恩替卡韦对慢性乙型肝炎抗病毒治疗的临床分析

目的探讨恩替卡韦对慢性乙型肝炎的抗病毒治疗疗效。方法选择37例未经抗病毒治疗的慢性乙型肝炎患者随机分为治疗组(18例)和对照组(19例),治疗组给予恩替卡韦片0.5 mg/d口服,对照组给予拉米夫定片100 mg/d口服。疗程为48~96周。观察两药对HBV DNA、ALT、e抗原/e抗体血清转换的影响及其所致不良反应。结果在治疗24周和48周时,治疗组和对照组未检测到HBV DNA的病例分别为55.56%、31.58%,83.33%、36.84%。e抗原阴转率与e抗原/e抗体血清学转换率以及不良反应两组无明显差异。结论恩替卡韦能更有效地抑制HBV复制,不良反应与拉米夫定相似。     

恩替卡韦对慢性乙型肝炎抗病毒治疗的疗效观察

目的研究分析恩替卡韦对慢性乙型肝炎抗病毒治疗的疗效。方法从我院慢性乙型肝炎患者中选取62例并将其分为治疗组(采用恩替卡韦进行治疗)和对照组(采用拉米夫定进行治疗),均为31例,对比两组患者治疗12、24、48周后HBV DNA<1×10³ IU/mL、HBeAg转阴率、e抗原,抗体转换率和血清ALT复常率。结果对比两组患者实施临床治疗后12、24、48周后HBV DNA<1×103 IU/mL、HBeAg转阴率、e抗原,抗体转换率和血清ALT复常率。结果对比两组患者实施临床治疗后12、24、48周后HBV DNA<1×10³IU/mL、HBeAg转阴率、e抗原/抗体转换率和血清ALT复常率,治疗组患者治疗后12、24、48周后HBV DNA<1×103IU/mL、HBeAg转阴率、e抗原/抗体转换率和血清ALT复常率,治疗组患者治疗后12、24、48周后HBV DNA<1×10³ IU/mL和血清ALT复常率均显著优于对照组患者的,P<0.05;两组患者治疗后12、24、48周后HBeAg转阴率和e抗原/抗体转换率相比没有差异性,P>0.05。结论在慢性乙型肝炎抗病毒临床上恩替卡韦临床效果显著。     

恩替卡韦治疗慢性乙型肝炎的疗效分析

目的研究恩替卡韦分散片治疗慢性乙型肝炎(CHB)的抗病毒疗效及安全性。方法将未接受过抗病毒治疗的22例患者作为第一组,口服恩替卡韦分散片0.5 mg,每天1次,疗程为48周;将接受过拉米夫定抗病毒治疗后耐药的14例患者作为第二组,口服恩替卡韦分散片1.0 mg,每天1次,疗程为48周。于治疗前后分别检测血清丙氨酸氨基转移酶(ALT)、HBV-DNA、乙型肝炎病毒e抗原(HBeAg)/乙型肝炎病毒e抗体(HBeAb)等。结果第一组患者治疗12、24、36、48周时ALT复常率,HBV-DNA、HBeAg/HBeAb阴转率均优于第二组。两组患者均未发生明显不良反应。结论恩替卡韦分散片是一种安全、有效的抗乙型肝炎病毒药物,且初治效果较好。     

恩替卡韦抗乙型肝炎病毒感染量效关系及安全性的研究

目的:探讨恩替卡韦(ETV)治疗慢性乙型肝炎抗病毒感染的量效关系及安全性。方法:采用随机、双盲、安慰剂对照的临床试验,选择未经抗病毒治疗的慢性乙型肝炎病毒(HBV)感染者,按1:1:1的比例分为3组:ETV0.5mg/d组、ETV0.1mg/d组和安慰剂组,治疗28d,停药观察56d,然后用ETV0.5mg/d开放治疗48周,再次停药观察24周。结果:ETV0.5mg/d的疗效优于0.1mg/d,停药后HBV DNA的反跳也较缓慢。开放治疗期间有81.6%的受试者HBV DNA<0.7mmol/ml,HBeAg/抗HBe的血清转换率为7.9%,但停药后80%的受试者HBV DNA再度升高。给药组和安慰剂组受试者不良事件发生率无统计学差异(P=0.428),开放治疗期间未发现与恩替卡韦相关的严重不良反应。结论:ETV有较强的抗HBV活性,其抗病毒作用与剂量相关。恩替卡韦0.5mg/d治疗慢性乙型肝炎更为有效和安全。     

恩替卡韦治疗慢性乙型肝炎50例效果分析

目的：评价恩替卡韦抗病毒治疗慢性乙型肝炎（CHB）48周的疗效和安全性。方法：选取慢性乙型肝炎患者100例,其中50例使用恩替卡韦（治疗组）,50例使用拉米夫定（对照组）,两组进行疗效比较。治疗组与对照组的治疗剂量分别为0.5mg/d和100mg/d,观察两药在第48周时的ALT（丙氨酸氨基转移酶）、HBVDNA（乙肝病毒脱氧核糖核酸）及e抗原血清转换情况。结果：治疗组与对照组在治疗第48周时ALT复常率、HBVDNA转阴率及e抗原血清学转阴率分别为90%和72%（P〈0.05）、92%和70%（P〈0.05）、40%和18%（P〈0.05）。结论：恩替卡韦能快速、强效地抑制乙肝病毒复制,安全性和耐受性良好。     

恩替卡韦治疗慢性乙型肝炎临床观察

目的评价恩替卡韦治疗慢性乙型肝炎的早期及远期疗效。方法 56例慢性乙型肝炎患者随机分为治疗组和对照组,治疗组(30例)予恩替卡韦0.5mg/d;对照组(26例)予拉米夫定100mg/d,用药时间最少24周,于第2周、24周时,分别检测血清乙肝病毒载量、e抗原定量及肝功能。结果治疗2周后治疗组HBVDNA定量、e抗原定量、肝功能较对照组明显下降(P<0.01);24周后治疗组HBVDNA阴转率为85.7%,对照组为81.2%,肝功能、e抗原定量治疗组与对照组差异无统计学意义。结论恩替卡韦能快速、强效地抑制乙肝病毒复制,在改善肝脏生化指标、抑制病毒方面均优于拉米夫定。     

恩替卡韦与拉米夫定治疗 e抗原阳性慢性乙型病毒性肝炎的临床研究

目的：评价恩替卡韦治疗e抗原阳性慢性乙型病毒性肝炎的临床疗效和安全性。方法80例乙型肝炎e抗原（ HBeAg ）阳性慢性乙肝患者随机分为恩替卡韦组（试验组）和拉米夫定组（对照组），各40例。试验组口服恩替卡韦片500 mg? d－1，对照组口服拉米夫定片100 mg? d－1，疗程均为48周，比较2组患者在8，12，24，36，48周时谷丙转氨酶（ ALT ）复常率、乙肝病毒 DNA （ HBV－DNA）低于下限率和HBeAg血清学转换率，且观察治疗期间2组患者的不良反应。结果在第8，12周时，试验组谷丙转氨酶复常率为47．50％，65．00％，明显高于对照组的25．00％，42．50％（ P＜0．05）；试验组在各时间点HBV－DNA低于下限率均明显高于对照组（ P＜0．05）；36，48周时，试验组HBeAg血清学转换率为32．50％，35．00％，明显高于对照组的12．50％，15．00％（ P＜0．05）。2组不良反应发生率差异无统计学意义（ P＞0．05）。结论恩替卡韦治疗HBeAg阳性慢性乙肝疗效好，不良反应发生率低。     

恩替卡韦与拉米夫定治疗e抗原阳性慢性乙型肝炎的疗效对比

目的：分析恩替卡韦与拉米夫定治疗e抗原阳性慢性乙型肝炎患者疗效的差异,为e抗原阳性慢性乙型肝炎初治患者提供合理的治疗方案。方法选择e抗原阳性慢性乙型肝炎患者155例,随机分为2组：恩替卡韦组79例和拉米夫定组76例。均治疗24个月,对比不同治疗时间点两组ALT复常率、HBeAg转阴率及HBV-DNA转阴率。结果恩替卡韦组在治疗第3、6个月时ALT复常率为36.7%、75.9%,拉米夫定组为38.2%、75.0%,两组差异无统计学意义,治疗12个月后两组ALT均恢复正常水平;治疗第3、6、12、24个月时,恩替卡韦组的HBV-DNA转阴率为29.1%、51.9%、77.2%,78.5%,拉米夫定组为19.7%、32.9%、48.7%,39.5%,两组差异有统计学意义（均P〈0.01）;治疗第3、6、12、24个月时,恩替卡韦组HBeAg转阴率为0、5.1%、22.8%、36.7%,拉米夫定组为0、2.6%、17.1%、26.3%,两组有差异有统计学意义（均P〈0.01）。两组均未发现严重的不良反应。结论恩替卡韦与拉米夫定治疗e抗原阳性慢性乙型肝炎在肝酶复常率方面差异无统计学意义,但在HBeAg转阴率及HBV-DNA转阴率方面的疗效恩替卡韦明显优于拉米夫定。     

拉米夫定联合阿德福韦酯与恩替卡韦单药治疗乙型肝炎肝硬化48周疗效对比研究

目的 比较拉米夫定联合阿德福韦酯与恩替卡韦单药治疗乙型肝炎肝硬化疗效差异,为乙型肝炎肝硬化提供治疗方案.方法 21例乙型肝炎肝硬化患者使用拉米夫定联合阿德福韦酯治疗,单药治疗组29例使用恩替卡韦治疗,进行基线情况及抗病毒48周时疗效的分析.结果 两组的性别、年龄、Child-Pugh评分、基线HBV DNA水平、HBeAg阳性率比较,差异均无统计学意义(P＞005).治疗48周时病毒转阴率、Child-Pugh评分均较治疗前好转,但两组之间疗效无统计学意义.结论拉米夫定联合阿德福韦及或恩替卡韦单药治疗乙型肝炎肝硬化患者,其HBV DNA水平下降、Child-Pugh分级明显改善.但治疗48周两组疗效无差异.     

恩替卡韦与拉米夫定治疗慢性乙型肝炎疗效比较

目的：比较恩替卡韦与拉米夫定治疗慢性乙型肝炎的临床疗效。方法选择2008-2011年在温州医科大学附属第二医院门诊或住院的慢性乙型肝炎患者54例,随机分为对照组（拉米夫定治疗）和观察组（恩替卡韦治疗）,每组各27例,对两组治疗前、治疗后3、6、12、24个月后乙肝病毒脱氧核糖核酸（HBV DNA）、e抗原血清转换情况进行观察和比较。结果与对照组比较,治疗24个月时观察组e抗原血清学转阴率明显升高,差异有统计学意义（P＜0.05）。治疗24个月时对照组耐药率明显高于观察组,差异有统计学意义（P〈0.05）。结论恩替卡韦较拉米夫定治疗慢性乙型肝炎具有更好的疗效,耐药率较低,且无明显的不良反应,能延缓和阻止疾病的进展。     

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.     

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.