白藜芦醇对高脂血症大鼠血小板聚集的影响及其机制研究

目的:研究白藜芦醇对高脂血症大鼠血小板聚集的影响及其可能机制.方法:建立大鼠的高脂血症模型,同时连续i.g.给予白藜芦醇(50mg· kg-1·d-1)或空白溶媒30 d,测定大鼠血浆TC、TG、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙二醛(MDA)、超氧化物歧化酶(SOD)、NO、内皮一氧化氮合酶(eNOS)、p-选择蛋白、血栓烷B2 (TXB2)和6-酮-前列腺素F1α(6-Keto-PGF1α),ADP诱导的血小板5 min最大聚集率.结果:与高脂模型组比较,高脂饲料白藜芦醇组大鼠在连续i.g.给予白藜芦醇(50 mg·kg-1·d-1)30 d后,大鼠血浆TG、TC、LDL-C含量均下降,分别下降19％、31％、51％,HDL-C含量增加1.33倍;SOD和eNOS活力升高,NO和6-Keto-PGF1α含量增加,MDA、p-选择蛋白、TXB2含量降低,ADP诱导的血小板5 min最大聚集率降低.结论:白藜芦醇能有效降低血小板聚集,可能是通过降低血脂水平,防止脂质过氧化和保护内皮细胞完整,影响NO合成,维持血浆或组织中的TXA2和PGI2平衡及细胞内外的钙离子平衡等多环节来发挥作用.     

消栓通络方有效成分组对大鼠急性血瘀模型的影响

在"中药复方有效成分组"理论指导下,观察消栓通络方有效成分组(the effective components group of Xiaoshuantongluo formula,XECG)对大鼠急性血瘀模型的影响。采用皮下注射肾上腺素加冰水浴制备大鼠急性血瘀模型,评价XECG对全血黏度、血浆黏度、红细胞聚集率、血小板聚集率等血液流变学指标,PT、APTT、TT和FIB等凝血指标以及体内6-keto-PGF1α、TXB2和D-dimer水平的影响。结果表明,XECG显著降低ADP诱导的血小板聚集,但对全血黏度、血浆黏度、红细胞聚集率无明显影响;能延长PT和TT,对APTT和FIB含量无影响;可显著降低急性血瘀大鼠血浆中D-dimer水平,轻微降低TXB2的含量,但对6-keto-PGF1α的含量无影响。结果提示,XECG的作用在抗血小板聚集方面表现得更为突出和专一。     

杏花雨注射液对大鼠血液流变学和血液凝固的影响

目的观察杏花雨注射液对大鼠血液流变学和血液凝固的影响,以探讨其抗缺血的机制。方法采用血淤模型测定大鼠血液流变学指标、PT、FIB、APTT及血小板聚集率和解聚时间。结果杏花雨注射液14、21mg·kg-1可使血浆粘度、全血粘度、红细胞压积、红细胞聚集指数、红细胞刚性指数、血沉方程K值明显下降(P<0.05或P<0.01)。17.5、35和70mg·kg-1可使PT时间明显延长和FIB降低(P<0.01或P<0.05),70mg·kg-1可使APTT缩短(P<0.05)。17.5、35和70mg·kg-1血小板最大聚集率降低和血小板开始解聚的时间缩短(P<0.01),且作用呈剂量依赖性。结论杏花雨注射液对血液流变学指标和血液凝固有明显的影响,可改善血液的高凝状态,对缺血性疾病有一定的预防作用。     

异莲心碱抗血小板聚集和抗凝血作用

目的:探讨异莲心碱(isoliensinineI,L)对大鼠体内血小板聚集和凝血功能的影响。方法:以二磷酸腺苷(ADP)诱导血小板聚集,采用比浊法观察IL对兔体内外血小板13,5,min聚集率和最大聚集率的影响,同时评价IL对大鼠凝血酶原时间(PT)、活化部分凝血激酶时间(APTT)及凝血酶时间(TT)的影响。结果:IL 4 mg.L-1和8 mg.L-1能显著抑制ADP诱导的兔体外血小板13,5,min聚集率和最大聚集率,其抑制率为14.4%和27.9%;IL 5 mg.kg-1和10 mg.kg-1能显著抑制ADP诱导的兔体内血小板1,35,min聚集率和最大聚集率,其抑制率为20.0%和32.6%;IL能显著延长大鼠PT、APTT和TT。结论:IL具有对抗血小板聚集和凝血作用。     

莲心碱对血小板聚集、凝血功能和血栓形成的影响

目的探讨莲心碱对大鼠体内血小板聚集和凝血功能的影响,同时评价其抗血栓作用。方法以二磷酸腺苷(ADP)诱导血小板聚集,采用比浊法观察莲心碱对大鼠体内血小板1、5min聚集率和最大聚集率的影响;通过毛细管法和减尾法分别研究莲心碱对小鼠凝血时间和尾出血时间的影响,同时评价莲心碱对大鼠凝血酶原时间(PT)、活化部分凝血激酶时间(APTT)及凝血酶时间(TT)的影响;采用Chandler法及动静脉旁路模型研究莲心碱对大鼠体外血栓和动静脉旁路血栓形成的影响。结果莲心碱5mg·L-1和10mg·L-1均能明显抑制ADP诱导的大鼠体内血小板1、5min聚集率和最大聚集率;明显延长大鼠PT、APTT和TT;明显延长小鼠凝血时间及尾出血时间;不同程度抑制大鼠体外血栓和动静脉旁路血栓形成,减轻血栓湿重和干重。结论莲心碱可明显对抗血栓形成,并具有对抗血小板聚集和凝血作用。     

香椿子水煎剂的抗血栓作用研究

目的:研究香椿子水煎剂的抗血栓作用。方法:测定正常大鼠凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)。复制大鼠静脉血栓模型并称取血栓湿重。复制血瘀证模型大鼠,并测定其血浆血栓素B(2TXB2)和6-酮前列腺素F1α(6-keto-PGF1α)含量以及血浆纤溶酶原激活物(t-PA)、纤溶酶原激活抑制物(PAI)含量。结果:280、700、980 mg·kg-1剂量下香椿子水煎剂均可延长大鼠PT、TT、APTT。700、980 mg·kg-1剂量下香椿子水煎剂可使静脉血栓模型大鼠血栓湿重显著降低(P<0.01)。香椿子水煎剂对血瘀证模型大鼠血浆TXB2含量无显著影响,700、980 mg·kg-1剂量下香椿子水煎剂能显著升高模型大鼠血浆6-Keto-PGF1α含量(P<0.01),但对t-PA、PAI含量无显著影响。结论:香椿子水煎剂有较强的抗血栓作用。     

1,6-二磷酸果糖对脓毒症大鼠凝血功能和血糖的影响

目的：观察1,6-二磷酸果糖（FDP）对脓毒症大鼠凝血功能、血小板聚集率以及血糖水平的影响。方法：盲肠结扎穿孔术建立Wistar大鼠的脓毒症模型,大鼠共分为4组：对照组,假手术组,脓毒症组和FDP组。对照组不给予任何处理,假手术组行开关腹手术,脓毒症组建立脓毒症模型,FDP组在建立脓毒症模型的基础上股静脉给予1,6-二磷酸果糖（FDG）,比较4组大鼠的凝血酶原时间（PT）、活化部分凝血酶时间（APTT）、纤维蛋白原（FIB）、凝血时间（TT）,D-二聚体（D-D）、抗凝血酶Ⅲ（ATⅢ）、血小板聚集率以及血糖水平。结果：脓毒症组的PT、APTT、TT、D-D明显高于对照组和假手术组,4组大鼠FIB无显著性差异。FDP组的PT、APTT、TT、D-D明显低于脓毒症组,PT、APTT、TT稍高于对照组,FIB、D-D和ATⅢ和对照组无显著性差异。脓毒症组血小板聚集率明显高于对照组和假手术组,FDP组血小板聚集率明显低于脓毒症组,但高于对照组和假手术组。第1,3,7天时脓毒症组和FDP组血糖水平均明显高于对照组和假手术组。FDP组第1,3,7天时血糖水平明显低于脓毒症组。结论：FDP能改善脓毒症大鼠的凝血功能,控制应激性的血糖升高。     

消瘀止血片治疗凝血障碍性出血性疾病的药效学研究

目的探讨消瘀止血片治疗凝血障碍性出血性疾病的作用机制。方法用消瘀止血片高剂量、中剂量、低剂量给大鼠连续灌胃5d,对照组给予等体积生理盐水(NS)。分别观察该药对正常大鼠的血小板数量、血小板功能及凝血系列的影响,以及对华法林致凝血功能障碍大鼠凝血系列的影响。结果本药各剂量组均可缩短正常大鼠的部分凝血活酶时间(APTT)(P<0.01);高、中剂量可缩短正常大鼠凝血酶时间(TT)、凝血酶原时间(PT)(P<0.05);对华法林致凝血功能障碍大鼠,本药高、中剂量组可缩短TT、PT、APTT(与模型组相比,P<0.05或P<0.01)。消瘀止血片对动物的血小板数量无显著影响,但各剂量组均可促进二磷酸腺苷(ADP)诱导的血小板最大聚集率,与对照组相比差异有统计学意义(P<0.01或P<0.05)。结论消瘀止血片可缩短大鼠PT、TT和APTT,增强血小板聚集,有促进止血、凝血作用。     

黄芪提取物与红花总黄酮配伍对急性血瘀大鼠血液流变学的改善作用

目的观察黄芪提取物(EAM)与红花总黄酮(ECT)配伍对急性血瘀模型大鼠血液流变学指标的影响。方法大鼠随机分为正常对照、急性血瘀模型、阳性对照阿司匹林100 mg·kg-1,EAM400 mg·kg-1,ECT 200 mg·kg-1,EAM 400 mg·kg-1+ECT 200 mg·kg-1组。每天早晚各给药1次,共7次。第5次给药后,大鼠sc给予肾上腺素加冰浴制备急性血瘀模型。锥板法测定全血黏度和血浆黏度;微量毛细管法测定血细胞比容(Hct);光电比浊法测定二磷酸腺苷(ADP)诱导的血小板聚集;光电电磁法测定凝血参数。结果与正常对照组相比,模型组大鼠全血黏度和血浆黏度升高,红细胞聚集指数和血小板最大聚集率显著增加,Hct显著升高,纤维蛋白原(Fib)含量显著增加,凝血酶时间(TT)、活化部分凝血活酶时间(APTT)和凝血酶原时间(PT)均显著缩短(P<0.01)。与模型组相比,单独应用EAM和ECT均能显著降低全血黏度及血浆黏度,明显降低Hct、红细胞聚集指数和血小板最大聚集率,其中EAM还能显著降低Fib含量,延长APTT和TT;ECT还能显著延长PT。与单独应用EAM或ECT相比,EAM与ECT配伍能进一步改善血液流变学指标,在延长TT上优于单用ECT(P<0.05),对血小板最大聚集率的抑制作用优于单用EAM或ECT(P<0.05)。与阿司匹林相比,单用EAM或ECT抑制血小板聚集的作用不及阿司匹林,但EAM降低Fib的作用较好,ECT延长PT的作用较好;EAM与ECT配伍对血液流变学的改善作用与阿司匹林相似。结论 EAM和ECT单用能显著改善血瘀模型大鼠血液流变学指数,且二者配伍后能增强对血瘀模型大鼠血液流变学的改善作用。     

聚乙二醇化降纤酶对血小板聚集和凝血功能的影响

目的研究聚乙二醇化降纤酶对血小板聚集和凝血功能的影响。方法以二磷酸腺苷(ADP)诱导血小板聚集,用Labor aggregometer-153型双道血小板聚集仪测定血小板最大聚集率,观察聚乙二醇化降纤酶对大鼠体内血小板聚集的影响;同时通过对Beagle犬各个时间点凝血指标:凝血酶时间(TT)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)和纤维蛋白原(FIB)含量的观察,研究聚乙二醇化降纤酶对beagle犬凝血功能的影响。结果聚乙二醇化降纤酶低、中、高剂量组均能明显抑制ADP诱导的大鼠血小板聚集作用;降低纤维蛋白原(FIB)含量,延长beagle犬TT、PT、APTT时间,等剂量的聚乙二醇化降纤酶药效达峰和维持时间均较阳性药降纤酶的长。结论聚乙二醇化降纤酶具有较强的对抗血小板聚集和凝血作用。     

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.     

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.