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

Criterios de la iniciativa de liderazgo mundial sobre malnutrición para el diagnóstico de la malnutrición en pacientes ingresados en la unidad de cuidados intensivos: Una revisión sistemática y meta-análisis

Antecedentes La desnutrición se asocia a un alto riesgo de morbilidad y mortalidad en pacientes con enfermedades críticas. El estado nutricional de los pacientes en la unidad de cuidados intensivos (UCI) es difícil de evaluar. La Global Leadership Initiative on Malnutrition (GLIM) es un novedoso marco utilizado para el diagnóstico de la desnutrición. Sin embargo, no se ha validado su eficacia en pacientes con enfermedades críticas en la UCI. Objetivo Investigar el uso y la validez de los criterios GLIM en pacientes adultos ingresados en la UCI. Métodos Se realizó una revisión sistemática y un metanálisis, y se buscaron estudios relevantes en siete bases de datos. Los criterios de selección incluyeron estudios que utilizaron los GLIM en pacientes adultos ingresados en la UCI. La evaluación de la calidad se realizó mediante la herramienta Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Resultados Se incluyeron cinco estudios en el análisis. Aproximadamente entre el 15% y el 68% de los pacientes fueron diagnosticados de desnutrición utilizando los criterios GLIM. Mientras tanto, entre el 48% y el 75% de los pacientes con desnutrición fueron identificados con la Evaluación Global Subjetiva (SGA). El criterio de inflamación se adjudicó fácilmente debido al estado crítico, y tres estudios compararon la GLIM y la SGA. Según la herramienta QUADAS-2, el proceso de evaluación nutricional no fue explícito en los estudios. El metaanálisis tuvo una sensibilidad global del 65,3% (IC 95%: 34,9%-86,9%) y una especificidad global del 88,8% (IC 95%: 58,1%-97,8%). En la validación prospectiva, la desnutrición evaluada según los criterios GLIM y la SGA se asoció con la mortalidad. Sin embargo, la asociación entre la duración de la estancia hospitalaria y la ventilación mecánica no estaba clara. Conclusiones El uso y la validez de los criterios GLIM entre los pacientes ingresados en la UCI son todavía limitados. Además, algunos estudios de validación concurrente y predictiva presentan limitaciones metodológicas. Deben realizarse más estudios para validar el uso de los criterios GLIM en la UCI.Background Malnutrition is associated with a high risk of morbidity and mortality in patients with critical illness. The nutrition status of patients in the intensive care unit (ICU) is challenging to assess. The Global Leadership Initiative on Malnutrition (GLIM) is a novel framework used for the diagnosis of malnutrition. However, its efficacy in patients with critical illness in the ICU has not been validated. Aim To investigate the use and validity of the GLIM criteria in adult patients admitted to the ICU. Methods A systematic review and meta-analysis were performed, and seven databases were searched for relevant studies. The selection criteria included studies that used the GLIM in adult patients admitted to the ICU. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Results Five studies were included in the analysis. Approximately 15%–68% of patients were diagnosed with malnutrition using the GLIM criteria. Meanwhile, 48%–75% of patients with malnutrition were identified with the Subjective Global Assessment (SGA). The inflammation criterion was easily adjudicated due to critical status, and three studies compared the GLIM and the SGA. According to the QUADAS-2 tool, the nutritional assessment process was not explicit in the studies. The meta-analysis had an overall sensitivity of 65.3% (95% CI: 34.9%–86.9%) and an overall specificity of 88.8% (95% CI: 58.1%–97.8%). In the prospective validation, malnutrition assessed by the GLIM criteria, and the SGA was associated with mortality. However, the association between length of hospital stay and mechanical ventilation was unclear. Conclusions The use and validity of the GLIM criteria among patients admitted to the ICU is still limited. Moreover, some concurrent and predictive validation studies have methodological limitations. Further studies must be performed to validate the use of the GLIM criteria in the ICU

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

Adição ao trabalho e interação familiar em enfermeiros

This study aims to identify the prevalence of workaholism and work-family interaction, their relationship and their variation according sociodemographic and occupational characteristics among nurses. A quantitative, descriptive, correlational and transversal study was conducted with a sample of 839 Portuguese nurses. Regarding workaholism, 27% of workaholic nurses were identified, scoring a higher mean value for excessive work. For work-family interaction, the dimensions showing the highest mean values were the negative work-family interaction and the positive family-work interaction. The variables identified as significant predictors of workaholism were the work-family interaction (39%), occupational variables (10.6%) and sociodemographic variables (1.2%). Among the occupational and professional variables, the women, age equal or less than 37 years and perception of stressful work, were highlighted. The confirmation of workaholism in nurses, as well as its predictive variables are significantly important for professionals and organizations to better understand the impact of this phenomenon, particularly in mental health and to encourage the development of programmes aiming to promote health at the workplace.O objetivo deste estudo foi identificar a prevalência da adição ao trabalho, os níveis de interação trabalho-família e a relação destes com características sociodemográficas e laborais em enfermeiros. Estudo quantitativo, descritivo, correcional e transversal numa amostra de 839 enfermeiros de Portugal continental. Relativamente à adição ao trabalho, identificaram-se 27,1% de enfermeiros adictos, com valor médio superior no trabalho excessivo. No que respeita à interação trabalho-família, as dimensões com médias superiores foram a interação negativa trabalho-família e a interação positiva família-trabalho. As variáveis identificadas como preditores significativos da adição ao trabalho foram a interação trabalhofamília (39%), as variáveis laborais (10,6%) e as sociodemográficas (1,2%). Das variáveis laborais e profissionais salienta-se o sexo feminino, idade igual ou inferior a 37 anos e a perceção de trabalho stressante. A confirmação deste fenómeno em enfermeiros, assim como, das variáveis que o podem potenciar, possibilita ao profissional e às organizações, uma maior consciencialização dos seus impactos, nomeadamente na saúde mental incentivando o desenvolvimento de programas que visem a promoção de saúde no local de trabalho.info:eu-repo/semantics/publishedVersio

Resultados preliminares de la terapia dialéctico-comportamental en población española: un estudio de caso

Tretzenes Jornades de Foment de la Investigació de la FCHS (Any 2007-2008)El trastorno límite de la personalidad (TLP) constituye uno de los cuadros psicopatológicos más complejos con los que puede enfrentarse un clínico. Dentro de los trastornos de personalidad, lo más característico del TLP es la inestabilidad persistente que aparece en todas áreas de funcionamiento principales: la cognición, la afectividad, la actividad interpersonal y el control de los impulsos. En los últimos años se ha producido un interés creciente por este trastorno, debido, sobre todo, a la constatación de la elevada frecuencia de este tipo de pacientes en los centros de asistencia psiquiátrica y el riesgo de autolesión y suicidio inherente a este problema. A pesar de la gravedad del trastorno, el desarrollo y puesta a prueba de estrategias de intervención eficaces es escaso. Estas razones han impulsado el estudio, en los últimos años, del desarrollo de estrategias de intervención para este trastorno. Uno de los programas de tratamiento que ha demostrado ser eficaz es la Terapia Dialéctico-Comportamental (TDC) para el trastorno límite de la personalidad, desarrollado por la Dra. Marsha Linehan y su grupo de investigación en la Universidad de Washington (EEUU). El equipo de investigación de la Dra. Cristina Botella, está desarrollando actualmente un proyecto denominado: “Tratamiento psicológico de la personalidad patològica en los trastornos de la conducta alimentaria”, dirigido por la Dra. Azucena García Palacios y financiado por el Plan de Promoción de la Investigación de la Universitat Jaume I. Este proyecto consiste en un ensayo clínico controlado que pretende poner prueba una adaptación de este programa para el tratamiento de la personalidad patológica en los trastornos de la conducta alimentaria (TCA). El objetivo del presente trabajo es ofrecer datos de la eficacia preliminar de esta adaptación con la presentación de un estudio de caso diagnosticado de TLP y bulimia nerviosa tras ser tratado en el Centro Clínico Previ durante seis meses

The role of emotion regulation strategies and dissociation in non-suicidal self-injury for women with borderline personality disorder and comorbid eating disorder

Different dysfunctional emotion regulation strategies are observed in patients with borderline personality disorder (BPD) and comorbid eating disorders (EDs) who report non-suicidal self-injury (NSSI). The objective of this study was to investigate the relationship of two well-defined emotion regulation strategies (i.e. expressive suppression and cognitive reappraisal) and dissociation with NSSI. The participants were sixty-eight women diagnosed with BPD and comorbid ED. A cross-sectional research design was used, and clinical interviews and self-report questionnaires were administered to collect data. Multiple regression was conducted to analyze the relationship of two emotion regulation strategies and dissociation with NSSI. According to the results, for low cognitive reappraisal scores, an increase in dissociation leads to an increase in NSSI; however, as cognitive reappraisal increases, higher dissociation is associated with fewer NSSI. When expressive suppression is low, an increase in cognitive reappraisal is associated with a decrease in NSSI; however, as suppression increases, a higher cognitive reappraisal has less effect on decreasing NSSI. These findings indicate that cognitive reappraisal reduces the harmful effects that dissociation has on NSSI, and that expressive suppression interferes with the beneficial effects of cognitive reappraisal on NSSI. Therefore, targeting expressive suppression before cognitive reappraisal is conducted may enhance treatment outcomes for patients with BPD and comorbid ED.The research presented in this paper was funded by Ministerio de Economía y Competitividad, Spain, proyectos de investigacion fundamental no orientada (PSI2010-21423/PSIC), Plan de Formación de la investigacion en la Universitat Jaume I (P11B2005-32), and Generalitat Valenciana, Redes de Excelencia ISIC (ISIC/2012/012)

Effect of adding photoprotective compounds in the diet of Palaemon macrodactylus and its role under ultraviolet radiation

During the past two decades, it has shown an increase in ultraviolet radiation (UVR) and particularly the UVB (280-315nm) above Earth's surface. There is some evidence that UV-B radiation (280-315 nm) and the shorter wavelengths of UV-A (315-400 nm) can significantly affect the biota in waters up to 20 m deep and have adverse on aquatic organisms such as damage in the genetic material and high mortality. It has been shown that many species of seaweeds synthesize and accumulate high concentrations of photoprotective compounds and may constitute an interesting alternative as a supplement in aquaculture feeds. In the present work the effects of UVR were studied in the animal model Palaemon macrodactylus which is a successful invader, known as the Oriental Shrimp, native to estuaries and coastal waters of the Northwest Pacific. In the south western Atlantic, the species was found in Mar del Plata harbour, Argentina, probably introduced from the Pacific with discharged ballast water The aim of this study was to determine the bioaccumulation of photoprotective compounds (PPC) from diets added with red seaweeds meal of the family Halymeneaceae on juvenile P. macrodactylus and its possible protective role under conditions of stress by UVR. Juveniles of P. macrodactylus collected from Mar del Plata harbour (38° 03′ S; 57° 31′ W) were placed in PVC tanks under controlled conditions of temperature, pH, and salinity, under two feeding treatments: one group with basal diet (B) (45% protein, 8% lipid, 7% water and 7% ash) and the other 2% diet added with red seaweed meal of the family Halymeneaceae (diet B2). After 15 days animals were subjected to two radiations in four treatments, by triplicate: a) Control PAR (400-700nm) and diet B b) PAR+ UVR (280-700nm) and diet B c) PAR and diet B2, d) PAR+ UVR and diet B2. Survival, percentage of weight gain, concentrations of PPC and carotenoids were determined. In treatment b mortality of 16% was recorded after 72 hours of exposition to UVR, while in those fed with the 2% added diet, the same mortality was observed after 120 h of exposure. Survival in the treatments (a, c) was 100%. At the end of the exposure radiation period, percentage of weight gain was higher in animals fed with diet B (77%) nevertheless concentration of PPC and carotenoids (determined as OD g tissue-1) recorded the highest values in the animals corresponding to treatment c (PPC: 1.9 ± 0.38 DO g-1; carotenoids: 0.48 ± 0.1 OD g-1). although there were no significant differences between other treatments. These results suggest that, a diet added with red seaweeds rich in photoprotective compounds constitutes and interesting alternative, not only for its contribution to a better physiological state of animals under stress conditions by UVR, but also for the particularity of being invasive species with potential commercial use

Psychometric properties of the Portuguese Dutch Work Addiction Scale

Objective: To analyse the psychometric properties of the Dutch Work Addiction Scale in a sample of Portuguese nurses. Method: A methodological study was conducted with 1,030 Portuguese nurses. A sociodemographic/professional questionnaire and the Dutch Work Addiction Scale applied between October and December 2019. Results: The Confirmatory Factorial Analyses confirmed the factorial structure of two dimensions, namely Working Excessively (α = .730) and Working Compulsively (α = .752), grounded on the theoretical model of workaholism; the reliability values were considered adequate. Nurses presented a moderate level of workaholism, with a higher mean value for Working Excessively. Conclusion: The results raised the issue of workaholism and highlighted the need for further study. The Portuguese version of the DUWAS presented good psychometric characteristics and can be considered a valid and useful instrument to identify this problem.Objetivo Analisar as propriedades psicométricas da Dutch Work Addiction Scale (Duwas) numa amostra de enfermeiros portugueses. Método Foi realizado um estudo metodológico com 1.030 enfermeiros portugueses. Um questionário sociodemográfico/profissional e a Duwas foram aplicados entre outubro e dezembro de 2019. Resultados A Análise Fatorial Confirmatória confirmou a estrutura fatorial de duas dimensões, a saber Trabalhar Excessivamente (α = 0,730) e Trabalhar Compulsivamente (α = 0,752), embasado no modelo teórico de workaholism; os valores de confiabilidade foram considerados adequados. Os enfermeiros apresentaram nível moderado de workaholism, com maior valor médio para Trabalhar Excessivamente. Conclusão Os resultados levantaram a questão da adição ao trabalho e destacaram a necessidade de estudos mais aprofundados. A versão em português do Duwas apresentou boas características psicométricas e pode ser considerada um instrumento válido e útil para identificar esse problema.Objetivo Analizar las propiedades psicométricas de la Dutch Work Addiction Scale (Duwas) en una muestra de enfermeros portugueses. Método Se realizó un estudio metodológico con 1.030 enfermeras portuguesas. Un cuestionario sociodemográfico/profesional y la Duwas fueron aplicados entre octubre y diciembre de 2019. Resultados Los análisis factoriales confirmatorios confirmaron la estructura factorial de dos dimensiones, a saber, Trabajar en exceso (α = .730) y Trabajar de forma compulsiva (α = .752), basado en el modelo teórico de la adicción al trabajo; los valores de fiabilidad se consideraron adecuados. Los enfermeros presentaron un nivel moderado de adicción al trabajo, con un valor medio más alto para Trabajar en exceso. Conclusión Los resultados plantearon el problema de la adicción al trabajo y destacaron la necesidad de realizar más estudios. La versión portuguesa del Duwas presentó buenas características psicométricas y puede considerarse un instrumento válido y útil para identificar este problema.info:eu-repo/semantics/publishedVersio