Obesity and hyperhomocysteinaemia after kidney transplantation.

Teplan V, Schuck O, Stollova M, Vitko S.

Department of Nephrology, Transplant Center, Institute for Clinical and Experimental Medicine, Chair of Nephrology, Institute for Postgraduate Medical Education, Prague, Czech Republic. vladimir.teplan medicon.cz

Obesity and hyperhomocysteinaemia are found very frequently after kidney transplantation (Tx). They may independently represent risk factors for development of atherosclerosis and chronic allograft nephropathy. In a prospective metabolic study, we monitored, over a period of 24 months, a total of 118 obese transplant patients [body mass index (BMI) > or =30 kg/m(2)] with hyperhomocysteinaemia. We compared the findings of a new therapeutic regimen at 1 year (start of the study) and 2 years after renal transplantation. Based on a Subjective Global Assessment Scoring Sheet, we started at the end of the first year with an individualized hypoenergic-hypolipidaemic diet (IHHD). Subsequently, after corticoid withdrawal, IHHD was supplemented regularly with orlistat at a dose of up to 3 x 120 mg/day, statins (pravastatin 10-40 mg), folic acid 5 mg/day and vitamin B6 50 mg/day, and followed-up for up to 2 years. All patients were on a regimen of cyclosporin A and mycophenolate mofetil. During the study period, there was a significant decrease in BMI (P < 0.025) and total homocysteine level (P < 0.001). Long-term therapy was associated with a significant decrease in serum leptin (P < 0.001) and lipid metabolism parameters (P < 0.01). The mean values of serum folate and vitamin B6 also increased significantly (P < 0.01); creatinine clearance, mean blood pressure, proteinuria, lipoprotein(a) and apolipoprotein E isoforms did not differ significantly. Based on our results, we assume that obesity and hyperhomocysteinaemia after renal transplantation can be treated effectively by modified immunosuppression (corticosteroid withdrawal), long-term diet (IHHD), folic acid and vitamin B6 supplementation, and drugs suppressing digestion or absorption to reduce atherosclerotic and chronic allograft nephrop-athy processes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12817077&dopt=Abstract orlistat Xenical online refs
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Diet, Weight Loss, and Cardiovascular Disease Prevention.

Bray GA, Ryan DH, Harsha DW.

Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA. HarshaDW pbrc.edu

Body weight, like cholesterol and blood pressure, are continuous variables. Overweight results when energy intake as food exceeds energy expenditure from exercise for a considerable period of time. When body weight becomes sufficiently high, it poses a risk to cardiovascular and metabolic health. The types of treatments considered by the physician and discussed with a patient should be based on this risk-benefit assessment. The body mass is the basic measurement for this assessment, and should be part of the "vital signs" when a patient is first evaluated by the medical staff. When the body mass index (BMI) is below 25 kg/m(2), there is little risk from the body weight, but because obesity is a "stigmatized" condition, many patients, particularly women, desire to lose weight even within the normal range. For this purpose, a high-quality diet like the Dietary Approaches to Stopping Hypertension (DASH) diet at a reduced-calorie intake would be our recommendation. When the BMI is above 25 kg/m(2), patients deserve dietary advice, but in addition to a reduced-calorie DASH-like diet, this is a place to consider using "portion-control" strategies, such as the nutrition labels that manufacturers provide on canned and frozen foods to guide patients in reducing calorie intake. In overweight individuals at high risk (ie, those with a BMI above 30 kg/m(2) or impaired glucose tolerance, hypertension, or the metabolic syndrome), the use of orlistat or sibutramine along with diet, exercise, lifestyle changes, and portion control should be considered. When the BMI is above 35 kg/m(2), bariatric surgery should also be discussed as an option for the "at-risk" individual. Evidence reviewed here shows that modest weight losses of 5% to 10% can reduce the risk of conversion from impaired glucose tolerance to diabetes and can maintain lower blood pressure over extended periods. All of the approaches described above can produce weight losses of this magnitude.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12834563&dopt=Abstract orlistat Xenical online refs
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Validation in an animal model of the carbon 13-labeled mixed triglyceride breath test for the detection of intestinal fat malabsorption.

Kalivianakis M, Elstrodt J, Havinga R, Kuipers F, Stellaard F, Sauer PJ, Vonk RJ, Verkade HJ.

Groningen University Institute for Drug Exploration, Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics, University Hospital Groningen, The Netherlands.

OBJECTIVE: To determine, in a rat model of fat malabsorption, the potency of the carbon 13-labeled mixed triglyceride ((13)C-MTG) breath test as a noninvasive, patient-friendly replacement for classic fat balance studies.Study design: Comparison of the percentage of fat absorption, detected by fat balance, with the (13)CO(2) recovery of the (13)C-MTG breath test in rats fed high-fat chow and varying amounts of the lipase inhibitor, orlistat (0, 50, 200, and 800 mg per kilogram of chow), for 5 days. RESULTS: On orlistat administration, total fat absorption decreased from 80.2% +/- 2.2% to 32.8% +/- 3.7% (mean +/- SEM, 0 mg and 800 mg of orlistat per kilogram of chow, respectively; P <.001). Correspondingly, breath (13)CO(2) recovery from (13)C-MTG at 6 hours decreased from 84.5% +/- 7.8% to 42.0% +/- 1.5% of the dose (0 mg and 800 mg of orlistat per kilogram of chow, respectively; P <.001). The 6-hour recovery of breath (13)CO(2) appeared to be highly correlated with the percentage of fat absorption (r = 0.88, P <.001). In rats with fat absorption higher than 70%, however, the coefficient of variation of the (13)C-MTG breath test was 3-fold larger than that of the fat balance. CONCLUSIONS: The (13)C-MTG breath test could potentially replace the fat balance method for comparing fat absorption efficacy between groups. Yet, a considerable interindividual variation of the (13)C-MTG breath test under conditions of relatively mild fat malabsorption does not support its application for diagnostic purposes in individuals.

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Orlistat treatment in obese prepubertal children: a pilot study.

Norgren S, Danielsson P, Jurold R, Lotborn M, Marcus C.

National Childhood Obesity Center and Pediatric Endocrine Research Unit, Department of Pediatrics, Karolinska Institutet and Huddinge University Hospital, Stockholm, Sweden. svante.norgren klinvet.ki.se

AIM: This study investigated orlistat treatment in obese prepubertal children with regard to tolerance, safety and psychological well-being. METHODS: 11 healthy, severely obese prepubertal children (age 8.3-12.3 y, body mass index standard deviation score 5.3-9.2) were recruited for a 12 wk open treatment. Before, during and after treatment, the participants were investigated by psychological evaluation, blood chemistry, and parameters reflecting obesity and fat mass. RESULTS: The participants were able to comply with the treatment, as indicated by pill counts and self reports, and expressed a desire to continue the treatment after the study period. Gastrointestinal side effects were mild and tolerable. No negative effects on psychological or physical well-being were detected, and the psychological evaluation demonstrated increased avoidance of fattening food, body shape preoccupation and oral control (p = 0.011). The median weight loss was 4.0 kg (range -12.7 to +2.5 kg, p = 0.016) and was highly correlated to decreased fat mass (regression coefficient 0.953, p < 0.01). CONCLUSION: This pilot study indicates that obese prepubertal children were able to reduce their fat intake to avoid gastrointestinal side effects. Thus, orlistat may be suitable as a component in behaviour-modification programmes for obese children, and the results prompt a placebo-controlled investigation of its effectiveness in promoting weight loss.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12856974&dopt=Abstract orlistat Xenical online refs
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[Pharmacological treatment of obesity]

[Article in Spanish]

Salvador J, Silva C, Santos E.

Departamento de Endocrinologia y Nutricion, Clinica Universitaria de Navarra, 31080 Pamplona. jsalvador unav.es

The foundation on which the treatment of obesity rests is made up of the procedures aimed at unbalancing the equation of energy balance in favour of calorie consumption. Pharmacological treatment is aimed at favouring a reduction of calorie intake or stimulating calorie production. Depending on their mechanism of action, the drugs that are used in the treatment of obesity can be divided into appetite inhibitors, inhibitors of food intake or blockers of fat digestion and stimulators of thermogenesis. Amongst the appetite inhibitors, besides the adrenergic agents such as those of the amphetamine type, which are forbidden because of their addictive effect, are the serotonin uptake inhibitors such as dexfenfluramine (withdrawn in 1997) and fluoxetine. The recent commercialisation of sibutramine, a serotonin and norepinephrine reuptake inhibitor with an appetite inhibiting and thermogenesis stimulating effect, offer new perspectives in this field. Amongst inhibitors, mention is deserved by orlistat that inhibits the absorption of upto 30% of ingested fat without causing secondary effects of significance. In the area of thermogenic drugs there are the ephedrine-caffeine association, and the adrenergic beta antagonists, which are still being researched. There are numerous future perspectives amongst which are leptin, analogs of GLP-1 and cholecystokinin and neuropeptide Y antagonists. It is necessary to have reliable predictive elements that make it possible to know the most useful drugs, as well as the sort of patients who will benefit most from the different pharmacological treatments.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12861278&dopt=Abstract orlistat Xenical online refs
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