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Volume 111 (1998)
- Issue 6 Pages 345-
- Issue 5 Pages 289-
- Issue 4 Pages 193-
- Issue 3 Pages 137-
- Issue 2 Pages 77-
- Issue 1 Pages 1-
Volume 111, Issue 3
Displaying 1-5 of 5 articles from this issue
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Chihiro Nishimura-YABE1998 Volume 111 Issue 3 Pages 137-145
Published: March 01, 1998
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSAldose reductase (AR), an enzyme in the polyol pathway, catalyzes the reduction of glucose to sorbitol. Sorbitol is subsequently converted to fructose by sorbitol dehydrogenase. The two enzymes constitute the sorbitol (polyol) pathway, the alternate route of glucose metabolism. The acceleration of this pathway and ensuing metabolic imbalances have been postulated to play a key role in the pathogenesis of diabetic complications. Using a transgenic animal model expressing human AR, we defined the primary role of this pathway in the development of functional and structural abnormalities elicited by diabetes. The inhibitors for AR would thus become effective therapeutic agents for diabetic complications. As AR is a member of the structurally related, NADPH-dependent aldo-keto reductase superfamily, other members of this family, coexisting with AR, may interact with the inhibitors to quench their action against AR. With our new immunoassay system, the levels of AR expressed in diabetic patients can be measured directly. The enzyme levels were significantly associated with the presence of complications, indicating that variable levels of AR expressed in diabetic individuals may affect the susceptibility or development of pathological changes associated with diabetes. In this review, recent advances in the understanding of the pathophysiological significance of AR are presented that would aid in the effective pharmacological intervention of diabetic complications.View full abstractDownload PDF (9741K) -
Yoshihisa KITAMURA1998 Volume 111 Issue 3 Pages 147-156
Published: March 01, 1998
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSRecent studies have indicated that glial cells such as astrocytes and microglia are activated in an early and delayed episode after brain damage. However, the mechanism and function of glial activation are still unclear. I examined whether the induction of inducible nitric oxide synthase (iNOS), heme oxygenase-1 (HO-1) and major histocompatibility complex (MHC) antigen was involved in the glial activation. The microinjection of interferon-7 and lipopolysaccharide into rat hippocampus induced MHC class II and iNOS in microglia. The iNOS induction may be involved in the activation of tyrosine kinases and transcription factors such as signal transducer and activator of transcription-1 (STAT1) and nuclear factor-κB (NF-κB). Subsequently, neuronal cell death occurred in the hippocampus, but cell death was undetectable in both microglia and astrocytes that expressed HO-1. Thus, induction of iNOS and HO-1 in glial cells may be involved in hippocampal neurodegeneration and resistance to oxidative stress in glial cells, respectively. In Alzheimer's disease (AD) brains, iNOS expression was at a very low level, although STAT1 and NF-κB were significantly increased. Also, Bcl-2, Bcl-x, Bak, Bad and p53 were increased in AD brains. These observations suggest that oxidative stress and glial activation without iNOS induction may be involved in neurodegeneration of AD brains.View full abstractDownload PDF (11335K) -
Shuji KANEKO1998 Volume 111 Issue 3 Pages 157-166
Published: March 01, 1998
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSXenopus oocytes are one of the most widely utilized expression systems for voltage-dependent ion channels. Here, I describe a new technique for voltage-clamp recording of Xenopus oocytes that enables fast and stable monitoring of transmembrane current as well as intracellular perfusion by cutting a part of the plasma membrane to open the cytoplasm to the recording chamber which is filled with artificial intracellular solution. The original method was developed and described by Dr. E. Stefani and his colleagues, and I have modified it by employing a push-pull cannula to exchange the intracellular solution. The main features of this technique are: 1) High frequency response and relatively low current noise; fast activation and deactivation of ionic currents can be precisely evaluated. 2) Stable recording conditions lasting for several hours; this is a marked advantage over the conventional and patch-clamp recording. 3) Control of the ionic composition of both the internal and external media; the cut-open configuration enables desired manipulation of the internal milieu of oocytes easily, which is suitable for the study of Ca2+ channel modulation by second messengers and drugs.View full abstractDownload PDF (7701K) -
Sadayoshi ONODERA, Masato TANAKA, Misao AOYAMA, Yoko ARAI, Masahiro SH ...1998 Volume 111 Issue 3 Pages 167-175
Published: March 01, 1998
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSEffect of lafutidine ((±)-2-(furfurylsulfinyl)-N-[4-[4-(piperidinomethyl)-2-pyridyl]oxy-(Z)-2-butenyl] acetamide, FRG-8813), a novel antiulcer agent, on the healing and relapse in acetic acid-induced gastric ulcer in rats was investigated. Lafutidine at 1, 3 or 10 mg/kg, twice daily for 10 days reduced the ulcer area in a dose-dependent manner, and the effect by 10 mg/kg of lafutidine was significant. The effect of famotidine at 1 mg/kg and cimetidine at 30 mg/kg, which have almost equal antisecretory activity to lafutidine at 10 mg/kg, on the ulcer area was not significant. Effect on the healing and relapse was assessed by endoscopy for 25 weeks after the induction of gastric ulcer. Drugs were administered twice daily for 11 weeks. Lafutidine at 3 mg/kg and famotidine at 1 mg/kg acceralated the healing, but cimetidine at 30 mg/kg did not. Cumulative relapse rate and inflammatory cell infiltration were significantly reduced in rats initially treated with lafutidine. Famotidine and cimetidine had no effect. In conclusion, lafutidine accelerated ulcer healing and prevented ulcer relapse in rats.View full abstractDownload PDF (9935K) -
Fusako TAKAYAMA, Toru EGASHIRA, Yasumitsu YAMANAKA1998 Volume 111 Issue 3 Pages 177-186
Published: March 01, 1998
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSTo evaluate occurrence of oxidative stress in circulating blood, we developed standard methods to assess (1) granulocytes status as a source of reactive oxygen species (ROS) and (2) lipid peroxidation (LPO). A simplified and highly sensitive assay was developed by utilizing the chemiluminescence (CL) from luminol oxidized by ROS. 1. The CL, from 300 μl medium containing 1 % blood, 10 μg/ml luminol and 0.025 μg/ml phorbol myristate acetate, well reflected the primed granulocyte status induced by in vitro contact with lipopolysaccharide (LPS). This CL was weakened slightly by superoxide dismutase and catalase, but markedly decreased by sodium azide. 2. We determined the optimal conditions for the t-butyl hydroperoxide (t-BuOOH)-stimulated CL method to evaluate plasma LPO in experiments on rat plasma added with phosphatidylethanolamine hydroperoxide (PEOOH). The CL from 300 μl medium containing 6.67% plasma, 10 μg/ml luminol and 5 μmol/ml t-BuOOH was proportional to the added PEOOH amount. The integrated CL of the plasma with 0-60 nmol of PEOOH gave values of 8.280-14.213×106 counts/60 min/tube. 3. Only 100 μl of freshly drawn blood was enough for the two CL methods to detect the generation of ROS and the occurrence of LPO. These CL methods enabled the determination of the time course of oxidative stress occurrence in circulating blood of rats treated with 5 mg/kg LPS, i.p.View full abstractDownload PDF (10269K)
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