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International Journal for Parasitology, Drugs and Drug Resistance

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https://www.readbyqxmd.com/read/29035735/transcriptome-profiling-identifies-genes-pathways-associated-with-experimental-resistance-to-paromomycin-in-leishmania-donovani
#1
Aditya Verma, Vasundhra Bhandari, Deepak Kumar Deep, Shyam Sundar, Jean Claude Dujardin, Ruchi Singh, Poonam Salotra
Widespread resistance towards antimony and reports of relapses following miltefosine treatment has severely affected the management of visceral leishmaniasis (VL) in the Indian subcontinent. Paromomycin (PMM), an aminoglycoside antibiotic, has been licensed for VL treatment in India in 2007. Although its use is still restricted in the field, unraveling the molecular mechanism of resistance towards PMM is the key to preserve the drug. In this study, PMM resistant lines were selected up to 100 μM of PMM in three distinct field isolates of Leishmania donovani at promastigote stage...
October 10, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29040909/treatment-with-fenofibrate-plus-a-low-dose-of-benznidazole-attenuates-cardiac-dysfunction-in-experimental-chagas-disease
#2
Ágata C Cevey, Gerardo A Mirkin, Martín Donato, María J Rada, Federico N Penas, Ricardo J Gelpi, Nora B Goren
Trypanosoma cruzi induces serious cardiac alterations during the chronic infection. Intense inflammatory response observed from the beginning of infection, is critical for the control of parasite proliferation and evolution of Chagas disease. Peroxisome proliferator-activated receptors (PPAR)-α, are known to modulate inflammation. In this study we investigated whether a PPAR-α agonist, Fenofibrate, improves cardiac function and inflammatory parameters in a murine model of T. cruzi infection. BALB/c mice were sequentially infected with two T...
October 7, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29035734/comparison-of-constitutive-and-thiabendazole-induced-expression-of-five-cytochrome-p450-genes-in-fourth-stage-larvae-of-haemonchus-contortus-isolates-with-different-drug-susceptibility-identifies-one-gene-with-high-constitutive-expression-in-a-multi-resistant
#3
Esra Yilmaz, Sabrina Ramünke, Janina Demeler, Jürgen Krücken
Benzimidazoles (BZs) remain amongst the most widely used anthelmintic drug classes against gastro-intestinal nematode infections, although their efficacy is increasingly compromised by resistance. The primary underlying mechanisms for BZ resistance are single-nucleotide polymorphisms (SNPs) in the isotype 1 β-tubulin gene causing the substitutions F167Y, E198A or F200Y. However, resistance is believed to be multi-genic and previous studies have shown that isolates carrying 90-100% F200Y can vary considerably in their resistance level in the egg hatch assay (EHA)...
October 7, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29032180/genomic-analysis-of-isometamidium-chloride-resistance-in-trypanosoma-congolense
#4
Eliane Tihon, Hideo Imamura, Frederik Van den Broeck, Lieve Vermeiren, Jean-Claude Dujardin, Jan Van Den Abbeele
Isometamidium Chloride (ISM) is one of the principal drugs used to counteract Trypanosoma congolense infection in livestock, both as a prophylactic as well as a curative treatment. However, numerous cases of ISM resistance have been reported in different African regions, representing a significant constraint in the battle against Animal African Trypanosomiasis. In order to identify genetic signatures associated with ISM resistance in T. congolense, the sensitive strain MSOROM7 was selected for induction of ISM resistance in a murine host...
October 6, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28988014/l-asparaginase-of-leishmania-donovani-metabolic-target-and-its-role-in-amphotericin-b-resistance
#5
Jasdeep Singh, Mohd Imran Khan, Shiv Pratap Singh Yadav, Ankit Srivastava, Kislay K Sinha, Ashish, Pradeep Das, Bishwajit Kundu
Emergence of Amphotericin B (AmB) resistant Leishmania donovani has posed major therapeutic challenge against the parasite. Consequently, combination therapy aimed at multiple molecular targets, based on proteome wise network analysis has been recommended. In this regard we had earlier identified and proposed L-asparaginase of Leishmania donovani (LdAI) as a crucial metabolic target. Here we report that both LdAI overexpressing axenic amastigote and promastigote forms of L. donovani survives better when challenged with AmB as compared to wild type strain...
September 28, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28918001/in%C3%A2-vitro-evaluation-of-antimicrobial-agents-on-acanthamoeba-sp-and-evidence-of-a-natural-resilience-to-amphotericin-b
#6
Alexandre Taravaud, Philippe M Loiseau, Sébastien Pomel
The free-living amoeba (FLA) Acanthamoeba sp. is an opportunistic pathogen that can cause amoebic keratitis (AK) or granulomatous amoebic encephalitis (GAE). While current treatments of AK are long with some relapses, no consensus therapy has been developed for GAE remaining lethal in 90% of the cases. In this context, efficient antiacanthamoebal drugs have to be identified. In this work, 15 drugs used in the treatment of AK or GAE or in other parasitic diseases were evaluated for their in vitro activity on A...
September 8, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28910741/drug-susceptibility-testing-in-microaerophilic-parasites-cysteine-strongly-affects-the-effectivities-of-metronidazole-and-auranofin-a-novel-and-promising-antimicrobial
#7
David Leitsch
The microaerophilic parasites Entamoeba histolytica, Trichomonas vaginalis, and Giardia lamblia annually cause hundreds of millions of human infections which are treated with antiparasitic drugs. Metronidazole is the most often prescribed drug but also other drugs are in use, and novel drugs with improved characteristics are constantly being developed. One of these novel drugs is auranofin, originally an antirheumatic which has been relabelled for the treatment of parasitic infections. Drug effectivity is arguably the most important criterion for its applicability and is commonly assessed in susceptibility assays using in vitro cultures of a given pathogen...
September 5, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28826037/diglycosyl-diselenides-alter-redox-homeostasis-and-glucose-consumption-of-infective-african-trypanosomes
#8
Jaime Franco, Florencia Sardi, László Szilágyi, Katalin E Kövér, Krisztina Fehér, Marcelo A Comini
With the aim to develop compounds able to target multiple metabolic pathways and, thus, to lower the chances of drug resistance, we investigated the anti-trypanosomal activity and selectivity of a series of symmetric diglycosyl diselenides and disulfides. Of 18 compounds tested the fully acetylated forms of di-β-D-glucopyranosyl and di-β-D-galactopyranosyl diselenides (13 and 15, respectively) displayed strong growth inhibition against the bloodstream stage of African trypanosomes (EC50 0.54 μM for 13 and 1...
August 12, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28886443/antiplasmodial-activities-of-dyes-against-plasmodium-falciparum-asexual-and-sexual-stages-contrasted-uptakes-of-triarylmethanes-brilliant-green-green-s-e142-and-patent-blue-v-e131-by-erythrocytes
#9
Louis-Jérôme Leba, Jean Popovici, Yannick Estevez, Stéphane Pelleau, Eric Legrand, Lise Musset, Christophe Duplais
The search for safe antimalarial compounds acting against asexual symptom-responsible stages and sexual transmission-responsible forms of Plasmodium species is one of the major challenges in malaria elimination programs. So far, among current drugs approved for human use, only primaquine has transmission-blocking activity. The discovery of small molecules targeting different Plasmodium falciparum life stages remains a priority in antimalarial drug research. In this context, several independent studies have recently reported antiplasmodial and transmission-blocking activities of commonly used stains, dyes and fluorescent probes against P...
August 2, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28623818/the-rule-of-five-should-not-impede-anti-parasitic-drug-development
#10
James H McKerrow, Christopher A Lipinski
The "rule of 5" has become a mainstay of decision-making in the pharmaceutical industry as well as in nonindustrial (academic and institutional) drug development. However the authors of the original paper never intended for "double cutoffs" to preclude development of new drug leads for parasitic diseases.
August 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28511056/elimination-of-schistosoma-mansoni-in-infected-mice-by-slow-release-of-artemisone
#11
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...
August 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
#12
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)...
August 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28494332/polymorphism-in-abc-transporter-genes-of-dirofilaria-immitis
#13
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...
August 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
#14
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)...
August 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
#15
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...
August 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
#16
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.
August 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
#17
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...
August 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
#18
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...
August 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
#19
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...
August 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
#20
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 in vivo...
August 2017: International Journal for Parasitology, Drugs and Drug Resistance
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