UMLS:C0028754 - FACTA Search

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Query: UMLS:C0028754 (obesity)
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The choice of a dialysis treatment depends on many factors, both medical and non-medical. A full and rational treatment requires easy access to a transplantation programme and to all dialysis modalities, extracorporeal or peritoneal. Presently, haemodialysis (HD) is used almost exclusively for in-centre or limited care treatment, peritoneal dialysis (PD) being preferred for home treatment. On HD, bicarbonate buffer is used in preference to acetate. Mixed convective-diffusive HD techniques have a very limited utilization world-wide because of their cost. Use of PD and automated PD continues to grow, although slowly. In our single-centre experience on a large number of patients, 10-year patient survival is not different on CAPD and HD, and there is initial lower risk of death on CAPD for patients > or = 75 years of age. Drop-out from CAPD has increased in recent years, mainly due to the patient/partner 'burn-out'. Drop-out is less for the elderly, and the difference in modality change between CAPD and HD decreases with increasing patient age, suggesting a clear indication for CAPD in the elderly, or in adults waiting for a transplant. The clinical background, e.g. the presence of diabetes mellitus, cardiovascular disease, dyslipidaemia or obesity, is also important in the choice of method.
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PMID:Differing dialysis treatment strategies and outcome. 880 14

Hypertensive patients have an excess of other cardiovascular risk factors. Moreover, traditional therapy based on diuretics and beta-blockers may aggravate these risk factors. Therefore, attention must be given to the identification of all pertinent risk factors and their amelioration by appropriate therapy. Such therapy must include lifestyle changes including cessation of smoking, reduction of obesity, moderation of sodium intake and alcohol consumption, and increased physical activity. When antihypertensive drugs are chosen, consideration should be given to their potential influences, either negative or positive, on other cardiovascular risk factors. In particular, the adverse effects of diuretics and beta-blockers on lipids and insulin sensitivity may preclude their use. alpha-Blockers and ACE inhibitors may have beneficial effects on these metabolic indices. Calcium antagonists are neutral in most regards. Whatever agents are chosen, the use of low doses in combination is being increasingly recognized as a better way to achieve the desired antihypertensive efficacy while minimizing adverse effects. As has been noted in the other papers in this supplement, the combination of an ACE inhibitor and a calcium antagonist is particularly attractive, not only to treat hypertension, but also to ameliorate other cardiovascular risk factors.
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PMID:The challenge of managing multiple cardiovascular risk factors. 923 94

In subjects with coronary artery diseases (obstructive and vasospastic angina pectoris (AP)) who have no diabetes, hypertension, obesity and physical inactivity, insulin sensitivity was significantly reduced with compensated hyperinsulinemia on OGTT. Insulin resistance significantly correlated with coronary atherosclerosis score. In vasospastic AP (VAP), those who fulfilled more than 3 risk factors out of 5 (hyperinsulinemia, obesity, glucose intolerance, hypertension, dyslipidemia) consist of 70 and 40% for smokers and nonsmokers respectively. Insulin resistance syndrome who fulfilled all the criteria was 9-10% for VAP. In atherothrombotic brain infarction (ATTI) with the same exclusion criteria, the similar insulin resistance and hyperinsulinemia have been observed, but not in embolic (cardiac origin) or lacunar infarction. In ATTI, high TG and apo B with low HDL-chol were noted in blood. In essential hypertension without diabetes and obesity, hyperinsulinemia was noted in 25-35% and insulin resistance in 56-88%. Reduction of blood pressure with alpha blocker (bunazosin), ACE inhibitor (cilazapril), long-acting Ca++ blocker (amlodipine) significantly improved lowered insulin sensitivity. Insulin resistance rather than hyperinsulinemia is more closely associated with blood pressure. Cardiovascular diseases (vasospastic and obstructive AP, brain cortical artery diseases) are prone to develop diabetes because of insulin resistance and also promote the generation of cumulative risk factors resulting in a vicious cycle. Efforts to alleviate insulin resistance is crucial for the primary and secondary prevention of cardiovascular diseases.
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PMID:Clinical impact of insulin resistance syndrome in cardiovascular diseases and its therapeutic approach. 924 Jul 71

We have investigated the possible involvement of endogenous corticosteroids in the maintenance of hypertension in aged lean and obese Zucker rats using the type II corticosteroid antagonist mifepristone. At 8 mo of age, the start of the study, obese Zuckers had been hypertensive for at least 2 mo (systolic blood pressure; 153 +/- 4 vs. 136 +/- 5 mmHg; n = 8-9; P < .05) and were hyperinsulinemic (756 +/- 98 vs. 193 +/- 61 microU x ml(-1)) and hypercorticosteronemic (524 +/- 83 vs. 260 +/- 97 ng x ml(-1)) compared to their lean littermates. There were no differences in plasma renin activity between lean and obese animals and plasma renin activity was unaffected by any treatment. Oral treatment of obese rats with mifepristone (40.0 mg x kg(-1) day(-1) for 9 days) resulted in a gradual reduction in SBP to lean levels by day 9. Mifepristone treatment did not affect plasma insulin or corticosterone levels but resulted in a significant reduction in plasma aldosterone concentration. Mifepristone was without significant effect on systolic blood pressure in lean rats. Oral treatment of lean rats with corticosterone-21-acetate (3.0 mg x kg(-1) day(-1) for 9 days) resulted in a rise in systolic blood pressure to levels similar to obese Zuckers after 9 days. Plasma insulin levels were unchanged but corticosterone immunoreactivity was significantly reduced. Plasma aldosterone levels were increased from 564 +/- 3 to 802 +/- 68 pg x ml(-1). Our data suggest that raised glucocorticoids and aldosterone may be factors contributing to hypertension in obesity.
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PMID:Effects of the glucocorticoid II receptor antagonist mifepristone on hypertension in the obese Zucker rat. 931 65

There has been increasing interest in the question of whether microalbuminuria can be used in the risk stratification of patients with essential hypertension. A cluster of cardiovascular and/or renal risk factors may be associated with microalbuminuria in hypertension. Despite this, prospective data about the potential role of microalbuminuria as a prognostic marker of cardiovascular and/or renal risk have been sparse and inconclusive until now. Blood pressure values have been considered the most important determinant of microalbuminuria in essential hypertension; however, hyperinsulinaemia--a metabolic component-was noted to be present in conjunction with high blood pressure. Furthermore, 2 other factors may be also related to microalbuminuria: salt sensitivity and renal structural changes (nephrosclerosis). We are now aware that the clinical and physiological implications of abnormal urinary albumin excretion (UAE) are much broader than anticipated, possibly involving haemodynamic, metabolic and vascular components overlapping several clinical syndromes. Achievement of short term UAE reduction with antihypertensive treatment depends on structural abnormalities established in the glomerulus, the extent of blood pressure reduction and the antihypertensive drug class used. In terms of UAE reduction, better results are obtained with ACE inhibitors or angiotensin II antagonists such as losartan and valsartan, than with other antihypertensive classes, although their true impact in preserving renal function needs to be assessed. The capacity of new calcium antagonists, such as amlodipine, lacidipine or mibefradil, to reduce UAE also needs to be assessed further. Thus, microalbuminuria may be seen as an integrated marker of risk and should be assessed in recently diagnosed patients with essential hypertension. In microalbuminuric patients, the target should be to decrease blood pressure < 135/85 mm Hg, reduce salt intake to around 100 mmol/day and prescribe a low-calorie diet if obesity is present. ACE inhibitors or angiotensin II antagonists have more potential benefits than the other classes of antihypertensive drugs in reducing UAE. Finally, a yearly assessment of microalbuminuria is recommended during treatment, to monitor the impact of therapy.
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PMID:Treatment of patients with essential hypertension and microalbuminuria. 942 93

The prevention of coronary artery disease is based on the control of several factors associated with a disease or clinical condition and suspected to play a pathogenetic role, defined as 'risk factors'. Smoking is a powerful risk factor for coronary artery disease, with risk of events increasing in relation to the number of cigarettes smoked daily. Smoking cessation is associated within 3-4 years, with a significant reduction in cardiovascular risk. Hyperlipidaemia is a powerful predictor of coronary disease with a strong, independent, continuous and graded positive association between cholesterol levels and risk of coronary events. Several large studies have shown the benefit of cholesterol reduction, and there is clear evidence of the efficacy of statins in the reduction of events in primary and secondary prevention. Hypertension is a significant, strong and independent risk factor for coronary artery disease morbidity and mortality and the reduction of events and mortality by antihypertensive treatment is well documented. Obesity is associated with an increase in all-cause mortality and cardiovascular mortality, with a particularly high risk for subjects with central obesity. Central obesity is also part of the so-called 'metabolic X syndrome' including insulin resistance, which appears to be associated with a particularly high risk of coronary artery disease. Type 1 and type 2 diabetes mellitus are associated with an increased risk of cardiovascular disease, especially in women. Several studies have shown that good metabolic control and multifactorial risk factor reduction significantly lower the coronary risk in these patients. Recent evidence is accumulating that some clotting factors (fibrinogen, factor VII, von Willebrand factor) and fibrinolytic factors (t-PA and PAI-1) are associated with an increased risk of coronary artery disease. The European Concerted Action on Thrombosis (ECAT) showed that the levels of fibrinogen, von Willebrand factor antigen, and t-PA antigen are independent predictors of subsequent coronary syndromes in patients with angina pectoris, and that low fibrinogen is associated with a low risk of events despite high cholesterol levels. Post-menopausal status is associated with increased risk of coronary artery disease, particularly when menopause is premature (before the age of 45) or abrupt (surgical). There is strong, thought not yet completely definite evidence that post-menopausal hormone replacement therapy may significantly reduce the risk of events and improve survival. Hyperhomocysteinaemia is an emerging risk factor independently associated with an increased risk of coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The administration of vitamin B6, B12 or folate seems to be useful and is currently under further evaluation. Recently, attention has been focused on the correlation between coronary artery disease and genetic factors, such as ACE gene polymorphism or the gene polymorphism for the IIIa-moiety of the platelet fibrinogen receptor IIb-IIIa. In primary prevention, control of the major risk factors mainly in patients with clustered factors will substantially reduce the risk of ischaemic events. Secondary prevention of CHD is based on: aggressive behavioural advice, blood pressure reduction in hypertensives, good metabolic control of diabetes, and cholesterol reduction. Aspirin, beta-blockers, ACE inhibitors, and oral anticoagulants, may be useful in selected patients.
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PMID:Classical risk factors and emerging elements in the risk profile for coronary artery disease. 951 44

Insulin action starts with binding to a membrane receptor (insulin receptor-tyrosine kinase) and with activating an insulin receptor substrate 1 (IRS-1) and substrate 2 (IRS-2). Insulin receptors interact at least with three cascade reactions, phosphorylating G proteins and IRS-1, that activate PLC "ras" and PI-3-K. NIDDM can be defined as a disease caused by defective transduction of insulin signals and IR as a complex phenotype manifesting itself, emphasized by individual and environmental factors, in the cellular systems of signal transduction. IRS is a syndrome characterized by NIDDM, hypertension, visceral obesity, CHD: the X syndrome. Up to day the described mutations of the insulin-receptor gene are rare (e.g. the leprechaunism): genetic IR. Obesity is the principal cause of IR by receptorial and post-receptorial defects: metabolic IR. The obese skeletal muscle shows a reduction of insulin receptor and IRS-1 phosphorylation and of PI-3-K activation; the scarce expression of these proteins would determine the muscular IR. IR is a pattern of essential hypertension. Hypertension, dyslipidemia and abnormality of glucose metabolism are linked by IR. The so called high erythrocyte Na(+)-Li+ counter-transport is a new biochemical marker for IR and hypertension. These drugs can reduce IR: metformin, sulphonilureas, fibrats, dexfenfluramine, troglitazone, doxazosin, ACE-inhibitors.
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PMID:[Insulin resistance. Receptor and post-receptor abnormalities]. 984 54

Obese hypertensive patients with cardiovascular risk factor clustering have increased plasma nonesterified fatty acid levels and are at high risk for atherosclerotic events. Our previous studies demonstrated that oleic acid induces a mitogenic response in rat aortic smooth muscle cells (RASMCs) through protein kinase C (PKC)- and extracellular signal-regulated kinase (ERK)-dependent pathways. In the present study we investigated the possibility that the generation of reactive oxygen species (ROS) constitutes a critical component of the oleic acid-induced mitogenic signaling pathway in RASMCs. We studied the effect(s) of oleic acid on the generation of ROS using the oxidant-sensitive fluoroprobe 2',7'-dichlorofluorescin diacetate. Relative fluorescence intensity and fluorescent images were obtained with laser confocal scanning microscopy from 1 to 5 minutes, since preliminary studies demonstrated that the peak fluorescence intensity occurred within 5 minutes. Oleic acid (100 micromol/L) induced a time-dependent increase of cell fluorescence that was >8-fold of that seen in control cells at 5 minutes. This was blocked by catalase, which suggests that H2O2 was the principal ROS. The oleic acid-induced increases in H2O2 were blocked when PKC was inhibited with the use of bisindolylmaleimide and when PKC activity was downregulated by exposing RASMCs to phorbol 12-myristate 13-acetate for 24 hours. Stearic and elaidic acids, which are weak PKC activators, did not significantly increase H2O2 production. The increase of H2O2 in response to oleic acid was inhibited by the antioxidant N-acetylcysteine. N-Acetylcysteine also completely blocked ERK activation and the increase of thymidine incorporation in response to oleic acid. The data suggest that generation of H2O2 in RASMCs exposed to oleic acid is PKC dependent. Moreover, H2O2 production emerges as a critical intermediary event in the oleic acid-mediated mitogenic signaling pathway between the activation of PKC and ERK. These observations raise the possibility that the elevated plasma nonesterified fatty acids, including oleic acid, in obese hypertensive patients contribute to vascular growth and remodeling by a PKC-dependent mechanism to generate ROS that subsequently activate ERK.
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PMID:Reactive oxygen species are critical in the oleic acid-mediated mitogenic signaling pathway in vascular smooth muscle cells. 985 64

For a given body mass index (BMI), mortality is higher in patients with central compared to generalized obesity. Glucocorticoids play an important role in determining body fat distribution, but circulating cortisol concentrations are reported to be normal in obese patients. Our recent studies show enhanced conversion of inactive cortisone (E) to active cortisol (F) through the expression of 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in cultured omental adipose stromal cells; the autocrine production of F may be a crucial factor in the pathogenesis of central obesity. We have now analyzed F metabolism in subjects with BMIs between 20-25 kg/m2 (group A), 25-30 kg/m2 (group B), and more than 30 kg/m2 (group C; n 12 in each group; six males and six premenopausal females; aged 23-44 yr). Glucose/insulin were measured using a 75-g oral glucose tolerance test, and each subject had total body and regional fat (scapular, waist, hip, and thigh) quantified using dual energy x-ray absorptiometry. Urinary total F metabolites (measured by gas chromatography/mass spectrometry) were increased in subjects with obesity [group A, 11,176 +/- 1,530 microg/24 h (mean +/- SE); group C, 13,661 +/- 1,444], although not significantly so (P = 0.08). There was a significant reduction in the urinary tetrahydrocortisol (THF) +/- 5alpha-THF/tetrahydrocortisone (THE) and the cortol/cortolone ratio in obesity (group A vs. C, 1.06 +/- 0.08 vs. 0.84 +/- 0.04 and 0.41 +/- 0.03 vs. 0.34 +/- 0.03, respectively; both P < 0.05). Urinary free F (UFF) excretion was similar in all three groups, as was the UFF/urinary free E (UFE) ratio. The 0900 h circulating F, E, and ACTH pre- and postovernight 1-mg dexamethasone suppression values were similar in all three groups, but a reduction in the generation of serum F from dexamethasone-suppressed values after oral cortisone acetate (25 mg) was evident in both obese groups [e.g. 546 +/- 37 nmol/L in group A vs. 412 +/- 40 in group B (P < 0.05) and 388 +/- 38 in group C (P < 0.01) 180 min post-E]. Insulin resistance was present in groups B and C, but regression analysis revealed no relationship between F metabolites or the THF +/- 5alpha-THF/THE ratio and insulin action (homeostasis model assessment analysis and insulin values in the oral glucose tolerance test). There was, however, a highly significant relationship between the THF +/- 5alpha-THF/THE ratio and BMI (t = -3.44; P < 0.01) and total body fat (t = -2.27; P < 0.05). Stepwise regression analyses indicated an inverse relationship between THF+/-5alpha-THF/THE and scapular and waist fat (t = -2.25; P = 0.03) and a direct relationship with hip and thigh fat (t = 2.42; P = 0.02) in both sexes. The fall in the THF + 5alpha-THF/THE ratio but unchanged UFF/UFE ratio together with impaired F concentrations after oral E indicates inhibition of 11betaHSD1 in subjects with obesity. This results in an increased MCR for F, explaining the increased F secretion rate in obesity in the face of normal circulating F concentrations. 11BetaHSD1 activity is highly related to body fat distribution, with android or central obesity, but not gynoid obesity, associated with reduced activity in both sexes. This reduction in 11betaHSD1 activity raises new questions as to the primary role of 11betaHSD1 in the pathogenesis of insulin resistance and central obesity.
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PMID:Cortisol metabolism in human obesity: impaired cortisone-->cortisol conversion in subjects with central adiposity. 1008 90

Many adolescents present with hirsutism and irregular menses. The challenge for the clinician is to distinguish physiologic anovulatory cycles from true menstrual disorders such as PCOS, and to differentiate PCOS from other causes of hyperandrogenism in hirsute adolescents. Common clinical features seen in adolescents with PCOS include hirsutism, acne, menstrual irregularity, and obesity. Biochemical abnormalities include hyperandrogenism, acyclic estrogen production, LH hypersecretion, decreased levels of SHBG, and hyperinsulinemia. Management strategies for a patient with PCOS include treatment of features which may cause distress to the adolescent, such as hirsutism, acne, and irregular menses, and prevention of long-term sequelae. Oral contraceptive pills, antiandrogens, and cosmetic treatments are used to treat hirsutism, acne, and menstrual irregularity. Oral contraceptive pills or medroxyprogesterone acetate are given to prevent endometrial hyperplasia and carcinoma. Counseling about weight loss and nutrition are essential, as weight loss may improve signs of hyperandrogenism and menstrual irregularity and may prevent NIDDM and cardiovascular disease. Insulin-sensitizing agents show promise in terms of decreasing hyperandrogenism, restoring ovulatory cycles, treating infertility, and preventing long-term sequelae. Finally, it is important to recognize that adolescents with PCOS may experience psychological distress because of the clinical manifestations of hyperandrogenism or when confronted with the information that they have a chronic illness. Psychological support should be available for these young women. Future research is likely to further elucidate the pathophysiology of PCOS, identify candidate genes, and clarify which adolescents are at risk for long-term sequelae. Prospective studies are needed to identify which therapies could potentially reduce the risk of infertility, diabetes, cardiovascular disease, and endometrial carcinoma in young women with PCOS.
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PMID:Polycystic ovary syndrome. 1037 Jul 13

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