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)

Orlistat is an anti-obesity agent that increases the fecal fat excretion, which promotes colon carcinogenesis. Therefore, the present study was designed to verify the effects of Orlistat on the formation of rat colonic aberrant crypt foci (ACF) and cell proliferation evaluated by the PCNA method. Male Wistar rats received either a standard diet or a high fat diet (HFD), supplemented or not with Orlistat (200mg/kg chow) and two doses of the carcinogen dimethyl-hydrazine (25mg/Kg). After 30 days, Orlistat was associated to a significant increase in the number of colonic ACFs and cell proliferation in DMH-treated animals, independently of the HFD.
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PMID:The anti-obesity agent Orlistat is associated to increase in colonic preneoplastic markers in rats treated with a chemical carcinogen. 1637 80

Acceptable adverse effects and a clinical relevant weight loss of 3 to 5 kilograms have been found in long-term randomized clinical trials for sibutramine (Reductil) and orlistat (Xenical); these drugs may be prescribed for treatment of obesity for a duration of one and four years, respectively. This also seems to be the case for rimonabant (Acomplia), which is expected to receive approval in 2005 or 2006. However, until data on morbidity and mortality are available from RCTs, there is no absolute indication for prescribing drugs for treatment of obesity.
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PMID:[Drug treatment of obesity]. 1640 42

Obesity is a chronic disease and prevalence and incidence are progressively increasing. Treatment of obesity is important to reduce mortality and associated diseases, like diabetes mellitus, hypertension, abnormal blood lipid levels, coronary heart disease, thromboembolic disease, cancer (endometrial, gallbladder, cervical, ovarian, breast, prostate and colorectal), polycystic ovary syndrome (PCOS), gallbladder disease, respiratory disease, arthritis, gout. Most of these pathologies profits by a modest weight loss (5-10%). A correct management of obesity should include integration of therapeutic strategies, that we have actually at disposal: diet, physical training, behaviour therapy, pharmacologic therapy and surgery. We should get together low-calorie and low-fat diet with behaviour change and physical training. Physical training induces a significant weight loss and reduces cardiovascular risks and insulin resistance. Orlistat, that reduces up to 30% lipid adsorption, is a valid remedy if with an adequate diet. A new drug, sibutramine, shows efficacy: it increases satiety and energy expenditure caused by thermogenesis in brown adipose tissue. Surgical approaches including some procedures, are indicated for great obesity (BMI >40).
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PMID:[Management of overweight and obese patient. New acquisition]. 1648 74

Nitric oxide (NO) is known to be a messenger molecule that plays an important role in physiological and pathological conditions. It is synthesized by an enzyme called nitric oxide synthase (NOS). Inducible NOS (iNOS), one of the three isomers of NOS, has both protective and toxic properties. In this study, the role of NO has been evaluated by gastrointestinal symptoms induced by orlistat which is used in obesity treatment. Orlistat was given to Wistar rats with and without iNOS inhibition. The effects of orlistat and inhibition of NOS were studied. Glucose, urea, alanine transaminase (ALT), and gamma glutamil transpeptidase (GGT) were descreased after short- and long- term orlistat applications. Dexamethasone increased level of these enzymes. Cholesterol and triglyceride were increased in all experimental groups than the controls. This increment was more severe in animals received orlistat and dexamethasone together. Small intestinal tissue also were researched histologically and NADPH-diaphorase (NADPH-d) histochemistrically. Orlistat caused histological damages in brush border membranes, connective tissues of villi, and lymphocyte migration also increased. Dexamethasone treatment prevented these damages partially while orlistat increased the NOS distribution in the tissue sections. Dexamethasone, which is an iNOS inhibitor, decreased NADPH-d histochemistry. There was a similiar NOS distribution both in the control and orlistat+dexamethasone group. Hence, we concluded that long- term trials with orlistat and similar drugs are needed.
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PMID:Effects of orlistat and its relationship with nitric oxide in the small intestinal mucosa. 1654 24

Some of the medications used for weight loss in the management of obesity have been associated with unacceptable morbidity and mortality. Safety concerns have led to the withdrawal of aminorex, followed by the fenfluramines in 1997, and phenylpropanolamine (norephedrine) in 2000. Aminorex was associated with an increased prevalence of primary pulmonary hypertension (PPH), fenfluramines with an increased prevalence of PPH and valvulopathy, and phenylpropanolamine with an increased risk of haemorrhagic stroke. Several studies have investigated the safety of the fenfluramines, yet the benefit-risk profile has not been conclusively quantified. This is due to several deficiencies in the published studies, including a lack of data on the baseline prevalences of comorbid conditions in obese subjects, and potential confounders and biases in the study designs. Although several studies and systematic reviews support an increased risk of PPH and valvulopathy in patients who have taken fenfluramines, without knowledge of the background prevalence it is not possible to determine if the exposure preceded the outcome. The population at higher risk of these adverse effects includes those taking higher doses or with a longer duration of exposure to fenfluramines and those with pre-existing cardiac disease or a genetic predisposition. Patients exposed to fenfluramines continue to be monitored, with some follow-up studies indicating no overall worsening in valvulopathy over time. There are limited efficacy and safety data for amfepramone (diethylpropion) and phentermine and their approval for the management of obesity is limited to short-term use. Orlistat and sibutramine are the only currently approved medications for long-term management of obesity. Although the benefit-risk profiles of sibutramine and orlistat appear positive, sibutramine continues to be monitored because of long-term safety concerns. The safety and efficacy of currently approved drug therapies have not been evaluated in children and elderly patient populations and there is limited information in adolescents, whilst the long-term safety of current and potential new drug therapies in adults will require several years of postmarketing surveillance to fully elucidate their adverse effect profiles.
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PMID:Safety of drug therapies used for weight loss and treatment of obesity. 1656 79

Orlistat (Xenical) is a reversible inhibitor of gastric and pancreatic lipases. In conjunction with a hypocaloric diet and moderate exercise, orlistat is an effective drug for use in the management of obesity in adults with or without comorbidities. Recent data have shown that orlistat is also effective as a component of weight management strategies in obese adolescents. In addition to its well established efficacy in achieving modest weight loss, orlistat has been shown to improve glycaemic parameters in obese adults with type 2 diabetes mellitus as well as some features of the metabolic syndrome. Orlistat is generally well tolerated. Thus, orlistat is an option for the treatment of obese patients with or without type 2 diabetes and also has a role in the management of obese patients with the metabolic syndrome, associated comorbidities or concomitant disorders.
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PMID:Orlistat: a review of its use in the management of obesity. 1695 13

Obesity poses a serious threat for health, being a risk factor for development of heart diseases, diabetes type II, tumors, and reproductive function failure. The aim of this study is to investigate the effect of orlistat (xenical) on the character of menstrual cycle and some metabolic indicators in women with obesity. 17 patients of reproductive age with I-III degree of obesity were investigated. The visceral type of obesity and disorders of menstrual cycle were observed in all patients: oligomenorrhea was observed in 9 (52.9%), amenorrhea in 4 (23.5%)and metrorrhagia in 4 (23.5 %) patients. All the patients received orlistat (xenical) 120 mg 3 times per day during 6 months. Orlistat (xenical) therapy results in significant reduction of body weight (12.3%), body mass index (13.3%), improvement of lipid and carbohydrates metabolisms. Normalization of hormonal levels was registered. As a result of all this the restoration of menstrual cycle and ovulation is registered. Orlistat (xenical) is effective in the treatment of women with obesity and menstrual cycle disorders.
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PMID:[Use of orlistat (xenical) in the treatment of women with obesity and disorders of menstrual cycle]. 1707 58

Obesity is a frequent complication following liver transplantation and is insufficiently responsive to dietary and life style advice. We studied the safety of orlistat treatment in obese and overweight liver transplant recipients (n = 15) on a stable tacrolimus-based immunosuppressive regimen. For safety reasons, the treatment period was restricted (6 months 120 mg t.i.d., 3 months 120 mg daily). Three patients dropped out, tacrolimus dose was adjusted in six of 12 remaining patients (dose reduction in 4, increase in 2, P = N.S.). All dose adjustments occurred during the 6 months of orlistat 120 mg t.i.d. therapy. No drug intolerance, adverse events or episodes of rejection occurred during the study. Efficacy of orlistat treatment in this population could not be shown, because a formal control population was not included in this safety trial. Moreover, only a significant decrease of waist circumference (P < 0.01 versus start of the study), but not of weight or body mass index, was achieved in the treated group. Orlistat treatment is well tolerated in liver transplant recipients and can be started safely, provided immunosuppressive drug levels and dietary adherence are closely monitored.
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PMID:Orlistat treatment is safe in overweight and obese liver transplant recipients: a prospective, open label trial. 1708 Dec 30

Antiobesity treatment is recommended for selected patients in whom lifestyle modification is unsuccessful. Two antiobesity drugs are currently licensed for long-term use. Orlistat, a gastrointestinal lipase inhibitor, reduces weight by around 3 kg on average and decreases progression to diabetes in high-risk patients; adverse gastrointestinal effects are common. Sibutramine, a monoamine-reuptake inhibitor, results in mean weight losses of 4-5 kg, but is associated with increases in blood pressure and pulse rate. Rimonabant, the first of the endocannabinoid receptor antagonists, reduces weight by 4-5 kg on average and improves waist circumference and concentrations of HDL cholesterol and triglyceride; however, an increased incidence of mood-related disorders has been reported. To date, all antiobesity drug trials have been limited by their high attrition rates and lack of long-term morbidity and mortality data. Other promising antiobesity drugs, including those acting within the central melanocortin pathway, are in development, but are years away from clinical use. In light of the lack of successful weight-loss treatments and the public-health implications of the obesity pandemic, the development of safe and effective drugs should be a priority. However, as new drugs are developed we suggest that the assessment processes should include both surrogate endpoints (ie, weight loss) and clinical outcomes (ie, major obesity-related morbidity and mortality). Only then can patients and their physicians be confident that the putative benefits of such drugs outweigh their risks and costs.
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PMID:Drug treatments for obesity: orlistat, sibutramine, and rimonabant. 1741 51

Nonalcoholic steatohepatitis (NASH) may cause progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Treatment, thus far, has been restricted to diet and weight loss, but without compelling results. In this study we aimed to evaluate the efficacy of orlistat therapy in obese patients with NASH. Fourteen obese patients with NASH underwent liver biopsy prior to and subsequent to 6 months treatment with orlistat (120 mg tid). Hepatic fat extension was graded as normal, mild, moderate, or severe. Hepatic fibrosis was scored on a scale from 0 to 4, with 0 denoting no fibrosis and 4, cirrhosis. Portal inflammation was scored as 0-3, with 0 = normal, 1 = mild, 2 = moderate, and 3 = severe inflammation. Fourteen patients had NASH associated with diabetes, hyperlipidemia, or obesity. Orlistat reduced fatty infiltration in 10 patients (70%; P<0.01), 3 of whom had normal liver fat content after treatment. Orlistat improved inflammatory activity by 2 grades in 28% and by 1 grade in 50% of patients and effected no change in 22% of patients. Five patients (35%) returned to normal inflammatory activity. Orlistat improved hepatic fibrosis by 2 grades in three patients (21%) and by 1 grade in seven patients (50%). There was no change in four patients (28%). Orlistat lowered aminotransferases levels, total cholesterol, triglycerides and low-density lipoprotein, respectively. Insulin resistance index and malonyl dialdehyde levels improved significantly after orlistat therapy, whereas HbAic remained unchanged. In conclusion, in obese patients with NASH, liver fibrosis and inflammation improved after therapy with orlistat.
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PMID:Orlistat reverse fatty infiltration and improves hepatic fibrosis in obese patients with nonalcoholic steatohepatitis (NASH). 1740 56


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