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61.
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AKIKO TANAKA MASAHIRO MATSUMOTO YUJIRO HAYASHI KOJI TAKEUCHI 《Journal of gastroenterology and hepatology》2006,20(1):38-45
Background and Aim: We recently reported that cyclooxygenase (COX)-2 is upregulated in the rat small intestine after administration of indomethacin, and this may be the key to non-steroidal anti-inflammatory drug (NSAID)-induced intestinal damage. The present study investigated the mechanism for COX-2 expression induced in the rat small intestine by indomethacin, in relation with ulcerogenic processes.
Methods: Animals were given indomethacin or SC-560 p.o., and the intestinal mucosa was examined 24 h later.
Results: Indomethacin caused hemorrhagic lesions in the small intestine, accompanied with an increase in intestinal motility, bacterial invasion and inducible nitric oxide synthase (iNOS) activity, as well as the expression of COX-2 mRNA in the mucosa. Although SC-560 did not cause any damage, this agent caused intestinal hypermotility, the bacterial invasion and the upregulation of COX-2 expression. The mucosal PGE2 content was decreased by SC-560 at 3 h but recovered 12 h later, and this recovery of PGE2 was attenuated by both atropine and ampicillin, in addition to rofecoxib. The intestinal hypermotility response to indomethacin was prevented by both 16,16-dimethyl PGE2 and atropine, but not ampicillin. Yet all these agents inhibited not only the bacterial invasion but also the expression of COX-2 and iNOS activity in the intestinal mucosa following indomethacin treatment, resulting in the prevention of intestinal lesions.
Conclusion: These results suggest that COX-2 expression in the intestinal mucosa following the administration of indomethacin is associated with intestinal hypermotility and bacterial invasion. The intestinal hypermotility caused by COX-1 inhibition may be a key to COX-2 expression after administration of NSAIDs and their intestinal ulcerogenic properties. 相似文献
Methods: Animals were given indomethacin or SC-560 p.o., and the intestinal mucosa was examined 24 h later.
Results: Indomethacin caused hemorrhagic lesions in the small intestine, accompanied with an increase in intestinal motility, bacterial invasion and inducible nitric oxide synthase (iNOS) activity, as well as the expression of COX-2 mRNA in the mucosa. Although SC-560 did not cause any damage, this agent caused intestinal hypermotility, the bacterial invasion and the upregulation of COX-2 expression. The mucosal PGE
Conclusion: These results suggest that COX-2 expression in the intestinal mucosa following the administration of indomethacin is associated with intestinal hypermotility and bacterial invasion. The intestinal hypermotility caused by COX-1 inhibition may be a key to COX-2 expression after administration of NSAIDs and their intestinal ulcerogenic properties. 相似文献
64.
Michael W. Anderson MD Kanika Sharma MD Colin M. Feeney MD 《Academic emergency medicine》1997,4(8):805-809
The incidence of wound botulism is increasing and the epidemiology of the disease is changing. The majority of new cases are associated with injection drug use, in particular, the use of Mexican black tar heroin. This case report and discussion of wound botulism illustrate the following important points: Dysphagia, dysphonia, diplopia, and descending paralysis, in association with injection drug use, should alert the treating physician to the possibility of wound botulism. In such patients, the onset of respiratory failure may be sudden and without clinically obvious signs of respiratory weakness. For the reported patient, maximum inspiratory force measurements were the only reliable indicator of respiratory muscle weakness. This is a measurement not routinely performed in the ED, but may prove essential for patients with suspected wound botulism. To minimize the effect of the botulinum toxin and to decrease length of hospital stay, antitoxin administration and surgical wound debridement should be performed early. 相似文献
65.
药物传递系统(DDS)Ⅳ腔道给药传递系统 总被引:2,自引:0,他引:2
腔道给药是能起全身作用、避开肝首过代谢作用、患者便于自用的非损伤性给药途径。本文着重介绍影响鼻腔、阴道给药药物吸收的生物因素和剂型因素及正在开发的腔道给药传递系统。 相似文献
66.
P. A. Milligan P. E. McGill C. W. Howden A. W. Kelman B. Whiting 《European journal of clinical pharmacology》1993,45(6):507-512
Summary A randomised crossover study was performed in subjects with rheumatoid arthritis (or other arthropathies) to investigate if any alteration in the steady pharmacokinetics of the NSAID piroxicam (a drug which is extensively metabolised via cytochrome P450) or its major metabolites occurred as a result of coadministering either cimetidine or nizatidine.Twelve females and 2 males with mean age, weight, and albumin concentrations of 58 years, 61 kg, and 40 g·L–1 respectively, completed the study. Comparisons were made between the following parameters: plasma piroxicam AUCs [AUC0-24(P)], plasma 5-hydroxypiroxicam AUCs [AUC0-24(5-OHP)], the ratio of these i.e. AUC0-24(5-OHP):AUC0-24(p), the % piroxicam daily dose excreted in urine as 5-hydroxypiroxicam (before and after glucuronidase incubation); and the mean of the steady state trough piroxicam, and 5-hydroxypiroxicam concentrations (obtained during each study phase in addition to the wash-out period).A statistically significant difference as a result of initiating either cimetidine or nizatidine was obtained only for the ratio AUC0-23(5-OHP):AUC0-24(P). This was indicative of a weak potential to inhibit piroxicam hydroxylation.No clinically significant alteration in the steady state pharmacokinetics of piroxicam occurred in these subjects as a result of cimetidine or nizatidine coadministration. Consequently it is unlikely that any adverse events would arise from these combinations. 相似文献
67.
With the advent of genomics, combinatorial paradigms and high-throughput screen (HTS)-based pharmacological testing, the number of compounds flowing through the discovery pipeline is likely to escalate. At the same time, with increased knowledge of the human drug-metabolizing enzymes and the availability of in vitro absorption-metabolism (AM) models, Preclinical Drug Metabolism is poised to meet the challenges of HTS. In order to be successful, however, a rational HTS strategy (vs. serendipitous HTS) has to be employed. Such a strategy is based on automation, validation and integration of in vitroAM models and database management (AVID). A generalized strategy for rational (AVID-based) HTS in Preclinical Drug Metabolism is described briefly. 相似文献
68.
Carlo Bertucci Enrico Domenici Piero Salvadori 《Journal of pharmaceutical and biomedical analysis》1990,8(8-12):843-846
The application of a circular dichroism (c.d.) detection system in HPLC using a chiral stationary phase is presented. The simultaneous measurement of the absorbance and c.d. signal allows the evaluation of the anisotropy factor (g = Δ/) and thus the determination of the enantiomeric excess (e.e.) of the eluates. When this detection system is used in preparative chiral chromatography the collection of the enantiomeric fractions can be readily optimized. 相似文献
69.
70.
[目的]观察比较异环磷酰胺(IFO)、顺铂(DDP)、5-氟尿嘧啶(5-Fu)联合方案(IPF方案)与DDP,5-Fu(PF方案)治疗晚期复发鼻咽癌(Ⅲ-Ⅳ期)的近期疗效及毒副反应。[方法]136例均经病理证实为晚期复发鼻咽癌患者,随机分为IPF组69例,PF组67例(对照组)[结果]IPF组和PF组有效率分别为69.56%(48/69)和43.3%(29/67),两组间差异有显著性(X2=8.519,P<0.01)。中位生存期:IPF组16个月(8-34个月),PF组为6.5个月(4-21个月),两组间差异有显著性(X2=22.36,P<0.05)。毒副作用主要为骨髓抑制,Ⅲ-Ⅳ度白细胞下降率IPF组为49.4%,PF组为5.97%,两组差异有显著性(X2=29.54,P<0.01)。Ⅲ-Ⅳ度血小板下降率IPF组为29.18%,PF组为0%(X2=30.29,P<0.01);Ⅲ-Ⅳ度消化道反应两组的发生率分别为15.94%和11.94%(x2=0.234,P>0.01).且以Ⅲ度为主。[结论]以IFO为主的方案联合治疗晚期复发鼻咽癌疗效好,毒副反应能耐受,可作为一线方案。 相似文献