Synthesis and study of biological activity of tetrahydro-1H-[3]-benzazepines

The 3-Benzazepines are an important class of compounds in drug discovery due to their biological activity such as analgesic, antihypertensive or anticancer properties as well as dopaminergic or antidopaminergic activity. In particular, the tetrahydro-1H-[3]- benzazepine is a common skeleton in a number of natural and pharmaceutical products. As consequence of the interesting biological properties, derivatives of the tetrahydro-1H-[3]-benzazepines, especially the 1-aryl substituted have been synthesized by different routes and evaluated their pharmacologic activity. [1,2] The stereoselective synthetic approaches of tetrahydro-1H-[3]-benzazepine have focused on ring enlargements, as the Stevens rearrangement (SR) which is a good regio- and diastereoselective synthetic methodology. In my research group, the reaction conditions to synthesize tetrahydro-1H-[3]-benzazepines 1,2-disubstituted by via SR from tetrahydroisoquinolinium salts conveniently functionalized have been optimized. [3,4] This methodology allowed us to obtain a wide variety of tetrahydro-1H-[3]- benzazepines 1,2-disubstituted with different substituents at A-ring (Cl, OMe) and the C-1 (-C6H4X, X = H, OMe, Cl, NO2, NMe2, NH2, SMe) and C-2 (Electron-withdrawing groups) positions. The demethylation of the synthesized tetrahydroisoquinolines and tetrahydro-1H-[3]-benzazepines 1,2-disubstituted, lead us to get catechol structure, an important requirement for their dopaminergic activity. We have studied the dopaminergic activity of the synthesized compounds by radioligand binding assays, establishing a structure-activity relationships. Literature: [1] A. Gini, Adv. Synth. Catal. 2016, 358, 4049. [2] H. Damsen, Eur. J. Org. Chem. 2015, 36, 7880. [3] M. Valpuesta, Eur. J. Org. Chem. 2010, 23, 4393. [4] M. Ariza, Eur. J. Org. Chem. 2011, 32, 6507.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Synthesis of bioactive compounds. Studies of their attachment to nanoparticles

The 1-aryl tetrahydroisoquinolines have attracted great attention in medicinal chemistry due to their biological activity. These compounds present antitumor, anti-HIV and antibacterial activities. Several analogues of 1-aryl tetrahydroisoquinoline are used for the treatment of neurodegenerative diseases such as Parkinson´s and Alzheimer´s diseases since also act as dopaminergic antagonists and N-methyl-D-aspartate receptor antagonist. [1] The 1-substituted tetrahydro-3-benzazepines have also been studied for their affinity to the Phencylclidine binding site of the NMDA receptor as well as for their affinity to the dopaminergic receptors. [2] In the last years, various methods have been carried out to satisfy the demand of novel tetrahydroisoquinolines and tetrahydro-3-benzazepines. We have synthesized nor-1-aryl tetrahydroisoquinolines with different substituents in the aryl group of C-1 (H, NMe2, SMe, NO2, NH2). In addition to this, we have performed the synthesis of nor-tetrahydro-3-benzazepinas by different routes, obtaining the best results via opening of epoxides by arylphenethylamines and subsequent cyclization. The nor-tetrahydroisoquinolines and nor-tetrahydro-3-benzazepines have been derivatized to obtain appropiate adsorbates which can be attached to nanoparticles. This fact is crutial in drug delivery systems as well as in the improvement of the biocompatibility of these compounds. Literature: [1] Toshiaki Saitoh, Eur. J. Med. Chem. 2006, 41, 241. Mattias Ludwig, Eur. J. Med. 2006, 41, 1003. [2] Olaf Krull, Bioorg. Med. Chem. 2004, 12, 1439.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Comparative study of dopaminergic activity of tetrahydro-1H-[3]-benzazepines and their precursors

The discovery of the tetrahydro-1H-[3]-benzazepine SCH23390 [1], represented one of the most important advances in the study of dopaminergic receptors due to their behavior as a selective D1 receptor antagonist. The high affinity and selectivity of this tetrahydro-1H-[3]-benzazepine has led to the search for new structures because of their potential dopaminergic activity, especially 1-aryl-substituted tetrahydro-1H-[3]-benzazepines. Furthermore, their precursors, the tetrahydroisoquinolines 1-substituted have shown to have activity for D1 and D2 dopaminergic receptors.[2] We have carried out the synthesis of tetrahydro-1H-[3]-benzazepines 1,2-di-substituted by Stevens rearrangement (SR) on tetrahydroisoquinolinium salts. Stevens rearrangement is an efficient regio- and diastereoselective synthetic methodology. [3a,b] As part of our studies, we have performed the synthesis of benzazepines with modifications at the C-1 and C-2 positions with chlorine and hydroxyl groups at A-ring which is an important factor to modulate affinity at dopaminergic receptors. The interaction of these molecules with D1 and D2 dopaminergic receptors have been studied to establish a structure-activity relationship by radioligand binding assays.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Políticas públicas: uma reflexão quanto aos jogos desportivos de 2014 e 2016

Esta monografia tem o objetivo de analisar a importância das políticas públicas desenvolvidas para a atração do investimento estrangeiro no Brasil para os eventos desportivos. Este estudo analisa o progresso da economia brasileira desde os tempos do período agroexportador , até a fase da abertura ao mercado externo, incluindo a entrada dos investimentos estrangeiros, com o foco para a área desportiva. Como molde para os eventos brasileiros de 2014 e 2016, será analisada a Copa da África do Sul de 2010. Dessa maneira, analisaremos as áreas prioritárias de investimento para a Copa do Brasil de 2014 e as Olimpíadas de 2016, que apesar de ser concentrada na cidade do Rio de Janeiro, também precisara de grandes investimentos

Comparing the behavior of polypropylene, polypropylene+poliglactin and polypropylene+titanium meshes in rat: inflammatory cytokines, tissue alterations and collagen deposition

Purpose: Incisional hernia occurs in approximately 11% of all laparotomies. Changes in collagen have been closely implicated in its pathogenesis. The high recurrence rate (45 to 54%) after primary suture has stimulated the development of meshes. Currently, meshes are the biomaterials implant group most used in medicine. This study aims to compare the serum and tissue inflammatory responses and collagen deposition caused by meshes made of polypropylene, polypropylene + polyglactin and polypropylene + titanium. Methods: Thirty Wistar rats were divided into three groups. In group A, a high-density polypropylene mesh was positioned on the abdominal wall. In groups B and C, lowdensity meshes were used in associations with polyglactin and titanium, respectively. Immediately before the operation and on the first, third and fortieth postoperative days, pro-inflammatory cytokines were assayed. On the 40th postoperative day, the region of the inserted prosthesis was biopsied. Hematoxylin-eosin and Masson’s trichrome colorations were used to value the tissue inflammatory reaction with a scale for objective scoring. The scale had six itens: cellular layers in granulomas periphery, inflammatory response in host tissue, inflammatory response in the mesh surface, tissue ingrowth, granulomas and muscular invasion by the inflammatory reaction. For collagen, picrosirius was used with data reading using the Image Tool computer software. Statistics tools: Kruskal Wallis and Dunn tests (HE e Masson) and ANOVA with Bonferroni test (collagen and cytokines). Results: Cytokines: there were no statistically significant differences between the groups. Histology: on the 40th postoperative day in group A, there were fewer inflammatory tissue response and greater collagen deposition (P0,05). Com relação à Histologia, no grupo A houve menor número de granulomas e de camadas de células na periferia dos mesmos, menos células gigantes, com maior fibrose, maturação tecidual e síntese de colágeno (P<0,01). No grupo B, foram encontrados maior número de granulomas e de camadas de células nos mesmos, mais células gigantes, com intensa reação inflamatória do tipo corpo estranho. Houve menor fibrose, maturação tecidual e deposição de colágeno (P<0,01). O grupo C apresentou valores intermediários entre os grupos B e A, exceto pelo menor processo inflamatório na superfície da tela. Conclusões: Não houve diferenças significativas nos níveis de citocinas entre os grupos estudados. Nos animais onde foi implantada a tela de polipropileno + poliglactina, houve processo inflamatório mais intenso tardio, com menor maturação tecidual e deposição de colágeno no 40°DPO. A tela de polipropileno apresentou menor processo inflamatório tardio, com maior maturação tecidual e deposição de colágeno. A tela de polipropileno+titânio apresentou valores intermediários entre as anteriores.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)TEDEBV UNIFESP: Teses e dissertaçõe

Ações da equipe de saúde para gestantes e puérperas tabagistas

OBJECTIVE: to identify activities developed by the healthcare team for pregnant and postpartum women who smoke. METHOD: cross-sectional study with a sample of 135 healthcare team members who assist pregnant and postpartum women in a university hospital located in southern Brazil. The data was collected using questionnaires and analyzed using the Statistical Package for Social Sciences software. RESULTS: 76 (56.3%) staff members reported that they always addressed smoking cessation; however, the approach occurred in only two periods of the hospitalization and/or prenatal consultations, not including family members. In regard to the effectiveness of their actions, the health team assessed it as fair or poor, and mentioned the need for updating knowledge regarding this issue. CONCLUSIONS: the health team did not perform the approach as recommended by the tobacco control guidelines, requiring training to offer a qualified and efficient intervention.OBJETIVO: identificar las actividades desarrolladas por el equipo de atención médica para las mujeres embarazadas y en posparto que fuman. MÉTODO: estudio transversal con una muestra de 135 miembros del equipo de salud que ayudan a las mujeres embarazadas y en posparto de un hospital universitario situado en el sur de Brasil. Los datos fueron recolectados a través de cuestionarios y analizados mediante el paquete estadístico para el software de las Ciencias Sociales. RESULTADOS: 76 (56,3%) de los miembros del equipo informaron que siempre sugerían el dejar de fumar; sin embargo, el acercamiento sucedió en sólo dos períodos de la hospitalización y/o en consultas prenatales, sin incluir a los miembros de la familia. En lo que respecta a la eficacia de sus acciones, el equipo de salud lo evaluó como regular o mala, y mencionó la necesidad de actualizar los conocimientos sobre este tema. CONCLUSIONES: el equipo de salud no realizó el acercamiento según las recomendaciones de las directrices de control del tabaco, lo que requiere la formación para ofrecer una intervención calificada y eficiente.OBJETIVO: identificar as ações desenvolvidas pela equipe de saúde para gestantes e puérperas tabagistas. MÉTODO: estudo transversal com amostra constituída por 135 membros da equipe de saúde que atendem gestantes e puérperas em um hospital universitário do Sul do Brasil. Os dados, coletados por meio de questionário, foram analisados no programa Statistical Package for Social Science. RESULTADOS: 76 (56,3%) membros da equipe abordaram sempre a cessação do tabagismo, entretanto, a abordagem ocorreu em apenas dois momentos da internação e/ou das consultas do pré-natal, não incluindo os familiares. Ao avaliar a eficácia de suas ações, a equipe de saúde a considerou regular ou ruim, bem como referiu a necessidade de atualizar seus conhecimentos na área. CONCLUSÕES: a equipe de saúde não realiza a abordagem conforme preconizado pelas diretrizes de controle do tabaco, necessitando de capacitação para que possa intervir de forma qualificada e eficiente

Contributo para Novas Metodologias de Avaliação e Monitorização dos Planos de Ordenamento da Orla Costeira em Portugal Continental

O contínuo aumento populacional nas zonas costeiras tem vindo a intensificar as várias situações de conflito de usos do solo, afectando fortemente os ecossistemas litorais, alterando os equilíbrios morfodinâmicos pré-existentes e destruindo irreversivelmente protecções naturais. Em Portugal, foram criados, em 1993, os Planos de Ordenamento da Orla Costeira (POOC), através do DL nº 309/93, de 2 de Setembro, com vista à compatibilização das actividades específicas da orla costeira e a conservação da natureza. Actualmente, todos os POOC, em Portugal Continental, já atingiram o seu tempo de vigência (10 anos) ou por situações diversas de desconformidade a sua revisão foi antecipada. Nesta fase do processo de planeamento conduzido pelos POOC, a avaliação, além de estar prevista na legislação em vigor, é de grande importância técnica, processual e de boa governança. Porém este facto raramente acontece em Portugal e os POOC com a excepção dos pertencentes à Região Tejo não avançaram neste sentido. Importa conferir aos futuros planos maior eficácia, por um lado, ao proceder-se a uma real avaliação da 1ª geração de planos, para que os erros cometidos não se repitam, e, por outro, ajustar às reais necessidades das populações e das especificidades dos territórios. A presente investigação tem o objectivo de contribuir para a avaliação e monitorização dos POOC, ao fornecer informação respectiva aos de 1ª geração, abordando também as actuais e futuras preocupações com as zonas costeiras

Recorte da experiência psicopedagógica clínica: Possibilidades de aplicação do inventário portage operacionalizado com sujeito com transtorno do espectro autista

The dynamism of the current society brings forward social, economical and cultural changes. Therewith, the school failure problem takes place, originating the demand for capable professionals to work in that area. So the clinical psychopedagogy – in a systemic approach - searches new possibilities of tools to assess the learning process, for the purpose of improving diagnosis and intervention. In that way, the Operational Portage Inventory (OPI) stands out and it is aimed to elucidate if the early stimulation can be promoted by its use in a systemic psychopedagogy approach, when the individual is stricken with Autism Spectrum Disorder. A delimitation of the clinical psychopedagogical experience was made, using the qualitative research for the case study. Regarding the sampling, it was chosen a two years old male individual, treated weekly in a private clinic. In the end, satisfying results were shown with the use of the OPI in a systemic psychopedagogic approach concerning the early stimulation.A dinamicidade da sociedade atual faz emergir mudanças sociais, econômicas e culturais. Com isso, o problema do fracasso escolar se destaca nas escolas, implicando na busca de profissionais capacitados a atuarem neste cenário. Então, com o diagnóstico e a intervenção psicopedagógica clínica em uma abordagem sistêmica, se busca investigar novas possibilidades de instrumentos de avaliação da aprendizagem, onde se destaca o Inventário Portage Operacionalizado (IPO). Desta forma, objetiva-se elucidar-se se por meio da utilização do IPO seria possível promover a estimulação precoce, em uma abordagem psicopedagógica sistêmica, com sujeito acometido por um Transtorno do Espectro Autista. Assim, fez-se um recorte da experiência psicopedagógica clínica, tendo como metodologia a abordagem qualitativa no âmbito de estudo de caso. No que tange a amostragem, delimitou-se um sujeito do sexo masculino, com idade de 2 anos, atendido semanalmente em uma clínica privada. Ao final, evidenciaram-se resultados satisfatórios com a utilização do instrumento IPO na abordagem psicopedagógica sistêmica, junto à perspectiva de estimulação precoce

“Y aunque los sueños se nos rompan en pedazos, resistiré”: narraciones digitales para analizar el impacto emocional de la pandemia en los estudiantes universitarios

Covid-19 generated an important impact on the mental health of university students. In this context, a double need arises: to analyse the effects of this impact and to work on emotional education with this educational sector. This study is part of a broader educational innovation project focused on working on the emotional education of university students. In this case, our purpose was to analyse the experiences of university students (N=6) during the pandemic through Digital Storytellings. The results showed revealing aspects regarding the influence that the pandemic had on students: the shortcomings of virtuality in teaching, the development of coping strategies, the lessons learned from the pandemic, etc. Finally, it was set out a number of implications for higher education, like the promotion of emotional education plans, the optimisation of online educational resources, and increased teacher training in digital issues and emotional support.La Covid-19 generó un importante impacto en la salud mental de los estudiantes universitarios. En este contexto, surge una doble necesidad: analizar los efectos de este impacto y trabajar la educación emocional con este sector educativo. Este estudio forma parte de un proyecto más amplio de innovación educativa centrado en trabajar la educación emocional de los estudiantes universitarios. En este caso, el principal objetivo del presente estudio fue analizar las experiencias de los estudiantes universitarios (N=6) durante la pandemia a través de Digital Storytellings. Los resultados muestran aspectos reveladores sobre la influencia que tuvo la pandemia en los estudiantes: las carencias de la virtualidad en la enseñanza, el desarrollo de estrategias para afrontar, las lecciones aprendidas de la pandemia, etc. Por último, se exponen una serie de implicaciones para la educación superior, como la promoción de planes de educación emocional, la optimización de los recursos educativos en línea y el aumento de la formación del profesorado en temas digitales y de apoyo emocional.Proyecto I+D+i in the framework of the Operational Programme FEDER “New Teaching Staff in Andalusian Universities: Academic, quantified and digitised identities” (Reference B_SEJ-534-UGR20)Ministry of Universities through the University Teacher Training Grants Programme (FPU19/00942

Review of higher education policy during the pandemic: A Spanish perspective

The COVID-19 pandemic has prompted profound changes in Higher Education. Thus, policymakers in different national contexts worldwide needed to design alternative responses to deal with new educational scenarios. In Spain, rethinking educational management in Higher Edu- cation remains an issue of current debate. Methodological readjustments towards virtual teaching, the digital divide due to socio-economic and cultural issues of the students, unequal access to education, or a decrease in internationalization have been some of the most significant adversities faced during this time. Amid this crisis, the measures taken by political leaders and university managers played an essential role. This study aims to provide an overview of the policy measures developed during this period, describing some of the most important decisions taken by different universities in Spain. To this end, an exploration based on secondary data from extensive literature reviews is carried out to construct a descriptive analysis of the measures implemented in Spanish universities. The findings highlight the coordinated action of the Spanish university system and the staunch defense of face-to-face teaching. This health crisis has also highlighted the deficits of this level of education and shed light on its future. Spain faces major challenges in the field of higher education. Consequently, the Spanish university system must begin building the foundations for educational innovation and training education professionals without fear of online scenarios. Finally, this article also proposes suggestions to guide policymakers in dealing with future adverse situations.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or pub- lication of this article: This work was supported by the State Research Agency, Spanish Ministry of Science and Innovation, through the project “The influence of neoliberalism on academic identities and on the level of professional satisfaction”—NEOACADEMIC—(PID2019-105631GA-I00/SRA (State Research Agency)/ 10.13039/501100011033); and by the R+D+i Project in the framework of the FEDER Operational Programme ‘Early career academics in Andalusian Universities: Academic identities, quantified and digitised.’ (B_SEJ- 534-UGR20). It also receives funding from the Ministry of Universities (Spain) through the University Teacher Training Grants Programme (FPU19/00942)