Oropouche Virus Infection And Pathogenesis Is Restricted By Mavs, Irf-3, Irf-7, And Type I Ifn Signaling Pathways In Non-myeloid Cells.

Oropouche virus (OROV) is a member of the Orthobunyavirus genus in the Bunyaviridae family and a prominent cause of insect-transmitted viral disease in Central and South America. Despite its clinical relevance, little is known about OROV pathogenesis. To define the host defense pathways that control OROV infection and disease, we evaluated OROV pathogenesis and immune responses in primary cells and mice that were deficient in the RIG-I-like receptor signaling pathway (MDA5, RIG-I, or MAVS), downstream regulatory transcription factors (IRF-3 or IRF-7), IFN-β, or the receptor for type I IFN signaling (IFNAR). OROV replicated to higher levels in primary fibroblasts and dendritic cells lacking MAVS signaling, the transcription factors IRF-3 and IRF-7, or IFNAR. In mice, deletion of IFNAR, MAVS, or IRF-3 and IRF-7 resulted in uncontrolled OROV replication, hypercytokinemia, extensive liver damage, and death whereas wild-type (WT) congenic animals failed to develop disease. Unexpectedly, mice with a selective deletion of IFNAR on myeloid cells (CD11c Cre(+) Ifnar(f/f) or LysM Cre(+) Ifnar(f/f)) did not sustain enhanced disease with OROV or La Crosse virus, a closely related encephalitic orthobunyavirus. In bone marrow chimera studies, recipient irradiated Ifnar(-/-) mice reconstituted with WT hematopoietic cells sustained high levels of OROV replication and liver damage, whereas WT mice reconstituted with Ifnar(-/-) bone marrow were resistant to disease. Collectively, these results establish a dominant protective role for MAVS, IRF-3 and IRF-7, and IFNAR in restricting OROV virus infection and tissue injury, and suggest that IFN signaling in non-myeloid cells contributes to the host defense against orthobunyaviruses. Oropouche virus (OROV) is an emerging arthropod-transmitted orthobunyavirus that causes episodic outbreaks of a debilitating febrile illness in humans in countries of South and Central America. The continued expansion of the range and number of its arthropod vectors increases the likelihood that OROV will spread into new regions. At present, the pathogenesis of OROV in humans or other vertebrate animals remains poorly understood. To define cellular mechanisms of control of OROV infection, we performed infection studies in a series of primary cells and mice that were deficient in key innate immune genes involved in pathogen recognition and control. Our results establish that a MAVS-dependent type I IFN signaling pathway has a dominant role in restricting OROV infection and pathogenesis in vivo.

Viral hepatitis in patients infected with human immunodeficiency virus

From 1992 to 1995 we studied 232 (69% male, 87% Caucasian) anti-human immunodeficiency virus (anti-HIV) positive Brazilian patients, through a questionnaire; HIV had been acquired sexually by 50%, from blood by 32%, sexually and/or from blood by 16.4% and by an unknown route by 1.7%. Intravenous drug use was reported by 29%; it was the most important risk factor for HIV transmission. The alanine aminotransferase quotient (qALT) was >1 for 40% of the patients, 93.6% had anti-hepatitis A virus antibody, 5.3% presented hepatitis B surface antigen, 44% were anti-hepatitis B core antigen positive and 53.8% were anti-hepatitis C virus (anti-HCV) positive. The anti-HCV test showed a significant association with qALT>1. Patients for whom the probable HIV transmission route was blood had a 10.8 times greater risk of being anti-HCV positive than patients infected by other routes. Among 30 patients submitted to liver biopsy, 18 presented chronic hepatitis.

Necrose cerebelar extensa na anemia falciforme: relato de um caso

A 6 month-old mulatto boy was admitted on account of acute gastroenteritis, malnutrition and dehydration. In the hospital, the child developed septicemia, and temperature reached up to 38.6°C. Despite intensive antibiotic treatment, the patient died 12 days after admission. Necropsy disclosed bilateral bronchopneumonia, bilateral fronto-parietal subarachnoid hemorrhage, and extensive necrosis of the inferior half of both cerebellar hemispheres. On histopathological examination of the necrotic cerebellar cortex, numerous sickled erythrocytes were observed in petechial hemorrhages and, in lesser quantities, inside capillaries. Lesions of the central nervous system in sickle cell anemia most often involve the cerebral cortex, and a single extensive cerebellar infarction as present in this case seems extremely rare. The pathogenetic mechanism of the necrosis is unclear, since thrombosis was not observed either in large blood vessels or in capillaries. Possible contributory factors were the infectious condition (septicemia), fever, and anoxia caused by the extensive bronchopneumonia.

Detection of human cytomegalovirus and Epstein-Barr virus in coronary atherosclerotic tissue

Previous studies indicated that patients with atherosclerosis are predominantly infected by human cytomegalovirus (HCMV), but rarely infected by type 1 Epstein-Barr virus (EBV-1). In this study, atheromas of 30 patients who underwent aortocoronary bypass surgery with coronary endartherectomy were tested for the presence of these two viruses. HCMV occurred in 93.3% of the samples and EBV-1 was present in 50% of them. Concurrent presence of both pathogens was detected in 43.3% of the samples.

Effect of Potato virus X on total phenol and alkaloid contents in Datura stramonium leaves

The present paper reports results of the effect of Potato virus X (PVX) on the contents of total phenols and alkaloids in leaves of Datura stramonium. A significant decrease in the contents of phenols and alkaloids was observed in leaves inoculated with PVX (X-I). However, there was an increase in the percentage of phenols in leaves rubbed with phosphate buffer (C1-I) and in leaves from the nodes immediately above, possibly induced by mechanical injury. Gas chromatography/mass spectroscopy revealed amounts of scopolamine in samples submitted to all treatments, except X-I, in which the amount of this alkaloid was low. High amounts of an unidentified compound (molecular ion m/z 302 and a prominent peak at m/z 129) were noted in extracts from leaves X-I, C1-I and leaves from the nodes immediately above the leaves inoculated with PVX. It is suggested that the synthesis and accumulation of the unidentified compound is a result of stress from mechanical injury and virus inoculation.

Cardioprotective effect of ornitho-kinin in an anesthetized, open-chest chicken model of acute coronary occlusion

The generation of bradykinin (BK; Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) in blood and kallidin (Lys-BK) in tissues by the action of the kallikrein-kinin system has received little attention in non-mammalian vertebrates. In mammals, kallidin can be generated by the coronary endothelium and myocytes in response to ischemia, mediating cardioprotective events. The plasma of birds lacks two key components of the kallikrein-kinin system: the low molecular weight kininogen and a prekallikrein activator analogous to mammalian factor XII, but treatment with bovine plasma kallikrein generates ornitho-kinin [Thr6,Leu8]-BK. The possible cardioprotective effect of ornitho-kinin infusion was investigated in an anesthetized, open-chest chicken model of acute coronary occlusion. A branch of the left main coronary artery was reversibly ligated to produce ischemia followed by reperfusion, after which the degree of myocardial necrosis (infarct size as a percent of area at risk) was assessed by tetrazolium staining. The iv injection of a low dose of ornitho-kinin (4 µg/kg) reduced mean arterial pressure from 88 ± 12 to 42 ± 7 mmHg and increased heart rate from 335 ± 38 to 402 ± 45 bpm (N = 5). The size of the infarct was reduced by pretreatment with ornitho-kinin (500 µg/kg infused over a period of 5 min) from 35 ± 3 to 10 ± 2% of the area at risk. These results suggest that the physiological role of the kallikrein-kinin system is preserved in this animal model in spite of the absence of two key components, i.e., low molecular weight kininogen and factor XII.

Culex nigripalpus Theobald (Diptera, Culicidae) feeding habit at the Parque Ecológico do Tietê, São Paulo, Brazil

The blood feeding of a population of Cx. nigripalpus from Parque Ecológico do Tietê (PET) was investigated using an indirect ELISA protocol. Mosquitoes were captured outside houses. Five hundred sixteen engorged females collected in a reforested area and 25 in an open area were tested. Rodents and dogs were the most common blood sources, accounting for approximately 65.3% of blood meals. Human blood was detected in 10.9%, dog blood in 26.1%, chicken blood in 2.4%, and rodent blood in 39.2% of the 541 insects tested. ELISA failed in identifying the blood sources of 233 engorged females, indicating that the mosquitoes may have fed on a host which was not tested. One hundred six individuals were positive for more than one host. The unweighted human blood index was 0.14 and the rodent/human, human/chicken, and dog/rodent feeding index values were 2.70, 1.51, and 1.33, respectively. Furthermore, rodents are defensive hosts for this haematophagous insect which looks for another host to complete blood-feeding. Considering that rodents are potential reservoirs for Mucambo virus and Saint Louis encephalitis virus and that Cx. nigripalpus feed on the blood of those mammals, we hypothesize that mosquito population in PET could participate in the transmission cycle of those arboviruses. Additionally, this species might be involved in the transmission of Dirofilaria immitis to dogs at this area.

Comparison of direct immunofluorescence, conventional cell culture and polymerase chain reaction techniques for detecting respiratory syncytial virus in nasopharyngeal aspirates from infants

A total of 316 samples of nasopharyngeal aspirate from infants up to two years of age with acute respiratory-tract illnesses were processed for detection of respiratory syncytial virus (RSV) using three different techniques: viral isolation, direct immunofluorescence, and PCR. Of the samples, 36 (11.4%) were positive for RSV, considering the three techniques. PCR was the most sensitive technique, providing positive findings in 35/316 (11.1%) of the samples, followed by direct immunofluorescence (25/316, 7.9%) and viral isolation (20/315, 6.3%) (p < 0.001). A sample was positive by immunofluorescence and negative by PCR, and 11 (31.4%) were positive only by RT-PCR. We conclude that RT-PCR is more sensitive than IF and viral isolation to detect RSV in nasopharyngeal aspirate specimens in newborn and infants.

Políticas públicas para o controle da anemia ferropriva

A anemia por deficiência de ferro configura um problema epidemiológico da maior relevância atuando nos gastos públicos de saúde, nas consequências sociais do aumento de riscos no período gestacional, na redução da produtividade e, ainda, nas consequências, em longo prazo, do desenvolvimento mental. Algumas datas marcam o envolvimento do governo brasileiro em busca de alternativas de controle da deficiência marcial: 1977 - 1ª Reunião do Ministério da Saúde (INAN), com especialistas nacionais e internacionais, para discutir perspectivas e intervenções para o controle da anemia; 1982/83 - distribuição de suplemento de ferro para a clientela do Programa de Atenção à Gestante e dosagem de hemoglobina na 1ª consulta; 1992 - assinatura de compromisso brasileiro de reduzir em 1/3 a prevalência de anemia em gestantes; 1994 - implantação do Programa de Leite Vivaleite, no estado de São Paulo, fornecendo leite fortificado com ferro a famílias com crianças até 6 anos e renda inferior a dois salários mínimos; 2002/junho 2004 - fortificação das farinhas de trigo e de milho com ferro; 2005 - programa de suplementação de ferro a lactentes; 2009/março - divulgação do resultado do levantamento de prevalência de anemia em mulheres (15-49 anos) e crianças (6 - 59 meses) no Brasil; 2009/agosto - foi reeditada a Portaria no 1793/GM/agosto/2009 do Ministério da Saúde, instituindo a Comissão Interinstitucional para implementação, acompanhamento e monitorização das ações de fortificação das farinhas de trigo e milho e seus subprodutos.

Mineral and vitamin content of beef, chicken, and turkey hydrolysates mineral and vitamin content of protein hydrolysates

The purpose of this study was to assess the concentration of vitamins and minerals in meat protein hydrolysates. Calcium, phosphorus and iron were analyzed by inductively coupled-plasma atomic emission spectrophotometry; vitamin C was analyzed by the reduction of cupric ions and vitamins B1 and B2 by fluorescence. Regarding minerals, the beef hydrolysate (BH) had more iron than the turkey hydrolysate (TH) and the chicken hydrolysate (CH); TH had a little more phosphorus. BH had the largest amount of vitamin C, and similar amounts of vitamins B1 and B2. The amount of these nutrients found in the hydrolysates suggests that it is possible to use them to enrich special dietary formulations.

Anemia em crianças de 6 a 59 meses e fatores associados no Município de Jordão, Estado do Acre, Brasil

Examinou-se a prevalência e fatores associados à anemia em estudo transversal com 429 crianças de 6 a 59 meses do Município de Jordão, Estado do Acre, Brasil. Modelos múltiplos de regressão de Poisson foram utilizados com seleção hierárquica das variáveis independentes. A anemia foi altamente prevalente (57,3%; IC95%: 52,5%-62,1%). Ter idade entre 6 e 23,9 meses [razão de prevalência - RP (IC95%): 1,40 (1,09-1,74)], morar na área rural [RP: 1,23 (1,04-1,44)], morar em domicílio com 5 a 14 crianças [RP: 1,23 (1,04-1,44)], ter mãe que fumou na gravidez [RP: 1,29 (1,09-1,53)], mãe anêmica [RP: 1,18 (1,00-1,39)] e apresentar déficit de altura para idade [RP: 1,19 (1,01-1,39)] foram fatores associados ao risco de anemia, e ter mãe que trabalha fora [RP: 0,78 (0,64-0,94)] foi fator de proteção. A anemia é um grave problema de saúde pública nesse município. Estratégias multissetoriais de combate à pobreza, aumento da cobertura e qualidade de serviços de assistência à saúde materno-infantil devem ser implementados.

Anemia e deficiência de ferro em pré-escolares da Amazônia Ocidental brasileira: prevalência e fatores associados

Estudo transversal de base populacional que investigou prevalênciasde anemia e fatores associados à anemia, anemia ferropriva e deficiência de ferro entre crianças de 6 a 60 meses da área urbana de dois municípios do Acre, Brasil (N = 624). Dosagens de hemoglobina sanguínea, ferritina e receptor solúvel de transferrina plasmáticas foram realizadas mediante sangue venoso. Condições sócio-econômicas, demográficas e de morbidade foram obtidas por questionário. Razões de prevalências foram calculadas por regressão de Poisson em modelo hierárquico. As prevalências de anemia, anemia ferropriva e deficiência de ferro foram de 30,6%, 20,9% e 43,5%, respectivamente. Menores de 24 meses apresentaram maior risco para anemia, anemia ferropriva e deficiência de ferro. Pertencer ao maior tercil do índice de riqueza conferiu proteção contra anemia ferropriva (RP = 0,62; IC95%: 0,40-0,98). Pertencer ao maior quartil do índice estatura/idade foi protetor contra anemia (0,62; 0,44-0,86) e anemia ferropriva (0,51; 0,33-0,79), e ocorrência recente de diarréia representou risco (anemia: 1,47; 1,12-1,92 e anemia ferropriva: 1,44; 1,03-2,01). A infestação por geohelmintos conferiu risco para anemia, anemia ferropriva e deficiência de ferro.

Circulation of antibodies against yellow fever virus in a simian population in the area of Porto Primavera Hydroelectric Plant, São Paulo, Brazil

Yellow fever (YF) is an acute viral infectious disease transmitted by mosquitoes which occurs in two distinct epidemiological cycles: sylvatic and urban. In the sylvatic cycle, the virus is maintained by monkey's infection and transovarian transmission in vectors. Surveillance of non-human primates is required for the detection of viral circulation during epizootics, and for the identification of unaffected or transition areas. An ELISA (enzyme-linked immunosorbent assay) was standardized for estimation of the prevalence of IgG antibodies against yellow fever virus in monkey sera (Alouatta caraya) from the reservoir area of Porto Primavera Hydroelectric Plant, in the state of São Paulo, Brazil. A total of 570 monkey sera samples were tested and none was reactive to antibodies against yellow fever virus. The results corroborate the epidemiology of yellow fever in the area. Even though it is considered a transition area, there were no reports to date of epizootics or yellow fever outbreaks in humans. Also, entomological investigations did not detect the presence of vectors of this arbovirus infection. ELISA proved to be fast, sensitive, an adequate assay, and an instrument for active search in the epidemiological surveillance of yellow fever allowing the implementation of prevention actions, even before the occurrence of epizootics.

Características clínicas da fase aguda da infecção experimental de felinos pelo vírus da imunodeficiência felina

A infecção dos felinos pelo Vírus da Imunodeficiência Felina (FIV) resulta no desenvolvimento da síndrome de imunodeficiência dos felinos. Gengivite, perda de peso, linfadenomegalia generalizada, anemia, insuficiência renal crônica, complicações neurológicas, diarréia crônica e infecções bacterianas são encontradas frequentemente. A fase aguda da infecção pode ser assintomática, retardando o estabelecimento do diagnóstico e a implantação de medidas profiláticas para restringir o contágio e a transmissão do agente aos felinos suscetíveis. Com a finalidade de estudar as características clínicas da fase aguda da infecção, dez felinos jovens, sem definição racial, com oito meses de idade foram inoculados por via endovenosa com 1mL de sangue venoso de um gato portador do FIV subtipo B. A confirmação da infecção foi obtida através de teste sorológico em quatro e oito semanas pós-inoculação (p.i.) e por nested-PCR. Foram realizados hemogramas semanais, exame ultrassonográfico do abdômen quinzenais e exame oftalmológico mensal, durante doze semanas p.i. Discreta tendência a linfopenia na segunda semana p.i. e a neutropenia entre a quinta e sétima semana p.i., febre intermitente em alguns gatos, linfadenomegalia e hepato-esplenomegalia entre a quarta e a 12ª semana p.i. foram as alterações clínicas observadas. Apenas um gato apresentou uveíte unilateral direita. A fase aguda da infecção transcorreu com alterações clínicas inespecíficas. A linfadenomegalia e a hepato-esplenomegalia observadas no decorrer da infecção, refletindo hiperplasia linfóide, sugerem a necessidade de se realizar o teste sorológico para o FIV, em todos os gatos que se apresentarem com essas alterações, o que permitirá o diagnóstico precoce da infecção e a adoção de medidas profiláticas no sentido de minimizar a propagação da infecção.