s364 Poster Session 2

P1433 Diabetic Hyperglycemia Lessens Hypoxia-Induced EEG Damage in Rats A. MMORI’, 0. Mokuda’, Y. Sakamoto*, N. Shimizu’. ‘Depurtmentoj Neurology, Teikyo University School of Medicine, Ichihara Hospital: ’ Third department of Internal Medicine, Teikyo Universiry School of Medicine, Ichihara Hospital

Purpose: The brain requires oxygen and glucose for energy metabolism. When the brain is exposed to an anoxic episode, glucose has the most important effect on brain function. In the present study, the effects of the diabetic hyperglycemia on cerebral damage due to hypoxic hypoxia induced by 100% nitrogen (Nz) gas inhalation were examined by record- ing electroencephalogram (EEG) activity as the parameter of cerebral function. Methods: Male Wistar rats were divided into 3 groups: a streptozo- tocin-induced diabetic hyperglycemic group, a normoglycemic group, and an insulin-induced hypoglycemic group. All rats were anesthetized with pentobarbital(5Omg/kg) by intraperitoneal injection. Electrodes were implanted into the cranium for EEG recording. Hypoxia was induced by ventilating with 100% Nz gas for 3 minutes. EEG was recorded before, during and after the Nr gas loading. Plasma glucose concentrations, mean arterial blood pressure, and arterial blood gases were monitored during the experiment. Results: EEG amplitude both 5 and 10 minutes after anoxia loading was higher in the diabetic hyperglycemic group than in the normoglycemic group, though not significantly. Time required for the occurrence of the EEG activity greater than 20 k V to decrease to 50% during anoxia loading was significantly longer in the hyperglycemic group than in the normoglycemic group. Time required for the occurrence of the EEG activity greater than 20 p V to recover to 50% after anoxia loading was significantly shorter in the hyperglycemic group and was longer, though not significantly, in the hypoglycemic group than normoglycemic group. Conclusion: These results suggest the brain is more tolerant to hypoxia during diabetic hyperglycemia than during normoglycemia.

P1434 Dual Modifications of (-)-SG-210 on Impaired Polyol Metabolism and Advanced Glyeation Endproducts Formation in Experimental Diabetes MeBitus HITOSHI NAGAI, Hiroshi Koshiba, Tomoyuki Maruyama, Yoko Sakai, Toshiaki Akira.

Recently, Advanced Glycation Endproducts(AGEs) have been implicated in induction and development of diabetic complications. We thus inves- tigated the dual effects of an aldose reductase inhibitor, (-)-SC-210, on AGE formation as well as on impaired polyol metabolism and, if any, their roles in improving diabetic neuropathy. Methods: Diabetic condition was induced by an intravenous injection of streptozotocin(STZ) to rats(8 weeks of age) at a dose of 60 mg/kg. Three weeks after STZ injection, the tail nerve conduction veIocity(NCV) was measured for comforming diabetic neuropathy and grouping. The diabetic animals, which showed a certain level reduction in tail NCV, were received 0.3-3 mg/kg of (-)-SG-210 or vehicle for 6 weeks, then measured their sciatic NCVs, sorbitol levels of red blood cell(RBC) and of sciatic nerve. Furthermore, we examined the efficacy of (-)-SG-210 on AGE formation(Hb-CMV) and polyol metabolism in same animals and investigated the formation of rat serum albumin-AGE(RSA-AGE) in cell free system. Results: (-)-SG-210 ameliorated the decrease in sciatic NCV, reduced either sorbitol levels of RBC and of sciatic nerve in a dose-dependent manner. Then (-)-SG-210 inhibited Hb-CMV contents, but didn‘t have in dose-dependency. (-)-SG-210 inhibited RSA-AGE formation and its effect was not concerned aldose reductase inhibition.

Conclusion: It was shown that (-)-SG-210 inhibits the formation of AGE in addition to aldose reductase inhibition. These effects may contribute to the inhibitory effects of (-)-SG-210 to diabetic neuropathy.

P1435 Effectiveness of Low Doses of Gamma Linoleaic Acid-Lipoic Acid Conjugate in Experimental Diabetic Neuropathy THIERRY CHARLES COSTE’, Alain Gerbil, Henri Portuga12, Philippe Vague ’ , Gerard Pieroni *, Denis Raccah ’ ’ Department of Diabetology, Timone Hospital, Marseille, France: ‘Lipids and Nutrition, INSERM lJ476, Marseille, France

Background: Impaired conversion of 1inoIeic acid to gamma linolenic acid (GLA) has been demonstrated in animal and human diabetes. This lead to a perturbation in the synthesis of prostaglandins and particularly a decrease in prostacyclin. These abnormalities impaired peripheral nerve function. Studies with GLA supplementation were effective in correcting nerve dysfunction. Lipoic acid (LA) was used in diabetic neuropathy but was less effective than GLA. By combining these two compounds in one conjugate (GLA-LA), one could expect a synergistic effect allowing to reduce doses. Aims: To determine whether supplementation with low doses of GLA-LA could prevent neuropathy in streptozotocin-diabetes. Materials and Methods: Diabetic rats were given daily supplementation with GLA-LA (10 or 30 mg.kg-1, in corn oil 50150 (w/w)). by gavage. After 8 weeks, nerve conduction velocity (NCV, in m.s-I), nerve blood flow (NBF, in arbitrary units), Na/K ATPase activity (in nmol Pi.mg pro- tein-l .h-1) and membrane phospholipid fatty acid composition of sciatic nerve were compared with diabetic controls supplemented with corn oil only (GLA-LA free). Results: GLA-LA (30 mg) totally prevented the decrease in NCV (49.9fl.l vs 34.9f0.9; pt0.05), NBF (121fll vs 50flO; ~~0.05) and Na/K ATPase activity (2910f278 vs 1862fll7; ~~0.05). GLA-LA (10 mg) totally prevented the decrease in NCV and Na/K ATPase activity but had a slightly less effect in correcting NBF when compared to control (112f7 vs 14lf8). Diabetes induced major changes in plasma fatty acid composition with accumulation of linoleic acid (piO.05) and di-homo gamma linolenic acid (p<O.O5), but the changes observed in sciatic nerve were only minor. Supplementation with GLA-LA showed an increase in plasma arachidonic acid level in control animals, and trend to a decrease in this fatty acid level, observed in diabetes, became significant (p<O.O5). Conclusions: These results demonstrate a protective effect of supplementation with very low doses of GLA-LA on physiologic and metabolic parameters implicated in ex- perimental diabetic neuropathy. Supplementation with GLA-LA clearly shows clinical potential in treating human diabetic neuropathy.

P1436 Neutrophil Function in Diabetes: Effect of Glycemic Control R.J. DASH, S. Dash, J.S. Virdi. PostgraduateMedical Institute, Chandigarh, India

Proneness to acute infections in diabetes is well known. This is related to the degree of hyperglycemia, significantly decreasing with control. To validate this hypothesis in part, we studied several parameters of polymorphonuclear leucocytic functions in the uncontrol state (FBS > 15 nmrolil, HbAlc > 11%) and following satisfactory glycemic control (FBS 5-9 mmol/L, HbAlc 6-7.5%) in 20 patients with type 2 diabetes and 15, of type 1 diabetes. Ten healthy subjects with no family history of diabetes provided the control data. The following parameters were studied: (1) phagocytic function (PF) at 20’ and (2) bactericidal activity (BA) at 2h using Staph aureus NCTC 6571 as the test organism (3) hexose mono-phosphate shut (HMPS) activity by the degree of conversion of 14~ - glucose to 14coz at 60’. The PF in the uncontrolled diabetics at 56.8 i 9.4 SE% was significantly lower (p < 0.05) to that in the control (72.4 & 3.6 SE%). The BA in uncontrolled diabetics at 68.6 f 8.9% SE was lower