Antiparasitic Agents

抗寄生虫药
  • 文章类型: Journal Article
    Cyathostomins是马中最大的寄生虫组,可由伊维菌素(IVM)控制。这项研究旨在对28只自然感染的纯种一岁鸟进行IVM的四剂量滴定试验。据记录,当地的Strongyle种群对IVM(200µg/kg)具有抗性。进行寄生虫粪便卵计数(FEC)以研究IVM处理后两周和五周(w2pt和w5pt)的卵再现期(ERP)。所有组的FEC在第0天>1000。尽管所有浓度在w2pt时都报告了100%的FEC减少,FEC在w5pt显示<83%的疗效。这项研究报告了使用标签剂量以及300和400µg/kg(双倍剂量)的IVM减少了ERP。该协议允许IVM显著抑制FECw2pt,尽管不能消除成虫蠕虫,未能保证延长其保护期超过8周。此外,w5pt的FEC可能意味着感染没有被清除,虫子重新产卵。当药物在w5pt时FEC减少少于80%时,我们提出了撤回控制程序的IVM的可能性。
    Cyathostomins are the largest group of parasites in horses that can be controlled by ivermectin (IVM). This study aimed to run a four-dose titration trial of IVM in 28 naturally infected Thoroughbred yearlings. The local Strongyle population had been recorded to be resistant to IVM (200 µg/kg). The parasite fecal egg count (FEC) was performed to investigate the egg reappearance period (ERP) of two and five weeks (w2pt and w5pt) after IVM treatment. FEC was > 1000 on day zero for all groups. Although 100% FEC reduction was reported at w2pt for all concentrations, the FEC at w5pt revealed < 83% efficacy. This study reports the reduction of ERP using the label dose as well as 300, and 400 µg/kg (double dose) of IVM. The protocol allowed IVM to significantly suppress FEC w2pt although not eliminating adult worms, failing to guarantee an extension of its protection period over 8 weeks. Moreover, the FEC at w5pt possibly means the infection was not cleared, and worms reestablished egg laying. We raised the possibility of withdrawing IVM of control programs when the drug has less than 80% FEC reduction at w5pt.
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  • 文章类型: Journal Article
    在现代研究动物计划中,小鼠毛皮螨通常被排除在外,然而,由于检测和控制方面的挑战,感染继续存在。因为所有的诊断方法和治疗方案都有局限性,当试图根除这些外寄生虫时,程序必须做出许多操作决定。这项研究的主要目的是通过PCR测试和毛皮检查确定,评估伊维菌素复合饮食在消除小鼠中的Radfordiaaffinis的各种治疗时间。与当前的8周方案相比,较短的治疗持续时间将是非常有利的,因为它将最大限度地减少动物管理计划的成本和时间。研究的障碍,和伊维菌素药物对感染动物的影响。五个实验组的R.affinis阳性小鼠接受饮食伊维菌素0、2、4、6或8周。负毛螨,每8周向每个组中添加未处理的小鼠,以使侵染持续下去并扩增任何剩余的毛螨种群。在各自的治疗结束后16周,对所有处理组连同阳性对照组(未处理)进行PCR测试。还在每个时间点通过直接显微镜对毛皮进行螨虫和卵的视觉检查。如通过PCR测试和毛皮检查两者所证实的,在治疗结束后16周时,所有治疗的小鼠都没有亲缘的R.这些发现表明,饮食伊维菌素治疗持续时间短至2周有效地消除了。使成功的根除举措更容易实现。
    Murine fur mites are commonly excluded in modern research animal programs, yet infestations continue to persist due to challenges in detection and control. Because all diagnostic methods and treatment options have limitations, programs must make many operational decisions when trying to eradicate these ectoparasites. The primary aim of this study was to assess various durations of treatment time with an ivermectin-compounded diet in eliminating Radfordia affinis in mice as determined by PCR testing and pelt examination. A shorter treatment duration would be highly advantageous as compared with the current regimen of 8 wk as it would minimize cost and time for animal management programs, impediments to research, and ivermectin drug effects on infested animals. Five experimental groups of R. affinis -positive mice received dietary ivermectin for 0, 2, 4, 6, or 8 wk. A fur mite-negative, naïve mouse was added to each group every 8 wk to perpetuate the infestation and amplify any remaining populations of fur mites. At 16 wk after the respective treatment end, PCR testing was performed for all treated groups in conjunction with the positive control group (no treatment). Visual examination of pelts for mites and eggs via direct microscopy was also performed at each time point. All treated mice were free of R. affinis at 16 wk after the end of treatment as confirmed by both PCR testing and pelt examination. These findings indicate that a dietary ivermectin treatment duration of as little as 2 wk is effective in eliminating R. affinis, making successful eradication initiatives more achievable.
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  • 文章类型: Letter
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  • 文章类型: Journal Article
    病原体如疟原虫,巴贝西亚,Theileria入侵并在宿主红细胞内繁殖,导致疟疾的病理后果,babesiosis,和Theileriosis。建立连续的体外培养系统和合适的动物模型对于研究这些病原体至关重要。这篇评论聚焦了小鼠培养(ICIM)模型中的Babesiaduncani作为推进生物学研究的有希望的资源,致病性,和红细胞内寄生虫的毒力。该模型提供了实际的好处,包括明确定义的培养条件,易于操纵,和一个注释良好的基因组。此外,B.duncani作为药物发现的代理系统,促进体外和动物体内新的抗寄生虫药物的评估,阐明他们的行动模式,并发现潜在的抵抗机制。因此,B.duncaniICIM模型作为一个具有深远意义的多方面工具出现,我们对寄生虫生物学的理解和未来疗法的发展有希望。
    Pathogens such as Plasmodium, Babesia, and Theileria invade and multiply within host red blood cells, leading to the pathological consequences of malaria, babesiosis, and theileriosis. Establishing continuous in vitro culture systems and suitable animal models is crucial for studying these pathogens. This review spotlights the Babesia duncani in culture-in mouse (ICIM) model as a promising resource for advancing research on the biology, pathogenicity, and virulence of intraerythrocytic parasites. The model offers practical benefits, encompassing well-defined culture conditions, ease of manipulation, and a well-annotated genome. Moreover, B. duncani serves as a surrogate system for drug discovery, facilitating the evaluation of new antiparasitic drugs in vitro and in animals, elucidating their modes of action, and uncovering potential resistance mechanisms. The B. duncani ICIM model thus emerges as a multifaceted tool with profound implications, promising advancements in our understanding of parasitic biology and shaping the development of future therapies.
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  • 文章类型: Journal Article
    Fluazuron是一种新型的兽用倾注型防虱制剂,可与牛繁殖管理策略同时应用。考虑到许多国家畜牧业的经济重要性,重要的是要知道抗寄生虫药如氟拉隆是否会导致胚胎丢失。本研究的目的是评估氟天隆在体外成熟过程中对牛卵母细胞的毒理学作用。在中国仓鼠卵巢(CHO)-K1细胞的初步实验中确定了最佳的氟天隆浓度,并进一步用于比较两种研究模型中的氟天隆毒性。膜联蛋白V和碱性单细胞凝胶电泳测定的结果表明,在所有测试浓度(50、75和100μg氟天隆/mL)下,氟天隆均在牛卵丘细胞中引起细胞毒性和遗传毒性。对皮质颗粒和线粒体分布的评估表明,氟氟隆处理不影响细胞质成熟。然而,中期II+极体的减少,在所有测试浓度下,都观察到了简并的卵母细胞以及极体中的染色质紊乱。而50μg/mL氟拉隆没有改变受精过程,胚胎发育率显著下降。在评估的任何氧化应激参数中均未观察到显着差异。这项研究有助于更好地了解牛中的氟氟隆,这表明抗寄生虫可能会影响牛的繁殖,并可能导致胚胎丢失。
    Fluazuron is a novel veterinary pour-on antitick formulation which can be applied simultaneously with bovine reproduction management strategies. Considering the economic importance of the livestock industry in many countries, it is important to know whether antiparasitics such as fluazuron may cause embryonic loss. The aim of this study was to evaluate the toxicological effect of fluazuron on bovine oocytes during in vitro maturation. The best fluazuron concentrations were determined in a preliminary experiment on Chinese hamster ovary (CHO)-K1 cells and further used to compare fluazuron toxicity in both study models. Results of the annexin V and alkaline single cell gel electrophoresis assays demonstrated that fluazuron caused cytotoxicity and genotoxicity in bovine cumulus cells at all the concentrations tested (50, 75 and 100 μg fluazuron/mL). The evaluation of cortical granules and mitochondria distribution showed that cytoplasmic maturation was not affected by fluazuron treatment. However, a decrease in metaphase II + polar body, degenerate oocytes as well as disorganized chromatin in polar body were observed at all concentrations tested. Whereas the fertilization process was not altered by 50 μg/mL fluazuron, the embryo development rate decreased significantly. No significant differences were observed in any of the oxidative stress parameters assessed. This study contributes to a better understanding of fluazuron in bovines, suggesting that the antiparasitic may affect bovine reproduction and might cause embryo loss.
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  • 文章类型: News
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  • 文章类型: Journal Article
    在印度东部,葛根的块茎(威尔德。)DC。因其广泛的药用和营养价值而被种族社区使用,特别是恢复牲畜健康和治疗蠕虫病。该研究旨在评估结核分枝杆菌作为驱虫药的民族兽医学重要性,验证其无毒性质,并通过计算机分子对接技术鉴定最有效的植物成分。使用八个定量指标对从185个线人收集的民族医学数据进行了定量分析,以突出使用多样性和植物中最常用的部分。采用的某些指数得分很高,如使用值(UV=0.52),保真度水平(FL=68.42%)和组织重要性值(TIV=1)清楚地说明了有关块茎部分用于治疗兽用动物肠道蠕虫病的医学营养益处的种族医学线索。基于这个民族指导的线索,块根已经通过对总酚的估计进行了化学分析研究,黄酮类化合物,单宁和生物碱,以及HPLC和GC-MS分析。通过对畜禽鸟类的某些蠕虫的体外研究,用块茎提取物评估了驱虫性能,它显示了对测试的寄生虫,即棉草,四角拉利蒂娜和塞洛里亚。使用Vero细胞和BALB/c小鼠通过体外和体内方法进行块茎提取物的毒性评估。即使在较高的实验剂量下,也观察到所研究的块茎提取物的无毒性质。在通过GC-MS分析鉴定的12种植物化合物中,一种化合物[Morphinan-4,5-环氧-3,6-二醇,6-(7-硝基苯并呋喃-4-基)氨基-]在最低结合能值的成本中表现出最佳的结合构象,其中包括一种抗炎药,一种抗氧化剂,和四种驱虫蛋白.我们的研究结果非常令人鼓舞,可以进一步深入评估这种块茎药物,以开发驱虫兽药。
    In eastern India, the tubers of Pueraria tuberosa (Willd.) DC. are used by the ethnic communities for its wide range of medicinal and nutritional value, especially to rejuvenate livestock health and to treat helminthiasis. The study is aimed to evaluate the ethnoveterinary medicinal importance of P. tuberosa as anthelmintic, to verify its nontoxic nature and identify the most potent phytoconstituents aided by in silico molecular docking technique. Ethnomedicinal data collected from 185 informants were quantitatively analyzed employing eight quantitative indices to highlight the use diversity and most frequently used part of the plant. High scores of certain indices employed, such as Use Value (UV = 0.52), Fidelity Level (FL = 68.42%) and Tissue Importance Value (TIV = 1) clearly illustrate an ethnomedicinal lead regarding medico-nutritional benefits of the tuber part used against intestinal helminthic diseases of veterinary animals. Based on this ethno-guided lead, root tuber has been investigated for its chemical profiling by the estimation of total phenolics, flavonoids, tannins and alkaloids, along with HPLC and GC-MS analyses. Anthelmintic property was evaluated with the tuber extracts by in vitro studies on some helminths of livestock and poultry birds, and it showed promising results against the tested parasites namely Cotylophoron cotylophorum, Raillietina tetragona and Setaria cervi. Toxicity assessments of tuber extract through in vitro and in vivo methods were performed using Vero cells and BALB/c mice. Nontoxic nature of the studied tuber extract was observed even in higher experimental doses. Out of 12 phytocompounds identified by GC-MS analysis, one compound [Morphinan-4,5-epoxy-3,6-di-ol,6- (7-nitrobenzofurazan-4-yl) amino-] exhibited the best binding conformations in cost of the lowest binding energy values with six target proteins that include one anti-inflammatory, one antioxidant, and four anthelmintic proteins. The findings of our study are found very encouraging to evaluate this tuber drug furthermore intensively towards the development of anthelmintic veterinary medicine.
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  • 文章类型: Journal Article
    恰加斯病是由寄生虫克氏锥虫引起的,影响全球700多万人。两种实际的治疗方法,苯并硝唑(Bzn)和硝呋替莫,导致严重的副作用,因为它们的高毒性导致患者放弃治疗。在这项工作中,我们提出DNAG-四链体(G4)作为这种感染性疾病的潜在治疗靶点.我们在克氏锥虫基因组中发现了每100,000个核苷酸174个PQS,并证实了三个频繁基序的G4形成。我们合成了基于二噻吩乙烯(DTE)支架的14个四链体配体家族,并证明了它们与这些鉴定的G4序列的结合。几种DTE衍生物对四种不同品系的克氏毛虫表现出微摩尔活性,在与BZN相同的浓度范围内。化合物L3和L4对色素动物具有显着的活性,血液中的活性形式,克氏杆菌SOL菌株(IC50=1.5-3.3μM,SI=25-40.9),活性比Bzn高40倍左右,选择性指数更好。
    Chagas disease is caused by the parasite Trypanosoma cruzi and affects over 7 million people worldwide. The two actual treatments, Benznidazole (Bzn) and Nifurtimox, cause serious side effects due to their high toxicity leading to treatment abandonment by the patients. In this work, we propose DNA G-quadruplexes (G4) as potential therapeutic targets for this infectious disease. We have found 174 PQS per 100,000 nucleotides in the genome of T. cruzi and confirmed G4 formation of three frequent motifs. We synthesized a family of 14 quadruplex ligands based in the dithienylethene (DTE) scaffold and demonstrated their binding to these identified G4 sequences. Several DTE derivatives exhibited micromolar activity against epimastigotes of four different strains of T. cruzi, in the same concentration range as Bzn. Compounds L3 and L4 presented remarkable activity against trypomastigotes, the active form in blood, of T. cruzi SOL strain (IC50 = 1.5-3.3 μM, SI = 25-40.9), being around 40 times more active than Bzn and displaying much better selectivity indexes.
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  • 文章类型: News
    你有没有在上个月的BBC的Springwatch上看到BVA总裁AnnaJudson,谈论兽医可以采取的措施来帮助减少杀寄生虫剂对环境的影响?
    Did you spot BVA President Anna Judson on BBC\'s Springwatch last month, talking about the measures vets can take to help minimise the impact of parasiticides on the environment?
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  • 文章类型: Journal Article
    伊维菌素(Ivermectin,IVM)是一种广泛使用的抗寄生虫药。人们对里奥德拉普拉塔盆地湿地的环境影响感到担忧,那里的牛已经接受了IVM治疗多年。这项研究调查了沉积物中与环境相关的IVM浓度对新热带鱼类Prochilodus谱系的亚致死作用。幼年假单胞菌暴露于掺有IVM的沉积物(2和20µg/Kg)14天,除了没有IVM的对照沉积物处理之外。在大脑中评估生化和氧化应激反应,ill,和肝脏组织,包括脂质损伤,谷胱甘肽水平,酶活性,和抗氧化能力。还测量了肌肉和脑乙酰胆碱酯酶活性(AChE)以及肌肉中13C和15N的稳定同位素。最低的IVM治疗导致脑脂质过氧化增加,通过硫代巴比妥酸反应性物质(TBARs)测量,减少的还原型谷胱甘肽(GSH)在胆和肝脏的水平,肝脏过氧化氢酶活性(CAT)增加,和减少的抗氧化能力对过氧化自由基(ACAP)在the和肝脏。最高IVM治疗显著降低肝脏中的GSH。在两种治疗中肌肉(AChE)均降低。多变量分析显示肝脏组织的总体影响显著,其次是ill和大脑。这些发现证明了IVM在直线疟原虫中的亚致死作用,强调在现实的暴露场景中考虑沉积物污染和营养习惯的重要性。
    Ivermectin (IVM) is a widely used antiparasitic. Concerns have been raised about its environmental effects in the wetlands of Río de la Plata basin where cattle have been treated with IVM for years. This study investigated the sublethal effects of environmentally relevant IVM concentrations in sediments on the Neotropical fish Prochilodus lineatus. Juvenile P. lineatus were exposed to IVM-spiked sediments (2 and 20 µg/Kg) for 14 days, alongside a control sediment treatment without IVM. Biochemical and oxidative stress responses were assessed in brain, gills, and liver tissues, including lipid damage, glutathione levels, enzyme activities, and antioxidant competence. Muscle and brain acetylcholinesterase activity (AChE) and stable isotopes of 13C and 15N in muscle were also measured. The lowest IVM treatment resulted in an increase in brain lipid peroxidation, as measured by thiobarbituric acid reactive substances (TBARs), decreased levels of reduced glutathione (GSH) in gills and liver, increased catalase activity (CAT) in the liver, and decreased antioxidant capacity against peroxyl radicals (ACAP) in gills and liver. The highest IVM treatment significantly reduced GSH in the liver. Muscle (AChE) was decreased in both treatments. Multivariate analysis showed significant overall effects in the liver tissue, followed by gills and brain. These findings demonstrate the sublethal effects of IVM in P. lineatus, emphasizing the importance of considering sediment contamination and trophic habits in realistic exposure scenarios.
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