Browsing by Author "Brito, Miguel"
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- 5' and 3' UTR thymidylate synthase polymorphisms modulate the risk of colorectal cancer independently of the intake of methyl group donorsPublication . Carmona, Bruno; Guerreiro, Catarina Sousa; Cravo, Marília; Leitão, Carlos Nobre; Brito, MiguelThymidylate synthase, as a rate-limiting step in DNA synthesis, catalyses the conversion of dUMP into dTMP using 5,10-methylenotetrahydrofolate as the methyl donor. Two polymorphisms have been described in this gene: a repeat polymorphism in the 5' promoter enhancer region (3R versus 2R) and a 6 bp deletion in the 3' unstranslated region. Both of these may affect protein levels. The present case control study was aimed at investigating the influence of these two polymorphisms on the development of colorectal cancer (CRC), as well as their potential interaction with folate, vitamin B6 and vitamin B12 intake. A total of 196 cases and 200 controls, matched for age and sex distribution, were included in the study. No association was found between CRC and the 28 bp repeat polymorphism, but it was observed that individuals with the 6 bp/del and del/del genotypes had a significantly lower risk of developing the disease (OR=0.47; 95% CI 0.30-0.72). A combined genotype (2R/2R; 6 bp/del+del/del) was also found, which was associated with an even lower risk of developing of the disease (OR=0.42; 95% CI 0.26-0.69). No significant interaction between these polymorphisms and vitamin intake was observed. These results indicate for the first time that the 6 bp/del allele might be a protective factor in the development of CRC, independent of the intake of methyl group donors.
- Aetiology of diahrroea in children under five at the Bengo General Hospital, AngolaPublication . Gasparinho, Carolina; Mirante, Maria Clara; Lima, Sónia; Nery, Susana Vaz; Istrate, Cláudia; Mayer, António Carlos; Brito, MiguelDiarrhoea is the second leading cause of death in children under five years being responsible for 760.000 deaths, corresponding to 9% of the total deaths in this age group. Africa is the region with more deaths due to diarrhoea (46%), followed by South Asia (38%). Three quarters of the total of deaths occurs within only 15 countries and Angola is in the 15th position with a record of 20,000 annual childhood deaths. Diarrhoeal disease can be caused by bacterial, viral and parasitic infectious agents and can be transmited through contaminated food or drinking water, or directly from person to person. Rotavirus and Escherichia coli were shown the most frequent pathogenic agents in developing countries. This study aims to identify the most frequent pathogenic agents of diarrhoea in children under five atttending the Bengo General Hospital (BGH)..
- Allergic sensitisation and relationship with asthma and other allergic diseases in children in the province of Bengo, AngolaPublication . Arrais, Margarete; Lulua, Ofélia; Quifica, Francisca; Gama, Jorge; Taborda-Barata, Luis; Brito, MiguelBackground: In recent decades, the prevalence of allergies has increased, especially in children. In Africa, few studies have evaluated allergic sensitization and in Angola, none. The aim of this study was to evaluate the profile of allergic sensitization in children with asthma and other allergic diseases. Method: This was a cross-sectional study, using the methodology of the International Study of Asthma and Allergic Diseases in Children (ISAAC), conducted from September to November 2017 in 5 to 14-year-old children in the Bengo Province, Angola. Out of a total of 33 public schools, 5 (15%) were randomly selected, 3 in urban and 2 in rural areas. Allergic sensitization was defined by positive skin prick tests (SPT) and/or positive inhalant Phadiatop. Data were analyzed with SPSS Statistics v25.0. Results: The sample consisted of 1023 children, 48% girls, 58% 10-14-year-old, 61% living in urban areas. Of these children, 8% had positive SPT with the most frequent sensitization being to mites (B.tropicalis, D.farinae, D.pteronyssinus) and cockroach mix, without statistically significant differences between sexes, age, and urban or rural area residents. About 56% of children were monosensitized, 44% were polysensitized, and most sensitized children (55%) were asymptomatic. No significant differences in allergen sensitization patterns were observed among atopic children who were asymptomatic, had asthma, rhinitis, or eczema. Conclusion: Allergic sensitization to dust mites, cockroach mix, and fungi is the most frequent pattern observed in 5-14-year-old Angolan children in Bengo but this was not different between sensitized children with and without allergic diseases.
- Alterações na coroide, retina e nervo ótico subsequentes a COVID-19Publication . Camacho, Pedro; Poças, Ilda Maria; Cunha, João Paulo; Silva, Carina; Ribeiro, Edna; Brito, Miguel; Mendonça, Paula; Barroqueiro, Olga; Lino, Pedro Miguel; Condado, Patrícia; Nicho, Inês; Carmo, Rita; Castelhano, Mariana; Carvalho, Francisca; Almeida, Júlio Costa; Prieto, IsabelEm março de 2022, foram registados 3413013 casos positivos (total acumulado). Conjuntivite, uveíte, vasculite, retinite e neuropatia óptica foram documentadas em modelos animais como possíveis complicações infeciosas com comportamento neurotropico semelhante ao SARS-COV. Considerando a retina uma extensão do SNC e o neurotropismo dos CoVs, a caracterização da retina, coroide e nervo ótico de pacientes infectados com COVID-19 poderá ser relevante devido a possíveis mecanismos de neurodegeneração e vascularização poderem estar envolvidos. Objetivo: Descrever as alterações que ocorrem ao nível da espessura da retina, complexo de células ganglionares, fibras nervosas peri-papilares e coróde sub-foveal em pacientes infetados por COVID-19 Vs grupo controlo.
- Alterações na retina, coróide e nervo ótico secundárias a SARS-CoVs-2Publication . Lino, Pedro Miguel; Cunha, João Paulo; Poças, Ilda Maria; Camacho, Pedro; Silva, Carina; Ribeiro, Edna; Brito, Miguel; Mendonça, Paula; Barroqueiro, Olga; Condado, Patrícia; Nicho, Inês; Carmo, Rita Barros; Castelhano, Mariana; Carvalho, Francisca; Almeida, Júlio Costa; Prieto, IsabelO novo coronavírus responsável pela síndrome respiratória aguda grave (SARSCoV- 2) surgiu associado a pandemia que hoje vivemos (COVID-19). Como para outros vírus respiratórios altamente contagiosos, as gotículas respiratórias são a principal via de transmissão do SARS-CoV-2. No entanto, outras formas de transmissão foram consideradas - filme lacrimal e saco conjuntival. O contacto próximo com indivíduos infetados e as mãos contaminadas poderão facilitar a sua transmissão mesmo em doentes que não apresentem queixas ou sintomas oculares. O olho pode ser, não só a porta de entrada dos CoVs2, mas também um dos órgãos alvo dos mesmos: conjuntivites, uveítes, vasculites, retinites, nevrites óticas. Apesar de grande parte da atenção dos estudos ser sobre o comprometimento do trato respiratório, o envolvimento da superfície ocular como a lágrima são também referidos em outros CoVs2 e a sua relação deve ser valorizada e estudada enquanto forma de contágio e transmissão. Enquanto ameaça a saúde publica em todo o mundo, a infeção por SARS-CoV-2, realça a necessidade de estudos para a caracterização e compreensão da doença mas também a transmissão de forma a adequar as respostas às necessidades de saúde inerentes. Apesar de grande parte da atenção dos estudos ser sobre o neurotropismo destes coronavírus (não só pela sua disseminação hematogénea mas também por via neuronal retrógrada) e ao possível compromisso vascular/isquémico, com as suas eventuais sequelas no SNC2-3 e envolvimento da retina humana pretendemos descrever as características tomográficas retinianas e coroideias de doentes previamente com COVID-19. Objetivo do estudo: Caracterizar diferentes métricas corio-retinianas em participantes recuperados de COVID-19 comparativamente ao grupo-controlo.
- An update review of new therapies in sickle cell disease: the prospects for drug combinationsPublication . Lugthart, Sanne; Ginete, Catarina; Kuona, Patience; Brito, Miguel; Inusa, Baba PsalmIntroduction: Sickle cell disease (SCD) is an inherited disorder characterized by polymerization of deoxygenated hemoglobin and microvascular obstruction. Generalized, it affects millions of people over 85% from low-and-middle-income countries. The cardinal feature is generalized pain referred to as vaso-occlusive crises (VOC), multi-organ damage, and premature death.). SCD is the most prevalent inherited reduced life-threatening disorder in the world and over 85% of the world's 400,000 annual births occur in low-and-middle-income countries. In the UK with about 250 annual births (1:200 live births, and over 14,00 living with the disorder. For decades span. Since 1998 Hydroxyurea remained the only disease-modifying therapy until the FDA approved L-glutamine (2017), Crizanlizumab and Voxelotor (2019), and gene therapies (Exa-cel and Lovo-cel, 2023). Areas covered: A literature review, we discuss established and new treatments. We provide an in-depth review of key clinical trials from 2013-2023. However, for pragmatic purposes we have approached this review in line with the different mechanisms of action, considering the possible options for the search performed in Pubmed Central using the search terms [sickle cell disease] or [sickle cell anemia] and the known treatments, i.e. Hydroxycarbamide/Hydroxyurea, L-Glutamine, Voxelotor, Crizanlizumab, Mitapivat, Etopivat, gene therapy, hematopoietic stem cell transplantation, and combination therapy. Clinical trials performed in the last 10 years (November 2013 - November 2023) were selected. Expert opinion: In our opinion section, we recommend the consideration of combination therapies for specific complications such as VOCs, pain, and renal impairment as well as personalized medicine based on disease phenotype and patient patience characteristics. Following the wake of the recent approval of gene therapy for SCD, the more curative option is now a reality, the challenge is addressing how to address issues such as access, affordability, and shared decision-making with families.
- Análise do efeito biológico de extratos de folhas de Carica papaya na viabilidade e na proliferação de células K562Publication . Canteiro, Beatriz; Mendes, Maria; Delgadinho, Mariana; Oliveira, Ketlyn; Ginete, Catarina; Gomes, Mário; Ribeiro, Edna; Brito, Miguel; Gomes, Anita Q.Introdução – A anemia falciforme é uma doença monogénica causada por mutações no gene da β-globina que afeta a estrutura da hemoglobina, sendo associada a diversas complicações clínicas com elevadas taxas de morbilidade e mortalidade. A reativação farmacológica da hemoglobina fetal (HbF) por compostos como a hidroxiureia (HU) é um dos tratamentos atualmente disponíveis; contudo, o seu perfil de segurança e o elevado custo em países subdesenvolvidos limitam a sua utilização. Nesse contexto é essencial estudar novos compostos indutores da HbF com baixa citotoxicidade e que possam estar amplamente disponíveis, como é o caso de extratos de folhas da Carica papaya (CP), uma planta medicinal com propriedades antioxidantes e anti-inflamatórias. Objetivos – Este estudo pretende avaliar o efeito do extrato metanólico das folhas de CP (EMFCP) em parâmetros biológicos como a proliferação e a viabilidade celular em células K562. Método – As células K562 foram expostas durante 72h ao EMFCP a 500 µg/mL e durante 24 horas ao EMFCP (0,5; 50; 100 µg/mL) e à HU (25 μg/mL). A proliferação e viabilidade celular foram analisadas através da quantificação celular pelo método de exclusão do azul de tripano. Resultados – Os resultados demonstram que a proliferação e a viabilidade celular foram afetadas pelo EMFCP apenas na concentração de 500 µg/mL, não se tendo verificado alteração nestes parâmetros nas restantes concentrações utilizadas. Conclusão – Os resultados mostraram que os EMFCP não são citotóxicos quando incubados em células K562 em concentrações inferiores ou iguais a 100 μg/mL, permitindo assim explorar este composto na avaliação do seu potencial terapêutico no contexto da anemia falciforme.
- Anemia in preschool children from AngolaPublication . Fançony, Cláudia; Lavinha, João; Brito, Miguel; Barros, HenriqueAngola is one of the southern African countries with the highest prevalence of anemia, and despite the high geographic heterogeneity of its distribution across the country, it was reported to be indicative of a severe public health problem in some areas, mainly in children. Despite the relevance of this condition in the country, there is still an important gap regarding scientific evidence and knowledge systematization in the indexed literature, that could be used to inform and optimize national public health policies willing to address it. Furthermore, the changes in anemia epidemiology among African preschool children and the late updates in nutrition-specific and nutrition-sensitive preventive strategies in the continent are of imperative relevance, as they could contribute to design context-specific national approaches to reduce anemia's morbidity and mortality. In this study, we intend to perform a systematic review regarding the sparse evidence available in the country regarding the prevalence of anemia, its associated factors, the prevention, and/or control strategies with the potential to reduce anemia that was implemented, and to discuss interventions targeting infections and/or nutrition conducted in other African countries.
- Antimicrobial storage and antibiotic knowledge in the community: a cross-sectional pilot study in north-western AngolaPublication . Cortez, Joana; Rosário, Edite; Pires, João E.; Taborda Lopes, João; Francisco, Moisés; Vlieghe, Erika; Brito, MiguelBackground - Antimicrobials are drugs that were once lifesavers and mainly curative. Nowadays their value is increasingly under pressure because of the fast and worldwide emergence of antimicrobial resistance, which, in low resources settings, frequently occurs in microorganisms that are likely to be transmitted in the community. Methods - A cross-sectional pilot study including 102 households within the 10th HDSS round in Dande, Bengo Province, Angola. Results - From the total 102 households piloted, 77.45% were urban (n = 79); the respondents were females in 56.44% (n = 57) and mean age was 39.70 (SD 15.35). Overall storage of antimicrobials was found in 55/102 (53.92%) of the households. More than 66% of the antimicrobials stored were prescribed by a health professional and the majority of antimicrobials were bought at pharmacies and at a street market. Penicillin and its derivates, antimalarial drugs and metronidazole are the most frequently antimicrobials stored. Households with female respondents reported to store more frequently any drugs at home (82.50%) (p = 0.002) and also more antimicrobials (64.91%; p = 0.016) as compared to households with male respondents. Reported use of antimicrobials was significantly higher in urban 60.76% (48/79) as compared to rural households 30.43% (7/23), (p = 0.010). Overall, 74/101 (73.26%) of respondents reported to have already heard about antibiotics. Among them, the common reasons for its use were cough and other respiratory symptoms, wounds, flu and body muscle pain, fever, bladder complaints, diarrhea and/or presumed typhoid fever. Nearly 40% (28/74) of the respondents thought that antibiotics should be stopped as soon as people dońt feel sick anymore. Conclusions - Community interventions for appropriate use of antibiotics should be designed with a special focus in women; through public awareness campaigns and improving access to reliable medical services. Drug prescribers are a keystone not only in adequate antimicrobial prescription but also adequate dispensing and strong advocates for the possible misconceptions on antimicrobial usage by laypeople.
- Aplicação de sistemas de vigilância demográfica e informação geográfica na investigação em saúdePublication . Rosário, Edite; Pedro, João de Almeida; Brito, MiguelO Projeto CISA visa a criação de um Centro de Investigação em Saúde em Angola. Foi criado em 2007 e resulta de uma parceria entre o governo angolano (Ministério da Saúde de Angola e o Governo Provincial do Bengo), o governo português (Ministério dos Negócios Estrangeiros, através do Camões IP) e a Fundação Calouste Gulbenkian. Os principais objetivos do Projeto CISA são melhorar as condições de saúde da população do Município do Dande através do fortalecimento assistencial dos seus serviços de saúde; criar um centro de investigação em Angola, que dará contributos à resolução dos principais problemas de saúde que afetam o país e a região, através de investigação epidemiológica e clínica nas doenças mais prevalentes ou relevantes para a saúde pública no contexto angolano (como sejam a malária, doenças tropicais negligenciadas, parasitas intestinais, desnutrição e as doenças não transmissíveis) e potenciar a participação nacional de Angola e Portugal a nível internacional na área da investigação direcionada às principais doenças que afetam os países em vias de desenvolvimento. Para a investigação em saúde, o conhecimento das características demográficas e da distribuição geográfica das populações é de extrema importância, uma vez que permite, entre outros, estabelecer denominadores para cálculos de taxas (e.g. mortalidade, morbilidade, prevalência, incidência) e analisar a associação entre saúde e ambiente (e.g. áreas de risco, períodos de exposição, acessibilidades a cuidados de saúde).