国产盐酸托烷司琼治疗顺铂化疗所致恶心、呕吐的疗效与安全性评价

目的:比较国产与进口盐酸托烷司琼在治疗顺铂化疗所致恶心、呕吐的疗效和安全性。方法:采用多中心、双盲、随机对照方法,128例接受顺铂化疗的恶性肿瘤患者随机分为进口盐酸托烷司琼组和国产盐酸托烷司琼组,于化疗前1d应用盐酸托烷司琼,5mg/次,1次/d,连用6d,观察并记录用药1wk内患者食欲减退、恶心、呕吐及其他不良反应。结果:128例患者按研究要求完成观察,2组在治疗恶心、呕吐方面及发生其他不良反应方面均无显著性差异(P>0.05)。结论:国产盐酸托烷司琼在治疗顺铂化疗所致恶心、呕吐的疗效和安全性与进口盐酸托烷司琼相当。     

国产盐酸托烷司琼防治NP方案化疗引起的胃肠道反应临床观察

目的:观察盐酸托烷司琼注射液防治长春瑞宾 顺铂方案(NP方案)治疗非小细胞肺癌(NSCLC)引起胃肠道反应的止吐作用和安全性,并与进口盐酸托烷司琼(欧必亭)对比.方法:采用随机、双盲、自身交叉对照试验,可评价的18例NSCLC患者随机分为AB组和BA组,AB组第l周期用试验药盐酸托烷司琼,第2周期用对照药欧必亭;BA组第l周期用欧必亭,第2周期用盐酸托烷司琼.21d为1个周期.结果:化疗d1～d6,对食欲不振的完全控制率试验药分别为83.3%,55.6%,22.2%,11.1%,16.7%,38.9%,对照药分别为77.8%,44.4%,27.8%,16.7%,22.2%,50.0%;对恶心的完全控制率试验药分别为83.3%,55.6%,27.8%,11.1%,22.2%,33.3%,对照药分别为77.8%,38.9%,22.2%,11.1%,16.7%,44.4%;对呕吐的完全控制率试验药分别为88.9%,72.2%,61.1%,55.6%,55.6%,72.2%,对照药分别为100.0%,61.1%,38.9%,44.4%,72.2%,83.3%.两者比较差异均无显著性(所有P值均＞0.05).两组不良反应发生率无统计学差异(P＞0.05).结论:盐酸托烷司琼在控制NP方案化疗药物引起的急性呕吐、恶心及食欲不振方面与进口药欧必亭的疗效和不良反应相似.     

盐酸帕洛诺司琼预防化疗药物所致胃肠道反应63例

目的 观察盐酸帕洛诺司琼预防化疗药物所致胃肠道反应的疗效和安全性,并与盐酸托烷司琼进行对比. 方法采用随机自身交叉对照,63例入选患者分为AB组32例和BA组31例,AB组第1周期应用盐酸帕洛诺司琼,第2周期应用盐酸托烷司琼;BA组则相反. 结果 可评价患者63例,化疗后0～24 h盐酸帕洛诺司琼和盐酸托烷司琼对化疗引起的食欲不振 、恶心和呕吐的有效率相似,在24～120 h和0～120 h,盐酸帕洛诺司琼对化疗引起的食欲不振 、恶心和呕吐的有效率优于盐酸托烷司琼,差异有统计学意义(P<0.05). 两药的不良反应相似,主要为头痛和便秘. 结论 盐酸帕洛诺司琼对延迟性恶心呕吐的有效性优于盐酸托烷司琼,值得临床推广应用.     

盐酸托烷司琼预防化疗引起的胃肠反应的临床研究

目的观察注射用盐酸托烷司琼预防顺铂、阿霉素引起的急性和迟发型胃肠反应的有效性和安全性,并与国产注射用盐酸格拉司琼相对照。方法采用多中心、分层随机、双盲双模拟、自身交叉对照研究方法。入选患者均接受两周期序贯化疗并随机分为两组,依据同一患者先后两个化疗周期给予对照止吐药物国产盐酸格拉司琼（A）或试验用止吐药物托烷司琼（B）的不同次序,划分为AB组和BA组。结果入组患者151例,可评价疗效140例,其中化疗方案中含顺铂70例,含阿霉素70例。AB组68例,BA组72例。在化疗后24h内,对于急性呕吐的完全控制率,注射用盐酸托烷司琼和国产注射用盐酸格拉司琼分别为52.55%和48.91%（P=0.4453）,差异无统计学意义。在化疗后第2～5天,对于迟发性呕吐的完全控制率,注射用盐酸托烷司琼和国产注射用盐酸格拉司琼分别为45.26%和33.58%（P=0.0022）,前者明显优于后者具有显著的统计学差异。在化疗后1～5d的全程观察中对于呕吐的完全控制率,注射用盐酸托烷司琼（36.50%）明显优于国产注射用格拉司琼（26.28%）,具有显著的统计学差异（P=0.0065）。对顺铂组或阿霉素组化疗药物所引起的食欲不振、恶心的控制作用,两种5-HT3受体抑制剂效果相当,差异无统计学意义。注射用盐酸托烷司琼的不良反应,主要有头痛、头晕、便秘、疲劳感、失眠、口干等,未出现II度以上的不良反应,且发生率与国产注射用盐酸格拉司琼相似,差异无统计学意义。结论注射用盐酸托烷司琼能预防化疗药物所致胃肠反应,其对于延迟性呕吐的控制效果优于国产注射用盐酸格拉司琼,且不良反应轻,是良好的化疗止吐药。     

阿瑞匹坦联合托烷司琼预防顺铂化疗引起呕吐的临床观察

目的:观察阿瑞匹坦联合托烷司琼方案预防顺铂化疗引起呕吐的疗效及不良反应。方法:采用随机、自身交叉对照的方法,将60例接受两周期含顺铂联合化疗的患者,随机分为AB、BA组。AB组第1周期应用阿瑞匹坦联合托烷司琼,第2周期应用托烷司琼;BA组第1周期应用托烷司琼,第2周期应用阿瑞匹坦联合托烷司琼。结果:可评价疗效的59例患者中,阿瑞匹坦联合托烷司琼方案和托烷司琼方案对急性呕吐的完全缓解率分别为74.6%和57.6%,有效控制率分别为91.5%和81.4%(Z=-2.017,P=0.044);对延迟性呕吐的完全缓解率分别为69.5%和42.4%,有效控制率分别为86.4%和71.2%(Z=-3.112,P=0.002)。两种方案的主要不良反应为呃逆、便秘、头痛、头晕、口干等,不良反应发生率比较差异无统计学意义(P>0.05)。结论:阿瑞匹坦联合托烷司琼方案对顺铂化疗引起急性呕吐与延迟性呕吐均有很好的疗效,不良反应可以耐受。     

枸橼酸托烷司琼与盐酸托烷司琼防治化疗药物所致恶心、呕吐的一项多中心Ⅱ期临床试验

目的以进口盐酸托烷司琼注射液作对照,观察国产枸橼酸托烷司琼防治化疗所致恶心、呕吐的有效性及安全性。方法采用多中心、随机、双盲、阳性药物、自身交叉对照设计,将110例肿瘤化疗患者随机分为国产枸橼酸托烷司琼-进口盐酸托烷司琼组和进口盐酸托烷司琼-国产枸橼酸托烷司琼组,分别设盲为A-B组和B-A组,以观察两药对预防患者化疗所致恶心、呕吐的有效性是否有差异。结果国产枸橼酸托烷司琼和进口盐酸托烷司琼用药后患者恶心、呕吐的控制情况相似,A-B组和B-A组对化疗药物所致急性恶心的有效控制率分别为78.1%和75.2%;对急性呕吐的有效控制率分别为88.6%和88.6%;对延迟性呕吐有效控制率两组均在73%以上,以上结果均无显著差异(P>0.05)。两组不良反应轻微,主要是疲倦、头痛、便秘等,发生率小于10%,发生率也无显著差异(P>0.05)。结论国产枸橼酸托烷司琼用于防治化疗所致恶心、呕吐安全有效。     

帕洛诺司琼联合地塞米松预防含多天顺铂方案化疗引起恶心、呕吐的临床观察

目的观察和比较5-HT3受体拮抗剂帕洛诺司琼与托烷司琼联合地塞米松预防含多天顺铂方案化疗引起恶心、呕吐的疗效及安全性。方法将连续使用2周期含多天顺铂方案化疗的住院恶性肿瘤患者,按随机、交叉自身对照的方法分为AB、BA组。AB组病例第1周期的第1、3天化疗前静脉滴注帕洛诺司琼0.25 mg,并于每天化疗前静脉滴注地塞米松10 mg。BA组病例第1周期的第1~3天化疗前均分别静脉滴注托烷司琼5 mg和地塞米松10 mg。第2周期的止吐方案为两组病例第1周期的止吐方案交叉使用。观察化疗开始后7 d内患者恶心、呕吐的控制情况及不良反应发生率。结果共入组49例病例,47例可评价疗效:AB组23例,BA组24例;两组患者在年龄、性别、有无化疗史及病种等方面无显著性差异(P>0.05)。帕洛诺司琼组在延迟期和全期的化疗相关性恶心呕吐(CINV)的完全控制率显著高于托烷司琼组,分别为57.4%(27/47)和34.0%(16/47),P=0.023;55.3%(26/47)和29.8%(14/47),P=0.012。但在急性CINV方面,两组患者的完全控制率无显著性差异,分别为63.8%(30/47)和53.2%(22/47),P>0.05。两种止吐药物的不良反应多表现为便秘、头痛、疲劳、呃逆等,发生率较低,程度较轻,差异无统计学意义(P>0.05)。结论帕洛诺司琼对含多天顺铂方案化疗引起的迟发性CINV的完全控制率优于托烷司琼。多剂量帕洛诺司琼联合全程使用地塞米松的不良反应轻微。     

盐酸帕洛诺司琼预防含顺铂方案化疗恶心、呕吐的临床观察

目的观察盐酸帕洛诺司琼预防含顺铂方案化疗中所致恶心、呕吐的疗效和安全性。方法选择含顺铂方案化疗的肿瘤患者60例,随机分为观察组和对照组;试验组为盐酸帕洛诺司琼注射液;对照组为盐酸托烷司琼注射液。对化疗及化疗后1~4d的恶心、呕吐程度、控制效果及不良反应进行评价。结果盐酸帕洛诺司琼治和盐酸托烷司琼治疗后急性恶心、呕吐发生程度有差异(P<0.05);延迟性呕吐两组差异有统计学意义(P<0.05);延迟性恶心两组差异无统计学意义(P>0.05)。结论盐酸帕洛诺司琼在防治含铂方案化疗所引起的急性恶心、急性及延迟性呕吐的疗效优于盐酸托烷司琼,且使用方便、安全性好,值得临床推广。     

盐酸托烷司琼预防肺癌患者化疗所致恶心呕吐的临床研究

目的：采用托烷司琼和格拉司琼预防肺癌含顺铂的联合化疗引起的恶心呕吐,并对其疗效进行观察。方法：用随机、交叉、自身对照方法,37例肺癌患者接受含顺铂的联合化疗,将其随机分为A组19例和B组18例,A组第1个周期用托烷司琼,第2个周期用格拉司琼,B组第1个周期用格拉司琼,第2个周期用托烷司琼。止吐方法采用两种方案,试验方案为托烷司琼5mg加入0.9%氯化钠溶液100ml中于化疗前30min静滴,对照方案为格拉司琼3mg加入0.9%氯化钠溶液100ml中于化疗前后各静滴1次,均化疗当日应用。观察两种方案化疗1～4d后的恶心呕吐情况。结果：两种方案化疗1～4d后恶心、呕吐的有效控制率试验方案略高于对照方案,但差异均无统计学意义（P〉0.05）。结论：在肺癌应用含顺铂的化疗中,盐酸托烷司琼可有效防止化疗导致的恶心呕吐,每日1次,更为方便。     

盐酸托烷司琼联合胃复安穴位注射预防化疗所致恶心呕吐的临床研究

目的：对比盐酸托烷司琼联合胃复安足三里穴位注射与单用盐酸托烷司琼预防化疗所致恶心呕吐的疗效。方法入选患者随机分为A-B组和B-A组,分别使用止吐方案A（盐酸托烷司琼联合胃复安足三里穴位注射）或止吐方案B（单用盐酸托烷司琼）。结果共入组60例患者,在含顺铂方案组及不含顺铂方案组,方案A预防恶心呕吐的疗效与方案B比较差异均无统计学意义（P〉0.05）,但是便秘的发生率分别为24.1%和46.3%,差异有统计学意义（P〈0.05）。结论盐酸托烷司琼联合胃复安足三里穴位注射与单用盐酸托烷司琼比较,未能有效地减轻化疗所致的恶心、呕吐,但可以减轻便秘,可作为减轻止吐药所致便秘的一种手段。     

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.