Revisão sistemática sobre febre hemorrágica do dengue

Trabalho final de mestrado integrado em Medicina àrea científica de Doenças Infecciosas, apresentado á Faculdade de Medicina da Universidade de CoimbraIntrodução – O dengue assume-se como uma das doenças infeciosas reemergentes do século XXI. As regiões onde o dengue é endémico têm-se expandido e as formas de doença severa, como a febre hemorrágica do dengue, são mais frequentes. Na Europa, o advento das viagens provocou um aumento do número de viajantes com febre causada por dengue no regresso ao país de origem. Objetivos – O trabalho debruçou-se sobre as atuais alterações na definição da entidade clínica referente à doença severa do dengue, febre hemorrágica do dengue, a sua epidemiologia e o mecanismo de patogénese de doença. Clinicamente, importou esclarecer as principais manifestações clínicas, as diferentes formas de realizar o diagnóstico, com que outras patologias pode ser feito o diagnóstico diferencial, o tratamento da doença e que desenvolvimentos se podem esperar, particularmente na abordagem terapêutica. Desenvolvimento - Na febre hemorrágica do dengue houveram diversas questões que suscitaram controvérsia na comunidade científica internacional, nomeadamente quanto aos critérios de classificação da doença, aos possíveis mecanismos de patogénese e qual deve ser o tratamento preconizado. A definição em uso foi considerada como não sendo a adequada, estando a aguardar validação uma nova definição. O mecanismo de patogénese permanece ainda em parte por esclarecer. Os mecanismos de imunopatogenese, dependente de anticorpos, foram aceites como uma possível teoria explicativa da doença. Clinicamente, a hipovolémia resultante do extravasamento plasmático foi conotada como a característica cardinal da doença. O correto diagnóstico deve ter em conta outras patologias febris. O tratamento base é a fluidoterapia: soros cristaloides ou coloides. Conclusões – Dada a massificação do turismo, os profissionais de saúde dos países não-endémicos poderão ser confrontados com doentes com infeções por dengue. Pela atual ausência de vacina profilática e de terapêutica específica, é essencial uma definição clínica e laboratorial clara que auxilie os profissionais de saúde a detetar e providenciar tratamento adequado em tempo útil. De forma a inverter a tendência epidemiológia da doença conclui-se que é necessário sensibilizar a população e os viajantes para regiões endémicas, bem como formar os profissionais de saúde.Introduction - Dengue is one of the reemerging infectious diseases of the twenty-first century. The regions where dengue is endemic have expanded and severe forms of disease such as dengue hemorrhagic fever are more frequent. In Europe, the advent of travel caused an increase in the number of travellers with fever caused by dengue returning to the country of origin. Objectives - The study focused on the current changes in the definition of the clinical entity related to the severe dengue disease, dengue hemorrhagic fever, its epidemiology and pathogenesis mechanisms of disease. Clinically, it is important to clarify the main clinical manifestations, different ways to perform the diagnosis, which other diseases 5 may be taken in account for the differential diagnosis, treatment of the disease and what developments can be expected, particularly in the therapeutic approach. Development - In dengue hemorrhagic fever, there were several issues that have raised controversy in the international scientific community, particularly as regards to the criteria for classification of the disease, the possible mechanisms of pathogenesis and what should be the recommended treatment. The definition in use was considered as not being adequate, waiting a validation of a new definition. The pathogenesis mechanism remains still partly unclear. The imunopathogenis, antibody dependent enhancement, were accepted as a possible explanatory theory of the disease. Clinically, the hypovolaemia resulting from plasma leakage was denoted as the cardinal feature of the disease. The correct diagnosis should take into account other febrile diseases. The treatment is based on the fluid: serum crystalloid or colloid. Conclusions - Given the mass tourism, health professionals from non-endemic countries may be confronted with patients with dengue infections. As there is no preventive vaccine at the moment and specific therapy, it is essential to define a clear clinical and laboratory definition to assist health professionals to detect and provide appropriate treatment in time. In order to reverse disease epidemiology, it comes to the conclusion that it is necessary to alert the population and travelers to endemic areas, and train health professionals

Association of 3-Phenoxybenzoic Acid Exposure during Pregnancy with Maternal Outcomes and Newborn Anthropometric Measures: Results from the IoMum Cohort Study

The aims of this study were to characterize the exposure of pregnant women living in Portugal to 3-phenoxybenzoic acid (3-PBA) and to evaluate the association of this exposure with maternal outcomes and newborn anthropometric measures. We also aimed to compare exposure in summer with exposure in winter. Pregnant women attending ultrasound scans from April 2018 to April 2019 at a central hospital in Porto, Portugal, were invited to participate. Inclusion criteria were: gestational week between 10 and 13, confirmed fetal vitality, and a signature of informed consent. 3-PBA was measured in spot urine samples by gas chromatography with mass spectrometry (GC-MS). The median 3-PBA concentration was 0.263 (0.167; 0.458) μg/g creatinine (n = 145). 3-PBA excretion was negatively associated with maternal pre-pregnancy body mass index (BMI) (p = 0.049), and it was higher during the summer when compared to winter (p < 0.001). The frequency of fish or yogurt consumption was associated positively with 3-PBA excretion, particularly during the winter (p = 0.002 and p = 0.015, respectively), when environmental exposure is low. Moreover, 3-PBA was associated with levothyroxine use (p = 0.01), a proxy for hypothyroidism, which could be due to a putative 3-PBA—thyroid hormone antagonistic effect. 3-PBA levels were not associated with the anthropometric measures of the newborn. In conclusion, pregnant women living in Portugal are exposed to 3-PBA, particularly during summer, and this exposure may be associated with maternal clinical features.This article was supported by national funds through the FCT Foundation for Science and Technology, I.P., within the scope of the projects RISE - LA/P/0053/2020; CINTESIS, R&D UNIT (reference UIDB/4255/2020) and LAQV (references: UIDB/50006/2020 AND UIDP/50006/2020). Virgínia Cruz Fernandes was funded by FCT/MCTES (Foundation for Science and Technology and Ministry of Science, Technology and Higher Education) and the ESF (European Social Fund) through NORTE 2020 (North Region Operational Program) through a grant of Post-Doc (reference SFRH/BPD/109153/2015). Juliana Guimarães was funded by FCT/MCTES (Foundation for Science and Technology and Ministry of Science, Technology and Higher Education) under CINTESIS by a PhD scholarship (reference UI/BD/152087/2021). The authors would like to thank the kind participation of all pregnant women and the support of the recruitment activities by the health professionals of the Department of Obstetrics, Centro Hospitalar Universitário S. João, Porto, Portugal and also to the professionals of REQUIMTE/LAQV, Instituto Superior de Engenharia, Politécnico do Porto, for their collaboration in carrying out the analyzes of the 3-PBA metabolite. This work received support from PT national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through the projects LA/P/0053/2020; UIDB/4255/2020; UIDB/5006/2020 and UIDP/50006/2020. Virgínia Cruz Fernandes thanks FCT/MCTES (Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) and ESF (European Social Fund) through NORTE 2020 (Programa Operacional Região Norte) for his/her Post-Doc grant ref. SFRH/BPD/109153/2015). Juliana Guimarães was funded by FCT/MCTES (Foundation for Science and Technology and Ministry of Science, Technology and Higher Education) under CINTESIS by a PhD scholarship (reference UI/BD/152087/2021).info:eu-repo/semantics/publishedVersio

Essential trace elements status in portuguese pregnant women and their association with maternal and neonatal outcomes: A prospective study from the IoMum Cohort

Cobalt (Co), copper (Cu), manganese (Mn), molybdenum (Mo), and zinc (Zn) are essential trace elements (ETEs) important in cellular chemical reactions and antioxidant defense. Ingestion of ETEs during pregnancy is crucial but their role in specific pregnancy outcomes is largely unknown. This study aimed to quantify urinary levels of these ETEs in pregnancy and to evaluate their role in pregnancy health. First trimester pregnant women of Porto and Lisbon regions provided a urine sample, and sociodemographic and lifestyle data. Clinical data were obtained from clinical records. Urinary ETEs were quantified by inductively coupled plasma mass spectrometry (ICP-MS). Our results show that having urinary Zn levels above the 50th percentile (P50) increases the risk of pre-eclampsia (PE). On the other hand, urinary Zn levels above the P50 decreased the risk of being born with head circumference small for gestational age but it increased the risk having length small for gestational age at birth. This study may provide valuable information for public health policies related to prenatal nutrition, while informing future efforts to de-fine urinary reference intervals for ETEs in pregnant womeninfo:eu-repo/semantics/publishedVersio

A Prospective Study from the IoMum Cohort

Cobalt (Co), copper (Cu), manganese (Mn), molybdenum (Mo), and zinc (Zn) are essential trace elements (ETEs) and important cofactors for intermediary metabolism or redox balance. These ETEs are crucial during pregnancy, their role on specific pregnancy outcomes is largely unknown. This prospective study (#NCT04010708) aimed to assess urinary levels of these ETEs in pregnancy and to evaluate their association with pregnancy outcomes. First trimester pregnant women of Porto and Lisbon provided a random spot urine sample, and sociodemographic and lifestyle data. Clinical data were obtained from clinical records. Urinary ETEs were quantified by inductively coupled plasma mass spectrometry (ICP-MS). A total of 635 mother:child pairs were included. Having urinary Zn levels above the 50th percentile (P50) was an independent risk factor for pre-eclampsia (PE) (aOR [95% CI]: 5.350 [1.044-27.423], p = 0.044). Urinary Zn levels above the P50 decreased the risk of small for gestational age (SGA) birth head circumference (aOR [95% CI]: 0.315 [0.113-0.883], p = 0.028), but it increased the risk SGA length (aOR [95% CI]: 2.531 [1.057-6.062], p = 0.037). This study may provide valuable information for public health policies related to prenatal nutrition, while informing future efforts to de-fine urinary reference intervals for ETEs in pregnant women.publishersversionpublishe

Insulinoma: Uma Causa Rara de Hipoglicemia

O insulinoma é o tumor neuroendócrino pancreático funcionante mais frequente. A apresentação clínica variável pode mimetizar outras patologias. Doente do sexo feminino, 61 anos, com vários episódios de alteração do comportamento. Num desses episódios verificou-se hipoglicemia. O estudo etiológico revelou valores inapropriadamente elevados de insulina e peptídeo-C, compatíveis com hiperinsulinismo endógeno. Apesar da tomografia computadorizada, ressonância magnética e cintigrafia dos recetores de somatostatina não revelarem nenhuma lesão, a ecoendoscopia demonstrou uma formação nodular infracentrimétrica pancreática cujo diagnóstico citológico foi concordante com insulinoma. A doente foi submetida a excisão da lesão e mantém-se sem queixas. Salientamos a apresentação clínica inespecífica e a pequena dimensão da lesão, o que pode levar a um hiato temporal significativo entre o início da sintomatologia e o  tratamento. Recebido: 02/06/2017 - Aceite: 27/10/201

Hipertensão de Causa Endócrina: Hiperaldosteronismo Primário por Síndrome de Conn

O hiperaldosteronismo primário é uma das principais causas de hipertensão secundária. Carateriza-se pela produção inapropriada e parcialmente autónoma de aldosterona pela suprarrenal. O diagnóstico pressupõe um rácio aldosterona/renina elevado e, na maioria dos casos, uma prova confirmatória positiva. O tratamento preconizado é a adrenalectomia laparoscópica ou terapêutica médica com antagonistas dos recetores dos mineralocorticoides. Descrevemos o caso de uma doente de 55 anos com hipocaliemia e hipertensão arterial refratária à terapêutica com 16 anos de evolução. A investigação diagnóstica foi compatível com hiperaldosteronismo primário por adenoma adrenal unilateral. Foi submetida a adrenalectomia laparoscópica direita, com melhoria franca do quadro clínico. O caso clínico apresentado pretende evidenciar uma causa de hipertensão secundária cuja identificação e orientação adequada pode permitir a resolução da hipertensão. Recebido: 10/10/2016 - Aceite: 03/06/201

Inflammation Enhances the Risks of Stroke and Death in Chronic Chagas Disease Patients

Submitted by sandra infurna ([email protected]) on 2016-06-19T18:59:10Z No. of bitstreams: 1 mariaadelaide_matta_etal_IOC_2016.pdf: 749988 bytes, checksum: 989d8777a371bcd276efecde9a5d4214 (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-06-19T19:21:52Z (GMT) No. of bitstreams: 1 mariaadelaide_matta_etal_IOC_2016.pdf: 749988 bytes, checksum: 989d8777a371bcd276efecde9a5d4214 (MD5)Made available in DSpace on 2016-06-19T19:21:52Z (GMT). No. of bitstreams: 1 mariaadelaide_matta_etal_IOC_2016.pdf: 749988 bytes, checksum: 989d8777a371bcd276efecde9a5d4214 (MD5) Previous issue date: 2016Made available in DSpace on 2016-07-08T12:21:49Z (GMT). No. of bitstreams: 3 mariaadelaide_matta_etal_IOC_2016.pdf.txt: 58546 bytes, checksum: d1a8f1e931ab9591fce414aa980fdaa1 (MD5) mariaadelaide_matta_etal_IOC_2016.pdf: 749988 bytes, checksum: 989d8777a371bcd276efecde9a5d4214 (MD5) license.txt: 2991 bytes, checksum: 5a560609d32a3863062d77ff32785d58 (MD5) Previous issue date: 2016Universidade Federal do Rio Grande do Norte. Departamento de Microbiologia e Parasiologia. Natal, RN, BrasilUniversidade do Estado do Rio Grande do Norte. Departamento de Ciências Biomédicas. Mossoró, RN, Brasil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brasil.Universidade Federal do Rio Grande do Norte. Departamento de Microbiologia e Parasiologia. Natal, RN, Brasil / Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brasil.Universidade Federal do Rio Grande do Norte. Departamento de Microbiologia e Parasiologia. Natal, RN, BrasilUniversidade Federal de Ouro Preto. Escola de Medicina. Ouro Preto, MG, Brasil.Univrsidade de São Paulo. Escola de Medicina de Ribeirão Preto. Ribeirão Preto, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório deUltraestrutura Celular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio Grande do Norte. Departmaneto de Análises Clínicas e Toxicológicas. Natal, RN, Brasil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brasil.Ischemic strokes have been implicated as a cause of death in Chagas disease patients. Inflammation has been recognized as a key component in all ischemic processes, including the intravascular events triggered by vessel interruption, brain damage and repair. In this study, we evaluated the association between inflammatory markers and the death risk (DR) and stroke risk (SR) of patients with different clinical forms of chronic Chagas disease. The mRNA expression levels of cytokines, transcription factors expressed in the adaptive immune response (Th1, Th2, Th9, Th17, Th22 and regulatory T cell), and iNOS were analyzed by realtime PCR in peripheral blood mononuclear cells of chagasic patients who exhibited the indeterminate, cardiac, digestive and cardiodigestive clinical forms of the disease, and the levels of these transcripts were correlated with the DR and SR. Cardiac patients exhibited lowermRNA expression levels of GATA-3, FoxP3, AHR, IL-4, IL-9, IL-10 and IL-22 but exhibited higher expression of IFN-γ and TNF-α compared with indeterminate patients. Digestive patients showed similar levels of GATA-3, IL-4 and IL-10 than indeterminate patients. Cardiodigestive patients exhibited higher levels of TNF-α compared with indeterminate and digestive patients. Furthermore, we demonstrated that patients with high DR and SR exhibited lower GATA-3, FoxP3, and IL-10 expression and higher IFN-γ, TNF-α and iNOS mRNA expression than patients with low DR and SR. A negative correlation was observed between Foxp3 and IL-10 mRNA expression and the DR and SR. Moreover, TNF-α and iNOS expression was positively correlated with DR and SR. Our data suggest that an inflammatory imbalance in chronic Chagas disease patients is associated with a high DR and SR. This study provides a better understanding of the stroke pathobiology in the general population and might aid the development of therapeutic strategies for controlling the morbidity and mortality of Chagas disease

Trypanosoma cruzi : blood parasitism kinetics and their correlation with heart parasitism intensity during long-term infection of Beagle dogs.

The goals of the present study were to evaluate the kinetics of blood parasitism by examination of fresh blood, blood culture (BC) and PCR assays and their correlation with heart parasitism during two years of infection in Beagle dogs inoculated with the Be-78, Y and ABC Trypanosoma cruzi strains. Our results showed that the parasite or its kDNA is easily detected during the acute phase in all infected animals. On the other hand, a reduced number of positive tests were verified during the chronic phase of the infection. The frequency of positive tests was correlated with T. cruzi strain. The percentage of positive BC and blood PCR performed in samples from animals inoculated with Be-78 and ABC strains were similar and significantly larger in relation to animals infected with the Y strain. Comparison of the positivity of PCR tests performed using blood and heart tissue samples obtained two years after infection showed two different patterns associated with the inoculated T. cruzi strain: (1) high PCR positivity for both blood and tissue was observed in animals infected with Be-78 or ABC strains; (2) lower and higher PCR positivity for the blood and tissue, respectively, was detected in animals infected with Y strains. These data suggest that the sensitivity of BC and blood PCR was T. cruzi strain dependent and, in contrast, the heart tissue PCR revealed higher sensitivity regardless of the parasite stock