急(慢)性乙型肝炎PBMC培养上清液IL-12水平与肝功能的关系

目的:研究急性乙型肝炎和慢性乙型肝炎PBMC培养上清液中IL-12水平与血清ALT及TBIL之间的关系。方法:应用FicollHypaque密度梯度离心法从肝素化血中分离外周血PBMC,用ELISA方法检测PBMC培养上清液IL-12和血清ALT及TBIL水平。结果:急性乙型肝炎和慢性乙型肝炎PBMC培养上清液中IL-12水平与血清ALT及TBIL水平呈正相关。结论:急性乙型肝炎和慢性乙型肝炎PBMC培养上清液中IL-12水平与肝功炎症活动密切相关。     

保肝降酶治疗对慢性乙型肝炎患者IL-17和ANA的影响

目的探讨保肝降酶治疗对慢性乙型肝炎(慢乙肝)患者血清IL-17和抗核抗体(ANA)水平的影响。方法对30例慢乙肝患者(慢肝组)给予复方甘草酸苷制剂治疗3周,随机抽取乙肝病毒携带者30例为对照组,检测血清IL-17和ANA表达。结果慢肝组患者使用复方甘草酸苷制剂治疗前后IL-17和ANA表达均无明显差异[(182.546±17.731)pg/ml vs.(177.201±16.247)pg/ml和0.867±0.446vs.0.645±0.285](P>0.05);但ANA表达均明显高于对照组的0.555±0.281(P<0.01和P<0.05)。结论仅使用保肝降酶治疗,不能有效降低血清IL-17及ANA水平。     

HBV感染者血清白介素(12,2,10)的水平及临床意义

目的检测HBV不同感染状态时血清IL-12、IL-2和IL-10水平,并探讨其临床意义。方法选择HBV不同感染状态,包括无症状携带者、无症状携带者重叠急性自限性肝炎、HBeAg阳性慢性乙型肝炎、HBeAg阴性慢性乙型肝炎和急性乙型肝炎患者等作为研究对象,以健康献血员作对照,采用双抗体夹心ELISA法检测血清IL-12、IL-2和IL-10水平并进行比较。结果无症状携带者血清IL-10水平明显高于健康对照,部分无症状携带者血清IL-12和IL-2高水平;重叠感染HAV、HEV感染IL-2、IL-10和IL-12水平急性期和恢复期相比无明显差异;慢性乙型肝炎患者发病急性期血清IL-12水平低下,血清IL-2和IL-10水平均较健康对照明显升高;急性乙型肝炎患者血清IL-12和IL-2水平与ALT水平并非完全平行关系,血清IL-10水平与ALT水平呈完全平行关系。结论血清IL-12和IL-2水平可考虑作为无症状携带者抗病毒治疗指征,慢性乙型肝炎活动与血清IL-12水平低下有关,血清IL-2水平升高与肝炎活动有关,其升高主要参与促进HBeAg/HBeAb血清转换。肝炎活动与血清IL-10水平无明显相关性。     

脑瘫患儿IFN-γ、TNF-α及IL-6水平的研究

目的:探讨干扰素-γ(IFN-γ)、肿瘤坏死因子(TNF)-α及白细胞介素(IL)-6在脑瘫中的作用。方法:采用酶联免疫吸附法检测28例脑瘫患儿及15例正常儿童外周血单核细胞(PBMC)中IFN-γ、TNF-α及IL-6的水平。结果:脑瘫患儿PBMC中IFN-γ、TNF-α、IL-6分别为(46.17±14.29)pg/ml、(28.65±11.44)pg/ml、(67.13±21.10)pg/ml,对照组分别为(37.31±16.64)pg/ml、(18.43±10.97)pg/ml、(46.44±23.39)pg/ml,差异均有统计学意义(P<005)。结论:脑瘫患儿IFN-γ、TNF-α及IL-6水平的升高,可能与脑瘫的发生有关,即脑瘫的发生与免疫系统及其功能异常有密切关系。     

IL-5在分泌性中耳炎及中耳积液患者中的作用机制探讨

目的探讨白介素-5(IL-5)在分泌性中耳炎发生发展过程中的作用机制。方法选择2010年3月-2012年9月我院耳鼻咽喉头颈外科确诊的分泌性中耳炎患者24例28耳作为试验组,其中以病程<3个月的患者为急性组,病程≥3个月的患者为慢性组。另从我院体检科体检的健康人员中选取22例健康人员作为对照组。采用双抗体夹心酶联免疫吸附试验(ELISA)检测所有人员血清中IL-5的表达水平。结果试验组中耳积液中IL-5浓度为(10.437±1.393)pg/ml高于血清中的(2.754±0.868)pg/ml,差异有统计学意义(P<0.01)。试验组血清中IL-5浓度(2.754±0.868)pg/ml低于对照组的(2.876±1.074)pg/ml,差异无统计学意义(P>0.05)。慢性组中耳积液中IL-5浓度为(11.374±1.457)pg/ml高于急性组的(9.550±0.776)pg/ml,差异有统计学意义(P<0.05)。结论 IL-5作为重要的变态反应性细胞因子,存在于分泌性中耳炎患者中耳积液中,中耳局部产生变态反应性炎症,IL-5可能在分泌性中耳炎的慢性病程中发挥重要作用。     

重症急性胰腺炎患者血清TNF-α和IL-6水平的动态变化及临床意义

目的探讨TNF-α和IL-6在重症急性胰腺炎(SAP)血清中的变化及临床意义。方法应用ELISA法检测23例重症急性胰腺炎和30例轻型急性胰腺炎(MAP)及20例对照组血清TNF-α、IL-6的水平变化。结果入院时SAP患者TNF-α水平(59.1±15.5)pg/ml显著高于MAP组(38.9±9.72)pg/ml和对照组(14.2±4.5)pg/ml,MAP患者血清TNF-α水平也较对照组显著升高,但IL-6水平SAP(45.5±11.7)pg/ml和MAP(43.4±13.3)pg/ml较对照组(39.3±11.0)pg/ml无明显升高;SAP血清IL-6在入院的第7天升高最明显(188.5±51.7)pg/ml,分别高于MAP组(115.8±27.8)pg/ml和对照组,MAP亦明显高于对照组;在入院第14天SAP血清TNF-α(36.4±7.6)pg/ml,IL-6(112.6±25.2)pg/ml仍然高于MAP(15.4±3.7)pg/ml、(44.7±13.2)pg/ml和对照组,而MAP与对照组无明显差别。结论检测血清TNF-α和IL-6的水平变化,对重症急性胰腺炎的早期诊断、病情判断和预后评估具有重要的应用价值。     

慢性阻塞性肺疾病患者血清白细胞介素17的表达

目的探讨白细胞介17(IL-17)在慢性阻塞性肺疾病(COPD)发病机制中的作用。方法抽取100例COPD急性加重期(A1组)、100例稳定期患者(A2组)及100例健康人(C组)静脉血标本,采用双抗体ELISA法测定血清IL-17水平。并作肺功能检查,计算第1秒用力呼气容积比(FEV1%)。结果 A1组血清IL-17明显高于A2组[(73.1±58.4)pg/mlvs.(34.8±21.6)pg/ml](P<0.01),A2组血清IL-17高于C组[(16.4±7.6)pg/ml](P<0.01)。A1组血清IL-17与FEV1%呈负相关(P<0.05)。结论 IL-17可能参与COPD的发病。     

白细胞介素6与慢性乙型肝炎患者肝细胞损伤和纤维化的关系

目的探讨血清白细胞介素6(IL-6)与慢性肝病的关系.方法采用ELISA法和放免法对76例慢性乙型肝炎(CHB)、肝炎肝硬化(LC)、慢性重型肝炎(CSH)患者血清IL-6和Ⅲ型前胶原蛋白(PCⅢ)及Ⅳ型胶原蛋白(ⅣC)测定,肝活检42例进行肝组织病理学分析.结果①CHB轻、中、重度、LC、CSH患者血清IL-6水平分别为(29.93±8.08)pg/ml、(50.36±4.51)pg/ml、(78.33±9.11)pg/ml、(71.59±8.23)pg/ml、(96.13±5.47)pg/ml,依次升高(P＜0.01或P＜0.05);明显高于对照组(7.10±1.80)pg/ml.②血清IL-6水平与PCⅢ及ⅣC呈正相关(P＜0.01),与肝组织炎症损伤及纤维化程度亦呈正相关.结论IL-6水平与慢性肝病严重程度关系密切.     

肺结核患者治疗前后外周血中IL-10、IL-22、IL-23水平变化及其临床意义

目的 分析肺结核患者治疗前后外周血中IL-10、IL-22、IL-23表达水平变化及其临床意义.方法 收集本院2014年10月至2015年5月收治的活动性肺结核患者49例,选择健康体检者30例为对照组.ELISA法检测肺结核患者治疗前、治疗6个月后以及对照组外周血血清中IL-10、IL-22、IL-23表达水平,并分析其相关性.结果 ELISA结果显示,肺结核患者治疗前外周血血清IL-10表达水平为(24.15±13.21) pg/ml,明显高于对照组[(14.91±8.23) pg/ml],P＜0.05,经抗结核常规治疗6个月后,血清IL-10表达水平为(17.11 ± 7.59) pg/ml,明显低于治疗前(P＜0.05),但仍高于对照组.肺结核患者治疗前外周血血清IL-22、IL-23表达水平分别为(20.56±7.41) pg/ml、(21.12 ± 2.68) pg/ml,明显低于对照组[(53.78±8.22) pg/ml、(36.42±2.16) pg/ml,P＜0.05],经抗结核常规治疗6个月后,血清IL-22、IL-23表达水平分别为(38.95±6.35) pg/ml、(29.89±3.74) pg/ml,明显高于治疗前(P＜0.05),但仍明显低于对照组(P＜ 0.05).Pearson相关分析结果表明,血清IL-22、IL-23呈正相关性.结论 肺结核患者外周血中IL-10、IL-22、IL-23在治疗前后表达水平发生变化,可能与机体结核免疫有关,有望作为评价肺结核疗效的参考指标.     

CHF患者血液单核细胞TNFα升高

Shui-ping zhao等研究充血性心力衰竭(CHF)患者外周血液单核细胞(PBMC)所产生的肿瘤坏死因子α(TNF-α)的变化,并测定113例各种心脏病患者血浆和PBMC培养上清液的TNFα浓度。结果表明,CHF患者[50例,(13.36±6.09)pg/ml]和恶病质CHF患者[26例,(19.20 10.42)pg/ml]的血浆TNF_2水平明显高于对照者[37例,(6.73±3.91)pg/ml]。CHF患者培养的PBMC上清液TNF_2(PBMC-TNFα)水平[(5.77±2.11)ng/ml]明显高于对照者[(2.27±     

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。     

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.     

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.     

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.     

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