Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver injury ranging from simple steatosis to steatohepatitis, fibrosis, and cirrhosis. Whereas simple steatosis has a benign clinical course, steatohepatitis is a recognized cause of progressive liver fibrosis and can develop into cirrhosis. NAFLD and nonalcoholic steatohepatitis (NASH) are the two most common chronic liver diseases in United States general population with a prevalence of 20% and 3%, respectively. Hepatic steatosis is frequently associated with obesity, type 2 diabetes, and hyperlipidemia with insulin resistance as a key pathogenic factor. A two-hit theory best describes the progression from simple steatosis to NASH, fibrosis, or cirrhosis. These two hits consist of the accumulation of excessive hepatic fat primarily owing to insulin resistance, and oxidative stress owing to reactive oxygen species (ROS). Mitochondria are the major cellular source of ROS in cases of NASH. Currently, treatment is focused on modifying risk factors such as obesity, diabetes mellitus, and hyperlipidemia. Antioxidants such as vitamin E, N-acetylcysteine, betaine, and others may be beneficial in the treatment of NASH.
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PMID:Nonalcoholic fatty liver disease: pathogenesis and the role of antioxidants. 1229 56

Steatohepatitis in children occurs in the childhood version of non-alcoholic fatty liver disease (NAFLD), as a result of hepatotoxicity and with certain genetic/metabolic diseases. Until recently, NAFLD was considered to be rare in children. It is now recognized as an important childhood liver disease, especially because childhood obesity is much more common. Children with NAFLD may present as young as 4 years old; males tend to predominate; fibrosis is often found on liver biopsy and cirrhosis has been reported. Treatment for childhood NAFLD currently consists of weight reduction plus regular aerobic exercise; vitamin E may be an effective adjunctive therapy. Drug hepatotoxicity and genetic/metabolic diseases that can cause fatty liver, such as Wilson's disease and cystic fibrosis, must be excluded since treatment is radically different. Other causes of chronic hepatitis, such as chronic viral hepatitis, must also be excluded. Multisystemic inherited diseases with hyperinsulinaemia plus insulin resistance may have NAFLD as hepatic involvement and should be identified.
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PMID:Steatohepatitis in children. 1240 43

Nonalcoholic fatty liver disease, an entity that includes nonalcoholic steatohepatitis, is typically a benign, indolent condition. However, in a subset of patients, the clinical course may progress to advanced cirrhosis, end-stage liver disease, or hepatocellular carcinoma. Unfortunately, the pathogenesis, natural history, and potential therapies for these disorders remain poorly understood. Identifying patients who should be targeted for potential treatment remains difficult. Liver biopsy should be considered to assess the degree of hepatic inflammation and fibrosis, because physical examination findings, biochemical parameters, and the results of radiographic studies have been shown to correlate poorly with the severity of steatohepatitis and fibrosis. Although there is some evidence suggesting that obesity, diabetes mellitus, older age, and perhaps an aspartate transaminase:alanine aminotransaminase ratio higher than 1 may be predictors of more advanced fibrosis, histology remains the gold standard. Most patients with simple hepatic steatosis appear to follow a benign course and probably do not require aggressive therapy. Conversely, patients with steatohepatitis with extensive inflammation and fibrosis are the patients who are most likely to benefit from effective therapies. The most commonly recommended treatment is weight loss. Existing data suggest that rapid weight loss may promote hepatic inflammation and fibrosis; therefore, gradual weight loss should be recommended. Large, randomized, controlled trials evaluating the long-term histologic impact and clinical outcomes of weight loss strategies are lacking. Potentially promising pharmacologic therapies include insulin-sensitizing oral hypoglycemic agents such as metformin and the thiazolidenediols, antihyperlipidemic agents such as gemfibrozil or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, vitamin E and other antioxidants, ursodeoxycholic acid, and betaine. As with weight loss, data regarding the efficacy of these pharmacologic options are limited. In addition, there are no widely accepted guidelines to help direct the clinician in the optimal use of these agents in patients with nonalcoholic fatty liver diseases.
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PMID:Therapeutic Options in Nonalcoholic Fatty Liver Disease. 1240 79

Oxidative stress appears to be of fundamental relevance to diseases as diverse as atherosclerosis, cancer, and Alzheimer's disease. Observational data in humans have suggested that antioxidant vitamin intake is associated with reduced cardiovascular disease. Animal studies are largely consistent with the concept that dietary supplementation with antioxidant vitamins reduces the progression of atherosclerosis. However, recent prospective, controlled clinical trials of vitamin E, including the Cardiovascular Disease, Hypertension and Hyperlipidemia, Adult-Onset Diabetes, Obesity, and Stroke (CHAOS) study, the Heart Outcomes Prevention Evaluation (HOPE) trial, Gruppo Italiano per lo Studio della Sopravvivvenza nell'Infarto Miocardico (GISSI)-Prevenzione trial, the Secondary Prevention with Antioxidants of Cardiovascular Disease in End Stage Renal Disease (SPACE) trial, and the Heart Protection Study (HPS) present a confused picture. The various possibilities that have been advanced to explain this discrepancy are discussed in this review. A striking feature of these and other trials of antioxidants is the absence of a biochemical basis for patient inclusion or, indeed, dose selection. Patients with high levels of oxidant stress or depletion of natural antioxidant defense systems may be the most likely to benefit from antioxidant therapy. If this is the case, then reliable, quantitative indices of in vivo oxidant stress such as urinary isoprostane levels should be considered as an inclusion criterion for patient selection. Future trials of antioxidant therapy in cardiovascular disease should then be targeted toward such patients with high levels of oxidant stress or patients with depletion of natural antioxidant defense systems. Furthermore, the dose of antioxidant should be chosen based on a surrogate readout that is a reliable, reproducible, and easily obtainable in vivo measure of oxidant stress. In the interim, although the safety of vitamin E up to doses of 800 IU/day has been determined, the conflicting nature of the results published to date encourages us to avoid making premature recommendations with respect to vitamin E supplementation in the prevention and treatment of cardiovascular disease.
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PMID:Treatment of atherosclerosis in the new millennium: is there a role for vitamin E? 1273 94

In recent years, vitamin E has been investigated as a cardioprotective agent. Experimental studies have identified potential mechanisms by which vitamin E may inhibit the development of atherosclerosis, and observational studies of individuals without coronary disease suggest that vitamin E intake may prevent future cardiovascular events. Secondary prevention trials to date have demonstrated little benefit from vitamin E supplementation. It remains possible, however, that supplementation may be useful among certain high-risk groups, including those with nutritional deficiencies. Limited data from completed primary prevention trials also indicate minimal cardioprotection from vitamin E, but large-scale trials now in progress may yet show benefit. Results from ongoing trials will contribute powerfully to the totality of evidence on which to formulate both appropriate clinical recommendations for individual patients and a rational public health policy for the population as a whole. At this time, there is insufficient evidence for issuing a public health recommendation to use vitamin E supplements to prevent cardiovascular disease (CVD). Rather, increased intake of fruits, vegetables, and other antioxidant-rich foods should be promoted as part of a healthy diet because they provide nutritional benefits beyond any potential antioxidant effect. Moreover, even if found to reduce CVD risk, vitamin supplement use should be considered an adjunct, not an alternative, to established cardioprotective measures, such as smoking abstention, avoidance of obesity, adequate physical activity, and control of high blood pressure and hyperlipidemia.
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PMID:Does vitamin E supplementation prevent cardiovascular events? 1274 15

Nonalcoholic fatty liver disease (NAFLD) is very common in the United States, and in some patients it may lead to cirrhosis, liver failure, and liver cancer. NAFLD encompasses a spectrum of liver injury, ranging from steatosis to steatohepatitis, advanced fibrosis, and cirrhosis. Nonalcoholic steatohepatitis (NASH), an advanced form of NAFLD, histologically comprises steatosis, balloon degeneration, inflammation, and fibrosis in varying degrees. It is generally believed that simple steatosis is benign with minimal risk of progression, whereas NASH is progressive and can lead to cirrhosis. The commonly associated risk factors for NAFLD include obesity, hyperlipidemia, and diabetes mellitus. The pathogenesis of NAFLD and NASH is not fully known; however, current evidence suggests that insulin resistance and lipid peroxidation play a role in the pathogenesis of this condition. Currently, there are no proven effective therapies available for the treatment of NASH. Although there are numerous studies that have explored various treatments for NASH, these generally consist of small numbers of patients with suboptimal endpoints. Treatment strategies for NAFLD and NASH can be broadly divided into 1) treatment or control of underlying risk factors such as hyperlipidemia, diabetes mellitus, and obesity; and 2) specific pharmacologic therapy such as insulin sensitizers, antioxidants, or cytoprotective agents. Newer thiazolidinediones, such as rosiglitazone and pioglitazone, have shown promise in the treatment of NASH in pilot studies. However, these agents should not be used in clinical practice until their efficacy and safety are firmly established in larger studies. Despite encouraging initial studies, the recently completed multicenter, randomized, controlled trial failed to show any efficacy for ursodeoxycholic acid in the treatment of NASH. Other agents, such as vitamin E, betaine, probucol, and atorvastatin, have been explored as therapeutic agents for NASH. However, none of these studies have shown convincingly their utility in the treatment of NASH. Attempts to identify optimal therapy for patients with NASH are being vigorously pursued by the research community and important advances are expected within next several years. Until then, subjects should be advised to avoid alcohol, lose weight, and exercise regularly, and meticulous attention should be paid to the control of their risk factors such as diabetes and hyperlipidemia.
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PMID:Treatment of Nonalcoholic Fatty Liver Disease. 1458 34

The purpose of the study was a more thorough assessment of the nutrition state of patients admitted to hospitals in Poland. The study was carried out in four hospitals at teaching centre level, in four hospitals at province level, and in four county hospitals. The patients for the study were selected randomly from 3310 adult patients (every 10th patient admitted to these hospitals). For the study 210 patients (122 women and 88 men) were qualified. Their mean age was 54 +/- 16 years (range 15-82 years). The patients were subjected to various biochemical tests including determination of antioxidant vitamins (vitamins A, E and C), vitamin B12, folic acid, ferritin, and homocysteine and blood lipids. Vitamin deficiency accepted as vitamin malnutrition was found in the case of vitamin C in 51.8% of the patients, folic acid in 32%, vitamin E in 10%, vitamin B12 in 6.8%, vitamin A in 1.4%. Vitamin deficiency was equally frequent in patients with malnutrition, overweight or with obesity. Lipid profile disturbances were found in 51% and high homocysteine level in 63% of the studied patients.
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PMID:[Nutritional status of patients in hospitals in Poland. More thorough assessment of nutritional status of adult patients]. 1464 80

Several cardiovascular risk factors are characterized by the coexistence of low-grade inflammation, enhanced oxidative stress and lipid peroxidation. It has been hypothesized that F2-isoprostanes, a product of in vivo lipid peroxidation, may transduce the effects of metabolic and hemodynamic abnormalities into increased cardiovascular risk. Thus, the formation of these compounds, including urinary 8-iso-Prostaglandin (PG) F2alpha, has been investigated in clinical settings putatively associated with oxidant stress. Enhanced lipid peroxidation together with increased in vivo platelet activation have been found in association with the major cardiovascular risk factors. Thus, F2-isoprostanes may transduce the effects of oxidant stress associated with complex metabolic disorders into specialized forms of cellular activation. In particular, the low-grade inflammatory state characterizing metabolic disorders such as obesity, hypercholesterolemia, type 2 diabetes mellitus, and homozygous homocystinuria may be the primary trigger of thromboxane-dependent platelet activation mediated, at least in part, through enhanced lipid peroxidation. Moreover, oxidative stress may promote endothelial dysfunction through increased production of reactive oxygen species that inactivate nitric oxide. Accumulation and activation of leukocytes plays a key role in atherosclerosis and its complications. Interestingly, neutrophil adhesion induced by minimally modified low-density lipoproteins is mainly mediated by F2-isoprostanes. Although epidemiological studies suggest an inverse relationship between antioxidant vitamin intake and cardiovascular disease, several clinical trials have obtained conflicting results on the effects of vitamin E supplementation on the risk of cardiovascular events. On the other hand, the use of F2-isoprostane formation as a biochemical end-point for dose-finding studies of vitamin E supplementation has helped clarifying the unique features of its pharmacodynamic effects on lipid peroxidation. This information could be extremely valuable in the selection of the appropriate patient subgroups that may benefit from antioxidant interventions.
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PMID:Determinants of F2-isoprostane biosynthesis and inhibition in man. 1503 60

Treatment of patients with nonalcoholic fatty liver disease (NAFLD) has typically been focused on the management of associated conditions such as obesity, diabetes mellitus and hyperlipidemia. NAFLD associated with obesity may resolve with weight reduction, although the benefits of weight loss have been inconsistent. Appropriate control of glucose and lipid levels is always recommended, but not always effective in reversing the liver condition. Results of pilot studies evaluating ursodeoxycholic acid, gemfibrozil, betaine, N-acetylcysteine, vitamin E (alpha-tocopherol), metformin and thiazolidinedione derivatives suggest that these medications may be of potential benefit for patients with NAFLD. These medications, however, need first to be tested in well-controlled trials with clinically relevant end-points and extended follow up. A better understanding of the pathogenesis and natural history of NAFLD will help to identify the subset of patients at risk of progressing to advanced liver disease, and hence, those patients who should derive the most benefit from medical therapy.
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PMID:Treatment of nonalcoholic fatty liver disease. 1511 91

Long-term glucocorticoid treatment is associated with severe side effects, such as obesity and osteoporosis. A palm oil-derived vitamin E mixture had been shown previously to be protective against osteoporosis in rats given 120 microg/kg dexamethasone daily for 12 weeks. In this study we determined the effects of two isomers of vitamin E (i.e., palm oil-derived gamma-tocotrienol and the commercially available alpha-tocopherol, 60 mg/kg of body weight/day) on body composition and bone calcium content in adrenalectomized rats replaced with two doses of dexamethasone, 120 microg/kg and 240 microg/kg daily. Treatment period was 8 weeks. gamma-Tocotrienol (60 mg/kg of body weight/day) was found to reduce body fat mass and increase the fourth lumbar vertebra bone calcium content in these rats, while alpha-tocopherol (60 mg/kg of body weight/day) was ineffective. Therefore, in conclusion, palm oil-derived gamma-tocotrienol has the potential to be utilized as a prophylactic agent in prevention of the side effects of long-term glucocorticoid use.
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PMID:Effects of tocopherols and tocotrienols on body composition and bone calcium content in adrenalectomized rats replaced with dexamethasone. 1511 52


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