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https://www.readbyqxmd.com/read/28225900/chronic-chagas-cardiomyopathy-a-review-of-the-main-pathogenic-mechanisms-and-the-efficacy-of-aetiological-treatment-following-the-benznidazole-evaluation-for-interrupting-trypanosomiasis-benefit-trial
#1
Anis Rassi, José Antonio Marin, Anis Rassi
Chagas cardiomyopathy is the most frequent and most severe manifestation of chronic Chagas disease, and is one of the leading causes of morbidity and death in Latin America. Although the pathogenesis of Chagas cardiomyopathy is incompletely understood, it may involve several mechanisms, including parasite-dependent myocardial damage, immune-mediated myocardial injury (induced by the parasite itself and by self-antigens), and microvascular and neurogenic disturbances. In the past three decades, a consensus has emerged that parasite persistence is crucial to the development and progression of Chagas cardiomyopathy...
March 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28225894/chronic-chagas-cardiomyopathy-a-review-of-the-main-pathogenic-mechanisms-and-the-efficacy-of-aetiological-treatment-following-the-benznidazole-evaluation-for-interrupting-trypanosomiasis-benefit-trial
#2
Anis Rassi, José Antonio Marin, Anis Rassi
Chagas cardiomyopathy is the most frequent and most severe manifestation of chronic Chagas disease, and is one of the leading causes of morbidity and death in Latin America. Although the pathogenesis of Chagas cardiomyopathy is incompletely understood, it may involve several mechanisms, including parasite-dependent myocardial damage, immune-mediated myocardial injury (induced by the parasite itself and by self-antigens), and microvascular and neurogenic disturbances. In the past three decades, a consensus has emerged that parasite persistence is crucial to the development and progression of Chagas cardiomyopathy...
February 16, 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28212811/polymorphisms-of-blood-forms-and-in-vitro-metacyclogenesis-of-trypanosoma-cruzi-i-ii-and-iv
#3
Camila Piva Abegg, Ana Paula de Abreu, Juliane Lopes da Silva, Silvana Marques de Araújo, Mônica Lúcia Gomes, Érika Cristina Ferreira, Max Jean de Ornelas Toledo
Trypanosoma cruzi is the etiologic agent of American trypanosomiasis has broad biological and genetic diversity. Remaining to be studied are polymorphisms of the blood forms and metacyclogenesis of different T. cruzi discrete typing units (DTUs). Our goal was to evaluate the relationship between T. cruzi DTUs, the morphology of blood trypomastigotes, and in vitro metacyclogenesis. T. cruzi strains that pertained to DTUs TcI, TcII, and TcIV from different Brazilian states were used. Parameters that were related to the morphology of eight strains were assessed in thin blood smears that were obtained from mice that were inoculated with blood or culture forms, depending on strain...
February 14, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28198632/engineering-oral-and-parenteral-amorphous-amphotericin-b-formulations-against-experimental-trypanosoma-cruzi-infections
#4
Miriam Rolón, Dolores R Serrano, Aikaterini Lalatsa, Esther de Pablo, Juan Jose Torrado, Maria Paloma Ballesteros, Anne Marie Healy, Celeste Vega, Cathia Coronel, Francisco Bolas-Fernández, Maria Auxiliadora Dea-Ayuela
Chagas disease (CD) is a parasitic zoonosis endemic in most mainland countries of Central and South America affecting nearly 10 million people, with 100 million people at high risk of contracting the disease. Treatment is only effective if received at the early stages of the disease. Only two drugs (benznidazole and nifurtimox) have so far been marketed and both share various limitations such as variable efficacy, many side effects and long duration of treatment, thus reducing compliance. The in vitro and in vivo efficacy of poly-aggregated amphotericin B (AmB), encapsulated poly-aggregated AmB in albumin microspheres (AmB-AME) and dimeric AmB - sodium deoxycholate micelles (AmB-NaDC) was evaluated...
February 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28194625/trypanosomiasis-challenge-estimation-using-the-diminazene-aceturate-berenil-index-in-zebu-in-gabon
#5
Brieuc G A Cossic, Brice Adjahoutonon, Pierre Gloaguen, Gui Lov Dibanganga, Gael Maganga, Pascal Leroy, Ewan T MacLeod, Kim Picozzi
A longitudinal study was conducted within a cattle ranch in Gabon to determine the diminazene aceturate (Berenil) index (DAI) in a group of Zebu, raised under low tsetse density; this measure providing an assessment of trypanosomiasis risk. The objective was to evaluate the trypanosomiasis pressure thus informing trypanosomiasis control methods and cattle management. Twenty female adult Zebu were monitored for 24 weeks during the dry season. Blood samples were collected on a weekly basis and subjected to parasitological and haematological analysis (n = 480), using the buffy-coat method and the packed cell volume value (PCV), respectively, infected animals were treated with a single intramuscular injection of diminazene aceturate (8 mg/kg)...
February 14, 2017: Tropical Animal Health and Production
https://www.readbyqxmd.com/read/28189085/synthesis-and-antitrypanosomal-activities-of-novel-pyridylchalcones
#6
Avninder S Bhambra, Ketan C Ruparelia, Hoon L Tan, Deniz Tasdemir, Hollie Burrell-Saward, Vanessa Yardley, Kenneth J M Beresford, Randolph R J Arroo
A library of novel pyridylchalcones were synthesised and screened against Trypanosoma brucei rhodesiense. Eight were shown to have good activity with the most potent 8 having an IC50 value of 0.29 μM. Cytotoxicity testing with human KB cells showed a good selectivity profile for this compound with a selectivity index of 47. Little activity was seen when the library was tested against Leishmania donovani. In conclusion, pyridylchalcones are promising leads in the development of novel compounds for the treatment of human African trypanosomiasis (HAT)...
January 23, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28187957/discovery-of-n-2-aminoethyl-n-benzyloxyphenyl-benzamides-new-potent-trypanosoma-brucei-inhibitors
#7
Andriy Buchynskyy, J Robert Gillespie, Matthew A Hulverson, Joshua McQueen, Sharon A Creason, Ranae M Ranade, Nicole A Duster, Michael H Gelb, Frederick S Buckner
A phenotypic screen of a compound library for antiparasitic activity on Trypanosoma brucei, the causative agent of Human African Trypanosomiasis (HAT), led to the identification of N-(2-aminoethyl)-N-phenyl benzamides as a starting point for hit-to-lead medicinal chemistry. Eighty two analogues were prepared, which led to the identification of a set of highly potent N-(2-aminoethyl)-N-benzyloxyphenyl benzamides with the most potent compound 73 having an in vitro EC50=0.001μM. The compounds displayed drug-like properties when tested in a number of in vitro assays...
November 12, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28185085/h-dependent-inorganic-phosphate-uptake-in-trypanosoma-brucei-is-influenced-by-myo-inositol-transporter
#8
Thais Russo-Abrahão, Carolina Macedo Koeller, Michael E Steinmann, Stephanie Silva-Rito, Thaissa Marins-Lucena, Michele Alves-Bezerra, Naira Ligia Lima-Giarola, Iron Francisco de-Paula, Amaia Gonzalez-Salgado, Erwin Sigel, Peter Bütikofer, Katia Calp Gondim, Norton Heise, José Roberto Meyer-Fernandes
Trypanosoma brucei is an extracellular protozoan parasite that causes human African trypanosomiasis or "sleeping sickness". During the different phases of its life cycle, T. brucei depends on exogenous inorganic phosphate (Pi), but little is known about the transport of Pi in this organism. In the present study, we showed that the transport of (32)Pi across the plasma membrane follows Michaelis-Menten kinetics and is modulated by pH variation, with higher activity at acidic pH. Bloodstream forms presented lower Pi transport in comparison to procyclic forms, that displayed an apparent K0...
February 9, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28162093/evaluating-the-impact-of-targeting-livestock-for-the-prevention-of-human-and-animal-trypanosomiasis-at-village-level-in-districts-newly-affected-with-t-b-rhodesiense-in-uganda
#9
Louise Hamill, Kim Picozzi, Jenna Fyfe, Beatrix von Wissmann, Sally Wastling, Nicola Wardrop, Richard Selby, Christine Amongi Acup, Kevin L Bardosh, Dennis Muhanguzi, John D Kabasa, Charles Waiswa, Susan C Welburn
BACKGROUND: Uganda has suffered from a series of epidemics of Human African Trypanosomiasis (HAT), a tsetse transmitted disease, also known as sleeping sickness. The area affected by acute Trypanosoma brucei rhodesiense HAT (rHAT) has been expanding, driven by importation of infected cattle into regions previously free of the disease. These regions are also affected by African Animal Trypanosomiasis (AAT) demanding a strategy for integrated disease control. METHODS: In 2008, the Public Private Partnership, Stamp Out Sleeping Sickness (SOS) administered a single dose of trypanocide to 31 486 head of cattle in 29 parishes in Dokolo and Kaberamaido districts...
February 6, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28157150/trypanocidal-activity-of-quinoxaline-1-4-di-n-oxide-derivatives-as-trypanothione-reductase-inhibitors
#10
Karla Fabiola Chacón-Vargas, Benjamin Nogueda-Torres, Luvia E Sánchez-Torres, Erick Suarez-Contreras, Juan Carlos Villalobos-Rocha, Yuridia Torres-Martinez, Edgar E Lara-Ramirez, Giulia Fiorani, R Luise Krauth-Siegel, Maria Laura Bolognesi, Antonio Monge, Gildardo Rivera
Chagas disease or American trypanosomiasis is a worldwide public health problem. In this work, we evaluated 26 new propyl and isopropyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives as potential trypanocidal agents. Additionally, molecular docking and enzymatic assays on trypanothione reductase (TR) were performed to provide a basis for their potential mechanism of action. Seven compounds showed better trypanocidal activity on epimastigotes than the reference drugs, and only four displayed activity on trypomastigotes; T-085 was the lead compound with an IC50 = 59...
February 1, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28153468/anti-malarial-synergy-of-secondary-metabolites-from-morinda-lucida-benth
#11
Bertha Chithambo, Xavier Siwe Noundou, Rui W M Krause
ETHNOPHARMACOLOGICAL RELEVANCE: The roots, stem and leaves of Morinda lucida are used in some African countries as treatment against different types of fevers including yellow fever, malaria, trypanosomiasis and feverish conditions during child birth. AIM OF THE STUDY: To determine the in vitro cell toxicity and anti-malarial activity of the extracts of stem bark of M. lucida and to identify the secondary metabolites in the extract that may be responsible for this activity...
January 30, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28117003/a-brief-review-of-drug-discovery-research-for-human-african-trypanosomiasis
#12
Danica R Cullen, Mauro Mocerino
Human African Trypanosomiasis (HAT), a neglected disease endemic in Sub-Saharan Africa, is usually fatal if left untreated. It is caused by the parasite Trypanosoma brucei, and is spread by the tsetse fly. The drugs currently available to treat HAT are few, and limited in efficacy. Furthermore, resistance towards these drugs is beginning to grow. In the last 25 years only one advance has been made into HAT treatment and consequently, there is an increasing need for new drugs to be sought that are able to effectively treat this disease...
January 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28110521/from-cells-to-mice-to-target-characterization-of-neu-1053-sb-443342-and-its-analogs-for-treatment-of-human-african-trypanosomiasis
#13
William G Devine, Rosario Díaz González, Gloria Ceballos-Perez, Domingo Isaac Rojas-Barros, Takashi Satoh, Westley Tear, Ranae M Ranade, Ximena Barros-Álvarez, Wim G J Hol, Frederick S Buckner, Miguel Navarro, Michael P Pollastri
Human African Trypanosomiasis is a neglected tropical disease that is lethal if left untreated. Existing therapeutics have limited efficacy and severe associated toxicities. 2-(2-(((3-((1H-Benzo[d]imidazol-2-yl)amino)propyl)amino)methyl)-4,6-dichloro-1H-indol-1-yl)ethan-1-ol (NEU-1053) has recently been identified from a high throughput screen of >42,000 compounds as a highly potent and fast acting trypanocidal agent capable of curing a blood stream infection of T. brucei in mice. We have designed a library of analogs to probe the SAR and improve the predicted CNS exposure of NEU-1053...
January 22, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28099874/igm-lgg-and-il-6-profiles-in-the-trypanosoma-brucei-brucei-monkey-model-of-human-african-trypanosomiasis
#14
Maxwell W Waema, Naomi W Maina, Maina Ngotho, Simon M Karanja, Beatrice M Gachie, Dawn N Maranga, John M Kagira
Human African trypanosomiasis (HAT) patients manifest immunological profiles, whose variations over time can be used to indicate disease progression. However, monitoring of these biomarkers in human patients is beset by several limitations which can be offset by using chronic animal models. A recent improved monkey model of HAT using a Trypanosoma brucei brucei isolate has been developed but the immunological profile has not been elucidated. The objectives of the current study was to determine the IgM, IgG and IL-6 profiles in blood and cerebrospinal fluid (CSF) in vervet monkeys infected with T...
January 15, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28087440/an-overlooked-horticultural-crop-smyrnium-olusatrum-as-a-potential-source-of-compounds-effective-against-african-trypanosomiasis
#15
Riccardo Petrelli, Farahnaz Ranjbarian, Stefano Dall'Acqua, Fabrizio Papa, Romilde Iannarelli, Stephane L Ngahang Kamte, Sauro Vittori, Giovanni Benelli, Filippo Maggi, Anders Hofer, Loredana Cappellacci
Among natural products, sesquiterpenes have shown promising inhibitory effects against bloodstream forms of Trypanosoma brucei, the protozoan parasite causing human African trypanosomiasis (HAT). Smyrnium olusatrum (Apiaceae), also known as Alexanders or wild celery, is a neglected horticultural crop characterized by oxygenated sesquiterpenes containing a furan ring. In the present work we explored the potential of its essential oils obtained from different organs and the main oxygenated sesquiterpenes, namely isofuranodiene, germacrone and β-acetoxyfuranoeudesm-4(15)-ene, as inhibitors of Trypanosoma brucei...
April 2017: Parasitology International
https://www.readbyqxmd.com/read/28074881/erratum-discovery-of-a-carbazole-derived-lead-drug-for-human-african-trypanosomiasis
#16
Sarah M Thomas, Andrei Purmal, Michael Pollastri, Kojo Mensa-Wilmot
No abstract text is available yet for this article.
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28071587/new-imidazole-based-compounds-active-against-trypanosoma-cruzi
#17
Oluyomi Stephen Adeyemi, Maria Teresa Molina, Abiodun Omokehinde Eseola, Cristina Fonseca-Berzal, Alicia Gomez-Barrio
Current drugs available for the treatment of Chagas disease are fraught with several challenges including severe toxicity and limited efficacy. These factors coupled with the absence of effective drugs for treating the chronic stage of the disease have rendered the development of new drugs against Chagas disease a priority. This study screened several imidazole-based compounds for anti-Trypanosoma potential. Using in vitro experimental infection model, several imidazole-based compounds were screened for anti-proliferative effect on Trypanosoma cruzi epimastigotes...
January 10, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28066534/chagas-disease-research-and-development-is-there-light-at-the-end-of-the-tunnel
#18
REVIEW
Eric Chatelain
Chagas disease, or American trypanosomiasis, is the result of infection by the parasite Trypanosoma cruzi. It is endemic in Latin America, and spreading around the globe due to human migration. Although it was first identified more than a century ago, only two old drugs are available for treatment and a lot of questions related to the disease progression, its pathologies, and not to mention the assessment of treatment efficacy, are subject to debate and remain to be answered. Indeed, the current status of evidence and data available does not allow any absolute statement related to treatment needs and outcome for Chagas patients to be made...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/28056016/predicting-the-impact-of-intervention-strategies-for-sleeping-sickness-in-two-high-endemicity-health-zones-of-the-democratic-republic-of-congo
#19
Kat S Rock, Steve J Torr, Crispin Lumbala, Matt J Keeling
Two goals have been set for Gambian human African trypanosomiasis (HAT), the first is to achieve elimination as a public health problem in 90% of foci by 2020, and the second is to achieve zero transmission globally by 2030. It remains unclear if certain HAT hotspots could achieve elimination as a public health problem by 2020 and, of greater concern, it appears that current interventions to control HAT in these areas may not be sufficient to achieve zero transmission by 2030. A mathematical model of disease dynamics was used to assess the potential impact of changing the intervention strategy in two high-endemicity health zones of Kwilu province, Democratic Republic of Congo...
January 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28043795/evaluation-of-substituted-ebselen-derivatives-as-potential-trypanocidal-agents
#20
Heeren M Gordhan, Stephen L Patrick, Maria I Swasy, Amber L Hackler, Mark Anayee, Jennifer E Golden, James C Morris, Daniel C Whitehead
Human African trypanosomiasis is a disease of sub-Saharan Africa, where millions are at risk for the illness. The disease, commonly referred to as African sleeping sickness, is caused by an infection by the eukaryotic pathogen, Trypanosoma brucei. Previously, a target-based high throughput screen revealed ebselen (EbSe), and its sulfur analog, EbS, to be potent in vitro inhibitors of the T. brucei hexokinase 1 (TbHK1). These molecules also exhibited potent trypanocidal activity in vivo. In this manuscript, we synthesized a series of sixteen EbSe and EbS derivatives bearing electron-withdrawing carboxylic acid and methyl ester functional groups, and evaluated the influence of these substituents on the biological efficacy of the parent scaffold...
February 1, 2017: Bioorganic & Medicinal Chemistry Letters
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