Reference

A model to study ischemic brain edema in rats and the influence of drugs

A model to study ischemic brain edema in rats and the influence of drugs. Gotoh, Osamu; Koide, Tohru; Asano, Takao; Takakura, Kintomo; Tamura, Akira; Sano, Keiji (Dep. Neurosurg., Univ. Tokyo Hosp., Japan). Recent Prog. Study Ther. Brain Edema, [Proc. Int. Symp. Brain Edema], 5th, Meeting Date 1982, 499-508. Edited by: Go, K. G.; Baethmann, A. Plenum: New York, N. Y. (English) 1984. CODEN: 51TOA5. DOCUMENT TYPE: Conference CA Section: 1 (Pharmacology) Section cross-reference(s): 2, 14 Occlusion of the middle cerebral artery in rats proved to be a very reliable model to study ischemic brain edema. Variability between individual animals was small and mortality was virtually absent. Although focal neurol. deficits were not obsd., progression of edema resulted in a general depression of spontaneous motor activity. Nevertheless, brain water content in affected hemispheres increased markedly, reaching a max. in untreated controls between 2-3 days after occlusion. Alterations of brain water developed directly, or inversely in proportion to the tissue Na+- and K+-content. The model appears to be suitable to study brain edema secondary to regional ischemia, particularly changes of chem. compn. of brain tissue and the effects of drugs. Both dexamethasone [50-02-2] and 1,2-bis(nicotinamido)propane [79455-30-4] suppressed the increase of brain water, but were less effective in their influence on cerebral electrolytes. The lack of dose-dependency in animals receiving dexamethasone suggests that the dose was near maximal, whereas dose-dependency of brain water content was clearly shown in animals with therapy with 1,2-bis(nicotinamido)propane.

Effects of AVS (1,2-bis(nicotinamido)propane) on platelet function and vascular endothelium

Effects of AVS (1,2-bis(nicotinamido)propane) on platelet function and vascular endothelium. Mizukami, M.; Neichi, T.; Yamazaki, T.; Koide, T.; Noda, Y.; Matsushita, H.; Hata, S.; Nakano, M. (Res. Lab., Chugai Pharm. Co., Ltd., Tokyo 171, Japan). Arzneim.-Forsch., 34(7), 764-8 (English) 1984. CODEN: ARZNAD. ISSN: 0004-4172. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The effects of 1,2-bis(nicotinamido)propane (AVS) (I) [79455-30-4] on platelet function and vascular endothelium were investigated in various exptl. thrombosis and vascular endothelial injury models. Neither in vitro platelet aggregation induced by ADP, collagen, or arachidonate nor ex vivo platelet aggregation by ADP or collagen could be antagonized by AVS. On the other hand, AVS prevented mice, rats, and rabbits from death by acute cerebral or pulmonary thromboembolism following the injection of arachidonate or collagen. These activities were as potent as those of acetylsalicylic acid. The disrupting actions of citrate and/or lipid peroxide (13-hydroperoxylinoleic acid) on the endothelium were inhibited by pretreatment with AVS. AVS did not inhibit cyclooxygenase but increased the PGI2 [35121-78-9]/TXA2 [57576-52-0] ratio in the coupled system of platelets and aortic microsomes. In conclusion, AVS inhibited thrombus formation in vivo but was ineffective in the in vitro platelet system, which may result from the actions of this agent on both platelets and vascular endothelium. The results show that AVS may be a new potent vascular antidamaging agent with both endothelium-stabilizing and PGI2-enhancing activities.