Consideraciones provisionales sobre la infección por el virus zika en mujeres gestantes. Documento destinado a profesionales de salud

El propósito de este documento es brindar a los profesionales de salud que asisten a mujeres gestantes, información actualizada en base a las mejores evidencias disponibles para prevenir la infección, diagnosticarla oportunamente, sugerir tratamiento, dar seguimiento a las embarazadas, así como notificar el caso a las autoridades sanitarias competentes. La información que se presenta en este documento se encuentra actualizada hasta el 22 de enero de 2016 y podrá ser modificada en caso de aparecer nueva evidencia sobre los efectos / consecuencias de la infección por virus Zika en embarazadas y sus hijos. Nuevas actualizaciones podrán encontrase periódicamente en el sitio www.paho.org/viruszika

Protocolo de vigilância e resposta à ocorrência de microcefalia relacionada à infecção pelo vírus Zika

Este protocolo tiene como objetivo proveer información general a los profesionales de salud acerca de las técnicas de vigilancia sobre la microcefalia en el territorio de Brasil.

Practice advisory: interim guidance for care of obstetric patients during a zika virus outbreak

Zika during pregnancy has been associated with birth defects, specifically significant microcephaly. Transmission of Zika to the fetus has been documented in all trimesters; Zika virus RNA has been detected in fetal tissue from early missed abortions, amniotic fluid, term neonates and the placenta. However, much is not yet known about Zika virus in pregnancy. Uncertainties include the incidence of Zika virus infection among pregnant women in areas of Zika virus transmission, the rate of vertical transmission and the rate with which infected fetuses manifest complications such as microcephaly or demise. The absence of this important information makes management and decision making in the setting of potential Zika virus exposure (i.e. travel to endemic areas) or maternal infection, difficult. Currently, there is no vaccine or treatment for this infection.

Kernicterus e icterícia neonatal : revisão teórica a propósito de um caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Diagnóstico da tuberculose pulmonar no adulto nos países de baixo rendimento : será o XPERT® MTB/RIF a escolha correcta?

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Epidemiologia e caracterização molecular dos vírus Dengue circulantes no Rio Grande do Norte, 2013-2014

Dengue is an acute infectious disease, usually transmitted by Aedes aegypti mosquitoes. The etiologic agents belong to the family Flaviviridae, genus Flavivirus, and occur as four antigenically related but distinct serotypes designated DENV-1, 2, 3, and 4. In Brazil, the disease represents a national public health problem. The purpose of the present study was to describe epidemiological aspects of dengue in the State of Rio Grande do Norte, from 2013 to 2014. A total of 483 blood or serum samples, collected from January 2013 to December 2014, were studied by RT-PCR for viral detection and typing. The infection was confirmed in 36.44% (176/483) of the cases studied. This study detected the circulation of three serotypes of dengue virus in Rio Grande do Norte, DENV-1, 2, and 4. The predominant serotype in 2013-2014 was the DENV-4, representing 83.51% (81/97) and 68.35% (54/79) of the positive cases, respectively. Regarding the spatial distribution, most of the cases occurred in Natal and Caicó, with 9.28% (9/97) and 18.99% (15/79), respectively. The months with the biggest viral circulation in RN were March 2013 and May 2014. The female gender was the most affected, representing 69.07% (67/97) in 2013 and 54.43% (43/79) in 2014. The most affected age groups were 21-30 years (2013) and 11-20 years (2014) with 25.77% (25/97) and 20.25% (16/79) positive cases, respectively. Phylogenetic analysis indicated that genotype V (DENV-1) and genotype II (DENV-4) circulated in the State. Our results provide information about the dynamics of DENV in the Rio Grande do Norte, important for the development of disease control strategies.

Herpesvírus

O herpesvírus está disseminado na população canina mundial, com uma seroprevalência de cerca de 40 a 80%. A infeção por herpesvírus canino causa elevadas taxas de mortalidade em cachorros e em cães adultos pode permanecer em estado latente ou ser reativado. A infeção por este vírus em canis de reprodução representa grandes perdas económicas, pelo que se pretende estudar a seroprevalência de herpesvírus em 52 cães pertencentes a dois canis de reprodução, para fins de venda de cães de raça. Foram analisados animais de ambos os sexos e com idades compreendidas entre 1 e 8 anos de idade. Devido a inexistências de terapia para cachorros com sintomatologia de infeção por HVC-1 pretende-se formular um protocolo de cuidados para ninhadas, suspeitas de serem portadoras deste vírus, e para os restantes cães da colónia. Estão descritos estudos que indicam o HVC-1 como um dos agentes indiretamente envolvidos na etiologia do linfoma canino, pelo que se procurou estudar a sua seroprevalência numa amostra de 28 cães com linfoma, sendo um dos objetivos a deteção de anticorpos HVC-1, nestes animais.

Estudo do papel da proteína multifuncional APE1/Ref-1 sobre a resposta inflamatória na meningite bacteriana

Despite advances in antibiotic therapy, bacterial meningitis (BM) remains with high mortality and morbidity rates in worldwide. One important mechanism associated to sequels during disease is the intense inflammatory response which promotes an oxidative burst and release of reactive oxygen species, consequently leading to cell death. Activation of DNA repair enzymes during oxidative stress has been demonstrated in several neurological disorders. APE1/Ref-1 is a multifunctional protein involved in DNA repair and plays a redox function on transcription factors such as NFkB and AP-1.The aim of this study was assess the role of APE1/Ref-1 on inflammatory response and the possibility of its modulation to reduce the sequels of the disease. Firstly it was performed an assay to measure cytokine in cerebrospinal fluid of patients with BM due to Streptococcus pneumoniae and Neisseriae meningitides. Further, a cellular model of inflammation was used to observe the effect of the inhibition of the endonuclease and redox activity of APE1/Ref-1 on cytokine levels. Additionally, APE1/Ref-1 expression in cortex and hippocampus of rat with MB after vitamin B6 treatment was evaluated. Altogether, results showed a similar profile of cytokines in the cerebrospinal fluid of patients from both pathogens, although IFNy showed higher expression in patients with BM caused by S. pneumoniae. On the other hand, inhibitors of APE1/Ref-1 reduced cytokine levels, mainly TNF-α. Reduction of oxidative stress markers was also observed after introduction of inhibitors in the LPS-stimulated cell. In the animal model, BM increased the expression of the protein APE1/Ref-1, while vitamin B6 promoted reduction. Thereby, this data rise important factors to be considered in pathogenesis of BM, e.g., IFNy can be used as prognostic factor during corticosteroid therapy, APE1/Ref-1 can be an important target to modulate the level of inflammation and VIII oxidative stress, and vitamin B6 seems modulates several proteins related to cell death. So, this study highlights a new understanding on the role of APE1/Ref-1 on the inflammation and the oxidative stress during inflammation condition

Análise do efeito de polimorfismos não-sinônimos em genes de reparo de DNA da via BER na resposta inflamatória da meningite

In vitro and in animal models, APE1, OGG1, and PARP-1 have been proposed as being involved with inflammatory response. In this work, we have investigated if the SNPs APE1 Asn148Glu, OGG1 Ser326Cys, and PARP-1 Val762Ala are associated to meningitis and also developed a system to enable the functional analysis of polymorphic proteins. Patients with bacterial meningitis (BM), aseptic meningitis (AM) and controls (non-infected) genotypes were investigated by PIRA-PCR or PCR-RFLP. DNA damages were detected in genomic DNA by Fpg treatment. IgG and IgA were measured from plasma and the cytokines and chemokines were measured from cerebrospinal fluid samples using Bio-Plex assays. The levels of NF-κB and c-Jun were measured in CSF by dot blot assays. A significant (P<0.05) increase in the frequency of APE1 148Glu allele in BM and AM patients was observed. A significant increase in the genotypes Asn/Asn in control group and Asn/Glu in BM group was also found. For the SNP OGG1 Ser326Cys, the genotype Cys/Cys was more frequent (P<0.05) in BM group. The frequency of PARP-1 Val/Val genotype was higher in control group (P<0.05). The occurrence of combined SNPs increased significantly in BM patients, indicating that these SNPs may be associated to the disease. Increasing in sensitive sites to Fpg was observed in carriers of APE1 148Glu allele or OGG1 326Cys allele, suggesting that SNPs affect DNA repair activity. Alterations in IgG production were observed in the presence of SNPs APE1Asn148Glu, OGG1Ser326Cys or PARP-1Val762Ala. Reductions in the levels ofIL-6, IL-1Ra, MCP-1/CCL2and IL-8/CXCL8 were observed in the presence of APE1148Glu allele in BM patients, however no differences were observed in the levels of NF-κB and c-Jun considering genotypes and analyzed groups. Using APE1 as model, a system to enable the analysis of cellular effects and functional characterization of polymorphic proteins was developed using strategies of cloning APE1 cDNA in pIRES2-EGFP vector, cellular transfection of the construction obtained, siRNA for endogenous APE1 and cellular cultures genotyping. In conclusion, we obtained evidences of an effect of SNPs in DNA repair genes on the regulation of immune response. This is a pioneering work in the field that shows association of BER variant enzymes with an infectious disease in human patients, suggesting that the SNPs analyzed may affect immune response and damage by oxidative stress level during brain infection. Considering these data, new approaches of functional characterization must be developed to better analysis and interactions of polymorphic proteins in response to this context

Chagas congénito de segunda generación en Uruguay: Primer caso sintomático descrito en el país

El Chagas congénito se produce cuando la embarazada infectada trasmite el parásito al feto, situación que puede suceder en cualquier estadio de la enfermedad y momento del embarazo. Es el único mecanismo de trasmisión presente actualmente en Uruguay, con una incidencia cercana al 4%. La mayoría de los neonatos infectados nacen asintomáticos y un 10% al 40% presentan síntomas que son indistinguibles de otras infecciones de trasmisión vertical. La prematurez, el bajo peso, la hepatoesplenomegalia y las alteraciones hematológicas son los síntomas más frecuentes. El diagnóstico representa un desafío en aquellos lugares del país en donde, si bien la enfermedad era considerada endémica, no se realiza actualmente el screening obligatorio de la embarazada. Se describe un lactante procedente de Paysandú, de medio socioeconómico deficitario, que fue pretérmino severo y que presentó al nacer alteraciones hematológicas de las tres series y hepatoesplenomegalia, lo cual motivó múltiples estudios. Sin embargo, no se sospechó la enfermedad hasta los 5 meses de vida, cuando volvió a ingresar por otra patología. Se confirmó la infección a los 9 meses mediante tres técnicas serológicas diferentes. Se indicó tratamiento con nifurtimox por 2 meses y a los 26 y 36 meses de vida presentó serología negativa. Consideramos importante tener alto índice de sospecha de la enfermedad en neonatos con signos de infección congénita y sin serología materna que la descarte. Es importante saber que el tratamiento antes del primer año de vida tiene una excelente respuesta y evita secuelas crónicas que pueden ser invalidantes en etapa adulta.

Atividade antimalárica de plantas medicinais da biorregião do Araripe-CE em modelo murino - Plasmodium berghei

Malaria, also popularly known as maleita , intermittent fever, paludism, impaludism, third fever or fourth fever, is an acute infectious febrile disease, which, in human beings, is caused by four species: Plasmodium falciparum, P. vivax, P. malariae and P. ovale. Malaria, one of the main infectious diseases in the world, is the most important parasitoses, with 250 million annual cases and more than 1 million deaths per year, mainly in children younger than live years of age. The prophylactic and therapeutic arsenal against malaria is quite restricted, since all the antimalarials currently in use have some limitation. Many plant species belonging to several families have been tested in vivo, using the murine experimental model Plasmodium berghei or in vitro against P. falciparum, and this search has been directed toward plants with antithermal, antimalarial or antiinflammatory properties used in popular Brazilian bolk medicine. Studies assessing the biological activity of medicinal plant essential oils have revealed activities of interest, such as insecticidal, spasmolytic and antiplasmodic action. It has also been scientifically established that around 60% of essential oils have antifungal properties and that 35% exhibit antibacterial properties. In our investigation, essential oils were obtained from the species Vanillosmopsis arborea, Lippia sidoides and Croton zethneri which are found in the bioregion of Araripe-Ceará. The chemical composition of these essential oils was partially characterized and the presence of monoterpenes and sesquiterpenes. The acute toxicity of these oils was assessed in healthy mice at different doses applied on a single day and on four consecutive days, and in vitro cytotoxicity in HeLa and Raw cell lines was determined at different concentrations. The in vivo tests obtained lethal dose values of 7,1 mg/Kg (doses administered on a single day) and 1,8 mg/Kg (doses administered over four days) for 50% of the animals. In the in vitro tests, the inhibitory concentration for 50% of cell growth in Hela cell lines was 588 μg/mL (essential oil from C. zethneri after 48 h), from 340-555 μg/mL (essential oil from L. sidoides, after 24 and 48 h). The essential oil from V. arborea showed no cytotoxicity and none of the essential oils were cytotoxic in Raw cell lines. These data suggest a moderate toxicity in the essential XVIII oils under study, a finding that does not impede their testing in in vivo antimalarial assays. Was shown the antimalarial activity of the essential oils in mice infected with P. berghei was assessed. The three species showed antimalarial activity from 36%-57% for the essential oil from the stem of V. arborea; from 32%-82% for the essential oil from the leaves of L. sidoides and from 40%-70% of reduction for the essential oil from the leaves of C. zethneri. This is the first study showing evidence of antimalarial activity with these species from northeast Brazil. Further studies to isolate the active ingredients of these oils are needed to determine if a single active ingredient accounts for the antimalarial activity or if a complex integration of all the compounds present occurs, a situation reflected in their biological activity

Clínica e cirurgia de espécies pecuárias

O presente relatório, inerente ao estágio curricular do Mestrado Integrado em Medicina Veterinária da Universidade de Évora, tem como objetivo descrever as atividades desenvolvidas durante o estágio na área da clínica e cirurgia de espécies pecuárias. A primeira parte do relatório consiste na descrição do local de estágio e na distribuição casuística das atividades acompanhadas. A segunda parte consiste numa revisão bibliográfica e no desenvolvimento de dois casos clínicos ocorridos em bovinos, relacionados com o tema, “necrobacilose hepática bovina” (NHB). A NHB é uma doença infecciosa de grande impacto económico, principalmente em explorações de bovinos de engorda intensiva. Carateriza-se pela formação de abcessos hepáticos, cujo agente etiológico primário é Fusobacterium necrophorum. É de difícil diagnóstico em vida, raramente demonstra sinais clínicos e o seu tratamento é pouco eficaz. A prevenção baseia-se na adição de antimicrobianos na alimentação, num correto maneio alimentar e eventualmente vacinação; Abstract: Medical and Surgical Pathology of livestock species The present report, inherent of the master in Veterinary Medicine from the University of Évora, aims to describe the activities carried out during the internship in the field of clinic and surgery of livestock species. The first part of the report is the description of the local of internship and the statistical distribution of activities. The second part consists of a literature review and the development of two clinical cases in cattle, related to the theme, “hepatic bovine necrobacillosis "(HBN). The HBN is an infectious disease of great economic impact, especially in feedlot cattle. It is characterized by the formation of liver abscesses, whose primary etiological agent is Fusobacterium necrophorum. It is difficult to diagnose in life, rarely show clinical signs and their treatment is ineffective. Prevention is based on the addition of antimicrobials in food, a correct feed management and eventually vaccination.

A influência do metabolismo redox na transmissão da doença de Chagas

As formas epimastigotas de Trypanosoma cruzi proliferam e se diferenciam no interior de diferentes compartimentos do trato digestivo dos triatomíneos. Esses ambientes antagônicos, no que diz respeito à concentração de nutrientes, pH e status redox, constituem um desafio para o protozoário por conterem moléculas e fatores capazes de deflagrar diferentes sinalizações e respostas no parasito. Por isso, testamos a influência de produtos abundantes do metabolismo do vetor e de status redox distintos, frente aos processos de proliferação e diferenciação in vivo e in vitro. Como exemplo temos o heme e a hemozoína, subprodutos da digestão da hemoglobina, e o urato, rico na urina dos insetos. O heme é uma importante molécula em todos os seres vivos. Nosso grupo mostrou seu papel na proliferação in vitro de T. cruzi e que esse sinal é governado pela enzima redox-sensível CaMKII (Lara et al., 2007; Souza et al., 2009). Esse efeito parece depender de uma sinalização redox, onde o heme e não seus análigos induz a formação de EROs, modulando a atividade da CaMKII (Nogueira et al, 2011). Apesar de gerar espécies reativas de oxigênio (EROs) em formas epimastigotas, o heme não alterou a ultraestrutura desses parasitos mostrando uma adaptação a ambientes oxidantes. Além disso, a adição de FCCP inibiu a formação de EROs mitocondrial, diminuindo a proliferação dos parasitos. Em contrapartida, a AA aumentou drasticamente a produção de EROs mitocondrial levando à morte dos epimastigotas. Estes resultados confirmam a hipótese de regulação redox do crescimento de epimastigotas. A formação de β- hematina (hemozoína) constitui uma elegante estratégia para minimizar o efeito tóxico do heme nos insetos hematófagos. Contudo, a β-hematina não influenciou a proliferação ou a metaciclogênese in vitro. Já o urato, e outros antioxidantes clássicos como o GSH e o NAC prejudicaram a proliferação in vitro de epimastigotas. Estes efeitos foram parcialmente revertidos quando os antioxidantes foram incubados juntamente com o heme. Durante a metaciclogênese in vitro, o NAC e o urato induziram um aumento significativo das formas tripomastigotas e levaram a diminuição da porcentagem de formas epimastigotas. Em contrapartida, o heme e a β-hematina apresentaram o efeito oposto, diminuindo a porcentagem de formas tripomastigotas e aumentando a de epimastigotas. No intuito de confirmar a influencia do status redox na biologia do parasito in vivo, nós quantificamos a carga parasitária nas porções anterior e posterior e no reto do triatomíneo alimentado na presença ou na ausência de NAC e urato por qPCR. O tratamento com os antioxidantes aumentou a carga parasitária em todas as partes do intestino analisadas. Posteriormente, para diferenciar as formas evolutivas responsáveis pelo incremento da carga parasitária, foram realizadas contagens diferenciais nas mesmas porções do intestino do inseto vetor. Cinco dias após a infecção foi observado aumento significativo de formas tripomastigotas e diminuição de formas epimastigotas in vivo. Em conjunto, estes dados sugerem que, assim como a concentração de nutrientes e o pH, o status redox também pode influenciar a biologia do T. cruzi no interior do inseto vetor. Neste cenário, moléculas oxidantes agiriam a favor da proliferação, e em contraste, antioxidantes parecem favorecer a metaciclogênese.

Modelo analítico para linhas de transmissão de energia elétrica: aplicação em linhas trifásicas com plano de simetria vertical

Pós-graduação em Engenharia Elétrica - FEIS

Estimação de parâmetros de linhas de transmissão utilizando técnicas de decomposição modal: Aplicação em linhas com plano de simetria vertical

Pós-graduação em Engenharia Elétrica - FEIS