Effect of diminazene aceturate,levamisole and vitamin C combination therapy in rats experimentally infected with Trypanosoma brucei brucei

Objective:To investigate the effect of diminazene aceturale(DA) alone or in combination with either levamisole and/or Vitamin C in albino rats experimentally infected with Trypanosoma brucei brucei.Methods:Thirty adult male albino rats,randomly assigned into 6 groups(A—F) of 5rats each were used.They were either infected with 1×10~a trypanosomes intraperitoneally(groups A-E) or uninfected(group F).The different groups were treated respectively as follows:group A-with 3.5 mg/kg DA;group B-3.5 mg/kg DA and 7.5 mg/kg levamisole;group C-3.S mg/kg DA and 100 mg/kg vitamin C;and group D-3.S mg/kg DA and 7.S mg/kg levamisole and 100 mg/kg vitamin C.Croup E was left untreated.Parameters assessed include:rectal temperature,body weight changes,packed cell volume(PCV),Haemoglobin concentration(Hb),total leucocyte count(TLC) differential leucocyte count(DLC),parasitaemia,clinical signs and survivability.Results:Average pre-patent period of 5 days was recorded.Parasites in the blood were cleared in all treated groups(A-D) within 48 hours post treatment(PT).Untreated rats in group E died between25 and 32 days post infection(PI).Relapse was not recorded in all the treated groups(A-D).The initial reduction in PCV,Hb,TLC and increases in rectal temperature following infection were reversed by the treatments.The rats that received drug combinations(groups B,C and D)showed faster and higher recovery rates than the uninfected control and group A.Conclusions:Levamisole and/or Vitamin C combination with DA were more effective in the treatment of rats infected with Trypanosoma brucei brucei.

Effect of liniment levamisole on cellular immune functions of patients with chronic hepatitis B

AIM: To explore the effects of liniment levamisole on cellular immune functions of patients with chronic hepatitis B. METHODS: The levels of T lymphocyte subsets and mlL-2R in peripheral blood mononuclear cells (PBMCs) were measured by biotin-streptavidin (BSA) technique in patients with chronic hepatitis B before and after the treatment with liniment levamisole. RESULTS: After one course of treatment with liniment levamisole, the levels of CD3+, CD4+, and the ratio of CD4+/CD8+ increased as compared to those before the treatment but the level of CD8+ decreased. The total expression level of mIL-2R in PBMCs increased before and after the treatment with liniment levamisole. CONCLUSION: Liniment levamisole may reinforce cellular immune functions of patients with chronic hepatitis B.

Immunostimulatory Effect of Levamisole on the Immune Response of Goats to <i>Peste des petits ruminants </i>(PPR) Vaccination

The use of Levamisole hydrochloride as an immunostimulant has been successful in the control of certain diseases such as Derzsy’s disease in chicken as well as in increasing lymphocytes and weight gain in pigs. However, its use as immunostimulant in the prevention of Peste des petits ruminants (PPR) in goats has not been investigated. In this study, the use of Levamisole in enhancing immune response to PPR vaccination including its effects on weight gain was investigated among groups of goats (groups A, B, C and D). Virus neutralization test was used to determine the antibody profile in vaccinated goats while the total and differential leucocyte counts and body mass index (BMI) were determined using standard procedures. Goats in group A (Levamisole primed and PPR vaccinated) seroconverted to more than 3-folds of the initial pre-vaccination geometric mean titre (GMT) of neutralizing antibody beginning from second week post-vaccination and remained high throughout the period of the experiment. Similarly, there was significant increase (p 0.05) in BMI of animals in other groups throughout the period of the experiment. The results of this study further confirm the immunostimulatory effect of Levamisole when used in combination with a vaccine.

Evaluation of the Fasciolicidal/Nematicidal Efficacy of an Intramuscular Combination of Clorsulon/Levamisole in Naturally Infected Dairy Cattle

The aim of the present study was to assess the fasciolicidal and nematicidal efficacy of a new combination of clorsulon/levamisole, which was formulated for intramuscular administration, in dairy cattle. For the study, sixteen Holstein-Freisian dairy cows were selected for inclusion in the trial based on finding Fasciola hepatica eggs or gastrointestinal nematodes (GIN) in the feces. Ten of these cows were naturally infected with F. hepatica, and 6 were naturally infected with GIN. On Day 0 (zero), all animals were treated with a combination of clorsulon (2.5 mg/kg/IM and levamisole (2.5 mg/kg/IM) administered at the dose recommended by the manufacturer (1 ml/20kg/bw). Subsequently, their feces were analyzed on days 0, 7, 14 and 21 post treatments by the Flukefinder sedimentation method and McMaster technique to determine the percentages of egg reduction in the animals, with reference to the egg load count on day 0. The results obtained in the current work indicated an efficacy of 100% that was determined by the percentage reduction of eggs of F. hepatica and/or GIN. This new fasciolicide/nematicide formulation exerted a remarkable effect and can be considered a new alternative to control F. hepatica and gastrointestinal worms in dairy cattle.

COMPARATIVE STUDY ON THE INHIBITORY EFFECT OF GREEN TEA, COFFEE AND LEVAMISOLE ON THE HEPATOCARCINOGENIC ACTION OF DIETHYLNITROSAMINE

The present study aimed at clarifying whether Chinese green tea, coffee and levamisole (LMS) have similar Inhibitory effect on hepatocarclnogenesis induced by diethylnltrosamine (DEN) as they had been proved in our previous aflatoxin B1 (AFB1) experiments. Male Wistar rates were divided into control (A), green tea (B), coffee (C) and levamisole (D) groups. All rats received the same basic DEN treatment according to the program originally designed by Solt and Farber. During the two weeks before and one week after i. p. injection of DEN, the group B, C and D were given 2. 5% green tea, 5% coffee and 0. 1% LMS diet, respectively. The results demonstrated that coffee, LMS and , in particular,green tea showed Inhibitory effect against DEN-induced hepatocarcinogenesis, indicating that green tea can be used as chemopreventive agent for DEN-, as well as for AFB1-induced hepatocarcinogenesis.

Levamisole-Adultered Cocaine: Vasoconstrictive and Vasculitis Effects Occurring Simultaneously

This case presents a rarely seen combination of two Cocaine-induced syndromes occurring simultaneously. Levamisole-adultered cocaine leads to Levamisole-induced Vasculitis (LIV), while cocaine’s vasoconstrictive effect causes destruction of the osteo-cartilaginous structures of nose called Cocaine-induced midline destructive lesions (CIMDL). This case raises awareness of a new pattern of recognition in order to avoid misdiagnosis. We present a case of a 51-year-old male cocaine user who developed severe left-sided ear pain and yellowish secretions with circular necrotic lesions in the nose, right earlobe, and dorsum of feet bilaterally. An extensive workup to assess purpuric lesions’ etiology, including vasculitis, collagen vasculitides, anti-phospholipid syndrome, hypercoagulable state and infectious process, was performed and found negative. He developed bilateral tympanic membrane perforation and purpuric necrotic skin lesions, at the same time, due to CIMDL and LIV, respectively. These two syndromes rarely present simultaneously in a patient. This case report exhibits a new Cocaine-induced clinical presentation that will help hospitalists recognize the disease and avoid misdiagnosis leading to unnecessary tests, prolonged hospitalization, and higher healthcare costs. Diagnosis is challenging, as it consists of establishing a temporal relationship between cocaine ingestion and symptoms’ onset. This disease usually has a benign progression because symptoms frequently resolve without intervention.

羟氯扎胺盐酸左旋咪唑复方混悬液对靶动物牛的安全性试验

为评价羟氯扎胺盐酸左旋咪唑复方混悬液的安全性,确定该药对靶动物牛的毒性风险,选用32头健康西门塔尔肉牛(10~12月龄),随机分为4组,每组8头,分别以推荐剂量的0、1、3、5倍剂量连续口服给药3 d,给药后观察14 d。在试验开始前(第0天)、给药结束后(第4天)及试验结束后(第18天)抽取试验牛血液进行血液学检查及血清生化检查。试验第4天,于0剂量组和5倍剂量组内随机选择4头牛进行安乐死(雌雄各半),试验结束后安乐死0剂量组及5倍剂量组剩余牛,进行组织病理学观察。综合体重、临床毒性观察、血液学检查、血清生化检查和组织病理学观察结果,评估药物的安全性。试验结果显示,1、3、5倍剂量组给药后12 h内多数牛均出现腹泻反应,5倍剂量组个别牛有短暂的表现呆滞、食欲减退,停药后副作用逐渐减弱或消失,试验第5天时临床各项观测结果均正常;其他剂量组未出现采食、饮水及精神状态异常,未观测到明显临床病理表现。试验结束后,0剂量组及1倍剂量组试验牛体重均有增加,但3倍剂量组及5倍剂量组试验牛体重下降;血液学检查及血清生化分析结果显示,与0剂量组相比,3倍剂量组及5倍剂量组试验牛部分指标存在显著差异(P<0.05);对试验牛剖检,组织病理学观察未发现肉眼可见明显病变。综上所述,连续3 d每天口服5倍推荐剂量的羟氯扎胺盐酸左旋咪唑复方混悬液靶动物牛仍可耐受,故临床按推荐剂量为0.25 mL/kg口服羟氯扎胺盐酸左旋咪唑复方混悬液具有安全性。

4种烟碱受体激动剂对松材线虫的毒杀活性

【目的】探究4种烟碱受体激动剂对松材线虫的杀虫作用。【方法】采用浸渍法以及马尾松松枝水培试验分别进行杀线虫活性测定,并测定4种烟碱受体激动剂水溶液对松材线虫体内三磷酸腺苷酶(ATP)、过氧化氢酶(CAT)、乙酰胆碱酯酶(AChE)、超氧化物歧化酶(SOD)的影响。【结果】盐酸左旋咪唑、盐酸四咪唑、烟碱、酒石酸噻吩嘧啶4种烟碱受体激动剂对松材线虫有良好的毒杀活性,4种药物水溶液浸渍处理松材线虫48 h,半致死浓度LC_(50)值分别为0.09、0.31、0.08、0.14 mg·mL^(-1);马尾松水培试验处理12 d后结果显示,盐酸左旋咪唑、盐酸四咪唑、烟碱、CK处理组松枝均不发病,病情指数为0,酒石酸噻吩嘧啶处理组部分枝叶变黄,病情指数为31%,“CK+线虫”松枝枝叶完全变黄萎蔫,病情指数为100%;4种烟碱受体激动剂水溶液浸渍处理48 h后松材线虫体内ATP、CAT、AChE、SOD酶活性均低于对照组(P<0.05)。【结论】盐酸左旋咪唑、盐酸四咪唑、烟碱、酒石酸噻吩嘧啶对松材线虫有良好的防治潜力,具有进一步深入研究和开发利用的前景。

HPLC法检测保健品口服液中的盐酸左旋咪唑

目的:建立高效液相色谱法检测保健品口服液中盐酸左旋咪唑的方法。方法:采用C18-WR色谱柱(4.6 mm×250 mm,5μm),流动相为乙腈-0.05 mol/L磷酸二氢钾溶液(用三乙胺调节pH=7)(25∶75,体积比),流速1.0 mL/min,检测波长210 nm,柱温30℃,进样量10μL。结果:盐酸左旋咪唑在8.634~86.340μg/mL时与峰面积线性关系良好(R=0.9997);低、中、高加标量对应的平均回收率分别为99.7%、99.2%和100.3%,RSD分别为1.40%、0.64%和0.78%,检测限为0.4317μg/mL。随机对市售16批样品进行检测,均未检出盐酸左旋咪唑。结论:该方法简便、快速、准确,可用于保健品口服液中非法添加盐酸左旋咪唑的检测。

痰热清注射液治疗慢性阻塞性肺病急性加重期作用机制探讨

目的:研究痰热清注射液治疗慢性阻塞性肺病急性加重期作用机制。方法:在线查询TCMSP数据库、既往文献获取黄芩、熊胆粉、山羊角、金银花、连翘等中药的主要活性成分,利用swisstargetprediction数据库获取其活性成分对应靶点;利用GeneCards、OMMI、Drug Bank等数据库获取慢性阻塞性肺病急性加重期靶点。利用Venny平台在线获取药物与疾病靶点交集,通过DAVID数据库对相交靶点进行基因本体分析和通路富集分析,使用STRING数据库构建蛋白相互作用网络,借助Cytoscapr软件行可视化处理并筛选主要活性成分、关键靶点。最后通过AutoDock vina软件将核心靶点与核心成分进行分子对接验证,并利用pymol可视化处理。结果:痰热清注射液中含主要活性成分90个,对应靶点557个;连翘、黄芩、金银花为痰热清注射液的关键作用药物;baicalein、Norwogonin、5,7,4’-Trihydroxy-8-methoxyflavone、5,2’,6’-Trihydroxy-7,8-dimethoxyflavone、(2R)-7-hydroxy-5-methoxy-2-phenylchroman-4-one、Panicolin、Skullcapflavone II、Moslosooflavone、5,7,2,5-tetrahydroxy-8,6-dimethoxyflavone、quercetin等为核心活性成分;STAT3、HSP90AA1、ESR1、SRC、EP300、AKT1、JUN、PIK3R1、RELA等靶点为蛋白互作网络中的核心靶点。结论:痰热清注射液治疗主要通过黄酮类物质调节细胞炎症反应、细胞增殖、凋亡等对慢性阻塞性肺病急性加重期发挥潜在作用。

基于网络药理学及分子对接探讨二至丸治疗早发性卵巢功能不全的作用机制

目的基于网络药理学方法探讨二至丸治疗早发性卵巢功能不全(POI)的可能分子作用机制。方法使用网络药理学平台(TCMSP)采集二至丸的有效成分和相关的基因;通过基因组注释数据平台(GeneCards)、人类孟德尔遗传数据库(OMIM)数据库获取POI疾病靶点;用蛋白互作网络数据库(STRING)构建蛋白质相互作用网络(PPI),通过CytoHubba筛选核心靶点。使用生物学信息注释数据库(DAVID)平台进行富集分析,采用Cytoscape 3.10.0软件进行拓扑学分析,利用AutoDockTools进行分子对接。结果二至丸内最主要的有效成分为槲皮素、木犀草素、山柰酚、刺槐素等,其中的AKT1、TP53等是关键靶点,包含的通路主要为PI3K-Akt信号通路、流体剪切应力和动脉粥样硬化信号通路等。分子对接验证大部分靶点与成分能进行有效结合。结论揭示二至丸能够经多种成分、靶点及多条信号通路对POI发挥协同治疗作用。

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

We acknowledge our sincere thanks to our reviewers. Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of our World Series Journals. Both the editors of the journals and authors of the manuscripts submitted to the journals are grateful to the following reviewers

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Gastrointestinal

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Gastrointestinal

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

We acknowledge our sincere thanks to our reviewers.Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of our World Series Journals.Both the editors of the journals and authors of the manuscripts submitted to the journals are grateful to the following reviewers for reviewing the articles(either published or rejected) over the past period of time.

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Gastrointestinal Pharmacology and Therapeutics. The editors

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Gastrointestinal Pharmacology and Therapeutics.The editors and authors of the articles submitted to the journal are grateful to the

基于TLR4信号通路探讨扶正膏增强细胞免疫功能机制

目的基于Toll样受体4(TLR4)信号通路探讨扶正膏增强细胞免疫功能的机制。方法(1)将20只雄性ICR小鼠随机分为正常组、免疫功能低下组、扶正膏组、左旋咪唑组,每组5只。除正常组外,其余组小鼠均连续3 d腹腔注射环磷酰胺建立免疫功能低下模型。造模成功后,扶正膏组给予扶正膏2250 mg/kg灌胃,左旋咪唑组给予左旋咪唑20 mg/kg灌胃,空白组和免疫功能低下组给予等量生理盐水灌胃,均连续灌胃28 d。流式细胞术检测脾脏组织中CD3^(+)、CD4^(+)、CD8^(+)T细胞比例,Western blot法检测脾脏组织中TLR4、髓样分化因子88(MyD88)、白细胞介素-1受体相关激酶4(IRAK4)、肿瘤坏死因子受体相关因子6(TRAF6)蛋白表达情况。(2)取大鼠20只,给予扶正膏69.6 g/(kg·d)连续灌胃14 d制备扶正膏含药血清。体外分离、培养正常小鼠脾淋巴细胞,分为4组:正常组体外正常培养;扶正膏含药血清组加入10%扶正膏含药血清培养48 h;MyD88抑制剂组加入5μmol/L MyD88抑制剂ST2825培养8 h;MyD88抑制剂+含药血清组加入5μmol/L ST2825培养8 h后,离心去上清,然后加入10%扶正膏含药血清培养48 h。ELISA法检测细胞上清液中白细胞介素-2(IL-2)、干扰素-γ(IFN-γ)表达水平,Wsetern blot法检测脾淋巴细胞中TLR4、MyD88、IRAK4、TRAF6蛋白表达情况。结果免疫功能低下组脾脏组织中CD4^(+)T细胞比例和TLR4、MyD88、IRAK4、TRAF6蛋白相对表达量均明显低于正常组(P均<0.05),扶正膏组和左旋咪唑组CD4^(+)T细胞比例和TLR4、MyD88、IRAK4、TRAF6蛋白相对表达量均明显高于免疫功能低下组(P均<0.05)。扶正膏含药血清组脾淋巴细胞中IL-2、IFN-γ表达水平和TLR4、MyD88、IRAK4、TRAF6蛋白相对表达量均明显高于正常组、MyD88抑制剂组和MyD88抑制剂+含药血清组(P均<0.05),MyD88抑制剂组和MyD88抑制剂+含药血清组IL-2、IFN-γ表达水平和TLR4、MyD88、IRAK4、TRAF6蛋白相对表达量均明显低于正常组(P均<0.05),MyD88抑制剂组和MyD88抑制剂+含药血清组上述各指标比较差异均无统计学意义(P均>0.05)。结论扶正膏可能通过激活TLR4信号通路增强细胞免疫功能。

《医宗金鉴·正骨心法要旨》中治疗伤科瘀肿疼痛方剂的用药规律分析

目的:分析《医宗金鉴·正骨心法要旨》中治疗伤科瘀肿疼痛方剂的用药规律。方法:收集《医宗金鉴·正骨心法要旨》中治疗伤科瘀肿疼痛的方剂,对组方中药物的出现频次及药性、药味、归经、功效进行统计,分析用药规律。结果:共收集到《医宗金鉴·正骨心法要旨》中治疗瘀肿疼痛的内服、外用方剂57首,涉及中药179味。出现频次≥5的药物有35味,当归出现频次最多。药性出现频次较高的为温、寒、平,药味出现频次较高的为辛、苦、甘,归经主要归肝经、脾经、心经,药物功效主要为补虚、活血、清热。关联药物数最多的药物是当归,规则支持度最高的药物组合为川芎-当归;增益最高的药物组合为生姜-人参、甘草。核心药物组合有4组,分别为人参-生姜-大枣-茯苓-白术、柴胡-栀子-半夏-黄芩、当归-川芎-熟地黄-白芍、血竭-木香-酒。结论:《医宗金鉴·正骨心法要旨》中治疗伤科瘀肿疼痛的方剂多采用性温、味辛、归肝经的药物,核心药物组合以健脾益气、疏肝清火、补血活血、活血止痛药物为主,用药规律符合其专从血论、气血并重、消补并用的治伤思想。

左旋咪唑和莫西菌素联合用药在小尾寒羊体内药代动力学研究

为了获得莫西菌素和左旋咪唑单独及联合用药在小尾寒羊体内的药物代谢动力学数据,并比较单独用药及联合用药时药动学参数差异,选择36只健康小尾寒羊,随机分为左旋咪唑皮下8 mg/kg组(LEVSC8)、莫西菌素皮下0.2 mg/kg组(MXDSC0.2)、联合用药组(LEVSC8+MXDSC0.2)皮下注射给药,每组12只小尾寒羊。给药后的不同时间段于颈静脉采集血液,离心获得血浆样本,通过高效液相色谱方法测定血浆中药物浓度,并通过Wlinnonlin软件获得药动学参数,通过统计学分析软件进行显著性差异比较。结果显示,左旋咪唑单独应用时,在小尾寒羊体内的达峰浓度为(1.79±0.69)μg/mL,达峰时间为(1.29±0.68)h,药时曲线下面积为(8.69±2.69)μg·h/mL,消除半衰期为(3.37±1.57)h;左旋咪唑和莫西菌素联合应用时,左旋咪唑在小尾寒羊体内的达峰浓度为(1.64±0.72)μg/mL,达峰时间为(1.35±0.73)h,药时曲线下面积为(8.03±2.69)μg·h/mL,消除半衰期为(3.69±1.71)h。左旋咪唑和莫西菌素联合用药时的药动学参数与左旋咪唑单独用药时相比,无显著性差异(P>0.05)。莫西菌素单独用药时,在小尾寒羊体内的达峰浓度为(40.57±10.06)ng/mL,达峰时间为(1.08±0.53)d,药时曲线下面积为(168.76±29.39)ng·d/mL,消除半衰期为(5.76±1.36)d;与左旋咪唑联合应用时,莫西菌素在小尾寒羊体内的达峰浓度为(39.89±13.49)ng/mL,达峰时间为(1.36±0.46)d,药时曲线下面积为(152.69±35.96)ng·d/mL,消除半衰期为(6.36±1.79)d。莫西菌素和左旋咪唑联合用药时的药动学参数与莫西菌素单独用药时,无显著性差异(P>0.05)。表明左旋咪唑和莫西菌素联合应用时,莫西菌素与左旋咪唑在小尾寒羊体内无动力学相互作用。研究结果可为左旋咪唑和莫西菌素在小尾寒羊上的联合应用提供依据。