异丙酚对体外循环肺缺血再灌注损伤影响

目的:探讨异丙酚对心肺转流术(CPB)肺缺血再灌注损伤的影响及可能机制。方法:选取20例年龄4～12岁小儿先天性心脏病,随机分为异丙酚组(P组)和对照组(C组),每组10例,P组诱导后按异丙酚3～5mg/(kg·h)微量泵持续泵入至术毕,C组用等量生理盐水代替。分别于麻醉诱导后5分钟(T0),阻断主动脉10分钟(T1),开放主动脉30分钟(T2),体外循环结束4小时(T3),体外循环结束24小时(T4)采集桡动脉血测细胞间黏附分子-1(ICAM-1),超氧化物歧化酶(SOD),丙二醛(MDA),根据动脉血气计算肺呼吸指数(RI)。结果:与T0比较,T1～4两组ICAM-1,SOD,MDA,RI值明显升高(P<0.01);与C组比较,P组T1～4ICAM-1,MDA,RI明显降低(P<0.05),SOD明显升高(P<0.05),T0两组差异不明显(P>0.05)。结论:异丙酚能降低CPB期间ICAM-1表达及减少氧自由基的生成,抑制机体的炎症反应和氧化损伤,对CPB肺缺血再灌注损伤有保护作用。     

七叶皂苷钠预处理对止血带引起肢体缺血-再灌注损伤的保护效应

目的 研究七叶皂苷钠预处理对止血带引起的肢体缺血-再灌注损伤的保护效应.方法 择期下肢手术患者75例均分为三组:A和B组在上止血带前30 min分别静脉滴注含有5 mg和10 mg七叶皂苷钠的注射液100 ml;C组给予等量生理盐水对照.测量上止血带前(T0)以及松止血带后5(T1)、10(T2)、20(T3)min血乳酸(Lac)、超氧化物歧化酶(SOD)、丙二醛(MDA)和一氧化氮(NO)的含量.结果 与T0比较,三组T1～T3乳酸水平均升高(P＜0.05).与C组比较,A、B组T1～T3 MDA和NO均下降、而SOD升高(P＜0.05).结论 静脉滴注七叶皂苷钠预处理可能通过提高SOD的活性和降低MDA、NO含量对止血带引起肢体缺血-再灌注损伤有保护效应.     

右美托咪定预处理对大鼠肢体缺血再灌注肺损伤时脂质过氧化的影响

目的探讨右美托咪定预处理对大鼠肢体缺血再灌注肺损伤时脂质过氧化反应的影响。方法 30只Wister雄性大鼠随机分成3组:假手术组(C组),肢体缺血再灌注组(M组),右美托咪定组(P组)。大鼠肢体缺血再灌注后肺损伤模型建立后,P组大鼠于缺血前30 min经尾静脉给予25μg/kg体重右美托咪定,其余两组给予相同容量的生理盐水。各组于再灌注末行血气分析,观察肺组织病理学变化,测定肺组织湿/干重比(W/D),测定肺组织中丙二醛(MDA)的含量和超氧化物歧化酶(SOD)活性。结果与C组比较,M组和P组均出现肺损伤;PaO2和SOD活性降低;W/D及MDA含量升高(P<0.05);与M组比较,P组肺组织损伤明显减轻;PaO2和SOD活性升高,W/D及MDA含量降低(P<0.05)。结论右美托咪定预处理可抑制肢体缺血再灌注肺损伤大鼠脂质过氧化反应而发挥肺保护作用。     

参脉注射液对下肢缺血-再灌注损伤的保护作用

目的 探讨参脉注射液(SM)对下肢缺血—再灌注(I-R)损伤的保护作用.方法 60例成人骨科下肢手术患者随机分为参脉组(SM组)和对照组(C组).SM组在止血带充气前静脉给予SM 60 ml;C组用等量生理盐水.测定下肢缺血前(To)、止血带充气30 min(T1)、放气后3min(T2)、30 min(T3)及术后24 h(T4)血K+、丙二醛(MDA)和超氧化物歧化酶(SOD);记录心电图.结果 与T0比较,两组止血带放气之后平均动脉压(MAP)均降低,SM组T2时高于C组(P＜0.05).SM组T2、T3时MDA均低于C组、而SOD均高于C组(P＜0.05).SM组止血带放气后心律失常发生率3.3％(1/30),明显低于C组的10％(3/30)(P＜0.01).结论 下肢止血带充气前静脉给予SM 60 ml可减轻下肢I-R损伤.     

右美托咪定预处理对止血带引起肢体缺血再灌注损伤肺的保护作用

目的 探讨右美托咪定预处理对止血带引起肢体缺血再灌注损伤肺保护作用.方法 将112例肢体手术患者随机分为观察组和对照组,观察组在使用止血带前10min使用右美托咪定静脉推注,对照组使用等量生理盐水静脉推注.测定两组上止血带前10min(T0)、松止血带后30min(T1)、2h(T2)、6h(T3)及24h(T)时刻动脉血浆一氧化氮(N0)、内皮素-1(ET-1)及NO/ET-1水平,并将结果进行比较.结果 两组NO、ET-1、NO/ET-1水平在T0、T1、T4时刻比较均无统计学意义(P＞0.05);观察组ET-1水平在T2、T3时点比对照组低(P＜0.05),NO水平和NO/ET-1值在T2、T3时点比对照组高(P＜0.05).结论 肢体手术患者使用止血带前10min静脉推注右美托咪定能有效保护内皮细胞,改善肺换气功能.     

山莨菪碱对下肢手术缺血/再灌注损伤的影响

目的评价山莨菪碱对下肢手术缺血/再灌注损伤的影响。方法将40例行单侧下肢骨科手术并且应用止血带的患者随机分为实验组（n=20,山莨菪碱4 mg）和对照组（n=20,等量生理盐水）。在术前应用止血带前（T1）和止血带放气后30 min（T2）抽静脉血,对比两组血清MDA变化。结果实验组从T1到T2时间内生成的血清MDA值低于对照组（P〈0.05）。结论山莨菪碱能减少缺血/再灌注引起的自由基生成量,减轻肢体缺血/再灌注自由基的损伤,对于止血带诱发的肢体缺血/再灌注损伤有一定的影响。     

血塞通注射液对缺血再灌注心肌的保护作用

目的 探讨血塞通注射液对大鼠心肌缺血再灌注损伤的保护作用.方法 将24只Wistar大鼠随机分为三组:心肌缺血再灌注组(MIR,n=8):术前给予生理盐水干预;血塞通治疗组(X,n=8):术前给予血塞通注射液600 mg/(kg·d)腹腔注射给药3天;假手术组(S,n=8):术前处理同MIR组.MIR和X组大鼠在结扎左前降支30分钟后行再灌注240分钟.S组所有操作同MIR组,大鼠仅穿线不结扎左前降支.分别于缺血再灌注240分钟采血,S组取相同时点采血.检测血清超氧化物歧化酶(SOD)活性、丙二醛(MDA)和肌钙蛋白I(cTnI)含量变化.结果 与X组和S组比较,MIR组血清SOD活性显著降低(P＜0.001),MDA、cTnI含量显著升高(P＜0.001);与S组比较,X组血清SOD、MDA浓度差异无显著性(P＞0.05),而血清cTnI显著升高(P＜0.01).结论 血塞通可能通过减少MDA的产生,增加SOD活性,减轻心肌缺血再灌注损伤.     

丹参大鼠肢体缺血再灌注后多器官水肿的预防作用

【摘要】 目的：探讨氧化应激（oxidative stress）在大鼠肢体缺血再灌注（LIR）致多器官水肿中的作用及丹参的影响。方法：Wistar大鼠24只随机分为三组（n=8）:对照组（C组）、缺血再灌注组（I/R组）和丹参预处理组(SM组)。以止血带法制作大鼠肢体缺血再灌注模型,SM组在再灌注前30min经尾静脉推注丹参注射液5ml／kg。手术准确留取每只动物的心、肝、肾、肺、脑、肠及骨骼肌组织各1g,恒温烘干后称其干重并计算各标本的湿干重比值(W/D)。采用生物化学方法测定血浆SOD、XOD活性及MDA含量。光镜下观察各组织的形态学变化。结果：LIR后各组织W/D均增加（P<0.01或P<0.05）,血浆SOD活性降低而XOD活性和MDA含量增加（P<0.01或P<0.05）,各组织镜下可见不同程度的结构紊乱、组织间隙增宽和炎细胞浸润等病理改变。而SM组与单纯再灌注组比较,血浆SOD活性回升而XOD活性和MDA含量降低（P<0.01或P<0.05）,镜下组织病理学变化有所减轻。结论：大鼠肢体缺血再灌注可导致多器官水肿,氧化应激是其重要机制之一。丹参可通过抗氧化在此过程中发挥抗水肿作用。     

喷他佐辛对止血带致下肢缺血再灌注后血清炎症因子的影响

目的:观察喷他佐辛对止血带致下肢缺血再灌注后血清中肿瘤坏死因子-α(TNF-α)、白介素6(IL-6)、白介素10(IL-10)的影响。方法:选取择期行单侧下肢骨科手术使用止血带患者40例,随机分为对照组(C组,n=20)和喷他佐辛治疗组(P组,n=20)。麻醉后P组患者给予喷他佐辛(0.5 mg/kg溶入100 m L生理盐水,30 min静脉滴注完毕),C组在相同时间点给予等量生理盐水。所有手术均采用蛛网膜下隙麻醉。记录患者一般情况以及上止血带前(T0),松止血带前(T1),松止血带1 min(T2),松止血带30 min(T3),术后24 h(T4)的心率、血氧饱和度、平均动脉压。分别在T0,T3,T4时刻采取外周静脉血5 m L,应用酶联免疫吸附测定法(ELISA)检测血清TNF-α,IL-6,IL-10的水平。结果:两组一般情况和术中血流动力学比较,差异无统计学意义(P>0.05)。两组相比三个时点的TNF-α均未见明显变化(P>0.05)。与C组比较,P组IL-6在T3,T4时点均明显降低(P<0.05);IL-10在T3时,明显升高(P<0.05);T4时点两组比较,差异无统计学意义(P>0.05)。结论:喷他佐辛可有效抑制下肢缺血再灌注后IL-6的生成,促进IL-10的生成,可能有利于患者的术后恢复。     

L-精氨酸复合缺血预处理对肢体缺血再灌注损伤的保护作用

为探讨L-精氨酸复合缺血预处理对肢体缺血再灌注损伤的保护作用，将75例需要上止血带充气止血的择期手术病人随机分为5组各15例：A组(缺血再灌注)；B组(上止血带前10min和松止血带前10min各静滴L-精氨酸150mg/kg)；C组(在B组处理基础上于术后5h静滴L-精氨酸150mg/kg)；D组(缺血前阻断血流5min，复流5min，重复3次)；E组(并用C、D两组处理)。各组止血带阻断下肢血流1-1．5h。分别于缺血前、再灌注45min、术后6h、术后24h抽术侧股静脉血，检测血浆肌酸磷酸激酶(CK)、丙二醛(MDA)水平。结果表明与缺血前比较，随着肢体血流的恢复，血浆CK及MDA的值逐渐升高，以术后6h最显著；但B、C、E组45min及D、E组术后24h的变化无显著性意义。C、D、E组与A组相应时段相比，CK和MDA均有显著性下降(P&;lt;0．05、P&;lt;0．01)。E组与C、D组相比亦有显著性下降。结论：L-精氨酸与缺血预处理合并应用对肢体再灌注损伤的保护作用优于单独应用。     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Synthesis and anti-inflammatory and analgesic activities of pyridyloxy- and phenoxyalkanoic acid derivatives

Synthesis of pyridyloxy-, pyridyloxyphenoxy- and phenoxylphenoxyalkanate derivatives and their anti-inflammatory and analgesic activities were investigated. Analysis of structure-activity relationships showed that in pyridyloxyalkanoic acid derivatives anti-edematous potency was associated with the presence of chlorophenoxypropionic acid moiety and 2-nitrated methyl propionates contributed to the analgesic activity.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983