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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 pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11592731&dopt=Abstract
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Pancreas. 2001 Nov;23(4):341-8.
Role of nonesterified fatty acids in necrotizing pancreatitis: an in vivo experimental study in rats.
Paye F, Presset O, Chariot J, Molas G, Roze C.
Institut National de la Sante et de la Recherche Medicale Unite U410, Neuroendocrinologie et Biologie Cellulaire Digestives, Faculte Xavier Bichat, 16 rue Henri Huchard, 75018 Paris, France.
INTRODUCTION: In acute pancreatitis, nonesterified fatty acids (NEFA) might be released by lipase and cause tissue necrosis by their detergent properties, but this has not been established in vivo. AIMS: To measure the release of NEFA in the blood stream, pancreatic tissue, and peritoneal cavity during taurocholate-induced acute necrotizing pancreatitis in rats. METHODOLOGY: Ascites and blood were repeatedly sampled; after 24 hours, pancreatic lesions were scored, and NEFA were measured in the pancreas. The effects of a specific lipase inhibitor (Tetrahydrolipstatin [THL]) were also studied. RESULTS: A slight transient increase (22%) of NEFA concentration was observed in systemic circulation but did not parallel the time course of lipase activity, arguing against an intravascular production of NEFA by circulating lipase. Pancreatic NEFA did not differ between rats with pancreatitis and control rats. NEFA in ascites increased to threefold the basal value immediately after taurocholate and decreased rapidly thereafter, whereas lipase increased later in ascites and remained elevated during the 24-hour duration of the experiment. Lipase inhibition by THL neither modified the early increase of NEFA in ascites, nor altered the macroscopic, enzymatic, and histologic evolution of pancreatitis. CONCLUSION: This in vivo study does not confirm the hypothetical role of NEFA produced by pancreatic lipase in the necrotic process and its systemic complications, up to now mainly suggested on the basis of ex vivo experiments.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11668201&dopt=Abstract
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J Clin Psychopharmacol. 2002 Feb;22(1):68-70.
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 pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11799345&dopt=Abstract
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