Ⅰ号软胶囊遗传毒性实验研究

目的：采用生物检测技术评价Ⅰ号软胶囊是否有急性经口毒性及遗传毒性,为其应用安全性提供依据。方法依据《保健食品安全性毒理学评价程序和检验方法规范》2003年版,进行了小鼠最大耐受量（ MTD）的测定、小鼠骨髓嗜多染红细胞微核试验及小鼠精子畸形试验。结果小鼠最大耐受量（MTD）大于74.08g· kg －1,相当于临床成人用量的1111.2倍;灌胃给予该受试物2.5g· kg －1-10.g· kg －1对小鼠体细胞及雄性生殖细胞无诱变性。结论在本受试剂量范围内Ⅰ号软胶囊无毒性,也未发现有遗传毒性。     

高营养活性胶囊对小鼠免疫功能的影响

高营养活性胶囊系提取特种昆虫（蛆虫）中的有效成分,配制而成的一种保健食品。在完成第一、二阶段毒性测试后,为证实其是否具有提高机体免疫力作用,科学地评价其作为保健食品的功效,我们研究了该受试物对小鼠免疫功能的影响。材料与方法１．受试物：高营养活性胶囊由...     

全蝎酶解物增强小鼠免疫功能的研究

目的基于半仿生技术,探究全蝎酶解物是否能增强小鼠免疫力。方法通过小鼠迟发型反应、抗体生成细胞、血清溶血素、碳廓清实验、腹腔巨噬细胞吞噬鸡红细胞实验、NK细胞活性实验,考察其对小鼠免疫力的影响。结果与对照组相比,全蝎酶解物高、中、低剂量组均能显著增加小鼠迟发型变态反应(P<0.05),单核-巨噬细胞碳廓清中剂量组,腹腔巨噬细胞吞噬鸡红细胞实验高、低剂量组,NK细胞活性高剂量组,均显著高于对照组(P<0.05);3个剂量组对小鼠体质量、脾脏与胸腺系数、小鼠抗体生成细胞以及小鼠血清溶血素能力影响差异无统计学意义(P>0.05)。结论全蝎酶解物具有一定的增强小鼠免疫功能的作用。     

聚酰胺微胶囊对小鼠细胞的遗传毒理学研究

目的:为确保聚酰胺微胶囊的生物安全性,对其进行了急性毒性和遗传毒性试验。方法:根据《食品安全性毒性评价程序》进行小鼠经口急性毒性试验、Ames试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验。结果:小鼠经口LD_(50)>50g·kg~(-1)体重,属无毒剂级,小鼠微核试验、Ames试验及小鼠精子畸形试验3项结果均为阴性。结论:受试物未见遗传毒性。     

虾青素软胶囊遗传毒性研究

目的 研究虾青素软胶囊的遗传毒性.方法 采用鼠伤寒沙门氏茵回复突变试验(Ames试验)、小鼠骨髓细胞微核试验和小鼠精子畸形试验等实验方法对虾青素软胶囊的遗传毒性进行研究.结果 虾青素软胶囊鼠伤寒沙门氏茵回复突变试验受试物各剂量组回变茵落数均未超过自发回变组回变茵落数的2倍,结果为阴性;小鼠骨髓细胞微核试验和小鼠精子畸形试验受试物各剂量组与空白对照组比较,微核率及精子畸变率无明显差异(P＞0.05),实验结果为阴性.结论 在本实验条件下,虾青素无遗传毒性.     

大豆分离蛋白和浓缩乳清蛋白复配蛋白粉增强小鼠免疫功能的研究

目的 探讨新型复配蛋白粉对小鼠免疫功能的影响。方法 将200只SPF级雌性ICR小鼠随机分为5批次,每批次分为4组,即高(3 333 mg/kg·bw·d)、中(1 667 mg/kg·bw·d)、低(833 mg/kg·bw·d)剂量组(分别相当于成人每日每千克体重推荐摄入量的20、10和5倍)和溶剂对照组。连续灌胃30 d,参照《保健食品检验与评价技术规范》(2003年版)的方法,第一和二批次小鼠进行细胞免疫试验和NK细胞活性测定,第三和四批次小鼠进行单核—巨噬细胞功能试验,第五批次小鼠进行体液免疫功能试验。结果 经口给予小鼠不同剂量的复配蛋白粉30 d,对各剂量小鼠增重、胸腺/体重比值和脾/体重比值无明显影响;可明显提高小鼠细胞、体液免疫功能以及单核—巨噬细胞功能和NK细胞活性。结论 该复配蛋白粉具有增强小鼠免疫力功能。     

氨磷汀的两项遗传毒理学实验

目的：考察受试物氨磷汀（ALD）是否具有遗传毒性,方法：采用活体小鼠同髓嗜多染色性红细胞（PEC）微核试验和体外中国仓鼠肺细胞（CHL）染色体畸变试验,对ALD进行诱变性研究,结果：ALD的小鼠骨髓PEC微核试验为阴性,CHL染色体畸变试验为阴性,结论：ALD在一定计是一范围内无致突变性和遗传毒性。     

牛初乳冲剂增强免疫力的实验研究

目的观察牛初乳冲剂对小鼠免疫功能的影响。方法 BALB/c小鼠连续灌胃30d后检测碳廓清能力、迟发型变态反应、抗体生成细胞数、血清溶血素水平、巨噬细胞吞噬鸡红细胞能力、NK细胞活性及ConA诱导的脾淋巴细胞转化能力等免疫指标。结果牛初乳冲剂对小鼠的脏/体比值、碳廓清能力及NK细胞活性无明显影响;对迟发型变态反应、抗体生成细胞数、HC50、巨噬细胞吞噬鸡红细胞能力及ConA诱导的小鼠淋巴细胞转化有显著作用。结论牛初乳冲剂能增强小鼠免疫力。     

贞芪扶正胶囊对免疫力低下小鼠免疫功能的影响研究

目的:研究贞芪扶正胶囊(ZQFZ)对免疫力低下小鼠免疫功能的影响。方法:用环磷酰胺复制小鼠免疫功能低下模型,通过测定腹腔巨噬细胞吞噬功能、迟发型超敏反应和溶血素抗体等指标,观察ZQFZ对小鼠非特异性免疫、细胞免疫和体液免疫功能的影响。结果:ZQFZ可显著促进小鼠腹腔巨噬细胞吞噬功能,提高吞噬率和吞噬指数;显著增强二硝基氯苯所致迟发型超敏反应;提高血清溶血素抗体水平。结论:ZQFZ对免疫力低下小鼠免疫功能有显著促进作用。     

应用胚胎干细胞试验(EST)评价邻苯二甲酸二(2-乙基)己酯(DEHP)的胚胎毒性

目的利用小鼠胚胎干细胞试验(EST)模型,初步评价邻苯二甲酸二(2-乙基)己酯(DEHP)的胚胎毒性。方法采用悬滴悬浮法培养小鼠胚胎干细胞(m ESCs),观察受试物对m ESCs分化能力的影响,结合CCK-8法判断受试物对m ESCs及小鼠胚胎成纤维细胞(3T3)的细胞毒性结果,预测受试物的胚胎毒性。用已知强胚胎毒性化合物5-氟尿嘧啶(5-Fluorouracil,5-FU)、无胚胎毒性化合物青霉素-G(P-G)对模型进行有效性验证,并将经过验证的EST模型用于评价受试物DEHP的胚胎毒性。结果利用建立的EST模型对5-FU、P-G胚胎毒性进行评价,结果表明5-FU为强胚胎毒性,P-G为无胚胎毒性,与文献报道一致;DEHP对m ESCs和3T3的半数抑制浓度分别为IC50m ESCs=315μmol/L(126μg/ml),IC503T3=307μmol/L(122.8μg/ml),m ESCs的半数抑制分化浓度为ID50m ESCs=323μmol/L(129.2μg/ml),经EST模型判断公式计算得出该化合物为弱胚胎毒性化合物。结论建立的EST模型的有效性验证结果与ECVAM的结论一致,可用于胚胎毒性的筛选和评价;经EST模型评价DEHP的胚胎毒性为弱胚胎毒性。     

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.