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International Journal for Parasitology, Drugs and Drug Resistance

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https://www.readbyqxmd.com/read/28511056/elimination-of-schistosoma-mansoni-in-infected-mice-by-slow-release-of-artemisone
#1
Daniel Gold, Mohammed Alian, Avraham Domb, Yara Karawani, Maysa Jbarien, Jacques Chollet, Richard K Haynes, Ho Ning Wong, Viola Buchholz, Andreas Greiner, Jacob Golenser
The current treatment of schistosomiasis is based on the anti-helminthic drug praziquantel (PZQ). PZQ affects only the adult stages of schistosomes. In addition, resistance to PZQ is emerging. We suggest a drug, which could serve as a potential alternative or complement to PZQ, and as a means of treating infections at earlier, pre-granuloma stage. Derivatives of the peroxidic antimalarial drug artemisinin have been indicated as alternatives, because both plasmodia and schistosomes are blood-feeding parasites...
May 4, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28501715/mutations-in-the-hco-mptl-1-gene-in-a-field-derived-monepantel-resistant-isolate-of-haemonchus-contortus
#2
Neil H Bagnall, Angela Ruffell, Ali Raza, Timothy P Elliott, Jane Lamb, Peter W Hunt, Andrew C Kotze
Resistance to the anthelmintic drug monepantel (Zolvix(®)) has emerged in parasitic worms infecting sheep and goats. The mechanism of resistance in these cases is unknown. The drug targets nicotinic acetylcholine receptors belonging to the nematode-specific DEG-3 subfamily. We examined the receptor gene, Hco-mptl-1, in a highly Zolvix(®)-resistant and a -susceptible isolate of the parasitic nematode Haemonchus contortus. cDNA coding for the full length receptor protein (Hco-MPTL-1) was present in all clones prepared from a pool of susceptible larvae (21/21 clones) and approximately 50% of those from the resistant isolate (17/33)...
May 4, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28494332/polymorphism-in-abc-transporter-genes-of-dirofilaria-immitis
#3
Thangadurai Mani, Catherine Bourguinat, Roger K Prichard
Dirofilaria immitis, a filarial nematode, causes dirofilariasis in dogs, cats and occasionally in humans. Prevention of the disease has been mainly by monthly use of the macrocyclic lactone (ML) endectocides during the mosquito transmission season. Recently, ML resistance has been confirmed in D. immitis and therefore, there is a need to find new classes of anthelmintics. One of the mechanisms associated with ML resistance in nematodes has been the possible role of ATP binding cassette (ABC) transporters in reducing drug concentrations at receptor sites...
April 29, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28453984/functional-and-genetic-evidence-that-nucleoside-transport-is-highly-conserved-in-leishmania-species-implications-for-pyrimidine-based-chemotherapy
#4
Khalid J H Alzahrani, Juma A M Ali, Anthonius A Eze, Wan Limm Looi, Daniel N A Tagoe, Darren J Creek, Michael P Barrett, Harry P de Koning
Leishmania pyrimidine salvage is replete with opportunities for therapeutic intervention with enzyme inhibitors or antimetabolites. Their uptake into cells depends upon specific transporters; therefore it is essential to establish whether various Leishmania species possess similar pyrimidine transporters capable of drug uptake. Here, we report a comprehensive characterization of pyrimidine transport in L. major and L. mexicana. In both species, two transporters for uridine/adenosine were detected, one of which also transported uracil and the antimetabolites 5-fluoruracil (5-FU) and 5F,2'deoxyuridine (5F,2'dUrd), and was designated uridine-uracil transporter 1 (UUT1); the other transporter mediated uptake of adenosine, uridine, 5F,2'dUrd and thymidine and was designated Nucleoside Transporter 1 (NT1)...
April 20, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28437733/the-establishment-of-in%C3%A2-vitro-culture-and-drug-screening-systems-for-a-newly-isolated-strain-of-trypanosoma-equiperdum
#5
Keisuke Suganuma, Shino Yamasaki, Nthatisi Innocentia Molefe, Peter Simon Musinguzi, Batdorj Davaasuren, Ehab Mossaad, Sandagdorj Narantsatsral, Banzragch Battur, Badgar Battsetseg, Noboru Inoue
Dourine is caused by Trypanosoma equiperdum via coitus with an infected horse. Although dourine is distributed in Equidae worldwide and is listed as an internationally important animal disease by the World Organization for Animal Health (OIE), no effective treatment strategies have been established. In addition, there are no reports on drug discovery, because no drug screening system exists for this parasite. A new T. equiperdum strain was recently isolated from the genital organ of a stallion that showed typical symptoms of dourine...
April 13, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28433520/corrigendum-to-therapeutic-effect-of-ursolic-acid-in-experimental-visceral-leishmaniasis-int-j-parasitol-drugs-drug-resist-7-2017-1-11
#6
Jessica A Jesus, Thais N Fragoso, Eduardo S Yamamoto, Marcia D Laurenti, Marcelo S Silva, Aurea F Ferreira, João Henrique G Lago, Gabriela Santos-Gomes, Luiz Felipe D Passero
No abstract text is available yet for this article.
April 4, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28395189/novel-carbazole-aminoalcohols-as-inhibitors-of-%C3%AE-hematin-formation-antiplasmodial-and-antischistosomal-activities
#7
Weisi Wang, Qiang Li, Yufen Wei, Jian Xue, Xiao Sun, Yang Yu, Zhuo Chen, Shizhu Li, Liping Duan
Malaria and schistosomiasis are two of the most socioeconomically devastating parasitic diseases in tropical and subtropical countries. Since current chemotherapeutic options are limited and defective, there is an urgent need to develop novel antiplasmodials and antischistosomals. Hemozoin is a disposal product formed from the hemoglobin digestion by some blood-feeding parasites. Hemozoin formation is an essential process for the parasites to detoxify free heme, which is a reliable therapeutic target for identifying novel antiparasitic agents...
April 2, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28366863/proteomic-and-functional-analyses-reveal-pleiotropic-action-of-the-anti-tumoral-compound-nbdhex-in-giardia-duodenalis
#8
Serena Camerini, Alessio Bocedi, Serena Cecchetti, Marialuisa Casella, Miriam Carbo, Veronica Morea, Edoardo Pozio, Giorgio Ricci, Marco Lalle
Giardiasis, a parasitic diarrheal disease caused by Giardia duodenalis, affects one billion people worldwide. Treatment relies only on a restricted armamentarium of drugs. The disease burden and the increase in treatment failure highlight the need for novel, safe and well characterized drug options. The antitumoral compound NBDHEX is effective in vitro against Giardia trophozoites and inhibits glycerol-3-phosphate dehydrogenase. Aim of this work was to search for additional NBDHEX protein targets. The intrinsic NBDHEX fluorescence was exploited in a proteomic analysis to select and detect modified proteins in drug treated Giardia...
March 29, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28384505/the-vivax-surveyor-online-mapping-database-for-plasmodium-vivax-clinical-trials
#9
REVIEW
R J Commons, K Thriemer, G Humphreys, I Suay, C H Sibley, P J Guerin, R N Price
INTRODUCTION: Recurrent P. vivax infections are associated with significant morbidity and mortality. Although radical cure can reduce recurrent infection, it is confounded by antimalarial resistance and the lack of safe and effective hypnozoitocidal treatment. This study documents the available literature of published clinical trials of P. vivax, providing an up to date, online, open access tool to view and download available information. METHODS: A systematic review was conducted according to PRISMA guidelines to identify prospective P...
March 24, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28371660/exposure-of-heligmosomoides-polygyrus-and-trichuris-muris-to-albendazole-albendazole-sulfoxide-mebendazole-and-oxantel-pamoate-in%C3%A2-vitro-and-in%C3%A2-vivo-to-elucidate-the-pathway-of-drug-entry-into-these-gastrointestinal-nematodes
#10
Noemi Cowan, Charles Meier, Anna Neodo, Jennifer Keiser
Millions of people are treated with anthelmintics to control soil-transmitted helminth infections; yet, drug distribution in the plasma and gastrointestinal tract compartments and the pathway of drug uptake into gastrointestinal nematodes responsible for the pharmacological effect are unknown. We assessed the distribution and uptake of albendazole, albendazole sulfoxide, albendazole sulfone in the hookworm Heligmosomoides polygyrus in vitro and in vivo as well as the distribution and uptake of albendazole, mebendazole, and oxantel pamoate in the whipworm Trichuris muris in vitro and invivo...
March 24, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28355531/using-a-genome-scale-metabolic-network-model-to-elucidate-the-mechanism-of-chloroquine-action-in-plasmodium-falciparum
#11
Shivendra G Tewari, Sean T Prigge, Jaques Reifman, Anders Wallqvist
Chloroquine, long the default first-line treatment against malaria, is now abandoned in large parts of the world because of widespread drug-resistance in Plasmodium falciparum. In spite of its importance as a cost-effective and efficient drug, a coherent understanding of the cellular mechanisms affected by chloroquine and how they influence the fitness and survival of the parasite remains elusive. Here, we used a systems biology approach to integrate genome-scale transcriptomics to map out the effects of chloroquine, identify targeted metabolic pathways, and translate these findings into mechanistic insights...
March 22, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28319724/interactions-between-tafenoquine-and-artemisinin-combination-therapy-partner-drug-in-asexual-and-sexual-stage-plasmodium-falciparum
#12
Karen Kemirembe, Mynthia Cabrera, Liwang Cui
The 8-aminoquinoline tafenoquine (TFQ), a primaquine derivative, is currently in late-stage clinical development for the radical cure of P. vivax. Here drug interactions between TFQ and chloroquine and six artemisinin-combination therapy (ACT) partner drugs in P. falciparum asexual stages and gametocytes were investigated. TFQ was mostly synergistic with the ACT-partner drugs in asexual parasites regardless of genetic backgrounds. However, at fixed ratios of 1:3, 1:1 and 3:1, TFQ only interacted synergistically with naphthoquine, pyronaridine and piperaquine in gametocytes...
March 11, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28376349/genetic-diversity-of-next-generation-antimalarial-targets-a-baseline-for-drug-resistance-surveillance-programmes
#13
Ana Rita Gomes, Matt Ravenhall, Ernest Diez Benavente, Arthur Talman, Colin Sutherland, Cally Roper, Taane G Clark, Susana Campino
Drug resistance is a recurrent problem in the fight against malaria. Genetic and epidemiological surveillance of antimalarial resistant parasite alleles is crucial to guide drug therapies and clinical management. New antimalarial compounds are currently at various stages of clinical trials and regulatory evaluation. Using ∼2000 Plasmodium falciparum genome sequences, we investigated the genetic diversity of eleven gene-targets of promising antimalarial compounds and assessed their potential efficiency across malaria endemic regions...
March 9, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28285258/4-nitro-styrylquinoline-is-an-antimalarial-inhibiting-multiple-stages-of-plasmodium-falciparum-asexual-life-cycle
#14
Bracken F Roberts, Yongsheng Zheng, Jacob Cleaveleand, Sukjun Lee, Eunyoung Lee, Lawrence Ayong, Yu Yuan, Debopam Chakrabarti
Drugs against malaria are losing their effectiveness because of emerging drug resistance. This underscores the need for novel therapeutic options for malaria with mechanism of actions distinct from current antimalarials. To identify novel pharmacophores against malaria we have screened compounds containing structural features of natural products that are pharmacologically relevant. This screening has identified a 4-nitro styrylquinoline (SQ) compound with submicromolar antiplasmodial activity and excellent selectivity...
April 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28279945/quantitative-characterization-of-hemozoin-in-plasmodium-berghei-and-vivax
#15
John M Pisciotta, Peter F Scholl, Joel L Shuman, Vladimir Shualev, David J Sullivan
The incidence and global distribution of chloroquine resistant (CR) Plasmodium vivax infection has increased since emerging in 1989. The mechanism of resistance in CR P. vivax has not been defined. The resistance likely relates to the formation and disposition of hemozoin as chloroquine's primary mechanism of action involves disruption of hemozoin formation. CR P. berghei strains, like CR P. vivax strains, are confined to reticulocyte host cells and reportedly they do not accumulate appreciable intraerythrocytic hemozoin...
April 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28189117/blocking-transmission-of-vector-borne-diseases
#16
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...
April 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
#17
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...
April 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
#18
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...
April 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
#19
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...
April 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
#20
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...
April 2017: International Journal for Parasitology, Drugs and Drug Resistance
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