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Volume 118 (2001)
- Issue 6 Pages 363-
- Issue 5 Pages 303-
- Issue 4 Pages 251-
- Issue 3 Pages 147-
- Issue 2 Pages 81-
- Issue 1 Pages 5-
Volume 118, Issue 6
Displaying 1-7 of 7 articles from this issue
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Reviews
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Keitaro HASHIMOTOSubject area: Others
2001 Volume 118 Issue 6 Pages 363-370
Published: 2001
Released on J-STAGE: September 27, 2002
JOURNAL FREE ACCESSCariporide, HOE642 (4-isopropyl-3-methylsulphonylbenzoyl-guanidine methanesulphonate), a novel Na+-H+ exchange (NHE) subtype 1 inhibitor, has cardioprotective effects including an antifibrillatory effect on the coronary ischemia/reperfusion induced arrhythmias not only in in vitro, but also in vivo animal hearts, which might be induced by intracellular Ca2+ overload following myocardial ischemia. This antifibrillatory effects on reperfusion arrhythmias were observed even when the drug was administered after induction of coronary ischemia or even when the drug was administered simultaneously with reperfusion. Other NHE inhibitors also have similar antiarrhythmic and antifibrillatory effects as cariporide and these drugs had almost no deleterious effects on the heart rate and blood pressure, nor ECG parameters. The antifibrillatory mechanism of NHE inhibitors may be due to their NHE inhibition as judged by the doses used, and they may become useful for treating or preventing arrhythmias in patients with coronary artery diseases.View full abstractDownload PDF (1396K) -
Chiho SUMI-ICHINOSE, Masatsugu OHTSUKI, Hiroaki SHIRAISHI, Takahide NO ...Subject area: Others
2001 Volume 118 Issue 6 Pages 371-377
Published: 2001
Released on J-STAGE: September 27, 2002
JOURNAL FREE ACCESSTetrahydrobiopterin ((6R)-L-erythro-tetrahydrobiopterin, BH4) is de novo synthesized from GTP. Enzymes involved in its synthesis are the rate limiting enzyme GTP cyclohydrolase I, 6-pyruvoyl tetrahydropterin synthase (PTPS) and sepiapterin reductase. Abnormalities in the metabolism of BH4 have been demonstrated in some diseases affecting the central nervous systems such as atypical phenylketonuria, hereditary progressive dystonia (Segawa’s disease). Furthermore, BH4 has been shown to be involved in vascular protection. It is suggested that the dysfunction of endothelial BH4 leads to atherosclerosis. Recently we established BH4-deficient mice by disrupting the PTPS gene to investigate the effects of BH4 depletion on the animals and the involvement of BH4 in regulating biological functions including neural systems. Investigation utilizing this model animal can contribute to the development of new therapeutic strategies toward various diseases involving neurological and vascular systems. Pterin derivatives other than biopterin may also be involved in the regulation of a variety of biological functions. We found that ciliated protozoan Tetrahymena pyriformis synthesizes tetrahydromonapterin, isomer of BH4, and its levels alter according to the progress of the cell cycle. How pterin derivatives are related to the human physiology and diseases is an interesting subject of investigation.View full abstractDownload PDF (1032K)
Technical Note
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Toshio OBATAArticle type: Others
Subject area: Others
2001 Volume 118 Issue 6 Pages 379-382
Published: 2001
Released on J-STAGE: September 27, 2002
JOURNAL FREE ACCESSThe microdialysis procedure is a technique that has been established for some years. The heart, however, has several difficulties in the application of this technique. The heart is the beating in vivo, in contrast to other organs. I developed the flexibly mounted microdialysis technique, which involves the synchronized movement of the tip of the probe with the beating heart to reduce tissue injury. With this technique, it is feasible to make stable and long-term measurements of interstitial biological substances. By employing the flexibly mounted microdialysis technique, I will demonstrate that the monitoring of free radical generation and the level of adenosine measured during AMP perfusion that gives an index of the activity of ecto-5’-nucleotidase in the tissue. In the future, this technique will have versatile applications for useful studies to elucidate the actual mechanism in the pathogenesis of heart disorders.View full abstractDownload PDF (551K) -
Fumikazu OKAJIMAArticle type: Others
Subject area: Others
2001 Volume 118 Issue 6 Pages 383-388
Published: 2001
Released on J-STAGE: September 27, 2002
JOURNAL FREE ACCESSSphingosine 1-phosphate (S1P), one of the spingolipid metabolites, has been shown to participate in a variety of cellular responses including proliferation, differentiation, adhesion, motility, and apoptosis. These cellular responses elicited by S1P were first thought to be mediated through an intracellular target(s), but extracellular mechanisms through G-protein-coupled S1P receptors have also been suggested. In addition to the studies examining the functions of the lipid on the cells and tissues, the measurement of the lipid concentration is also important for understanding the physiological and pathophysiological roles of the lipid. We have recently developed a novel quantitative method for measurement of S1P, which was based on the competition of S1P in the samples with the labeled S1P on the S1P receptor Edg-1. Here, we compared our method with previously published ones in several points including specificity and simplicity. We further presented our recent results obtained by using this novel quantitative method and finally mentioned the prospects of the S1O measurement in lipid research, especially in relation to several disorders.View full abstractDownload PDF (747K)
Drug Development Now
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Yoji HIRAKAWA, Hiroaki SHIMOKAWAArticle type: Others
Subject area: Others
2001 Volume 118 Issue 6 Pages 389-395
Published: 2001
Released on J-STAGE: September 27, 2002
JOURNAL FREE ACCESSAccumulating evidences in recent major clinical studies have shown the importance of anti-hyperlipidemic treatment in preventing atherosclerotic cardiovascular diseases. Lipid-lowering drugs can be divided into HMG-CoA reductase inhibitors (statins), bile-acid sequestrants (resins), nicotinic acid, fibrates and probucol. Among them, statins had revolutionary impact on the treatment of hyperlipidemia since pravastatin, which was developed in Japan, was launched in 1989. Several lipid-lowering drugs are now under development in Japan, including pitavastatin, rosuvastatin, F-1394 (ACAT inhibitor), CS-505 (ACAT inhibitor) and NO-1886 (LPL activator). In this review, characteristics of these new lipid-lowering drugs will be discussed.View full abstractDownload PDF (728K)
Review on New Drug
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Yuri MOTOBAYASHI, Wataru IMAGAWA, Kooichi SAIDASubject area: Others
2001 Volume 118 Issue 6 Pages 397-402
Published: 2001
Released on J-STAGE: September 27, 2002
JOURNAL FREE ACCESSBayer has been interested in the observations that metabolites of arachidonic acid are involved in allergy and inflammation. Ramatroban was thus developed as a therapeutic agent for allergic and inflammatory diseases. Ramatroban showed an antagonistic action on the thromboxane A2 (TXA2) receptor in in vitro experiments using platelets or arteries. It inhibited the permeability of capillary and also the infiltration of eosinophils in nasal mucosa. Ramatroban had an inhibitory effect on the nasal resistance stimulated by either U-46619 or antigen challenge in in vivo experiments. The concentration of nasal TXA2 was increased when the antigen was challenged to allergic patients. Clinical trials demonstrated that ramatroban decreased sneezing, rhinorrhea, and rhinostenosis in patients enrolled in the study. No serious adverse reaction of ramatroban was observed in patients throughout the trials. The treatment with ramatroban is safe and improves nasal symptoms.View full abstractDownload PDF (1007K)
Original Article
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Taiichiro IMANISHI, Kaname ONOZAWA, Akiko HAYASHI, Jun BABASubject area: Others
2001 Volume 118 Issue 6 Pages 403-410
Published: 2001
Released on J-STAGE: September 27, 2002
JOURNAL FREE ACCESSFluvoxamine, a selective serotonin reuptake inhibitor, is frequently used along with benzodiazepine anxiolytics in clinics. In this study, the effects of fluvoxamine on the anxiolytic effects as well as adverse effects of benzodiazepines were examined in the light/dark box, rota-rod and passive avoidance tests using mice. Diazepam, ethyl loflazepate and its active metabolite, CM7116, were used as benzodiazepine anxiolytics. The anxiolytic effects of diazepam, ethyl loflazepate and CM7116 were potentiated by intraperitoneal treatment with fluvoxamine at 10 mg/kg, whereas only those of ethyl loflazepate were potentiated by fluvoxamine at 45 mg/kg. The motor incoordination and amnesia induced by ethyl loflazepate and CM7116 were not affected by fluvoxamine, although these adverse effects of diazepam were potentiated by fluvoxamine at 45 mg/kg. Fluvoxamine itself showed no effects in any of the tests. These results suggest that low-dose fluvoxamine potentiates the anxiolytic effects of benzodiazepines, while high-dose fluvoxamine augments the adverse effects depending on the benzodiazepine used. Consequently, when fluvoxamine is administered along with benzodiazepines, the doses of both fluvoxamine and benzodiazepines should be carefully chosen to achieve anxiolytic effects without any adverse results.View full abstractDownload PDF (1113K)
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