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Introduction: Dengue virus (DENV), the etiologic agent of dengue fever illness, represents a global public health concern, mainly in tropical and subtropical areas across the globe. It is well known that this acute viral disease can progress to severe hemorrhagic stages in some individuals, however, the immunopathogenic basis of the development of more severe forms by these patients is yet to be fully understood. Objective: In this context, we investigated and characterized the histopathological features as well as the cytokine profile and cell subpopulations present in liver tissues from three fatal cases of DENV in children. Methods: Hematoxylin and Eosin, Periodic Acid Schiff and Picro Sirius Red staining were utilized for the histopathological analysis. Immunohistochemistry assay was performed to characterize the inflammatory response and cell expression patterns. Results: Vascular dysfunctions such as hemorrhage, vascular congestion and edema associated with a mononuclear infiltrate were observedin all three cases. Liver tissues exhibited increased presence of CD68+ and TCD8+ cells as well as high expression of MMP-9, TNF-a, RANTES, VEGFR-2 mediators. Viral replication was confirmed by the detection of NS3 protein. Conclusion: Taken together, these results evidenced key factors that may be involved in the development of severe alterations in liver tissues of children in response to DENV infection.
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Vírus da Dengue , Dengue , Humanos , Criança , Mediadores da Inflamação/metabolismo , Antígenos Virais/metabolismo , Fígado/patologiaRESUMO
Dengue virus (DENV) infection represents a worldwide public health concern and can cause damage to multiple organs, including the kidney. In this work, we investigated the histopathological changes caused by dengue virus infection along with the detection of inflammatory mediators, cytokines, and cell expression patterns in the renal tissue of three fatal cases in children. Hematoxylin and Eosin staining was performed to analyze these histopathological changes. Immunohistochemistry allowed for the detection of immunological inflammatory markers in renal tissues that were quantified and further analyzed. Vascular congestion, edema and glomerular infiltrate were observed in the three cases, in addition to the thickening of the matrix area around the glomerular capillaries and mononuclear infiltrate associated with vascular congestion in the medullary region. The renal tissues exhibited collagen deposition and high expression of CD68+ Mø, CD8+ T, CD56+ cells and MMP-9, and the cytokine profile was mainly characterized by the expression of IFN-γ and TNF-α. Additionally, the expression of RANTES, VEGFR-2 and VCAM-1 were observed. The replication of DENV was evidenced by the detection of the NS3 protein. These results contributed to clarifying the main factors that may be involved in changes in the renal tissue of fatal cases of dengue in children.
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Although vertical transmission of CHIKV has been reported, little is known about the role of placenta in the transmission of this virus and the effects of infection on the maternal-fetal interface. In this work we investigated five placentas from pregnant women who became infected during the gestational period. Four formalin-fixed paraffin-embedded samples of placenta (cases 1-4) were positive for CHIKV by RT-PCR. One (case 5) had no positive test of placenta, but had positive RT-PCR for CHIKV in the serum of the mother and the baby, confirming vertical transmission. The placentas were analyzed regarding histopathological and immunological aspects. The main histopathological changes were: deciduitis, villous edema, deposits, villous necrosis, dystrophic calcification, thrombosis and stem vessel obliteration. In infected placentas we noted increase of cells (CD8+ and CD163+) and pro- (IFN-γ and TNF-α) and anti-inflammatory (TGF-ß and IL-10) cytokines compared to control placentas. Moreover, CHIKV antigen was detected in decidual cell, trophoblastic cells, stroma villi, Hofbauer cells, and endothelial cells. In conclusion, CHIKV infection seems to disrupt placental homeostasis leading to histopathological alterations in addition to increase in cellularity and cytokines overproduction, evidencing an altered and harmful environment to the pregnant woman and fetus.
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Chikungunya virus (CHIKV) is an arthropod-borne virus first isolated in Tanzania, Africa. The virus has spread to Asia as well as South and Central America through infected Aedes mosquitoes. Vertical transmission may also occur, and was first documented during a chikungunya outbreak in La Réunion Island in 2005. Since then, some authors have been discussing the role of the placenta in maternal-fetal CHIKV transmission. CHIKV infection is characterized by fever, headache, rash, and arthralgia. However, atypical manifestations and clinical complications, including neurological, cardiac, renal, ocular, and dermal, may occur in some cases. In this report, we describe the case of a pregnant woman infected by CHIKV during the third trimester of gestation, who presented with severe dermatological manifestations during the epidemic in Rio de Janeiro, Brazil in 2019. CHIKV RNA and antigens were detected in the placental tissue, which presented with histopathological (deciduitis, fibrin deposition, edema, fetal vessel thickening, and chorioamnionitis) and ultrastructural alterations (cytotrophoblast with mitochondrial swelling and dilated cisterns in endoplasmic reticulum, vesicles in syncytiotrophoblasts, and thickening of the basement membrane of the endothelium).
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Dengue viral (DENV) infections can lead to acute pancreatitis and associated tissue damage. This study examined the pancreas from two fatal cases of DENV for histopathological changes as well as for the detection of cytokines, and other inflammatory mediators. Tissue sections were prepared for examination by ultrastructural and histopathological techniques. Sections from the pancreas of non-infected individuals were prepared in parallel as a control. The presence of viral replication in macrophages was detected by co-staining for the proteins NS3 and CD68 by immunofluorescence. Immunohistochemistry was used to detect cells that expressed cytokines and inflammatory mediators to characterize the inflammatory response. Edema, acinar necrosis and fibrosis areas associated with a mononuclear infiltrate were found in infected tissues. The major site of virus replication appeared to be macrophages based on their exclusive presentation of the viral protein NS3. Pancreatic tissues from the infected individuals also displayed increased levels of high mobility group box-1, caspase-3, gelatinase B and tumor necrosis factor alpha compared to controls. The presence of virus replicating macrophages in the pancreas was associated with multiple changes in tissue structure that included elevated levels of cytokines and inflammatory markers that may differentiate acute pancreatitis due to DENV infections from other causes.
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Biomarcadores/metabolismo , Citocinas/metabolismo , Vírus da Dengue/isolamento & purificação , Dengue/complicações , Mediadores da Inflamação/metabolismo , Pancreatite/patologia , Adulto , Apoptose , Dengue/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/metabolismo , Pancreatite/virologia , Adulto JovemRESUMO
Intrauterine transmission of the Chikungunya virus (CHIKV) during early pregnancy has rarely been reported, although vertical transmission has been observed in newborns. Here, we report four cases of spontaneous abortion in women who became infected with CHIKV between the 11th and 17th weeks of pregnancy. Laboratorial confirmation of the infection was conducted by RT-PCR on a urine sample for one case, and the other three were by detection of IgM anti-CHIKV antibodies. Hematoxylin and eosin (H&E) staining and an electron microscopy assay allowed us to find histopathological, such as inflammatory infiltrate in the decidua and chorionic villi, as well as areas of calcification, edema and the deposition of fibrinoid material, and ultrastructural changes, such as mitochondria with fewer cristae and ruptured membranes, endoplasmic reticulum with dilated cisterns, dispersed chromatin in the nuclei and the presence of an apoptotic body in case 1. In addition, by immunohistochemistry (IHC), we found a positivity for the anti-CHIKV antibody in cells of the endometrial glands, decidual cells, syncytiotrophoblasts, cytotrophoblasts, Hofbauer cells and decidual macrophages. Electron microscopy also helped in identifying virus-like particles in the aborted material with a diameter of 40-50 nm, which was consistent with the size of CHIKV particles in the literature. Our findings in this study suggest early maternal fetal transmission, adding more evidence on the role of CHIKV in fetal death.
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Feto Abortado/patologia , Aborto Espontâneo/patologia , Aborto Espontâneo/virologia , Febre de Chikungunya/complicações , Transmissão Vertical de Doenças Infecciosas , Feto Abortado/virologia , Adulto , Anticorpos Antivirais/sangue , Febre de Chikungunya/virologia , Vírus Chikungunya/patogenicidade , Feminino , Técnicas Histológicas , Humanos , Imunoglobulina M/sangue , GravidezRESUMO
Dengue is an arboviral disease caused by dengue virus (DENV), which is transmitted to humans by Aedes aegypti mosquitoes. Infection by DENV most commonly results in a mild flu-like illness; however, the disease has been increasingly associated with neurological symptomatology. This association draws attention to further investigations on the impact of DENV infection in the host's central nervous system. Here, we analyzed brain samples of three fatal dengue cases that occurred in 2002 during an outbreak in Rio de Janeiro, Brazil. Brain tissues of these cases were marked by histopathological alterations, such as degenerated neurons, demyelination, hemorrhage, edema, and increased numbers of astrocytes and microglial cells. Samples were also characterized by lymphocytic infiltrates mainly composed of CD8 T cells. DENV replication was evidenced in neurons, microglia and endothelial cells through immunohistochemistry and in situ hybridization techniques. Pro-inflammatory cytokines, such as TNF-α and IFN-γ were detected in microglia, while endothelial cells were marked by the expression of RANTES/CCL5. Cytoplasmic HMGB1 and the production of nitric oxide were also found in neurons and microglial cells. This work highlights the possible participation of several local pro-inflammatory mediators in the establishment of dengue neuropathogenesis.
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Encéfalo/virologia , Dengue/patologia , Replicação Viral , Adulto , Astrócitos/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Quimiocina CCL5/metabolismo , Dengue/mortalidade , Dengue/virologia , Feminino , Humanos , Interferon gama/metabolismo , Microglia/patologia , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/metabolismo , Adulto JovemRESUMO
Mycobacterium haemophilum is a nontuberculous mycobacterium that causes localized or disseminated disease, mainly in immunocompromised hosts. We report the case of a 35-year-old HIV-infected woman who presented with several enlarging cutaneous lesions over the arms and legs. Histopathological examination revealed the diagnosis of a cutaneous mycobacterial disease. Mycobacterial analyses unveiled M. haemophilum infection. Six months after completion of a successful antimycobacterial treatment, she developed an immune reconstitution inflammatory syndrome (IRIS). This paradoxical relapse presented as tenderness, redness and swelling at the precise sites of the healed lesions and took place in the setting of significant recovery of the CD4 cell count (from 05 to 318 cells/mm 3 ). Microbiological analyses of these worsening lesions were negative, and they spontaneously remitted without the initiation of a novel antimycobacterial treatment cycle. M. haemophilum infection should always be considered as a cause of skin lesions in immunocompromised subjects. Physicians should be aware of the possibility of IRIS as a complication of successful antiretroviral therapy in HIV-infected patients with M. haemophilum infection.
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Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Antirretrovirais/efeitos adversos , Síndrome Inflamatória da Reconstituição Imune/microbiologia , Infecções por Mycobacterium/microbiologia , Mycobacterium haemophilum/isolamento & purificação , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Feminino , Humanos , Síndrome Inflamatória da Reconstituição Imune/imunologia , Síndrome Inflamatória da Reconstituição Imune/metabolismo , Hospedeiro Imunocomprometido , Masculino , Infecções por Mycobacterium/imunologiaRESUMO
Dengue virus (DENV) infections may result in asymptomatic cases or evolve into a severe disease, which involves multiple organ failure. Renal involvement in dengue can be potentially related to an increased mortality. Aiming to better understand the role of DENV in renal injury observed in human fatal cases, post-mortem investigations were performed in four DENV-4 renal autopsies during dengue epidemics in Brazil. Tissues were submitted to histopathology, immunohistochemistry, viral quantification, and characterization of cytokines and inflammatory mediators. Probably due the high viral load, several lesions were observed in the renal tissue, such as diffuse mononuclear infiltration around the glomerulus in the cortical region and in the medullary vessels, hyalinosis arteriolar, lymphocytic infiltrate, increased capsular fibrosis, proximal convoluted tubule (PCT) damage, edema, PCT debris formation, and thickening of the basal vessel membrane. These changes were associated with DENV-4 infection, as confirmed by the presence of DENV-specific NS3 protein, indicative of viral replication. The exacerbated presence of mononuclear cells at several renal tissue sites culminated in the secretion of proinflammatory cytokines and chemokines. Moreover, it can be suggested that the renal tissue injury observed here may have been due to the combination of both high viral load and exacerbated host immune response.
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Dengue virus (DENV) is an emerging virus involved in outbreaks in Brazil. The association between the virus and vertical transmission, with disorders in the placenta, has raised a worldwide concern. On the 29th gestational week, a pregnant woman presented severe complications due to a DENV infection leading to maternal and fetus death. Postmortem analysis of fetal organs demonstrated the presence of DENV using reverse transcriptase polymerase chain reaction (RT-PCR) in the fetal brain and DENV non-structural protein 3 (NS3) staining in placenta and several peripheral fetal tissues, such as the brain, liver, lungs, and spleen. Histological analysis of the placenta and fetal organs revealed different types of tissue abnormalities, which included inflammation, hemorrhage, edema, and necrosis in placenta and tissue disorganization in the fetus, such as spongiform parenchyma, microglial inflammation, steatosis, hyalinose arteriolar, inflammatory cells in the alveolar septa, and disorganization of the lymphoid follicle. Increased cellularity (macrophage, Hofbauer cells and TCD8+ lymphocytes) and up-regulation of inflammatory mediators such as IFN-γ, TNF-α, RANTES/CCL5, MCP1/CCL2, and VEGF/R2 were detected in the liver, lung, spleen, brain, and placenta, supporting placental and fetus peripheral tissues inflammation. Maternal infection leading to the production of those vascular mediators may alter the vascular permeability, facilitating the virus entry and tissue and barrier dysfunction.
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Dengue/patologia , Dengue/virologia , Mediadores da Inflamação/metabolismo , Complicações Infecciosas na Gravidez/patologia , Complicações Infecciosas na Gravidez/virologia , Adulto , Brasil , Dengue/fisiopatologia , Vírus da Dengue/isolamento & purificação , Vírus da Dengue/fisiologia , Feminino , Feto/metabolismo , Feto/patologia , Feto/virologia , Idade Gestacional , Humanos , Transmissão Vertical de Doenças Infecciosas , Morte Materna , Placenta/metabolismo , Placenta/patologia , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/fisiopatologia , NatimortoRESUMO
Dengue is a mild flu-like arboviral illness caused by dengue virus (DENV) that occurs in tropical and subtropical countries. An increasing number of reports have been indicating that dengue is also associated to neurological manifestations, however, little is known regarding the neuropathogenesis of the disease. Here, using BALB/c mice intravenously infected with DENV-2 strain 66985, we demonstrated that the virus is capable of invading and damaging the host's central nervous system (CNS). Brain and cerebellum of infected animals revealed histological alterations such as the presence of inflammatory infiltrates, thickening of pia matter and disorganization of white matter. Additionally, it was also seen that infection lead to altered morphology of neuroglial cells and apoptotic cell death. Such observations highlighted possible alterations that DENV may promote in the host's CNS during a natural infection, hence, helping us to better understand the neuropathological component of the disease.
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Sistema Nervoso Central/patologia , Sistema Nervoso Central/virologia , Vírus da Dengue/patogenicidade , Adulto , Animais , Encéfalo/patologia , Encéfalo/virologia , Linhagem Celular , Cerebelo/patologia , Cerebelo/virologia , Modelos Animais de Doenças , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
In the large Zika virus (ZIKV) epidemic that occurred in Brazil in 2015, the intrauterine fetal exposure to ZIKV was associated with a significant risk of developing microcephaly and neurological disorders in the infected infants. ZIKV-associated disease has since been reported in 24 countries in the Americas. At present, definitive evidence is lacking regarding the intrauterine co-exposure to ZIKV and other viral infections and whether the coinfection impacts the risk of acquiring either infection or disease severity. Here, we provide evidence of intrauterine exposure to both ZIKV and human immunodeficiency virus (HIV) infections, causing congenital Zika syndrome in an HIV-exposed uninfected infant. Clinical, imaging and laboratory examinations of the pregnant woman and the newborn were performed. Histopathology, ZIKV/HIV-specific immunoassays, and ultrastructural evaluation of the placenta were performed. The Zika-asymptomatic, HIV-positive pregnant woman underwent ultrasounds revealing fetal cerebral ventriculomegaly, microcephaly, and brain atrophy. Her baby girl was born small for gestational age and with the neurological sequelae of congenital Zika syndrome. The evaluation of the abnormally large term placenta revealed severe damage to the maternal decidua and chorionic villi, cells positive for ZIKV-specific antigens but not for HIV antigens, and intracellular membranous clusters of virus-like particles approximately 25 nm in diameter. The rapid progression and severity of the congenital Zika syndrome may be related to the uncontrolled HIV disease in the mother. The poor inflammatory response observed in the placenta may have reduced the inherent risk of mother-to-child transmission of HIV.
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Dengue is an important infectious disease that presents high incidence and yields a relevant number of fatal cases (about 20,000) every year worldwide. Despite its epidemiological relevance, there are many knowledge gaps concerning dengue pathogenesis, especially with regards to the circumstances that drive a mild clinical course to a severe disease. In this work, we investigated the participation of high mobility group box 1 (HMGB1), an important modulator of inflammation, in dengue fatal cases. Histopathological and ultrastructural analyses revealed that liver, lung and heart post-mortem samples were marked by tissue abnormalities, such as necrosis and apoptotic cell death. These observations go in line with an HMGB1-mediated response and raised concerns regarding the participation of this cytokine in promoting/perpetuating inflammation in severe dengue. Further experiments of immunohistochemistry (IHC) showed increased expression of cytoplasmic HMGB1 in dengue-extracted tissues when compared to non-dengue controls. Co-staining of DENV RNA and HMGB1 in the host cell cytoplasm, as found by in situ hybridization and IHC, confirmed the virus specific induction of the HMGB1-mediated response in these peripheral tissues. This report brings the first in-situ evidence of the participation of HMGB1 in severe dengue and highlights novel considerations in the development of dengue immunopathogenesis.
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Vírus da Dengue/patogenicidade , Dengue/metabolismo , Dengue/patologia , Proteína HMGB1/metabolismo , Adulto , Citocinas/metabolismo , Feminino , Proteína HMGB1/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Marcação In Situ das Extremidades Cortadas , Inflamação/metabolismo , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Adulto JovemRESUMO
Dengue disease is an acute viral illness caused by dengue virus (DENV) that can progress to hemorrhagic stages leading to about 20000 deaths every year worldwide. Despite many clinical investigations regarding dengue, the immunopathogenic process by which infected patients evolve to the severe forms is not fully understood. Apart from differences in virulence and the antibody cross reactivity that can potentially augment virus replication, imbalanced cellular immunity is also seen as a major concern in the establishment of severe dengue. In this context, the investigation of cellular immunity and its products in dengue fatal cases may provide valuable data to help revealing dengue immunopathogenesis. Here, based in four dengue fatal cases infected by the serotype 3 in Brazil, different peripheral organs (livers, lungs and kidneys) were studied to evaluate the presence of cell infiltrates and the patterns of local cytokine response. The overall scenario of the studied cases revealed a considerable systemic involvement of infection with mononuclear cells targeted to all of the evaluated organs, as measured by immunohistochemistry (IHC). Quantification of cytokine-expressing cells in peripheral tissues was also performed to characterize the ongoing inflammatory process by the severe stage of the disease. Increased levels of IFN-γ- and TNF-α-expressing cells in liver, lung and kidney samples of post-mortem subjects evidenced a strong pro-inflammatory induction in these tissues. The presence of increased RANTES-producing cell numbers in all analyzed organs suggested a possible link between the clinical status and altered vascular permeability. Co-staining of DENV RNA and IFN-γ or TNF-α using in situ hibridization and IHC confirmed the virus-specific trigger of the pro-inflammatory response. Taken together, this work provided additional evidences that corroborated with the traditional theories regarding the "cytokine storm" and the occurrence of uneven cellular immunity in response to DENV as major reasons for progress to severe disease.
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Quimiocina CCL5/fisiologia , Dengue/complicações , Interferon gama/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Adulto , Quimiocina CCL5/metabolismo , Citocinas/metabolismo , Citocinas/fisiologia , Dengue/imunologia , Dengue/mortalidade , Feminino , Humanos , Imunidade Celular , Interferon gama/metabolismo , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Dengue is the most important mosquito-borne viral disease in the world. Dengue virus infection may be asymptomatic or lead to undifferentiated fever, dengue fever with or without warning signs, or severe dengue. Lower respiratory symptoms are unusual and lung-imaging data in patients with dengue are scarce. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate lung changes associated with dengue infection, we retrospectively analyzed 2,020 confirmed cases of dengue. Twenty-nine of these patients (11 females and 18 males aged 16-90 years) underwent chest computed tomography (CT), which yielded abnormal findings in 17 patients: 16 patients had pleural effusion (the sole finding in six patients) and 11 patients had pulmonary abnormalities. Lung parenchyma involvement ranged from subtle to moderate unilateral and bilateral abnormalities. The most common finding was ground-glass opacity in eight patients, followed by consolidation in six patients. Less common findings were airspace nodules (two patients), interlobular septal thickening (two patients), and peribronchovascular interstitial thickening (one patient). Lung histopathological findings in four fatal cases showed thickening of the alveolar septa, hemorrhage, and interstitial edema. CONCLUSIONS/SIGNIFICANCE: In this largest series involving the use of chest CT to evaluate lung involvement in patients with dengue, CT findings of lower respiratory tract involvement were uncommon. When abnormalities were present, pleural effusion was the most frequent finding and lung involvement was often mild or moderate and bilateral. Extensive lung abnormalities are infrequent even in severe disease and when present should lead physicians to consider other diagnostic possibilities.
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Dengue/patologia , Pulmão/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Após a dissecção de cérebro de uma paciente em 1868, Charcot definiu uma evidência histopatológica mais assertiva para a esclerose múltipla (EM): "sclerose en plaque". Entretanto, mais de um século depois, poucos estudos examinando o substrato patológico específico de fenótipos clínicos diferentes da EM são encontrados na literatura. O objetivo deste estudo é uma revisão da literatura sobre achados post-mortem (autopsia, exame histopatológico e técnicas imuno-histoquímicas) em pacientes com EM. Utilizando os termos "autopsy", "necropsy", "pathology", "post-mortem" e "multiple sclerosis", a pesquisa foi desenvolvida sobre a literatura e recursos presentes no MEDLINE no período janeiro 1990 a agosto 2012. Artigos relevantes baseados em análise macro/microscópica das lesões da EM e o uso de técnicas imuno-histoquímicas (marcadores imunológicos e neurobiológicos) foram revistos. Tratados de patologia cirúrgica e neuropatologia em suas últimas edições foram também consultados. Além dos estudos no início dos anos 2000 que identificaram padrões diferentes de desmielinização em casos de autópsia, considerando a perda de mielina, a geografia e extensão das lesões, a destruição dos oligodendrócitos e a evidência do dano imunopatológico, estudos mais detalhados e baseados em aspectos anatomopatológicos e implicações patogênicas são raros. A maioria destes poucos e específicos estudos reportam que as lesões da EM tipicamente aparecem na substância branca, mas são também abundantes na substância cinza, heterogeneidade de lesões inter-paciente e homogeneidade intra-paciente, graus diferentes para perda de mielina e estágios de atividade, foco de atividade inflamatória que origina gliose fibrilar, distrofia de oligodendrócitos e densidade axonal central diminuída. Desmielinização é um importante indicador de progressão clínica e a remielinização pode ser incompleta ou decresce com a cronicidade da doença. A importância das lesões na substância branca de aparência normal e na substância cinzenta tem sido cada vez mais reconhecida em recentes estudos com técnicas imuno-histoquímicas. Não há ainda um consenso se as diferenças entre as formas clínicas são fundamentalmente quantitativas ou qualitativas em relação ao substrato patológico e mais estudos sobre autopsias utilizando exame histopatológico e técnicas modernas de imuno-histoquímica são necessários para dirimir esta questão. Um melhor entendimento sobre a heterogeneidade das lesões da esclerose múltipla proporcionará o desenvolvimento de métodos terapêuticos mais direcionados e eficazes.
After dissection of a female brain in 1868, Charcot outlined a more assertive histopathological evidence of Multiple Sclerosis: "sclerose en plaque". However, more than a century later, very few studies examining the specific underlying pathology of a defined MS clinical phenotype are found in literature. The purpose of this study is to provide a literature review of post-mortem findings (histopathology and immunohistochemical techniques) in MS patients. The literature in MEDLINE was searched from January 1990 to August 2012 using the terms "autopsy", "necropsy", "pathology", "postmortem" and "multiple sclerosis". Relevant papers based on macroscopic/microscopic analysis of the MS lesions and the use of broad spectrum of immunological and neurobiological markers (immunohistochemistry) were reviewed. Textbooks of Surgical Pathology and Neuropathology in latest editions were also consulted.Besides the studies in the early 2000s that identified different patterns of demyelination in autopsy cases, consider the myelin impairment, the geography and extension of lesions, the oligodendrocyte destruction and the evidence of immunopathological damage, more detailed studies based on anatomopathological aspects and pathogenic implications are rare. Most of these few specific studies reported that MS lesions typically appear in the white matter, but are also abundant in grey matter, inter-patient lesions heterogeneity with intra-patient homogeneity, different degree of myelin loss and stage of activity, focus of inflammatory activity that gives way to fibrillary gliosis, oligodendrocyte dystrophy and decreased central axonal density. Demyelination is an important pathological correlate of clinical progression and remyelination could be incomplete or decreases with disease chronicity. The importance of healthy-appearing white matter damage and grey matter demyelination has been increasingly recognized in recent studies using immunohistochemical techniques. There is still no consensus on whether the differences between the clinical forms of MS are fundamentally quantitative or qualitative in relation to the pathological substrate, and more detailed studies with data on autopsies is required to resolve this issue. A better understanding of the pathogenetic heterogeneity of MS lesions will lead the development of more effective treatment methods.
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Humanos , Masculino , Feminino , Adulto , Inflamação/imunologia , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Imuno-Histoquímica/métodos , Biomarcadores , Doenças Autoimunes Desmielinizantes do Sistema Nervoso CentralRESUMO
Loiasis is a filarial disease transmitted by the Chrysops spp. tabanid flies in West and Central Africa. It is most commonly diagnosed by the clinical manifestations of Calabar swellings (transient localized inflammatory edema) or, most dramatically, by the appearance of a migrating worm through the conjunctival tissues or the bridge of the nose. We report the case of a 35-year-old resident in the city of Rio de Janeiro who displayed a moving Loa loa in the bulbar conjunctival tissue two years after returning from a six-month trip to Uganda. Surgical removal of the worm was performed.
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Doenças da Túnica Conjuntiva/diagnóstico , Infecções Oculares Parasitárias/diagnóstico , Loíase/diagnóstico , Adulto , Animais , Doenças da Túnica Conjuntiva/história , Doenças da Túnica Conjuntiva/parasitologia , Infecções Oculares Parasitárias/história , História do Século XX , Humanos , Loíase/história , Masculino , Viagem , UgandaRESUMO
Loiasis is a filarial disease transmitted by the Chrysops spp. tabanid flies in West and Central Africa. It is most commonly diagnosed by the clinical manifestations of Calabar swellings (transient localized inflammatory edema) or, most dramatically, by the appearance of a migrating worm through the conjunctival tissues or the bridge of the nose. We report the case of a 35-year-old resident in the city of Rio de Janeiro who displayed a moving Loa loa in the bulbar conjunctival tissue two years after returning from a six-month trip to Uganda. Surgical removal of the worm was performed.
A loaíase é uma filaríase transmitida por tabanídeos (mutucas) do gênero Chrysops na África central e ocidental, comumente diagnosticada pela apresentação clínica de edema de Calabar (edema inflamatório transitório e localizado) ou, mais dramaticamente, pela migração de um verme adulto pelo tecido conjuntival ou asa do nariz. Descrevemos o caso clínico de um paciente do sexo masculino, 35 anos, residente no Rio de Janeiro, que se apresentou com um verme adulto de Loa loa migrando sobre o tecido conjuntival bulbar dois anos após retornar de uma viagem de seis meses de duração a Uganda. Procedeu-se a remoção cirúrgica do verme.
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Adulto , Animais , História do Século XX , Humanos , Masculino , Doenças da Túnica Conjuntiva/diagnóstico , Infecções Oculares Parasitárias/diagnóstico , Loíase/diagnóstico , Doenças da Túnica Conjuntiva/história , Doenças da Túnica Conjuntiva/parasitologia , Infecções Oculares Parasitárias/história , Loíase/história , Viagem , UgandaRESUMO
BACKGROUND: A rubella mass vaccination campaign targeting 15-29-year-old women was performed in Brazil in 2001-2002. Rubella vaccination was contraindicated during pregnancy. A follow-up protocol was implemented for pregnant women who were vaccinated as well as their newborns. The risks of congenital rubella syndrome (CRS) and congenital rubella infection (CRI) after vaccination were assessed according to the pregnant women's immune status. METHODS: This was a prospective, noncontrolled study of pregnancy outcomes in women vaccinated against rubella in the state of Rio de Janeiro, including clinical and laboratory evaluations. RESULTS: Of 2292 reported pregnant women who were vaccinated, 1636 had known outcomes: there were 1577 newborns (96.4%), 52 miscarriages (3.2%), and 7 stillbirths (0.4%). Gestational age at vaccination was ≤ 5 weeks in 75% of the susceptible, vaccinated pregnant women. Nine newborns were positive for immunoglobulin M; 4 were born to susceptible pregnant women, for a 2.0% CRI rate (95% confidence interval, .5%-4.9%); 4 were born to vaccinated pregnant women with indeterminate or unknown status; and 1 had CRS, with a wild-type virus infection. CONCLUSIONS: The absence of vaccine-related CRS cases further supports recommendations to not interrupt a pregnancy exposed to rubella vaccine virus. Monitoring pregnancy outcomes and CRI with vaccine virus can distinguish between wild-type and vaccine virus infections, especially in situations of viral circulation.
Assuntos
Resultado da Gravidez , Vacina contra Rubéola/administração & dosagem , Vacina contra Rubéola/imunologia , Rubéola (Sarampo Alemão)/congênito , Rubéola (Sarampo Alemão)/prevenção & controle , Aborto Espontâneo , Adolescente , Adulto , Anticorpos Antivirais/sangue , Brasil/epidemiologia , Controle de Doenças Transmissíveis , Suscetibilidade a Doenças , Feminino , Humanos , Imunoglobulina G/sangue , Recém-Nascido , Vacinação em Massa/efeitos adversos , Pessoa de Meia-Idade , Gravidez , Complicações Infecciosas na Gravidez , Vacina contra Rubéola/efeitos adversos , Adulto JovemRESUMO
Lymphoproliferative disorders associated with hepatitis C virus (HCV) make up a heterogeneous group of diseases, including lymphomas. It was only recently that HCV was recognised as being a potential cause for the development of non-Hodgkin's lymphoma. The authors report a case of an older woman with chronic hepatitis C who developed primary spleen lymphoma. This case report points out the pathophysiological mechanisms of this disease and the importance of considering this disease in the differential diagnosis of patients with chronic HCV infection.