YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
124 巻, 3 号
選択された号の論文の8件中1~8を表示しています
総説
  • 渡辺 俊明, 田中 正彦, 渡邉 和俊, 高松 康雄, 戸部 昭広
    2004 年 124 巻 3 号 p. 99-111
    発行日: 2004/03/01
    公開日: 2004/02/25
    ジャーナル フリー
      Increasing data suggest that oxygen free radical species play detrimental roles in ischemic diseases. A free radical scavenger capable of inhibiting oxidative injury is expected to become a new drug for the treatment of ischemic diseases such as cerebral ischemia. Edaravon (3-methyl-1-phenyl-2-pyrazolin-5-one), which has been developed as an neuroprotective agent for more than 15 years since its discovery, is approved for the treatment of acute cerebral infarction. In this paper, the pharmacologic characteristics and clinical effects of edaravone are reviewed. In early stage of investigation, edaravone was found to have promising activities as an antioxidative radical scavenger, quenching hydroxyl radical (•OH) and inhibiting both •OH-dependent and •OH-independent lipid peroxidation. Edaravone showed inhibitory effects on both water-soluble and lipid-soluble peroxyl radical-induced peroxidation systems, which are different from the inhibitory effects of vitamins C and E in each system, respectively. Oxidative injury to cultured endothelial cells caused by arachidonate (AA) peroxides is prevented in the existence of edaravone. To clarify the characteristics of this free radical scavenger, further investigation was carried out. Edaravone ameliorated exacerbation of cortical edema induced by a focal ischemia-reperfusion model in rats, suggesting inhibitory effects on oxidative injury to the blood-brain barrier (BBB). Additionally, edaravone also prevented rat cortical edema caused by intracortical AA infusion in which free radical production and subsequent oxidative injury to the BBB are involved. With advances in in vivo measurement technology of oxygen radicals, edaravone was shown to inhibit postischemic increases in •OH production and tissue injury in the penumbral or recirculated area in rat cerebral ischemia models. In clinical studies, edaravone improved the core neurologic deficits, activities of daily living, and functional outcome of stroke patients. Furthermore, a study using proton magnetic resonance spectroscopic techniques showed that edaravone preserved N-acetyl-aspartate in stroke patients, a promising neuronal marker in the brain. Further investigation is essential for a better understanding of free radical-mediated cerebral injury during ischemia followed by recirculation. We hope that edaravone represents a promising neuroprotectant for drug therapy in acute cerebral ischemia.
  • 鍜冶 利幸
    2004 年 124 巻 3 号 p. 113-120
    発行日: 2004/03/01
    公開日: 2004/02/25
    ジャーナル フリー
      Cadmium and lead are heavy metals that have been shown to induce vascular disorders such as atherosclerosis in experimental animals. However, little is known about the mechanisms by which cadmium and lead induce vascular toxicity. The toxicity was investigated using a culture system of vascular endothelial and smooth muscle cells. Cadmium destroys the monolayer of endothelial cells and the cytotoxicity is protected by zinc and copper without metallothionein induction. On the other hand, lead does not exhibit cytotoxicity but inhibits the repair of endothelial monolayers after wounding by a lower response to endogenous basic fibroblast growth factor mediated by suppression of the synthesis of perlecan, a large heparan sulfate proteoglycan. In addition, cadmium and lead reduce endothelial fibrinolytic activity by induction of plasminogen activator inhibitor type 1 synthesis and by inhibition of tissue-type plasminogen activator, respectively. In vascular smooth muscle cells, cadmium and lead can promote their proliferation and influence proteoglycan synthesis and fibrinolysis in different manners. These results indicate that cadmium and lead have specific toxicities in the proliferation, fibrinolysis, and extracellular matrix formation of vascular endothelial and smooth muscle cells.
一般論文
  • Takashi TOKORO, Juyong WANG, Isao KITAJIMA
    原稿種別: Regular Article
    2004 年 124 巻 3 号 p. 121-126
    発行日: 2004/03/01
    公開日: 2004/02/25
    ジャーナル フリー
      This study sought to induce the effect of nitric oxide (NO) production in vascular endothelial cells by Pitavastatin, which is a novel HMG-CoA reductase inhibitor (statin). The growth capacity of vascular endothelial cells significantly (p<0.01) declined when stimulated with TNF-α (10 ng/ml). The growth capacity of the TNF-α treated cells recovered, when the TNF-α stimulation was performed after Pitavastatin (100 nM) pretreatment. The recovery of the growth capacity of the cells was suppressed by the presence of the NO synthase inhibitor, L-NAME. Pitavastatin increased NO production by the vascular endothelial cells in a dose and time dependent manner. The NO production was suppressed by the presence of mevalonic acid and geranylgeranyl pyrophosphate. In addition, the expression of endothelial nitric oxide synthase was strongly induced by Pitavastatin, and was suppressed by mevalonic acid and geranylgeranyl pyrophosphate by Western blot analysis. Our results show that Pitavastatin induces NO production by vascular endothelial cells, and protects vascular endothelial cells from injury due to the inflammatory reaction induced by TNF-α.
  • Hitoshi NAKAMURA, Yoshitsugu YANAGIHARA, Hiroko SEKIGUCHI, Fusao KOMAD ...
    原稿種別: Regular Article
    2004 年 124 巻 3 号 p. 127-134
    発行日: 2004/03/01
    公開日: 2004/02/25
    ジャーナル フリー
      By using lactose colored with erythrocin, we investigated the effects of mixing methods on mixing degree during the preparation of trituration with a mortar and pestle. The extent of powder dilution was set to 4 to 64 fold in the experiments. We compared the results obtained by using two methods: (1) one-step mixing of powders after addition of diluents and (2) gradual mixing of powders after addition of diluents. As diluents, we used crystallized lactose and powdered lactose for the preparation of trituration. In the preparation of 64-fold trituration, an excellent degree of mixing was obtained, with CV values of less than 6.08%, for both preparation methods and for the two kinds of diluents. The mixing of two kinds of powders whose distributions of particle sizes were similar resulted in much better degree of mixing, with CV values of less than 3.0%. However, the concentration of principal agents in 64-fold trituration was reduced by 20% due to the adsorption of dye to the apparatus. Under conditions in which a much higher dilution rate and/or much better degree of dilution was required, it must be necessary to dilute powders with considering their physicality and to determine the concentrations of principal agents after the mixing.
  • Hitoshi NAKAMURA, Yoshitsugu YANAGIHARA, Hiroko SEKIGUCHI, Michiteru O ...
    原稿種別: Regular Article
    2004 年 124 巻 3 号 p. 135-139
    発行日: 2004/03/01
    公開日: 2004/02/25
    ジャーナル フリー
      By using lactose colored with erythrocin, we examined the effect of particle size on mixing degree during the preparation of triturations with a mortar and pestle. We used powders with different distributions of particle sizes, i.e., powder that passed through 32-mesh but was trapped on a 42-mesh sieve (32/42-mesh powder), powder that passed through a 42-mesh sieve but was trapped on a 60-mesh sieve (42/60-mesh powder), powder that passed through a 60-mesh sieve but was trapped on a 100-mesh sieve (60/100-mesh powder), and powder that passes through a 100-mesh sieve (>100-mesh powder). The mixing degree of colored powder and non-colored powder whose distribution of particle sizes was the same as that of the colored powder was excellent. The coefficient of variation (CV) value of the mixing degree was 6.08% after 40 rotations when colored powder was mixed with non-colored powder that both passed through a 100-mesh sieve. The CV value of the mixing degree was low in the case of mixing of colored and non-colored powders with different particle size distributions. After mixing, about 50% of 42/60-mesh powder had become smaller particles, whereas the distribution of particle sizes was not influenced by the mixing of 60/100-mesh powder. It was suggested that the mixing degree is affected by distribution of particle sizes. It may be important to determine the mixing degrees for drugs with narrow therapeutic ranges.
  • 近藤 伸一, 古田 陽司, 大北 信太郎, 笹井 泰志, 荒巻 秀樹, 葛谷 昌之
    2004 年 124 巻 3 号 p. 141-148
    発行日: 2004/03/01
    公開日: 2004/02/25
    ジャーナル フリー
      The mechanochemical reaction of free riboflavin (FR) due to vibratory ball milling was carried out in a stainless steel vessel at room temperature under anaerobic conditions. The ESR of the fractured sample showed a broad single-line spectrum. It is suggested that the solid-state single-electron transfer (SSET) reaction from the surface of the stainless steel vessel to FR proceeded during the vibratory milling, resulting in the formation of the corresponding anion radicals. When the mechanochemical reaction of FR in the presence of calcium pantothenate (PC) was carried out, the radical concentration increased with the increasing PC content. It was shown that the anion radical in the metal complex was stable for a lengthy period of time even in highly humid air.
ノート
  • 石本 敬三, 大坪 泰昭, 田村 ちひろ, 内田 豊, 石光 淳, 神谷 晃
    2004 年 124 巻 3 号 p. 149-157
    発行日: 2004/03/01
    公開日: 2004/02/25
    ジャーナル フリー
      To promote cancer chemotherapy among outpatients, a special room for cancer chemotherapy (outpatient drip infusion room) was established in Yamaguchi University Hospital in April 2002. Since then, pharmacists have played a central role in all aspects, including decisions on the flow rate for prescriptions/injections, protocol checking, preparation of injections, aseptic preparation of anticancer agents, provision of information to patients, and financial impact analysis. In this study, we analyzed the current status of these activities and conducted a questionnaire survey regarding the involvement of pharmacists in chemotherapy at the outpatient clinic among patients and physicians. Pharmacists contributed to the administration of anticancer agents, including protocol checking and aseptic preparation, and no malpractice incident has occurred since the outpatient drip infusion room was established. According to responses from patients, 28 of 29 patients reported that they underwent treatment without anxiety. According to responses from physicians, 15 of 18 physicians considered the involvement of pharmacists beneficial. In addition, the amount claimed for health insurance as of March 2003 was 500000 yen, which was about 5-fold that before the establishment of the outpatient drip infusion room. These results suggest that pharmacists contribute to the promotion of cancer chemotherapy in outpatients with respect to the safety of medical practice, patient services, and hospital management. Therefore participation in cancer chemotherapy at the outpatient clinic may become a primary activity of pharmacists.
  • 山口 友明, 井田 隆, 平賀 正純, 大石 一彦, 内田 幸宏, 越前 宏俊
    2004 年 124 巻 3 号 p. 159-163
    発行日: 2004年
    公開日: 2004/02/25
    ジャーナル フリー
      Proliferation of vascular smooth muscle cells (VSMC) stimulated by oxidative stresses and reactive oxygen species (ROS) may play a pivotal role in the pathogenesis of atherosclerosis. Antiatherosclerotic effects of angiotensin II receptor blockers, angiotensin converting enzyme inhibitors, HMG CoA reductase inhibitors, calcium channel blocker and epalrestat were studied with an in vitro guinea-pig basilar artery smooth muscle cell (GBa-SM3) culture system over 3 days incubated with 0 to 10% of fetal bovine serum. Results demonstrated that simvastatin (0.1 mM), fluvastatin (0.3 mM), amlodipine (0.2 mM) and epalrestat (1 mM) elicited significant (p<0.05 or 0.01) antiproliferative effects, whereas losartan (1 mM), valsartan (1 mM), enalapril (0.1 mM), captopril (1 mM), trandolapril (0.01 mM), pravastatin (0.7 mM) did not. In conclusion, the present in vitro VSMC culture system may serve as a comprehensive screening method for pleiotropic effects of commonly used therapeutic agents.
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