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Volume 123 (2004)
- Issue 6 Pages 382-
- Issue 5 Pages 311-
- Issue 4 Pages 235-
- Issue 3 Pages 134-
- Issue 2 Pages 55-
- Issue 1 Pages 5-
Volume 123, Issue 5
Displaying 1-6 of 6 articles from this issue
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Review
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Takashi ITO, Junichi AZUMA2004 Volume 123 Issue 5 Pages 311-317
Published: 2004
Released on J-STAGE: April 27, 2004
JOURNAL FREE ACCESSAtherosclerosis-related ischemic heart diseases are the principal cause of death in the last few years. Recently, several reports implicated that taurine, sulfur-containing beta-amino acid, prevented the progression of atherosclerosis through various anti-pathogenetic modifications. Firstly, taurine treatment inhibited lipid peroxidation and/or lowered serum LDL/VLDL cholesterol and elevated HDL, and as a result, it prevented lipid accumulation on the aortic valve in hypercholesterolaemic animals. Secondly, taurine administration prevented endothelial dysfunction, one of the initial events in the formation of lesions of atherosclerosis, through the amelioration of the impairment of monocyte function. Thirdly, while it is well known that taurine scavenges hypochlorous acid (HOCl) produced by myeloperoxidase in neutrophils and macrophages, recent studies revealed that HOCl was one of the major factors oxidizing LDL, implying that the anti-oxidative role of taurine contributes to the anti-atherosclerotic effect. Additionally, TauCl, produced by the reaction of taurine with HOCl, inhibits the activation of NF-κB followed by the inhibition of the production of the pro-inflammatory mediators.
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Hisamitsu UJIHARA2004 Volume 123 Issue 5 Pages 319-328
Published: 2004
Released on J-STAGE: April 27, 2004
JOURNAL FREE ACCESSNewly available psychotropics seem to put the practical psychiatry to a stage of reform. In addition, the recent advancements in the study of neurogenesis in the adult brain force the change of the therapeutic strategy of mental disorders. The fact that the central nervous tissues can repair even after the maturation and that the replacement of neurons continues during adulthood will alter our understanding about their pathogenesis. The action of several psychiatric medications such as antidepressants, mood stabilizers, antipsychotics, and electroconvulsive therapy is converging at neurogenesis and/or neuroprotection. When the validity of the “neurogenesis/neuroprotection hypothesis” of psychiatric medication will be proved in psychiatric practice, we can establish a more rational and more effective treatment of mental disorders.
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Technical Note
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Hideyuki ISHIDA2004 Volume 123 Issue 5 Pages 329-334
Published: 2004
Released on J-STAGE: April 27, 2004
JOURNAL FREE ACCESSMitochondria play a key role in the regulation of cell death, necrosis, and apoptosis. It is well known that the opening of the mitochondrial permeability transition pore (PTP) induces the cytochrome C release and results in apoptosis. Also, it has been reported that the inhibition of PTP by cyclosporin A prevents the ischemia/reperfusion-induced necrosis. Thus, the opening of mitochondrial PTP may be a central coordinating event of apoptotic and necrotic cell death. However, the relationship between PTP opening and both modes of cell death remains elusive. In this paper, we report the recent state of our research method and the role of mitochondrial PTP in cardiac cell death.
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Drug Development Now
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Kenji OHMORI, Kei ADACHI, Haruhiko MANABE, Daisuke HARADA, Etsuo OHSHI ...2004 Volume 123 Issue 5 Pages 335-348
Published: 2004
Released on J-STAGE: April 27, 2004
JOURNAL FREE ACCESSDue to the prevalence of allergic diseases such as bronchial asthma, allergic rhinoconjunctivitis and dermallergosis, efforts at the discovery of novel and effective medications for prevention and treatment of these conditions have been reinforced. Recently, it has been recognized that these allergic diseases are a chronic inflammatory disorder of the lower and upper airways and skin. In this article, we reviewed the recent development of the following new antiallergic therapies: anti-Th2 cytokine antibodies, decoy receptors, receptor antibodies, anti-IgE antibodies, anti-cell adhesion molecules antibodies, antisense oligonucleotides, keratinocyte modulators, inhibitors of phosphodiesterase 4, tachykinin receptor antagonists, and anti-histaminic drugs. Most of these new agents are aimed to inhibit various components of allergic inflammation. The future use of allergic disease therapies hold great promise and excitement.
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Review on New Drug
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Hiroyuki YAMAZAKI, Hideki FUJINO, Mizuho KANAZAWA, Taro TAMAKI, Fumiya ...2004 Volume 123 Issue 5 Pages 349-362
Published: 2004
Released on J-STAGE: April 27, 2004
JOURNAL FREE ACCESSToday 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are the most often prescribed drugs among the therapeutics for hypercholesterolemia. Pitavastatin is a novel statin that has been developed entirely in Japan from the biological screening to clinical studies persuing more efficatious statin than hitherto known. Preclinical studies on drug metabolism revealed that pitavastatin is distributed selectively to the liver, excreted into bile without metabolic modification, and efficiently re-circulates to the liver to show a prolonged plasma half-life. In guinea pigs, pitavastatin enhanced hepatic LDL receptor activity and reduced VLDL secretion in a liver perfusion study, and it lowered plasma total cholesterol (TC) levels at 0.3 mg/kg and triglyceride (TG) levels at 1 mg/kg, respectively, and more. From these results, pitavastatin is assumed to lower LDL cholesterol (LDL-C) by promoting LDL receptor expression and further potentiate the cholesterol-lowering effect and exert TG-lowering effect by reducing VLDL secretion. 14C-Pitavastatin is metabolized with CYP2C9 to 8-hydroxy derivative, but its Vmax /Km was about 2 µl/min/mg, about 1/8 to 1/100 in comparison to the reported values of other statins, indicating that pitavastatin is hardly metabolized. Also, other human P450 species were not inhibited by pitavastatin. Therefore, pitavastatin is considered to have little interaction with drugs through P450. In the summarized clinical results with 862 patients, pitavastatin lowered TC and LDL-C by 28% and 40%, respectively. There was no difference in the frequency of side effects and no serious adverse effect was observed for pitavastatin. Pitavastatin possesses superior plasma lipid-improving effects, induces little drug interaction, and is expected to make a good contribution to the medication of hypercholesterolemia.
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Original Article
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Masayuki UCHIDA, Manabu NAKAJIMA, Megumi KOGANEI, Taketo YAMAJI2004 Volume 123 Issue 5 Pages 363-371
Published: 2004
Released on J-STAGE: April 27, 2004
JOURNAL FREE ACCESSOxybutynin has been used for neurogenic bladder disorders in clinic and known to have anti-cholinergic and spasmolytic properties. Metabolite of oxybutynin, 4-ethylamino-2-butynyl(2-cyclohexyl-2-phenyl) glycolate (N-desethyloxybutynin: DEOB) has been known to have similar anti-cholinergic and spasmolytic properties. However, the effect of DEOB on the urinary bladder has not been clarified in situ. Therefore, in the present study, we studied the effect of DEOB on acetylcholine-induced urinary bladder contraction in comparison with oxybutynin in anesthetized dogs. Intravenously administered DEOB dose-dependently inhibited acetylcholine-induced contractions. Oxybutynin also showed similar efficacy. From the Schild plot, it was found that the slope of DEOB and oxybutynin were 0.78 (95% confidence limit: 0.45-1.11) and 1.49 (95% confidence limit: 0.91-2.08), respectively. The dose of DEOB or oxybutynin needed to shift the concentration-dependent curve of acetylcholine rightward to a two times higher dose was calculated. The doses of DEOB and oxybutynin were 6.4 µg/kg (95% confidence limit: 1.7-12.8 µg/kg) and 13.9 µg/kg (95% confidence limit: 6.3-24.5 µg/kg), respectively. From the above results, it was found that DEOB has the same anti-cholinergic property as oxybutynin and that its activity was almost equipotent to that of oxybutynin. Therefore, DEOB was suggested to play an important role during oxybutynin therapy for neurogenic bladder disorder.
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