YAKUGAKU ZASSHI
 Abstracts 
Vol.121, No. 4 (2001)

 
  The Pharmaceutical Society of Japan  

YAKUGAKU ZASSHI, 121(4),259-264, 2001

--Reviews--

Assessment of Anti-Tremorogenic Drugs Using Nicotine-Induced Tail-Tremor Model and Elucidation of the Mechanism

Katsuya SUEMARU, Hiroaki ARAKI, and Yutaka GOMITA

Department of Hospital Pharmacy, Okayama University Medical School, 2-5-1, Shikata-cho, Okayama 700-8558, Japan

Repeated administration of nicotine causes a tremor only in the tail (tail-tremor) of rats. The tremor is accompanied with locomotor hyperactivity without rigidity and immobility of the whole body, suggesting the involvement of the mechanism associated with the movement. The tail-tremor induced by nicotine was suppressed by nicotinic acethylcholine (nACh) receptor antagonists, but not by muscarinic acethylcholine (mACh) receptor antagonists. Moreover, the tail-tremor was suppressed by β-adrenoceptor antagonists and benzodizepines. The tremor at rest is observed only in Parkinson's disease, which is improved by the use of mACh receptor antagonists. An essential tremor is one of the typical tremor connected with the movement (postural tremor) and improved with β-adrenoceptor antagonists. These findings and results suggest that the nicotine-induced tail-tremor is useful for the study of the essential tremor as an animal model. On the other hand, daily administration of nicotine resulted in an augmentation of the tail-tremor. The development of the tail-tremor was suppressed by nACh receptor antagonists, N-methyl-D-aspartate (NMDA) receptor antagonists and nitric oxide (NO) synthase inhibitors. These results suggest that central nACh receptors are essential for the onset and further development of the tail-tremor induced by repeated administration of nicotine, and that NO formation mediated by NMDA receptors is involved in the developmental mechanisms.

Key words--nicotine; tail-tremor; essential tremor


YAKUGAKU ZASSHI, 121(4),265-270, 2001

--Regular Articles--

Superoxide Scavenging Activities of Sixty Chinese Medicines Determined by an ESR Spin-Trapping Method Using Electrogenerated Superoxide

Wenwei LIU,a Tateaki OGATA,*,a Shigeyoshi SATO,a Kei UNOURA,b and Jun-ichi ONODERAc

Graduate School of Science and Engineering, Yamagata University,a Yonezawa 992-8510, Japan, Department of Material and Biological Chemistry, Faculty of Science, Yamagata University,b Yamagata 990-8560, Japan, and Department of Chemistry and Chemical Engineering, Faculty of Engineering, Yamagata University,c Yonezawa 992-8510, Japan

Superoxide-scavenging activities of 60 kinds of Chinese herbal medicines were determined accurately by an electron spin resonance (ESR) spin-trapping technique using 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) as a spin-trapping reagent. As a source of superoxide in this method, superoxide generated by one-electron reduction of the oxygen molecule in dimethyl sulfoxide solution was used. As a result of these studies, very powerful scavenging activity was found in Chinese medicines for inflammation, diseases of blood circulation and for tumors.

Key words--Chinese medicines; superoxide; scavenging activity; ESR; electrolysis of oxygen


YAKUGAKU ZASSHI, 121(4),271-275, 2001

--Regular Articles--

Cytotoxic Activity and Cytokine Gene Induction of Asp-hemolysin to Vascular Endothelial Cells

Takeshi KUMAGAI,*,a Takayuki NAGATA,a Yoichi KUDO,b Yuji FUKUCHI,c Keiichi EBINA,a and Katsushi YOKOTAa

The First Department of Hygienic Chemistry, Tohoku Pharmaceutical University,a 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan, Hygiene Research Laboratory, Sendai Hospital of East Japan Railway Company,b 1-3-1 Itsutsubashi, Aoba-ku, Sendai 980-8508, Japan, and Japanese Red Cross Sendai Hospital,c 2-43-3 Yagiyamahon-cho, Taihaku-ku, Sendai, 982-8508, Japan

We examined the effects of Asp-hemolysin from Aspergillus fumigatus Fresenius-Muramatsu strain on the viability and cytokine gene expression of human umbilical vein endothelial cells (HUVEC). The cell viability of HUVEC was reduced to 50% by 100 μg/ml of Asp-hemolysin. However, lower concentration of Asp-hemolysin ( 〈30 μg/ml) had no effect on the cell viability. The mRNA expression of such cytokines as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8 and granulocyte-macrophage colony stimulating factor (GM-CSF) were also observed in HUVEC cultured with 30 μg/ml of Asp-hemolysin.

Key words--Asp-hemolysin; vascular endothelial cell; cytotoxic activity; cytokine mRNA


YAKUGAKU ZASSHI, 121(4),277-281, 2001

--Notes--

Effects of Low Density Lipoprotein and Oxidized Low Density Lipoprotein on the Cytotoxic Activity of Asp-hemolysin to Murine Macrophages

Takeshi KUMAGAI,*,a Takayuki NAGATA,a Yoichi KUDO,b Yuji FUKUCHI,c Keiichi EBINA,a and Katsushi YOKOTAa

The First Department of Hygienic Chemistry, Tohoku Pharmaceutical University,a 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan, Hygiene Research Laboratory, Sendai Hospital of East Japan Railway Company,b 1-3-1 Itsutsubashi, Aoba-ku, Sendai 980-8508, Japan, and Japanese Red Cross Sendai Hospital,c 2-43-3 Yagiyamahon-cho, Taihaku-ku, Sendai, 982-8508, Japan

We examined the effects of human low density lipoprotein (LDL) and oxidized LDL (Ox-LDL) on the cytotoxic activity of Asp-hemolysin from Aspergillus fumigatus Fresenius-Muramatsu strain to mouse peritoneal macrophages (Mφ). The inhibitory effects of LDL and Ox-LDL on the cytotoxic activity of Asp-hemolysin to Mφ increased in a dose-dependent manner, and the effect of Ox-LDL was greater than the inhibitory effect of LDL. Furthermore, the binding of Asp-hemolysin to LDL or Ox-LDL was observed by western blot analysis of the culture medium. These results suggest that the inhibition by LDL or Ox-LDL on the cytotoxic activity of Asp-hemolysin to Mφ was due to the binding of LDL or Ox-LDL to Asp-hemolysin in the culture medium.

Key words--Asp-hemolysin; cytotoxic activity; low density lipoprotein; oxidized-low density lipoprotein


YAKUGAKU ZASSHI, 121(4),283-288, 2001

--Articles--

Evaluation of Absorbed Dose-Distribution in the X-Ray or Gamma-Irradiator for Blood Products

Satoshi MORIYAMA,* Katsuhiko KURIHARA, Nobuhiko YOKOKAWA, Masahiro SATAKE, and Takeo JUJI

Department of Blood Processing, Japanese Red Cross Central Blood Center, 4-1-31, Hiroo, Shibuya-ku, Tokyo, 150-0012, Japan

Irradiation of blood products abrogates the proliferation of lymphocytes present in cellular component, which is currently the only accepted methodology to prevent transfusion-associated graft versus host disease (TA-GVHD). A range of irradiation dose levels between 15 Gy and 50 Gy is being used, but the majority of facilities are employing 15 Gy. It should, however, be recognized that the delivered dose in the instrument canister might differ from the actual dose absorbed by the blood bag. This study have evaluated the actual dose distribution under practical conditions where a container was loaded with blood products or water bags, or filled with distilled water. This approach provides data that the maximum attenuation occurred when the container was completely filled with a blood-compatible material. Thus, an error of approximately 20 percent should be considered in the dose measured in the in-air condition. A dose calibration in an in-air condition may lead to substantial underexposure of the blood products. A dose distribution study using adequately prearranged exposure period verified that the absorbed dose of 15 Gy was attained at any point in the container for both linear accelerator and gamma-irradiator. The maximal difference in the absorbed dose between measured points was 1.5- and 1.6-fold for linear accelerator and gamma-irradiator, respectively. In conclusion, using blood-compatible materials, a careful dose calibration study should be employed in which the absorbed dose of 15 Gy is obtained at the point where the lowest dose could be expected.

Key words--transfusion-associated graft versus host disease (TA-GVHD); gamma-irradiator; linear accelerator; dose calibration


YAKUGAKU ZASSHI, 121(4),289-293 2001

--Articles--

Estimation of Radiation Exposed Area by the Nuclear Accident Occurred at Tokai Village Using ESR Measurements of Household Sugar

Masayuki KUZUYA,* Shin-ichi KONDO, Kousuke ITO, and Takashi SAWA

Laboratory of Pharmaceutical Physical Chemistry, Gifu Pharmaceutical University, 5-6-1, Mitahora-Higashi, Gifu 502-8585, Japan

The area of radiation exposure by the nuclear accident occurred at Tokai village in 1999 was estimated by the ESR measurement of 95 household sugar samples collected from the accident area. These samples were roughly classified into three types of sugar, fine white sugar, fine brown sugar and coarse brown sugar. The control fine white sugar showed no radical in the ESR spectrum, while those of fine brown sugar and coarse brown sugar showed the presence of a small amount of radicals. It was also shown that, among these three kinds of sugar, the radical concentration of fine white sugar sampled from wooden houses at the area similar to each other did not vary much with the samples, while those of fine brown sugar and coarse brown sugar varied to a considerable extent. Thus, the fine white sugar is considered to be more suitable for the estimation of the level of radiation exposure. The radical concentration of each fine white sugar sample was plotted against the distance from the site of the nuclear accident with a correction of the difference in the shielding effect between concrete houses and wooden houses. The samples obtained at more than 2 km north of the site of nuclear accident showed no ESR spectral signal to a detectable extent. On the other hand, the ESR spectra were observed from the samples obtained within 10 km south and 4 km west of the accident site. These results suggest that the radiation exposure by the contaminant blown by the northeast wind blowing on the day of the accident may occur at the south and west areas.

Key words--electron spin resonance (ESR); sugar radical; nuclear accident; radiation; plasma


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