Evidence for specific ceramidase present in the intestinal contents of rats and humans.

Duan RD, Cheng Y, Yang L, Ohlsson L, Nilsson A.

Department of Cell Biology B, Biomedical Center, University of Lund, Sweden. Rui-dong.duan med.lu.se

A neutral ceramidase activity stimulated by bile salt was previously identified in the intestinal content. Recently, bile salt stimulated lipase (BSSL) was found to have ceramidase activity. It is unknown whether the ceramidase activity previously found is attributable to BSSL. To address this question, we compared the behaviors of high quaternary aminoethyl (HQ) anion exchange chromatography, the distributions, the stability, and the responses to lipase inhibitor between ceramidase and pancreatic BSSL. The proteins from whole small intestinal contents of humans and rats were precipitated by acetone and dissolved in 20 mM Tris buffer pH 8.2. These proteins had neutral ceramidase activity but not BSSL activity against p-nitrophenyl acetate. When the proteins were subject to HQ chromatography, two peaks of ceramidase activity were identified, which had acid and neutral pH optima, respectively. Neither of them had BSSL activity against p-nitrophenyl acetate. Western blot using BSSL antiserum failed to identify BSSL protein in the fractions with high neutral ceramidase activity. In rat intestinal tract, pancreatic BSSL activity was high in the duodenum and declined rapidly in the small intestine, whereas neutral ceramidase activity was low in the duodenum and maintained a high level until the distal part of the small intestine. In addition, orlistat, the inhibitor of lipase, abolished human BSSL activity against p-nitrophenyl acetate and slightly reduced its activity against ceramide but had no inhibitory effect on ceramidase activity isolated by HQ chromatography. In conclusion, we provide the evidence for a specific ceramidase other than pancreatic BSSL present in the intestinal content. The enzyme may play important roles in digestion of dietary sphingolipids.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11592731&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


[Therapy of obesity. Setting realistic goals]

[Article in German]

Hauner H.

Klinische Abteilung, Deutsches Diabetes-Forschungsinstitut an der Heinrich-Heine-Universitat Dusseldorf. hauner ddfi.uni-duesseldorf.de

Every third German needs to lose weight for health reasons. Risk assessment of obesity is based on the BMI, the distribution pattern of body fat, and the presence of concomitant diseases and sequelae of obesity. The most important prerequisites are personal motivation and the ability of the patient to self-manage his/her problem. The basic long-term weight-reduction program includes a low-calory diet, increased physical activity, and specific measures aimed at modifying eating habits. Should the basic programs fail to produce the necessary results, the two weight-reducing drugs Sibutramine and Orlistat are available--with appropriate consideration being given to contraindications. Surgical measures, such as gastric banding and gastroplasty are reserved for patients that prove resistant to conservative measures.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11697284&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


[Hypertension and cardiomyopathy in obesity. Treat the heart simultaneously]

[Article in German]

Wirth A.

Teutoburger-Wald-Klinik, Bad Rothenfelde. alfred.wirth lva-hannover.de

The prevalence of hypertension among the obese is twice as high as that in persons of normal weight. Not only the BMI, but, and in particular, the circumference of the waist correlates with blood pressure. A relationship also obtains between BMI and left-ventricular muscle mass, with left-ventricular hypertrophy occurring twelve times more often among the obese than among slim persons. Obesity puts a strain on both the hemodynamics and metabolism of the heart. On the one hand, long-term sequelae include disordered cardiac function extending to cardiomyopathy, on the other, obesity is responsible for sympatho-adrenergic stimulation considered to be a cause of insulin resistance, and is thus, in particular in the hypertensive, closely associated with metabolic syndrome. Specific nondrug treatment options include weight reduction, a low-salt diet and physical exercise. In some cases, Sibutramine and Orlistat may have a supporting role. For the antihypertensive treatment of the obese, drugs with a favorable hemodynamic and metabolic effect should be used.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11697285&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


The effect of orlistat on plasma levels of psychotropic drugs in patients with long-term psychopharmacotherapy.

Hilger E, Quiner S, Ginzel I, Walter H, Saria L, Barnas C.

Department of General Psychiatry, University of Vienna, Vienna, Austria.

Weight gain induced by long-term psychopharmacotherapy has emerged as a relevant clinical issue because it is a major problem affecting compliance and long-term outcome. The novel antiobesity drug orlistat inhibits gastrointestinal lipases, thus lowering the absorption of dietary fat and raising the possibility of decreased absorption of fat-soluble vitamins and certain concomitantly administered drugs in some individuals. We monitored plasma levels of several psychotropic agents in eight psychiatric patients receiving orlistat to determine the potential influence of orlistat on the bioavailability of these drugs. We found no clinically relevant changes in plasma concentrations of haloperidol, clozapine, clomipramine, desipramine, or carbamazepine over an 8-week period in orlistat recipients. We therefore consider orlistat to be compatible with use during long-term pharmacotherapy. Our preliminary findings suggest that orlistat may offer a pharmacological treatment option to support dietary efforts in obese and overweight psychiatric patients. However, so far no data about the potential influence of orlistat on pharmacokinetics of psychotropics have been published; therefore, plasma level monitoring is recommended.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11799345&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


A health economic model to assess the long-term effects and cost-effectiveness of orlistat in obese type 2 diabetic patients.

Lamotte M, Annemans L, Lefever A, Nechelput M, Masure J.

Health Economics and Disease Management, Brusselsteenweg 91, B-1860 Meise, Belgium.

OBJECTIVES: Obesity is a common condition in type 2 diabetic patients. Treating obesity may enhance hypoglycemic treatment and contribute to the reduction of long-term microvascular and macrovascular complications. Orlistat reduces cardiovascular risk factors in obese type 2 diabetic patients. The objectives of this study were to estimate the long-term clinical consequences of this weight loss and the resulting cost-effectiveness of treating obese type 2 diabetic patients with orlistat. RESEARCH DESIGN AND METHODS: A Markov model was developed to predict, over a 10-year period, the complication rates and mortality with and without a 2-year orlistat treatment, assuming a 5-year catch-up period after treatment. A stepwise approach was used to obtain the clinical data. First, the impact of weight loss with orlistat on HbA(1c), blood pressure, and cholesterol was assessed; then, the impact on mortality and micro- and macrovascular complications of decreasing these risk factors was applied. Four subgroups were studied based on the presence of risk factors. RESULTS: Cost-effectiveness varies between 3,462 Euro/life-year gained (LYG) for obese diabetic patients with hypertension and hypercholesterolemia and 19,986 Euro/LYG for obese diabetic patients without other risk factors. The latter result is not robust according to sensitivity analyses. CONCLUSIONS: Our results suggest that orlistat is cost-effective in the management of obese type 2 diabetic patients, especially in those with the presence of hypercholesterolemia and/or hypertension. Evidence on longer-term benefits of orlistat (>2 years) will be of importance for future decision-making.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11815500&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)