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Volume 112, Issue 2
Displaying 1-5 of 5 articles from this issue
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Hiroshi NAKANISHI, Kenji YAMAMOTO1998 Volume 112 Issue 2 Pages 77-88
Published: 1998
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSMuch attention has been paid to proteinases derived from not only neurons but also microglia in relation to neuronal death. There is accumulating evidence that intra and extracellular proteinases in these cells are part of the basic machinery of neuronal death pathways. Some members of the ced-3/interleukin-1β converting enzyme (ICE) (caspase) family of cysteine proteinases have been thought to play a major role in apoptosis of not only non-neuronal cells but also neurons. Calpain has also been demonstrated to be a mediator of the neurodegenerative response. Recent studies have shown that excitotoxic and ischemic neuronal injury could be attenuated by inhibitors of caspases and calpain. Several recent studies have suggested the involvement of endosomal/lysosomal proteinases, including cathepsins B, D and E, in neuronal death induced by excitotoxins and ischemia. Furthermore, it has been reported that the extracellular tissue-type plasminogen activator/plasmin proteolytic cascade is involved in excitotoxic injury of the hippocampal neurons. In addition to such neuronal proteinases, microglial proteinases are believed to be important for the modification of neuronal functions positively or negatively. Cathepsins E and S derived from microglia have been suggested to contribute to neuronal survival through degradation and removal of β-amyloid, damaged neurons and cellular debris. On the other hand, 6-hydroxydopamine-induced microglial cell death was inhibited by inhibitors of aspartic proteinases and caspases, suggesting the involvement of cathepsins E and D and caspases in microglial cell death. Therefore, identification of which proteinases play a causative role in neuronal death execution and clarification of the regulators and substrates for such proteinases is very important for understanding the molecular basis of the neuronal death pathways and to develop novel neuroprotective agents.View full abstractDownload PDF (12656K) -
Toru KAWANISHI1998 Volume 112 Issue 2 Pages 89-96
Published: 1998
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSRecently, the technique for high time- and spatial-resolution imaging of intracellular calcium ion concentration ([Ca2+]i) has been developed using rapid scanning confocal microscopy to investigate calcium dynamics in restricted areas of cells. Here, the techniques are summarized and the images obtained are introduced. For such imaging, the development of fast scanning confocal microscopes was indispensable. Therefore, the UV-applicable video-rate (30 frames/sec) scanning confocal microscope in which a resonant galvanometer scanner is used for fast horizontal scans has been developed. The microscope enabled us to obtain ratio-images of [Ca2+]i using indo-1, a ratio-imaging probe. The key to success in high time- and temporal-resolution imaging is to find the best probe-loading condition, which depends on the probes and the cells. It is also very important to increase the signal-to-noise ratio value without any effects on the cells. Using the technique, we have succeeded in kinetic analysis of calcium waves in cultured hepatocytes. We have also succeeded in determining the relationship between calcium sparks to calcium transients in excitation-contraction coupling.View full abstractDownload PDF (7393K) -
Effect of plaunotol on trinitrobenzene sulfonic acid and acetic acid induced colonic lesions in ratsMitsuko MAKINO, Yuka INOMATA, Keiichi ITO, Keiichi TABATA1998 Volume 112 Issue 2 Pages 97-106
Published: 1998
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThe aim of this study was to assess the effect of plaunotol, an anti-ulcer agent, on trinitrobenzene sulfonic acid (TNB)- and acetic acid-induced colonic lesions in rats. Plaunotol significantly reduced the severity of colonic mucosal lesions induced by TNB at a dose of 600 mg/kg/day. Moreover, plaunotol, at a dose of 600 mg/kg/day, significantly depressed the myeloperoxidase activity of the lesioned area induced by TNB of the rat colon. In the model of colitis induced by acetic acid, plaunotol reduced the area of lesions dosedependently and significantly at doses of 60, 200 and 600 mg/kg/day as asessed by macroscopic observation. Microscopic observation showed obvious changes by administration of plaunotol such as reduction of epithelial cell necrosis, decreased mucin production and a decreased infiltration of a large number of neutrophils. In conclusion, plaunotol showed a protective effect against colonic lesion formation induced by TNB and acetic acid in rats. This study suggests the possibility that plaunotol may be effective and useful for treatment of inflammatory bowel disease in humans.View full abstractDownload PDF (10512K) -
Hirotoshi ARAI, Yukio MORI, Midori MIZUO, Noriko URATA, Norihisa KOMAE ...1998 Volume 112 Issue 2 Pages 107-116
Published: 1998
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESST-593 consists of two optical isomers, (−)-S and (+)-R. Our previous report showed that T-593 has biphasic effects, that is a long-lasting antisecretory action and an improving effect on gastric mucosal blood flow (GMBF). In this study, we compared the sole potency of each isomer on these bi-phasic effects. On the anti-secretory action investigated by the pylorus-ligation method, the (−)-S-isomer showed strong inhibition, while the (+)-R-isomer showed no effect, whereas the GMBF improvement was provided by the (+)-R-isomer. These results show the bi-phasic effects of racemic T-593 are separately derived from each isomer. The (−)-S-isomer strongly inhibited acute gastric mucosal lesion formation, with a potency comparable to T-593 itself, while the (+)-R-isomer showed less effect. Chronic gastric ulcer induced by acetic acid was, however, not healed by the sole treatment of each optical isomer, while racemic T-593 showed a significant effect. This result shows not only anti-secretion but also GMBF improvement is necessary to heal the chronic ulcer. This interesting property of T-593 is expected to raise the quality of ulcer healing (QOUH) and also may prevent ulcer recurrence.View full abstractDownload PDF (8660K) -
Hirotoshi ARAI, Midori MIZUO, Shigeki MARUBUCHI, Masaya NAKAGAWA, Yuki ...1998 Volume 112 Issue 2 Pages 117-124
Published: 1998
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThe effect of T-593, a novel antiulcer agent, was investigated with respect to gastric bleeding and lesions induced by indomethacin (3mg/kg, s.c.) and water (23°C) immersion stress (IM-WIS) with perfusion of HCl (0.13N) into the rat stomach. It was found that the total amounts of gastric bleeding and lesions after IM-WIS with perfusion of HCl were more significantly decreased in T-593 (1mg/kg, i.v., 0.1mg/kg/hr, d.i.)- and secretin (15CU/kg/hr, d.i.)-treated rats, respectively. On the other hand, famotidine (1mg/kg, i.v.) did not affect gastric bleeding and lesions. The gastric mucosal blood flow (GMBF) reduction was induced by IM-WIS. T-593 (0.03-0.1mg/kg/hr, d.i.) inhibited the GMBF reduction dose-dependently. The GMBF improvement by T-593 disappeared with pretreatment of L-NAME (2mg/kg, s.c.) and was recoveyed by L-arginine (50mg/kg, i.v.). This indicates that GMBF improvement by T-593 is dependent on EDRF (NO). This interesting property of T-593 is expected to contribute to the clinical promotion of ulcer healing.View full abstractDownload PDF (7714K)
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