SARS-CoV-2 Spike Protein Enhances Carboxypeptidase Activity of Angiotensin-Converting Enzyme 2.

In this study, we investigated whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein may modify angiotensin-converting enzyme 2 (ACE2) activity in the plasma, heart, kidney, liver, lung, and six brain regions (amygdala, brain stem, cortex, hippocampus, hypothalamus, and striatum) of diabetic and hypertensive rats. We determine ACE2 activity in the plasma and lysates of heart, kidney, liver, lung, and six brain regions. MLN-4760 inhibits ACE2 activity in the plasma and all organs. On the other hand, soluble ACE2 (sACE2) activity increased in the plasma of diabetic rats, and there was no change in the plasma of hypertensive rats. ACE2 activity was augmented in the liver, brain stem, and striatum, while it decreased in the kidney, amygdala, cortex, and hippocampus of diabetic rats. ACE2 activity increased in the kidney, liver, and lung, while it decreased in the heart, amygdala, cortex, and hypothalamus of hypertensive rats. We measured the ACE2 content via enzyme-linked immunosorbent assay and found that ACE2 protein levels increased in the heart, while it decreased in the plasma, kidney, brain stem, cortex, hippocampus, hypothalamus, and striatum of diabetic rats. ACE2 protein levels decreased in the brain stem, cortex, hippocampus, and hypothalamus of hypertensive rats. Our data showed that the spike protein enhanced ACE2 activity in the liver and lungs of diabetic rats, as well as in the heart and three of the brain regions (cortex, hypothalamus, and striatum) of hypertensive rats.

Hipertensión arterial sistémica posterior a COVID-19 / Systemic arterial hypertension after COVID-19

Introducción: un nuevo tipo de coronavirus que se nombró SARSCoV-2, responsable de la enfermedad por COVID-19, tuvo esparcimiento rápido en el mundo, por alta transmisión que resultó en pandemia. Se registraron 2'397,216 casos confirmados, con 162,956 defunciones en el mundo, de acuerdo con la Organización Mundial de la Salud (OMS), en abril de 2020. Sin embargo, la hipertensión afecta a 40% de adultos, lo que significa que alrededor de 250 millones de personas padecen de presión alta. La OMS, de acuerdo con sus reportes, refiere que la hipertensión es el factor de riesgo número uno de muerte. Uno de cada cuatro mexicanos padece hipertensión arterial. Objetivos: establecer la incidencia de la hipertensión arterial sistémica posterior a padecer COVID-19 en pacientes de la Unidad de Medicina Familiar (UMF) No. 48. Material y métodos: es un estudio transversal, observacional y descriptivo, conformado por 3,238 pacientes con diagnóstico de COVID-19 positivo, de ambos sexos, con edades entre 18 y 70 años. Por medio de la fórmula para poblaciones infinitas se obtiene una muestra de 348 pacientes. Se realizó revisión de expedientes en el Sistema de Información de Medicina Familiar, versión 6.2, para obtención de la información correspondiente. Resultados: 27 pacientes diagnosticados con hipertensión arterial posterior al diagnóstico de COVID-19, 52% del sexo masculino y 48% del femenino, con media de edad de 39 años, 74% correspondió a enfermedad leve por COVID-19 y 26% a enfermedad moderada. Se documenta mediana de ocho días por periodo de infección por COVID-19. En el círculo femenino el promedio de la aparición de hipertensión arterial fue de 13 meses y en el masculino la media de desarrollo de hipertensión arterial posterior a COVID-19 fue de seis meses (AU)

Introduction: a new type of coronavirus that was named SARSCoV-2, responsible for the COVID-19 disease, with rapid spread in the world, due to high transmission that resulted in pandemic. There were 2'397,216 confirmed cases, with 162,956 deaths in the world, according to the WHO in April 2020. However, hypertension affects 40% of adults and means that around 250 million people suffer from high blood pressure. The WHO, according to its reports, refers that hypertension is the number one risk factor for death. One in four Mexicans suffers from high blood pressure. Objectives: to establish the incidence of systemic arterial hypertension after suffering from COVID-19 in patients of the UMF No. 48. Material and methods: it is a cross-sectional, observational and descriptive study, consisting of 3,238 patients with a positive COVID-19 diagnosis of both sexes, aged 18-70 years. Through the formula for infinite populations a sample of 348 patients is obtained. Will proceed with review of files in the Family Medicine Information System, version 6.2, to obtain the corresponding information. Results: 27 patients diagnosed with hypertension after the diagnosis of COVID-19, 52% of the male sex and 48% of the female sex, with a mean age of 39 years; 74% corresponds to a mild illness by COVID-19 and 26% to moderate disease. A median of 8 days per period of infection by COVID-19 is documented. In the female circle, the average onset of hypertension was 13 months and as for the male sex, the mean development of hypertension after COVID-19 was six months (AU)

Standardized Centella asiatica extract ECa 233 alleviates pain hypersensitivity by modulating P2X3 in trigeminal neuropathic pain

Abstract During oral surgery and temporomandibular joint repositioning, pain hypersensitivity often occurs due to irritation or inflammation of the nerve endings in the orofacial region. Objective: This study aimed to investigate the effects of ECa 233, a Centella asiatica-standardized extract, on the development of mechanical hyperalgesia and allodynia induced by chronic constriction injury of the infraorbital nerve in mice. Methodology: The right infraorbital nerves of the mice were ligated. Oral carbamazepine (20 mg/kg) or ECa 233 (30, 100, or 300 mg/kg) was administered daily for 21 days. Von Frey and air-puff tests were performed on both sides of the whisker pad on days 0, 7, 14, and 21. Thereafter, the expression of purinergic receptor subtype 3 (P2X3) and voltage-gated sodium channel 1.7 (NaV1.7), a transmembrane protein, in the trigeminal ganglion and c-fos immunoreactivity-positive neurons in the trigeminal nucleus caudalis was assessed. Results: After 21 days of infraorbital nerve ligation, the mice showed allodynia- and hyperalgesia-like behavior, P2X3 and NaV1.7 were upregulated in the trigeminal ganglion, and nociceptive activity increased in the trigeminal nucleus caudalis. However, the oral administration of carbamazepine (20 mg/kg), ECa 233 (100 mg/kg), or ECa 233 (300 mg/kg) mitigated these effects. Nevertheless, ECa 233 failed to affect NaV1.7 protein expression. Conclusion: Carbamazepine and ECa 233 can prevent pain hypersensitivity in mice. Considering the side effects of the long-term use of carbamazepine, ECa 233 monotherapy or combined ECa 233 and carbamazepine therapy can be used as an alternative for regulating the development of hypersensitivity in trigeminal pain. However, further detailed clinical studies should be conducted to provide comprehensive information on the use of ECa 233.

Embodied Conversational Agents Providing Motivational Interviewing to Improve Health-Related Behaviors: Scoping Review.

BACKGROUND: Embodied conversational agents (ECAs) are advanced human-like interfaces that engage users in natural face-to-face conversations and interactions. These traits position ECAs as innovative tools for delivering interventions for promoting health-related behavior adoption. This includes motivational interviewing (MI), a therapeutic approach that combines brief interventions with motivational techniques to encourage the adoption of healthier behaviors. OBJECTIVE: This study aims to identify the health issues addressed by ECAs delivering MI interventions, explore the key characteristics of these ECAs (eg, appearance, dialogue mechanism, emotional model), analyze the implementation of MI principles and techniques within ECAs, and examine the evaluation methods and primary outcomes of studies that use ECAs providing MI interventions. METHODS: We conducted a scoping review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) methodology. Our systematic search covered the PubMed, Scopus, IEEE Xplore, ACM Digital, and PsycINFO databases for papers published between January 2008 and December 2022. We included papers describing ECAs developed for delivering MI interventions targeting health-related behaviors and excluded articles that did not describe ECAs with human appearances and without the necessary evaluation or MI explanation. In a multistage process, 3 independent reviewers performed screening and data extraction, and the collected data were synthesized using a narrative approach. RESULTS: The initial search identified 404 articles, of which 3.5% (n=14) were included in the review. ECAs primarily focused on reducing alcohol use (n=5, 36%), took on female representations (n=9, 64%), and gave limited consideration to user ethnicity (n=9, 64%). Most of them used rules-driven dialogue mechanisms (n=13, 93%), include emotional behavior to convey empathy (n=8, 57%) but without an automatic recognition of user emotions (n=12, 86%). Regarding MI implementation, of 14 studies, 3 (21%) covered all MI principles, 4 (29%) included all processes, and none covered all techniques. Most studies (8/14, 57%) conducted acceptability, usability, and user experience assessments, whereas a smaller proportion (4/14, 29%) used randomized controlled trials to evaluate behavior changes. Overall, the studies reported positive results regarding acceptability, usability, and user experience and showed promising outcomes in changes in attitudes, beliefs, motivation, and behavior. CONCLUSIONS: This study revealed significant advancements in the use of ECAs for delivering MI interventions aimed at promoting healthier behaviors over the past 15 years. However, this review emphasizes the need for a more in-depth exploration of ECA characteristics. In addition, there is a need for the enhanced integration of MI principles, processes, and techniques into ECAs. Although acceptability and usability have received considerable attention, there is a compelling argument for placing a stronger emphasis on assessing changes in attitudes, beliefs, motivation, and behavior. Consequently, inclusion of more randomized controlled trials is essential for comprehensive intervention evaluations.

Enzima convertidora de angiotensina homóloga (ECA2) y actividad de ROCK en la falla cardíaca experimental / ACE 2 and ROCK activity in experimental congestive heart failure

Antecedentes: La ECA2 ha mostrado ser un regulador esencial de la funcionalidad cardíaca. En un modelo experimental de insuficiencia cardíaca (IC) con Fier, modelo de coartación de aorta (COA), se encontró activación de la vía Rho-kinasa. La inhibición de esta vía con fasudil no mejoró el remodelado cardíaco ni la disfunción sistólica. Se desconoce en este modelo, si el deterioro de la función cardíaca y activación de la vía rho-kinasa se asocia con una disminución de la ECA2 cardíaca y si la inhibición de Rho-kinasa tiene un efecto sobre la expresión de ECA2. Objetivo: Nuestro objetivo es determinar si en la falla cardaca experimental por coartación aórtica, los niveles proteicos de ECA2 en el miocardio se asocian a disfunción sistólica y cual es su interacción con la actividad de ROCK en el miocardio. Métodos: Ratones C57BL6J machos de 7-8 semanas se randomizaron en 3 grupos experimentales. Grupo COA por anudación de la aorta + vehículo; Grupo COA + Fasudil (100 mg/Kg día) por bomba osmótica desde la semana 5 post-cirugía; y grupo control o Sham. Se determinaron las dimensiones y función cardíaca por ecocardiografía. Posterior a la eutanasia, se determinaron los niveles de ECA2 del VI por Western-blot y actividad de la Rho-kinasa Resultados: En los grupos COA+vehículo y COA-FAS hubo deterioro de la función cardíaca, reflejada por la reducción de la FE (47,9 ± 1,53 y 45,5 ± 2,10, p < 0,05, respectivamente) versus SHAM (68,6 ± 1,19). Además, aumentaron las dimensiones cardíacas y hubo desarrollo de hipertrofia (0,53 ± 0,02 / 0,53 ± 0,01, p < 0,05) medida por aumento de la masa cardíaca relativa respecto del grupo SHAM (0,40 ± 0,01). En los grupos COA+vehículo y COA-FAS se encontró una disminución significativa del 35% en la expresión de ECA2 cardíaca respecto al grupo control. Conclusiones: La disfunción sistólica por coartación aórtica se asocia con aumento de la actividad de Rho-kinasa y significativa disminución de la expresión de ECA2. La inhibición de Rho-kinasa no mejoró el remodelado cardíaco, la disfunción sistólica y tampoco modificó los niveles de ECA2 cardíaca.

Background: ACE2 has been described as an essential regulator of cardiac function. In an experimental model of heart failure (HF) and heart failure reduced ejection fraction (HFrEF), the aortic coarctation (COA) model, activation of the Rho-kinase pathway of cardiac remodeling was found. Inhibition of this pathway did not improve cardiac remodeling or systolic ventricular dysfunction. It is unknown in this model whether the impairment of cardiac function and activation of the rho-kinase pathway is associated with a decrease in ACE2 and whether rho-kinase inhibition has an effect on ACE2 expression. Objective: To determine if in experimental heart failure due to aortic coarctation, ACE2 protein levels in the myocardium are associated with systolic dysfunction and what is its interaction with ROCK activity in the myocardium. Methods: Male C57BL6J mice aged 7-8 weeks were divided into 3 groups and anesthetized: One group underwent COA+ vehicle; A second group COA + Fasudil (100 mg/Kg/d) by osmotic pump from week 5 post-surgery and; the third group, control(SHAM). Echocardiograms were performed to determine cardiac dimensions and systolic function. Rats were then euthanized. Ventricular expression of ACE2, activity of the Rho-kinase pathway by MYPT-1 phosphorylation, relative cardiac mass, area and perimeter of cardiomyocytes were determined by Western blot. Results: In both COA+vehicle and COA+FAS groups there was deterioration of cardiac function, reflected in the reduction of EF (47.9 ± 1.53 and 45.5 ± 2.10, p < 0.05, respectively) versus the SHAM group (68.6 ± 1.19). In addition, cardiac dimensions and hypertrophy increased (0.53 ± 0.02 / 0.53 ± 0.01, p < 0.05) due to increased relative cardiac mass compared to the SHAM group (0.40 ± 0.01). In the COA+vehicle and COA+FAS groups a significant decrease of 35% in cardiac ACE2 expression was found compared to the control group. Conclusions: Systolic dysfunction due to aortic coarctation is associated with increased Rhokinase activity and a significant decrease in ACE2 expression. Rho-kinase inhibition did not improve cardiac remodeling, systolic dysfunction, nor did it change cardiac ACE2 levels.

Análisis de los polimorfismos ECA y ACTN3 con la agilidad en seleccionados nacionales de deportes de conjunto de Costa Rica. Estudio piloto / ACE and ACTN3 polymorphisms analysis on agility test in national players in team sports of Costa Rica. Pilot study / Análise dos polimorfismos ECA e ACTN3 com agilidade em jogadores esportivos selecionados da seleção costarriquenha. Estudo piloto

Resumen: Objetivo: Analizar las diferencias de los polimorfismos de los genes ECA y ACTN3 en el rendimiento de una prueba de agilidad en jugadores élite de deportes colectivos pertenecientes a selecciones nacionales de Costa Rica. Metodología: Se contó con una muestra de 33 jugadores hombres, de deportes colectivos (fútbol sala, rugby, voleibol y balonmano). Para la evaluación de la agilidad se utilizó el test de Illinois. Se realizaron dos visitas, en la primera se obtuvo muestras de células por medio de un enjuague y en la segunda se aplicó la prueba de agilidad. Se utilizó la prueba de Chi-cuadrado (X2) para conocer las diferencias entre las frecuencias de los polimorfismos de los genes ECA y ACTN3 y el tipo de deporte. Resultados: La mayor distribución de los polimorfismos del gen ECA, de jugadores de selecciones nacionales de deportes de conjunto, se encuentra en el ID (X2= 6.87, p= .334) y en ACTN3 el RX (X2= 6.33, p= .388). Además, tampoco se encontraron diferencias significativas entre el tiempo efectuado en el test de Illinois y los polimorfismos del gen ECA (F= 2.150, p= .134), de igual forma para los polimorfismos del gen ACTN3 (F= .950, p= .339). Conclusiones: Los polimorfismos de los genes ECA y ACTN3 no se relacionaron estadísticamente con el tipo de deporte colectivo. La agilidad no se ve asociada por un tipo de polimorfismo, lo que indica que, de forma independiente al gen, esta cualidad física se puede entrenar y generar buenos resultados en la población en general.

Abstract: Objective: To analyze the differences in the polymorphisms of the ACE and ACTN3 genes on agility test performance in elite players of collective sports from National teams of Costa Rica. Methods: a sample of 33 male team sports players (futsal, rugby, volleyball, and handball). All subjects were tested with the Illinois Agility Test. Two days of measurements were made; on the first day, cell samples were obtained and on the second day, the agility test was applied. The Chi-square test (x2) was used to determine the differences between the frequencies of the polymorphisms of the ACE and ACTN3 genes and the type of sport. Results: The highest distribution of polymorphisms of the ECA gene of players from national teams of collective sports was found in the ACE ID (X2 = 6.87, p = .334), and in ACTN3 the RX (X2 = 6.33, p =. 388). Furthermore, no significant relationship was found between the Illinois test performance and the polymorphisms of the ECA gene (F = 2,150, p = .134). Conclusions: The ACE and ACTN3 genes polymorphisms were not statistically related to the type of team sport. Agility is not associated with the type of polymorphism, which indicates that regardless of the gene, this physical quality can be trained and generate good results in the general population.

Resumo: Objetivo: analisar as diferenças dos polimorfismos dos genes ECA e ACTN3 na realização de um teste de agilidade em jogadores de elite de equipes esportivas pertencentes a equipes nacionais costarriquenhas. Metodologia: foi utilizada uma amostra de 33 jogadores de futebol masculino (futsal, rúgbi, vôlei e handebol). O teste de Illinois foi usado para avaliar a agilidade. Foram feitas duas visitas; na primeira foram obtidas amostras de uma célula por lavagem e na segunda foi aplicado o teste de agilidade. O teste qui-quadrado (X2) foi usado para determinar as diferenças entre as frequências dos polimorfismos dos genes ECA e ACTN3 e o tipo de esporte. Resultados: A maior distribuição de polimorfismos do gene ECA em jogadores de equipes nacionais de esportes coletivos é encontrada no ID (X2= 6,87, p= 0,334) e no ACTN3 no RX (X2= 6,33, p= 0,388). Além disso, não foram encontradas diferenças significativas entre o tempo gasto no teste de Illinois e os polimorfismos do gene ECA (F= 2,150, p= 0,134), assim como para os polimorfismos do gene ACTN3 (F= 0,950, p= 0,339). Conclusões: Os polimorfismos dos genes ECA e ACTN3 não estavam estatisticamente relacionados com o tipo de esporte coletivo. A agilidade não está associada pelo tipo de polimorfismo, indicando que, independentemente do gene, essa qualidade física pode ser treinada e gerar bons resultados na população em geral.

Telmisartán y losartán: las marcadas diferencias entre sus propiedades químicas y farmacológicas pueden explicar la diferencia en la eficacia terapéutica en pacientes hospitalizados con covid-19 / Telmisartan and losartan: marked differences in chemical and pharmacological properties may explain differences in therapeutic efficacy in hospitalized patients with COVID-19

El objetivo de este artículo es comparar las propiedades químicas y farmacológicas del telmisartán y el losartán, y su metabolito activo EXP3174, con el fin de entender por qué el telmisartán es efectivo en pacientes hospitalizados con Covid-19 mientras que el losartán no lo es. Se llevó a cabo una revisión bibliográfica exhaustiva de las propiedades químicas, farmacocinéticas y farmacodinámicas de ambos fármacos y se destacaron las diferencias más importantes que podrían estar relacionadas con su efectividad en pacientes con Covid-19. Se concluyó que las propiedades farmacológicas del telmisartán, como su mayor afinidad por el receptor AT1, su duración de acción prolongada y su capacidad para modular la inflamación podrían explicar su efectividad en pacientes con Covid-19. Por otro lado, las propiedades farmacológicas del losartán, como su menor afinidad por el receptor AT1 y su rápido metabolismo, pueden limitar su efectividad en pacientes con Covid-19. Estos resultados resaltan la importancia de comprender las propiedades químicas y farmacológicas de los medicamentos para identificar posibles candidatos terapéuticos efectivos en el tratamiento de Covid-19. (AU)

The objective of this article is to compare the chemical and pharmacological properties of telmisartan and losartan and their active metabolite EXP3174 to understand why telmisartan is effective in hospitalized patients with COVID-19 while losartan is not. A comprehensive literature review of the chemical, pharmacokinetic and pharmacodynamic properties of both drugs was done to highlight the most important differences that may be related to their efficacy in patients with COVID-19. It was concluded that the pharmacological properties of telmisartan, such as its higher affinity for the AT1 receptor, its long duration of action and its ability to modulate inflammation, could explain its efficacy in patients with COVID-19. On the other hand, the pharmacological properties of losartan, such as its lower affinity for the AT1 receptor and its rapid metabolism, may limit its efficacy in patients with COVID-19. These results highlight the importance of understanding the chemical and pharmacological properties of drugs to identify potential effective therapeutic candidates for the treatment of COVID-19. (AU)

Effects of Amazonian flying rivers on frog biodiversity and populations in the Atlantic rainforest.

Given the speed at which humans are changing the climate, species with high degrees of endemism may not have time to avoid extinction through adaptation. We investigated through teleconnection analysis the origin of rainfall that determines the phylogenetic diversity of rainforest frogs and the effects of microclimate differences in shaping the morphological traits of isolated populations (which contribute to greater phylogenetic diversity and speciation). We also investigated through teleconnection analysis how deforestation in Amazonia can affect ecosystem services that are fundamental to maintaining the climate of the Atlantic rainforest biodiversity hotspot. Seasonal winds known as flying rivers carry water vapor from Amazonia to the Atlantic Forest, and the breaking of this ecosystem service could lead Atlantic Forest species to population decline and extinction in the short term. Our results suggest that the selection of morphological traits that shape Atlantic Forest frog diversity and their population dynamics are influenced by the Amazonian flying rivers. Our results also suggest that the increases of temperature anomalies in the Atlantic Ocean due to global warming and in the Amazon forest due to deforestation are already breaking this cycle and threaten the biodiversity of the Atlantic Forest hotspot.

Efectos de los ríos voladores de la Amazonía sobre la diversidad y las poblaciones de ranas en la Mata Atlántica Resumen Con la velocidad a la que la humanidad está alterando el clima, puede que las especies con un nivel elevado de endemismo no cuenten con tiempo suficiente para adaptarse y evitar la extinción. Usamos un análisis de teleconexión para investigar el origen de las precipitaciones que determinan la diversidad filogenética de las ranas selváticas y los efectos de las diferencias microclimáticas sobre la determinación de las características morfológicas de las poblaciones aisladas, las cuales contribuyen a una mayor especiación y diversidad filogenética. También utilizamos este análisis para investigar cómo la deforestación en la Amazonía puede afectar los servicios ambientales que son fundamentales para mantener el punto caliente de biodiversidad que es la Mata Atlántica. Los ríos voladores son vientos estacionales que transportan vapor de agua desde la Amazonía hasta la Mata Atlántica; la interrupción de este servicio ambiental podría derivar en la declinación poblacional y la extinción a corto plazo de las especies en este ecosistema. Nuestros resultados sugieren que los ríos voladores de la Amazonía influyen sobre la selección de las características morfológicas que determinan la diversidad de ranas y sus dinámicas poblacionales en la Mata Atlántica. Nuestros resultados también sugieren que el incremento de anomalías térmicas en el Océano Atlántico, causadas por el calentamiento global, y en la Amazonía, causadas por la deforestación, ya están interrumpiendo este ciclo y son una amenaza para la biodiversidad del punto caliente que es la Mata Atlántica.

Tratamientos y bioterapias para COVID-19 / Therapeutics and biotherapies for covid-19

INTRODUCCIÓN: Un nuevo brote de coronavirus surgió en 2019 en Wuhan, China, causando conmoción en el sistema sanitario de todo el mundo; el Comité Internacional de Taxonomía de Virus lo denominó SARS-CoV-2, agente causante de la enfermedad COVID-19.El espectro de gravedad de la enfermedad es muy amplio: la mayoría de los pacientes no presentan gravedad, pero otros pueden desarrollar neumonías, y la insuficiencia respiratoria aguda es la causa más frecuente de mortalidad. Objetivo: analizar y desarrollar las distintas alternativas terapéuticas aportadas por la Biotecnología para tratar los síntomas de aquellos pacientes con COVID-19. Metodología: se realizó una revisión de la bibliografía disponible, a partir de enero de 2020 en PubMed, acerca de los tratamientos que se encuentran aún en ensayos clínicos y aquellos que cuentan con aprobación bajo uso de emergencia para la enfermedad COVID-19. También se realizaron búsquedas a través de Google y Google Académico para publicaciones de organismos de Salud en referencia a políticas de salud establecidas para la terapéutica durante dicha pandemia. Resultados: este trabajo aborda las nuevas alternativas terapéuticas para COVID-19 derivadas de la Biotecnología, que se encuentran tanto en uso como en etapas de ensayos clínicos comprendidos dentro del segmento de los biofármacos y las bioterapias. Se incluye un breve resumen del estatus regulatorio de entidades de salud, el mecanismo de acción de dichas terapias y características generales de cada uno. Se incluyen novedosas bioterapias que se empezaron a implementar para afrontar la pandemia. Conclusiones: la pandemia de coronavirus está poniendo a prueba el sistema sanitario internacional, para brindar soluciones tanto desde el diagnóstico y prevención como para el tratamiento de la población a fin de disminuir la mortalidad. Esto incluyó, obviamente también, al área de la Biotecnología aplicada a la salud, que ha aportado en los tres aspectos mencionados; el presente trabajo se centra en las respuestas de tipo terapéutico que ha brindado y que están comercializadas o en fases clínicas. (AU)

INTRODUCTION: A new coronavirus outbreak emerged in 2019 in Wuhan, China, causing a shock to the healthcare system around the world; the International Committee on Taxonomy of Viruses named it SARS-CoV- 2, the infectious agent of the COVID-19 disease. The spectrum of severity of the disease is very wide, most patients are not serious, but others can develop pneumonia, with acute respiratory failure being the most frequent cause of mortality. Objective: to analyze and develop the different therapeutic alternatives provided by Biotechnology dedicated to Health, to treat the symptoms of those COVID-19 patients who require it, and thus reduce mortality.Methodology: a review of the available literature from January 2020 in PubMed of the treatments that are still in clinical trials and those that have been approved under emergency use for the disease COVID-19 was performed. Searches were also carried out through Google and Google Scholar for publications of Health organizations in reference to health policies established for therapeutics during the mentioned pandemic. Results: this work addresses the new therapeutic alternatives derived from Biotechnology, which are both in use and in stages of clinical trials, to treat patients who developed COVID-19 included within the segment of biopharmaceuticals and biotherapies. A brief summary of the regulatory status of health entities, the mechanism of action of said therapies and general characteristics of each one is included. Innovative biotherapies that began to be implemented to face the pandemic are included. Conclusions: The coronavirus pandemic has driven the international health system to the test, to provide solutions both from the diagnosis, prevention and treatment of the population to reduce the mortality of patients. This obviously also included the area of Biotechnology applied to health, which has contributed in the three aspects mentioned. The present work focuses on the therapeutic responses that it has provided and that are commercialized or in clinical phases. (AU)

Uso de anticorpos monoclonais por pacientes com covid-19 interfere na concentração sérica de angiotensina II? / Does the use of monoclonal drugs by patients with COVID-19 interfere with the serum concentration of angiotensin II? / ¿El uso de fármacos monoclonales por pacientes con COVID-19 interfiere con la concentración sérica de angiotensina II?

Introdução:uma vez conhecidos os mecanismos de patogênese do SARS-CoV-2, vários métodos de tratamento para a COVID-19 foram desenvolvidos, dentre eles destaca-se o uso dos anticorpos monoclonais para o contexto de pacientes em estágios graves da doença. Objetivo: compreender se o uso dos anticorpos monoclonais para tratamento da COVID-19 grave interfere nos níveis séricos da angiotensina II. Metodologia:Para a realização dessa pesquisa foram selecionados através do DeCS e MeSH os descritores "COVID-19", "Angiotensin II" e "Antibodies, Monoclonal" e seus respectivos "entry terms" sugeridos pela base MeSH. Posteriormente,utilizando-se os operadores booleanos OR e AND, foi montada uma estratégia de busca, a qual foi utilizada nas bases de dados PUBMED, EMBASE, Web of Science, Cochrane Library e Scopus, sem restrição dedata de publicação ou idioma. Resultados:ao final do processo de seleção dos artigos, 29 foram selecionados para a leitura e análise completa. Nesta revisão, foram abordados diferentes tipos de anticorpos monoclonais, os quais foram oportunamente agrupados de acordo com o seu mecanismo de ação. Conclusão: foi possível concluir que das cinco classes de anticorpos monoclonais tratadas neste trabalho, três potencialmente podem causar alterações nos níveis séricos de angiotensina II (AU).

Introduction:once the mechanisms of pathogenesis of SARS-CoV-2 are known, several methods of treatment for COVID-19 have been developed, among them the use of monoclonal antibodies for the context of patients in severe stages of the disease. Purpose:to understand whether the use of monoclonal antibodies for the treatment of severe COVID-19 interferes with serum angiotensin II levels. Methodology:For this research were selected through DeCS and MeSH the descriptors "COVID-19", "Angiotensin II" and "Antibodies, Monoclonal" and their respective entry "Terms" suggested by the MeSH database. Subsequently, using the boolean operators OR and AND, a search strategy was set up, which was used in the databases PUBMED, EMBASE, Web of Science, Cochrane Library and Scopus, without restriction of publication date or language. Results:at the end of the article selection process, 29 were selected for reading and full analysis. In this review, different types of monoclonal antibodies were addressed, which were opportunely grouped according to their mechanism of action. Conclusion:it was possible to conclude that of the five classes of monoclonal antibodies treated in this study, three potentially can cause changes in serum levels of angiotensin II (AU).

Introducción:Una vez conocidos los mecanismos de patogénesis del SARSCoV-2, se desarrollaron variosmétodos de tratamiento para el COVID-19, entre ellos, el uso de anticuerpos monoclonales para el contexto de pacientes en fases graves de la enfermedad. Objetivo:Comprender si el uso de anticuerpos monoclonales para el tratamiento de la COVID-19 grave interfiere en los niveles séricos de angiotensina II. Metodología:Los descriptores "COVID-19", "Angiotensina II", "Anticuerpos, Monoclonales" y sus respectivos "entry terms" (términos de entrada) sugeridos por el MeSH fueron seleccionados a través de DeCS yMeSH. Posteriormente, utilizando los operadores booleanos OR y AND, se estableció una estrategia de búsqueda que se utilizó en las bases de datos PUBMED, EMBASE, Web of Science, Cochrane Library y Scopus, sin restricción de fecha de publicación ni de idioma. Resultados:Al final del proceso de selección de artículos, se seleccionaron 29 artículos para su lectura y análisis completos. En esta revisión se han abordado diferentes tipos de anticuerpos monoclonales, que se han agrupado oportunamente según su mecanismo de acción. Conclusión:Se pudo concluir que de las cinco clases de anticuerpos monoclonales tratados en este trabajo, tres pueden potencialmente causar alteraciones en los niveles séricos de angiotensina II (AU).

Marital betrayal, culture and prejudice.

In our consulting rooms we find, depending on the period, certain conditions that relate closely to current cultural prejudices. In our culture, divorce and the reconstituted family can bring both creativity but also emotional difficulty, often triggered by marital betrayal. This paper explores marital betrayal in relation to childhood experiences of fidelity, infidelity and the lack of love. It asks whether there is a cultural prejudice related to marital fidelity, and whether sexuality only belongs in a loving couple, whether this is a patriarchal contract, and what role the anima plays in a loving bond; this is related to 'altericide' and need for respect for the other, as the libido seeks 'living symbols'.

Suivant les périodes, nous retrouvons dans nos salles de consultation des situations qui ont beaucoup à voir avec les préjudices culturels en vigueur. Dans notre culture le divorce et la famille reconstituée peuvent apporter à la fois de la créativité et de la difficulté émotionnelle, souvent déclenchée par la trahison dans le couple. Cet article explore la trahison dans le couple en relation avec les expériences infantiles de fidélité, d'infidélité, et de manque d'amour. L'article s'interroge: y-a-t-il un préjudice culturel lié à la fidélité dans le couple? La sexualité appartient-elle seulement à un couple qui éprouve de l'amour? S'agit-il là d'un contrat patriarcal? Et quel rôle joue l'anima dans une relation aimante? Ceci est mis en lien avec « l'altéricide ¼ et le besoin de respect à l'égard de l'autre, alors que la libido recherche des « symboles vivants ¼.

Encontramos en nuestros consultorios, dependiendo del período, ciertas condiciones que se relacionan cercanamente con prejuicios culturales vigentes. En nuestra cultura, el divorcio y la familia reconstituida puede brindar tanto creatividad como dificultades emocionales, a menudo ambas activadas por la traición marital. El presente trabajo explora la traición marital con relación a experiencias infantiles de fidelidad, infidelidad, y de falta de amor. Pregunta si existe un prejuicio cultural respecto a la fidelidad marital, si la sexualidad solamente pertenece a la pareja amorosa, si ésta es un contrato patriarcal y que rol juega el ánima en un vínculo amoroso. Esto está relacionado al 'altericidio' y a la necesidad de respeto por el otro, a medida que la libido busca 'símbolos vivos'.

Em nossas salas de consultório encontramos, dependendo do período, certas condições que se relacionam intimamente com os preconceitos culturais atuais. Em nossa cultura, o divórcio e a família reconstituída podem trazer criatividade, mas também dificuldade emocional, muitas vezes desencadeada pela traição conjugal. Este artigo explora a traição conjugal em relação às experiências infantis de fidelidade, infidelidade e falta de amor. Pergunta se há um preconceito cultural relacionado à fidelidade conjugal e se a sexualidade pertence apenas a um casal amoroso, se este é um contrato patriarcal e qual papel a anima desempenha em um vínculo amoroso; isso está relacionado ao "altericídio" e à necessidade de respeito pelo outro, já que a libido busca "símbolos vivos".

Creating our own Black Books: keeping a journal as a loom of life.

Jung's The Black Books are annotations of his inner world after his process of self-experimentation, which he called his 'confrontation with the unconscious'. They preceded The Red Book in which, as a scribe, he reworked his initial notes and drawings. This was the raw material for the work that Jung developed over the rest of his life. From his experimentation, he formulated the method of active imagination and the concept of the transcendent function, a psychological function that creates symbols and integrates the unconscious contents in consciousness. Jung invites us, with his experience, to write and paint our own Black Books and to explore our inner images. With this proposal to keep a journal as a loom of life, we welcome his invitation, which allows us to weave and integrate the visible and invisible substances of our lives. Our intention for the journalling is to provide a space for the unfolding of the individuation process. In Jung's invitation we see that a life that does not confront itself cannot be realized as such.

Les Livres Noirs de Jung sont des annotations sur son monde intérieur suite à son processus d'expérimentation sur lui-même, qu'il a appelé sa « confrontation avec l'inconscient ¼. Ils ont précédé le Livre Rouge dans lequel, comme un scribe, il retravailla ses notes et dessins initiaux. Ce fut le matériel brut pour le travail que Jung développa jusqu'à la fin de sa vie. A partir de son expérimentation, il formula la méthode d'imagination active et le concept de fonction transcendante, une fonction psychologique qui crée des symboles et intègre les contenus inconscients dans la conscience. Par son expérience Jung nous invite à écrire et à peindre nos propres Livres Noirs et à explorer nos images intérieures. Avec cette proposition de tenir un journal en tant que métier à tisser de la vie, nous accueillons son invitation, qui nous permet de tisser et d'intégrer les substances visibles et invisibles de nos vies. Notre intention dans cette expérience de tenir un journal est de fournir un espace pour le déploiement du processus d'individuation. Dans l'invitation de Jung nous voyons qu'une vie qui ne se confronte pas à elle-même ne peut pas se réaliser en tant que telle.

Los Libros Negros de Jung son anotaciones de su mundo interno tras su proceso de auto experimentación, al que denominó su "confrontación con lo inconsciente". Estos antecedieron al Libro Rojo, en el que como un escriba reelaboraba sus notas y dibujos iniciales. Esta fue la materia prima del trabajo que Jung desarrolló por el resto de su vida. A partir de su experimentación formuló el método de la imaginación activa y el concepto de la función transcendente, función psicológica creadora de símbolos e integradora de contenidos inconscientes en la conciencia. Jung nos invita con su experiencia a escribir nuestros propios Libros Negros y a explorar nuestras imágenes interiores. Con nuestra propuesta de llevar un diario como telar de la vida hemos acogido esta invitación, que nos permite, tejer e integrar la sustancia visible e invisible de nuestras vidas. Nuestra intención con el diario es facilitar un espacio para el desenvolvimiento del proceso de individuación. En la invitación de Jung vemos que una vida que no se confronte consigo misma, no se puede realizar como tal.

Os Livros Negros de Jung são anotações de seu mundo interior após seu processo de autoexperimentação, que ele chamou de seu "confronto com o inconsciente". Eles precederam o Livro Vermelho no qual, como escriba, ele reformulou suas notas e desenhos iniciais. Esta foi a matéria-prima para o trabalho que Jung desenvolveu pelo resto de sua vida. A partir de sua experimentação, ele formulou o método da imaginação ativa e o conceito de função transcendente, uma função psicológica que cria símbolos e integra os conteúdos inconscientes na consciência. Jung nos convida, com sua experiência, a escrever e pintar nossos próprios Livros Negros e explorar nossas imagens internas. Com esta proposta de manter um diário como um tear da vida, saudamos seu convite, que nos permite tecer e integrar as substâncias visíveis e invisíveis de nossas vidas. Nossa intenção para o diário é fornecer um espaço para o desdobramento do processo de individuação. No convite de Jung, vemos que uma vida que não se confronta não pode ser realizada como tal.

Future assessment of the impact of the COVID-19 pandemic on the electricity market based on a stochastic socioeconomic model.

This paper proposes a time-series stochastic socioeconomic model for analyzing the impact of the pandemic on the regulated distribution electricity market. The proposed methodology combines the optimized tariff model (socioeconomic market model) and the random walk concept (risk assessment technique) to ensure robustness/accuracy. The model enables both a past and future analysis of the impact of the pandemic, which is essential to prepare regulatory agencies beforehand and allow enough time for the development of efficient public policies. By applying it to six Brazilian concession areas, results demonstrate that consumers have been/will be heavily affected in general, mainly due to the high electricity tariffs that took place with the pandemic, overcoming the natural trend of the market. In contrast, the model demonstrates that the pandemic did not/will not significantly harm power distribution companies in general, mainly due to the loan granted by the regulator agency, named COVID-account. Socioeconomic welfare losses averaging 500 (MR$/month) are estimated for the equivalent concession area, i.e., the sum of the six analyzed concession areas. Furthermore, this paper proposes a stochastic optimization problem to mitigate the impact of the pandemic on the electricity market over time, considering the interests of consumers, power distribution companies, and the government. Results demonstrate that it is successful as the tariffs provided by the algorithm compensate for the reduction in demand while increasing the socioeconomic welfare of the market.

Implicações da COVID-19 no Sistema Cardiovascular: uma Revisão de Literatura / Implications of COVID-19 on the Cardiovascular System: a Literature Review

Introdução: O novo coronavírus da Síndrome Respiratória Aguda Grave 2 (SARS-CoV-2), responsável pela Doença do Coronavírus 2019 (COVID-19), é um vírus capaz de causar pneumonia viral, além de complicações extrapulmonares. Revisou-se conceitos básicos sobre a COVID-19, focando nos seus efeitos sobre o sistema cardiovascular. Métodos: Realizou-se revisão de literatura a partir de buscas nas bases de dados PUBMED, Scielo e LILACS entre Janeiro de 2019 a Maio de 2020, com as palavras chaves: "COVID-19" AND "Cardiovascular" e seus correlatos em português e inglês. Foram excluídos estudos repetidos, relatos de caso, estudos experimentais em animais, cartas ao editor, comentários, estudos não disponíveis em inglês ou português e os que limitavam-se à terapêutica da doença. Selecionaram-se estudos observacionais, estudos descritivos, revisões de literatura e revisões sistemáticas. Resultados: A ligação entre a injúria miocárdica e a infecção pelo novo coronavírus é consequência, em grande parte, da sua relação fisiopatológica com o receptor ECA-2, interação capaz de desequilibrar os sistemas imune e cardiovascular. As complicações mais comuns incluem arritmia, lesão cardíaca, miocardite fulminante, insuficiência cardíaca, embolia pulmonar e Coagulação Intravascular Disseminada (CIVD). Ademais, pacientes com condições cardíacas prévias possuem risco aumentado, inclusive para morbimortalidade hospitalar. Conclusão: Conclui-se que a COVID-19 é uma doença com tropismo por vários órgãos, capaz de gerar agressões em diversos sistemas, entre eles, o cardiovascular, cujos danos se devem a mecanismos que afetam tanto a estrutura do miocárdio quanto dos vasos, podendo levar ao óbito. Desta forma, há necessidade de avaliação precoce e monitoramento contínuo dos danos cardíacos.

Immunolocalization of angiotensin-(1-7), angiotensin II and angiotensin- converting enzyme 2 in goat ovary / Imunolocalização de angiotensina-(1-7), angiotensina II e enzima-conversora de angiotensina 2 em ovário de cabras

There is increasing evidence as to the participation of the ovarian renin-angiotensin system in important reproductive processes. The inhibition of the angiotensin-converting enzyme (ACE) caused an increase in the rate of ovulation and pregnancy in the artificial insemination protocol has fixed time (TFIA). This study aimed to investigate the presence and location of Ang II, Ang- (1-7) and ACE2 in goat ovaries and the possibility of the involvement of these peptides in previous results. Ten ovaries from goats were collected in a slaughterhouse, washed in buffered PBS, perfused with protease inhibitor solution and processed for immunohistochemistry protocol. The search for peptides was performed using the avidin–biotin–peroxidase method. A strong immunoreactivity for Ang II in theca cells of antral follicles and corpus luteum was observed. Antral follicles (theca cells), corpus luteum and oocyte cytoplasm in early antral follicles exhibited strong immunoreactivity for Ang-(1-7). There was strong immunoreactivity for ACE2 in the cytoplasm of luteal cells and theca cells of antral follicles. In this study, for the first time, the presence and location of Ang II, Ang-(1-7) and ACE2 are reported in goat ovary, suggesting that there is participation in follicular development, oocyte maturation and corpus luteum development.

Há evidências crescentes quanto à participação do sistema renina-angiotensina ovariano em processos reprodutivos importantes. A inibição da enzima conversora de angiotensina (ECA) ocasionou aumento na taxa de ovulação e gravidez no protocolo de inseminação artificial por tempo fixo (TFIA). Este estudo teve como objetivo investigar a presença e localização de Ang II, Ang-(1-7) e ECA2 em ovários de cabras e a possibilidade do envolvimento desses peptídeos em resultados anterio-res. Dez ovários de cabras foram coletados em abatedouro, lavados em PBS tamponado, perfundidos com solução inibidora de protease e processados para protocolo de imunohistoquímica. A busca por peptídeos foi realizada usando o método avidina-bio-tina-peroxidase. Foi observada uma forte imunorreatividade para Ang II em células da teca de folículos antrais e corpo lúteo. Os folículos antrais (células da teca), corpo lúteo e citoplasma do oócito nos folículos antrais iniciais exibiram forte imunor-reatividade para Ang-(1-7). Houve forte imunorreatividade para ECA2 no citoplasma das células luteais e células da teca dos folículos antrais. Neste estudo, pela primeira vez, a presença e localização de Ang II, Ang- (1-7) e ECA2 são relatadas em ovário caprino, sugerindo que há participação no desenvolvimento folicular, maturação oocitária e desenvolvimento do corpo lúteo.

Immunolocalization of angiotensin-(1-7), angiotensin II and angiotensin- converting enzyme 2 in goat ovary / Imunolocalização de angiotensina-(1-7), angiotensina II e enzima-conversora de angiotensina 2 em ovário de cabras

There is increasing evidence as to the participation of the ovarian renin-angiotensin system in important reproductive processes. The inhibition of the angiotensin-converting enzyme (ACE) caused an increase in the rate of ovulation and pregnancy in the artificial insemination protocol has fixed time (TFIA). This study aimed to investigate the presence and location of Ang II, Ang- (1-7) and ACE2 in goat ovaries and the possibility of the involvement of these peptides in previous results. Ten ovaries from goats were collected in a slaughterhouse, washed in buffered PBS, perfused with protease inhibitor solution and processed for immunohistochemistry protocol. The search for peptides was performed using the avidin–biotin–peroxidase method. A strong immunoreactivity for Ang II in theca cells of antral follicles and corpus luteum was observed. Antral follicles (theca cells), corpus luteum and oocyte cytoplasm in early antral follicles exhibited strong immunoreactivity for Ang-(1-7). There was strong immunoreactivity for ACE2 in the cytoplasm of luteal cells and theca cells of antral follicles. In this study, for the first time, the presence and location of Ang II, Ang-(1-7) and ACE2 are reported in goat ovary, suggesting that there is participation in follicular development, oocyte maturation and corpus luteum development.(AU)

Há evidências crescentes quanto à participação do sistema renina-angiotensina ovariano em processos reprodutivos importantes. A inibição da enzima conversora de angiotensina (ECA) ocasionou aumento na taxa de ovulação e gravidez no protocolo de inseminação artificial por tempo fixo (TFIA). Este estudo teve como objetivo investigar a presença e localização de Ang II, Ang-(1-7) e ECA2 em ovários de cabras e a possibilidade do envolvimento desses peptídeos em resultados anterio-res. Dez ovários de cabras foram coletados em abatedouro, lavados em PBS tamponado, perfundidos com solução inibidora de protease e processados para protocolo de imunohistoquímica. A busca por peptídeos foi realizada usando o método avidina-bio-tina-peroxidase. Foi observada uma forte imunorreatividade para Ang II em células da teca de folículos antrais e corpo lúteo. Os folículos antrais (células da teca), corpo lúteo e citoplasma do oócito nos folículos antrais iniciais exibiram forte imunor-reatividade para Ang-(1-7). Houve forte imunorreatividade para ECA2 no citoplasma das células luteais e células da teca dos folículos antrais. Neste estudo, pela primeira vez, a presença e localização de Ang II, Ang- (1-7) e ECA2 são relatadas em ovário caprino, sugerindo que há participação no desenvolvimento folicular, maturação oocitária e desenvolvimento do corpo lúteo.(AU)

COVID-19 from a cardiovascular perspective / COVID-19 desde una perspectiva cardiovascular

Currently, myocardial injury has been reported in patients hospitalized with coronavirus disease 2019 (COVID-19). The studies also show a correlation between cardiac events and severe forms of the disease. COVID-19 begins with an early infection phase in which the virus infiltrates the lung parenchyma and proliferates. It then progresses to the pulmonary phase, where the initial inflammatory process, characterized by vasodilation, vascular permeability, and leukocyte recruitment, leads to lung damage, hypoxemia, and cardiovascular stress. The renin angiotensin aldosterone system is important in the pathophysiology of severe acute respiratory syndrome coronavirus 2 infection and in the propagation of systemic inflammation. Within this system, the pathway mediated by angiotensin-converting enzyme 2 (ACE2) produces vasodilation, cardioprotection, anti-oxidation, and anti-inflammation. Furthermore, the free form of ECA2 prevents binding of the virus to host cells and reduces its damage to the lung.

Actualmente, se ha reportado injuria miocárdica en pacientes hospitalizados por enfermedad por coronavirus 2019 (COVID-19). Los estudios, además, demuestran una correlación entre los eventos cardiacos y formas severas de la enfermedad. La COVID-19 comienza con una fase de infección temprana en la que el virus infiltra el parénquima pulmonar y prolifera. Luego progresa a la fase pulmonar, donde el proceso inflamatorio inicial, caracterizado por vasodilatación, permeabilidad vascular y reclutamiento de leucocitos, lleva a daño pulmonar, hipoxemia y estrés cardiovascular. El sistema renina angiotensina aldosterona es importante en la fisiopatología de la infección por el coronavirus 2 del síndrome respiratorio agudo grave y en la propagación de la inflamación sistémica. Dentro de este sistema, la vía mediada por la enzima convertidora de angiotensina 2 (ECA2) produce vasodilatación, cardioprotección, antioxidación y antiinflamación. Además, la forma libre de la ECA2 previene la unión del virus a las células huésped y reduce su daño al pulmón.

SARS-CoV-2 impact on oral health: a general view / Impacto del SARS-CoV-2 en la salud oral: una visión general

Abstract Coronavirus disease 2019 (COVID-19) is a new disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. China reported the first case of COVID-19 in December 2019, and a few months later, the World Health Organization declared it as a pandemic. Oral ulcers in adult patients have been associated with COVID-19. However, no cases have yet been documented in children. The angiotensin-converting enzyme-2 (ACE2) receptor has been identified in tissues of the oral cavity. Studies have identified the tongue as the site with the highest expression of ACE2, and the oral epithelium, gingival epithelium, and salivary glands as sites of lesser extent expression. ACE2 expression is lower in children and varies with age. SARS-CoV-2 in saliva has been identified in various studies, which suggests that this could be a useful sample for diagnosis. However, its presence in saliva would indicate the high risk of contagion of this fluid.

Resumen La COVID-19 es una nueva enfermedad causada por el SARS-CoV-2 (coronavirus tipo 2 del síndrome respiratorio agudo grave). El primer caso de COVID-19 se reportó en China en diciembre de 2019, y unos meses después la Organización Mundial de la Salud la declaró como una pandemia. En pacientes adultos se han asociado úlceras orales a la COVID-19; en niños aún no se han documentado casos. El receptor de la enzima convertidora de la angiotensina 2 (ECA2) se ha identificado en tejidos de la cavidad oral. Los estudios han identificado que la lengua es el sitio con mayor expresión del receptor de la ECA2, y el epitelio bucal, el epitelio gingival y las glándulas salivales lo son en menor medida. La expresión de la ECA2 es menor en los niños y va aumentando con la edad. En diversos estudios se ha identificado el SARS-CoV-2 en la saliva, lo que sugiere que podría ser una muestra útil para el diagnóstico de este virus. Sin embargo, su presencia en saliva indicaría un alto riesgo de contagio de este fluido.

A biotechnological tool for glycoprotein desialylation based on immobilized neuraminidase from Clostridium perfringens.

BACKGROUND: Sialic acids are widely distributed in nature and have biological relevance owing to their varied structural and functional roles. Immobilized neuraminidase can selectively remove terminal N-acetyl neuraminic acid from glycoproteins without altering the protein backbone while it can be easily removed from the reaction mixture avoiding sample contamination. This enables the evaluation of changes in glycoprotein performance upon desialylation. METHODS: Neuraminidase was immobilized onto agarose activated with cyanate ester groups and further used for desialylation of model glycoproteins, a lysate from tumour cells and tumour cells. Desialylation process was analysed by lectin binding assay, determination of sialyl-Tn or flow cytometry. RESULTS: Clostridium perfringens neuraminidase was immobilized with 91 % yield and expressed activity yield was of 41%. It was effective in the desialylation of bovine fetal serum fetuin, bovine lactoferrin and ovine submaxilar mucin. A decrease in sialic-specific SNA lectin recognition of 83% and 53 % was observed for fetuin and lactoferrin with a concomitant increase in galactose specific ECA and PNA lectin recognition. Likewise, a decrease in the recognition of a specific antibody (82%) upon mucin desialylation was observed. Moreover, desialylation of a protein lysate from the sialic acid-rich cell line TA3/Ha was also possible leading to a decrease in 47 % in SNA recognition. Immobilized neuraminidase kept 100% of its initial activity upon five desialylation cycles. CONCLUSIONS: Immobilized neuraminidase is an interesting as well as a robust biotechnological tool for enzymatic desialylation purposes. GENERAL SIGNIFICANCE: Immobilized neuraminidase would contribute to understand the role of sialic acid in biological processes.

Na covid-19 é real a não suspensão dos inibidores do sistema renina angiotensina aldosterona? / In covid-19, the non-suspension of inhibitors of the renina angiotensin aldosterone system is real?

A interação dos bloqueadores do sistema renina angiotensina com o SARS-CoV-2 permanece obscura. Os inibidores do sistema renina angiotensina aldosterona (IECAs) e os bloqueadores do receptor AT1 da angiotensina 2 (BRAs) são fármacos com evidências robustas para terapia farmacológica de pacientes portadores, principalmente de hipertensão arterial e insuficiência cardíaca, além de outras comorbidades cardiovasculares. Os pacientes que se beneficiam desta terapêutica são considerados grupos de risco para má evolução desta virose e não há na literatura um consenso a respeito desta questão, em vista do vírus utilizar a expressão da ECA2 para penetração no ser humano. Apesar destas considerações fisiopatológicas da biologia do vírus, as principais diretrizes recomendam não suspender a terapia dos pacientes em uso dos bloqueadores do sistema renina angiotensina aldosterona no curso da infecção com o COVID-19. Aditivamente, o estudo BRACE-CORONA trouxe evidências mais consistentes para não suspensão desses fármacos

The interaction of blockers of the renin angiotensin system with SARS-COV-2 remains unclear. Inhibitors of the renin angiotensin aldosterone system (ACE inhibitors) and angiotensin 2 AT1 receptor blockers (BRAs) are drugs with robust evidence for pharmacological therapy for patients with mainly arterial hypertension and heart failure, and other cardiovascular comorbidities. Patients who benefit from this therapy are considered groups at risk for poor evolution of this virus and the literature still does not have a consensus on this issue, in view of the virus using the expression of ECA2 to penetrate in humans. Despite these athophysiological considerations of the biology of the virus, the main guidelines recommend not to suspend therapy for patients using blockers of the renin angiotensin aldosterone system in the course of infection with COVID-19. In addition, the BRACE corona study has more consistent evidence for not suspending these drugs.