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International Journal for Parasitology, Drugs and Drug Resistance

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/27733308/profiling-the-macrofilaricidal-effects-of-flubendazole-on-adult-female-brugia-malayi-using-rnaseq
#15
Maeghan O'Neill, Cristina Ballesteros, Lucienne Tritten, Erica Burkman, Weam I Zaky, Jianguo Xia, Andrew Moorhead, Steven A Williams, Timothy G Geary
The use of microfilaricidal drugs for the control of onchocerciasis and lymphatic filariasis (LF) necessitates prolonged yearly dosing. Prospects for elimination or eradication of these diseases would be enhanced by the availability of a macrofilaricidal drug. Flubendazole (FLBZ), a benzimidazole anthelmintic, is an appealing candidate. FLBZ has demonstrated potent macrofilaricidal effects in a number of experimental rodent models and in one human trial. Unfortunately, FLBZ was deemed unsatisfactory for use in mass drug administration campaigns due to its limited oral bioavailability...
December 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27718413/exploring-the-scope-of-new-arylamino-alcohol-derivatives-synthesis-antimalarial-evaluation-toxicological-studies-and-target-exploration
#16
Miguel Quiliano, Adela Mendoza, Kim Y Fong, Adriana Pabón, Nathan E Goldfarb, Isabelle Fabing, Ariane Vettorazzi, Adela López de Cerain, Ben M Dunn, Giovanny Garavito, David W Wright, Eric Deharo, Silvia Pérez-Silanes, Ignacio Aldana, Silvia Galiano
Synthesis of new 1-aryl-3-substituted propanol derivatives followed by structure-activity relationship, in silico drug-likeness, cytotoxicity, genotoxicity, in silico metabolism, in silico pharmacophore modeling, and in vivo studies led to the identification of compounds 22 and 23 with significant in vitro antiplasmodial activity against drug sensitive (D6 IC50 ≤ 0.19 μM) and multidrug resistant (FCR-3 IC50 ≤ 0.40 μM and C235 IC50 ≤ 0.28 μM) strains of Plasmodium falciparum. Adequate selectivity index and absence of genotoxicity was also observed...
December 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27705841/human-dihydrofolate-reductase-influences-the-sensitivity-of-the-malaria-parasite-plasmodium-falciparum-to-ketotifen-a-cautionary-tale-in-screening-transgenic-parasites
#17
Phuong N Tran, Cameron J Tate, Melanie C Ridgway, Kevin J Saliba, Kiaran Kirk, Alexander G Maier
Ketotifen has recently been reported to inhibit the growth of both asexual and sexual malaria parasites. A parasite transporter, PfgABCG2, has been implicated in its mechanism of action. Human dihydrofolate reductase (hDHFR) is the most commonly used selectable marker to create transgenic Plasmodium falciparum cell lines. Growth assays using transgenic P. falciparum parasites with different selectable markers revealed that the presence of hDHFR rather than the absence of PfgABCG2 is responsible for a shift in the parasite's sensitivity to ketotifen...
December 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27693536/research-for-new-drugs-for-elimination-of-onchocerciasis-in-africa
#18
REVIEW
Annette C Kuesel
Onchocerciasis is a parasitic, vector borne disease caused by the filarial nematode Onchocerca volvulus. More than 99% of the population at risk of infection live in Africa. Onchocerciasis control was initiated in West Africa in 1974 with vector control, later complemented by ivermectin mass drug administration and in the other African endemic countries in 1995 with annual community directed treatment with ivermectin (CDTI.) This has significantly reduced infection prevalence. Together with proof-of-concept for onchocerciasis elimination with annual CDTI from foci in Senegal and Mali, this has resulted in targeting onchocerciasis elimination in selected African countries by 2020 and in 80% of African countries by 2025...
December 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27682348/erratum-to-profiling-the-anti-protozoal-activity-of-anti-cancer-hdac-inhibitors-against-plasmodium-and-trypanosoma-parasites-int-j-parasitol-drugs-drug-res-5-2015-117-126
#19
Jessica A Engel, Amy J Jones, Vicky M Avery, Subathdrage D M Sumanadasa, Susanna S Ng, David P Fairlie, Tina Skinner-Adams, Katherine T Andrews
No abstract text is available yet for this article.
December 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/27682347/polymorphism-in-ion-channel-genes-of-dirofilaria-immitis-relevant-knowledge-for-future-anthelmintic-drug-design
#20
Thangadurai Mani, Catherine Bourguinat, Kathy Keller, Elena Carreton, Andrew Peregrine, Roger K Prichard
Dirofilaria immitis, a filarial parasite, causes cardiopulmonary dirofilariasis in dogs, cats and wild canids. The macrocyclic lactone (ML) class of drugs has been used to prevent heartworm infection. There is confirmed ML resistance in D. immitis and thus there is an urgent need to find new anthelmintics that could prevent and/or control the disease. Targeting ion channels of D. immitis for drug design has obvious advantages. These channels, present in the nematode nervous system, control movement, feeding, mating and respond to environmental cues which are necessary for survival of the parasite...
December 2016: International Journal for Parasitology, Drugs and Drug Resistance
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