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1.
Viruses ; 15(12)2023 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-38140542

RESUMEN

Monkeypox virus (MPXV), belonging to the Poxviridae family and Orthopoxvirus genus, is closely related to the smallpox virus. Initial prodromal symptoms typically include headache, fever, and lymphadenopathy. This review aims to detail various ocular manifestations and immune evasion associated with the monkeypox viral infection and its complications, making it appropriate as a narrative review. Common external ocular manifestations of MPXV typically involve a generalized pustular rash, keratitis, discharges, and dried secretions related to conjunctival pustules, photophobia, and lacrimation. Orthopoxviruses can evade host immune responses by secreting proteins that antagonize the functions of host IFNγ, CC and CXC chemokines, IL-1ß, and the complement system. One of the most important transcription factors downstream of pattern recognition receptors binding is IRF3, which controls the expression of the crucial antiviral molecules IFNα and IFNß. We strongly recommend that ophthalmologists include MPXV as part of their differential diagnosis when they encounter similar cases presenting with ophthalmic manifestations such as conjunctivitis, blepharitis, or corneal lesions. Furthermore, because non-vaccinated individuals are more likely to exhibit these symptoms, it is recommended that healthcare administrators prioritize smallpox vaccination for at-risk groups, including very young children, pregnant women, older adults, and immunocompromised individuals, especially those in close contact with MPXV cases.


Asunto(s)
Enfermedades de la Córnea , Monkeypox virus , Niño , Humanos , Femenino , Embarazo , Preescolar , Anciano , Evasión Inmune , Vacunación , Párpados
2.
Histopathology ; 75(5): 638-648, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31087672

RESUMEN

AIMS: The clinical spectrum of yellow fever (YF) ranges from asymptomatic to fulminant hepatitis. During the sylvatic YF epidemic in the metropolitan area of São Paulo, Brazil in 2018, seven orthotopic liver transplantations (OLTs) were performed in our institution to treat fulminant YF hepatitis. Three patients recovered, while four patients died following OLT. The autopsy findings of all these cases are presented herein as the first description of YF in transplanted patients. METHODS AND RESULTS: All patients were men, aged 16-40 years, without vaccination to YF virus (YFV). All organs were examined, with tissue sampling for histopathological analysis. Detection of YF virus antigens (YFV Ag) was performed with two primary antibodies (mouse polyclonal anti-YFV antibody directed to wild strain and a goat anti-YF virus antibody), and RT-PCR assays were utilised to detect YFV-RNA. All the cases depicted typical findings of YF hepatitis in the engrafted liver. The main extrahepatic findings were cerebral oedema, pulmonary haemorrhage, pneumonia, acute tubular necrosis and ischaemic/reperfusion pancreatitis. Of the four cases, the YVF Ag was detected in the heart in one case, liver and testis in three cases, and the kidney and spleen in all four cases. All four cases had YF virus RNA detected by RT-PCR in the liver and in other organs. CONCLUSIONS: Infection of the engrafted liver and other organs by YFV, possibly combined with major ischaemic systemic lesions, may have led to the death of four of the seven patients undergoing OLT.


Asunto(s)
Trasplante de Hígado , Necrosis Hepática Masiva/virología , Trasplantes/virología , Fiebre Amarilla , Virus de la Fiebre Amarilla , Adolescente , Adulto , Autopsia , Brasil , Humanos , Trasplante de Hígado/mortalidad , Masculino , Fiebre Amarilla/patología , Fiebre Amarilla/cirugía , Fiebre Amarilla/virología , Adulto Joven
3.
Microb Pathog ; 78: 29-36, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25450888

RESUMEN

Jorge Lobo's disease is a rare mycosis characterized by chronic inflammation, which causes skin lesions in the absence of visceral dissemination. The disease occurs mainly in hot and humid climates and most cases have been registered in the Brazilian Amazon region. This study investigated possible microvascular alterations in skin lesions caused by infection with Lacazia loboi which may interfere with the clinical progression of the disease. Immunohistochemistry was used to evaluate the density of blood and lymphatic vessels, as well as expression of the cell adhesion molecules ICAM-1, VCAM-1 and E-selectin. The results showed a reduced number of blood (62.66 ± 20.30 vessels/mm(2)) and lymphatic vessels (3.55 ± 5.84 vessels/mm(2)) in Jorge Lobo's disease when compared to control skin (169.66 ± 66.38 blood vessels/mm(2) and 8 ± 2.17 lymphatic vessels/mm(2)). There were a larger number of vessels expressing ICAM-1 (27.58 ± 15.32 vessels/mm(2)) and VCAM-1 (7.55 ± 6.2 vessels/mm(2)). No difference was observed in the expression of E-selectin (4.66 ± 11 vessels/mm(2)). Taken together, the results indicate changes in the local microvasculature which may interfere with the development of an efficient cell-mediated immune response and may explain restriction of the fungus to the site of injury.


Asunto(s)
Células Endoteliales/patología , Lacazia/fisiología , Lobomicosis/patología , Microvasos/patología , Piel/irrigación sanguínea , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Brasil , Selectina E/genética , Selectina E/metabolismo , Células Endoteliales/metabolismo , Femenino , Humanos , Inmunohistoquímica , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Lobomicosis/genética , Lobomicosis/metabolismo , Lobomicosis/microbiología , Masculino , Microvasos/metabolismo , Microvasos/microbiología , Persona de Mediana Edad , Piel/metabolismo , Piel/patología , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismo , Adulto Joven
4.
BMC Infect Dis ; 14: 491, 2014 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-25200768

RESUMEN

BACKGROUND: In this paper we study the distribution of leukocyte populations and of cytokine-producing cells in the spleen of a patient with visceral leishmaniasis resistant to clinical treatment. It is the first attempt to compare the distribution of leukocyte populations and cytokine-producing cells in the splenic compartments of a patient with visceral leishmaniasis with those observed in patients without the disease. CASE PRESENTATION: A 25-year-old male, farmer, was hospitalized on several occasions with diagnosis of visceral leishmaniasis and received all recommended treatments for the disease with only transient improvement followed by relapse. He was eventually subjected to splenectomy in order to control the effects of hypersplenism and to potentially overcome infection. After surgery and combined chemotherapy, the disease evolved to cure. In comparison with the spleens of the other two patients without visceral leishmaniasis, an increase was observed in the CD4/CD8 ratio and in the number of IL-10- and FoxP3-producing cells, while the number of IL-17-producing cells was lower in the spleen of the patient with visceral leishmaniasis. CONCLUSION: This report confirms previous data on changes in the CD4/CD8 ratio in the spleens of patients with visceral leishmaniasis. Additionally the data presented herein suggests that splenic FoxP3- and IL-17-producing cells are involved in the chronicity of visceral leishmaniasis.


Asunto(s)
Citocinas/genética , Leishmaniasis Visceral/terapia , Leucocitos/citología , Bazo/inmunología , Adulto , Citocinas/inmunología , Humanos , Leishmania infantum/fisiología , Leishmaniasis Visceral/tratamiento farmacológico , Leishmaniasis Visceral/genética , Leishmaniasis Visceral/inmunología , Recuento de Leucocitos , Leucocitos/inmunología , Masculino , Persona de Mediana Edad , Bazo/citología , Insuficiencia del Tratamiento
5.
Rev Med Virol ; 23(5): 305-18, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23873723

RESUMEN

Yellow fever is a viral hemorrhagic fever, which affects people living in Africa and South America and is caused by the yellow fever virus, the prototype species in the Flavivirus genus (Flaviviridae family). Yellow fever virus infection can produce a wide spectrum of symptoms, ranging from asymptomatic infection or oligosymptomatic illness to severe disease with a high fatality rate. In this review, we focus in the mechanisms associated with the physiopathology of yellow fever in humans and animal models. It has been demonstrated that several factors play a role in the pathological outcome of the severe form of the disease including direct viral cytopathic effect, necrosis and apoptosis of hepatocyte cells in the midzone, and a minimal inflammatory response as well as low-flow hypoxia and cytokine overproduction. New information has filled several gaps in the understanding of yellow fever pathogenesis and helped comprehend the course of illness. Finally, we discuss prospects for an immune therapy in the light of new immunologic, viral, and pathologic tools.


Asunto(s)
Fiebre Amarilla/inmunología , Fiebre Amarilla/patología , Virus de la Fiebre Amarilla/inmunología , África , Animales , Modelos Animales de Enfermedad , Humanos , Inmunoterapia/métodos , América del Sur , Fiebre Amarilla/terapia , Virus de la Fiebre Amarilla/fisiología
6.
Med Mycol ; 50(2): 187-92, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21526912

RESUMEN

The increase in solid organ transplantations may soon create a rise in the occurrence of endemic fungal diseases, such as paracoccidioidomycosis, due to the lack of rigorous screening of donors from endemic areas. Here we present the first case of an immunocompetent and asymptomatic kidney donor who had Paracoccidioides brasiliensis infected-adrenal tissue but no glandular dysfunction.


Asunto(s)
Trasplante de Riñón/efectos adversos , Paracoccidioides/aislamiento & purificación , Paracoccidioidomicosis/transmisión , Donantes de Tejidos , Glándulas Suprarrenales/microbiología , Glándulas Suprarrenales/patología , Antígenos Fúngicos/inmunología , Enfermedades Endémicas , Proteínas Fúngicas/inmunología , Glicoproteínas/inmunología , Humanos , Inmunohistoquímica , Trasplante de Riñón/métodos , Masculino , Persona de Mediana Edad , Paracoccidioides/inmunología , Paracoccidioidomicosis/diagnóstico , Paracoccidioidomicosis/inmunología
7.
Trans R Soc Trop Med Hyg ; 101(2): 161-8, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16872652

RESUMEN

The study of the in-situ cellular immune response is very important for the understanding of different liver infections. In the present study, 53 liver samples obtained by viscerotomy from patients who died during the course of jungle yellow fever were analyzed. The diagnosis was confirmed by serology, viral isolation and virus-specific immunohistochemistry. The specimens were analyzed by immunohistochemistry using specific antibodies for apoptosis, CD45RO, CD4, CD8, CD20, S100, CD57 and CD68. Quantitative analysis of the labeling pattern showed a clear predominance of the different phenotypes in the portal tract and midzone region of the acini. There was a predominance of T CD4+ lymphocytes, accompanied by the presence of T CD8+ lymphocytes, natural killer cells (CD57), macrophages and antigen-presenting cells (S100). The disproportion between the intensity of inflammation and the degree of hepatic injury was probably due to the intense apoptotic component, which classically does not induce an inflammatory response. The present study demonstrates that, despite the disproportion between injury and inflammation, the cellular immune response plays an important role in the pathogenesis of the hepatocytic injury observed in yellow fever, probably as a result of cytolytic actions through mechanisms involving MHC II and the activation of Fas receptors and granzymes/perforins.


Asunto(s)
Hepatocitos/patología , Fiebre Amarilla/patología , Análisis de Varianza , Anticuerpos Antivirales/inmunología , Biomarcadores , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Femenino , Hepatocitos/inmunología , Humanos , Inmunidad Celular , Inmunohistoquímica , Masculino , Proteínas S100/inmunología , Fiebre Amarilla/inmunología , Virus de la Fiebre Amarilla/inmunología
8.
Med Hypotheses ; 67(3): 618-21, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16650626

RESUMEN

Yellow fever is an acute infectious, non-contagious disease characterized by intense vasculopathy and lesions in different organs. In the liver, one of the main targets of the virus, the infection induces a characteristic midzonal injury characterized by hepatocyte necrosis, apoptosis and steatosis. This characteristics pattern of liver injury in yellow fever is also observed in conditions of low-flow hypoxia and other infections such as dengue and Rift Valley fever. There are no reports in the literature explaining the genesis of this peculiar histopathological pattern in yellow fever. Some hypotheses have been proposed to explain the mechanism of this midzonal distribution pattern observed in the liver such as low-flow hypoxia and tropism of the virus toward hepatocytes in this area. These hypotheses are discussed in view of more recent findings regarding the pathogenesis of yellow fever and regarding hepatic physiopathology, and a new hypothesis is proposed: the midzonal necrosis is consequence of action of combined factors mainly the direct cytopathic effect of YFV associated with a potent immune response in which CD4+ and CD8+ lymphocytes and the cytokines, especially TGF-beta, but also TNF-alpha and IFN-gamma play an important role.


Asunto(s)
Hepatocitos/patología , Hepatocitos/virología , Hígado/lesiones , Fiebre Amarilla/inmunología , Fiebre Amarilla/patología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Humanos , Inflamación/patología , Interferón gamma/inmunología , Modelos Inmunológicos , Necrosis/patología , Factor de Necrosis Tumoral alfa/inmunología , Fiebre Amarilla/virología , Virus de la Fiebre Amarilla/aislamiento & purificación
9.
Virology ; 345(1): 22-30, 2006 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-16278000

RESUMEN

Flavivirus infection as dengue and yellow fever persists as a terrible menace to pandemics, due to Aedes prevalence in the Americas. Yellow fever is characterized by hepatocyte damage, with steatosis, apoptosis and necrosis, mainly in the midzonal region of the liver, but the injury mechanism has not been studied at the light of recent knowledge, such as the advances in cell death mechanisms, inflammatory response and cytokine cell expression tools. We studied 53 human liver paraffin embedded blocks from patients who died with yellow fever, all with histological demonstration of higher prevalence of apoptosis over necrosis and mild disproportionate inflammatory response. Viral antigens were found most frequently in hepatocytes from the midzonal area than other lobule areas, as detected by specific immunohistochemistry. Infiltrating cell subpopulations showed mainly CD4+ T lymphocytes, with small numbers of CD8+ cytotoxic lymphocytes, CD20+ B lymphocytes, NKT+ cells and S100+ dendritic cells in the sites of inflammation, as compared to normal and leptospirosis liver blocks. Some cells expressed TNF-alpha and IFN-gamma, but a much more intense proportion of TGF-beta expressing cells were found, suggesting both a Th1 and Th3 patterns of immune response in yellow fever. Most affected hepatocyte presented apoptosis markers that appear at the cell death main pathway in this infection. Viral antigens, which production could interfere in hepatocyte biology, could induce the activation of apoptosis cascade, but TGF-beta was also an apoptosis promoter. Our finding supports the key effect of the yellow fever virus in hepatocyte injury, resulting in prevalence of apoptosis over necrosis, aside from a TGF-beta action induced by the inflammatory response.


Asunto(s)
Apoptosis , Hepatocitos/virología , Células Asesinas Naturales/inmunología , Factor de Crecimiento Transformador beta/análisis , Factor de Necrosis Tumoral alfa/análisis , Fiebre Amarilla/patología , Adolescente , Adulto , Anciano , Antígenos Virales/análisis , Niño , Preescolar , Células Dendríticas/patología , Femenino , Hepatocitos/patología , Histocitoquímica , Humanos , Inmunohistoquímica , Inflamación/patología , Subgrupos Linfocitarios/patología , Masculino , Persona de Mediana Edad , Necrosis , Adhesión en Parafina , Fiebre Amarilla/inmunología , Fiebre Amarilla/virología , Virus de la Fiebre Amarilla/aislamiento & purificación
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