急性冠状动脉综合征患者血清可溶性细胞间黏附分子-1和肿瘤坏死因子-α水平及阿托伐他汀对其影响

目的：探讨急性冠脉综合征（ACS）患者可溶性细胞间粘附分子-1（sICAM-1）和肿瘤坏死因子-α（TNF—α）的变化及阿托伐他汀对sICAM-1和TNF—α的作用。方法：测定60例ACS患者、40例稳定型心绞痛（SA）患者和30例正常对照者的血清sICAM-1和TNF—α浓度。并将60例ACS患者随机分为两组：他汀组和常规组,两组均予常规治疗,他汀组加服阿托伐他汀钙片。干预4周后对他汀组及常规组再次采血测定上述指标．比较两组药物干预后血清sICAM-1、TNF—α的变化及相关性。结果：ACS组sICAM—1和TNF—α水平均明显高于SA组及对照组．差异有统计学意义。他汀组和常规组比较sICAM-1和TNF—α治疗后明显下降,差异有统计学意义。结论：阿托伐他汀具有降低ACS患者血清sICAM-1和TNF-的作用。     

尖锐湿疣患者血清IL-6、TNF-α、sICAM-1、sE-selectin水平的检测

目的 为了解尖锐湿疣患者部分细胞因子及血清可溶性粘附分子水平。方法 采用ELISA法检测了46例尖锐湿疣患者血清中自介素-6（IL-6）、肿瘤坏死因子α（TNF-α）可溶性细胞间粘附分子-1（sICAM-1）和可溶性E-选择素（sE-selectin）水平。结果 患者血清IL-6明显低于正常对照组（P〈0．01），TNF-α、sE-selectin明显高于正常对照组（P〈0。01），sICAM-Ⅰ差异无显著意义。结论 尖锐湿疣患者存在免疫缺路和血清粘附分子水平的异常，可能与本病的复发有一定关系。     

氯沙坦,卡托普利治疗早期糖尿病肾尿病的比较研究

目的：观察氯沙坦、卡托普利（巯甲丙脯酸）对早期糖尿病肾病变的治疗效果。方法：３６例早期糖尿病肾病患者随机分为氯沙坦组１８例和卡托普利组１８例，疗程均为４周。治疗前后分别测定尿白蛋白排泄率（ＵＡＥＲ）、血、尿β２－微球蛋白（β２－ＭＧ）；治疗过程中观察药物不良反应。结果：两组治疗后上述指标均比治疗前明显降低，且氯沙坦组不良反应发生率明显低于卡托普利组。结论：氯沙坦与卡托普利疗效相似，其不良反应较少，     

脑卒中患者血浆细胞粘附分子及其相关因素测定的临床意义

目的：探讨缺血性脑卒中患者外周血粘附分子及相关因素的变化及临床意义。方法：分别对脑卒中患者（脑血栓30例、脑出血21例）及健康者30例外周血的可溶性细胞间粘附分子－1（sICAM-1)、可溶性血管粘附分子－1（sVCAM-1)、血小板第4因子（PF4）和D－二聚体（D－D）进行检测。结果：脑血栓组发病24h及发病1周时血的sICAM-1、sVCAM－1和PF4均明显高于对照组（P＜0．01）；脑血栓组发病24h以上各指标高于脑出血组（P＜0．01）；且发病24h及1周血sICAM－1、sVCAM－1和PF4均有相关性（P＜0．01）。结论：缺血性脑卒中患者从发病初期到发病1周sICAM-1、sVCAM－1表达增强，血小板活性增强，为缺血性脑卒中发病早期使用抗粘附分子抗体及药物治疗提供临床试验依据。     

卡托普利、氯沙坦合用常规药物对冠心病患者细胞因子水平的影响

目的:观察卡托普利与氯沙坦合用对冠心病患者血清炎症细胞因子:TNF-αI、L-6和IL-8的影响。方法:62例冠心病患者被随机分为两组(每组31例),对照组给予常规治疗(硝酸酯类、β-受体阻滞剂及阿司匹林),治疗组在常规治疗基础上加用卡托普利(12.5 mg/次,2次/d)和氯沙坦(50 mg/次,1次/d),两组疗程均8周。结果:治疗组TNF-αI、L-6I、L-8比治疗前分别下降了30.7%、42.7%和39.5%(P<0.01);与对照组治疗后比较有显著性差异(P<0.05)。结论:卡托普利与氯沙坦合用能明显减少冠心病患者血清炎症细胞因子的水平。     

不稳定型心绞痛患者血清细胞间粘附分子-1的变化及他汀类药物的早期干预

目的：探讨血清细胞间粘附分子－1（ICAM－1）在不稳定型心绞痛（UAP患者血清中的变化及他汀类药物对其影响作用，方法：32例UAP患者于治疗前，后采用ELISA方法测定可溶性ICAM－1（sICAM-1)，结果：UAP患者经治后血清sICAM-1浓度均明显降低，加用他汀类药物组降低更明显，结论：ICAM－1参与了UAP的发生，早期应用他汀类药物是有益的。     

卵巢癌病人血清中几种细胞因子关系的探讨

目的：评价两种细胞因子一转化生长因子α、β（TGF－α、TGF－β1）在卵巢癌诊断和监测中的临床价值。方法：用放射免疫及酶联法（ELISA）测定了10例正常妇女，22例卵巢良性肿瘤病人和30例卵巢上皮性癌病人术前、术后血清TGF－α、TGF－β1和CA－125的值。结果：绝大多数正常妇女和卵巢良性肿瘤病人的血清TGF－α、TGF－β1、CA－125水平明显低于卵巢癌病人；卵巢癌病人术后30天血清TGF－αβ1、CA－125降低，TGF－β1升高，各型及各期间无差异；TGF－α在卵巢癌病人血清中的异常检出率为65％，TGF－β1为75％，CA－125为80％，三总的异常检出率为95％。结论：TGF－α、TGF－β1与卵巢癌的发生、发展有关，TGF-α、TGF－β1和CA－125联合检测对卵巢癌的鉴别诊断、病情监测及提高总的异常检出率具有价值。     

Lipo-PGE1对2型糖尿病肾病血清TNF-α及TGF-β1的影响

目的：探讨脂微球前列腺素E1（Lipo—PGE1）对2型糖尿病。肾病（DN）患者血清炎性因子的影响及其治疗2型DN的机制。方法：2型DN患者61例分为治疗组和对照组。采用常规降糖、控制血压,病情稳定2周后,对照组采用疏血通治疗2周。治疗组采用Lipo—PGE1 10μg加入生理盐水20ml,静脉10min缓慢推人,每日1次。治疗前后检测患者空腹血糖（FPG）、糖化血红蛋白（HbA1c）、尿素氮（BUN）、血肌酐（Scr）、血清肿瘤坏死因子-α（TNF—α）、转化生长因子-β1（TGF—β1）、24h尿白蛋白定量（Uab）。结果：治疗后治疗组血TNF—α、TGF-β1、24h尿白蛋白定量、Scr、BUN较对照组明显下降,差异有极显著性（P〈0．01）。结论：Lipo-PGE1对2型DN患者有显著降低血清TNF—α、TGF—β1及尿白蛋白的作用,有效改善肾功能。     

速避凝对缺血性脑卒中患者外周血可溶性粘附分子的影响

目的：通过比较速避凝治疗急性缺血性脑卒中患者过程中血浆可溶性粘附分子－1水平的变化,了解其对脑缺血性卒中患者外周血可溶性粘附分子－1的作用。方法：将36例24小时内发病的急性缺血性脑卒中患者随机分为速避凝组与丹参组,两组各18例,用ELISA方法测定治疗前与治疗后第3天和第7天的血浆可溶性粘附分子－1水平。结果：速避凝组治疗后第3天的血浆可溶性粘附分子－1水平与治疗前相比显著降低（P＜0．05）,丹参组治疗后第3天的血浆可溶性粘附分子－1水平与治疗前相比,则无明显差异（P＞0．05）。速避凝组治疗后第7天的可溶性粘附分子－1水平与治疗前相比,有极明显下降（P＜0．01）,丹参组治疗后第7天的可溶性粘附分子－1水平与治疗前相比,有显著差异（P＜0．05）。结论：速避凝在治疗缺血性脑卒中的过程中对降低患者外周血可溶性粘附分子－1的效果较丹参组更为显著。     

iNOS通路生成的NO对人成骨细胞生长影响的实验研究

目的：探讨iNOS通路产生的NO对人成骨细胞生长的影响及其在骨愈合中的作用。方法：从流产胎儿的颅骨分离培养人成骨细胞分为3组：对照组：TNF－α、INF－r、IL－1β组；TNF－α、INF－r、IL－1β加L－NMMA组。通过细胞计数，流氏细胞仪检测DNA含量及透射电镜观察超微结构的变化。结果：细胞计数加入TNF－α、INF-r、IL-1β组数量明显少于对照组（P＜0．05）及加入L－NMMA组（P＜0．05），TNF－α、IMF-r、IL-1β组S期DNA含量明显减低；电镜可见线粒体减少，粗面内质网减少。结论：高浓度NO对成骨细胞具有明显的细胞毒性作用，而iNOS选择抑制剂L－NMMA能有效减轻NO对成骨细胞的影响。     

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.     

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.     

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.     

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。     

Self-stimulation and amphetamine: Tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate

The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.     

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.     

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.     

Alprazolam and lorazepam single and multiple-dose effects on psychomotor skills and sleep

Summary The effects of alprazolam 0.5 mg and lorazepam 2 mg on cognitive and psychomotor skills were assessed in twelve normal volunteer subjects in a randomised, double-blind, crossover design. Single and multiple dose effects were monitored using a battery of tests comprising critical flicker fusion threshold (CFFT), choice reaction time (CRT), simulated car tracking, and subjective ratings of perceived sedation (LARS) and of sleep behaviour (LSEQ). Compared with placebo baseline scores, treatment with lorazepam 2 mg (both single and multiple doses) resulted in a widespread impairment of CRT, tracking accuracy, and CFFT. Single doses of alprazolam 0.5 mg reduced CFFT with respect to the placebo baseline. Single and multiple dose treatment with both drugs resulted in subjective reports of sedation, a reduction of sleep onset latency, and improved sleep quality. Only lorazepam 2 mg significantly disrupted the integrity of behaviour on waking from sleep. These results suggest important pharmacodynamic differences between the two drugs in the doses used.