Synthesis of catecholic amino acids and peptides or conjugates of catechols with amino acids and peptides

Dissertação de mestrado em Medicinal ChemistryOxidative stress is an imbalance between the amount of oxidants and antioxidants in favour of the oxidants. Thus, when there is excessive production of reactive oxygen species (ROS) or antioxidant defence mechanisms are diminished, oxidative stress occurs. In order to maintain normal cellular functioning any excess of ROS must be continuously inactivated through the use of antioxidants.1,2 Phenolic amino acids, such as tyrosine, exhibit a wide range of biological activities and have shown to be effective antioxidants in different in vitro antioxidant activities studies. Phenolic acids coupled with amino acids are involved in suppressing the adverse effects of oxidative stress and have a wide range of biological activities, such as antioxidant,3 anticancer4 and antimicrobial.5 In this work a strategy based on the Ugi reaction was developed for the synthesis of new phenolic amino acids. Hydroxybenzaldehyde derivatives were reacted with 4-methoxybenzylamine, cyclohexyl isocyanide and benzoic acid, phenolic acids or catecholic acids to give Ugi adducts that were treated with trifluoroacetic acid, yielding N-acyl (hydroxyphenyl)glycine amides in good yields. The use of N-benzyloxycarbonylglycine as acid component allowed the preparation of a 3,4-dihydroxyphenylglycyl dipeptide derivative. Radical-scavenging activity studies of the polyphenolic amino acid derivatives showed a sharp increase in activity with the increase in number of hydroxyl or catechol groups present. Several studies suggest that a cocktail of antioxidants, endowed with different mechanisms of action, results more effectively than a single antioxidant because of the synergistic effect of the molecules. To promote possible synergistic mechanisms and to better understand the mechanistic aspects, the use of modified and/or dualistic molecules is a valuable approach.6 Dehydroamino acids constitute an important class of non-proteinogenic amino acids with various biological activities, including antioxidant. N-phenolic and N-catecholic derivatives of dehydrophenylalanine were synthesized using a method which comprises coupling phenolic or catecholic acids and/or phenolic or catecholic amines.O stress oxidativo é um desequilíbrio entre a quantidade de oxidantes e antioxidantes em favor dos oxidantes. Assim, quando há uma produção excessiva de espécies reativas de oxigénio (ROS) ou os mecanismos de defesa antioxidante estão diminuídos, ocorre stress oxidativo. Para manter o funcionamento celular normal, qualquer excesso de ROS deve ser continuamente inativado através da utilização de antioxidantes.1,2 Aminoácidos fenólicos, como a tirosina, exibem uma ampla gama de atividades biológicas e mostraram-se antioxidantes eficazes em diferentes estudos de atividade antioxidante in vitro. Os ácidos fenólicos acoplados a aminoácidos estão envolvidos na supressão dos efeitos adversos do stresse oxidativo e possuem uma ampla gama de atividades biológicas, como antioxidante,3 anticancerígeno4 e antimicrobiano.5 Neste trabalho foi desenvolvida uma estratégia baseada na reação de Ugi para a síntese de novos aminoácidos fenólicos. Os derivados de hidroxibenzaldeido foram feitos reagir com 4-metoxibenzilamina, isocianeto de ciclohexilo e ácido benzóico, ácidos fenólicos ou ácidos catecólicos para dar origem a aductos Ugi que foram tratados com ácido trifluoroacético originando amidas N-acil hidroxifenilglicina com bons rendimentos. A utilização de N-benziloxicarbonilglicina como componente ácido permitiu a preparação de um derivado dipeptídico de 3,4-di-hidroxifenilglicil. Estudos de atividade de eliminação de radicais dos derivados de aminoácidos polifenólicos mostraram um aumento acentuado na atividade com o aumento do número de grupos hidroxilo ou catecol presentes. Vários estudos sugerem que, devido ao efeito sinérgico das moléculas, um cocktail de antioxidantes dotados de diferentes mecanismos de ação, resulta mais eficazmente do que um único antioxidante. Para promover possíveis mecanismos sinérgicos e compreender melhor os aspetos mecanísticos, o uso de moléculas modificadas e/ou dualísticas é uma abordagem valiosa.6 Desidroaminoácidos constituem uma classe importante de aminoácidos não proteinogénicos com várias atividades biológicas, incluindo antioxidante. Derivados N-fenólicos e N-catecólicos da desidrofenilalanina foram sintetizados usando um método que compreende o acoplamento de ácidos fenólicos ou catecólicos e/ou aminas fenólicas ou catecólicas

Is there a relation between environmental exposure to teratogenic substances during pregnancy and congenital anomalies in the newborn? A pilot study in Portugal

Background: Maternal occupation as a proxy of environmental exposure has been consistently associated with specific congenital anomalies (CA) in the foetus and newborn. On the other hand, geographical location of the mother such as place of residence and place of work have not been used as proxy for environmental exposures during pregnancy. We designed a pilot study aiming to investigate the association between maternal place of residence and workplace during pregnancy and CA in Portugal. Methods: Cases and controls are identified in the maternity unit. Cases are all live births with at least one CA delivered in the Barreiro hospital located in a heavy industrial area near Lisboa. Controls are the two normal births following each case. Residents outside the study area, stillbirths and women who decline to participate or are incapable of giving consent are excluded. A health professional interviews the mothers using a questionnaire adapted from the registry form of the Portuguese national registry of CA and includes information on places during pregnancy (residence, workplace, leisure), and demographic characterization as place of birth, infant sex, weight, description of CA, age of mother, ethnicity, maternal birth place. Maternal health and obstetric history, education, smoking, alcohol, drugs and medication use is also collected as potential confounders. Results: The pilot study started in January 2016 and at the moment two cases and four controls have been recruited without refusals. The study will continue to be implemented and it is proposed to start in other hospital units during 2016

Anafilaxia em idade pediátrica: uma visão global

Anaphylaxis is defined as an acute severe, life-threatening hypersensitivity reaction. The condition’s real prevalence and incidence are difficult to estimate, but seem to be increasing, particularly in children. Anaphylaxis clinical presentation varies according to age and other individual factors. Although consensual clinical criteria exist, including in pediatric age, diagnosis can be challenging. Food allergy is the most common anaphylaxis cause in children, particularly in preschool age. Drug-induced reactions and hymenoptera venom sting are other major triggers, which importance increases after adolescence. Management involves diagnosis, appropriate identification of possible triggers, acute phase treatment, and long-term planning. Prompt referral to a Pediatric Allergy specialist is recommended, as complete allergy workup is usually required to implement future preventive measures. In this review, the authors discuss particular aspects regarding anaphylaxis in pediatric age to provide information that can help improve disease management.info:eu-repo/semantics/publishedVersio

Relação entre a exposição ambiental a substâncias teratogénicas durante a gravidez e anomalias congénitas no recém-nascido: um estudo piloto em Portugal

Introdução e objetivos: Na gravidez, a exposição a factores ambientais teratogénicos pode ser nociva no desenvolvimento fetal. Neste trabalho avaliou-se a exequibilidade de um estudo sobre exposição residencial e laboral da grávida a substâncias ambientais teratogénicas e o desenvolvimento de anomalias congénitas (AC), apresentando-se dados do estudo-piloto. Metodologia: Estudo epidemiológico observacional, do tipo caso-controlo, decorrido no CHBM em 2016. Exposição ambiental caracterizada (1) pela profissão materna e potencial contato profissional com substâncias teratogénicas e (2) localização geográfica da residência, emprego e zonas de lazer durante a gestação. Dados recolhidos em entrevista com questionário adaptado do formulário de notificação do RENAC. A análise descritiva avaliou a qualidade dos dados e % de valores omissos. Resultados: Amostra constituida por 78 notificações (26 casos, 52 controlos). A maioria dos casos residia na Moita (46%), e a maioria dos controlos no Barreiro (35%), seguindo-se o Montijo. A maioria tanto dos casos como dos controlos trabalhava em Lisboa, seguindo-se Barreiro, Moita e Montijo. Nos casos, o local preferencial de lazer foi a Moita (34,6%) e nos controlos o Barreiro (30%). As anomalias do sistema musculo-esquelético foram as mais reportadas (38,5%). Na avaliação da exequibilidade do estudo, a apreciação da equipa no campo mostrou adequação dos documentos de apoio e tempo de aplicação do questionário. A implementação do estudo foi considerada “fácil”, com taxa de participação 99%. A maior percentagem de valores omissos verificou-se nos controlos. Conclusões: Apesar destes resultados não terem ainda dimensão suficiente para extrapolar relações, este estudo demonstrou a exequibilidade do projeto e da sua continuação.N/

Unilateral optic neuritis as a presentation of neurobrucellosis

Neurobrucellosis manifesting as optic neuritis is a rare disease in childhood. We report a case of neurobrucellosis in a 11 year old girl leading to visual impairment and headache. Physical examination revealed mild oedema of right tibiotarsic joint and optic neuritis. Investigations showed CSF pleocytosis and a Brucella serum agglutination titer of 1/640. Complete reversal of the symptoms was observed after appropriate antibiotic treatment. To our knowledge only four cases of neurobrucellosis manifesting with visual impairment in childhood are previously reported in literature

Recurrent neck swelling after iodinated contrast media administration

A 74-year-old male with an abdominal aortic aneurism reported 2 episodes of neck swelling 16 hours after an abdominal CT with iodinated contrast media that reappeared in a subsequent CT, although the use of pre-medication. The tests used to exclude the hypersensitivity hypothesis where negative and once a new CT where needed we decided to do it with close monitoring. We performed a facial picture and cervical ultrasound exam before and 24 hours after the exam. The neck swelling and the ultrasound findings 24 hours after the CT made the diagnosis of contrast induced sialoadenitis possible. Contrast induced sialadentis is an uncommon adverse reaction to iodinated contrast media. As it presents with neck swelling it is important to exclude a hypersensitivity reaction because it's further limitations and make a differential diagnosis.info:eu-repo/semantics/publishedVersio

Is there a relation between environmental exposure during pregnancy and congenital anomalies in newborn? Preliminary results from a case-control study

Poster publicado em: European Journal of Medical Genetics. 2018;61(9):571. https://doi.org/10.1016/j.ejmg.2018.06.071BACKGROUND: Maternal exposure to environmental factors has been associated to the birth of a child with specific congenital anomalies (CA). The aiming of this study is to investigate the association between occupational exposure, maternal place of residence, workplace and leisure activities during pregnancy and CA METHODS: In 2016, an observational, case control study was developed and is still in progress. Cases are live births, identified in the maternity unit, with at least one CA and controls are the two births without anomaly following each case. Residents outside the study area, stillbirths and women who decline to participate or are incapable to give consent are excluded RESULTS: Were recruited to the study 116 live births (38 cases and 78 controls). The majority of cases reported living (68.4%) and spend leisure time (63.2%) in the industrial area. 57.7 of controls lives and 46.9% spend leisure time in same area. However no statistical differences were detected between them (p=0.195 for residency and p=0.175 for place of leisure). Cases work more frequently in Lisbon (21%) and residence area (15.8%) compared to controls (17.3% and 15.4% respectively) (p=0.057). A total of 44 CA were detected and the most frequently reported groups was the musculoskeletal system (34.1%) followed by CA of the ear and genital group (15.9% and 15.9 respectively). CONCLUSION: Due to the small sample size, no statistically significant difference was found between cases and controls. Reason why it is necessary to continue the study and obtain the collaboration of other hospitals in the same area.info:eu-repo/semantics/publishedVersio

Teaching and educational memory: Unveiling subjectivity in teacher education

Esse trabalho tem por objetivo apresentar pesquisa exploratória em banco de dissertações e teses do Programa de Pós-Graduação-PPGE/UnB, tendo como escopo principal levantar e analisar as pesquisas que utilizaram a Memória Educativa como dispositivo de pesquisa. Apresentamos os trabalhos desenvolvidos ao longo dos últimos 10 anos e as possíveis contribuições na constituição da identidade pessoal e profissional de professores em formação inicial e/ou continuada a partir da realização da escrita desse dispositivo, como desvelador do inconsciente, por meios de reminiscências de memórias. e constituição da subjetividade humana. Estes trabalhos totalizaram 18 pesquisas, sendo 15 dissertações e 3 teses, com 264 dispositivos analisados. O aporte teórico psicanalítico freudiano referendou o desenvolvimento das pesquisas assim como autores contemporâneos que pesquisam a conexão entre Psicanálise e Educação. Os resultados evidenciaram que das investigações, ressaltam-se a constituição dos sujeitos, a relação dos sujeitos com seus professores no passado, com a profissão, seu ofício, com os saberes, o processo de formação de professores, as relações estabelecidas com crianças, adolescentes e seus pares. Ao escrever o dispositivo os traços mnêmicos, as lembranças, as recordações se reeditam nas relações do docente com seus pares e seus alunos, sugerindo que os professores repensem suas práticas, seu fazer pedagógico, pois marcas subjetivas repercutem na formação pessoal e profissionalThis paper aims to present an exploratory research in the dissertation and thesis bank of the Postgraduate Program - PPGE / UnB, whose main purpose is to survey and analyze the research that used the Educational Memory as a research device. We present the works developed during the last 10 years and the possible contributions in the constitution of the personal and professional identity of teachers in initial formation and / or continued from the accomplishment of the writing of this device, as unveiling of the unconscious, by means of reminiscences of memories. and the constitution of human subjectivity. These works totaled 18 researches, being 15 dissertations and 3 theses, with 264 analyzed devices. The Freudian psychoanalytic theoretical contribution supported the development of research as well as contemporary authors who research the connection between Psychoanalysis and Education. The results evidenced that the investigations emphasize the subjects' constitution, the relationship of the subjects with their teachers in the past, with the profession, their craft, with the knowledge, the process of teacher training, relationships established with children, adolescents and their peers. When writing the device, memory traits, memories and memories are re-edited in the teacher's relations with their peers and their students, suggesting that teachers rethink their practices, their pedagogical doing, because subjective marks have repercussions on personal and professional formatio

Isolation and characterization of essential oils from selected plants

The interest in plants as a potential source of bioactive molecules with application in different areas, from cosmetics to pharmaceuticals, to the food industry and perfumes is increasing [1]. Essential oils, also referred to as volatile oils or essences, can be obtained from plants by using different extraction techniques and are isolated and their chemical composition determined by characterization techniques such as NMR spectroscopy, mass spectrometry and different types of chromatography [2]. In general, essential oils are complex mixtures, and may contain from 50 to 200 compounds of different volatilities. They generally have an intense characteristic aroma, are soluble in organic solvents and insoluble or poorly soluble in water. Identification of its composition is only possible in many cases by comparison of chromatographic data and mass spectrometry of authentic samples. The work presented describes the extraction of essential oils from three sources of plant origin (Ginkgo biloba, laurel and rosemary) with various techniques (soxhlet extraction, hydrodistillation and steam distillation). The extracts were isolated, the major compounds identified and characterised by mass spectrometry, 1H- and 13C-NMR, and the spectra obtained were compared/confirmed with the literature.The author acknowledge to the Fundação para a Ciência e Tecnologia (FCT, Portugal) for financial support to the NMR Portuguese network (PTNMR, Bruker Avance III 400-Univ. Minho), and FCT and FEDER (European Fund for Regional Development)-COMPETE-QREN-EU for funds provided through the Chemistry Research Centre of the University of Minho (Ref. UID/QUI/00686/2013 and UID/QUI/0686/2016).info:eu-repo/semantics/publishedVersio

Subjetividade docente na perspectiva escolar: memórias de professoras do Distrito Federal

Este artigo apresenta resultados de pesquisa a respeito da constituição do sujeito professor em situação de trabalho. A reflexão parte de escritos sobre suas memórias como dispositivo chamado "Memória Educativa". A leitura e interpretação levou à dramatização de cenas por eles narradas. A partir de uma perspectiva psicanalítica, traz à tona a dimensão do infantil como categoria permitindo compreender o lugar da constituição subjetiva do professor em seu ofício. Quando os professores problematizam sobre sua prática pedagógica pelo pensamento da experiência freudiana num contexto mais amplo, favorecem o resgatar das capacidades de “criar” e libertar-se dos modismos metodológicos