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31.
M Yoshioka H Fujimori T Deguchi H Masayasu K Suzuki K Inamura A Kosasayama F Ishikawa 《Biochemical pharmacology》1990,39(1):37-47
The effects of L-arginine (Arg) derivatives on soluble guanylate cyclase from neuroblastoma N1E 115 cells were examined. The Arg derivatives were modified at the -NH2, -COOH, C alpha-proton or guanidino group of Arg. Among the synthesized derivatives, eight compounds, i.e. the 5-(dimethylamino)-1-naphthalenesulfonyl (DNS) ones, especially N-cyclohexyl-2-(N-DNSamino)-5-guanidino-2-methylvaleramide and 1-[2-(N-DNSamino)-2-(2-imino-1,2,3,4,5,6-hexahydropyrimidin- 4-yl)acetyl]- piperidine, were found to inhibit the activity of crude guanylate cyclase in the 105,000 g supernatant fraction of the cell homogenate. The enzyme, partially purified by a column of Chelex 100 Na+, was also inhibited by these eight compounds. The mode of the inhibition was competitive. The Ki values were in the range of 2-8 microM for the enzyme in the 105,000 g supernatant fraction and 3-16 microM for the partially purified enzyme, in the presence of Mg2+ as a metal cofactor. In contrast, a new derivative, methyl 2-amino-5-guanidinovalerate (M Arg ME), as well as the Arg methyl ester (Arg ME) and Arg; were found to enhance the activity of the partially purified guanylate cyclase; KA values of M Arg ME, Arg ME and Arg were approximately 9, 4 and 3 microM respectively. From these results, the free guanidino group including 2-imino-1,2,3,4,5,6-hexahydropyrimidin-4-yl or 2-imino-1,2,3,4,5,6-hexahydropyrimidin-5-yl and modification of the --NH2 residue with a hydrophobic group such as DNS seemed to be essential for inhibition of the guanylate cyclase; however, the guanidino and --NH2 residue of Arg should be free for activation by these Arg derivatives. 相似文献
32.
Ester prodrugs of zidovudine 总被引:1,自引:0,他引:1
Ten novel ester prodrugs of zidovudine (azidothymidine; AZT) were synthesized with aliphatic acids (acetic-stearic), and the enzymatic regeneration of AZT from the prodrugs was investigated both in vitro and in vivo. The enzymatic hydrolysis rates of the AZT esters in the presence of mouse enzyme systems (plasma, liver, and intestine, and kidney) were highly dependent on the lengths of the acyl chains of the prodrugs. The caprate or caprylate of AZT showed the highest reactivity to three of the four enzyme systems; either the decrease or the increase in the acyl chain length resulted in the decrease of the reactivity to the enzymes. Zidovudine (AZT) and three of the prodrugs (acetate, caprate, and stearate) were administered to mice intraperitoneally, and the plasma concentrations of AZT and a corresponding prodrug were measured. The AZT concentrations in plasma following the acetate administration rapidly decreased with a half-life of 14.5 min. This tendency is similar to that shown in direct AZT administration. On the other hand, the concentrations following the caprate or stearate administration decreased slowly and were maintained for as long as 4 h after dosing. The prodrug concentrations in plasma after the prodrug administration were under the detection limit (0.01 micrograms/mL), except for acetate. The absence of the caprate and stearate in plasma may be attributed to the high hydrophobicity or favorable tissue distribution of the ester derivatives. 相似文献
33.
O Hirai H Handa H Kikuchi M Ishikawa Y Kinuta 《No shinkei geka. Neurological surgery》1988,16(10):1141-1147
Lumbar subarachnoid pressure (LSP) was continuously monitored via intrathecally introduced polyethylene catheter to select the patients for shunt operation. A total of seventy cases included so-called normal pressure hydrocephalus (NPH) secondary to subarachnoid hemorrhage (SAH; 34 cases), idiopathic NPH (17 cases), secondary NPH whose symptoms developed after operations for brain tumors, head injuries or meningitis (12 cases) and other intracranial diseases including pseudotumor cerebri or meningeal carcinomatosis, etc. (7 cases). Shunt operation was effective in 36 cases and not effective in 9 cases, while 25 cases were not shunted since LSP was not elevated or clinical manifestations were slight. Mean values of baseline pressure and maximum pressure in shunt effective group, shunt non-effective group and non-shunted group were 14.5, 12.7, 9.0 and 29.9, 25.0, 17.9 mmHg, respectively. Statistical difference was observed between shunt effective group and non-shunted group. Frequency of pressure waves was also significantly higher in shunt effective group than in non-shunted group. Above all, measurement of LSP was regarded as useful in idiopathic NPH. However, preoperative clinical symptoms had a closer relationship to shunt response than results of LSP in post SAH patients. Complication related to this monitoring was negligible except in one case of meningitis which was easily treated by administration of antibiotics. Follow-up study also justified our selection since no further deterioration was noted in non-shunted group. The present study indicates that measurement of LSP would be useful in selecting the patients who will benefit from shunting and in eliminating unnecessary shunt operations because this simple method is easily performed at bed side without perforating the skull.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
34.
35.
36.
Pharmacologic preconditioning effects: Prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver 总被引:1,自引:0,他引:1
Ken-ichi Matsuo M.D. Shinji Togo M.D. Ph.D. Hitoshi Sekido M.D. Ph.D. Tomoyuki Morita M.D. Ph.D. Masako Kamiyama Ph.D. Daisuke Morioka M.D. Ph.D. Toru Kubota M.D. Ph.D. Yasuhiko Miura M.D. Ph.D. Kuniya Tanaka M.D. Ph.D. Takashi Ishikawa M.D. Ph.D. Yasushi Ichikawa M.D. Ph.D. Itaru Endo M.D. Ph.D. Hitoshi Goto M.D. Ph.D. Hiroyuki Nitanda M.D. Ph.D. Yasushi Okazaki M.D. Ph.D. Yoshihide Hayashizaki M.D. Ph.D. Hiroshi Shimada M.D. Ph.D. 《Journal of gastrointestinal surgery》2005,9(6):758-768
Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver. 相似文献
37.
38.
T. Koseki Y. Benno Y. J. Zhang-Koseki M. Umeda I. Ishikawa 《Oral microbiology and immunology》1996,11(3):203-208
Selected media were compared for primary isolation and detection of oral treponemes from clinical samples. Forty-eight subgingival plaque samples from 45 patients suffering from periodontitis were anaerobically cultivated for 2 weeks at 37°C. Of the 9 media studied, Medium 10 (M10), which was supplemented with 10% rabbit serum and incubated using the plate-in-bottle method, supported the highest colony-forming units of the anaerobes. The treponemal colonies were detected at least on one medium from 83% of the subgingival plaque samples. The new oral spirochete medium in an anaerobic chamber supported the highest detection frequency of the oral treponemes (64% of samples); however, M10 in the plate-in-bottle was found to produce the highest colony-forming unit recovery of the oral treponemes (median 3.6% of the total colony-forming units). This study suggests that M10 in the plate-in-bottle and new oral spirochete medium in the anaerobic chamber are essential in cultivating oral treponemes. 相似文献
39.
Hiroshi Inada Hiroyuki Horio Kiyomu Ishikawa Hiromichi Yoshikawa Eishi Harasawa Hidehiro Hosaka 《Journal of medical systems》1993,17(3-4):257-266
A filing system for ocular fundscopic image data was developed by using a personal computer for the Twin AMHTS. The development of the system was tried as one of the data transfer system including image data between two similar AMHTSs named the Twin AMHTS through the information network system. The filing system is capable of storing 26782 data of ophthalmoscopic pictures with a data compression mode by using a magneto-optical disk (MOD) whose storage capacity of both sides is 616 MB. It takes no long time for retrieval and display of the image data in the filing system. Good quality of compression and decompression obtained and reproducibility of the ocular fundus picture is favorable regardless of normal or abnormal cases. As a result, it is suggested that the developed system has practical utility although it requires more improvement. 相似文献
40.
Chien-Huang Lin Feng-Nien Ko Hisahi Ishii Tsutomu Ishikawa Ih-Sheng Chen Che-Ming Teng H.-P. Kuo 《Naunyn-Schmiedeberg's archives of pharmacology》1997,355(2):210-216
We investigated the effects of a novel platelet-activating factor (PAF) receptor antagonist, CIS-19 [cis-2-(3, 4-dimethoxyphenyl)-6-isopropoxy-7-methoxy-1-(N-methylformamido)-1,
2, 3, 4-tetrahydronaphthalene], on PAF-, histamine-, substance P- and antigen-induced bronchoconstriction and microvascular
leakage, as well as PAF- and antigen-induced bronchial hyperreactivity to methacholine in urethane-anesthetized guinea-pigs.
Administration of CIS-19 (0.5–5 mg/kg, i.v.) inhibited the increase in lung resistance induced by PAF (30 ng/kg, i.v.) in
a dose-dependent manner, but failed to inhibit the increase induced by histamine (30 μg/kg, i.v.) or substance P (6.5 μg/kg,
i.v.). CIS-19 (5 mg/kg, i.v.) did not inhibit the increase in lung resistance induced by ovalbumin (2 mg/kg, i.v.) in actively
sensitized guinea-pigs. PAF (30 ng/kg, i.v.)-induced microvascular leakage, measured by the extravasation of Evans blue dye,
was dose-dependently inhibited by CIS-19 (0.5–5 mg/kg, i.v.) in the trachea, main bronchi and intrapulmonary airways, but
it did not affect histamine (30 μg/kg, i.v.)- or substance P (6.5 μg/kg, i.v.)-induced microvascular leakage at all airway
levels. CIS-19 (2.5 and 5 mg/kg) did not affect ovalbumin (2 mg/kg, i.v.)-induced microvascular leakage in all airway levels
in actively sensitized guinea-pigs. CIS-19 (2.5 and 5 mg/kg, i.v.) significantly inhibited PAF-induced enhancement of the
bronchial response to methacholine, but had no effect on ovalbumin (0.05 mg/kg, i.v.)-induced bronchial hyperreactivity in
actively sensitized guinea-pigs. It is concluded that CIS-19 is a potent PAF receptor antagonist which inhibits PAF- but not
antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity. These results suggest that PAF plays
little or no role in early airway responses following antigen challenge.
Received: 29 April 1996 / Accepted: 10 October 1996 相似文献