银耳孢糖的抗肿瘤作用

目的研究银耳孢糖单独及与化疗药物伍用的抗肿瘤作用。方法采用小鼠肝癌H22和Lewis肺癌肿瘤模型,通过称瘤质量计算抑瘤率考察银耳孢糖抗肿瘤作用。结果银耳孢糖(25、50、100 mg.kg-1)单独使用对小鼠肝癌H22和Lewis肺癌肿瘤有明显的抑制作用,抑瘤率大于35%;当银耳孢糖(50 mg.kg-1)与环磷酰胺(5、10、20 mg.kg-1)合用时,抑瘤率分别为58.2%、70.5%和76.0%;银耳孢糖对动物体质量增长无明显影响,但对环磷酰胺所致动物体质量增长减慢有缓解作用。结论银耳孢糖体内具有明显的抗肿瘤作用;与化疗药合用有增效减毒作用。     

银耳孢糖对小鼠体内移植性肿瘤及免疫功能的影响

目的 研究银耳孢糖(Tremella fuciformis spores polysaccharide,TSP)对小鼠移植性肿瘤及免疫功能的影响.方法利用小鼠肝癌H22及小鼠肉瘤S180的体内移植性肿瘤模型,腹腔连续给予TSP 12 d,称小鼠体重及肿瘤、脾脏和胸腺重量,测定脾淋巴细胞转化率及NK细胞杀伤活性.同时观察TSP对正常小鼠免疫器官重量和碳粒廓清的影响.结果TSP 25,50,100mg·kg-1对小鼠肝癌H22及小鼠肉瘤S180有一定的抑制作用,抑瘤率分别为17.8%,27.6%,34.9%;32.8%,36.1%,44.0%;TSP 50,100 mg·kg-1能提高荷瘤小鼠脾NK细胞杀伤活性及淋巴细胞转化率(P<0.05).此外,TSP 50,100mg·kg-1亦能明显提高正常小鼠脾脏和胸腺的重量及网状内皮系统吞噬功能(P<0.05).结论 TSP对小鼠移植性肿瘤有一定的对抗作用,其抗肿瘤作用可能与增强机体免疫能力有关.     

银耳孢糖对小鼠体内移植性肿瘤及免疫功能的影响

目的研究银耳孢糖(Tremella fuciformis spores polysaccharide,TSP)对小鼠移植性肿瘤及免疫功能的影响。方法利用小鼠肝癌H22及小鼠肉瘤S180的体内移植性肿瘤模型,腹腔连续给予TSP12d,称小鼠体重及肿瘤、脾脏和胸腺重量,测定脾淋巴细胞转化率及NK细胞杀伤活性。同时观察TSP对正常小鼠免疫器官重量和碳粒廓清的影响。结果TSP25,50,100mg·kg^-1对小鼠肝癌H22及小鼠肉瘤S₁₈₀有一定的抑制作用,抑瘤率分别为17.8%,27.6%,34.9%;32.8%,36.1%,44.0%;TSP50,100mg·kg^-1能提高荷瘤小鼠脾NK细胞杀伤活性及淋巴细胞转化率(P<0.05)。此外,TSP50,100mg·kg^-1亦能明显提高正常小鼠脾脏和胸腺的重量及网状内皮系统吞噬功能(P<0.05)。结论TSP对小鼠移植性肿瘤有一定的对抗作用,其抗肿瘤作用可能与增强机体免疫能力有关。     

盐酸小檗碱对小鼠移植性肿瘤的抑制作用

目的 研究盐酸小檗碱的体内抗肿瘤活性.方法 应用移植性实体瘤H22,宫颈癌U14,肉瘤S180荷瘤小鼠作为动物模型,腹腔给药观察小鼠生长情况,并计算抑瘤率.结果 盐酸小檗碱10,20,25 mg/kg剂量对肝癌H22的抑制率分别为25.82%,36.81%和40.66%;盐酸小檗碱10,20 mg/kg剂量对宫颈癌U14抑制率分别为37.80%和59.90%;盐酸小檗碱15,20 mg/kg剂量对肉瘤S180的抑制率分别为30.85%和39.80%.结论 盐酸小檗碱可抑制肝癌H22、宫颈癌U14、肉瘤S180在小鼠体内的生长.     

白花蛇舌草多糖对S180和H22荷瘤小鼠的抗肿瘤作用研究

目的研究白花蛇舌草多糖对S180和H22荷瘤小鼠的抑瘤作用及对免疫器官的影响。方法应用肉瘤S180、肝癌H22荷瘤小鼠作为动物模型,连续灌胃给药10 d后脱颈椎处死,剥离肿瘤、胸腺、脾脏,称质量,计算抑瘤率及胸腺、脾脏指数。结果分别以30,20和10 mg.kg-1剂量的白花蛇舌草多糖灌胃,对肉瘤S180的抑制率分别为36.09%,28.66%和17.54%,对肝癌H22的抑制率分别为49.68%,40.47%和27.19%,相比模型组有显著性差异(P<0.05),对荷瘤小鼠的胸腺指数、脾脏指数无明显影响。结论白花蛇舌草多糖对S180和H22荷瘤小鼠均有抗肿瘤作用,并呈现一定的量效关系。     

克癌新对荷瘤小鼠肿瘤生长及免疫功能的影响

目的:探讨克癌新对荷瘤小鼠肿瘤生长及免疫功能的影响.方法:建立小鼠肉瘤S180及小鼠肝癌H22移植性肿瘤模型,观察克癌新对荷瘤小鼠肿瘤生长的抑制作用;采用腹腔巨噬细胞吞噬试验、淋巴细胞转化试验及Elisa法测定细胞因子IL-2和IL-6的水平,探讨克癌新对荷瘤小鼠免疫功能的影响.结果:克癌新在150和300 mg·kg-1时对小鼠肉瘤S180的生长抑制率分别为38.52%和47.88%,对肝癌H22生长抑制率分别为32.17%和40.18%,且能提高荷瘤小鼠的脾指数和胸腺指数;克癌新能增强荷瘤小鼠腹腔巨噬细胞的吞噬功能,促进淋巴细胞转化反应,升高荷瘤小鼠细胞因子IL-2和IL-6的水平.结论:克癌新有较强的体内抗肿瘤活性,其抗肿瘤机制可能与增强机体免疫功能有关.     

银耳孢糖对荷瘤小鼠环磷酰胺化疗的增效作用

目的:研究银耳孢糖(Tremella fuciformis spores polysaccharide,TSP)对环磷酰胺(CTX)化疗H22及S180荷瘤小鼠的增效作用.方法:建立小鼠肝癌H22及小鼠肉瘤S180的体内移植性肿瘤模型,随机分为对照组,TSP小、中、大剂量组,CTX小、大剂量组,TSP(小、中、大剂量) CTX小剂量组,TSP(小、中、大剂量) CTX大剂量组等12组,接种肿瘤次日开始每天分别腹腔给予0.9%氯化钠注射液、TSP(25,50及100 mg·kg-1)、CTX(10,20 mg·kg-1)、TSP(25,50,100 mg·kg-1) CTX 10 mg·kg-1及TSP(25,50及100 mg·kg-1) CTX 20 mg·kg-1,连续12～14 d,称小鼠的瘤重,测定TSP对CTX的增效作用,每批实验重复3次.结果:TSP 25,50,100 mg·kg-1可明显增加CTX(10,20 mg·kg-1)对H22及S180荷瘤小鼠的抑制作用,抑瘤率分别提高6.82～92.01%,3.90～24.27%(P<0.05,0.01);9.50～87.04%,2.41～21.51%(P<0.05,0.01).结论:TSP与CTX合用对抑制荷瘤小鼠H22及S180有明显的增效作用.     

复方蛇舌草口服液对移植性动物肿瘤的影响

目的考察复方蛇舌草口服液的抗肿瘤作用。方法采用S180肉瘤、H22肝癌作为实验瘤株,进行移植性动物肿瘤实验,观察复方蛇舌草口服液对S180肉瘤的抗瘤作用及对H22腹水型肝癌生存期的影响。结果复方蛇舌草口服液对小鼠S180移植性实体瘤有明显抑制作用,抑制率为34.46%,对H22腹水型肝癌小鼠的生存期无明显延长;其最大给药量为生药10.25.gkg-1;加用化学药5-氟尿嘧啶(5-FU)的增效试验显示,高、中剂量组抑制率分别为68.04%、52.40%。结论复方蛇舌草口服液具有一定的抗肿瘤作用,与化学药5-FU合用的增效作用不明显。     

女贞子提取物的体内抗肿瘤作用

目的：观察女贞子中含有熊果酸和齐墩果酸粗提物的抗肿瘤作用。方法：采用小鼠移植性肿瘤模型，观察了女贞子提取物（Extract of Nu Zhen Zi,ENZZ）对H22肝癌、S180肉瘤荷瘤小鼠的抑瘤作用，对S180荷瘤小鼠的生命延长作用。结果：女贞子提取物对小鼠移植性肿瘤H22有抑制，ENZZ250mg/kg，500mg/kg，1000mg/kg组平均抑瘤率分别为41.49%、48.32%、45.45%，对S180肉瘤实体型有抑制作用，上述三个剂量的抑瘤率分别为37.50%、44.23%、46.15%；女贞子提取物对S180肉瘤腹水型，H22肝癌腹水型无生命延长作用。结论：女贞子提取物对移植性肿瘤H22肝癌、S180肉瘤有抑制作用。     

参苓胶囊对实验性肿瘤的治疗及对化疗药减毒作用研究

目的：研究参苓胶囊对小鼠移植性肿瘤S180肉瘤,H22肝癌和Lewis肺癌的抗肿瘤作用及对环磷酰胺（CTX）所致小鼠免疫功能抑制的保护作用。方法：根据抗癌药物筛选标准进行体内抑瘤试验。采用CTX制备免疫功能低下模型,测定参苓胶囊与CTX配伍对小鼠白细胞数、胸腺指数、脾指数和NK细胞活性的影响。结果：不同浓度的参苓胶囊对小鼠移植性肿瘤S180肉瘤,H22肝癌和Lewis肺癌均有抑制作用,其中高剂量组效果最佳,抑制率分别为44．8％,52．2％,43．3％（P〈0．01）,且对小鼠体重生长无明显影响。参芩胶囊可明显减少CTX所致的小鼠白细胞下降,免疫器官重量和NK细胞活性降低等副作用。结论：参苓胶囊具有明显的抗肿瘤和免疫增强作用。     

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.