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.     

Bile Salt–Fatty Acid Mixed Micelles as Nasal Absorption Promoters of Peptides. I. Effects of Ionic Strength,Adjuvant Composition,and Lipid Structure on the Nasal Absorption of [D-Arg2]Kyotorphin

Bile salts and synthetic surfactants have been used to promote nasal absorption of peptide drugs. Although a marked increase in nasal absorption has been achieved, this may not be adequate and the possibility of adjuvant-induced membrane toxicity exists. The present study employs a rat in situ nasal perfusion technique and mixed micelles between sodium glycocholate (NaGC) and various lipids as potential nasal absorption enhancers of a stable model dipeptide, [D-Arg²]kyotorphin. NaGC alone enhanced the nasal absorption of the dipeptide in a concentration-dependent manner. When linoleic acid was added to form mixed micelles with NaGC, the absorption was further enhanced (P < 0.01). The effect of mixed micelles was synergistic and much greater than with single adjuvants. Increasing ionic strength was found to increase the adjuvant activity of both NaGC and NaGC–lipid mixed micelles. Structure of the lipid component of the mixed micelles also affected the adjuvant potency. Oleic acid, a cis-unsaturated fatty acid, was more effective than elaidic acid, the trans-isomer, whereas cis-linoleic acid and trans-linolelaidic acid were equally effective ( = 0.05). Mixed micelles of mono-glycerides such as monoolein and monolinolein were also more effective than NaGC alone ( = 0.05). Micellar solubilization of these polar lipids by NaGC appears to be important for nasal absorption enhancement to occur. Reversal of the membrane permeability was also observed within approximately 20–40 min after removal of the adjuvants from the rat nasal cavity. These observations are similar to the effects of mixed micelles on the rectal mucosa and may involve the same mechanism.     

Nationality differences in distributions of serum lipids, lipoproteins and apolipoproteins levels in Xinjiang China

目的　种族间血脂水平的差异已有研究。本文拟探讨民族间血脂、脂蛋白及载脂蛋白水平是否也存在差异。方法　作者对新疆地区的汉族居民 911人 (男性 4 6 6人 ,女性 4 45人 )及哈萨克族居民 773人 (男性 36 0人 ,女性4 13人 )随机个体血总胆固醇 (TC)、甘油三酯 (TG)、高密度脂蛋白胆固醇 (HDL c)、低密度脂蛋白胆固醇 (LDL c)、脂蛋白 (a) (Lp(a) )及载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)进行测定。结果　与汉族人群比较 ,哈萨克族人群男、女均分别有较高的HDL c(P <0 0 0 1)和ApoA1(P <0 0 0 1)水平与较低的TG(P <0 0 1,P <0 0 0 1)、Lp(a) (P <0 0 0 5 )、ApoB(P <0 0 0 5 ,P <0 0 0 1)及较低的ApoB/ApoA1值 (P <0 0 1,P<0 0 0 1) ;汉族人群有 2 0 7%的个体ApoA1水平值低于 1 2g/L ,而在哈萨克族人群中只有 9 8%的个体ApoA1值低于 1 2g/L ,汉族人群有 18 6 %的个值ApoB值高于 1 2g/L ,而在哈萨克族人群中只有 14 3%的个体ApoB水平值超过 1 2g/L ;多因素相关与回归分析发现 :TG、HDL c、Lp(a)、ApoAI及ApoB/ApoAI值水平均与民族有密切的相关关系。结论　血脂、Lp(a)、ApoA1及ApoB水平存在显著的民族间的差异 ,哈萨克族人群具有较汉族人群明显为优的血脂谱 ,推测遗传因素可能控制和影响着个体     

大豆胚轴甲醇提取物对糖尿病大鼠血糖、血脂及血清过氧化脂质的影响

[目的 ]研究大豆胚轴甲醇提取物对糖尿病大鼠血糖、血脂及过氧化脂质代谢的影响 .[方法 ]甲醇提取大豆胚轴中的异黄酮类和皂甙 ,以薄层色谱法、高效液相色谱法检测其组成 .给GK/Jcl糖尿病大鼠长期食用添加 10 0 g/kg大豆胚轴甲醇提取物的饲料 ,观察和测定相应生物化学指标 .[结果 ]长期食用大豆胚轴甲醇提取物的糖尿病大鼠的血糖水平下降 ,血清过氧化脂质降低 ,高密度脂蛋白胆固醇增高 ,血清总胆固醇和甘油三脂却无明显变化 .[结论 ]大豆胚轴甲醇提取物具有显著的降低血糖、改善糖耐量、降低脂质过氧化和升高高密度脂蛋白胆固醇的作用     

家兔肝缺血再灌注损伤脂质过氧化的动态变化及川芎嗪干预的机制

目的：观察肝缺血再灌注损伤时脂质过氧化的动态变化和川芎嗪的干预作用,并探讨其机制。方法：复制健康家兔肝缺血再灌注损伤模型,随机分为对照组（n=10）和川芎嗪组（n=10）。连续观察缺血前、缺血25min、再灌注25min、60min及120min时血浆中丙二醛（MDA）含量、超氧化物歧化酶（SOD）、黄嘌呤氧化酶（XO）及谷丙转氨酶（ALT）活性的动态变化,并观察川芎嗪对不同时限上述指标的影响。结果：随缺备再灌注时间的延长,对照组的MDA、XO和ALT呈阶梯式的明显升高,SOD呈逐渐显降低的变化;川芎嗪组的上述指标在再灌注的各时限与对照组比较差异均有显或非常显性意义（P＜0.05或P＜0.01）。结论：肝缺血再灌注损伤时脂质过氧化反应呈进行加重的变化;川芎嗪能抑制氧自由基的生成,增强对氧自由基的清除,从而起着良好的抗脂质过氧化作用。     

血脂康与烟酸肌醇酯调脂疗效比较

目的：探讨血脂康的调脂疗效。方法：对８４例原发性高脂血症患随机分为血脂康组和烟酸肌醇酯组,。服用血脂康组４４例,酸肌醇酯组４０例,观察用药８周（ｗｋ）后血脂变化,并对二进行比较。结果：显示血脂康有较好的调脂（降ＴＣ、ＴＧ、ＴＣ－ＨＤＬ－ｃｈ／ＨＤＬ－ｃｈ及升ＨＤＬ－ｃｈ）作用,且优于烟酸肌醇酯。结论：提示血脂康调脂职效确切,服用方便,副作用少,可作为较好的临床调脂药物推广使用。     

氧化型染发剂主要成分对皮肤细胞DNA、脂质和蛋白质合成能力的影响

目的 :探讨氧化型染发剂主要成分对皮肤角朊细胞DNA和脂质合成能力及对真皮成纤维细胞蛋白质合成能力的影响。方法 :用氧化型染发剂的 2种主要成分双氧水 (H2 O2 )和对苯二胺 (PPD)及两者的混合物对大鼠角朊细胞和真皮成纤维细胞进行染毒 ,然后进行放射性核素标记产物的掺入 ,在BeckmanLS 5 0 0 0TD液体闪烁仪上测定cpm值。结果 :经12h染毒后 ,受试样品对大鼠皮肤细胞的DNA、脂质和蛋白质合成均有不同程度的抑制作用 ,随着染毒剂量的升高 ,细胞毒性逐渐增强 ,染毒剂量与cpm值之间呈剂量反应关系。结论 :氧化型染发剂对皮肤细胞DNA、脂质和蛋白质合成能力有抑制作用 ,可能会破坏皮肤的结构和功能     

荷叶大豆及其合剂调脂活性部位的研究

目的：通过体内外实验探讨荷叶大豆调脂的活性部位及其作用特点,方法：以急性高脂血症小鼠为整体模型观察药物对血清胆固醇及甘油三酯的影响,体外给药观察药物对肝细胞合成胆固醇的影响。结果：荷叶大豆的水提取部分及其生物碱和黄酮均有调脂作用,大豆黄酮对体外肝细胞合成胆固醇有抑制的趋势。结论：荷叶和大豆均有调脂作用,其主要活性部位在黄酮和生物碱,其作用特点在于促进胆固醇的代谢方面。     

酞菁钴作为双功能模拟酶的研究

设计并合成4种金属酞菁(六羧基酞菁钴、四羧基酞菁钴、六磺酸基酞菁钴、四磺酸基酞菁钴)作为SOD和CAT双功能模拟酶。对其仿SOD和CAT的部分生物学功能进行检测。结果显示核黄素-蛋氨酸光明法证实它们在10-5～10-6mol/L浓度范围内有清除O2-的作用;分光光度法证实它们能催化H2O2的分解,且分解率随浓度增大而增大;用小鼠肝匀浆法测定4种金属酞菁、SOD和CAT,均表明有良好抗脂质过氧化作用;用多形核白细胞（PMN）-鲁米诺化学发光测定呼吸爆发中的活性氧,表明模拟酶对活性氧有清除作用;大鼠心脏缺血再灌注实验表明六羧基酞菁钴能降低活性氧对心肌的损伤程度,对再灌注损伤心肌有保护作用。