SUMMARYNinety percent depancreatized rats received daily intraperitoneal injection of 0.5 g/kg nicotinamide and 0.05 g/kg 3-aminobenzamide, potent inhibitors of islet poly(ADP-ribose) synthetase. One to three months after the partial pancreatectomy, urinary and plasma glucose levels in nicotinamide-and 3-aminobenzamide-treated rats were markedly lower than those in saline-treated control rats. Morphologic examination of the remaining pancreata revealed that islets in the poly(ADP-ribose) synthetase inhibitor-treated rats were markedly enlarged and consisted largely of B-cells. These results suggest that poly(ADP-ribose) synthetase inhibitors induce islet B-cell regeneration, thereby preventing or improving diabetes mellitus in partially depancreatized rats. DIABETES 33:401-404, April 1984. R emoval of the insulin-producing pancreatic Bcells from an animal induces a syndrome that features many of the acute metabolic derangements of diabetes as they are known in man. Mering and Minkowski 1 in 1890 were the first to produce this form of diabetes by surgically removing the pancreata of dogs. Alloxan in 1943 2 and streptozotocin in 1963 3 were found to be highly selective B-cytotoxins and thereafter have been widely used to produce diabetes in experimental animals. Recently, Okamoto and his colleagues 4 " 10 have clarified that alloxan and streptozotocin cause DNA strand breaks in pancreatic B-cells to stimulate nuclear poly(ADP-ribose) syn4hetase, thereby depleting the intracellular nicotinamide-adenine dinucleotide (NAD) level and inhibiting B-cell functions including proinsulin synthesis. We also reported that alloxan- and streptozotocin-induced diabetes can be prevented by inhibiting poly(ADP-ribose) synthetase of B-cells.
8" 10 In this article we show that poly(ADP-ribose) synthetase inhibitors prevent experimental diabetes caused by surgically removing the pancreata of rats. Morphologic evidence indicates that regeneration or proliferation of the pancreatic B-cells occurs in the poly(ADP-ribose) synthetase inhibitor-treated rats.
MATERIALS AND METHODSMale Wistar rats weighing 180-200 g were 90% depancreatized according to the technique described by Foglia 11 and maintained on standard rat chow. From 7 days before the partial pancreatectomy, nicotinamide, at a dose of 0.5 g/kg body wt in 2 ml saline, and 3-aminobenzamide • HCI, at a dose of 0.05 g/kg body wt in 2 ml saline, were injected intraperitoneally into each group of five rats every day. Nicotinamide and 3-aminobenzamide are inhibitors of pancreatic B-cell poly(ADP-ribose) synthetase; the inhibitory ability of the latter is about 10-fold as potent as that of the former. 9 The injection was continued until the ninetieth postoperative day. Five control rats received saline daily before and after the partial pancreatectomy. The residual pancreatic tissue, referred to as the remaining pancreas, was removed 3 mo after the partial pancreatectomy and fixed in Bouin's solution. Hydrated 5-|xm sections of paraffin-embedded pancreatic tissues were stained for insul...
Background/Aims: The prevalence of endoscopic esophagitis in young Japanese individuals is not fully apparent. The aim of this study was to determine the prevalence of reflux esophagitis (RE) and Helicobacter pylori infection and their relationship in young healthy Japanese volunteers. Methods: Upper gastrointestinal endoscopy was performed in 242 young healthy Japanese medical students (age range 22–29 years, mean 23.2 years) at Saga Medical School between 2008 and 2010. H. pylori infection was determined by detecting urinary IgG antibodies to H. pylori. Results:H. pylori antibodies were detected in 30 of the 242 subjects (12.4%). All 30 subjects had endoscopic chronic gastritis without peptic ulcers. Endoscopic RE was present in 27 of the 242 subjects (11.2%), corresponding to grade A in 19 subjects (7.9%), grade B in 7 (2.9%) and grade C in 1 (0.4%). Only 1 subject with RE was H. pylori-positive; the other 26 subjects with esophagitis were H. pylori-negative. We found no risk factors for H. pylori infection, but a risk factor for endoscopic esophagitis was alcohol consumption. Conclusion: The prevalence of H. pylori infection and endoscopic RE was 12.4 and 11.2%, respectively, in young healthy Japanese volunteers. Alcohol consumption was a risk factor for RE.
We report a cirrhotic patient with complete occlusion of the portal vein with marked cavernous transformation due to chronic thrombosis in whom a transjugular intrahepatic portosystemic shunt (TIPS) was successfully created after direct minilaparotomy mesenteric vein catheterization, lysis and aspiration of the thrombus, and stenting in the portal vein. The methods used, we believe, provide a new technique for performing TIPS in chronically thrombosed portal veins in which previously no effective surgical therapeutic options were available.
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