disease (CAD) or > or = 2 risk factors, or LDL-C > or = 190 mg/dL (4.9 mmol/L) with no CAD and < 2 risk factors. All had triglyceride (TG) levels < or = 350 mg/dL (4.0 mmol/L). After 8 weeks of treatment, fluvastatin produced significant reductions from baseline of 17.4% (p < 0.001) in LDL-C, 13.2% (p < 0.001) in total cholesterol (TC), 13.8% (p < 0.001) in very low-density lipoprotein cholesterol (VLDL-C), and 6.4% (NS) in TG. High-density lipoprotein cholesterol (HDL-C) was increased by 5.6% (p < 0.001), and the ratio of LDL-C:HDL-C (Friedewald) was decreased by 21.2% (p < 0.001). Gemfibrozil reduced LDL-C by 15.8%, TC by 13.4%, VLDL-C by 32.2%, LDL-C:HDL-C by 24.8%, and TG by 34.2%, and increased HDL-C by 13.9% (all changes were statistically significant, p < 0.001) compared with baseline. Gemfibrozil produced significantly greater changes in VLDL-C (p < 0.01), HDL-C (p < 0.001), and TG (p < 0.001), but not in LDL-C: HDL-C, compared with fluvastatin. Both drugs significantly reduced apolipoprotein (apo) B and lipoparticles (Lp) E:B, and increased apo A-I but had divergent effects on LpA-I (increased with fluvastatin and reduced with gemfibrozil; p < 0.05). At the end of the study, 43.8% of fluvastatin patients and 45% of gemfibrozil patients achieved a reduction of > 20% in LDL-C levels. Normalization of LDL-C levels was achieved (according to European Atherosclerosis Society guidelines) by 13.4% of fluvastatin- and 14.6% of gemfibrozil-treated patients. Both drugs were well tolerated; adverse events occurred in 36.6% of fluvastatin recipients compared with 58.5% of patients taking gemfibrozil. No clinically notable elevations of aspartate or alanine aminotransferases, alkaline phosphatase, or creatine phosphokinase occurred. No patient developed new or worsening lens opacities associated with a reduction in optically corrected visual acuity. The most commonly reported adverse events were headache and gastrointestinal upset. There were no serious drug-related adverse events.
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PMID:Comparison of lipid-lowering effects of low-dose fluvastatin and conventional-dose gemfibrozil in patients with primary hypercholesterolemia. 801 67

Sixty-six dogs with hypothyroidism were identified from dogs examined over a 5-year period. Hypothyroidism was diagnosed only if the dog had a low, resting serum thyroxine concentration and serum thyroxine concentration was not higher than the lower limits of the reference range 6 hours after IV administration of bovine thyrotropin. The prevalence of hypothyroidism was 0.2%. Neutering was determined to be the most significant gender-associated risk factor for development of hypothyroidism. Neutered male and spayed female dogs had a higher relative risk of developing hypothyroidism than did sexually intact females. Sexually intact females had a lower relative risk. Breeds with a significantly increased risk, compared with other breeds, were the Doberman Pinscher and Golden Retriever. The most common clinical findings were obesity (41%), seborrhea (39%), alopecia (26%), weakness (21%), lethargy (20%), bradycardia (14%), and pyoderma (11%). Low voltage R-waves were found on 58% of ECG. Clinicopathologic abnormalities included hypercholesterolemia (73%), nonregenerative anemia (32%), high serum alkaline phosphatase activity (30%), and high serum creatine kinase activity (18%). Serum total triiodothyronine concentrations were within reference ranges in 15% of the hypothyroid dogs. Response to treatment was good in most dogs, but those with severe concurrent disease or neurologic abnormalities were less likely to respond with complete resolution of clinical signs.
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PMID:Hypothyroidism in dogs: 66 cases (1987-1992). 817 72

There is little quantitative information about the influence of weight change before and during hemodialysis on the concentration of proteins, lipoproteins, lipids, enzymes and other dialysis-resistant compounds in blood. We studied the concentration of 12 such compounds before and at the end of high-flux hemodialyses, 1.5 h after the start and 1, 2 and 3 h postdialysis and have developed formulae for roughly predicting the near steady-state 2-3 h postdialysis concentration. For hemoglobin, albumin, total protein and total cholesterol, the relationship of mean change in concentration to weight loss in groups was linear, and the % increase in concentration correlation correlated with % weight reduction (r = 0.64-0.81 and p = 0.002-0.0002). Correlations with ultrafiltration rate were comparable. By 3 h postdialysis values were relatively stable; the average fall in concentration for theses 4 compounds was 25% from end dialysis. The simplest formula we found which roughly predicts the % increase in concentration from predialysis to 3 h postdialysis is to multiply the % loss in body weight in kg during dialysis by 3.3. More accurate formulae were developed using combined and specific regression equations relating % weight loss during dialysis to % concentration rise. Mean values for alkaline phosphatase, triglycerides, lipoprotein (a), high-density lipoprotein cholesterol, calcium, apolipoprotein B, bilirubin and aspartate aminotransferase also rose appreciably during dialysis with significant increases for the first five. With major interdialytic weight gain, the reduction in predialysis concentrations of hemoglobin and cholesterol may be enough to inappropriately modify treatment decisions about anemia (e.g. erythropoietin) or hypercholesterolemia, and to cause false concern about the concentration of albumin for nutrition and prognosis. Major weight gain may also contribute to concentration changes in numerous other compounds resistant to dialysis.
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PMID:Prediction of reduction in predialysis concentrations due to interdialysis weight gain. 853 51


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