Characterization of the Gamboa virus serogroup (Orthobunyavirus genus, Peribunyaviridae family)

Comprehensive comparative phylogenetic analyses were performed on 17 Gamboa serogroup viruses (GAMSVs) from distinct geographic regions in the Americas and other representative members of the genus Orthobunyavirus (Peribunyaviridae), based on small (S), medium (M), and large (L) open reading frame full-length and partial sequences. Genome characterization showed that the GAMSVs divide into four clades or genotypes. The GAMSVs have a genetic organization similar to other orthobunyaviruses, except that they have a larger NSm protein than other orthobunyaviruses. A serosurvey for Gamboa virus antibodies was performed in plasma from birds, other wild animals, and humans living around the Tucuruí hydroelectric dam in Pará state, northern Brazil, a known focus of GAMSV activity. Newborn chicks (Gallus gallus domesticus) were experimentally infected with a GAMSV, and the pathogenesis is described. Histopathological changes were primarily in the lungs and liver. Also, a review of the ecology of the GAMSVs in the Americas is included. In sum, this study presents the genomic and evolutionary characterization of the Gamboa group and the potential model of pathogenesis, which would be helpful for diagnostic purposes, epidemiology, and immunopathogenesis studies

Emergence of new immunopathogenic factors in human yellow fever: polarization of the M1/M2 macrophage response in the renal parenchyma

This research was funded by grant number 457664/2013-4 and 303999/2016-0.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Universidade do Estado do Pará. Departamento de Patologia. Belém, PA, Brazil / Universidade de São Paulo. Faculdade de Medicina. São Paulo, SP, Brazil.Universidade do Estado do Pará. Departamento de Patologia. Belém, PA, Brazil.Universidade do Estado do Pará. Departamento de Patologia. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Universidade de São Paulo. Faculdade de Medicina. São Paulo, SP, Brazil.Universidade do Estado do Pará. Departamento de Patologia. Belém, PA, Brazil.Universidade do Estado do Pará. Departamento de Patologia. Belém, PA, Brazil.Universidade do Estado do Pará. Departamento de Patologia. Belém, PA, Brazil / Universidade de São Paulo. Faculdade de Medicina. São Paulo, SP, Brazil / Universidade Federal do Pará. Núcleo de Medicina Tropical. Belém, PA, Brazil.Macrophages in the kidney play a pathogenic role in inflammation and fibrosis. Our study aimed to understand the polarisation of the M1 and M2 phenotypic profiles of macrophages in injured kidney tissue retrieved from fatal cases of yellow fever virus (YFV). A total of 11 renal tissue biopsies obtained from patients who died of yellow fever (YF) were analysed. To detect antibodies that promote the classical and alternative pathways of macrophage activation, immunohistochemical analysis was performed to detect CD163, CD68, inducible nitric oxide synthase (iNOS), arginase 1, interleukin (IL)-4, IL-10, interferon (IFN)-γ, IFN-β, tumour necrosis factor (TNF)-α, IL-13, and transforming growth factor (TGF)-β. There was a difference in the marker expression between fatal cases of YFV and control samples, with increased expression in the cortical region of the renal parenchyma. The immunoexpression of CD68 and CD163 receptors suggests the presence of activated macrophages migrating to infectious foci. The rise in IL-10, IL-4, and IL-13 indicated their potential role in the inactivation of the inflammatory macrophage response and phenotypic modulation of M2 macrophages. The altered expression of IFN-γ and IFN-β demonstrates the importance of the innate immune response in combating microorganisms. Our findings indicate that the polarisation of M1 and M2 macrophages plays a vital role in the renal immune response to YFV

Evaluation of the immunoexpression of the monoclonal antibody MIB-1 in the breast epithelium adjacent to the fibroadenoma the womem in menacme treated with tamoxifen

A quimioprofilaxia do cancer mamario com tamoxifeno tem reduzido em 45 por cento a incidencia de cancer em mulheres de alto risco, segundo dados do National Cancer Institute (l998). Seus efeitos sobre o tecido mamario normal sao pouco conhecidos, bem como sua interacao com os receptores esteroides e a dose-efeito. Estudou-se por tecnica imunohistoquimica, atraves da imunoexpressao do anticorpo monoclonal MIB-1 (IMUNOTECH, catalogo n. 0505, lote OO1), a atividade proliferativa no epitello mamario adjacente ao fibroadenoma de 44 pacientes, de forma aleatoria em duplo-cego, divididas em 3 grupos: A =l6; placebo), B (N=15; tamoxifeno, 10mg) e C (N=13; tamoxifeno, 2Omg). O medicamento foi utilizado por 22 dias, a partir do 20 dia do ciclo menstrual, sendo a cirurgia realizada no 23º dia. O perfil hormonal foi analisado pela dosagem serica de estradiol, progesterona, SHBG (globulina transportadora de horrnonlos esteroides), FSH (horrnonio foliculo-estimulante), LH (honnonlo luteinizante) e prolactina, entre os dias 21 e 24 do ciclo menstrual previo, e no dia da cirurgia. Os grupos B e C apresentaram aumento significante nos niveis de progesterona (p=O,O38), estradiol (p<O,OOl) e SHBG (p=O,OOl). No grupo C, observou-se elevacao na concentracao serica de FSH (p=O,OO45) e queda dos niveis de prolactina (p=O,OO55). A porcentagem media de nucleos corados por 1000 celulas no grupo A foi 9,2; no grupo B, 4,5; e no grupo C, 3,2. O teste de Fisher revelou que o tamoxifeno reduziu de forma significante a imunoexpressao do MIB-1 nas doses de 10 e 2Omg em comparacao com o grupo placebo (P<O,OOOI) e nao houve variacao significante da atividade prollferativa nas doses de 1O e 2Omg de tamoxifeno (p=O,21). Conclui-se que o tamoxifeno reduziu de forma significante a atividade proliferativa do epitelio mamario, nas doses de 10 e20mg/diaBV UNIFESP: Teses e dissertaçõe

Nerve Growth Factor and Pathogenesis of Leprosy: Review and Update

Neurotrophins are a family of proteins that regulate different aspects of biological development and neural function and are of great importance in neuroplasticity. This group of proteins has multiple functions in neuronal cells, as well as in other cellular populations. Nerve growth factor (NGF) is a neurotrophin that is endogenously produced during development and maturation by multiple cell types, including neurons, Schwann cells, oligodendrocytes, lymphocytes, mast cells, macrophages, keratinocytes, and fibroblasts. These cells produce proNGF, which is transformed by proteolytic cleavage into the biologically active NGF in the endoplasmic reticulum. The present review describes the role of NGF in the pathogenesis of leprosy and its correlations with different clinical forms of the disease and with the phenomena of regeneration and neural injury observed during infection. We discuss the involvement of NGF in the induction of neural damage and the pathophysiology of pain associated with peripheral neuropathy in leprosy. We also discuss the roles of immune factors in the evolution of this pathological process. Finally, we highlight avenues of investigation for future research to broaden our understanding of the role of NGF in the pathogenesis of leprosy. Our analysis of the literature indicates that NGF plays an important role in the evolution and outcome of Mycobacterium leprae infection. The findings described here highlight an important area of investigation, as leprosy is one of the main causes of infection in the peripheral nervous system

Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases

This work was funded by the Council for Scientific and Technological Development – CNPq/Brazil (Grant numbers 302553/2015-0 and 116427/2016-7) and Coordination of Superior Level Staff Improvement - CAPES/Brazil. Program of support for qualified production – PAPQ/ UFPA.Federal University of Pará. Tropical Medicine Center. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil / State University of Pará. Center of Biological and Health Sciences. Belém, PA, Brazil.Federal University of Pará. Tropical Medicine Center. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil / State University of Pará. Center of Biological and Health Sciences. Belém, PA, Brazil / University, São Paulo. School of Medicine. São Paulo, SP, Brazil.Macrophages are a functionally heterogeneous group of cells with specialized functions depending not only on their subgroup but also on the function of the organ or tissue in which the cells are located. The concept of macrophage phenotypic heterogeneity has been investigated since the 1980s, and more recent studies have identified a diverse spectrum of phenotypic subpopulations. Several types of macrophages play a central role in the response to infectious agents and, along with other components of the immune system, determine the clinical outcome of major infectious diseases. Here, we review the functions of various macrophage phenotypic subpopulations, the concept of macrophage polarization, and the influence of these cells on the evolution of infections. In addition, we emphasize their role in the immune response in vivo and in situ, as well as the molecular effectors and signaling mechanisms used by these cells. Furthermore, we highlight the mechanisms of immune evasion triggered by infectious agents to counter the actions of macrophages and their consequences. Our aim here is to provide an overview of the role of macrophages in the pathogenesis of critical transmissible diseases and discuss how elucidation of this relationship could enhance our understanding of the host–pathogen association in organ-specific immune response