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D Lau BJ Hering A El-Ouaghlidi H Jahr H Brandhorst D Brandhorst R Vietzke K Federlin RG Bretzel 《Canadian Metallurgical Quarterly》1999,77(1):175-177
The shikimate pathway presents an attractive target for malaria chemotherapy. Three shikimic acid analogs exhibited different effects on Plasmodium falciparum growth. (6R)-6-Fluoro-shikimate and (6S)-6-fluoro-shikimate inhibited growth (50% inhibitory concentrations, 1.5 x 10(-5) and 2.7 x 10(-4) M, respectively), whereas 2-fluoro-shikimate had no effect. para-Aminobenzoic acid abrogated the inhibition, demonstrating that the shikimate pathway was specifically targeted. 相似文献
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JT Green GA Thomas J Rhodes BK Evans MA Russell C Feyerabend GS Fuller RG Newcombe WJ Sandborn 《Canadian Metallurgical Quarterly》1997,61(3):340-348
BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic value in the active disease. Because side effects are common, we developed a topical enema formulation of nicotine. OBJECTIVE: To study the pharmacokinetics of nicotine complexed with a polyacrylic carbomer and administered by enema to eight healthy volunteers and to eight patients with active ulcerative colitis, verified sigmoidoscopically. PATIENTS AND METHODS: All 16 subjects were nonsmokers. The mean age for normal subjects was 33 years; the mean for patients with ulcerative colitis was 60 years. Median stool frequency for patients with ulcerative colitis was four daily. Patients were taking 5-amino salicylic acid compounds and five were taking oral prednisolone (median dose, 12 mg daily). Nicotine, 6 mg, complexed with carbomer 974P, 400 mg, was administered in a 100 ml enema after an overnight fast, with serial blood measurements taken over 8 hours. Serum nicotine and cotinine were measured by gas liquid chromatography. Area under the concentration-time curves were calculated by the trapezoidal method, and the terminal elimination half-life was derived by extrapolation of the log-linear terminal phase. RESULTS: With the exception of nicotine time to reach peak concentration, which was longer in patients (median of 60 minutes compared with 45 minutes; p < 0.005), other comparisons between normal subjects and patients showed no statistically significant difference, although there was considerable inter-subject variation. Maximum concentration of nicotine, 8.1 +/- 3.5 ng/ml, in the 16 subjects occurred after a median of 60 minutes (range, 30 to 180 minutes); maximum cotinine concentrations of 60.4 +/- 11.5 ng/ml occurred after 4 hours. Side effects in five subjects were mild (four subjects) or moderate (one subject) and included lightheadedness, nausea, and headache; these five subjects were female lifelong nonsmokers of low body weight. CONCLUSION: Because most of the active ingredient of nicotine is converted to continine on the first pass through the liver, substantial concentrations can be achieved at the site of disease with only modest rises in serum nicotine, which are responsible for side effects; cotinine has low pharmacologic activity. Topical administration of nicotine may be useful treatment for distal ulcerative colitis. 相似文献
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Cerumen impaction represents the most common otologic problem encountered by physicians. It can affect up to 6% of the general population and a much higher percentage in the mentally retarded population. Cerumen is a mixture of secretory products of two glands in the external auditory canal where it serves a protective function. The external auditory canal possesses a unique anatomy and physiology that permits an efficient self-cleaning system. In most cases, a breakdown in the epithelial migration of the external auditory canal is thought to cause cerumen impaction. The management of cerumen impaction include direct removal, irrigation, and the use of cerumenolytics. 相似文献
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RG Sachs 《Canadian Metallurgical Quarterly》1986,33(11):3283-3292
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