Contribution of Monoamine Oxidase(MAO) to the Binding of Tertiary Basic Drugs in Isolated Perfused Rat Lung

The effect of tertiary basic drugs on mitochondrial MAO activity and the effect of MAO inhibitors (MAOIs) on basic drug accumulation in the isolated perfused rat lung were studied to clarify the role of MAO in drug binding to lung tissue. In the perfused lung preparation, the inhibition of MAO by basic drugs correlated well with their lipid solubilities and followed competitive kinetics. The inhibitory rank order (imipramine diphenhydramine > quinine > metoclopramide > procainamide) also correlated with their accumulation in the perfused lung. Moreover, MAOI treatment decreased the accumulation of basic drugs in the lung, and the potency of MAOIs to inhibit drug accumulation in the lung correlated with their MAO inhibitory activity. These results indicate that lung MAO has specific binding sites for basic drugs and may function as a drug reservoir.     

淋病奈瑟氏菌中国流行株gyrA和parC基因与喹诺酮类耐药性的相关性

目的　调查中国地区淋病奈瑟氏菌 (NG)对喹诺酮类的耐药性状况 ,探讨高水平耐药的基因突变株对喹诺酮类耐药机制的作用 .方法　对 9a来临床分离保存淋球菌流行株进行了体外环丙沙星 (CIP)药敏实验 .筛选出 76株高水平CIP耐药株 ,通过 PCR扩增了其中的 1 8株 NG的 gyr A和par C喹诺酮耐药决定区基因 ,并对扩增子直接测序 .通过N he I酶切、脉冲电场凝胶电泳 (PFEG)分析了这些菌株的遗传关系 .结果　环丙沙星的耐药检出率有逐年增高的趋势 ,MIC≥ 1 .0 mg· L- 1的菌株由 1 993年的 5 .1 %上升到 2 0 0 1年的 2 1 .4% .对照组中的 1 8株敏感菌只有两株发生了 gyr A的单一突变 ,未发现 par C变异 ;而耐药组中 89% (1 6 )菌株的gyr A发生了 Ser- 91向 Phe的单一突变株或 (和 ) par C的双突变 .88.9% (1 5 )的菌株的 gyr A发生了 Ser- 91向 Phe和 Asp-95向 Gly的突变 .在发生 par C突变中 72 %属于 Asp- 86向Asn突变 .PFEG分析发现 1 0株具有完全一致的 gyr A和par C突变模式 .同时也发现来自不同地区的菌株的 PFEG指纹图是不同的 .结论　研究表明 ,在中国 NG流行株对喹诺酮类耐药率呈增长趋势 ;NG流行株对喹诺酮产生耐药性与gyr A和 par C基因双重突变有着密切的关系     

口腔颌面鳞癌术前诱导化疗二种方式临床疗效分析

目的 :探讨口腔颌面鳞癌术前诱导化疗二种方式应用的疗效、主要毒副反应差别 ,以及临床适应证。为术前诱导化疗的选择提供临床指导。方法 :本文回顾了 1 0 4例可评价近期疗效的口腔颌面鳞癌术前诱导化疗的病例。其中全身化疗 5 6例 ,颈外动脉插管化疗 48例。结果 :以肿瘤体积缩小 5 0 %以上作为化疗有效指标 ,全身化疗组有效率为 6 4.3%。颈外动脉插管化疗组有效率为79.2 % ,两组总有效率为 71 .2 % (P<0 .0 5 )。全身化疗组的主要毒副反应为胃肠反应、白细胞减少和脱发 ;颈外动脉插管化疗组主要为口腔粘膜溃疡、糜烂及灼痛感。结论 :作为术前诱导的全身化疗较适合于全身状况良好的患者 ,而颈外动脉插管灌注化疗较适合于全身状况稍差、无转移、肿瘤范围不广的患者。     

环孢素A对实验大鼠脑缺血治疗作用的组织化学研究

【目的】进一步证实免疫因素在脑缺血病理变化中的作用。【方法】将 6 0只局部脑缺血模型SD大鼠分为缺血 3d ,1周和 2周 3个缺血时间组 ,每组分为生理盐水对照和环孢素A治疗两个部分 ,进行TTC和HE组化染色实验 ,并对结果进行统计处理 (t检验 )。【结果】脑缺血 1周 ,环孢素处理组的组织病理学变化较生理盐水对照组明显减轻 ,脑梗塞体积和死亡的神经元数量在环孢素A处理组分别为 3 2 %和 15 8/ 0 0 6 2 5mm2 ,而生理盐水组则为 5 9%和 2 2 1/ 0 0 6 2 5mm2 ,两组之间有显著差异 (P <0 0 5 )。但在脑缺血 3d和 2周组 ,上述变化两组之间无统计学差异。【结论】环孢素A对实验大鼠的缺血性神经元具有一定保护作用 ,结果提示免疫因素的介入 ,加重了脑缺血性损伤。     

强的松龙.葡聚糖连接物在大鼠胃肠道内容物中的水解

观察强的松龙．葡聚糖连接物的结肠定向释放特性。方法通过将所合成的强的松龙．葡聚糖连接珠与大鼠胃肠道不同部位内容物稀释液一起孵育,观察强的松龙的释放情况。结果在１６０ｍｉｎ的卵育过程中,强的松龙．葡聚糖连接物的在胃肠道上部内容物中水解释放出少量强的松龙及强的椴龙琥珀酸半酯,最在释放量小于３μｍｏｌ．Ｌ＾－１;而在胃肠道下部内容物中水解释放出大量强的松龙及强的松龙琥珀酸半酯最大释放量为１４μｍｏｌ．Ｌ     

Rat Jejunal Permeability and Metabolism of μ-Selective Tetrapeptides in Gastrointestinal Fluids from Humans and Rats

Purpose. To study intestinal transport and metabolism of three new -selective tetrapeptide enkephalin analogues, LEF537, LEF553 and TAPP These peptides are stabilized against enzymatic hydrolysis by having a D-aminoacid in position 2 and a blocked COOH-terminal. Methods. We used a single-pass perfusion technique to study the transport of the peptides in rat jejunum. To reduce luminal and/or brush-border metabolism during the perfusion we used protease inhibitors (Pefabloc^® SC, bestatin and thiorphan). The rate of metabolism was studied by incubations in rat jejunal homogenate, rat jejunal fluid and human gastric and jejunal fluid with and without these inhibitors. Results. The jejunal permeabilities (P_eff) of the peptides were 0.43–0.78 10^–4 cm/s without inhibitors and 0.09–0.45 10^–4 cm/s in presence of the inhibitors. All three peptides were rather rapidly degraded by enzymes in rat jejunal homogenate with half-lives of between 11.9 ± 0.5 and 31.7 ± 1.5 min. The addition of inhibitors to the homogenate prolonged the half-lives substantially for LEF553 (167 ± 35 min) and TAPP (147 ± 2 min), but only slightly for LEF537 (16.4 ± 0.5 min). LEF553 and TAPP were both hydrolyzed in rat and human jejunal fluid, while LEF537 was metabolized less in these fluids. When LEF553 and TAPP were incubated with intestinal fluid in the presence of inhibitors, metabolism was almost completely inhibited. There was no metabolism for any of the peptides in human gastric juice. Conclusions. The replacement of the terminal free carboxylic group with an amide group did not increase the stability of the peptides in jejunal tissue enough to allow successful oral drug delivery.     

氯化钾缓释片对充血性心力衰竭104例的保钾疗效

充血性心力衰竭患者１０４例（正在使用地高辛加排钾利尿剂）随机均分为氯化钾缓释片（Ｓｌｏｗ－Ｋ）及普通氯化钾片（ＲＫＣｌ）２组进行保钾治疗２ｗｋ,而后改换进入另１组作自身对照。结果：Ｓｌｏｗ－Ｋ组治疗１ｗｋ末血钾即显著增加,服药承受性较好;ＲＫＣｌ组治疗２ｗｋ末血钾才显著增加,且服药承受性较差,不良反应高达２６．９％。＊Ｐ＜０．０１。±２８９ｍｇ／ｄ）。在验证过程中所用利尿剂剂量不变。３观察项目服药前测血钾（Ｋ）、钠（Ｎａ）、氯（Ｃｌ）、肌酐（Ｃｒ）、尿素氮（ＢＵＮ）和心电图。服药后每１ｗｋ复查Ｋ,Ｎａ,Ｃｌ和心电图,每２ｗｋ加复查Ｃｒ和ＢＵＮ。结果Ｓｌｏｗ－Ｋ组１０４例患者全部完成研究。ＲＫＣｌ组在研究过程中共脱落１３例（其中坚持出院者３例,心衰严重救治无效而死亡３例,因胃肠道不良反应难以耐受而改服Ｓｌｏｗ－Ｋ导致研究中断者７例）,故能完成统计分析者为９１例。血清电解质治疗前后的变化２组治疗前的血Ｋ＋参数总体看来尚属正常范围,可能是由于在住院后短时间内测定血Ｋ＋,．所用排Ｋ＋利尿剂时间不长的关系。其中只有５例的血Ｋ＋在２－３ｍｍｏｌ／Ｌ的低水平。加服Ｓｌｏｗ－Ｋ片或ＲＫＣｌ片后,均能有效地使患者的血Ｋ＋提升?     

Cannabis laws: an analysis of costs

There is evidence that the use of cannabis is increasing in Australia, with stable black-market prices, despite the 9-year National Campaign Against Drug Abuse, increasing expenditure to enforce the laws against cannabis use, and the seizure of large plantations of cannabis plants. Recent government data are used to estimate the conservative cost of drug-law enforcement against cannabis use as being $329m in 1991-92. Alternatives to the existing regime are examined, including expiation, decriminalization, and legalization.     

The development of guidelines for drug and alcohol dependence treatment: affecting policy and practice

The rationale and methodology behind the Australian Quality Assurance Project is described. The Project aimed to develop guidelines for treatment content based on three sources of information: research findings, current practice and expert opinion. The issue of the gap between research and practice is discussed, as well as the role of dissemination in altering clinician behaviour.