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Trypanosomiasis

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https://www.readbyqxmd.com/read/27894362/the-trypanosome-alternative-oxidase-a-potential-drug-target
#1
Stefanie K Menzies, Lindsay B Tulloch, Gordon J Florence, Terry K Smith
New drugs against Trypanosoma brucei, the causative agent of Human African Trypanosomiasis, are urgently needed to replace the highly toxic and largely ineffective therapies currently used. The trypanosome alternative oxidase (TAO) is an essential and unique mitochondrial protein in these parasites and is absent from mammalian mitochondria, making it an attractive drug target. The structure and function of the protein are now well characterized, with several inhibitors reported in the literature, which show potential as clinical drug candidates...
November 29, 2016: Parasitology
https://www.readbyqxmd.com/read/27894360/the-relationship-of-endotoxaemia-to-peripheral-and-central-nervous-system-inflammatory-responses-in-human-african-trypanosomiasis
#2
Lorna Maclean, Eltayb A Aboubaker, Peter G E Kennedy, Jeremy M Sternberg
Endotoxaemia has been described in cases of Human African trypanosomiasis (HAT), but it is unclear if this phenomenon influences inflammatory pathology either in the periphery or central nervous system (CNS). We studied endotoxin concentrations in the plasma and cerebrospinal fluid (CSF) of Trypanosoma brucei rhodesiense patients using the chromogenic Limulus Amoebocyte lysate assay. The relationship of endotoxin concentration to the presentation of gross signs of inflammation and the inflammatory/counter-inflammatory cytokine profile of the relevant compartments were analysed...
November 29, 2016: Parasitology
https://www.readbyqxmd.com/read/27884172/spatial-distribution-and-trypanosome-infection-of-tsetse-flies-in-the-sleeping-sickness-focus-of-zimbabwe-in-hurungwe-district
#3
William Shereni, Neil E Anderson, Learnmore Nyakupinda, Giuliano Cecchi
BACKGROUND: In Zimbabwe, cases of human African trypanosomiasis (HAT) are caused by the unicellular protozoan Trypanosoma brucei, sub-species T. b. rhodesiense. They are reported from the tsetse-infested area in the northern part of the country, broadly corresponding to the valley of the Zambezi River. Tsetse-transmitted trypanosomes, in particular T. congolense and T. vivax, also cause morbidity and mortality in livestock, thus generating poverty and food insecurity. Two species of tsetse fly, Glossina morsistans morsitans and G...
November 25, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27882478/unexpected-hosts-imaging-parasitic-diseases
#4
REVIEW
Pablo Rodríguez Carnero, Paula Hernández Mateo, Susana Martín-Garre, Ángela García Pérez, Lourdes Del Campo
Radiologists seldom encounter parasitic diseases in their daily practice in most of Europe, although the incidence of these diseases is increasing due to migration and tourism from/to endemic areas. Moreover, some parasitic diseases are still endemic in certain European regions, and immunocompromised individuals also pose a higher risk of developing these conditions. This article reviews and summarises the imaging findings of some of the most important and frequent human parasitic diseases, including information about the parasite's life cycle, pathophysiology, clinical findings, diagnosis, and treatment...
November 23, 2016: Insights Into Imaging
https://www.readbyqxmd.com/read/27876900/the-common-zoonotic-protozoal-diseases-causing-abortion
#5
REVIEW
Raafat Mohamed Shaapan
Toxoplasmosis, neosporosis, sarcosporidiosis (sarcocystosis) and trypanosomiasis are the common zoonotic protozoal diseases causing abortion which caused by single-celled protozoan parasites; Toxoplasma gondii, Neospora caninum, Sarcocystis spp and Trypanosoma evansi, respectively. Toxoplasmosis is generally considered the most important disease that causing abortion of both pregnant women and different female animals throughout the world, about third of human being population had antibodies against T. gondii...
December 2016: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
https://www.readbyqxmd.com/read/27876646/outcome-of-oral-infection-in-mice-inoculated-with-trypanosoma-cruzi-iv-of-the-western-brazilian-amazon
#6
Ana Paula Margioto Teston, Ana Paula de Abreu, Camila Piva Abegg, Mônica Lúcia Gomes, Max Jean de Ornelas Toledo
A new epidemiological view of American trypanosomiasis or Chagas disease has been formulated in recent decades. Oral transmission of the etiological agent of Chagas disease, Trypanosoma cruzi, has been the most common form of transmission. The T. cruzi discrete typing units TcI and TcIV have been involved in tens outbreaks of acute cases of Chagas disease in the Brazilian Amazon region. We investigated the intensity of infection in mice that were orally inoculated (OR group) with four strains of TcIV that were isolated from two outbreaks of acute Chagas disease that was orally acquired in the state of Amazonas, Brazil...
November 19, 2016: Acta Tropica
https://www.readbyqxmd.com/read/27872081/novel-effects-of-lapatinib-revealed-in-the-african-trypanosome-using-hypothesis-generating-proteomics-and-chemical-biology-strategies
#7
Paul J Guyett, Ranjan Behera, Yuko Ogata, Michael Pollastri, Kojo Mensa-Wilmot
Human African trypanosomiasis is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei Lapatinib, a human epidermal growth factor receptor (EGFR) inhibitor, can cure 25% of trypanosome-infected mice, although the parasite lacks EGFR-like tyrosine kinases. Four trypanosome protein kinases associate with lapatinib, suggesting the drug may be a multi-targeted inhibitor of phosphoprotein signaling in the bloodstream trypanosome. Phosphoprotein signaling pathways in T. brucei have diverged significantly from those in humans...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27867276/ursolic-acid-a-natural-pentacylcic-triterpene-from-ochrosia-elliptica-and-its-role-in-the-management-of-certain-neglected-tropical-diseases
#8
Rola M Labib, Sherif S Ebada, Fadia S Youssef, Mohamed L Ashour, Samir A Ross
BACKGROUND: Leishmaniasis and African trypanosomiasis are recognized as the leading causes of mortality and morbidity with the greatest prevalence in the developing countries. They affect more than one billion of the poorest people on the globe. OBJECTIVE: To find a cheap, affordable, safe, and efficacious antileshmanial and antitrypanosomal natural drug and to elucidate its probable mode of action. MATERIALS AND METHODS: Phytochemical investigation of the non-polar fraction of the methanol extract of leaves of Ochrosia elliptica Labill...
October 2016: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/27856732/trypanosoma-brucei-metabolite-indolepyruvate-decreases-hif-1%C3%AE-and-glycolysis-in-macrophages-as-a-mechanism-of-innate-immune-evasion
#9
Anne F McGettrick, Sarah E Corcoran, Paul J G Barry, Jennifer McFarland, Cécile Crès, Anne M Curtis, Edward Franklin, Sinéad C Corr, K Hun Mok, Eoin P Cummins, Cormac T Taylor, Luke A J O'Neill, Derek P Nolan
The parasite Trypanasoma brucei causes African trypanosomiasis, known as sleeping sickness in humans and nagana in domestic animals. These diseases are a major burden in the 36 sub-Saharan African countries where the tsetse fly vector is endemic. Untreated trypanosomiasis is fatal and the current treatments are stage-dependent and can be problematic during the meningoencephalitic stage, where no new therapies have been developed in recent years and the current drugs have a low therapeutic index. There is a need for more effective treatments and a better understanding of how these parasites evade the host immune response will help in this regard...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27855164/trypanosoma-brucei-cyp51-essentiality-and-targeting-therapy-in-an-experimental-model
#10
Frédéric-Antoine Dauchy, Mélanie Bonhivers, Nicolas Landrein, Denis Dacheux, Pierrette Courtois, Florian Lauruol, Sylvie Daulouède, Philippe Vincendeau, Derrick R Robinson
Trypanosoma brucei gambiense is the main causative agent of Human African Trypanosomiasis (HAT), also known as sleeping sickness. Because of limited alternatives and treatment toxicities, new therapeutic options are urgently needed for patients with HAT. Sterol 14alpha-demethylase (CYP51) is a potential drug target but its essentiality has not been determined in T. brucei. We used a tetracycline-inducible RNAi system to assess the essentiality of CYP51 in T. brucei bloodstream form (BSF) cells and we evaluated the effect of posaconazole, a well-tolerated triazole drug, within a panel of virulent strains in vitro and in a murine model...
November 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27849517/a-targeted-door-to-door-strategy-for-sleeping-sickness-detection-in-low-prevalence-settings-in-c%C3%A3-te-d-ivoire
#11
Mathurin Koffi, Martial N'Djetchi, Hamidou Ilboudo, Dramane Kaba, Bamoro Coulibaly, Emmanuel N'Gouan, Lingué Kouakou, Bruno Bucheton, Philippe Solano, Fabrice Courtin, Stephan Ehrhardt, Vincent Jamonneau
Significant efforts to control human African trypanosomiasis (HAT) over the three past decades have resulted in drastic reductions of disease prevalence in Côte d'Ivoire. In this context, the costly and labor-intensive active mass screening strategy is no longer efficient. In addition to a more cost-effective passive surveillance system being implemented in this low-prevalence context, our aim was to develop an alternative targeted active screening strategy. In 2012, we carried out a targeted door-to-door (TDD) survey focused on the immediate vicinities of former HAT patients detected in the HAT focus of Bonon and compared the results to those obtained during classical active mass screening (AMS) surveys conducted from 2000 to 2012 in the same area...
2016: Parasite: Journal de la Société Française de Parasitologie
https://www.readbyqxmd.com/read/27828620/prevalence-of-american-trypanosomiasis-and-leishmaniases-in-domestic-dogs-in-a-rural-area-of-the-municipality-of-s%C3%A3-o-jo%C3%A3-o-do-piau%C3%A3-piau%C3%A3-state-brazil
#12
Taliha Dias Perez, Fabiano Borges Figueiredo, Artur Augusto Mendes Velho Junior, Valmir Laurentino Silva, Maria de Fátima Madeira, Reginaldo Peçanha Brazil, José Rodrigues Coura
Chagas disease and the leishmaniases are endemic zoonoses of great importance to public health in the state of Piauí, Brazil. The domestic dog (Canis familiaris) is a major reservoir, host of Trypanosoma cruzi and Leishmania spp. in both urban and rural areas, playing an important role in the transmission of these parasites. The present study evaluated the prevalence of both infectious diseases in dogs of a rural area in the municipality of São João do Piauí, Piauí State. One hundred twenty-nine blood samples were collected for serological assessment: for the leishmaniases, 49 (38%) animals tested positive by the Dual-Path Platform technology (DPP), nine (6%) by the Enzyme-linked Immunosorbent Assay (ELISA), and 19 (14...
November 3, 2016: Revista do Instituto de Medicina Tropical de São Paulo
https://www.readbyqxmd.com/read/27812090/diagnosis-of-persistent-fever-in-the-tropics-set-of-standard-operating-procedures-used-in-the-nidiag-febrile-syndrome-study
#13
Emilie Alirol, Ninon Seiko Horie, Barbara Barbé, Veerle Lejon, Kristien Verdonck, Philippe Gillet, Jan Jacobs, Philippe Büscher, Basudha Kanal, Narayan Raj Bhattarai, Sayda El Safi, Thong Phe, Kruy Lim, Long Leng, Pascal Lutumba, Deby Mukendi, Emmanuel Bottieau, Marleen Boelaert, Suman Rijal, François Chappuis
In resource-limited settings, the scarcity of skilled personnel and adequate laboratory facilities makes the differential diagnosis of fevers complex [1-5]. Febrile illnesses are diagnosed clinically in most rural centers, and both Rapid Diagnostic Tests (RDTs) and clinical algorithms can be valuable aids to health workers and facilitate therapeutic decisions [6,7]. The persistent fever syndrome targeted by NIDIAG is defined as presence of fever for at least one week. The NIDIAG clinical research consortium focused on potentially severe and treatable infections and therefore targeted the following conditions as differential diagnosis of persistent fever: visceral leishmaniasis (VL), human African trypanosomiasis (HAT), enteric (typhoid and paratyphoid) fever, brucellosis, melioidosis, leptospirosis, malaria, tuberculosis, amoebic liver abscess, relapsing fever, HIV/AIDS, rickettsiosis, and other infectious diseases (e...
November 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27805593/detection-of-trypanosoma-brucei-variant-surface-glycoprotein-switching-by-magnetic-activated-cell-sorting-and-flow-cytometry
#14
Danae Schulz, Monica R Mugnier, Catherine E Boothroyd, F Nina Papavasiliou
Trypanosoma brucei, a protozoan parasite that causes both Human and Animal African Trypanosomiasis (known as sleeping sickness and nagana, respectively) cycles between a tsetse vector and a mammalian host. It evades the mammalian host immune system by periodically switching the dense, variant surface glycoprotein (VSG) that covers its surface. The detection of antigenic variation in Trypanosoma brucei can be both cumbersome and labor intensive. Here, we present a method for quantifying the number of parasites that have 'switched' to express a new VSG in a given population...
October 19, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27788467/structure-guided-design-of-novel-trypanosoma-brucei-methionyl-trna-synthetase-inhibitors
#15
Wenlin Huang, Zhongsheng Zhang, Ximena Barros-Álvarez, Cho Yeow Koh, Ranae M Ranade, J Robert Gillespie, Sharon A Creason, Sayaka Shibata, Christophe L M J Verlinde, Wim G J Hol, Frederick S Buckner, Erkang Fan
A screening hit 1 against Trypanosoma brucei methionyl-tRNA synthetase was optimized using a structure-guided approach. The optimization led to the identification of two novel series of potent inhibitors, the cyclic linker and linear linker series. Compounds of both series were potent in a T. brucei growth inhibition assay while showing low toxicity to mammalian cells. The best compound of each series, 16 and 31, exhibited EC50s of 39 and 22 nM, respectively. Compounds 16 and 31 also exhibited promising PK properties after oral dosing in mice...
November 29, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27787206/characteristics-behaviors-and-association-between-human-african-trypanosomiasis-and-hiv-seropositivity-among-volunteer-blood-donors-in-a-semi-rural-area-a-survey-from-kikwit-the-democratic-republic-of-congo
#16
Lefils Kasiama Ndilu, Mathilde Bothale Ekila, Donald Fundji Mayuma, Alain Musaka, Roger Wumba, Michel Ntetani Aloni
Blood safety is a major element in the strategy to control the HIV epidemic. The aim of this study was to determine the prevalence and the associated factors of a positive HIV test among blood donors and its association between Human African Trypanosomiasis in Kikwit, the Democratic Republic of Congo. A cross-sectional study was conducted between November 2012 and May 2013. An anonymous questionnaire was designed to extract relevant data. The average mean age of participants was 30 years. The majority were man (67...
December 1, 2016: Acta Parasitologica
https://www.readbyqxmd.com/read/27786284/crystal-structures-and-inhibition-of-trypanosoma-brucei-hypoxanthine-guanine-phosphoribosyltransferase
#17
David Terán, Dana Hocková, Michal Česnek, Alena Zíková, Lieve Naesens, Dianne T Keough, Luke W Guddat
Human African Trypanosomiasis (HAT) is a life-threatening infectious disease caused by the protozoan parasite, Trypanosoma brucei (Tbr). Due to the debilitating side effects of the current therapeutics and the emergence of resistance to these drugs, new medications for this disease need to be developed. One potential new drug target is 6-oxopurine phosphoribosyltransferase (PRT), an enzyme central to the purine salvage pathway and whose activity is critical for the production of the nucleotides (GMP and IMP) required for DNA/RNA synthesis within this protozoan parasite...
October 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27784230/targets-and-patented-drugs-for-chemotherapy-of-chagas-disease-in-the-last-15-years-period
#18
Vilma G Duschak
The American trypanosomiasis, Chagas disease, is a parasitic infection typically spread by triatomine vectors affecting millions of people all over Latin America. Existing chemotherapy is centered on the nitroaromatic compounds benznidazole and nifurtimox that provide unsatisfactory results and substantial side effects. So, the finding and exploration of novel ways to challenge this neglected disease is a main priority. The biologic and biochemical progress in the scientific knowledge of Trypanosoma cruzi in the period comprising the last 15-years, has increased the identification of multiple targets for Chagas´ disease chemotherapy...
October 24, 2016: Recent Patents on Anti-infective Drug Discovery
https://www.readbyqxmd.com/read/27775577/the-potential-of-secondary-metabolites-from-plants-as-drugs-or-leads-against-protozoan-neglected-diseases-part-iii-in-silico-molecular-docking-investigations
#19
Ifedayo Victor Ogungbe, William N Setzer
Malaria, leishmaniasis, Chagas disease, and human African trypanosomiasis continue to cause considerable suffering and death in developing countries. Current treatment options for these parasitic protozoal diseases generally have severe side effects, may be ineffective or unavailable, and resistance is emerging. There is a constant need to discover new chemotherapeutic agents for these parasitic infections, and natural products continue to serve as a potential source. This review presents molecular docking studies of potential phytochemicals that target key protein targets in Leishmania spp...
October 19, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27759763/heterochromatin-base-pair-composition-and-diversification-in-holocentric-chromosomes-of-kissing-bugs-hemiptera-reduviidae
#20
Vanessa Bellini Bardella, Sebastián Pita, André Luis Laforga Vanzela, Cleber Galvão, Francisco Panzera
The subfamily Triatominae (Hemiptera, Reduviidae) includes 150 species of blood-sucking insects, vectors of Chagas disease or American trypanosomiasis. Karyotypic information reveals a striking stability in the number of autosomes. However, this group shows substantial variability in genome size, the amount and distribution of C-heterochromatin, and the chromosome positions of 45S rDNA clusters. Here, we analysed the karyotypes of 41 species from six different genera with C-fluorescence banding in order to evaluate the base-pair richness of heterochromatic regions...
October 2016: Memórias do Instituto Oswaldo Cruz
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