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排序方式: 共有235条查询结果,搜索用时 31 毫秒
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Hematologic Toxicity of AZT and ddC Administered as Single Agents and in Combination to Rats and Mice 总被引:2,自引:0,他引:2
THOMPSON M. B.; DUNNICK J. K.; SUTPHIN M. E.; GILES H. D.; IRWIN R. D.; PREJEANT J. D. 《Toxicological sciences》1991,17(1):159-176
Hematologic Toxicity of AZT and ddC Administered as Single Agentsand in Combination to Rats and Mice. THOMPSON, M. B., DUNNICK,J. K., SUTPHIN, M. E., GILES, H. D., IRWIN, R. D., AND PREJEAN,J. D. (1991). Fundam. Appl. Toxicol. 17, 159-176. Toxicity studiesof 3'-azido-2',3'-dideoxythymidine (AZT) and 2',3'-dideoxycytidine(ddC) were conducted in F344/N rats and B6C3F, mice. The drugswere administered as single agents and in combination. In allstudies, animals were treated by oral gavage twice a day, 7days a week. In studies of the individual compounds, each wasadministered for 13 weeks at the following concentrations; AZTin rats, 0, 125, 250, 500, 1000 mg/kg and in mice, 0, 25, 50,100, 400, 1000 mg/kg; ddC in rats and mice, 0, 250, 1000, 2000mg/kg. Additional male rats and female mice that were treatedwith 0, 250, 1000, or 2000 mg/kg ddC and male and female micetreated with 0, 50, 400, 1000 mg/kg AZT were maintained for30 days after treatment was stopped (at 94 days) to evaluatethe reversibility of toxic effects. Hematologic variables weremeasured on Days 5, 23, and 94 (last day of dosing), and onDay 123 (after a 30-day period without treatment). AZT and ddCproduced dose-related, poorly regenerative, macrocytic anemiasas evidenced by decreases in erythrocyte counts, he-matocrits,and hemoglobin concentrations and increases in mean corpuscularhemoglobin and mean corpuscular volume. Bone marrow samplesin rats treated with AZT were hyperplastic whereas those inmice treated with AZT and rats and mice treated with ddC werehypoplastic. The hematologic toxicity of AZT was more severethan that of ddC. Generally, toxic effects of either chemicalwere greater in mice than in rats and more pronounced in femalethan in male animals. After 30 days without dosing, hematologiceffects either resolved or dramatically improved. In studiesin which ddC and AZT were administered in combination for 4weeks at concentrations of 0/0, 0/500, 500/0, 10/500, 100/500,500/500, and 500/1000 mg/kg ddC/AZT, there was macrocytic anemiain animals in the lower doses and marked microcytic anemia insurviving male mice in higher dose groups. Most female micedied in the 500/500 and 500/1000 mg/kg ddC/ AZT dose groups.At lower concentrations (100/500, 500/1000 mg/kg ddC/AZT), effectsof the two drugs were similar to those in the single drug studies.At higher concentrations (500/500 and 500/1000 mg/kg ddC/AZT),the combination treatment produced enhanced hematopoietic toxicity.These studies demonstrated the early and progressive time courseof toxicity of AZT and ddC, species differences in sensitivitiesand responses, and reversibility of effects after terminationof treatment. Based on these findings, a chronic toxicity studyis being conducted with AZT in mice. 相似文献
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REDDY VANGA K.; DESHPANDE SHARAD S.; CINTRA WAGNER M.; SCOBLE GILES T.; ALBUQUERQUE EDSON X. 《Toxicological sciences》1991,17(4):746-760
Effectiveness of Oximes 2-PAM and HI-6 in Recovery of MuscleFunction Depressed by Organophosphate Agents in the Rat Hemidiaphragm:An in vitro Study. REDDY, V. K., DESHPANDE, S. S., CINTRA, W.M., SCOBLE, G. T., AND ALBUQUERQUE, E. X. (1991). Fundam. Appl.Toxicol. 17, 746760. Phrenic nerve diaphragm musclesof young adult rats were used to study the ability of the oximes2-PAM and HI-6 to recover muscle function depressed by organophosphate(OP) agents. The single twitch of diaphragm muscles which wereexposed to soman (0.2 mm) recovered after washing with salinefor 3 hr, but the muscles pretreated with sarin (0.4 µM),VX (0.2 µM), or tabun (0.4 µM) showed only partialrecovery. In addition, after 3 hr washing, the muscles pretreatedwith soman as well as with tabun did not recover the tetanussustaining ability (TSA), yet complete recovery was observedwith muscles pretreated with sarin and VX. These results indicatethat the OPs have different effects on muscle contractile propertiesand that VX- and sarin-pretreated muscles recover equally wellafter wash with physiological solution. The recovery of twitchtension of diaphragm muscles by 2-PAM and HI-6 was similar tothat achieved by washing with saline for 3 hr for sarin- andsoman-exposed muscles. The most remarkable differences wereseen in the recovery of TSA. Both 2-PAM and HI-6 recovered theTSA of muscles that were pretreated with sarin and VX. Although2-PAM recovered the TSA after tabun pretreatment, HI-6 had nodiscernible effect. On the other hand, HI-6 recovered the TSAof soman-pretreated muscles but 2-PAM did not. The effectivenessof muscle function recovery was not related to the oximes' abilityto reactivate AChE, thus indicating that the recovery of musclecontractility may be attributed to a direct effect of thesecompounds on the muscle. 相似文献
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Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium 总被引:12,自引:0,他引:12
van Hinsbergh VW; Bertina RM; van Wijngaarden A; van Tilburg NH; Emeis JJ; Haverkate F 《Blood》1985,65(2):444-451
Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator- inhibitor. High concentrations of thrombin-but not of factor Xa or IXa-- had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor. 相似文献
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HUMAN ZYGAPOPHYSEAL JOINT CAPSULE AND SYNOVIAL FOLD INNERVATION 总被引:1,自引:0,他引:1
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KH Neppelenbroek RS Seó VM Urban S Silva LN Dovigo JH Jorge NH Campanha 《Oral diseases》2014,20(4):329-344
In healthy individuals, Candida species are considered commensal yeasts of the oral cavity. However, these microorganisms can also act as opportunist pathogens, particularly the so‐called non‐albicans Candida species that are increasingly recognized as important agents of human infection. Several surveys have documented increased rates of C. glabrata, C. tropicalis, C. guilliermondii, C. dubliniensis, C. parapsilosis, and C. krusei in local and systemic fungal infections. Some of these species are resistant to antifungal agents. Consequently, rapid and correct identification of species can play an important role in the management of candidiasis. Conventional methods for identification of Candida species are based on morphological and physiological attributes. However, accurate identification of all isolates from clinical samples is often complex and time‐consuming. Hence, several manual and automated rapid commercial systems for identifying these organisms have been developed, some of which may have significant sensitivity issues. To overcome these limitations, newer molecular typing techniques have been developed that allow accurate and rapid identification of Candida species. This study reviewed the current state of identification methods for yeasts, particularly Candida species. 相似文献