Rodrigo Corrêa‐Oliveira

Fundação Oswaldo Cruz

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i-10 index

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Andréa Teixeira‐Carvalho

Fundação Oswaldo Cruz

Jeffrey M. Bethony

George Washington University

Juliana de Assis Silva Gomes

Universidade Federal de Minas Gerais

Alexandre Barbosa Reis

Universidade Federal de Ouro Preto

Olindo Assis Martins‐Filho

Fundação Oswaldo Cruz

Andréa Gazzinelli

Universidade Federal de Minas Gerais

Rodolfo Cordeiro Giunchetti

Universidade Federal de Minas Gerais

Manoel Otávio da Costa Rocha

Universidade Federal de Minas Gerais

Silvana Maria Elói-Santos

Universidade Federal de Minas Gerais

Ricardo Toshio Fujiwara

Universidade Federal de Minas Gerais

Cooperative Institutions

Universidade Federal de Minas Gerais

430

Fundação Oswaldo Cruz

384

Universidade Federal de Ouro Preto

114

Universidade de São Paulo

111

Universidade Federal do Rio de Janeiro

National Institutes of Health

Hospital das Clínicas da Universidade Federal de Minas Gerais

Universidade Federal de Juiz de Fora

George Washington University

National Institute of Allergy and Infectious Diseases

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Pharmacokinetics and Tissue Distribution of Benznidazole after Oral Administration in Mice

Antimicrobial Agents and Chemotherapy (2017)

Luísa Perin Rodrigo Moreira da Silva Kátia da Silva Fonseca Rodrigo Cardoso de Oliveira Fernando Augusto Siqueira Mathias

ABSTRACT 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 method with a UV detector (HPLC-UV) 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. The developed method was linear in the BNZ concentration, which ranged from 0.1 to 100.0 μg/ml for plasma, spleen, brain, colon, heart, lung, and kidney and from 0.2 to 100.0 μg/ml for liver. Validation assays demonstrated good stability for BNZ under all conditions evaluated. Pharmacokinetic parameters confirmed rapid, but low, absorption of BNZ after oral administration. Biodistribution assays demonstrated different maximum concentrations in organs and similar times to maximum concentration and mean residence times, with means of 40 min and 2.5 h, respectively. Therefore, the biodistribution of BNZ is extensive, reaching organs such as the heart and colon, which are the most relevant organs affected by Trypanosoma cruzi infection, and also the spleen, brain, liver, lungs, and kidneys. Simultaneous analyses of tissues and plasma indicated high BNZ metabolism in the liver. Our results suggest that low bioavailability, instead of inadequate biodistribution, could be responsible for therapeutic failure during the chronic phase of Chagas disease.

Biodistribution

Benznidazole

Chagas Disease

10.1128/aac.02410-16

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Citations (52)

Distribution and Schistosoma mansoni infection of Biomphalaria glabrata in different habitats in a rural area in the Jequitinhonha Valley, Minas Gerais, Brazil: environmental and epidemiological aspects

Memórias do Instituto Oswaldo Cruz (2004)

Helmut Kloos Liana Kanovaloff Janotti Passos Philip T. LoVerde Rodrigo Corrêa‐Oliveira Andréa Gazzinelli

This paper examines the distribution and infection of Biomphalaria glabrata with Schistosoma mansoni in all aquatic snail habitats in a rural area in the state of Minas Gerais, Brazil, in relation to physico/biotic and behavioral factors. Snail and environmental surveys were carried out semi-annually between July 2001 and November 2002 at 106 sites. Collected snails were examined in the laboratory for infection. B. glabrata densities were highest in overflow ponds, irrigation ponds, springs, canals and wells, and lowest in fishponds and water tanks. Snail densities were higher during the hot, rainy season except for streams and canals and were statistically associated with the presence of fish, pollution, and vegetation density. Tilapia fish and an unidentified Diptera larva were found to be predators of B. glabrata but ducks were not. Twenty-four of the 25 infected snails were collected in 2001(1.4% infection rate) and only one in 2002, after mass chemotherapy. The occurrence of B. glabrata in all 11 snail habitats both at and away from water contact sites studied indicates widespread risk of human infection in the study area. In spite of the strong association between B. glabrata and tilapia in fishponds we do not recommend its use in schistosomiasis control for ecological reasons and its relative inefficiency in streams and dams.

Biomphalaria glabrata

Aquaculture of tilapia

10.1590/s0074-02762004000700002

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Citations (39)

Comparative study of the presence of Trypanosoma cruzi kDNA, inflammation and denervation in chagasic patients with and without megaesophagus

Parasitology (2005)

Alexandre Barcelos Morais da Silveira Rosa Maria Esteves Arantes A Vágó E. M. Lemos Sheila Jorge Adad

Neuronal lesions have been considered the hallmark of chagasic megaesophagus, but the role of Trypanosoma cruzi and the participation of the inflammatory cells in this process are still debated. In the present study we counted neurons in the oesophagus from patients with and without megaesophagus and further examined these samples for the presence of parasite kDNA and cells with cytolytic potential (Natural Killer cells, cytotoxic lymphocytes and macrophages). The presence of parasite kDNA was demonstrated in 100% of cases with megaesophagus and in 60% of patients without megaesophagus. When analysed for the number of neurons, the patients without megaesophagus could be classified into 2 groups, as having normal or a decreased number of neurons. The former group did not show any inflammatory process, but interestingly, all patients without megaesophagus presenting decreased number of neurons also presented both parasite kDNA and inflammatory process in the organ. We further observed that the numbers of cytotoxic cells in the myenteric plexus region inversely correlate with the number of neurons. These data together strongly suggest that chronic lesions in chagasic megaesophagus might be a consequence of immune-mediated mechanisms, that last until the chronic phase of infection, and are dependent on the persistence of parasite in the host's tissue.

Megaesophagus

Chagas Disease

10.1017/s0031182005008061

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Citations (58)

Human schistosomiasis mansoni: intensity of infection differentially affects the production of interleukin-10, interferon-γ and interleukin-13 by soluble egg antigen or adult worm antigen stimulated cultures

Transactions of the Royal Society of Tropical Medicine and Hygiene (2004)

Alda Maria Soares Silveira Giovanni Gazzinelli Lucia F. Alves‐Oliveira Jeffrey M. Bethony Andréa Gazzinelli

The effect of the intensity of infection (eggs per gram faeces, epg) on the production of interferon-gamma (INF-gamma), interleukin (IL)-10 and IL-13 by peripheral blood mononuclear cells (PBMCs) from individuals living in a Schistosoma mansoni-endemic area was evaluated. In vitro stimulation of PBMCs with soluble egg antigen (SEA) resulted in significantly higher secretion levels of IFN-gamma in egg-negative individuals compared with those with an intensity of infection of more than 100 epg. In contrast, the egg-positive group produced significantly higher amounts of IL-10. Levels of IL-13 did not differ significantly between egg-positive and egg-negative groups. These findings suggest that IL-10 is an important cytokine in the control of the T helper cell (Th) type 1 responses during human S. mansoni infection, shifting the immune response from Th0 in egg-negative individuals from an endemic area to a Th2 polarization in chronic infected individuals.

10.1016/j.trstmh.2003.11.009

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Citations (45)

Evidence of Different IL-1β Activation Pathways in Innate Immune Cells From Indeterminate and Cardiac Patients With Chronic Chagas Disease

Frontiers in Immunology (2019)

Nayara I. Medeiros Bruna Fernandes Pinto Silvana Maria Elói-Santos Andréa Teixeira‐Carvalho Luísa Mourão Dias Magalhães

Background: Chagas cardiomyopathy is the main fibrosing myocarditis among known heart diseases. Development of cardiomyopathy has been related to extracellular matrix (ECM) remodeling, wich are controlled by matrix metalloproteinases (MMPs) and cytokines, especially interleukin (IL)-1β. The convertion of 31KDa inactive precursor, the proIL-1β in 17KDa active IL-1β peptide, is controlled by caspase-1-dependent pathway, associated with inflammasomes. Other caspase-1 independent mechanisms mediated by proteases, especially as MMPs, have already been described. Methods: We evaluated IL-1β activation pathways in neutrophils and monocyte subsets from patients with different clinical forms of Chagas disease after T. cruzi antigen stimulation by multiparameter flow cytometry. Results: Our data demonstrated that Chagas patients with the indeterminate clinical form (IND) showed increased levels of IL-1β post-stimulation as well as increased expression of MMP-2, NLRP3, and CASP1, which are associated with the classical caspase-1-dependent pathway. Conversely, patients with the cardiac clinical form (CARD) showed increased IL-1β after stimulation associated with MMP-9 and alternative caspase-1-independent pathway. Conclusions: We suggest some distinct molecular mechanisms for production of IL-1 in innate immune cells from patients with different clinical forms of Chagas disease. MMP-2 and MMP-9 gelatinases are associated with distinct disease outcomes and IL-1 production.

Chagas Disease

10.3389/fimmu.2019.00800

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Citations (13)

Estimation of the local synthesis of immunoglobulin G (IgG) in the central nervous system of patients with spinal cord schistosomiasis by the IgG index

Transactions of the Royal Society of Tropical Medicine and Hygiene (1999)

Teresa Cristina Abreu Ferrari Rodrigo Corrêa‐Oliveira Marcelo Antônio Pascoal-Xavier Giovanni Gazzinelli A. S. Cunha

Journal Article Estimation of the local synthesis of immunoglobulin G (IgG) in the central nervous system of patients with spinal cord schistosomiasis by the IgG index Get access Teresa C.A. Ferrari, Teresa C.A. Ferrari ∗ 1Departamento de Clinica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil2Laboratorio de Gastroenterologia de Adultos, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil ∗Address for correspondence: Dr Teresa Cristina de Abreu Ferrari, Department of Internal Medicine, Faculty of Medicine, Federal University of Minas Gerais, Av. Alfredo Balena, 190, CEP: 30130-100, Belo Horizonte, MG, Brazil; fax +55 31 2734985. tferrari@medicina.ufmg.br Search for other works by this author on: Oxford Academic PubMed Google Scholar Rodrigo Correa-Oliveira, Rodrigo Correa-Oliveira 3Laboratório de Imunologia Celular e Molecular, Centra de Pesquisas Renè-Rachou-FIOCRUZ, BH, MG, Brazil Search for other works by this author on: Oxford Academic PubMed Google Scholar Marcelo A.P. Xavier, Marcelo A.P. Xavier 2Laboratorio de Gastroenterologia de Adultos, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil Search for other works by this author on: Oxford Academic PubMed Google Scholar Giovanni Gazzinelli, Giovanni Gazzinelli 3Laboratório de Imunologia Celular e Molecular, Centra de Pesquisas Renè-Rachou-FIOCRUZ, BH, MG, Brazil Search for other works by this author on: Oxford Academic PubMed Google Scholar Aloísio S. Cunha Aloísio S. Cunha 1Departamento de Clinica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil2Laboratorio de Gastroenterologia de Adultos, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 93, Issue 5, September-October 1999, Pages 558–559, https://doi.org/10.1016/S0035-9203(99)90381-4 Published: 01 September 1999 Article history Received: 09 March 1999 Revision received: 28 May 1999 Accepted: 02 June 1999 Published: 01 September 1999

10.1016/s0035-9203(99)90381-4

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Citations (16)

The immunodominant surface antigen of Plasmodium gallinaceum is present in both the salivary gland and oocyst sporozoites.

PubMed (1990)

Eliana Maria Maurício da Rocha Rodrigo Corrêa‐Oliveira Célia R. Whitaker Carneiro José Daniel Lopes A U Krettli

1. Monoclonal antibodies (MAbs) against surface antigens of Plasmodium gallinaceum sporozoites, an avian malaria parasite, were produced using spleen cells from mice immunized with sporozoites from mosquito salivary glands (SGS) or from midguts containing oocysts (OoS). 2. All of the 15 MAbs tested (11 anti-SGS and 4 anti-OoS) reacted with SGS and OoS by indirect immunofluorescence and circumsporozoite precipitation reactions. Fourteen of these MAbs (11 anti-SGS and 3 anti-OoS) produced a Western blot (WB) pattern identical to that produced with serum from mice hyperimmunized with viable intact sporozoites. 3. All MAbs and the immune sera recognized only two polypeptide bands of approximate molecular weight 76 and 64 kDa. 4. No difference in the WB pattern was observed when 9- or 12-day SGS or OoS extracts were used as antigens in WB. This antigenic similarity was confirmed when the total protein extracts were visualized on silver-stained SDS-PAGE gel.

Plasmodium gallinaceum

Immunofluorescence

Plasmodium (life cycle)

Circumsporozoite protein

Source

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Citations (8)

Cytokines as determinants of resistance and pathology in human Schistosoma mansoni infection

Brazilian Journal of Medical and Biological Research (1998)

Rodrigo Corrêa‐Oliveira Luiz Cosme Cotta Malaquias Patrícia Lima Falcão Iramaya R. C. Viana Lilian M. G. Bahia‐Oliveira

The role of different cytokines in the peripheral blood mononuclear cell (PBMC) proliferative response and in in vitro granuloma formation was evaluated in a cross-sectional study with patients with the different clinical forms and phases of Schistosoma mansoni infection, as well as a group of individuals "naturally" resistant to infection named normal endemic (NE). The blockage of IL-4 and IL-5 using anti-IL-4 and anti-IL-5 antibodies significantly reduced the PBMC proliferative response to soluble egg (SEA) and adult worm (SWAP) antigens in acute (ACT), chronic intestinal (INT) and hepatosplenic (HS) patients. Similar results were obtained in the in vitro granuloma formation. Blockage of IL-10 had no significant effect on either assay using PBMC from ACT or HS. In contrast, the addition of anti-IL-10 antibodies to PBMC cultures from INT patients significantly increased the proliferative response to SEA and SWAP as well as the in vitro granuloma formation. Interestingly, association of anti-IL-4 and anti-IL-10 antibodies did not increase the PBMC proliferative response of these patients, suggesting that IL-10 may act by modulating IL-4 and IL-5 secretion. Addition of recombinant IL-10 decreased the proliferative response to undetectable levels when PBMC from patients with the different clinical forms were used. Analysis of IFN-g in the supernatants showed that PBMC from INT patients secreted low levels of IFN-g upon antigenic stimulation. In contrast, PBMC from NE secreted high levels of IFN-g. These data suggest that IL-10 is an important cytokine in regulating the immune response and possibly controlling morbidity in human schistosomiasis mansoni, and that the production of IFN-g may be associated with resistance to infection.

Mononuclear cell infiltration

10.1590/s0100-879x1998000100024

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Citations (78)

Regulatory T cells: Friends or foe in human Mycobacterium leprae infection?

Immunobiology (2017)

Ana Thereza Chaves Atvaldo F. Ribeiro-Junior Sandra Lyon Nayara I. Medeiros Fábio Cassirer-Costa

Mycobacterium leprae

10.1016/j.imbio.2017.11.002

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Citations (10)

Sm21.6 a novel EF-hand family protein member located on the surface of Schistosoma mansoni adult worm that failed to induce protection against challenge infection but reduced liver pathology

Vaccine (2009)

Débora de Oliveira Lopes Leonardo F. Paiva Maurício A. Martins Fernanda C. Cardoso Matheus Andrade Rajão

Schistosomiasis continues to be a significant public health problem that affects 200 million people worldwide. This is one of the most important parasitic diseases, and one whose effective control is unlikely in the absence of a vaccine. In this study, we have isolated a cDNA clone encoding the Schistosoma mansoni Sm21.6 protein that has 45% and 44% identity with Sm22.6 and Sj21.7 EF-hand containing antigens, respectively. Confocal microscopy analysis revealed that Sm21.6 is a membrane-associated protein localized on the S. mansoni adult worm. Mouse immunization with rSm21.6 induced a mixed Th1/Th2 cytokine profile and no protection against infection. However, vaccination with rSm21.6 reduced by 28% of liver granuloma numbers, 21% of granuloma area and 34% of fibrosis. Finally, rSm21.6 was recognized by sera from individuals resistant to reinfection compared with patients susceptible to reinfection and this molecule should be further studied as potential biomarker for disease resistance. In conclusion, Sm21.6 is a new tegument protein from S. mansoni that plays an important role in reducing pathology induced by parasite infection.

Schistosoma

Viral tegument

Parasitic Disease

10.1016/j.vaccine.2009.04.068

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Citations (30)