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T. Cruzi

Alice Ricardo-Silva, Teresa Cristina Monte Gonçalves, José Francisco Luitgards-Moura, Catarina Macedo Lopes, Silvano Pedrosa da Silva, Amanda Queiroz Bastos, Nathalia Coelho Vargas, Maria-Rosa Goreti Freitas
During a medical entomology course in Boa Vista, Roraima, colonies of Triatoma maculata closely associated with pigeon nests were observed in concrete air-conditioner box located on the external plastered and cemented walls of a modern brick-built apartment block. In only one eight-hole ceramic brick, located inside one air-conditioner box, 127 specimens of T. maculata were collected. T. maculata is a recognised vector of Trypanosoma cruzi in the surrounding area and its domiciliation increases the risk of Chagas disease transmission...
October 13, 2016: Memórias do Instituto Oswaldo Cruz
J A DE Fuentes-Vicente, M Cabrera-Bravo, J N Enríquez-Vara, M I Bucio-Torres, A E Gutiérrez-Cabrera, D G Vidal-López, J A Martínez-Ibarra, P M Salazar-Schettino, A Córdoba-Aguilar
Little is known about how the virulence of a human pathogen varies in the environment it shares with its vector. This study focused on whether the virulence of Trypanosoma cruzi (Trypanosomatida: Trypanosomatidae), the causal agent of Chagas' disease, is related to altitude. Accordingly, Triatoma dimidiata (Hemiptera: Reduviidae) specimens were collected at three different altitudes (300, 700 and 1400 m a.s.l.) in Chiapas, Mexico. The parasite was then isolated to infect uninfected T. dimidiata from the same altitudes, as well as female CD-1 mice...
October 18, 2016: Medical and Veterinary Entomology
Christopher A Seid, Kathryn M Jones, Jeroen Pollet, Brian Keegan, Elissa Hudspeth, Molly Hammond, Junfei Wei, C Patrick McAtee, Leroy Versteeg, Amanda Gutierrez, Zhuyun Liu, Bin Zhan, Jonathan L Respress, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez
A therapeutic vaccine for human Chagas disease is under development by the Sabin Vaccine Institute Product Development Partnership. The aim of the vaccine is to significantly reduce the parasite burden of Trypanosoma cruzi in humans, either as a standalone product or in combination with conventional chemotherapy. Vaccination of mice with Tc24 formulated with monophosphoryl-lipid A (MPLA) adjuvant results in a Th1 skewed immune response with elevated IgG2a and IFNγ levels and a statistically significant decrease in parasitemia following T...
October 13, 2016: Human Vaccines & Immunotherapeutics
Paula Regina Elias, Gleicekelly Silva Coelho, Viviane Flores Xavier, Policarpo Ademar Sales Junior, Alvaro José Romanha, Silvane Maria Fonseca Murta, Claudia Martins Carneiro, Nilton Soares Camilo, Flaviane Francisco Hilário, Jason Guy Taylor
A series of novel xylitan derivatives derived from xylitol were synthesized using operationally simple procedures. A xylitan acetonide was the key intermediate used to prepare benzoate, arylsulfonate esters and 1,2,3-triazole derivatives of xylitan. These compounds were evaluated for their in vitro anti-Trypanosoma cruzi activity against trypomastigote and amastigote forms of the parasite in T. cruzi-infected cell lineages. Benznidazole was used as positive control against T. cruzi and cytotoxicity was determined in mammalian L929 cells...
October 10, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Monica Rodríguez-Bolaños, Nallely Cabrera, Ruy Perez-Montfort
The reactivation of triosephosphate isomerase (TIM) from unfolded monomers induced by guanidine hydrochloride involves different amino acids of its sequence in different stages of protein refolding. We describe a systematic mutagenesis method to find critical residues for certain physico-chemical properties of a protein. The two similar TIMs of Trypanosoma brucei and Trypanosoma cruzi have different reactivation velocities and efficiencies. We used a small number of chimeric enzymes, additive mutants and planned site-directed mutants to produce an enzyme from T...
October 2016: Open Biology
M B Huante, S Gupta, V C Calderon, S J Koo, M Sinha, B A Luxon, N J Garg, J J Endsley
Pathogens frequently exploit or evade inflammasome activation in order to survive and proliferate. Alternatively, inadequate inflammasome activation by attenuated microorganisms or adjuvanted subunit vaccines may contribute to poor longevity of protection. To further understand these pathways, we determined the differential inflammasome transcriptome of human THP monocyte-derived macrophages in response to Mycobacterium bovis BCG, as compared to LPS or Trypanosoma cruzi. The results identify the highly specific innate recognition programs associated with inflammasome activation by human macrophages exposed to these microbial stimuli...
September 28, 2016: Tuberculosis
Lygia M Malvestio, Mara Rúbia N Celes, Linda A Jelicks, Herbert B Tanowitz, Cibele M Prado
Dystrophin, an important protein of the dystrophin-glycoprotein complex, has been implicated in the pathogenesis of experimental Chagas disease. It is important for the maintenance of cell shape and contraction force transmission. Dystrophin loss has been related to end-stage cardiac myopathies and proposed as a common route for myocardial dysfunction and progression to advanced heart failure. Evidence suggests that calpains, calcium-dependent proteases, digest dystrophin when the calcium concentration is compatible with their activation...
October 11, 2016: Parasitology Research
Gyongseon Yang, Nakyung Lee, Jean-Robert Ioset, Joo Hwan No
In order to understand the key parameters influencing drug susceptibility, different Trypanosoma cruzi assay protocols were evaluated using a comparative assay design. The assays compared in this study were an image-based intracellular T. cruzi assay quantified through an image-mining algorithm and an intracellular assay utilizing a β-galactosidase-expressing T. cruzi strain. Thirty-one reference compounds known to exhibit activities against intracellular T. cruzi were used as benchmarks. Initial comparison using EC50 values from two assays showed a very poor correlation, with an R(2) value of 0...
October 11, 2016: Journal of Biomolecular Screening
Verónica Seguel, Lorena Castro, Chantal Reigada, Leonel Cortes, María V Díaz, Mariana R Miranda, Claudio A Pereira, Michel Lapier, Carolina Campos-Estrada, Antonio Morello, Ulrike Kemmerling, Juan D Maya, Rodrigo López-Muñoz
Benznidazole is the first-line drug used in treating Chagas disease, which is caused by the parasite Trypanosoma cruzi (T. cruzi). However, benznidazole has limited efficacy and several adverse reactions. Pentamidine is an antiprotozoal drug used in the treatment of leishmaniasis and African trypanosomiasis. In T. cruzi, pentamidine blocks the transport of putrescine, a precursor of trypanothione, which constitutes an essential molecule in the resistance of T. cruzi to benznidazole. In the present study, we describe the effect of the combination of benznidazole and pentamidine on isolated parasites, mammalian cells and in mice infected with T...
October 8, 2016: Experimental Parasitology
Deyanira Pérez-Morales, Karla Daniela Rodríguez Hernández, Ignacio Martínez, Lourdes Teresa Agredano-Moreno, Luis Felipe Jiménez-García, Bertha Espinoza
Trypanosoma cruzi is the etiological agent of Chagas disease. The life cycle of this protozoan parasite is digenetic because it alternates its different developmental forms through two hosts, a vector insect and a vertebrate host. As a result, the parasites are exposed to sudden and drastic environmental changes causing cellular stress. The stress response to some types of stress has been studied in T. cruzi, mainly at the molecular level; however, data about ultrastructure and physiological state of the cells in stress conditions are scarce or null...
October 6, 2016: Cell Stress & Chaperones
Qiana L Matthews, Anitra L Farrow, Girish Rachakonda, Linlin Gu, Pius Nde, Alexandre Krendelchtchikov, Siddharth Pratap, Shruti S Sakhare, Steffanie Sabbaj, Maria F Lima, Fernando Villalta
BACKGROUND: Previously we reported that a hexon-modified adenovirus (Ad) vector containing the invasive neutralizing epitope of Trypanosoma cruzi (T. cruzi) trypomastigote gp83 (Ad5-gp83) provided immunoprotection against T. cruzi infection. The purpose of this work was to design an improved vaccine for T. cruzi using a novel epitope capsid incorporation strategy. Thus, we evaluated the immunoprotection raised by co-immunization with Ad5-gp83 and an Ad vector containing an epitope (ASP-M) of the T...
October 2016: Pathogens & Immunity
Diego Montenegro, Mauricio Vera, Liliana Zuleta, Violeta Llanos, Angela Junqueira
Objectives Present a strategy to determine the baseline in endemic areas in the process of vector interruption for Chagas disease (CHD). Methods A social and environmental questionnaire and an entomological survey evaluated the physical conditions of dwellings, the inhabitants' knowledge of CHD, the entomological triatomine indicators and the statistical relationship among these variables. Results Colonization and natural infection with Trypanosoma cruzi exist in Rhodnius prolixus, the principal vector of CHD in Colombia...
June 2016: Revista Panamericana de Salud Pública, Pan American Journal of Public Health
Luz M Rodeles, Miguel H Vicco, Iván A Bontempi, Alvaro Siano, Georgina Tonarelli, Oscar A Bottasso, Pablo Arias, Iván S Marcipar
OBJECTIVE: Autoantibodies cross-reacting with the β1 adrenergic receptor (anti-β1AR and anti-p2β) and cardiac myosin antigens (anti-B13), have been related to the pathogenesis of chronic Chagas heart disease (CCHD). Studies exploring their levels in different stages are scarce. We aimed to evaluate the relationship of these autoantibodies with the clinical profile of chronic patients, especially regarding their classificatory accuracy in severe presentation with heart failure. METHODS AND RESULTS: We conducted a cross-sectional study of 155 T...
October 3, 2016: Tropical Medicine & International Health: TM & IH
Sue-Jie Koo, Imran Chowdhury, Bartosz Szczesny, Xianxiu Wan, Nisha J Garg
BACKGROUND: Trypanosoma cruzi is the causative agent of chronic chagasic cardiomyopathy. Why macrophages (mϕs), the early responders to infection, fail to achieve parasite clearance is not known. METHODS: Mouse (RAW 264.7) and human (THP-1 and primary) mϕs were infected with T. cruzi TcI isolates, SylvioX10/4 (SYL, virulent) and TCC (non-pathogenic), for 3 h and 18 h that represent mϕ stimulation and infection states, respectively. Mϕs incubated with LPS/IFN-γ and IL-4 were used as controls...
October 3, 2016: Infection and Immunity
Carlos Ramon Nascimento Brito, Craig S McKay, Maíra Araújo Azevedo, Luíza Costa Brandão Santos, Ana Paula Venuto, Daniela Ferreira Nunes, Daniella Alchaar D'Ávila, Gisele Macedo Rodrigues da Cunha, Igor Correia Almeida, Ricardo Tostes Gazzinelli, Lucia Maria Cunha Galvão, Egler Chiari, Carlos A Sanhueza, M G Finn, Alexandre Ferreira Marques
The α-Gal antigen [Galα(1,3)Galβ(1,4)GlcNAcα] is an immunodominant epitope displayed by infective trypomastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease. A virus-like particle displaying a high density of α-Gal was found to be a superior reagent for the ELISA-based serological diagnosis of Chagas disease and the assessment of treatment effectiveness. A panel of sera from patients chronically infected with T. cruzi, both untreated and benznidazole-treated, was compared with sera from patients with leishmaniasis and from healthy donors...
October 4, 2016: ACS Infectious Diseases
Catherine W Cai, Jennifer R Blase, Xiuli Zhang, Christopher S Eickhoff, Daniel F Hoft
Th17 cells are a subset of CD4+ T cells known to play a central role in the pathogenesis of many autoimmune diseases, as well as in the defense against some extracellular bacteria and fungi. However, Th17 cells are not believed to have a significant function against intracellular infections. In contrast to this paradigm, we have discovered that Th17 cells provide robust protection against Trypanosoma cruzi, the intracellular protozoan parasite that causes Chagas disease. Th17 cells confer significantly stronger protection against T...
October 2016: PLoS Pathogens
D Musuyu Muganza, B Fruth, J Lami Nzunzu, E Tuenter, K Foubert, P Cos, L Maes, R Cimanga Kanyanga, V Exarchou, S Apers, L Pieters
ETHNOPHARMACOLOGICAL RELEVANCE: The Nkundo people (Nkundo area of Bolongo, Mai-Ndombe district, Bandundu Province, DR Congo) use various plant parts of the tree Greenwayodendron suaveolens (Engl. & Diels) Verdc. (syn. Polyalthia suaveolens Engl. & Diels) (Annonaceae) against malaria, but its antiprotozoal constituents are not known. MATERIALS AND METHODS: The crude 80% ethanol extract from the fruits, leaves, root bark and stem bark and 16 fractions were assessed in vitro for their antiprotozoal activity against Trypanosoma brucei brucei, T...
September 29, 2016: Journal of Ethnopharmacology
Federico Nicolás Penas, Ágata Carolina Cevey, Sofía Siffo, Gerardo Ariel Mirkin, Nora Beatriz Goren
Trypanosoma cruzi, the etiological agent of Chagas' disease, causes an intense inflammatory response in several tissues, including the liver. Since this organ is central to metabolism, its infection may be reflected in the outcome of the disease. 15-deoxy-Δ(12,14) prostaglandin J2 (15dPGJ2), a natural agonist of peroxisome-proliferator activated receptor (PPAR) γ, has been shown to exert anti-inflammatory effects in the heart upon T. cruzi infection. However, its role in the restoration of liver function and reduction of liver inflammation has not been studied yet...
September 28, 2016: Experimental Parasitology
Guilherme de Paula Costa, Laís Roquete Lopes, Maria Cláudia da Silva, Aline Luciano Horta, Washington Martins Pontes, Cristiane M Milanezi, Paulo Marcos da Mata Guedes, Wanderson Geraldo de Lima, Richard Schulz, João Santana da Silva, Andre Talvani
Chemokines (CKs) and chemokine receptors (CKR) promote leukocyte recruitment into cardiac tissue infected by the Trypanosoma cruzi. This study investigated the long-term treatment with subantimicrobial doses of doxycycline (Dox) in association, or not, with benznidazole (Bz) on the expression of CK and CKR in cardiac tissue. Thirty mongrel dogs were infected, or not, with the Berenice-78 strain of T. cruzi and grouped according their treatments: (i) two months after infection, Dox (50 mg/kg) 2x/day for 12 months; (ii) nine months after infection, Bz (3,5 mg/kg) 2x/day for 60 days; (iii) Dox + Bz; and (iv) vehicle...
2016: Mediators of Inflammation
C Díaz-Luján, M F Triquell, C Castillo, D Hardisson, U Kemmerling, R E Fretes
American trypanosomiasis has long been a neglected disease endemic in LatinAmerica, but congenital transmission has now spread Chagas disease to cause a global health problem. As the early stages of the infection of placental tissue and the vertical transmission by Trypanosoma cruzi are still not well understood, it is important to investigate the relevance of the first structure of the placental barrier in chorionic villi infection by T. cruzi during the initial stage of the infection. Explants of human chorionic villi from healthy pregnant women at term were denuded of their syncytiotrophoblast and co-cultured for 3h, 24h and 96h with 800,000 trypomastigotes (simulating acute infection)...
September 26, 2016: Acta Tropica
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