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Trypanosomiasis

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https://www.readbyqxmd.com/read/28645659/synthesis-in-vitro-and-in-vivo-giardicidal-activity-of-nitrothiazole-nsaid-chimeras-displaying-broad-antiprotozoal-spectrum
#1
Blanca Colín-Lozano, Ismael León-Rivera, Manuel Jesús Chan-Bacab, Benjamín Otto Ortega-Morales, Rosa Moo-Puc, Vanessa López-Guerrero, Emanuel Hernández-Núñez, Raúl Argüello-Garcia, Thomas Scior, Elizabeth Barbosa-Cabrera, Gabriel Navarrete-Vázquez
We designed and synthesized five new 5-nitrothiazole-NSAID chimeras as analogues of nitazoxanide, using a DCC-activated amidation. Compounds 1-5 were tested in vitro against a panel of five protozoa: 2 amitochondriates (Giardia intestinalis, Trichomonas vaginalis) and 3 kinetoplastids (Leishmania mexicana, Leishmania amazonensis and Trypanosoma cruzi). All chimeras showed broad spectrum and potent antiprotozoal activities, with IC50 values ranging from the low micromolar to nanomolar order. Compounds 1-5 were even more active than metronidazole and nitazoxanide, two marketed first-line drugs against giardiasis...
May 24, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28641558/bis-2-aminoimidazolines-and-bisguanidines-synthetic-approaches-antiparasitic-activity-and-dna-binding-properties
#2
Christophe Dardonville, J Jonathan Nué Martínez
BACKGROUND: Parasitic diseases caused by protozoan parasites of the genus Trypanosoma and Plasmodium cause some of the deadliest and disabling human infections in tropical and subtropical areas. Diphenyl-based bis(2-phenylimino)imidazolidines and bisguanidines are extremely potent antiparasitic agents against Trypanosoma brucei (etiological agent of African trypanosomiasis) and Plasmodium falciparum (etiological agent of severe malaria). Many of these compounds are also curative in mouse models of stage 1 African trypanosomiasis representing promising leads for the development of antitrypanosomal drugs...
June 22, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28637278/functional-and-structural-analysis-of-at-specific-minor-groove-binders-that-disrupt-dna-protein-interactions-and-cause-disintegration-of-the-trypanosoma-brucei-kinetoplast
#3
Cinthia R Millan, Francisco J Acosta-Reyes, Laura Lagartera, Godwin U Ebiloma, Leandro Lemgruber, J Jonathan Nué Martínez, Núria Saperas, Christophe Dardonville, Harry P de Koning, J Lourdes Campos
Trypanosoma brucei, the causative agent of sleeping sickness (Human African Trypanosomiasis, HAT), contains a kinetoplast with the mitochondrial DNA (kDNA), comprising of >70% AT base pairs. This has prompted studies of drugs interacting with AT-rich DNA, such as the N-phenylbenzamide bis(2-aminoimidazoline) derivatives 1 [4-((4,5-dihydro-1H-imidazol-2-yl)amino)-N-(4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)benzamide dihydrochloride] and 2 [N-(3-chloro-4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)-4-((4,5-dihydro-1H-imidazol-2-yl)amino)benzamide] as potential drugs for HAT...
June 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28636879/delineating-neuroinflammation-parasite-cns-invasion-and-blood-brain-barrier-dysfunction-in-an-experimental-murine-model-of-human-african-trypanosomiasis
#4
Jean Rodgers, Barbara Bradley, Peter G E Kennedy
Although Trypanosoma brucei spp. was first detected by Aldo Castellani in CSF samples taken from sleeping sickness patients over a century ago there is still a great deal of debate surrounding the timing, route and effects of transmigration of the parasite from the blood to the CNS. In this investigation, we have applied contrast-enhance magnetic resonance imaging (MRI) to study the effects of trypanosome infection on the blood-brain barrier (BBB) in the well-established GVR35 mouse model of sleeping sickness...
June 18, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28632168/a-comparative-study-of-the-structural-dynamics-of-four-terminal-uridylyl-transferases
#5
Kevin J Cheng, Özlem Demir, Rommie E Amaro
African trypanosomiasis occurs in 36 countries in sub-Saharan Africa with 10,000 reported cases annually. No definitive remedy is currently available and if left untreated, the disease becomes fatal. Structural and biochemical studies of trypanosomal terminal uridylyl transferases (TUTases) demonstrated their functional role in extensive uridylate insertion/deletion of RNA. Trypanosoma brucei RNA Editing TUTase 1 (TbRET1) is involved in guide RNA 3' end uridylation and maturation, while TbRET2 is responsible for U-insertion at RNA editing sites...
June 20, 2017: Genes
https://www.readbyqxmd.com/read/28628444/case-of-nigeria-acquired-human-african-trypanosomiasis-in-united-kingdom-2016
#6
Akish Luintel, Patricia Lowe, Anneli Cooper, Annette MacLeod, Philippe Büscher, Tim Brooks, Mike Brown
Human African trypanosomiasis has not been reported in Nigeria since 2012. Nevertheless, limitations of current surveillance programs mean that undetected infections may persist. We report a recent case of stage 2 trypanosomiasis caused by Trypanosoma brucei gambiense acquired in Nigeria and imported into the United Kingdom.
July 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28624143/a-small-molecule-screen-identifies-the-antitrypanosomal-agent-suramin-and-analogues-nf023-and-nf449-as-inhibitors-of-stat5a-b
#7
Angela Berg, Thorsten Berg
The transcription factor STAT5a is a potential target for tumor therapy. We present a fluorescence polarization-based, high-throughput screen of chemical libraries containing natural products and known bioactive molecules, for the identification of small-molecule inhibitors of the STAT5a SH2 domain. This screen identified suramin, a drug used to treat African trypanosomiasis, and its analogues NF023 and NF449 as inhibitors of the SH2 domains of STAT5a/b. Our data extend the known in vitro targets of suramin and analogues to include members of the STAT protein family...
June 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28623292/structural-and-biochemical-characterization-of-poly-adp-ribose-polymerase-from-trypanosoma-brucei
#8
Teemu Haikarainen, Mariana Schlesinger, Ezeogo Obaji, Silvia H Fernández Villamil, Lari Lehtiö
Trypanosoma brucei is a unicellular parasite responsible for African trypanosomiasis or sleeping sickness. It contains a single PARP enzyme opposed to many higher eukaryotes, which have numerous PARPs. PARPs are responsible for a post-translational modification, ADP-ribosylation, regulating a multitude of cellular events. T. brucei PARP, like human PARPs-1-3, is activated by DNA binding and it potentially functions in DNA repair processes. Here we characterized activation requirements, structure and subcellular localization of T...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615837/trypanocidal-action-of-lippia-alba-and-lippia-origanoides-essential-oils-against-trypanosoma-evansi-in-vitro-and-in-vivo-used-mice-as-experimental-model
#9
Matheus D Baldissera, Carine de Freitas Souza, Rosa Helena Veras Mourão, Lenise Vargas Flores da Silva, Silvia G Monteiro
Parasitic diseases have an enormous health and economic impact and are a particular problem in tropical regions of the world. Disease caused by protozoa, such as trypanosomiasis, are the cause of most parasite related morbidity and mortality. Thus, the aim of this study was to verify the trypanocidal effectiveness of Lippia alba and Lippia origanoides against Trypanosoma evansi in vitro and in vivo. L. alba and L. origanoides were used in vitro on trypomastigotes at different concentrations (0.5, 1.0 and 2...
June 2017: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
https://www.readbyqxmd.com/read/28608214/use-of-zymography-in-trypanosomiasis-studies
#10
Jéssyka Fernanda Santiago Monte, Cláudia Jassica Gonçalves Moreno, Joana Patrícia Molato Figueiredo Lopes Monteiro, Hugo Alexandre de Oliveira Rocha, Aline Rimoldi Ribeiro, Marcelo Sousa Silva
Zymography assay is a semiquantitative technique, very sensitive, and commonly used to determine metalloproteinase levels in different types of biological samples, including tissues, cells, and extracts of protein. Samples containing metalloproteinases are loaded onto a polyacrylamide gel containing sodium dodecyl sulphate (SDS) and a specific substrate (gelatin, casein, collagen, etc.). Then proteins are allowed to migrate under an electric current and the distance of migration is inversely correlated with the molecular weight...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28591404/sexual-transmission-of-american-trypanosomiasis-in-humans-a-new-potential-pandemic-route-for-chagas-parasites
#11
Perla F Araujo, Adriana B Almeida, Carlos F Pimentel, Adriano R Silva, Alessandro Sousa, Sebastião A Valente, Vera C Valente, Manuela M Britto, Ana C Rosa, Rozeneide M Alves, Luciana Hagström, Antonio Rl Teixeira
BACKGROUND: The Trypanosoma cruzi infection endemic in Latin America has now spread to several countries across four continents; this endemic involves triatomine vector-free protists. We hypothesised that the sexual transmission of T. cruzi contributes to the ongoing spread of Chagas disease. OBJECTIVES: A short-term longitudinal study was conducted to evaluate this hypothesis. METHODS: The study population comprised 109 subjects from four families, among whom 21 had been diagnosed with acute Chagas disease by direct parasitological analysis...
June 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28590590/repurposing-of-human-kinase-inhibitors-in-neglected-protozoan-diseases
#12
Maria Dichiara, Agostino Marrazzo, Orazio Prezzavento, Simona Collina, Antonio Rescifina, Emanuele Amata
Human African trypanosomiasis (HAT), Chagas disease and leishmaniasis, belong to a group of infectious diseases defined as neglected tropical diseases, induced by infection with protozoan parasites named trypanosomatids. Current drugs present several issues and the development of new candidates appears to be needed. The majority of the current therapeutic trypanosomatid targets are represented by enzymes or cell surface receptors. Among these, eukaryotic protein kinases represent a major group of protein targets whose modulation may be beneficial for the treatment of neglected tropical protozoan diseases...
June 7, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28586253/characterization-of-recombinant-trypanosoma-brucei-gambiense-translationally-controlled-tumor-protein-rtbgtctp-and-its-interaction-with-glossina-midgut-bacteria
#13
Géraldine Bossard, Manon Bartoli, Marie-Laure Fardeau, Philippe Hozmuller, Bernard Ollivier, Anne Geiger
In humans, sleeping sickness (i.e. Human African Trypanosomiasis) is caused by the protozoan parasites Trypanosoma brucei gambiense (Tbg) in West and Central Africa, and T. b. rhodesiense in East Africa. We previously showed in vitro that Tbg is able to excrete/secrete a large number of proteins, including Translationally Controlled Tumour Protein (TCTP). Moreover, the tctp gene was previously described to be expressed in Tbg-infected flies. Aside from its involvement in diverse cellular processes, we have investigated a possible alternative role within the interactions occurring between the trypanosome parasite, its tsetse fly vector, and the associated midgut bacteria...
June 6, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28584177/structural-drivers-of-vulnerability-to-zoonotic-disease-in-africa
#14
Vupenyu Dzingirai, Salome Bukachi, Melissa Leach, Lindiwe Mangwanya, Ian Scoones, Annie Wilkinson
This paper argues that addressing the underlying structural drivers of disease vulnerability is essential for a 'One Health' approach to tackling zoonotic diseases in Africa. Through three case studies-trypanosomiasis in Zimbabwe, Ebola and Lassa fever in Sierra Leone and Rift Valley fever in Kenya-we show how political interests, commercial investments and conflict and securitization all generate patterns of vulnerability, reshaping the political ecology of disease landscapes, influencing traditional coping mechanisms and affecting health service provision and outbreak responses...
July 19, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28584171/local-disease-ecosystem-livelihood-dynamics-reflections-from-comparative-case-studies-in-africa
#15
Melissa Leach, Bernard Bett, M Said, Salome Bukachi, Rosemary Sang, Neil Anderson, Noreen Machila, Joanna Kuleszo, Kathryn Schaten, Vupenyu Dzingirai, Lindiwe Mangwanya, Yaa Ntiamoa-Baidu, Elaine Lawson, Kofi Amponsah-Mensah, Lina M Moses, Annie Wilkinson, Donald S Grant, James Koninga
This article explores the implications for human health of local interactions between disease, ecosystems and livelihoods. Five interdisciplinary case studies addressed zoonotic diseases in African settings: Rift Valley fever (RVF) in Kenya, human African trypanosomiasis in Zambia and Zimbabwe, Lassa fever in Sierra Leone and henipaviruses in Ghana. Each explored how ecological changes and human-ecosystem interactions affect pathogen dynamics and hence the likelihood of zoonotic spillover and transmission, and how socially differentiated peoples' interactions with ecosystems and animals affect their exposure to disease...
July 19, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28579388/targeting-cysteine-proteases-in-trypanosomatid-disease-drug-discovery
#16
REVIEW
Leonardo G Ferreira, Adriano D Andricopulo
Chagas disease and human African trypanosomiasis are endemic conditions in Latin America and Africa, respectively, for which no effective and safe therapy is available. Efforts in drug discovery have focused on several enzymes from these protozoans, among which cysteine proteases have been validated as molecular targets for pharmacological intervention. These enzymes are expressed during the entire life cycle of trypanosomatid parasites and are essential to many biological processes, including infectivity to the human host...
June 1, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28578742/applicability-of-plant-based-products-in-the-treatment-of-trypanosoma-cruzi-and-trypanosoma-brucei-infections-a-systematic-review-of-preclinical-in-vivo-evidence
#17
Rodrigo M Pereira, Glícia M Z Greco, Andreia M Moreira, Pablo F Chagas, Ivo S Caldas, Reggiani V Gonçalves, Rômulo D Novaes
Chagas disease and sleeping sickness are neglected tropical diseases closely related to poverty, for which the development of plant-derived treatments has not been a promising prospect. Thus, we systematicaly review the preclinical in vivo evidence on the applicability of plant-based products in the treatment of Trypanosoma cruzi and Trypanosoma brucei infections. Characteristics such as disease models, treatments, toxicological safety and methodological bias were analysed. We recovered 66 full text articles from 16 countries investigating 91 plant species...
June 5, 2017: Parasitology
https://www.readbyqxmd.com/read/28572816/ergosterol-isolated-from-the-basidiomycete-pleurotus-salmoneostramineus-affects-trypanosoma-cruzi-plasma-membrane-and-mitochondria
#18
Tatiana Rodrigues Alexandre, Marta Lopes Lima, Mariana Kolos Galuppo, Juliana Tonini Mesquita, Matilia Ana do Nascimento, Augusto Leonardo Dos Santos, Patricia Sartorelli, Daniel Carvalho Pimenta, Andre Gustavo Tempone
BACKGROUND: Major drawbacks of the available treatment against Chagas disease (American trypanosomiasis) include its toxicity and therapeutic inefficiency in the chronic phase of the infection, which makes it a concern among neglected diseases. Therefore, the discovery of alternative drugs for treating chronic Chagas disease requires immediate action. In this work, we evaluated the mushroom Pleurotus salmoneostramineus in the search for potential antiparasitic compounds. METHODS: Fruit bodies of the basidiomycete Pleurotus salmoneostramineus were triturated and submitted to organic solvent extraction...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28570558/introducing-the-trypanogen-biobank-a-valuable-resource-for-the-elimination-of-human-african-trypanosomiasis
#19
Hamidou Ilboudo, Harry Noyes, Julius Mulindwa, Magambo Phillip Kimuda, Mathurin Koffi, Justin Windingoudi Kaboré, Bernadin Ahouty, Dieudonné Mumba Ngoyi, Olivier Fataki, Gustave Simo, Elvis Ofon, John Enyaru, John Chisi, Kelita Kamoto, Martin Simuunza, Vincent P Alibu, Veerle Lejon, Vincent Jamonneau, Annette Macleod, Mamadou Camara, Bruno Bucheton, Christiane Hertz-Fowler, Issa Sidibe, Enock Matovu
No abstract text is available yet for this article.
June 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28567189/polymerase-chain-reaction-identification-of-trypanosoma-brucei-rhodesiense-in-wild-tsetse-flies-from-nkhotakota-wildlife-reserve-malawi
#20
Janelisa Musaya, John Chisi, Edward Senga, Peter Nambala, Emmanuel Maganga, Enock Matovu, John Enyaru
BACKGROUND: Trypanosoma brucei rhodesiense is the causative agent of acute human African trypanosomiasis. Identification of T. b. rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessng human disease risk, and monitoring spatiotemporal trends and impact of control interventions. Accurate detection and characterisation of trypanosomes in vectors relies on molecular techniques. For the first time in Malawi, a molecular technique has been used to detect trypanosomes in tsetse flies in Nkhotakota Wildlife Reserve...
March 2017: Malawi Medical Journal: the Journal of Medical Association of Malawi
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