药品行政保护品种介绍:抗组胺药(一)(待续)

地氯雷他定片剂通用名:地氯雷他定(desloratadine).商品名:Aerius片剂.化学名:8-氯-6,11-二氢-11-(4-哌啶亚基)-5H-苯[5,6]-环庚[1,2-b]吡啶.结构式见图1.     

注射用姜黄素脂质体过敏现象的初步研究

目的 比较3种不同粒径注射用姜黄素脂质体（CLI）引起的过敏反应,并判断可能的过敏反应类型。方法 将平均粒径约为70、100、130 nm的CLI （剂量为20 mg/kg,以姜黄素计）分别尾iv给予大鼠,分别于注射前,注射后10 min、7 d,眼眶采血,分离血清,ELISA法检测注射前后血清中过敏相关因子——补体C3a、C3b和C5a,组胺和抗体IgE、IgG、IgM的含量变化。将平均粒径约为100 nm的CLI和抗过敏药地塞米松（预处理2 h,2 mg/kg）联用给予大鼠,观察血清中补体C3a、C5a和组胺的含量变化。结果 给予3种粒径的CLI,血清中补体C3a、C3b、C5a和组胺含量均明显升高,与给药前比较差异具有统计学意义（P<0.01）;血清中抗体IgE、IgG、IgM的含量均无明显变化。预先给予地塞米松,在注射CLI前后C3a和C5a的含量无明显变化,组胺含量极低。结论 3种不同粒径CLI在体内引起的过敏反应一致,且可能是补体激活相关的假性过敏反应。     

Gastric inhibitory effects of CM57755

Summary The gastric inhibitory effects of CM57755, a new histamine H₂ receptor antagonist, have been compared in ten healthy male volunteers with the actions of an equal dose of cimetidine and with placebo. The inhibitory effect of CM57755 was virtually identical with, and not significantly different from the effects of cimetidine on nocturnal gastric secretion of acid, while neither drug influenced the secretion of pepsin. Neither drug, administered in the evening, influenced the intragastric pH and acidity during the following day, from breakfast onwards. The therapeutic impact of the new drug is likely to resemble that of cimetidine and clinical application will depend on the safety profile.     

Experimental testing of skin reactions to insulin detemir in diabetes patients naïve to insulin detemir

Background/aims: Sporadic reports on immediate and delayed cutaneous reactions to insulin detemir, a modern insulin analogue, have raised unsupported claims of allergy of type I, III and IV. The purpose of this experimental study using a provocative design was to elucidate the potential mechanisms behind such skin reactions. Material and methods: A total of 40 patients with type 1 diabetes or insulin‐requiring type 2 diabetes, all naïve to insulin detemir, were injected on the thigh with 0.l mL of insulin detemir (Levemir^®) administered with an 8 mm needle at three different depths, i.e. intradermal, subdermal and subcutaneously. Saline was injected as control. Any cutaneous reactions were assessed after 10 and 30 min, after 24 and 48 h and after 7 days. Histopathology of positive reactions on day 7 was obtained. The study was randomized, controlled, double‐blinded, and conducted in accordance with ICH‐GCP guidelines. Blood flow was recorded with the Periflux PF5010, and skin colour (a^*) with the DSMII colorimeter. Results: Clinical reading, flowmetry and colorimetry consistently showed delayed reactions after intradermal insulin injection (35 of 40 patients reacted with mainly weak reactions, P<0.05), peaking after 48 h, contrasting no special reaction immediately after injection, except for reactions attributed to needle trauma. A total of 22 patients reacted on subdermal injection and 21 on subcutaneous injection. Histopathology on day 7 from 22 reactions in 15 patients showed a consistent pattern of inflammation with eosinophilia as typically observed in adverse skin reactions to a variety of medicines. Reactions were interpreted as non‐specific biologic responses to the insulin different from direct toxic actions and classical allergic reaction patterns. Only one person registered itch/discomfort. A prick test vs. histamine reference excluded insulin detemir to be a pharmacological histamine releaser. Thus, provocative testing with insulin detemir produced delayed skin reaction but no immediate reaction. Measurement of circulating insulin detemir‐specific antibodies by RIA before and after 3 months showed no increase. Conclusion: Non‐allergic delayed skin reactions from intradermal and, to a minor degree, subdermal and subcutaneous injections of insulin detemir were frequent in this experimental study and showed a consistent histology pattern of inflammation with eosinophilia. Immediate reactions were not produced. The reactions are unlikely to be specific for insulin detemir, and other insulins should be studied in a similar provocative design.     

西咪替丁和雷尼替丁对大鼠小肠纵行肌条运动的影响

观察西咪替丁和雷尼替丁对大鼠小肠纵行肌条自发收缩活动的影响 .结果表明 :1西咪替丁 4mmol· L-1降低回肠肌条的收缩波平均振幅 ,雷尼替丁 2 mmol· L-1增大回肠肌条的收缩波平均振幅 . 2西咪替丁 1 - 4mmol· L-1,雷尼替丁 5mmol·L-1对十二指肠 ,头端空肠 ,末端空肠肌条的收缩活动呈抑制作用 ,雷尼替丁 2 mmol· L-1呈兴奋作用 .结果提示 :1西咪替丁抑制大鼠回肠肌条 ,而雷尼替丁兴奋大鼠回肠肌条 . 2西咪替丁和雷尼替丁对十二指肠 ,头端空肠及末端空肠肌条的抑制作用并非经由 H2 受体介导     

平溃散对急性胃溃疡及胃黏膜损伤的保护作用

目的:研究平溃散(绞股蓝,沙棘等)对抗急性溃疡的作用.方法:采用组织胺和消炎痛法建立大鼠实验模型,测量溃疡面积和胃黏液的量.结果:平溃散对组胺引起的急性溃疡有一定的抑制作用,对消炎痛引起的胃黏膜分泌的减少有一定的抑制作用.结论:平溃散具有抗溃疡、保护胃黏膜的作用.     

消风宣窍汤对变应性鼻炎豚鼠模型IgE、IL-4、IFN-γ、组胺的调控作用

[目的]探讨消风宣窍汤治疗变应性鼻炎（Allergic Rhinitis,AR）的作用机理。[方法]将60只Hartley豚鼠随机分为正常组、模型组、消风宣窍汤高、中、低剂量组、氯雷他定组。卵蛋白（OVA）建立变应性鼻炎豚鼠模型,药物干预后,ELISA法检测各组豚鼠血清总IgE、IL-4、IFN-γ、组胺的水平。[结果]与正常组比较,模型组IgE、IL-4、组胺水平显著升高、IFN-γ水平明显下降（P〈0.01）;与模型组比较,消风宣窍汤高剂量组能显著降低血清总IgE、IL-4、组胺水平,升高IFN-γ水平（P〈0.01）,消风宣窍汤中、低剂量组、氯雷他定组能降低血清总IgE、IL-4、组胺水平,升高IFN-γ水平（P〈0.05）。[结论]消风宣窍汤能促进IFN-γ的产生,抑制IL-4的形成,促进Th1/Th2分泌的细胞因子之间恢复平衡,从而减轻EOS的活化,减少IgE的合成,减少组胺的释放,从多方面阻止变应性鼻炎的炎症反应,达到治疗效果。     

西咪替丁和雷尼替丁对大鼠小肠纵行肌条运动的影响

观察西咪替丁和雷尼替丁对大鼠小肠纵行肌条自发收缩活动的影响. 结果表明：①西咪替丁4 mmol·L^-1降低回肠肌条的收缩波平均振幅，雷尼替丁2 mmol·L^-1增大回肠肌条的收缩波平均振幅. ②西咪替丁1-4 mmol·L^-1，雷尼替丁5 mmol·L^-1对十二指肠，头端空肠，末端空肠肌条的收缩活动呈抑制作用，雷尼替丁2 mmol·L^-1呈兴奋作用. 结果提示:①西咪替丁抑制大鼠回肠肌条，而雷尼替丁兴奋大鼠回肠肌条. ②西咪替丁和雷尼替丁对十二指肠，头端空肠及末端空肠肌条的抑制作用并非经由H₂受体介导.     

白萝卜提取物对实验动物胃肠运动的影响

目的:探讨白萝卜提取物(Er)对胃肠运动的影响及其可能的作用机制。方法:灌胃给药后,测定小鼠胃内容物的残留率、小肠中阿拉伯胶活性炭粉混合物的推进距离;制作豚鼠回肠离体肠段标本,测定给药前后肠段平滑肌收缩强度和频率的变化情况。结果:白萝卜粗提物(Ecr)、石油醚(Ept)、氯仿(Ecl)和水提物(Eaq)均可剂量依赖性地使离体豚鼠回肠平滑肌收缩,该作用可完全被吡拉明所阻断,且粗提物作用最强;白萝卜粗提物在30~100 mg.kg-1时可使胃残留率明显减少,小肠推进百分比明显增加。结论:白萝卜提取物可促进胃肠运动,该作用的发挥可能是通过激动组胺H1受体实现的。     

Permeation properties of a non-selective cation channel in human vascular endothelial cells

Summary Endothelial cells obtained from human umbilical chord have been studied by the patch clamp method. An ion channel is described that is activated by M concentrations of histamine and shows a slow run-down in cell-attached patches. After excision, channel activity quickly runs down to zero open probability. In symmetrical potassium concentrations (140 mM K in the bath and the pipette), the single channel conductance is 28±2 pS and the reversal potential is 0.3±0.8 mV (mean ± SEM, n=4). With 140 mM Na in the pipette, the conductance is 26±2 pS. A reversal potential of -1.5±0.9 mV (n=7) was measured. With 60 mM Ca and 70 mM Na in the pipette, 140 mM K in the bath, the reversal potential was -11±3 mV, the single channel conductance 16±3 pS (n=5). The single channel conductance in 110 mM Ca (pipette) and 140 mM K (bath) is 8±2 pS and the reversal potential is –18±6 mV (n=3). From analysis of the reversal potentials, a permeation ratio of KNaCa=10.90.2 was calculated. This ligand-gated non-selective cation channel in human endothelial cells is Ca permeable and could induce a sustained agonist mediated Ca influx.