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51.
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
52.
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
53.
54.
Role of macrophage and smooth muscle cell apoptosis in association with oxidized low-density lipoprotein in the atherosclerotic development. 总被引:5,自引:0,他引:5
Yuri Akishima Yoshikiyo Akasaka Yukio Ishikawa Zhang Lijun Hideko Kiguchi Kinji Ito Hiroyuki Itabe Toshiharu Ishii 《Modern pathology》2005,18(3):365-373
To examine the role of the apoptosis of macrophages and smooth muscle cells in the development of atherosclerosis, human aortic tissues with intimal lesions were immunostained with antibodies against terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL), single-stranded DNA (clone F7-26), and active caspase-3. Apoptotic cells were detected in the intima using both TUNEL and single-stranded DNA, however, the latter method was the more sensitive one for detecting apoptotic cells in the early stages of atherosclerosis. The number of apoptotic cells increased as the disease progressed. It implies that the apoptosis of intimal cells is involved in the formation of atherosclerotic lesions. In addition, quantitative analyses of the cell types undergoing apoptosis using double-immunostaining revealed that the susceptibility of macrophages and smooth muscle cells to apoptosis was greater specifically in atheroma than in the other atherosclerotic lesions, and macrophages were more susceptible to apoptosis than smooth muscle cells. The frequency and spatial distribution of oxidized low-density lipoprotein (oxLDL) (FOH1a/DLH3)-positive cells were examined by immunohistochemistry, and the results resembled those of apoptotic cells. The number of oxLDL-positive cells in the intima significantly correlated with the susceptibility of smooth muscle cells, but not with that of macrophages, to apoptosis. These results suggest that oxLDL affects the apoptosis of smooth muscle cells during the atherosclerotic development. 相似文献
55.
56.
57.
Yoshikiyo Akasaka MD PhD ; Kinji Ito PhD ; Kazuko Fujita PhD ; Kazuo Komiyama DDS ; Ichiro Ono MD PhD ; Yukio Ishikawa MD PhD ; Yuri Akishima MD PhD ; Hiroko Sato MD PhD ; Toshiharu Ishii MD PhD 《Wound repair and regeneration》2005,13(4):373-382
To characterize apoptosis in keloids and the mechanisms responsible for this process, the expression of activated caspase-9 and -3 in fibroblasts obtained from keloids was analyzed. Immunohistochemistry revealed that the number of fibroblasts positive for terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) or activated caspase-9 or -3 was low but was significantly higher in keloid tissues than in normal scar tissues. Significant relationships between the number of caspase-positive fibroblasts and TUNEL-positive fibroblasts suggested that the activation of caspase-9 and -3 induces apoptosis in a subpopulation of keloid fibroblasts. All keloid fibroblast cell lines established in this study showed activation of caspase-9 and -3 after serum deprivation for 3 or 4 hours, as shown using Western blotting. Furthermore, serum deprivation-induced apoptosis in a keloid fibroblast line was blocked by a caspase-9 inhibitor (acetyl-Leu-Glu-His-Asp-al), indicating that activation of caspase-9 was necessary for the process of apoptosis in keloid fibroblasts. Although serum deprivation did not significantly change the level of apoptosis protease activating factor-1 in any of the lines, cytochrome c release was detected in cytosolic fractions of the lines after serum deprivation for 3 or 4 hours. These results strongly suggest that keloid fibroblasts are predisposed to apoptosis and cytochrome c release and that caspase-9 activation may underlie regulation of apoptosis in keloid fibroblasts in vivo. 相似文献
58.
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
59.
60.
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