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青蒿琥酯皮肤擦剂在小鼠和兔体内的药代动力学研究 总被引:1,自引:0,他引:1
将青蒿琥酯溶于苯二甲酸二甲酯,加适量氨酮制成皮肤擦剂。给兔脱毛后,皮肤涂抹此擦剂25mg/kg后,血药浓度达峰时间平均为2 h,峰浓度平均为1.80μg/ml。药物在兔体内平均驻留时间为3.54 h,清除半衰期约为2.46 h。给小鼠脱毛皮肤涂抹擦剂6.7,31.3和71.4 mg/kg,血药浓度在给药后0.5~4 h达高峰,峰浓度分别为0.82,2.05和7.11μg/ml,体内药物平均驻留时间为3.39,2.79及3.54 h,清除半衰期为2.35,1.93及2.45 h。可见,给兔及小鼠皮肤擦剂后,青蒿琥酯吸收良好,血药浓度维持时间较长。 相似文献
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Acute health effects of the Sea Empress oil spill 总被引:5,自引:1,他引:4
R. A. Lyons J. M. Temple D. Evans D. L. Fone S. R. Palmer 《Journal of epidemiology and community health》1999,53(5):306-310
STUDY OBJECTIVE: To investigate whether residents in the vicinity of the Sea Empress tanker spill suffered an increase in self reported physical and psychological symptoms, which might be attributable to exposure to crude oil. DESIGN: Retrospective cohort study; postal questionnaire including demographic details, a symptom checklist, beliefs about health effects of oil and the Hospital Anxiety and Depression and SF-36 mental health scales. SETTING: Populations living in four coastal towns on the exposed south Pembrokeshire coast and two control towns on the unexposed north coast. PATIENTS: 539 exposed and 550 unexposed people sampled at random from the family health services authority age-sex register who completed questionnaires. MAIN RESULTS: Adjusted odds ratios for self reported physical symptoms; scores on the Hospital Anxiety and Depression and SF-36 mental health scales, in 1089 people who responded out of a possible 1585 (69%). CONCLUSIONS: Living in areas exposed to the crude oil spillage was significantly associated with higher anxiety and depression scores, worse mental health; and self reported headache (odds ratio = 2.35, 95% CI 1.56, 3.55), sore eyes (odds ratio = 1.96, 95% CI 1.06, 3.62), and sore throat (odds ratio = 1.70, 95% CI 1.12, 2.60) after adjusting for age, sex, smoking status, anxiety, and the belief that oil had affected health. People living in exposed areas reported higher rates of physical and psychological symptoms than control areas. Symptoms significantly associated with exposure after adjustment for anxiety and health beliefs were those expected from the known toxicological effect of oil, suggesting a direct health effect on the exposed population. 相似文献
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Modification of 5-HT2 receptor mediated behaviour in the rat by oleamide and the role of cannabinoid receptors 总被引:5,自引:0,他引:5
Oleamide (cis-9,10-octadecenoamide) is an endogenous brain lipid which has been suggested to induce sleep in experimental animals. The mechanism of action is unclear but shares many of the characteristics of endogenous cannabinoids such as anandamide and has been shown to enhance in vitro responses to 5-HT and GABA. In the present study we investigated the effects of oleamide on two motor behaviours, back muscle contractions (BMC) and wet-dog shakes (WDS) induced in rats by treatment with the 5-HT2 receptor agonist DOI ((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride). We then examined the potential involvement of CB1 cannabinoid receptors in the responses to oleamide and the mechanism of interaction between CB1 and 5-HT2 receptors. Oleamide and the cannabinoid receptor agonist HU210 (6aR)-trans-3-(1,1-dimethylheptyl)6a,7,10,10a-tetrahydro-1-h ydroxy-6,6-dimethyl-6H-dibenzo[b,d]pyran-9-methanol) produced a hypolocomotion which was prevented by the CB1 antagonist SR141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide hydrochloride). Despite having no effect alone, oleamide and HU210 potentiated BMC induced by treatment with DOI. SR141716A alone did not affect the response to DOI but it blocked the potentiations caused by oleamide or HU210. WDS were unaffected by oleamide and slightly reduced by HU210. In vitro, oleamide and HU210 enhanced the high affinity binding of 5-HT to 5-HT2 receptors on rat cerebral cortex membranes labelled with 3H-ketanserin. Neither agent, however, altered 5-HT-stimulated phosphoinositide hydrolysis in rat cerebral cortex slices. Oleamide occupied CB1 cannabinoid receptors on rat brain membranes labelled with 3H-CP55940 with an IC50 of 10 microM. The data presented are consistent with oleamide acting via a cannabinoid recognition site to enhance 5-HT2 receptor function in vivo. The mechanism of the modulation is still unclear but it does not appear to involve a potentiation of 5-HT2 receptor-stimulated phosphoinositide hydrolysis. 相似文献