Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monocrotaline (MONO), a pyrrolizidine alkaloid, causes pulmonary arterial hypertension and right ventricular hypertrophy due to hepatic metabolism to the alkylating pyrrole dehydromonocrotaline. Taurine a sulfonic amino acid, is hepato- and cardioprotective in a variety of conditions. We have examined the effects of taurine and its amidino analog, guanidinoethane sulfonate (GES), in rats injected i.p. with MONO (65 mg/kg). Taurine and GES were given as 1% solutions in drinking water beginning 14 days before administration of MONO and continuing for 14 days therafter, when the rats were killed. The MONO group had right ventricular hypertrophy and pulmonary hyperplasia. Compared with control, no significant changes in the right ventricle/left ventricle weight ratio, or the right ventricle/body weight ratio occurred in rats also given taurine of GES. Lung weights in these two groups were higher than in the control group, but below that of the MONO-alone group. The lethality of MONO over 14 days was decreased by taurine (LD50 for MONO alone 80 mg/kg; for MONO + taurine 121 mg/kg). Rats given only MONO had lower hepatic concentrations of GSH and cysteine (Cys), and higher activities of microsomal GSH transferase activity were no different from control. Gamma-Glutamylcysteine (Glu-Cys) synthetase and gamma-glutamyl transpeptidase activities were elevated. In MONO-injected rats given GES, hepatic GSH levels were higher and Cys levels were lower than in either the MONO alone or MONO + taurine groups. Gamma-Glu-Cys synthetase activity was depressed. Microsomal GSH transferase, GSH peroxidase and gamma-glutamyl transpeptidase activities were elevated. Livers of MONO-injected animals showed higher levels of serine (reversed by both taurine and GES) and glycine (Gly; reversed by GES) and lower levels of glutamine. Compared with control rats, the following changes occurred in serum amino acids: MONO alone: increased aspartate, taurine and lysine; taurine-supplemented: increased taurine, methionine (Met) and lysine, and decreased Gly; GES-supplemented: decreased asparagine, serine, Gly, arginine, taurine, and valine. Compared with the MONO-alone group, the taurine-supplemented group had higher glutamate (Glu), Met and alanine, and the GES-supplemented group higher alanine and lower serine, Gly, arginine and valine. We conclude that taurine protects against MONO-induced lethality and right ventricular hypertrophy. GES also protects against right ventricular hypertrophy. However, these agents act by different mechanisms, taurine preventing many of the biochemical changes induced by MONO, with GES inducing additional changes.
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PMID:Effects of taurine and guanidinoethane sulfonate on toxicity of the pyrrolizidine alkaloid monocrotaline. 857 99

Monocrotaline (MONO), a pyrrolizidine alkaloid, causes veno-occlusive disease of the liver, pulmonary arterial hypertension, and right ventricular hypertrophy. Toxicity is due to the hepatic formation of a pyrolic metabolite that can be detoxified by conjugation with glutathione (GSH). We have shown that the GSH content of the liver affects the quantity of the pyrrolic metabolite that is released from the liver. We have now examined whether MONO, in turn, affects GSH metabolism. Twenty-four hours after administration of MONO to rats (65 mg/kg, i.p.), the highest concentration of bound pyrrolic metabolites was found in the liver, followed by the lung and kidney. Heart and brain contained lower concentrations of these metabolites. Significantly higher levels of GSH were found in liver and lungs of MONO-treated rats than in saline-injected control animals. In the liver, activities of the following enzymes were elevated: gamma-glutamylcysteine synthetase, GSH synthetase, gamma-glutamyl transpeptidase, dipeptidase, and microsomal GSH transferase. The same changes were seen in the lung. In the heart, gamma-glutamyl transpeptidase activity was decreased markedly, and cytosolic GSH transferase activity was elevated. In the kidney, the activities of GSH synthetase, gamma-glutamyl transpeptidase, and cytosolic GSH transferase were increased. Our results establish a mutual interaction of MONO and sulfur metabolism. It appears that an early metabolic action of MONO is to modify sulfur amino acid metabolism, diverting cysteine metabolism from oxidation to taurine towards synthesis of GSH.
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PMID:Effects of monocrotaline, a pyrrolizidine alkaloid, on glutathione metabolism in the rat. 857 5

The effects of the treatment with benazepril (BEN) on blood pressure and renal function have been evaluated in nine adult patients affected by mild to moderate hypertension. BEN was administered orally, at a single daily dose of 10 mg for four weeks. BEN induced a clinically significant decrease in blood pressure, from a mean basal value of 155/98 mm Hg (+/- 15/7 SD) to 146/92 (+/- 12/9) after seven days of therapy and 139/88 (+/- 11/10) after 28 days in supine position and from 152/104 (+/- 17/6) to 144/97 (+/- 14/6) after seven days and 145/99 (+/- 16/9) after 28 days in a standing position. Plasma urea, creatinine, uric acid and their clearances as well as urine enzymes (GGT, ALP, LDH) remained stable throughout the duration of the therapy. GFR showed a modest increase, from 61.3 +/- 13.2 ml/min to 65.3 +/- 18.3 ERPF showed a slightly more evident increase, from 246.7 +/- 68.1 ml/min to 276.9 +/- 75.6. Plasma levels of glucose, cholesterol and triglycerides were not influenced by BEN. Plasma potassium increased from 4.0 +/- 0.3 to 4.4 +/- 0.5 mEq/liter. The results of this study indicate that BEN is a safe and effective antihypertensive agent that does not cause any adverse renal or metabolic effects.
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PMID:Antihypertensive activity and renal effects of benazepril in humans. 874 26

A significant association between elevations of serum gamma-glutamyl transpeptidase (gamma-GTP) levels and those of blood pressure and hypertension has been reported separately in drinkers and nondrinkers. The aim of the present study is to evaluate whether the relationship between serum gamma-GTP and the prevalence of hypertension is the same or similar in both drinkers and nondrinkers. The study subjects comprised 4,920 male nondrinkers, 9,390 male daily drinkers, 8,081 female nondrinkers, and 278 female daily drinkers, who were aged 40 to 59 years. The prevalence of hypertension in the male and female daily drinkers was 1.5 and 1.3 times, respectively, higher than in the nondrinkers. Mean systolic blood pressure in the male and female drinkers was 4.4 and 3.1 mmHg, respectively, higher than in the nondrinkers. After adjusting for age, body mass index, and serum gamma-GTP levels, the differences in the prevalence of hypertension and the mean systolic blood pressure level between the drinkers and nondrinkers decreased to 1.2 times and 2.7 mmHg, respectively. Although these small differences remained statistically significant, the association between serum gamma-GTP and hypertension appears to be quite similar in both drinkers and nondrinkers, suggesting that hepatic steatosis may play a common, pathogenetic role in the development of hypertension.
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PMID:The relationship between serum gamma-glutamyl transpeptidase levels and hypertension: common in drinkers and nondrinkers. 874 7

In most cases of glomerulonephritis (GN) long-term course lead to chronic renal failure. The cause of inevitably gradually progress of GN to end-stage renal disease (ESRD) is unclear. The histological abnormalities seen in patients with progressive renal failure consist of focal and segmental glomerulosclerosis and tubulointerstitial nephritis. At present it is considered that tubulointerstitial changes attends almost all forms of progressive glomerular and vascular injury. It was known that chronic tubulointerstitial nephritis is characterized morphologically by tubular atrophy, interstitial fibrosis and interstitial inflammation of variable severity. The pathomechanism of this changes is complicated. Tubular ischaemia results from obliteration of peritubular capillaries, adaptation of tubular function with increased oxygen consumption and increased glomerular capillary permeability to macromolecules are reasons of chronic tubular damage. Injured tubules release growth factors and cytokines, which induce interstitial fibroblast proliferation, chemo-attraction and proliferation of infiltrating cells, and disruption of the balance between synthesis and degradation of cellular constituents. The consequences of these processes are tubular atrophy and interstitial fibrosis. Because of many studies concurred that tubulointerstitial changes determinant the progression of GN, tubular injury markers were searched for. Although over 50 enzymes were detected in human urine, only a few have been used for diagnosis in renal disease. The most widely used are lysosomal enzyme N acetyl-beta-D-glucosaminidase (NAG) and brush border enzymes alanine-aminopeptidase (AAP) and gamma-glutamyltransferase (GGT). tubular damage in hypertension, diabetes and in diagnostics of renal disease. AAP and GGT, brush border enzymes seem to be sensitive markers of renal injury too. Pathological value of GGT was observed even in the early stage of disease. Measurement of urinary excretion of low molecular weight proteins was valuable supplement in estimation of tubulointerstitial system malfunction. These proteins are readily filtered by normal glomeruli and virtually completely reabsorbed by normal proximal tubules. Favour are alpha-1-microglobulin (alpha-1-m) and retinol-binding protein (RBP) because they are less affected than beta-2-microglobulin (beta-2-m) by low urine pH. Above presented review confirm that further research in correlation between activity of disease, histological picture, deterioration in renal function and changes in urinary excretion of markers proteins (for example alpha-1-m, AAP, NAG, GGT) is advisable, and can contribute to use in clinic diagnostics of GN.
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PMID:[The role of tubulointerstitial changes in progression of kidney function failure in patients with chronic glomerulonephritis (GN)]. 875 11

The relationships of change in body mass index (BMI) on blood pressure, blood and serum tests, and of life style, working posture and job category on change in BMI after age twenty were investigated in a cross sectional study. A total of 771 male employees aged 21 or older (mean age 29.9 +/- 9.1 years) of a semiconductor factory were examined in December 1993. BMI change of each subject was expressed as percent increase after age twenty. BMI value at age twenty was calculated from self-reported body weight at twenty and height measured at the 1993 health examination. Prevalences of high blood pressure (systolic blood pressure > or = 160 mmHg or diastolic blood pressure > or = 95 mmHg), high blood pressure including borderline hypertension (systolic blood pressure > or = 140 mmHg or diastolic blood pressure > or = 90 mmHg) and abnormal values of serum GOT, GPT, gamma-GPT, total cholesterol, triglyceride, HDL-cholesterol, uric acid and fasting blood glucose were greater in the high BMI change group than in the low BMI change group (Chi-square test, P < 0.1). With the exception of hypertension, these associations remained virtually unchanged after adjusting for age, alcoholic consumption, smoking habits and BMI at 20 years of age by multiple logistic regression analysis. After adjustment for age by the Mantel-Henszael method, increases in BMI after 20 years of age were positively associated with the following eight items (p < 0.05): shorter standing time, shorter walking time, lower meal skipping frequency, shorter meal time, longer sitting time during work, larger meal size, greater frequency of salad consumption, and sedentary work such as clerk and engineer. Greater rice consumption and higher frequency of instant foods consumption were weakly associated with the increase in BMI (0.05 < p < 0.1). Job categories such as clerk and engineer were significantly associated with longer sitting time and shorter meal time, resulting in greater BMI increase after 20 years of age. Multiple logistic regression analysis revealed that shorter standing time, shorter meal time, larger meal size, greater frequency of instant foods consumption and greater frequency of salad consumption were independently correlated with the increase in BMI (p < 0.05). Larger rice consumption was slightly correlated with increasing BMI (0.05 < p < 0.1). This study showed that job category, working posture and food intake patterns were strongly associated with BMI change after age 20 in young male workers. This study provides useful information for health care and health promotion programs in young male workers.
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PMID:[Relation of life style, working posture and job category to body mass index change in young male workers]. 883 15

Plasma/serum beta-hexosaminidase (Hex) activity is known to be increased in chronic alcoholism, liver disorders, pregnancy and diabetes mellitus. Hex activity also shows an association with risk factors for vascular disease and heredity for arteriosclerosis. There are several isoenzymes of Hex. Using an enzyme immunoassay for Hex isoenzymes (Hex A and Hex B) we studied possible determinants of Hex isoenzymes and their relation to vascular disease in randomly invited (n = 244) 35-95-year-old men and women. In both sexes there were significant age-related increases in Hex activities and men exhibited higher activity of both isoenzymes. Both Hex isoenzymes correlated with age, systolic blood pressure, serum triglycerides and liver enzymes, whereas Hex A was distinguished from Hex B by its stronger correlation with blood glucose. In multiple linear regression analysis Hex A was explained to 20.7% by blood glucose, age, serum aspartate aminotransferase and glutamyl transpeptidase. Hex B was explained to 14% by age, serum glutamyl transpeptidase and serum triglycerides. There was no significant increase in Hex isoenzymes in subjects with hypertension, diabetes mellitus or myocardial disease, nor did current smokers exhibit any increase of these enzymes compared to non-smokers. The main conclusion in that liver function, as reflected by the level of liver enzymes and glucose metabolism, is the major determinant for Hex isoenzymes in plasma.
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PMID:beta-Hexosaminidase isoenzymes A and B in middle-aged and elderly subjects: determinants of plasma levels and relation to vascular disease. 888 76

Interferon (IFN) therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and is often limited by side effects. Cyclosporine A (CsA) is a potent immunosuppressant widely used in organ transplantation. We conducted a pilot study to determine whether CsA therapy could affect aminotransferase activity and hepatitis C virus RNA levels in patients with chronic hepatitis C. Cyclosporine A was administered to 10 patients (mean age of 59 years; male:female = 9:1) who did not respond to IFN therapy previously and who had elevated serum alanine aminotransferase (ALT) values for at least 6 months. All patients were positive for HCV-RNA by RT-PCR with genotype 1b. Their mean duration of hepatitis was 15 years. Oral CsA was given for 3 months in a dose that was increased at 1 month intervals from 1.5-2.0 to 2.0-3.0 and 3.0-4.0 mg/kg per day. All patients completed the treatment schedule, although two patients developed mild non-symptomatic hypertension. Serum ALT levels gradually decreased in all but one patient. The mean percentage decrease was 59.5% at the end of therapy (from 153 +/- 82 to 62 +/- 48 IU/L; P < 0.02). The ALT levels fell to the normal range in five patients, although once therapy was discontinued the enzyme levels tended to return to pretreatment levels. Serum aspartate aminotransferase and g-glutamyl transpeptidase levels similarly decreased. The serum HCV-RNA titre, determined by competitive RT-PCR, did not change in any patient throughout the study period. There were no appreciable alterations in other laboratory tests, such as serum creatinine levels and lymphocyte subsets, except for an increase in serum alkaline phosphatase levels. These findings suggest that CsA, even in a relatively low dose, reduces serum aminotransferase levels without serious side effects in patients with chronic hepatitis C, although an antiviral effect was not noted.
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PMID:Cyclosporine therapy affects aminotransferase activity but not hepatitis C virus RNA levels in chronic hepatitis C. 907 26

In 1987, the National Institute for Occupational Safety and Health conducted a cross-sectional medical study to examine the long-term health effects of occupational exposure to chemicals and materials contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). This study compared living workers employed more than 15 years earlier in the production of sodium trichlorophenol (NaTCP), and 2,4,5-trichlorophenoxyacetic ester (2,4,5-T ester) with an unexposed comparison group. Health status of the worker and comparison populations was collected through a comprehensive set of standardized interviews and medical examinations. Lipid adjusted serum TCDD levels were also measured. Workers had a statistically significantly elevated mean serum lipid-adjusted TCDD level (workers = 220 pg per g of lipid [range = not detected-3,400 pg per g of lipid], and referents 7 pg per g of lipid [range not detected-20 pg per g of lipid], P < 0.001). Compared to a community-based referent population, the prevalence of chronic bronchitis, chronic obstructive pulmonary disease, peripheral neuropathy, depression, cardiovascular outcomes (myocardial infarction, angina, cardiac arrhythmias, hypertension, and abnormal peripheral arterial flow), abnormal porphyrin levels, and abnormal ventilatory function parameters FEV1.0, FVC, or FEV1.0/FVC% in workers, was not statistically significantly different. In contrast, relationships were observed between serum 2,3,7,8-TCDD levels and the enzyme gamma-glutamyltransferase (GGT), the reproductive hormones serum testosterone, luteinizing, and follicle-stimulating hormones, and abnormal high-density lipoprotein concentration, counts of CD3/Ta1 cells (helper lymphocytes), and fasting serum glucose levels. Current diagnosis of chloracne was associated with the highest levels of serum 2,3,7,8-TCDD. Analysis of other endpoints continues.
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PMID:Review and update of the results of the NIOSH medical study of workers exposed to chemicals contaminated with 2,3,7,8-tetrachlorodibenzodioxin. 950 33

A review of findings in randomised trials with at least one-year follow-up suggests that primary care physicians can intervene briefly and successfully for patients manifesting symptoms of excessive drinking but no serious dependence. The risk level can be assessed by summing the preceding week's intake of spirits, wine and beer in standard measures and then convert it into grams of pure alcohol. Denial is minimised by using a non-judgmental lifestyle approach, and defining problems in terms of lifestyle habits and its consequences. Nervous problems, hypertension and dyspepsia are the most common diagnoses in the target group. Measurement of biochemical markers can be used, the serum gamma-glutamyl transpeptidase (GGT) level being still the most useful. Questionnaires are of limited value as they are associated with high false-positive rates. To motivate patients to reduce alcohol consumption, an intervention strategy with feedback is proposed, mainly based on the monitoring of symptoms and clinical findings including biochemical markers, and a self-help pamphlet is recommended. It is emphasised that the goal should be realistic to the patient, and that controlled drinking is an acceptable goal even in cases of mild dependence.
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PMID:[How can primary health care influence patients' alcohol drinking habits. "Simple intervention" results in a new therapeutic perspective]. 982 60


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