急性重复高原缺氧对机体氧自由基代谢的影响

目的：探讨急性重复高原缺氧对机体氧自由基代谢的影响。方法：对担负军事运输的某汽车部队随机挑选16名驾驶员，在开运前10天（海拔1400m）、完成4次高原（海拔1400-5400m）运输任务中途（海拔3700m）及运输任务结束（完成8次高原运输任务）后1个月（海拔1400m），分别进行3次血中抗氧化酶、抗氧化物和脂质过氧化物的检测。结果：运输前轻运输中途血红蛋白（Hb）、脂质过氧化物（LPO）、丙二醛（MDA）低，相差非常显著（P＜0．01）；红细胞超氧化物歧化酶（RBC—SOD）和VitE高，相差显著（P＜0．05）；运输前较运输后RBC－SOD和VitE高，LPO和MDA低，均相差非常显著（P＜0．01）。运输中途较运输结束Hb和RBC－SOD增高，相差非常显著和相差显著（P＜0．01和P＜0．05）。结论：低氧应激状态下和重复应激作用停止后的一定时间内，体内脂类过氧化活动显著增强，且持续时间较长。     

高原昏迷与脂质过氧化反应

本文于喀喇昆仑山海拔3700m地区对收治的22例高原昏迷患者在治疗前和治愈后分别检测了血Hb、RBC－SOD、LPO和VitC，并与初入高原的健康青年做对照。结果：高原昏迷患者治愈后RBC－SOD显著低于治疗前（P＜0．01），更低于对照组（P＜0．001）、治愈后LPO较治疗前无显著差异（P＞0．05），但显著高于对照组（P＜0．001）。治愈后VitC显著高于治疗前（P＜0．05），显著低于对照组（P＜0．001）。作者认为，高原昏迷的发生与急性缺氧引发的机体一系列自由基损伤关系十分密切。     

进驻不同海拔高度健康青年尿SOD和血乳酸的变化分析

目的：探讨某部队进驻不同海拔高度健康青年尿超氧化物歧化酶（μ－SOD）和血乳酸（BLA）的变化。方法：随机选择从平原进驻海拔3700、5070和5380m高原地区第10天的青年分别进行u－SOD和BLA含量检测,并与平原海拔1400m健康青年人对照。结果：发现3700、5070、5380m较1400m的u-SOD活性随海拔的升高而降低,BLA随海拔升高而增加,差异非常显著（P＜0．01）。海拔5070、5380m较3700mu－SOD降低和BLA增加非常显著（P＜0．01）。而海拔5380m较5070m的u－SOD活性下降不显著(P＞0．05)、BLA增加非常显著（P＜0．01）。结论：海拔越高,机体缺氧越严重是体内U－SOD活性下降和BLA增加的主要原因。     

进驻海拔5,380m不同时间的青年人血液流变性和RBC—SOD的变化

本文对进驻海拔5，380m第3天、第25天、第4个月，第11个月的20名青年血液流变性和RBC－SOD进行了随访调查，并与进驻高原前作对照，结果：随进驻高原时间的延续，HCT、ηb、PFc、TK、MST、TFL递增，RBC－SOD递减（P＜0．01或P＜0．05）。作者认为缺氧引起HCT增高是血液粘度增高的重要因素；缺氧引起ATP生成减少和红细胞内液粘度增高是红细胞变形能力降低的主要原因。高原低氧环境使体内自由基生成增多，SOD活性降低。     

进驻高原不同海拔高度不同时间健康青年血清心肌酶活性的变化

为探讨进驻高原不同海拔高度和不同居住时间健康青年血清心肌酶活性的变化,对从平原（海拔1400m）进驻海拔3700m和5380m高度第7天及半年的84名青年,进行血清AST、CK、LDH、α－HBDH检测,并与平原健康青年作对照。结果显示：进驻高原AST、CK、LDH及α─HBDH均显著高于平原（P＜0．05或P＜001）。进驻海拔3700m,第7天较居住半年时LDH显著增高（P＜0．05）,AST、CK、α－HBDH虽然增高但无统计学差异（P＞0．05）,进驻5380m第7天较居住半年时AST显著增高（P＜0．05）,LDH、CK、α—HBDH增高非常显著（P＜0．01）。进驻高原第7天,5380m较3700mAST、LDH增高显著（P＜0．05）,CK、α—HBDH增高非常显著（P＜0．01）,进驻高原半年时,海拔5380m与3700m比较LDH、CK增高显著（P＜0．05）,α—HBDH增高非常显著（P＜0．01）,AST无显著性差异（P＞0．05）。笔者认为,高原低氧对心肌细胞有损伤,其损伤程度可能与急、慢性缺氧程度有关。     

急性重复缺氧对人脑功能的影响

探讨急性重复缺氧对人脑功能的影响程度，为高原脑功能研究积累借鉴资料。随机选择常年频繁出入海拔3000－5400m的某部汽车兵50名（急性重复缺氧组）及驻守海拔3700m与5380m1年的40名健康青年，采用韦氏成人智力量表（WAIS—RC）简式四合一及韦氏记忆量表甲式（WMS）现场进行智力与记忆功能的心理测验，并设置平原对照组。结果：急性重复缺氧组与平原对照组（海拔1400m）、高原甲组（海拔3700m移居1年）及高原乙组（海拔5380m移居1年）比较，VIQ（语言）PIQ（操作）FIQ（智商）均无显著性差异（P＞0．05）；急性重复缺氧组的记忆功能与平原对照组比较，1－100、积累、记图、再认、再生、联想、触摸得分降低非常显著（P＜0．01），与高原甲组比较，1－100、再认、触摸降低非常显著（P＜0．01），再生、理解、MQ（记忆商数）得分显著增高（P＜0．01或P＜0．05）。与高原乙组比较，1—100、再认、触摸、降低非常显著（P＜0．01），100－1、理解、背数、MQ得分显著增高（P＜0．01或P＜0．05）。结论：急性重复缺氧机体产生间歇性的低氧适应，脑功能较不同程度的持续性缺氧损害轻，但记忆功能仍低于平原正常人水平。     

益气通络丹对冠心病病人红细胞过氧化反应及红细胞变形性的影响

目的和方法：本实验检测了41例冠心病病人使用益气通络丹治疗前后循环血中红细胞超氧化物歧化酶（SOD）活力；全血谷胱苷肽过氧化物酶（GSH－Px)、过氧化氢酶（CAT）活力；血浆总抗氧化能力（AOA）；红细胞膜丙二醛（MDA）含量；红细胞滤过指数（IF）的变化。结果：治疗前红细胞SOD、全血GSH－Px、CAT活力、血浆AOA明显下降（P＜0．05），红细胞膜MDA含量明显升高（P＜0．05），红细胞IF明显升高（P＜0．01）。治疗后与治疗前比较，红细胞SOD、全血GSH－Px、CAT活力、血浆AOA明显升高（P＜0．01），红细胞膜MDA含量明显降低（P＜0．01），红细胞IF明显降低（P＜0．01）。结论：益气通络丹能减轻病人血液过氧化反应，改善红细胞变形性（ED）。     

在高原居留1年与3年移居青年的血流动力学比较观察

本文对西藏阿里地区海拔4300m居住1年与3年的青年采用安徽电子计算机厂生产的XG—Ⅱ型血液循环功能自动测试仪进行了血流动力学检测并与海拔1400m青年比较。结果：居住1年者P、TPR、AR、η、CCP增加非常显著，BV、SV、VPE、mAP减少非常显著（P＜0.01或P＜0．001）；ALT、PAWP增加显著，ETK减少显著（P＜0.05）。进驻3年较进驻1年者η和ALT增加非常显著（P＜0．01），SV和mAP减少显著；TPR、AN、PAWP、CCP增加，BV、VPE、ETK减少，但无统计学意义。其结果表示，青年人进驻海拔4300m1年时血流动力学为低排高阻性改变；进驻海拔4300m3年时其低排高阻性改变较1年有所加重。     

吸烟对血液过氧化与抗氧化平衡的影响

比较吸烟与不吸烟人静脉血血浆及红细胞脂质过氧化物-丙二醛（MDA）含量，血浆及红细胞超氧化物歧化酶（SOD）活力、全血谷胱甘肽过氧化物酶（GSH－Px）活力及血浆总抗氧化能力（AOA）．结果表明：吸烟组血浆及红细胞MDA的含量高于不吸烟组（P＜0．01），红细胞SOD含量高于不吸烟组（P＜0．01），血浆SOD、全血GSH－Px活力．血浆AOA均低0于不吸烟组（P＜0．01，P＜0．05，P＜0.05）．提示长期吸烟可使血中氧化与抗氧化失去平衡。     

左归饮治疗前后冠心病病人红细胞过氧化反应及红细胞变形性的变化

本实验检测了37例冠心病病人使用左归饮治疗前后循环血中红细胞超氧化物歧化酶（SOD）活力;全血谷胱苷肽迂氧化物酶（GSH－PX）、过氧化氨酶（CAT）活力;血浆总抗氧化能力（AOA）;红细胞膜丙二醛（MDA）含量;红细胞滤过指数（IN）的变化．结果显示,治疗前红细胞SOD、全血GSH－PX、CAT活力、血浆AOA明显下降（P＜0．01）,红细胞膜MDA含量明显升高（P＜0．01）,红细胞IF明显升高（P＞0．01）。治疗后与治疗前比较,红细胞SOD、全血GSH－PX、CAT活力、血浆AOA明显升高（P＜0．05）,红细胞膜MDA含量明显降低（P＜0．01）,红细胞IF明显降低（P＜0．01）。提示左归饮能减轻病人血液过氧化反应,改善红细胞变形性（ED）。     

联合检测血清Hcy和Lp (a)与UA对冠心病患者预后评估的价值探讨

目的 探讨血清同型半胱氨酸(Hcy)、脂蛋白a[Lp(a)]和尿酸(UA)联合检测对冠状动脉粥样硬化性心脏病(CHD)的病情及预后的评估价值.方法 选取CHD患者96例(疾病组)和体检健康者50例(正常组),采集清晨空腹静脉血,检测血清Hcy、Lp(a)和UA.观察组(疾病组)随访1年,91例病情缓解或无进展,5例发展为急性心肌梗死(AMI).采用受试者工作特征曲线分析血清Hcy、Lp(a)和UA单独及联合检测对CHD患者预后的诊断价值.结果 疾病组血清Hcy、Lp(a)和UA水平均高于正常组(均P＜ 0.05);随访发展为AMI患者入院时血清Hcy、Lp(a)和UA水平均高于病情缓解或无进展者(均P＜ 0.01).Hcy、Lp(a)和UA联合检测对CHD患者预后评估的AUC为0.855、敏感性为89.4％、特异性为80.2％、阳性预测值86.4％,均高于3项单独检测.结论 冠状动脉粥样硬化性心脏病患者血清Hcy、Lp (a)和UA水平均升高,其水平变化可反映冠状动脉粥样硬化性心脏病病情,三者联合检测可提高对患者预后的判断价值.     

Comparison of the inhibition potential of parthenolide and micheliolide on various UDP-glucuronosyltransferase isoforms

Abstract

1. Parthenolide (PTL) and micheliolide (MCL) are sesquiterpene lactones with similar structures, and both of them have been reported to exhibit multiple biochemical and pharmacological activities. This study aims to investigate the inhibition of these two compounds on the activity of UDP-glucuronosyltransferases (UGTs).

2. In vitro incubation mixture for recombinant UGTs-catalyzed glucuronidation metabolism of 4-methylumbelliferone (4-MU) was utilized to investigate the inhibition potential. Inhibition kinetics (including inhibition type and parameters) were determined, and in silico docking was employed to elucidate the inhibition difference between PTL and MCL on UGT1A1.

3. MCL showed no inhibition toward all the UGT isoforms, and PTL showed strong inhibition toward UGT1A1. The half-maximal inhibitory concentration (IC₅₀) of PTL on the activity of UGT1A1 was determined to be 64.4?μM. Inhibition kinetics determination showed that PTL exerted noncompetitive inhibition toward UGT1A1, and the inhibition kinetic constant (K_i) was determined to be 12.1?μM. In silico docking method has been employed to show that hydrogen bonds between PTL and the activity cavity of UGT1A1 contributed to the stronger inhibition of PTL on the activity of UGT1A1 than MCL. In conclusion, PTL can more easily induce drug–drug interaction (DDI) with clinical drugs mainly undergoing UGT1A1-catalyzed glucuronidation.

     

The effect of halothane on the stability of Ca2+ transport activity of isolated fragmented sarcoplasmic reticulum

The effects of the inhalation anaesthetic agent, halothane (CF₃CHBrCl), on the stability of the calcium transport system of isolated rabbit white skeletal muscle sarcoplasmic reticulum have been studied. Calcium transport activity was unaffected when suspensions of sarcoplasmic reticulum vesicles were preincubated at 37° and pH 6.8 at concentrations of halothane below 5 mM, but was progressively inactivated at higher concentrations. (Ca²⁺,Mg²⁺)-ATPase activity was enhanced during inactivation of calcium transport. At pH 6.3 and 5.8, halothane increased the first order rate constants of inactivation and effects were noted in the anaesthetic range of concentration (1–2 mM). The inulin inaccessible space of membrane vesicles did not change appreciably during the period of treatment with halothane, excluding increased permeability as an explanation of the inhibition of calcium accumulation. Inactivation was irreversible and highly temperature dependent, with an activation energy of 52.7 kcal/mol. Calcium ions had a protective effect against inactivation (K_{0.5 (Ca2+) = 1.5 × 10^?6M}), as did ATP ($\text{K}{}_{\mathrm{<mtext>0.5\; (</mtext><mtext>Atp</mtext><mtext>)</mtext>}}\text{? 10}{}^{\mathrm{?6}}\text{M}$). It is concluded that mild acid conditions and halothane act synergistically during inactivation of the calcium transport system of sarcoplasmic reticulum membranes. These studies suggest that halothane interacts with the (Ca²⁺, Mg²⁺)-ATPase protein at the ATP-specific binding site or that it disrupts protein-lipid associations in the membrane. In either case the destabilizing effect of halothane may be modified by the conformational state of the protein.     

Theoretical π-π* absorption and circular dichroic spectra of cyclic dipeptides

The dipole interaction model, treated by the partially dispersive normal mode method, is used to calculate circular dichroic spectra of cyclo(Gly-Gly), cyclo (Ala-Gly), cyclo(Ala-Ala), cyclo(Pro-Gly), cyclo(Pro-Ala), cyclo(Pro-Val), cyclo (Pro-D-Val), and cyclo(Pro-Pro) in the amide π-π* absorption band near 190 nm. Assuming a standard backbone geometry, spectra which are in fair to good agreement wth experiment are obtained for these molecules. The spectra are predicted to be sensitive to conformations of Pro and Val side chains. The effects of dipeptide ring folding on calculated CD spectra are mostly consistent with those found by other workers, except that it is found that a planar ring conformation of cyclo (Ala-Ala) and cyclo (Ala-Gly) gives predicted spectra comparable to experiment. The same model gives theoretical absorption spectra consistent with available experimental data.     

HPLC法测定丝裂霉素C聚氰基丙烯酸正丁酯纳米粒中丝裂霉素C的含量

目的:建立高效液相色谱法测定丝裂霉素 C 聚氰基丙烯酸正丁酯纳米粒(MMC-PBCA-NP)中药物含量。方法:采用C_(18)柱(4.6 mm×150 mm,5 μm),以混合磷酸盐缓冲液-乙腈(85:15)为流动相,流速为1 mL·min~(-1),紫外检测器,检测波长为365 nm。结果:丝裂霉素 C(MMC)浓度在5～250 μg·mL~(-1)范围内与峰面积呈良好的线性关系,r=0.9998;平均回收率(n=6)为98.15%。结论:本法专属性强,操作简便,结果准确。适用于 MMC-PBCA-NP 的质量控制。     

AFP、AFU、DSA-GGT联合检测对原发性肝癌的诊断价值

目的探讨甲胎蛋白(AFP)、α-L-岩藻糖苷酶(AFU)和欧蔓陀罗凝集素(DSA)强结合的γ-谷氨酰转移酶(DSA-GGT)联合检测对原发性肝癌(PHC)的诊断价值。方法对58例PHC和167例良性肝病患者,以及36例其它肿瘤患者,进行AFP、AFU和DSA-GGT指标联合检测,分析3项指标对PHC的诊断价值。结果PHC组的AFP、AFU、DSA-GGT的阳性率均明显高于良性肝病和其它肿瘤组(P<0.01);AFP、AFU和DSA-GGT对PHC的诊断敏感性分别为68.97%、67.24%和65.52%,特异性分别为90.64%,89.66%和91.13%;PHC患者血清AFP、AFU、DSA-GGT之间无相关性,联合检测对PHC有互补诊断价值,阳性率达96.55%。结论AFP、AFU和DSA-GGT等3个指标联合应用,可提高PHC的诊断灵敏度,提高诊断水平。     

运动对糖尿病肾病早期相关指标的影响

目的研究运动对糖尿病肾病(DN)早期诊断指标如尿微量白蛋白(Alb)、尿转铁蛋白(TRF)、尿铜蓝蛋白(CP)、尿视黄醇结合蛋白(RBP)的影响。方法对45名2型糖尿病患者做次极量运动试验,运动前后分别测尿Alb、尿TRF、尿CP、尿RBP及尿肌酐(Cr),并以26名非糖尿病人做对照。结果糖尿病患者运动后尿Alb/Cr较运动前增加(P>0.01),尿TRF/Cr,CP/Cr,RBP/Cr运动前后无明显改变;非糖尿病人运动后尿Alb/Cr也较运动前增加(P>0.05),尿TRF/Cr,CP/Cr,RBP/Cr运动前后也无明显改变。而在相关分析中发现,尿RBP/Cr与Alb/Cr无显著相关性。尿TRF/Cr,CP/Cr与Alb/Cr有显著相关性。结论尿Alb/Cr受运动影响而尿TRF/Cr、CP/Cr不受运动影响,可作为DN早期诊断指标之一。     

GC法检测浙八味药材中有机氯农药的残留

目的 测定与分析白术、白芍、玄参等8种药材中9种有机氯农药残留量.方法 以混合溶剂超声提取样品、浓硫酸磺化净化,采用毛细管气相色谱,用HP-5弹性石英毛细管柱程序升温分离,微电子捕获检测器检测,峰面积外标法定量.结果 延胡索、麦冬和杭白菊均检出滴滴涕,含量分别为0.439、45.017、5.434 ng·g<'-1>;杭白菊检出五氯硝基苯,含量为1.030 ng·g<'-1>;其余药材均未检出有机氯农药残留.结论 浙八味药材大部分未检出有机氯农药残留或含量较低,均在规定的安全范围内.     

脑脊液转铁蛋白及免疫球蛋白含量变化在小儿中枢神经系统感染时的临床意义

目的　通过对小儿中枢神经系统感染时Tf、Ig在脑脊液中含量的变化及其相关性分析 ,为鉴别诊断及更切实的判定病情和估计预后提供参考依据。方法　应用速率散射比浊法测定脑脊液中Tf、Ig。结果　 (1 )三组急性期脑脊液中Tf、Ig含量均高于恢复期。 (2 )结脑组Tf、IgG增高明显 ,化脑组IgM增高明显。病脑组变化最小。 (3)恢复期脑脊液中Tf、Ig含量与对照组比较 ,结脑中Tf、IgG、IgM高于对照组 ,化脑和病脑组IgM均高于对照组 ,Tf、IgG均无差异 ,各组IgA与对照组相比无显著性差异。 (4)病脑急性期Tf与IgG呈正相关 ,恢复期与IgA呈正相关 ;化脑组急性期Tf与IgM、IgG呈正相关 ,恢复期与IgM呈正相关 ;结脑急性期Tf与IgA、IgM均呈正相关 ,恢复期与IgG呈正相关。结论　 (1 )Tf与IgG是诊断结脑的良好指标 ,IgM是诊断化脑的良好指标 ,当脑脊液中IgM >30mg L时 ,可基本除外病脑 ,当脑脊液中IgM <60mg L时 ,化脑的可能性较小。 (2 )Tf与Ig一样 ,可作为判断中枢神经系统感染时血脑屏障及脑损伤与恢复程度的重要指标     

Anti-ischemic effects of nimesulide, a cyclooxygenase-2 inhibitor on the ischemic model of rabbit induced by isoproterenol

The objective was to devise an animal model of myocardial infarction (MI) against which cardioprotective drugs might be tested. We describe the effects of nimesulide, a COX experience with development and validation of such a model. The rabbit was chosen in preference to rodents because its heart and cardiac circulation more closely resemble those of human. Thus, the cardiovascular system of anaesthetized male rabbits, 1 to 1.5 kg (n=11), was stressed by a single bolus intravenous injection of isoprenaline (ISP), 65 mg/kg. The effects of the injection were followed for sixteen days and were evaluated in four ways: 1) measurements of creatinine kinase isozyme and troponin-I (TPI) in serum 2) Electrocardiographic (ECG) changes (ST elevation and Q wave development) 3) Cardiac histopathology observed in tissue sections of the isolated of the heart. The histopathological analysis showed that rabbit heart on 2nd day after ISP injection showed changes of coagulation necrosis. Day 4 total coagulation with the loss of nuclear and striation associated with heavy interstitial infiltrate of neutrophils was found. Day 8 after infarction showed collagen deposition with capillary channels in between the remaining islands of myocytes in the infarcted area. On the 16th day scarring was complete. Coronary perfusion rates (CPR) and heart rate (HR) of the infarcted and nimesulide (a COX-2 inhibitor) treated rabbits displayed significant improvement (n=11) on each corresponding day after infarction as compared to the infarcted and saline treated rabbits (P<0.05). All four indices revealed similarities with effects commonly associated with MI in humans.