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https://www.readbyqxmd.com/read/28938533/trans-sialidase-based-vaccine-candidate-protects-against-trypanosoma-cruzi-infection-not-only-inducing-an-effector-immune-response-but-also-affecting-cells-with-regulatory-suppressor-phenotype
#1
Estefanía Prochetto, Carolina Roldán, Iván A Bontempi, Daiana Bertona, Luz Peverengo, Miguel H Vicco, Luz M Rodeles, Ana R Pérez, Iván S Marcipar, Gabriel Cabrera
Prophylactic and/or therapeutic vaccines have an important potential to control Trypanosoma cruzi (T. cruzi)infection. The involvement of regulatory/suppressor immune cells after an immunization treatment and T. cruzi infection has never been addressed. Here we show that a new trans-sialidase-based immunogen (TSf) was able to confer protection, correlating not only with beneficial changes in effector immune parameters, but also influencing populations of cells related to immune control. Regarding the effector response, mice immunized with TSf showed a TS-specific antibody response, significant delayed-type hypersensitivity (DTH) reactivity and increased production of IFN-γ by CD8+ splenocytes...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28935948/novel-scaffolds-for-inhibition-of-cruzipain-identified-from-high-throughput-screening-of-anti-kinetoplastid-chemical-boxes
#2
Emir Salas-Sarduy, Lionel Urán Landaburu, Joel X Karpiak, Kevin P Madauss, Juan José Cazzulo, Fernán Agüero, Vanina Eder Alvarez
American Trypanosomiasis or Chagas disease is a prevalent, neglected and serious debilitating illness caused by the kinetoplastid protozoan parasite Trypanosoma cruzi. The current chemotherapy is limited only to nifurtimox and benznidazole, two drugs that have poor efficacy in the chronic phase and are rather toxic. In this scenario, more efficacious and safer drugs, preferentially acting through a different mechanism of action and directed against novel targets, are particularly welcome. Cruzipain, the main papain-like cysteine peptidase of T...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935551/anti-trypanosoma-anti-leishmania-and-cytotoxic-activities-of-natural-products-from-psidium-brownianum-mart-ex-dc-and-psidium-guajava-var-pomifera-analysed-by-lc-ms
#3
Celestina Elba Sobral de Souza, Ana Raquel Pereira da Silva, Maria Celeste Vega Gomez, Míriam Rolóm, Cathia Coronel, José Galberto Martins da Costa, Amanda K Sousa, Larissa A Rolim, Francisco Hugo Sobral de Souza, Henrique Douglas Melo Coutinho
Neglected diseases are those that are prevalent in developing countries, even with a rich biodiversity. These diseases still persist because of the lack of scientific studies, government negligence or failures of the public health system. This study aims to identify the composition of extracts and fractions from Psidium brownianum and Psidium guajava through LC-MS, to evaluate its in vitro anti-parasitic and cytotoxic activity against Trypanosoma cruzi, Leishmania brasiliensis and L. infantum epismastigote and promastigote forms, as well as mammalian cells...
September 18, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28926763/synthesis-and-2d-qsar-studies-of-neolignan-based-diaryl-tetrahydrofuran-and-furan-analogues-with-remarkable-activity-against-trypanosoma-cruzi-and-assessment-of-the-trypanothione-reductase-activity
#4
Ana Paula Hartmann, Marcelo Rodrigues de Carvalho, Lilian Sibelle Campos Bernardes, Milena Hoehr de Moraes, Eduardo Borges de Melo, Carla Duque Lopes, Mario Steindel, João Santana da Silva, Ivone Carvalho
Two series of diaryl-tetrahydrofuran and -furan were synthesised and screened for anti-trypanosomal activity against trypomastigote and amastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease. Based on evidence that modification of a natural product may result in a more effective drug than the natural product itself, and using known neolignan inhibitors veraguensin 1 and grandisin 2 as templates to synthesise simpler analogues, remarkable anti-trypanosomal activity and selectivity were found for 3,5-dimethoxylated diaryl-furan 5c and 2,4-dimethoxylated diaryl-tetrahydrofuran 4e analogues with EC50 0...
September 4, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28924146/apols-with-low-ph-dependence-can-kill-all-african-trypanosomes
#5
Frédéric Fontaine, Laurence Lecordier, Gilles Vanwalleghem, Pierrick Uzureau, Nick Van Reet, Martina Fontaine, Patricia Tebabi, Benoit Vanhollebeke, Philippe Büscher, David Pérez-Morga, Etienne Pays
The primate-specific serum protein apolipoprotein L1 (APOL1) is the only secreted member of a family of cell death promoting proteins (1-4) . APOL1 kills the bloodstream parasite Trypanosoma brucei brucei, but not the human sleeping sickness agents T.b. rhodesiense and T.b. gambiense (3) . We considered the possibility that intracellular members of the APOL1 family, against which extracellular trypanosomes could not have evolved resistance, could kill pathogenic T. brucei subspecies. Here we show that recombinant APOL3 (rAPOL3) kills all African trypanosomes, including T...
September 18, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28923601/beneficial-immunomodulatory-and-neuro-digestive-effect-in-trypanosoma-cruzi-infection-after-lycopodium-clavatum-13c-treatment
#6
Camila Fernanda Brustolin Aleixo, Fabiana Nabarro Ferraz, Paula Fernanda Massini, Carina Ribeiro Lopes, Gislaine Janaina Falkowski Temporini, Denise Lessa Aleixo, Silvana Marques de Araújo
Studies show that highly diluted medications demonstrate benefits in treating infections, constituting an alternative for their treatment. The present study evaluated the effects of Lycopodium clavatum, dynamization 13c, in Wistar rats infected with T. cruzi. In this study 42 male rats were intraperitoneally inoculated with T. cruzi - Y strain and allocated into groups: IC (infected control group) and Ly (treated with L. clavatum 13c). The cytokines dosage (IFN-γ, IL-12, IL-10, IL-4), quantification and morphometry of myenteric neurons were evaluated...
September 15, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28919885/trypanosoma-cruzi-evades-the-complement-system-as-an-efficient-strategy-to-survive-in-the-mammalian-host-the-specific-roles-of-host-parasite-molecules-and-trypanosoma-cruzi-calreticulin
#7
REVIEW
Galia Ramírez-Toloza, Arturo Ferreira
American Trypanosomiasis is an important neglected reemerging tropical parasitism, infecting about 8 million people worldwide. Its agent, Trypanosoma cruzi, exhibits multiple mechanisms to evade the host immune response and infect host cells. An important immune evasion strategy of T. cruzi infective stages is its capacity to inhibit the complement system activation on the parasite surface, avoiding opsonizing, immune stimulating and lytic effects. Epimastigotes, the non-infective form of the parasite, present in triatomine arthropod vectors, are highly susceptible to complement-mediated lysis while trypomastigotes, the infective form, present in host bloodstream, are resistant...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28915432/new-uses-for-old-complexes-the-very-first-report-on-the-trypanocidal-activity-of-symmetric-trinuclear-ruthenium-complexes
#8
Bruna Possato, Zumira Aparecida Carneiro, Sérgio de Albuquerque, Sofia Nikolaou
This work reports on the trypanocidal activity of a series of symmetric triruthenium complexes combined with azanaphthalene ligands of general formula [Ru3O(CH3COO)6(L)3]PF6 (L=(1) quinazoline (qui), (2) 5-nitroisoquinoline (5-nitroiq), (3) 5-bromoisoquinoline (5-briq), (4) isoquinoline (iq), (5) 5-aminoisoquinoline (5-amiq), and (6) 5,6,7,8-tetrahydroisoquinoline (thiq)). All complexes within the series presented in vitro trypanocidal activity against both the trypomastigote and amastigote forms of T. cruzi...
August 31, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28911515/chronic-chagas-heart-disease%C3%A2-management-from-etiology-to-cardiomyopathy-treatment
#9
REVIEW
Edimar Alcides Bocchi, Reinaldo Bulgarelli Bestetti, Mauricio Ibrahim Scanavacca, Edecio Cunha Neto, Victor Sarli Issa
Trypanosoma cruzi (T. cruzi) infection is endemic in Latin America and is becoming a worldwide health burden. It may lead to heterogeneous phenotypes. Early diagnosis of T. cruzi infection is crucial. Several biomarkers have been reported in Chagas heart disease (ChHD), but most are nonspecific for T. cruzi infection. Prognosis of ChHD patients is worse compared with other etiologies, with sudden cardiac death as an important mode of death. Most ChHD patients display diffuse myocarditis with fibrosis and hypertrophy...
September 19, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28905716/lack-of-trypanosoma-cruzi-infection-in-urban-roof-rats-rattus-rattus-at-a-texas-facility-housing-naturally-infected-nonhuman-primates
#10
Carolyn L Hodo, Nicole R Bertolini, John C Bernal, John L VandeBerg, Sarah A Hamer
The protozoan parasite Trypanosoma cruzi causes Chagas disease, uses kissing bugs as a vector, and is maintained in nature by a variety of wildlife reservoirs. Many natural cases of Chagas disease have been reported in NHP at facilities across the southern United States, where infected vectors and wildlife occur. Infection of NHP with T. cruzi can diminish their value as research models and lead to health problems and death. Identifying the modes of transmission and role of wildlife reservoirs in these facilities is therefore critical to guide interventions to reduce transmission...
January 1, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28895840/crucial-role-for-t-cell-intrinsic-il-18r-myd88-signaling-in-cognate-immune-response-to-intracellular-parasite-infection
#11
Ana-Carolina Oliveira, João Francisco Gomes-Neto, Carlos-Henrique Dantas Barbosa, Alessandra Granato, Bernardo S Reis, Bruno Maia Santos, Rita Fucs, Fábio B Canto, Helder I Nakaya, Alberto Nóbrega, Maria Bellio
MyD88 is the main adaptor molecule for TLR and IL-1R family members. Here, we demonstrated that T-cell intrinsic MyD88 signaling is required for proliferation, protection from apoptosis and expression of activation/memory genes during infection with the intracellular parasite Trypanosoma cruzi, as evidenced by transcriptome and cytometry analyses in mixed bone-marrow (BM) chimeras. The lack of direct IL-18R signaling in T cells, but not of IL-1R, phenocopied the absence of the MyD88 pathway, indicating that IL-18R is a critical MyD88-upstream pathway involved in the establishment of the Th1 response against an in vivo infection, a presently controvert subject...
September 12, 2017: ELife
https://www.readbyqxmd.com/read/28892479/towards-chagas-disease-elimination-neonatal-screening-for-congenital-transmission-in-rural-communities
#12
Pamela Marie Pennington, José Guillermo Juárez, Margarita Rivera Arrivillaga, Sandra María De Urioste-Stone, Katherine Doktor, Joe P Bryan, Clara Yaseli Escobar, Celia Cordón-Rosales
Chagas disease is a neglected tropical disease that continues to affect populations living in extreme poverty in Latin America. After successful vector control programs, congenital transmission remains as a challenge to disease elimination. We used the PRECEDE-PROCEED planning model to develop strategies for neonatal screening of congenital Chagas disease in rural communities of Guatemala. These communities have persistent high triatomine infestations and low access to healthcare. We used mixed methods with multiple stakeholders to identify and address maternal-infant health behaviors through semi-structured interviews, participatory group meetings, archival reviews and a cross-sectional survey in high risk communities...
September 11, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28892370/mass-spectrometry-based-chemical-cartography-of-a-cardiac-parasitic-infection
#13
Laura-Isobel McCall, James T Morton, Jean A Bernatchez, Jair Lage de Siqueira-Neto, Rob Knight, Pieter C Dorrestein, James H McKerrow
Trypanosoma cruzi parasites are the causative agents of Chagas disease, a leading infectious form of heart failure whose pathogenesis is still not fully characterized. In this work, we applied untargeted liquid chromatography-tandem mass spectrometry to heart sections from T. cruzi-infected and uninfected mice. We combined molecular networking and three-dimensional modeling to generate chemical cartographical heart models. This approach revealed for the first time preferential parasite localization to the base of the heart and regiospecific distributions of nucleoside derivatives and eicosanoids, which we correlated to tissue-damaging immune responses...
September 22, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28887214/trypanocidal-activity-of-polysaccharide-extract-from-genipa-americana-leaves
#14
Racquel Oliveira da Silva Souza, Paloma Leão Sousa, Ramon Róseo Paula Pessoa Bezerra de Menezes, Tiago Lima Sampaio, Louise Donadello Tessarolo, Francisca Crislandia Oliveira Silva, Maria Gonçalves Pereira, Alice Maria Costa Martins
ETHNOPHARMACOLOGICAL RELEVANCE: The parts of the Genipa americana (Rubiaceae) tree, also known as "jenipapo" or "jenipapeiro", has been used in traditional Medicine in parasitic and bacterial infections. Thus, the experimental evolution of the antiparasitic activity of polysaccharide extracts from Genipa americana leaves, and correlation with antiparasitic and popular use is important. AIM OF THE STUDY: To evaluate the effect of polysaccharide extract obtained from Genipa americana leaves on all Trypanosoma cruzi (Y strain: benznidazole-resistant) developmental forms, a protozoan that causes Chagas' disease...
September 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28884498/aldo-keto-reductase-and-alcohol-dehydrogenase-contribute-to-benznidazole-natural-resistance-in-trypanosoma-cruzi
#15
Laura González, Paola García-Huertas, Omar Triana-Chávez, Gabriela Andrea García, Silvane Maria Fonseca Murta, Ana M Mejía-Jaramillo
The improvement of Chagas disease treatment is focused not only on the development of new drugs but also in understanding mechanisms of action and resistance to drugs conventionally used. Thus, some strategies aim to detect specific changes in proteins between sensitive and resistant parasites and to evaluate the role played in these processes by functional genomics. In this work, we used a natural Trypanosoma cruzi population resistant to benznidazole, which has clones with different susceptibilities to this drug without alterations in the NTR I gene...
September 7, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28881289/efficacy-of-a-series-of-alpha-pyrone-derivatives-against-leishmania-l-infantum-and-trypanosoma-cruzi
#16
Andre Gustavo Tempone, Daiane Dias Ferreira, Marta Lopes Lima, Thais Alves Costa Silva, Samanta E T Borborema, Juliana Quero Reimão, Mariana K Galuppo, Juliana Mariotti Guerra, Angelie J Russell, Graham M Wynne, Roy Y L Lai, Melissa M Cadelis, Brent R Copp
The neglected tropical diseases Chagas disease and leishmaniasis affect together more than 20 million people living mainly in developing countries. The mainstay of treatment is chemotherapy, however the drugs of choice, which include benznidazole and miltefosine, are toxic and have numerous side effects. Safe and effective therapies are urgently needed. Marine alpha-pyrones have been previously identified as scaffolds with potential antiprotozoan activities. In this work, using a phenotypic screen, twenty-seven examples of 3-substituted 4-hydroxy-6-methyl alpha-pyrones were synthesized and their antiparasitic efficacy evaluated against Leishmania (L...
September 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28877735/priming-astrocytes-with-tnf-enhances-their-susceptibility-to-trypanosoma-cruzi-infection-and-creates-a-self-sustaining-inflammatory-milieu
#17
Andrea Alice Silva, Rafael Rodrigues Silva, Daniel Gibaldi, Rafael Meyer Mariante, Jessica Brandão Dos Santos, Isabela Resende Pereira, Otacílio Cruz Moreira, Joseli Lannes-Vieira
BACKGROUND: In conditions of immunosuppression, the central nervous sty 5ystem (CNS) is the main target tissue for the reactivation of infection by Trypanosoma cruzi, the causative agent of Chagas disease. In experimental T. cruzi infection, interferon gamma (IFNγ)(+) microglial cells surround astrocytes harboring amastigote parasites. In vitro, IFNγ fuels astrocyte infection by T. cruzi, and IFNγ-stimulated infected astrocytes are implicated as potential sources of tumor necrosis factor (TNF)...
September 6, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28873423/an-immunosignature-test-distinguishes-trypanosoma-cruzi-hepatitis-b-hepatitis-c-and-west-nile-virus-seropositivity-among-asymptomatic-blood-donors
#18
Michael Rowe, Jonathan Melnick, Robert Gerwien, Joseph B Legutki, Jessica Pfeilsticker, Theodore M Tarasow, Kathryn F Sykes
BACKGROUND: The complexity of the eukaryotic parasite Trypanosoma (T.) cruzi manifests in its highly dynamic genome, multi-host life cycle, progressive morphologies and immune-evasion mechanisms. Accurate determination of infection or Chagas' disease activity and prognosis continues to challenge researchers. We hypothesized that a diagnostic platform with higher ligand complexity than previously employed may hold value. METHODOLOGY: We applied the ImmunoSignature Technology (IST) for the detection of T...
September 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28870526/drug-repurposing-strategy-against-trypanosoma-cruzi-infection-in-vitro-and-in-vivo-assessment-of-the-activity-of-metronidazole-in-mono-and-combined-therapy
#19
M R Simões-Silva, J S De Araújo, G M Oliveira, K C Demarque, R B Peres, I D'Almeida-Melo, D G J Batista, C F Da Silva, C Cardoso-Santos, P B Da Silva, M M Batista, M T Bahia, M N C Soeiro
Metronidazole (Mtz) is a commercial broad-spectrum nitroimidazolic derivative with relevant antimicrobial activity and relative safety profile. Therefore, it is fair to consider Mtz a candidate for drug repurposing for other neglected conditions such as Chagas disease (CD), a parasitic pathology caused by Trypanosoma cruzi. CD is treated only with benznidazole (Bz) and nifurtimox, both introduced in clinics decades ago despite important limitations, including low efficacy on the later disease stage (chronic form) and severe side effects...
September 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28870247/seropositivity-for-trypanosoma-cruzi-in-domestic-dogs-from-sonora-mexico
#20
Minerva Arce-Fonseca, Silvia C Carrillo-Sánchez, Ramón M Molina-Barrios, Mariana Martínez-Cruz, Jesús R Cedillo-Cobián, Yuly A Henao-Díaz, Olivia Rodríguez-Morales
BACKGROUND: Chagas disease is an important health problem in Latin America due to its incapacitating effects and associated mortality. Studies on seropositivity for Trypanosoma cruzi in Mexican dogs have demonstrated a direct correlation between seropositivity in humans and dogs, which can act as sentinels for the disease in this region. The objective of this study was to determine the seropositivity for T.cruzi infection in dogs from Sonora, a northern borderstate of Mexico. METHODS: Responsible pet owners were selected at random from an urban area of Empalme municipality, Sonora, Mexico, and from there, 180 dog samples were collected...
September 5, 2017: Infectious Diseases of Poverty
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