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Chaga's disease

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https://www.readbyqxmd.com/read/28203518/inositol-1-4-5-trisphosphate-receptor-determines-intracellular-ca-2-concentration-in-trypanosoma-cruzi-throughout-its-life-cycle
#1
Muneaki Hashimoto, Motomichi Doi, Nagomi Kurebayashi, Koji Furukawa, Hiroko Hirawake-Mogi, Yoshihiro Ohmiya, Takashi Sakurai, Toshihiro Mita, Katsuhiko Mikoshiba, Takeshi Nara
Regulation of intracellular Ca(2+) concentration ([Ca(2+)]i) is vital for eukaryotic organisms. Recently, we identified a Ca(2+) channel (TcIP 3R) associated with intracellular Ca(2+) stores in Trypanosoma cruzi, the parasitic protist that causes Chagas disease. In this study, we measured [Ca(2+)]i during the parasite life cycle and determined whether TcIP 3R is involved in the observed variations. Parasites expressing R-GECO1, a red fluorescent, genetically encoded Ca(2+) indicator for optical imaging that fluoresces when bound to Ca(2+), were produced...
December 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28202792/towards-a-new-strategy-for-the-diagnosis-of-congenital-trypanosoma-cruzi-infection
#2
Alba Abras, Carmen Muñoz, Cristina Ballart, Pere Berenguer, Teresa Llovet, Mercedes Herrero, Silvia Tebar, María-Jesús Pinazo, Elizabeth Posada, Carmen Martí, Victoria Fumadó, Jordi Bosch, Oriol Coll, Teresa Juncosa, Gemma Ginovart, Josep Armengol, Joaquim Gascón, Montserrat Portús, Montserrat Gállego
The immigration of Latin American women of childbearing age has spread the congenital transmission of Chagas disease to non-endemic areas, and the disease is now a worldwide problem. Some European health authorities have implemented screening programs to prevent vertical transmission, but the lack of a uniform protocol calls for the urgent establishment of a new strategy, common for all laboratories. Our aims were (i) to analyze the trend of passive IgG antibodies in the newborn by means of five serological tests for the diagnosis and follow-up of congenital Trypanosoma cruzi infection, (ii) to assess the utility of these techniques for diagnosing a congenital transmission, and (iii) to propose a strategy for a prompt, efficient and cost-effective diagnosis of T...
February 15, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28202039/immune-modulation-of-some-autoimmune-diseases-the-critical-role-of-macrophages-and-neutrophils-in-the-innate-and-adaptive-immunity
#3
REVIEW
Kely Campos Navegantes, Rafaelli de Souza Gomes, Priscilla Aparecida Tártari Pereira, Paula Giselle Czaikoski, Carolina Heitmann Mares Azevedo, Marta Chagas Monteiro
Macrophages and neutrophils are key components involved in the regulation of numerous chronic inflammatory diseases, infectious disorders, and especially certain autoimmune disease. However, little is known regarding the contribution of these cells to the pathogenesis of autoimmune disorders. Recent studies have aimed to clarify certain important factors affecting the immunogenicity of these cells, including the type and dose of antigen, the microenvironment of the cell-antigen encounter, and the number, subset, and phenotype of these cells, which can prevent or induce autoimmune responses...
February 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28199333/comparative-and-functional-triatomine-genomics-reveals-reductions-and-expansions-in-insecticide-resistance-related-gene-families
#4
Lucila Traverso, Andrés Lavore, Ivana Sierra, Victorio Palacio, Jesús Martinez-Barnetche, José Manuel Latorre-Estivalis, Gaston Mougabure-Cueto, Flavio Francini, Marcelo G Lorenzo, Mario Henry Rodríguez, Sheila Ons, Rolando V Rivera-Pomar
BACKGROUND: Triatomine insects are vectors of Trypanosoma cruzi, a protozoan parasite that is the causative agent of Chagas' disease. This is a neglected disease affecting approximately 8 million people in Latin America. The existence of diverse pyrethroid resistant populations of at least two species demonstrates the potential of triatomines to develop high levels of insecticide resistance. Therefore, the incorporation of strategies for resistance management is a main concern for vector control programs...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28198632/engineering-oral-and-parenteral-amorphous-amphotericin-b-formulations-against-experimental-trypanosoma-cruzi-infections
#5
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/28192425/improving-access-to-chagas-disease-diagnosis-and-etiologic-treatment-in-remote-rural-communities-of-the-argentine-chaco-through-strengthened-primary-health-care-and-broad-social-participation
#6
Paula Sartor, Ivana Colaianni, M Victoria Cardinal, Jacqueline Bua, Héctor Freilij, Ricardo E Gürtler
BACKGROUND: Rural populations in the Gran Chaco region have large prevalence rates of Trypanosoma cruzi infection and very limited access to diagnosis and treatment. We implemented an innovative strategy to bridge these gaps in 13 rural villages of Pampa del Indio held under sustained vector surveillance and control. METHODOLOGY: The non-randomized treatment program included participatory workshops, capacity strengthening of local health personnel, serodiagnosis, qualitative and quantitative PCRs, a 60-day treatment course with benznidazole and follow-up...
February 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28189084/synthesis-and-trypanocidal-activity-of-a-library-of-4-substituted-2-1h-pyrrolo-3-2-c-pyridin-2-yl-propan-2-ols
#7
Michael N Balfour, Caio H Franco, Carolina B Moraes, Lucio H Freitas-Junior, Hélio A Stefani
A library of 16 4-substituted 2-(1H-pyrrolo[3,2-c]pyridin-2-yl)propan-2-ols 17-32 has been synthesized for use in biological testing against Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. The 4-substituted 2-(1H-pyrrolo[3,2-c]pyridin-2-yl)propan-2-ols 17-32 were subjected to biological testing to evaluate their efficacy against intracellular Trypanosoma cruzi (Y strain) amastigotes infecting U2OS human cells, with benznidazole as a reference compound. The assay was performed in duplicate (two independent experiments) and submitted to High Content Analysis (HCA) for determination of trypanocidal activity...
February 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28185987/real-time-pcr-strategy-for-the-identification-of-trypanosoma-cruzi-discrete-typing-units-directly-in-chronically-infected-human-blood
#8
Catalina Muñoz-San Martín, Werner Apt, Inés Zulantay
The protozoan Trypanosoma cruzi is the causative agent of Chagas disease, a major public health problem in Latin America. This parasite has a complex population structure comprised by six or seven major evolutionary lineages (discrete typing units or DTUs) TcI-TcVI and TcBat, some of which have apparently resulted from ancient hybridization events. Because of the existence of significant biological differences between these lineages, strain characterization methods have been essential to study T. cruzi in its different vectors and hosts...
February 6, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28185826/chaetocin-a-histone-methyltransferase-inhibitor-impairs-proliferation-arrests-cell-cycle-and-induces-nucleolar-disassembly-in-trypanosoma-cruzi
#9
Aline Araujo Zuma, Jean de Oliveira Santos, Isabela Mendes, Wanderley de Souza, Carlos Renato Machado, E Maria Cristina M Motta
The Trypanosomatidae family includes pathogenic species of medical and veterinary interest. Chagas disease is endemic in Latin America, and about 8 million people are infected worldwide. There is a need for more effective drugs for the acute, undetermined and chronic phases of the disease that, in addition, do not cause side effects, stimulating the search for identification of new drug targets, as well as new chemotherapeutic targets. Trypanosomatids contain characteristic structures, such as the nucleus that undergoes a closed mitosis without chromosome formation and variations of chromatin packing in the different protozoa developmental stages...
February 6, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28185724/simplifying-nature-towards-the-design-of-broad-spectrum-kinetoplastid-inhibitors-inspired-by-acetogenins
#10
Eoin R Gould, Elizabeth F B King, Stefanie K Menzies, Andrew L Fraser, Lindsay B Tulloch, Marija K Zacharova, Terry K Smith, Gordon J Florence
The need for new treatments for the neglected tropical diseases African sleeping sickness, Chagas disease and Leishmaniasis remains urgent with the diseases widespread in tropical regions, affecting the world's very poorest. We have previously reported bis-tetrahydropyran 1,4-triazole analogues designed as mimics of the annonaceous acetogenin natural product chamuvarinin, which maintained trypanocidal activity. Building upon these studies, we here report related triazole compounds with pendant heterocycles, mimicking the original butenolide of the natural product...
January 28, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28179991/a-homolog-of-cyclophilin-d-is-expressed-in-trypanosoma-cruzi-and-is-involved-in-the-oxidative-stress-damage-response
#11
Patricia L Bustos, Bibiana J Volta, Alina E Perrone, Natalia Milduberger, Jacqueline Bua
Mitochondria have an important role in energy production, homeostasis and cell death. The opening of the mitochondrial permeability transition pore (mPTP) is considered one of the key events in apoptosis and necrosis, modulated by cyclophilin D (CyPD), a crucial component of this protein complex. In Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, we have previously described that mitochondrial permeability transition occurs after oxidative stress induction in a cyclosporin A-dependent manner, a well-known cyclophilin inhibitor...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28179568/kinetics-subcellular-localization-and-contribution-to-parasite-virulence-of-a-trypanosoma-cruzi-hybrid-type-a-heme-peroxidase-tcapx-ccp
#12
Martín Hugo, Alejandra Martínez, Madia Trujillo, Damián Estrada, Mauricio Mastrogiovanni, Edlaine Linares, Ohara Augusto, Federico Issoglio, Ari Zeida, Darío A Estrín, Harry F G Heijnen, Lucía Piacenza, Rafael Radi
The Trypanosoma cruzi ascorbate peroxidase is, by sequence analysis, a hybrid type A member of class I heme peroxidases [TcAPx-cytochrome c peroxidase (CcP)], suggesting both ascorbate (Asc) and cytochrome c (Cc) peroxidase activity. Here, we show that the enzyme reacts fast with H2O2 (k = 2.9 × 10(7) M(-1)⋅s(-1)) and catalytically decomposes H2O2 using Cc as the reducing substrate with higher efficiency than Asc (kcat/Km = 2.1 × 10(5) versus 3.5 × 10(4) M(-1)⋅s(-1), respectively). Visible-absorption spectra of purified recombinant TcAPx-CcP after H2O2 reaction denote the formation of a compound I-like product, characteristic of the generation of a tryptophanyl radical-cation (Trp(233•+))...
February 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28179034/hosts-and-vectors-of-trypanosoma-cruzi-discrete-typing-units-in-the-chagas-disease-endemic-region-of-the-paraguayan-chaco
#13
Nidia Acosta, Elsa López, Michael D Lewis, Martin S Llewellyn, Ana Gómez, Fabiola Román, Michael A Miles, Matthew Yeo
Active Trypanosoma cruzi transmission persists in the Gran Chaco region, which is considered hyperendemic for Chagas disease. Understanding domestic and sylvatic transmission cycles and therefore the relationship between vectors and mammalian hosts is crucial to designing and implementing improved effective control strategies. Here we describe the species of triatomine vectors and the sylvatic mammal reservoirs of T. cruzi, in different localities of the Paraguayan and Bolivian Chaco. We identify the T. cruzi genotypes discrete typing units (DTUs) and provide a map of their geographical distribution...
February 9, 2017: Parasitology
https://www.readbyqxmd.com/read/28178282/trypanosoma-cruzi-high-mobility-group-b-tchmgb-can-act-as-an-inflammatory-mediator-on-mammalian-cells
#14
Pamela Cribb, Virginia Perdomo, Victoria L Alonso, Romina Manarin, Jorge Barrios-Payan, Brenda Marquina-Castillo, Luis Tavernelli, Rogelio Hernández-Pando
BACKGROUND: High Mobility Group B (HMGB) proteins are nuclear architectural factors involved in chromatin remodeling and important nuclear events. HMGBs also play key roles outside the cell acting as alarmins or Damage-associated Molecular Patterns (DAMPs). In response to a danger signal these proteins act as immune mediators in the extracellular milieu. Moreover, these molecules play a central role in the pathogenesis of many autoimmune and both infectious and sterile inflammatory chronic diseases...
February 8, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28177036/correction-2-nd-brazilian-consensus-on-chagas-disease-2015
#15
(no author information available yet)
[This corrects the article doi: 10.1590/0037-8682-0505-2016].
February 6, 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28176530/effects-of-castration-on-penile-extracellular-matrix-morphology-in-domestic-cats
#16
Nathalia Cs Borges, Marco A Pereira-Sampaio, Vivian Alves Pereira, Marcelo Abidu-Figueiredo, Maurício Alves Chagas
Objectives This study was undertaken to verify the possible modifications caused by hormonal deprivation in the extracellular matrix in the penises of neutered cats. Methods Twenty-seven penises from domestic shorthair cats were collected: 14 samples from intact cats and 13 from neutered cats. Sections were stained with Weigert's resorcin-fuchsin, hematoxylin and eosin, and picrosirius red. Histomorphometric analysis was performed using light microscopy and image analysis software. The following parameters were analyzed: density of the elastic fibers and collagen fibers in the corpus spongiosum; density of the elastic fibers in the tunica albuginea of the corpus cavernosum and the tunica albuginea of the corpus spongiosum; luminal area of the urethra; area of the corpus spongiosum; area of the corpus cavernosum; and thickness of the urethral epithelium...
February 1, 2017: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/28173858/mortality-trends-for-neglected-tropical-diseases-in-the-state-of-sergipe-brazil-1980-2013
#17
Marcos Antônio Costa de Albuquerque, Danielle Menezes Dias, Lucas Teixeira Vieira, Carlos Anselmo Lima, Angela Maria da Silva
BACKGROUND: Neglected Tropical Diseases are a set of communicable diseases that affect the population so low socioeconomic status, particularly 1.4 billion people who are living below the poverty level. This study has investigated the magnitude and mortality time trends for these diseases in the state of Sergipe, Northeast Region of Brazil. METHODS: We conducted an ecological study of time series, based on secondary data derived from the Mortality Information System of the Ministry of Health...
February 8, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28167589/trypanosoma-cruzi-agent-of-chagas-disease-in-sympatric-human-and-dog-populations-in-colonias-of-the-lower-rio-grande-valley-of-texas
#18
Rachel Curtis-Robles, Italo B Zecca, Valery Roman-Cruz, Ester S Carbajal, Lisa D Auckland, Isidore Flores, Ann V Millard, Sarah A Hamer
The zoonotic, vector-borne parasite Trypanosoma cruzi causes Chagas disease throughout the Americas, but human and veterinary health burdens in the United States are unknown. We conducted a cross-sectional prevalence study in indigent, medically underserved human and cohabiting canine populations of seven south Texas border communities, known as colonias. Defining positivity as those samples that were positive on two or more independent tests, we found 1.3% seroprevalence in 233 humans, including one child born in the United States with only short-duration travel to Mexico...
February 6, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28167559/anti-trypanosomal-activity-of-sterol-14%C3%AE-demethylase-cyp51-inhibitors-vni-and-vfv-in-the-swiss-mouse-models-of-chagas-disease-induced-by-the-y-strain-trypanosoma-cruzi
#19
F H Guedes-da-Silva, D G J Batista, C F Da Silva, J S De Araújo, B P Pavão, M R Simões-Silva, M B Meuser, K C Demarque, O C Moreira, C Britto, G I Lepesheva, M N C Soeiro
Chagas disease is a life-threatening infection caused by a variety of genetically diverse strains of the protozoan parasite Trypanosoma cruzi The current treatment (benznidazole and nifurtimox) is unsatisfactory, and potential alternatives include inhibitors of sterol 14α-demethylase (CYP51), the cytochrome P450 enzyme essential for biosynthesis of sterols in eukaryotes and the major target for clinical and agricultural antifungals. Here we performed a comparative investigation of two protozoa-specific CYP51 inhibitors, VNI and its CYP51 structure-based derivative VFV, in the murine models of infection caused by the Y strain T...
February 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28167558/pharmacokinetic-and-tissue-distribution-of-benznidazole-after-oral-administration-in-mice
#20
Luísa Perin, Rodrigo Moreira da Silva, Kátia da Silva Fonseca, Jamille Mirelle de Oliveira Cardoso, Fernando Augusto Siqueira Mathias, Levi Eduardo Soares Reis, Israel Molina, Rodrigo Correa-Oliveira, Paula Melo de Abreu Vieira, Cláudia Martins Carneiro
Specific chemotherapy using Benznidazole (BNZ) for Chagas disease during the chronic stage is controversial due to its limited efficacy and toxic effects. Although BNZ has been used to treat Chagas disease since the 1970s, few studies about the biodistribution of this drug exist. In this study, BNZ tissue biodistribution in a murine model and its pharmacokinetic profile in plasma were monitored. A bioanalytical high-performance liquid chromatography with an ultraviolet detector (HPLC-UV) method was developed and validated according to the European Medicines Agency for quantification of BNZ in organs and plasma samples prepared by liquid-liquid extraction using ethyl acetate...
February 6, 2017: Antimicrobial Agents and Chemotherapy
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