Anthelmintics

驱虫药
  • 文章类型: Journal Article
    背景:依赖吡喹酮治疗和控制血吸虫病可能会促进耐药性的出现。迫切需要针对成年和幼年血吸虫的联合治疗,以提高吡喹酮的疗效并延迟潜在的耐药性发展。我们评估了单剂量吡喹酮联合单剂量青蒿琥酯加次硫烯-乙胺嘧啶治疗肯尼亚血吸虫病儿童的疗效和安全性。
    方法:这是一个开放标签,纳入426名学龄儿童(7-15岁)的随机临床试验被诊断为曼氏血吸虫(Kato-Katz)或血吸虫链球菌(通过尿液过滤)。他们被随机分配(1:1:1)接受单剂量吡喹酮(40mg/kg),单剂量青蒿琥酯加次硫烯-乙胺嘧啶(12mg/kg青蒿琥酯)或使用单剂量吡喹酮(40mg/kg)联合单剂量青蒿琥酯加次硫烯-乙胺嘧啶(12mg/kg青蒿琥酯)的联合治疗。主要结果是在可用病例人群中治疗后6周时的治愈和减卵率。治疗后3小时内评估不良事件。
    结果:在注册的426名儿童中,135收到吡喹酮,150名接受青蒿琥酯加亚硫烯-乙胺嘧啶,141人接受联合治疗。结果数据为348(81.7%)儿童。对于S.mansoni感染的儿童(n=335),治愈率为75.6%,60.7%,77.8%,减蛋率为80.1%,85.0%,吡喹酮占88.4%,青蒿琥酯加次硫烯-乙胺嘧啶,和联合治疗,分别。对于S.Hematomium感染的儿童(n=145),相应的治愈率为81.4%,71.1%,和82.2%,产蛋率为95.6%,97.1%,和97.7%,分别。71名(16.7%)儿童报告轻度不良事件。药物耐受性良好,未报告严重不良事件。
    结论:单次口服吡喹酮联合青蒿琥酯加次硫烯-乙胺嘧啶可治愈高比例的儿童血吸虫病,但对泌尿或肠道血吸虫病的治疗效果均无显著改善。吡喹酮和青蒿琥酯加次硫烯-乙胺嘧啶的顺序给药可提高疗效和安全性。
    BACKGROUND: Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult and juvenile schistosome worms is urgently needed to improve praziquantel efficacy and delay the potential development of drug resistance. We assessed the efficacy and safety of single-dose praziquantel combined with single-dose artesunate plus sulfalene-pyrimethamine in the treatment of Kenyan children with schistosomiasis.
    METHODS: This was an open-label, randomised clinical trial involving 426 school-aged children (7-15 years old) diagnosed with Schistosoma mansoni (by Kato-Katz) or S. haematobium (by urine filtration). They were randomly assigned (1:1:1) to receive a single dose of praziquantel (40 mg/kg), a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate) or combination therapy using a single dose of praziquantel (40 mg/kg) combined with a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate). The primary outcome was cure and egg reduction rates at 6 weeks post-treatment in the available case population. Adverse events were assessed within 3 h after treatment.
    RESULTS: Of the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data were available for 348 (81.7%) children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and the egg reduction rates were 80.1%, 85.0%, and 88.4% for praziquantel, artesunate plus sulfalene-pyrimethamine, and combination therapy, respectively. For S. haematobium-infected children (n = 145), the corresponding cure rates were 81.4%, 71.1%, and 82.2%, and the egg reduction rates were 95.6%, 97.1%, and 97.7%, respectively. Seventy-one (16.7%) children reported mild-intensity adverse events. The drugs were well tolerated and no serious adverse events were reported.
    CONCLUSIONS: A single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not significantly improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes.
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  • 文章类型: Journal Article
    基线制图显示,血吸虫病在塞拉利昂9个地区高度/中度流行。2009年开始使用吡喹酮进行大规模药物治疗(MDA),经过多轮治疗,我们在2016年进行了影响评估,随后在2022年采用整群抽样进行了第二次重新评估,为完善cheefdom(分区)治疗策略提供更细粒度的数据.
    平均而言,每个地区按与9个地区的人口规模成正比的概率系统地选择了20个农村村庄。调查是在学校进行的,随机抽取24名年龄在5至14岁之间的学童,男孩和女孩的数量相等。每个儿童收集一个粪便样本和一个尿液样本。每个粪便检查了两个Kato-Katz载玻片是否感染曼氏血吸虫。使用Hemastix条带作为血尿阳性样品的卵计数的尿液过滤的替代。
    总共,在125个酋长领地的200所学校中检查了4,736个粪便样本和4,618个尿液样本。总的来说,曼氏链球菌的患病率为16.3%(95%CI:15.3-17.4%),而血尿的总患病率为2.0%(95%CI:1.6-2.4%)。MansoniS.和HematobiumS.重型感染的患病率分别为1.5%(95%CI:1.1-1.9%)和0.02%(95%CI:0.0-0.14%),分别。在接受调查的125个酋长中,在65个土族中,血吸虫病的总体患病率<10%,在47个酋长领地中占10-49.9%,在13个酋长领地中≥50%。学童中的血吸虫病与学校中的WASH接触之间存在混合关系。
    经过十年的MDA干预,塞拉利昂在降低全国血吸虫病患病率方面取得了重大进展。然而,一些热点地区的流行率仍然很高。接下来的步骤是国家计划,以调查和解决任何潜在的问题,例如对血吸虫病风险行为的覆盖率低或知识不足,在适当的情况下,考虑扩大到热点酋长或社区的社区范围治疗。
    UNASSIGNED: Baseline mapping showed that schistosomiasis was highly/moderately endemic in nine districts in Sierra Leone. Mass drug administration (MDA) with praziquantel started in 2009, and after multiple rounds of treatment, an impact assessment was conducted in 2016 followed by a second re-assessment in 2022 using cluster sampling to provide more granular data for refining chiefdom (sub-district) treatment strategies.
    UNASSIGNED: On average, 20 rural villages were systematically selected per district by probability proportional to population size across the nine districts. Surveys were conducted in schools, and 24 school children aged between 5 and 14 years were randomly selected, with an equal number of boys and girls. One stool sample and one urine sample were collected per child. Two Kato-Katz slides were examined per stool for Schistosoma mansoni infection. Hemastix strips were used as a proxy for S. haematobium infection with urine filtration used for egg counts on hematuria-positive samples.
    UNASSIGNED: In total, 4,736 stool samples and 4,618 urine samples were examined across 200 schools in 125 chiefdoms. Overall, the prevalence of S. mansoni was 16.3% (95% CI: 15.3-17.4%), while the overall prevalence of S. haematobium was 2.0% (95% CI: 1.6-2.4%) by hematuria. The prevalence of heavy infections for S. mansoni and S. haematobium was 1.5% (95% CI: 1.1-1.9%) and 0.02% (95% CI: 0.0-0.14%), respectively. Among 125 chiefdoms surveyed, the overall schistosomiasis prevalence was <10% in 65 chiefdoms, 10-49.9% in 47 chiefdoms, and ≥ 50% in 13 chiefdoms. There was a mixed relationship between schistosomiasis in school children and WASH access in schools.
    UNASSIGNED: Sierra Leone has made significant progress in reducing schistosomiasis prevalence across the country after a decade of MDA intervention. However, high prevalence remains in some hotspot chiefdoms. The next steps are for the national program to investigate and address any potential issues such as low coverage or poor knowledge of schistosomiasis risk behaviors and, where appropriate, consider broadening to community-wide treatment in hotspot chiefdoms or communities.
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  • 文章类型: Case Reports
    背景:血吸虫病是许多发展中国家的地方性寄生虫病之一。尽管如此,即使在某些流行地区,血吸虫病继发的阑尾炎也是一种罕见的疾病。血吸虫阑尾炎,偶然发现的与血吸虫病组织学发现相关的阑尾炎,主要影响年轻男性。及时诊断和治疗,包括阑尾切除术和抗蠕虫疗法,是至关重要的。
    方法:一名24岁的苏丹男性患者出现腹痛。诊断为急性阑尾炎,他做了阑尾切除术,显示阑尾炎症与血吸虫卵的组织病理学。腹部超声检测无并发症。注意到血吸虫血清学弱阳性,但粪便和尿液分析显示没有感染证据。处方吡喹酮,患者术后3年随访,无并发症.
    结论:本病例报告强调了在阑尾炎的鉴别诊断中包括血吸虫病的重要性,特别是在疾病流行的地区。它强调了组织病理学评估对准确诊断的必要性,强调在类似环境中对临床实践的潜在影响。
    BACKGROUND: Schistosomiasis is one of the endemic parasitic diseases in many developing countries. Despite this, appendicitis secondary to schistosomiasis is an uncommon condition even in some endemic areas. Schistosomal appendicitis, an incidentally discovered appendicitis associated with schistosomiasis histological findings, affects young males predominantly. Timely diagnosis and treatment, including appendectomy and anti-helminthic therapy, are crucial.
    METHODS: A 24-year-old Sudanese male patient presented with abdominal pain. Diagnosed with acute appendicitis, he underwent appendectomy, revealing appendix inflammation with Schistosoma ova in histopathology. Abdominal ultrasound detected no complications. Weakly positive Schistosoma serology was noted, but stool and urine analysis showed no infection evidence. Prescribed praziquantel, patient had 3-year post-op follow-up without complications.
    CONCLUSIONS: This case report underscores the significance of including schistosomiasis in the differential diagnosis of appendicitis, particularly in regions where the disease is endemic. It underscores the necessity of histopathological evaluations for accurate diagnosis, emphasizing the potential implications for clinical practice in similar settings.
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  • 文章类型: Journal Article
    肝片吸虫引起的筋膜病是世界范围内的重大公共卫生和经济问题。由于缺乏成功的疫苗和新出现的对药物曲拉莫达唑的耐药性,正在研究替代的植物治疗方法。这项研究调查了薰衣草(Lavandulaangustifolia)和角豆树(CeratoniasiliquaL.)精油(EOs)对肝菌的体外驱虫活性。体外研究基于卵孵化试验(EHA),成人运动抑制试验,DNA损伤,活性氧(ROS)水平以及几种氧化应激生物标志物,包括谷胱甘肽过氧化物酶(GSH),和谷胱甘肽-S-转移酶(GST),超氧化物歧化酶(SOD)和丙二醛(MDA)。为此,不同浓度的L.angustifolia和C.siliquaEOs(1,5,10,25和50mg/mL)用于评估对不同生命阶段的驱虫作用,包括鸡蛋,和成人肝肝病毒24小时。结果表明,这些EO作为驱虫药起重要作用,效果取决于时间和浓度。在体外处理的F.hepitca蠕虫与L.angustifolia和C.siliquaEOs增加DNA损伤,ROS的产生和氧化应激的诱导(降低SOD,GST和GSH,并增加MDA),与对照组相比。因此,可以得出结论,沙棘状芽孢杆菌和C.siliquaEO具有用作控制和治疗肝肠弧菌感染的新型药物的潜力。需要进一步的研究来研究其用于治疗寄生虫感染的体内药理学潜力和有效性。
    Fasciolosis caused by Fasciola hepatica is a major public health and economic problem worldwide. Due to the lack of a successful vaccine and emerging resistance to the drug triclabendazole, alternative phytotherapeutic approaches are being investigated. This study investigated the in vitro anthelmintic activity of Lavender (Lavandula angustifolia) and carob (Ceratonia siliqua L.) essential oils (EOs) against F. hepatica. The in vitro study was based on an egg hatch assay (EHA), adult motility inhibition assays, DNA damage, reactive oxygen species (ROS) level along with several oxidative stress biomarkers including glutathione peroxidase (GSH), and glutathione-S-transferase (GST), superoxide dismutase (SOD) and malondialdehyde (MDA). To this end, different concentrations of L. angustifolia and C. siliqua EOs (1, 5, 10, 25 and 50 mg/mL) were used to assess anthelmintic effects on different life stages including egg, and adults of F. hepatica for 24 hrs. The results indicated that these EOs play a significant role as anthelminthics, and the effect was dependent on time and concentration. The in vitro treatment of F. hepatica worms with both L. angustifolia and C. siliqua EOs increased DNA damage, ROS production and induction of oxidative stress (decreased SOD, GST and GSH, and increased MDA), significantly compared to control. Therefore, it can be concluded that L. angustifolia and C. siliqua EOs have the potential to be used as novel agents for the control and treatment of F. hepatica infections. Further studies are required to investigate their pharmacological potential and effectiveness in vivo for the treatment of parasitic infections.
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  • 文章类型: Journal Article
    扭曲血门是一种以血液为食的胃肠道寄生虫,会影响放牧的绵羊,在动物生产中造成经济损失。由于其驱虫抗性,有必要探索替代的抗寄生虫治疗方法,例如基于植物的驱虫药。蒿属植物正己烷提取物和乙酸乙酯提取物对H.contortus具有驱虫活性,正己烷更活跃。为了发现额外的生物活性代谢物,对乙酸乙酯提取物进行了化学分析,其LC90为3.30mg/mL,并允许分离11-[(1R,5S,7R,8R,10S,)-1,8-二羟基-5,10-二甲基-4-氧代十氢氮烯-7-基]丙烯酸。通过一维和二维NMR鉴定了这种新的倍半萜。该化合物命名为肉桂酸,LC50为0.13(0.11-0.14)mg/mL,LC90为0.40(0.37-0.44)mg/mL,which,与乙酸乙酯提取物的杀幼虫活性相比,在LC50时活性高256倍,在LC90时活性高15.71倍。在这项研究中,从蒿蒿的乙酸乙酯提取物中分离出一种对H.contortusL3感染幼虫具有杀虫活性的新倍半萜。
    Haemonchus contortus is a blood-feeding gastrointestinal parasite that impacts grazing sheep, causing economic losses in animal production. Due to its anthelmintic resistance, alternative antiparasitic treatments like plant-based anthelmintics are necessary to explore. Artemisia cina (Asteraceae) is a plant whose n-hexane extract and ethyl acetate extract exhibit anthelmintic activity against H. contortus, the n-hexane more active. To discover additional bioactive metabolites, a chemical analysis was performed on ethyl acetate extract, which presented an LC90 of 3.30 mg/mL and allowed the isolation of 11-[(1R,5S,7R,8R,10S,)-1,8-dihydroxy-5,10-dimethyl-4-oxodecahydroazulen-7-yl] acrylic acid. This new sesquiterpene was identified through one and two-dimensional NMR. The compound was named cinic acid and displayed an LC50 of 0.13 (0.11-0.14) mg/mL and LC90 of 0.40 (0.37-0.44) mg/mL, which, compared with ethyl acetate extract larvicidal activity, was 256-fold more active at LC50 and 15.71-fold at LC90. In this study, a new sesquiterpene with larvicidal activity against H. contortus L3 infective larvae was isolated from the ethyl acetate extract of Artemisia cina.
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  • 文章类型: Journal Article
    在苏丹,最近有报道称,南达尔富尔的牛和山羊对苯并咪唑具有抗药性。在这里,在南达尔富尔的三个研究区域的绵羊和山羊中评估了伊维菌素对胃肠道线虫(GINs)的功效。粪便卵数减少试验(FECRT)用于评估伊维菌素在Bulbul地区自然感染GINs的绵羊和山羊(山羊:n=106)中的功效,卡斯(山羊:n=40)和尼亚拉(Domaia(绵羊:n=47,山羊:n=77)和大学农场(山羊:n=52)),使用不同的治疗方案,治疗后12天评价疗效。还使用来自Kass和Nyala的局部hemonchuscontortus分离株在实验感染的山羊中评估了伊维菌素的功效。收获了在Bulbul和Nyala的山羊中存活的伊维菌素处理的线虫,并使用幼虫感染无蠕虫的雄性绵羊(n=6,≤6个月大)。每八天对感染的绵羊皮下给予伊维菌素,剂量从0.2mg/kg增加到1.6mg/kg体重(bw)。在四个研究地点的绵羊和山羊中发现伊维菌素功效降低。使用成对统计量,治疗剂量在绵羊中的功效为75.6%(90%可信上限(UCrL):77.5%),而推荐剂量的两倍导致92.6%的减少(90%UCrL:93.3%)。在山羊中,Bulbul治疗剂量的FECRs为72.9-95.3%(90%UCrL范围:73.6-95.7%),尼亚拉·多玛亚,尼亚拉大学农场和卡斯。推荐给Bulbul山羊的剂量的两倍显示90%UCrL为87.6%。所有处理后的粪便培养物仅包含Haemonchusspp。幼虫.绵羊和山羊的实验性感染试验支持我们从田间试验中得出的发现,并计算出90%CrL的上限低于98.9%。在苏丹的绵羊和山羊中首次发现了高度抗伊维菌素的H.contortus种群,抗性得到了实验证实。
    In Sudan, resistance to benzimidazoles has been reported recently in cattle and goats from South Darfur. Herein, ivermectin efficacy against gastrointestinal nematodes (GINs) was evaluated in sheep and goats in three study areas in South Darfur. The faecal egg count reduction test (FECRT) was used to evaluate the efficacy of ivermectin in sheep and goats naturally infected with GINs in the region of Bulbul (goats: n = 106), Kass (goats: n = 40) and Nyala (Domaia (sheep: n = 47, goats: n = 77) and the University farm (goats: n = 52)), using different treatment plans, and the efficacy was evaluated 12 days after treatment. Ivermectin efficacy was also evaluated in goats experimentally infected using local Haemonchus contortus isolates from Kass and Nyala. Nematodes surviving ivermectin treatment in goats in Bulbul and Nyala were harvested and larvae used to infect worm-free male sheep (n = 6, ≤6 months old). Infected sheep were dosed subcutaneously with ivermectin every eight days with increasing doses from 0.2 mg/kg to 1.6 mg/kg bodyweight (bw). Reduced ivermectin efficacy was identified in sheep and goats in the four study locations. Using a paired statistic, the efficacy of a therapeutic dose in sheep was 75.6% (90% upper credible limit (UCrL): 77.5%), while twice the recommended dose led to a reduction of 92.6% (90% UCrL: 93.3%). In goats, the FECRs of a therapeutic dose were 72.9-95.3% (90% UCrL range: 73.6-95.7%) in Bulbul, Nyala Domaia, Nyala University farm and Kass. Twice the dose recommended for goats in Bulbul revealed a 90% UCrL of 87.6%. All post-treatment faecal cultures contained only Haemonchus spp. larvae. The experimental infection trials in sheep and goats supported our findings from field trials and calculated upper 90% CrL of below 98.9%. For the first time highly ivermectin resistant H. contortus populations have been identified in sheep and goats in Sudan, and resistance was experimentally confirmed.
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  • 文章类型: Journal Article
    WHO建议在感染率超过20%的地区对肠道蠕虫感染进行大规模药物管理(MDA)。最近的Cochrane荟萃分析支持对感染个体的治疗,但建议不要使用MDA。我们对多剂量MDA的效果进行了理论不可知的随机效应荟萃分析和成本-效果分析。我们估计MDA对儿童体重的显着影响(0.15kg,95%CI:0.07,0.24;P<0.001),中上臂周长(0.20cm,95%CI:0.03,0.37;P=0.02),和高度(0.09厘米,95%CI:0.01,0.16;P=0.02)当患病率超过20%但Hb(0.06g/dL,95%CI:-0.01,0.14;P=0.1)。这些结果表明MDA是一种具有成本效益的干预措施,特别是在世界卫生组织推荐的环境中。
    The WHO recommends mass drug administration (MDA) for intestinal worm infections in areas with over 20% infection prevalence. Recent Cochrane meta-analyses endorse treatment of infected individuals but recommend against MDA. We conducted a theory-agnostic random-effects meta-analysis of the effect of multiple-dose MDA and a cost-effectiveness analysis. We estimate significant effects of MDA on child weight (0.15 kg, 95% CI: 0.07, 0.24; P < 0.001), mid-upper arm circumference (0.20 cm, 95% CI: 0.03, 0.37; P = 0.02), and height (0.09 cm, 95% CI: 0.01, 0.16; P = 0.02) when prevalence is over 20% but not on Hb (0.06 g/dL, 95% CI: -0.01, 0.14; P = 0.1). These results suggest that MDA is a cost-effective intervention, particularly in the settings where it is recommended by the WHO.
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  • 文章类型: Journal Article
    BrugiaMalayi是线状寄生虫,是淋巴丝虫病(LF)的病因之一。现有的治疗LF的驱虫药可有效减少人血液中的幼虫微丝病(mf)计数,但对成年寄生虫的作用较差。为了测试潜在的候选药物,我们报道了一种多参数表型检测方法,该方法是在体外追踪成年马来西亚芽孢杆菌和mf的运动性。对于成年B.Malayi,运动性的特征是质心速度,路径曲率,角速度,偏心率,范围,欧拉数。在使用三种驱虫药的实验中评估这些参数。对于B.MalayiMf,从不断发展的身体骨架中提取运动性,以在74个关键点处产生位置数据和弯曲角度。我们实现了复杂蠕虫姿势的高保真跟踪(自遮挡,欧米茄转身,身体弯曲,和逆转),同时在空间和时间尺度上提供姿势估计和行为属性的视觉表示。
    Brugia malayi are thread-like parasitic worms and one of the etiological agents of Lymphatic filariasis (LF). Existing anthelmintic drugs to treat LF are effective in reducing the larval microfilaria (mf) counts in human bloodstream but are less effective on adult parasites. To test potential drug candidates, we report a multi-parameter phenotypic assay based on tracking the motility of adult B. malayi and mf in vitro. For adult B. malayi, motility is characterized by the centroid velocity, path curvature, angular velocity, eccentricity, extent, and Euler Number. These parameters are evaluated in experiments with three anthelmintic drugs. For B. malayi mf, motility is extracted from the evolving body skeleton to yield positional data and bending angles at 74 key point. We achieved high-fidelity tracking of complex worm postures (self-occlusions, omega turns, body bending, and reversals) while providing a visual representation of pose estimates and behavioral attributes in both space and time scales.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    秀丽隐杆线虫是实验进化和抗寄生虫药物工作的一个有吸引力的工具,从了解药物作用和耐药性的分子机制到发现新的药物靶点。我们提出了一种研究抗寄生虫药物对秀丽隐杆线虫影响的新方法。粘性培养基最初设计用于在长期进化实验期间维持秀丽隐杆线虫。粘性培养基提供了比标准线虫生长培养基琼脂结构较少的环境,然而细菌食物来源仍然暂停。Further,粘性介质为蠕虫种群提供了足够的支持来自由移动,mate,并以与标准琼脂培养物相当的速度繁殖。这里,粘性培养基适用于抗寄生虫研究。我们观察到秀丽隐杆线虫对驱虫药的敏感性与标准液体培养基相似,并且通过幼虫发育测定与标准琼脂培养基有统计学差异。在秀丽隐杆线虫研究中使用粘性培养基将大大提高抗寄生虫抗性研究,这种培养基可用于旨在了解长期多代药物活性的研究。
    Caenorhabditis elegans is an appealing tool for experimental evolution and for working with antiparasitic drugs, from understanding the molecular mechanisms of drug action and resistance to uncover new drug targets. We present a new methodology for studying the impact of antiparasitic drugs in C. elegans. Viscous medium was initially designed for C. elegans maintenance during long-term evolution experiments. Viscous medium provides a less structured environment than the standard nematode growth media agar, yet the bacteria food source remains suspended. Further, the Viscous medium offers the worm population enough support to move freely, mate, and reproduce at a rate comparable to standard agar cultures. Here, the Viscous medium was adapted for use in antiparasitic research. We observed a similar sensitivity of C. elegans to anthelmintic drugs as in standard liquid media and statistical difference to the standard agar media through a larval development assay. Using Viscous medium in C. elegans studies will considerably improve antiparasitic resistance research, and this medium could be used in studies aimed at understanding long-term multigenerational drug activity.
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