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International Journal for Parasitology, Drugs and Drug Resistance

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https://www.readbyqxmd.com/read/28189117/blocking-transmission-of-vector-borne-diseases
#1
REVIEW
Sandra Schorderet-Weber, Sandra Noack, Paul M Selzer, Ronald Kaminsky
Vector-borne diseases are responsible for significant health problems in humans, as well as in companion and farm animals. Killing the vectors with ectoparasitic drugs before they have the opportunity to pass on their pathogens could be the ideal way to prevent vector borne diseases. Blocking of transmission might work when transmission is delayed during blood meal, as often happens in ticks. The recently described systemic isoxazolines have been shown to successfully prevent disease transmission under conditions of delayed pathogen transfer...
January 30, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28171818/a-novel-in%C3%A2-vitro-image-based-assay-identifies-new-drug-leads-for-giardiasis
#2
Christopher J S Hart, Taylah Munro, Katherine T Andrews, John H Ryan, Andrew G Riches, Tina S Skinner-Adams
Giardia duodenalis is an intestinal parasite that causes giardiasis, a widespread human gastrointestinal disease. Treatment of giardiasis relies on a small arsenal of compounds that can suffer from limitations including side-effects, variable treatment efficacy and parasite drug resistance. Thus new anti-Giardia drug leads are required. The search for new compounds with anti-Giardia activity currently depends on assays that can be labour-intensive, expensive and restricted to measuring activity at a single time-point...
January 27, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28161555/investigating-anthelmintic-efficacy-against-gastrointestinal-nematodes-in-cattle-by-considering-appropriate-probability-distributions-for-faecal-egg-count-data
#3
J W Love, L A Kelly, H E Lester, I Nanjiani, M A Taylor, C Robertson
The Faecal Egg Count Reduction Test (FECRT) is the most widely used field-based method for estimating anthelmintic efficacy and as an indicator of the presence of anthelmintic resistant nematodes in cattle, despite never having been validated against the gold standard of controlled slaughter studies. The objectives of this study were to assess the normality of cattle faecal egg count (FEC) data and their transformed versions, since confidence intervals used to aid the interpretation of the FECRT, are derived from data assumed to be normally distributed, and violation of this assumption could potentially lead to the misclassification of anthelmintic efficacy...
January 16, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28129569/investigating-the-antiplasmodial-activity-of-primary-sulfonamide-compounds-identified-in-open-source-malaria-data
#4
Gillian M Fisher, Silvia Bua, Sonia Del Prete, Megan S J Arnold, Clemente Capasso, Claudiu T Supuran, Katherine T Andrews, Sally-Ann Poulsen
In the past decade there has been a significant reduction in deaths due to malaria, in part due to the success of the gold standard antimalarial treatment - artemisinin combination therapies (ACTs). However the potential threat of ACT failure and the lack of a broadly effective malaria vaccine are driving efforts to discover new chemical entities (NCEs) to target this disease. The primary sulfonamide (PS) moiety is a component of several clinical drugs, including those for treatment of kidney disease, glaucoma and epilepsy, however this chemotype has not yet been exploited for malaria...
January 13, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28110187/insecticidal-activities-of-histone-deacetylase-inhibitors-against-a-dipteran-parasite-of-sheep-lucilia-cuprina
#5
Neil H Bagnall, Barney M Hines, Andrew J Lucke, Praveer K Gupta, Robert C Reid, David P Fairlie, Andrew C Kotze
Histone deacetylase inhibitors (HDACi) are being investigated for the control of various human parasites. Here we investigate their potential as insecticides for the control of a major ecto-parasite of sheep, the Australian sheep blowfly, Lucilia cuprina. We assessed the ability of HDACi from various chemical classes to inhibit the development of blowfly larvae in vitro, and to inhibit HDAC activity in nuclear protein extracts prepared from blowfly eggs. The HDACi prodrug romidepsin, a cyclic depsipeptide that forms a thiolate, was the most potent inhibitor of larval growth, with equivalent or greater potency than three commercial blowfly insecticides...
January 10, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28107750/effect-of-clinically-approved-hdac-inhibitors-on-plasmodium-leishmania-and-schistosoma-parasite-growth
#6
Ming Jang Chua, Megan S J Arnold, Weijun Xu, Julien Lancelot, Suzanne Lamotte, Gerald F Späth, Eric Prina, Raymond J Pierce, David P Fairlie, Tina S Skinner-Adams, Katherine T Andrews
Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. In this study, four clinically approved anti-cancer drugs (Vorinostat, Belinostat, Panobinostat and Romidepsin) that target histone/lysine deacetylase enzymes were examined for in vitro activity against Plasmodium knowlesi, Schistosoma mansoni, Leishmania amazonensis and L...
December 23, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28040568/in%C3%A2-vitro-drug-susceptibility-of-two-strains-of-the-wildlife-trypanosome-trypanosoma-copemani-a-comparison-with-trypanosoma-cruzi
#7
Adriana Botero, Sarah Keatley, Christopher Peacock, R C Andrew Thompson
Trypanosomes are blood protozoan parasites that are capable of producing illness in the vertebrate host. Within Australia, several native Trypanosoma species have been described infecting wildlife. However, only Trypanosoma copemani has been associated with pathological lesions in wildlife hosts and more recently has been associated with the drastic decline of the critically endangered woylie (Bettongia penicillata). The impact that some trypanosomes have on the health of the vertebrate host has led to the development of numerous drug compounds that could inhibit the growth or kill the parasite...
December 23, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28038431/comparative-effects-of-histone-deacetylases-inhibitors-and-resveratrol-on-trypanosoma-cruzi-replication-differentiation-infectivity-and-gene-expression
#8
Vanina A Campo
Histone post-translational modification, mediated by histone acetyltransferases and deacetylases, is one of the most studied factors affecting gene expression. Recent data showing differential histone acetylation states during the Trypanosoma cruzi cell cycle suggest a role for epigenetics in the control of this process. As a starting point to study the role of histone deacetylases in the control of gene expression and the consequences of their inhibition and activation in the biology of T. cruzi, two inhibitors for different histone deacetylases: trichostatin A for class I/II and sirtinol for class III and the activator resveratrol for class III, were tested on proliferative and infective forms of this parasite...
December 21, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28033523/-s-5-ethynyl-anabasine-a-novel-compound-is-a-more-potent-agonist-than-other-nicotine-alkaloids-on-the-nematode-asu-acr-16-receptor
#9
Fudan Zheng, Xiangwei Du, Tsung-Han Chou, Alan P Robertson, Edward W Yu, Brett VanVeller, Richard J Martin
Nematode parasites infect ∼2 billion people world-wide. Infections are treated and prevented by anthelmintic drugs, some of which act on nicotinic acetylcholine receptors (nAChRs). There is an unmet need for novel therapeutic agents because of concerns about the development of resistance. We have selected Asu-ACR-16 from a significant nematode parasite genus, Ascaris suum, as a pharmaceutical target and nicotine as our basic moiety (EC50 6.21 ± 0.56 μM, Imax 82.39 ± 2.52%) to facilitate the development of more effective anthelmintics...
December 9, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27984757/therapeutic-effect-of-ursolic-acid-in-experimental-visceral-leishmaniasis
#10
Jéssica A Jesus, Thais N Fragoso, Eduardo S Yamamoto, Márcia D Laurenti, Marcelo S Silva, Aurea F Ferreira, João Henrique G Lago, Gabriela S Gomes, Luiz Felipe D Passero
Leishmaniasis is an important neglected tropical disease, affecting more than 12 million people worldwide. The available treatments are not well tolerated and present diverse side effects in patients, justifying the search for new therapeutic compounds. In the present study, the therapeutic potential and toxicity of ursolic acid (UA), isolated from the leaves of Baccharis uncinella C. DC. (Asteraceae), were evaluated in experimental visceral leishmaniasis. To evaluate the therapeutic potential of UA, hamsters infected with L...
December 8, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27915061/modelling-the-consequences-of-targeted-selective-treatment-strategies-on-performance-and-emergence-of-anthelmintic-resistance-amongst-grazing-calves
#11
Zoe Berk, Yan C S M Laurenson, Andrew B Forbes, Ilias Kyriazakis
The development of anthelmintic resistance by helminths can be slowed by maintaining refugia on pasture or in untreated hosts. Targeted selective treatments (TST) may achieve this through the treatment only of individuals that would benefit most from anthelmintic, according to certain criteria. However TST consequences on cattle are uncertain, mainly due to difficulties of comparison between alternative strategies. We developed a mathematical model to compare: 1) the most 'beneficial' indicator for treatment selection and 2) the method of selection of calves exposed to Ostertagia ostertagi, i...
December 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27888770/the-effect-of-the-disulfideisomerase-domain-containing-protein-in-the-defense-against-polyhexamethylene-biguanide-of-highly-tolerant-acanthamoeba-at-the-trophozoite-stage
#12
Fu-Chin Huang, Tao-Shen Liu, Sung-Chou Li, Min-Hsiu Shih, Jyh-Wei Shin, Wei-Chen Lin
Acanthamoeba castellanii is a free-living protozoan pathogen capable of causing a blinding keratitis and fatal granulomatous encephalitis. Current treatment generally involves an hourly application of polyhexamethylene biguanide (PHMB) over a period of several days but this is not entirely effective against all strains/isolates. The tolerance mechanisms of PHMB in Acanthamoeba cells remain unclear. In this study, we found that the mRNA expression level of disulfideisomerase domain containing protein (PDI) increased rapidly in surviving cells of the highly PHMB-tolerant Acanthamoeba castellanii strain, NCKH_D, during PHMB treatment, but not in the ATCC standard strain...
December 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27835769/efficacy-of-ivermectin-against-gastrointestinal-nematodes-of-cattle-in-denmark-evaluated-by-different-methods-for-analysis-of-faecal-egg-count-reduction
#13
Miguel Peña-Espinoza, Stig M Thamsborg, Matthew J Denwood, Markus Drag, Tina V Hansen, Vibeke F Jensen, Heidi L Enemark
The efficacy of ivermectin (IVM) against gastrointestinal nematodes in Danish cattle was assessed by faecal egg count reduction test (FECRT). Six cattle farms with history of clinical parasitism and avermectin use were included. On the day of treatment (Day 0), 20 naturally infected calves per farm (total n = 120) were stratified by initial faecal egg counts (FEC) and randomly allocated to a treatment group dosed with 0.2 mg IVM kg(-1) body weight s.c. (IVM; n = 10) or an untreated control group (CTL; n = 10)...
December 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27821282/benzimidazole-resistance-survey-for-haemonchus-teladorsagia-and-trichostrongylus-in-three-european-countries-using-pyrosequencing-including-the-development-of-new-assays-for-trichostrongylus
#14
Sabrina Ramünke, Lynsey Melville, Laura Rinaldi, Hubertus Hertzberg, Theo de Waal, Georg von Samson-Himmelstjerna, Giuseppe Cringoli, Fabien Mavrot, Philip Skuce, Jürgen Krücken, Janina Demeler
Resistance to benzimidazoles (BZs) in trichostrongyloid nematodes is a worldwide problem for livestock production, particularly regarding small ruminants. Sensitive and reliable methods are required to assess anthelmintic resistance status. Currently available methods for BZ resistance detection can be divided into three main groups, in vivo (e.g. faecal egg count reduction test), in vitro (e.g. egg hatch assay) and molecular tests. Three single nucleotide polymorphisms (SNPs) in the isotype-1 β-tubulin gene of various nematode species correlate with BZ resistance...
December 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27821281/molecular-determinants-of-sulfadoxine-pyrimethamine-resistance-in-plasmodium-falciparum-in-nigeria-and-the-regional-emergence-of-dhps-431v
#15
Mary C Oguike, Catherine O Falade, Elvis Shu, Izehiuwa G Enato, Ismaila Watila, Ebenezer S Baba, Jane Bruce, Jayne Webster, Prudence Hamade, Sylvia Meek, Daniel Chandramohan, Colin J Sutherland, David Warhurst, Cally Roper
There are few published reports of mutations in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr) genes in P. falciparum populations in Nigeria, but one previous study has recorded a novel dhps mutation at codon 431 among infections imported to the United Kingdom from Nigeria. To assess how widespread this mutation is among parasites in different parts of the country and consequently fill the gap in sulfadoxine-pyrimethamine (SP) resistance data in Nigeria, we retrospectively analysed 1000 filter paper blood spots collected in surveys of pregnant women and children with uncomplicated falciparum malaria between 2003 and 2015 from four sites in the south and north...
December 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27814986/anthelmintics-from-discovery-to-resistance-ii-san-diego-2016
#16
REVIEW
Richard J Martin, Adrian J Wolstenholme, Conor R Caffrey
The second scientific meeting in the series: "Anthelmintics: From Discovery to Resistance" was held in San Diego in February, 2016. The focus topics of the meeting, related to anthelmintic discovery and resistance, were novel technologies, bioinformatics, commercial interests, anthelmintic modes of action and anthelmintic resistance. Basic scientific, human and veterinary interests were addressed in oral and poster presentations. The delegates were from universities and industries in the US, Europe, Australia and New Zealand...
December 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27770751/effects-of-a-novel-%C3%AE-lapachone-derivative-on-trypanosoma-cruzi-parasite-death-involving-apoptosis-autophagy-and-necrosis
#17
Danielle Oliveira Dos Anjos, Eliomara Sousa Sobral Alves, Vinicius Tomaz Gonçalves, Sheila Suarez Fontes, Mateus Lima Nogueira, Ana Márcia Suarez-Fontes, João Batista Neves da Costa, Fabricio Rios-Santos, Marcos André Vannier-Santos
Natural products comprise valuable sources for new antiparasitic drugs. Here we tested the effects of a novel β-lapachone derivative on Trypanosoma cruzi parasite survival and proliferation and used microscopy and cytometry techniques to approach the mechanism(s) underlying parasite death. The selectivity index determination indicate that the compound trypanocidal activity was over ten-fold more cytotoxic to epimastigotes than to macrophages or splenocytes. Scanning electron microscopy analysis revealed that the R72 β-lapachone derivative affected the T...
December 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27760394/two-benzimidazole-resistance-associated-snps-in-the-isotype-1-%C3%AE-tubulin-gene-predominate-in-haemonchus-contortus-populations-from-eight-regions-in-china
#18
Zongze Zhang, Robin B Gasser, Xin Yang, Fangyuan Yin, Guanghui Zhao, Min Bao, Baoliang Pan, Weiyi Huang, Chunren Wang, Fengcai Zou, Yanqin Zhou, Junlong Zhao, Rui Fang, Min Hu
Haemonchus contortus is one of the most important parasitic nematodes of small ruminants around the world, particularly in tropical and subtropical regions. The control of haemonchosis relies mainly on anthelmintics, but the excessive and prolonged use of anthelmintics is causing serious drug resistance issues in many countries. As benzimidazole (BZ) anthelmintics have been broadly used in China, we hypothesized that resistance is widespread. Given the link between three known single nucleotide polymorphisms (SNPs, designated F167Y, E198A and F200Y) in the isotype-1 β-tubulin gene and BZ resistance, our goal here was to explore the presence of these mutations in H...
December 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27751868/microfluidic-platform-for-electrophysiological-recordings-from-host-stage-hookworm-and-ascaris-suum-larvae-a-new-tool-for-anthelmintic-research
#19
Janis C Weeks, William M Roberts, Kristin J Robinson, Melissa Keaney, Jon J Vermeire, Joseph F Urban, Shawn R Lockery, John M Hawdon
The screening of candidate compounds and natural products for anthelmintic activity is important for discovering new drugs against human and animal parasites. We previously validated in Caenorhabditis elegans a microfluidic device ('chip') that records non-invasively the tiny electrophysiological signals generated by rhythmic contraction (pumping) of the worm's pharynx. These electropharyngeograms (EPGs) are recorded simultaneously from multiple worms per chip, providing a medium-throughput readout of muscular and neural activity that is especially useful for compounds targeting neurotransmitter receptors and ion channels...
December 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27746191/in-silico-analysis-of-the-binding-of-anthelmintics-to-caenorhabditis-elegansp-glycoprotein-1
#20
Marion A David, Stéphane Orlowski, Roger K Prichard, Shaima Hashem, François André, Anne Lespine
Macrocyclic lactones (ML) are important anthelmintics used in animals and humans against parasite nematodes, but their therapeutic success is compromised by the spread of ML resistance. Some ABC transporters, such as p-glycoproteins (Pgps), are selected and overexpressed in ML-resistant nematodes, supporting a role for some drug efflux proteins in ML resistance. However, the role of such proteins in ML transport remains to be clarified at the molecular level. Recently, Caenorhabditis elegans Pgp-1 (Cel-Pgp-1) has been crystallized, and its drug-modulated ATPase function characterized in vitro revealed Cel-Pgp-1 as a multidrug transporter...
December 2016: International Journal for Parasitology, Drugs and Drug Resistance
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