CK，LDH，AST在脑损伤患者中的变化及意义

目的探讨肌酸激酶（CK）、乳酸脱氢酶（LDH）、谷草转氨酶（AST）在脑损伤疾病中的变化。方法对79例脑损伤患者和50例健康对照组，采用速率法检测CK、LDH、AST。结果①脑损伤后5d内，患者血清CK、LDH、AST活力显著升高，第3天后开始下降，第7天趋于正常；②酶活性为脑挫裂伤〉脑干损伤〉硬膜下血肿〉硬膜外血肿。结论脑损伤后，测定CK、LDH、AST可作为脑损伤患者诊断疗效观察的重要指标。     

EPO对缺氧缺血性脑损伤新生大鼠脑组织TERT及BCL-2表达的影响

目的:本研究旨在在观察促红细胞生成素(EPO)对缺氧缺血性脑损伤新生大鼠脑组织TERT及Bcl-2表达的影响,探讨EPO对新生大鼠缺氧缺血性脑损伤(HIBD)的保护作用及可能机制.方法:采用单侧颈总动脉结扎后给予低浓度氧制备缺氧缺血性脑损伤动物模型.Wistar新生大鼠90只,随机选取对30只仔鼠作为对照组,剩余60只制作HIBD模型,随机分为HIBD组和EPO组.其中EPO组大鼠在缺氧缺血后立即腹腔内注射EPO5000u/kg,HIBD组给予等容积生理盐水.对造模后即刻、6h、12h、24h、72h各组大鼠每组选6只取脑组织检测TERT及Bcl-2表达情况.结果:对照组可见各时间点脑组织中Bcl-2有极少量的表达;HI BD组在脑组织中TERT于造模后6h开始增加,12h升高明显,24高峰,72h开始下降,各个时间点均高于对照组(P＜0.05).EPO组中TERT蛋白的表达规律与HIBD组相似,在12h和24h时表达量高于HIBD组(P＜0.05).HIBD组大鼠缺氧缺血后6h Bcl-2表达开始增多,12h达高峰,以后逐渐减少,各个时间点均高于对照组(P＜0.05); EPO组Bcl-2表达规律与HIBD组相似,在24h时表达量高于HIBD组(P＜0.05).结论:EPO对新生大鼠缺氧缺血性脑损伤脑组织有保护性作用,此作用可能与其调节TERT及Bcl-2表达水平有关.     

弥漫性脑损伤中基质金属蛋白酶的动态变化及其意义

目的 探寻弥漫性脑损伤后基质金属蛋白酶(MMP)表达的动态变化及其与细胞凋亡的关系.方法 84只大鼠随机分为3组:空白组(不做脑室注射)、盐水组(脑室注射生理盐水)和实验组(脑室注射抑制剂),分别在伤后30 min、1、3、6 h、1、3和7 d处死大鼠,断头取脑.用TUNEL法检测细胞凋亡,明胶酶谱法检测MMP表达.结果 酶原型MMP-9在伤后30 min就有表达,1 d时达到峰值,而后下降,7 d后未回落到伤后30 min水平;酶原型MMP-2,呈双峰形式,30 min就有表达,6 h到达第1个高峰,然后下降,3 d时再次升高到达第2个峰值,7 d后小幅回落;活性型MMP-2的表达呈逐渐上升形式,30 min就有表达,7 d时达到高峰.MMP抑制剂对各种MMP表达的作用各不相同,它可上调酶原型MMP-9的表达(P<0.01),下调活性型MMP-2的表达(P<0.01),对酶原型MMP-2的表达无影响.MMP抑制剂在各个时间点上,均可减少细胞凋亡(P<0.01).结论 弥漫性脑损伤后,不同的MMP有不同的表达形式:酶原型MMP-9呈单峰型,酶原型MMP-2呈双峰型,活性型MMP-2呈上升型.MMP抑制剂能上调酶原型MMP-9的表达,抑制活性型MMP-2的表达,可降低细胞凋亡,具有一定的神经保护作用.     

全反式维甲酸对大鼠脑损伤后TGF-β_1 mRNA表达的影响

目的探讨全反维甲酸在脑损伤早期的保护机制。方法将55只SD雄性大鼠随机分为对照组、盐水对照组,全反式维甲酸组,用Feeney's法制备脑外伤模型,于8h、1d、2d、3d、7d五个时间点,测量TGF-β1mRNA的表达水平,采用SPSS11.0软件系统进行统计学分析,P<0.05具有统计学意义。结果在正常大鼠脑组织中有低水平表达,于伤后8h表达增高;损伤后2~3d达到高峰,7d后开始下降。伤后1d、2d、3d、7d全反式维甲酸组与盐水对照组TGF-β1mRNA的表达相比较有显著性差异(P<0.01)。结论脑外伤后局部及周围组织的TGF-β1表达水平升高,全反维甲酸能抑制TGF-β1的表达,对损伤后脑组织的保护与修复有一定的积极作用。     

孕酮对大鼠创伤性脑损伤后的神经保护作用

目的 观察孕酮对大鼠创伤性脑损伤(TBI)后皮质核因子-κB(NF-κB)和半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)表达的影响.探讨孕酮神经保护作用的可能机制.方法 将♂SD大鼠随机分为假手术组、脑损伤组、治疗组.按改进后的Feeney自由落体损伤装置制作大鼠脑损伤模型,于伤后6、24、48h时取材;采用免疫组织化学方法检测各组大鼠脑组织中NF-κB和Caspase-3的表达.结果 治疗组大鼠的NF-κB和Caspase-3表达较损伤组减少,伤后6、24、48 h时,治疗组的NF-κB和Caspase一3阳性细胞数与脑损伤组之间的差异有统计学意义(P<0.05).结论 孕酮可能通过抑制脑损伤后NF-κB的活性.下调Caspase-3的表达而发挥神经保护作用.     

大鼠脑损伤早期胰岛素样生长因子-1和Bcl-2的表达变化

目的探讨大鼠脑损伤后胰岛素样生长因子-1(IGF-1)和Bcl-2的表达规律,为脑损伤的法医学研究提供理论依据。方法参照Feeney法建立大鼠脑挫伤模型,通过组织学[苏木素-伊红(HE)染色]和免疫组织化学、蛋白印迹法对正常及伤后不同时间(6,12,24,36,48和72h)大鼠脑组织内IGF-1,Bcl-2蛋白的表达进行检测。结果正常大鼠脑组织内有低水平的IGF-1和Bcl-2表达,损伤后IGF-1表达即呈持续升高趋势,IGF-1免疫阳性细胞以神经元和胶质细胞为主。Bcl-2在伤后的表达呈现双峰现象,即伤后Bcl-2表达即开始升高,于伤后24h时达到峰值,此后开始下降,48h时又开始升高,72h时又达高峰,并较前一峰高,Bcl-2免疫阳性细胞也以神经元和胶质细胞为主。各实验组与对照组比较差异有统计学意义(P<0.05)。结论脑损伤后IGF-1和Bcl-2基因表达开始升高,呈时间依赖性,可以作为法医学损伤时间推断的生物学指标,并可协同发挥神经元保护作用。     

高压氧抑制缺氧缺血性脑损伤新生大鼠脑细胞凋亡的分子机制

目的通过检测Caspase-3,Caspase-9的表达情况,探讨高压氧（HBO）对缺氧缺血新生大鼠神经细胞凋亡的影响。方法建立缺氧缺血性脑损伤（HIBD）大鼠模型,将其分为HIBD组及HBO处理组,观察HBO对脑损伤的改善情况,并设立假手术（Sham）组,用免疫组化的方法检测Caspase-3及Caspase-9的蛋白表达。结果HIBD组18、24、48和96 h时间点大脑皮层区Caspase-3,Caspase-9蛋白的表达均明显高于Sham组（P〈0.05）;HBO处理组则显著缓解,Caspase-3,Caspase-9表达的升高程度均低于HIBD组（P〈0.05）。结论HBO能减轻新生大鼠HIBD模型大脑皮层区神经细胞的凋亡。     

急性脑外伤后外周血腺垂体激素的变化及其与脑损伤程度的关系

目的 探讨急性脑外伤后早期,外周血腺垂体激素含量的变化及其与腩损伤程度的关系.方法 将69例急性脑外伤患者根据GCS评分分为轻型脑损伤组(GCS>8分)和重型脑损伤组(GCS≤8分);用磁性分离酶联免疫法检测患者受伤后6、12、24、48 h血清中腺垂体激素(TSH、ACTH、FSH、LH、GH和PRL)的含量;并比较对照组,轻型脑损伤组和重型脑损伤组血清腺垂体激素含量的差异.结果 急性脑外伤后,6 h轻型脑损伤组PRL高于对照组(P<0.05),12 h达到高峰(P<0.05),24h仍与对照组有差异(P<0.05),48 h与对照组比较差异无统计学意义;重型脑损伤组各时相均高于轻型组和对照组(P<0.05);而TSH、ACTH、FSH、LH和GH在各组之间以及同组各时相之间差异均尤统计学意义.结论 急性脑外伤后,外周血泌乳素水平升高,表现出时间依赖性变化,升高的程度与脑损伤的程度有关.     

大鼠电击伤后血清CK和LDH变化与损伤时间关系的研究

目的：研究大鼠在电击伤后血清中乳酸脱氢酶（LDH）和肌酸激酶（CK）含量的变化与损伤时间的关系,为法医学上电击伤损伤时间的推断提供依据。方法：建立大鼠电击损伤模型,电击伤组于电击后0、1、2、4、8、12h和1、2、3d麻醉抽取5ml心室血,应用全自动生化分析仪检测样本中CK和LDH酶活性。并对数据进行统计学处理。结果：电击伤后大鼠血清中LDH和CK酶活性出现动态变化,呈现一定的规律,反映出电击损伤发生的时间,LDH活性在电击损伤早期（电击伤后4、8、12h）明显升高,CK活性在电击伤后8h达到高峰,之后逐渐下降。结论：电击伤后血清中CK和LDH含量变化,可以为电击损伤时间的推断提供理论依据。     

ET-1mRNA在弥漫性脑损伤中的表达及与脑水肿的关系

目的 探讨弥漫性脑损伤脑组织不同时间段ET-1mRNA表达及与脑组织水肿的关系.方法 依据Marmarou's弥漫性脑损伤动物模型改进,应用SD雄性大鼠55只,随机分为2组:假手术(对照组)(n=5)和弥漫性脑损伤组(n=50),损伤组再按照不同时间段分组(n=5),损伤后大鼠自由进食饮水,按0.5h、1h、3h、6h、12h、24h、48h、72h、1周、2周等时间段处死大鼠,提取大鼠皮层脑组织.应用分析天平测定组织干重,应用脑组织干湿重比表示脑组织含水量.结果 对照组,0.5h、1h、3h、6h、12h、24h、48h、72h、1周、2周时间段外伤组ET-1mRNA Ct值不同时间组之间差别有统计学意义;脑组织含水量对照组不同时间组之间含水量差别有统计学意义(P<0.01).结论 ①弥漫性脑损伤后ET-1mRNA表达短期增加,6h就达到高峰.②弥漫性脑损伤后脑组织含水量增加,6h增幅快,12h到达较高水平,持续2周.③ET-1mRNA早期高表达可能是导致脑组织含水量增加的一个原因.     

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.     

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.     

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     

Isolation and characterization of glycosylated and non-glycosylated prolactins from alligator and crocodile

Two molecular forms of prolactin (PRL). glycosylated and non-glycosylated, were isolated from pituitary glands of two reptiles, alligator and crocodile. The reptilian PRLs were extracted under alkaline conditions from the precipitate obtained after pituitaries were first extracted with 0.25 m sucrose, 1 mM NH₄HCO₃, pH 6.3. Purification was performed by ion exchange chromatography on DE-52, gel filtration on Sephadex G-75 superfine, and reversed phase high performance liquid chromatography. Two forms of both alligator and crocodile PRL, designated PRLI and PRLII, with molecular weights of 26000 and 24000 were isolated. Alligator and crocodile PRLI and PRLII were stained specifically in immunoblots with anti-sea turtle PRL and anti-ostrich PRL. Sequence analysis revealed that both forms of alligator and crocodile PRLs consisted of 199 amino acid residues with a glycosylation consensus sequence (Asn-Ala-Ser) at position 60 in alligator and crocodile PRLs with a molecular weight of 26000 (PRLI). In contrast, Thr was substituted for Asn at position 60 in the PRLs with a molecular weight of 24000 (PRLII). The sequences of alligator PRLs differed from crocodile PRLs only in position 134: Val for alligator PRLs and He for crocodile PRLs. There is a high degree of structural conservation between the reptilian PRLs isolated in this study and avian PRL; each showed 92% sequence identity with chicken PRL and 89% with turkey PRL.     

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.