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International Journal for Parasitology, Drugs and Drug Resistance

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https://www.readbyqxmd.com/read/28826037/diglycosyl-diselenides-alter-redox-homeostasis-and-glucose-consumption-of-infective-african-trypanosomes
#1
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/28738214/plasmodium-falciparum-in%C3%A2-vitro-continuous-culture-conditions-a-comparison-of-parasite-susceptibility-and-tolerance-to-anti-malarial-drugs-throughout-the-asexual-intra-erythrocytic-life-cycle
#2
Sandra Duffy, Vicky M Avery
The continuous culture of Plasmodium falciparum is often seen as a means to an end, that end being to probe the biology of the parasite in question, and ultimately for many in the malaria drug discovery arena, to identify means of killing the parasite in order to treat malaria. In vitro continuous culture of Plasmodium falciparum is a fundamental requirement when undertaking malaria research where the primary objectives utilise viable parasites of a desired lifecycle stage. This investigation, and resulting data, compared the impact culturing Plasmodium falciparum long term (4 months) in different environmental conditions had on experimental outcomes and thus conclusions...
July 15, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28692943/progressive-increase-in-point-mutations-associates-chloroquine-resistance-even-after-withdrawal-of-chloroquine-use-in-india
#3
Sabyasachi Das, Satyajit Tripathy, Sourav Chattopadhayay, Balaram Das, Santanu Kar Mahapatra, Amiya Kumar Hati, Somenath Roy
Chloroquine (CQ) is highly effective against P. vivax, due to the rapid spread of CQ resistance in P. falciparum parasites; it is no longer the drug of choice against P. falciparum. This study elucidates the scenario of chloroquine efficacy at times that coincided with a new drug policy and especially assessed the chloroquine resistant molecular markers after withdrawal of chloroquine in Kolkata and Purulia, two malaria endemic zones of West Bengal, India. In vitro CQ susceptibility was tested in 781 patients with P...
June 29, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28719882/antileishmanial-activity-and-tubulin-polymerization-inhibition-of-podophyllotoxin-derivatives-on-leishmania-infantum
#4
José Miguel Escudero-Martínez, Yolanda Pérez-Pertejo, Rosa M Reguera, María Ángeles Castro, María Victoria Rojo, Carolina Santiago, Andrés Abad, Pablo Anselmo García, José Luis López-Pérez, Arturo San Feliciano, Rafael Balaña-Fouce
Leishmania microtubules play an important role not only in cell division, but also in keeping the shape of the parasite and motility of its free-living stages. Microtubules result from the self-assembly of alpha and beta tubulins, two phylogenetically conserved and very abundant eukaryotic proteins in kinetoplastids. The colchicine binding domain has inspired the discovery and development of several drugs currently in clinical use against parasites. However, this domain is less conserved in kinetoplastids and may be selectively targeted by new compounds...
June 28, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28697451/reduced-efficacy-of-albendazole-against-ascaris-lumbricoides-in-rwandan-schoolchildren
#5
Jürgen Krücken, Kira Fraundorfer, Jean Claude Mugisha, Sabrina Ramünke, Kevin C Sifft, Dominik Geus, Felix Habarugira, Jules Ndoli, Augustin Sendegeya, Caritas Mukampunga, Claude Bayingana, Toni Aebischer, Janina Demeler, Jean Bosco Gahutu, Frank P Mockenhaupt, Georg von Samson-Himmelstjerna
Control of human soil-transmitted helminths (STHs) relies on preventive chemotherapy of schoolchildren applying the benzimidazoles (BZ) albendazole or mebendazole. Anthelmintic resistance (AR) is a common problem in nematodes of veterinary importance but for human STHs, information on drug efficacy is limited and routine monitoring is rarely implemented. Herein, the efficacy of single dose albendazole (400 mg) was evaluated in 12 schools in the Huye district of Rwanda where Ascaris is the predominant STH. Ascaris eggs were detected by wet mount microscopy and the Mini-FLOTAC method to assess cure rate (CR) and faecal egg count reduction (FECR)...
June 23, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28732272/screening-of-the-open-scaffolds-collection-from-compounds-australia-identifies-a-new-chemical-entity-with-anthelmintic-activities-against-different-developmental-stages-of-the-barber-s-pole-worm-and-other-parasitic-nematodes
#6
Sarah Preston, Yaqing Jiao, Jonathan B Baell, Jennifer Keiser, Simon Crawford, Anson V Koehler, Tao Wang, Moana M Simpson, Ray M Kaplan, Karla J Cowley, Kaylene J Simpson, Andreas Hofmann, Abdul Jabbar, Robin B Gasser
The discovery and development of novel anthelmintic classes is essential to sustain the control of socioeconomically important parasitic worms of humans and animals. With the aim of offering novel, lead-like scaffolds for drug discovery, Compounds Australia released the 'Open Scaffolds' collection containing 33,999 compounds, with extensive information available on the physicochemical properties of these chemicals. In the present study, we screened 14,464 prioritised compounds from the 'Open Scaffolds' collection against the exsheathed third-stage larvae (xL3s) of Haemonchus contortus using recently developed whole-organism screening assays...
May 28, 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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
https://www.readbyqxmd.com/read/28366863/proteomic-and-functional-analyses-reveal-pleiotropic-action-of-the-anti-tumoral-compound-nbdhex-in-giardia-duodenalis
#18
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...
August 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
#19
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...
August 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
#20
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...
August 2017: International Journal for Parasitology, Drugs and Drug Resistance
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