Protective effect of hyperbaric oxygen treatment on rat intestinal mucosa after mesenteric ischaemia and reperfusion.

INTRODUCTION: Mesenteric ischaemia results from a lack of adequate blood flow to and oxygenation of the mesentery and intestines. The aim of the present study was to evaluate the effect of hyperbaric oxygen treatment (HBOT) on the healing process in intestinal mucosa of rats undergoing mesenteric ischaemia and reperfusion. METHODS: Thirty-two Wistar-Albino rats were divided into four groups of eight: 1) ischaemia/reperfusion (I/R); 2) sham operation; 3) I/R+HBOT started 6 hours after reperfusion; 4) I/R+HBOT started 12 hours after reperfusion. In the I/R groups, a vascular clamp was placed across the superior mesenteric artery to occlude arterial circulation for 60 minutes, followed by reperfusion. A dose of HBOT consisted of 100% oxygen breathing for 90 minutes at 2.5 atmospheres absolute pressure. Thirteen doses of HBOT were administered after ischaemia. The rats were sacrificed on the eighth day, and their intestinal tissues were harvested for histopathologic analysis. The tissue levels of catalase, malondialdehyde, and glutathione were determined. RESULTS: The histopathological scores (HSCORE) were consistent with macroscopic examinations. The scores were significantly higher (worse) in Group 1 compared to Group 2, Group 3, and Group 4 (for all comparisons, P < 0.05). Group 4's HSCORE was significantly higher than those of Group 2 and Group 3 (for both comparisons P < 0.05). Group 3's HSCOREs were only marginally higher than Group 2. Group 3 exhibited higher glutathione levels than Group 1 (P < 0.05). There were no significant differences across the groups with respect to malondialdehyde and catalase levels. CONCLUSION: A beneficial effect of HBOT was observed on oxidative stress and inflammation in acute mesenteric ischaemia-reperfusion.

Evaluation of insulin resistant diabetes mellitus in Alström syndrome: a long-term prospective follow-up of three siblings.

Alström syndrome is a rare cause of diabetes mellitus. We studied two generations of a Turkish family in whom four members were affected by Alström syndrome. The natural course of the syndrome in three sisters was followed for 13 yr. The three sisters had short stature and truncal obesity, and developed complete blindness due to retinitis pigmentosa at 10, 5 and 13 yr of age. Two had sensorineural hearing loss and mild mental retardation, while the other developed diabetic ketoacidosis (DKA) at 14 yr and was treated with insulin from onset of diabetes. In the second case, diagnosis of diabetes was made by an OGTT at age 20 yr, and controlled with diet alone for 11 yr, then with a sulphonylurea for 2.5 yr, then with insulin. The third case developed acute hyperglycaemia at 20 yr, and required insulin from onset. Moreover, transitional features of impaired carbohydrate and fat metabolism (severe hyperinsulinaemia and insulin resistance progressing to islet beta cell failure, and hypertriglyceridaemia with fatty liver) were demonstrated, in accord with the literature. Previously unreported findings characteristic of nephro-uropathy with early-onset hypertension were also detected, and included in all cases proteinuria, glomerulopathy, and abnormal locations of the kidneys, narrowed uretero-renal junctions and dilated ureters.

Effects of methylprednisolone pulse therapy on insulin injections in patients with insulin-dependent diabetes mellitus.

In this study we evaluated 31 insulin-dependent diabetes mellitus (IDDM) patients (ages 12.1 +/- 3.4 years, 18 males/13 females) who started on multiple subcutaneous insulin injections (MSII) within six weeks of diagnosis and achieved either complete (CR: no insulin requirement and near-normoglycemia for at least two weeks) or incomplete (ICR: minimum 50% decline in insulin requirement while maintaining near-normoglycemia for two weeks or more) remissions within the first 12 weeks of the MSII trial. Methylprednisolone pulse therapy (MP) was administered four times per day by i.v. bolus at a dose of 30 mg/kg (max. 1000 mg) on alternative days. Eleven patients did not accept "MP-pulse" therapy; therefore, we followed these cases (7 males/4 females) as the control group. During the first year of follow-up, 13 patients from the "MP pulse" group achieved CR (3 males/1 female) or ICR (5 males/4 females) in 3.5 to 14 months. Remission occurred in only two of the control group cases (1 male CR for 17 days and 1 female CR for 7 months). Of those with CR in the "MP-pulse" and control groups, all were greater than 12 years of age, and all but one in the "MP-pulse" group were males. The stimulation capacity of beta cells (as defined by percentage increase in serum C-peptide levels after glucagon injection) among CR cases was found to be higher than that of non-remitted (NR) cases (p < 0.05 at onset, p < 0.001 during MSII-induced remission and p < 0.05 at the end of the first year of follow-up). Although patients with CR or ICR had higher beta cell reserves than NR cases at onset, only CR cases could sustain this capacity during the MSII-induced remission phase and one year after "MP-pulse" therapy. From this preliminary study, we conclude that "MP-pulse" therapy, may lead to prolonged near-normal beta cell function or partly preserved residual beta cell reserve during the MSII-induced remission phase of IDDM, The beneficial effects of MP could be seen clearly in patients diagnosed during the late childhood years.

The antitumor effect of bleomycin combined with bestatin against Ehrlich ascites carcinoma in mice.

The effect of bleomycin against Ehrlich ascites carcinoma transplanted subcutaneously to mice used in combination with bestatin was investigated. Male Balb/c mice weighting approximately 20 g and bred in our laboratories were used in this study. Each mouse was injected in its left lateral abdominal region subcutaneously with 7 X 10(6) tumor cells in 0.2 ml of ascites fluid. The mice were divided into four groups: control, bestatin alone (5 mg/kg intraperitoneally on Days 9-14), bleomycin alone (10 mg/kg intraperitoneally on Days 7 and 8), and bestatin plus bleomycin. Our results show that bestatin enhances the antitumor effect of bleomycin against Ehrlich ascites carcinoma as measured by the increased survival rates. Being an agent of very low toxicity, bestatin should be considered as a part of the chemoimmunotherapy protocol.

Synthesis and release of proinsulin and insulin by isolated rat islets of Langerhans.

Isolated rat islets of Langerhans were incubated for 60, 120, and 180 min and the incorporation of leucine-(3)H into proinsulin and insulin moieties was followed. Synthesis and release of these hormones could be followed by separate extractions of islets and incubation media. RELEASE OF NEWLY SYNTHESIZED PROINSULIN AND INSULIN OCCURRED UNDER THE FOLLOWING CONDITIONS: (a) incubation for greater than 60 min; (b) glucose concentrations above 5.3 mmoles/liter; (c) incubation with 5 mM dibutyryl cyclic AMP or theophylline in 5.3 mM glucose (potentiated by 16 mM glucose); and (d) incubation with 5 mM tolbutamide and 16 mM glucose. Synthesis of proinsulin and insulin was enhanced by time of incubation, high glucose concentrations, by dibutyryl cyclic AMP or theophylline, and by tolbutamide only at 16 mM glucose. Synthesis was totally inhibited by tolbutamide at 5.3 mM glucose.