Biomechanical Effects of Angiotensin 1-7 in Diabetes Rats Femur / Efectos Biomecánicos de la Angiotensina 1-7 en el Fémur de Ratas Diabéticas

SUMMARY: It is known that diabetes mellitus has late complications, including microvascular and macrovascular diseases. Diabetes can affect bones through biochemical markers of bone structure, density, and turnover. This study aimed to biomechanically investigate the bone-protective effects of angiotensin 1-7 (Ang 1-7), one of the active peptides in the renin-angiotensin system, in rats with diabetes. Thirty male Wistar albino rats, three months old and weighing 250-300 g, were divided into four groups: diabetes, Ang 1- 7, diabetes plus Ang 1-7, and control. One month later, diabetes developed in rats; the rats were sacrificed, and their right femur was removed. Three-point bending biomechanical tests were performed on the femurs. The diabetic group had significantly higher bone fragility than the other groups (Pr >.05). Bone fragility was lower, and bone flexibility was higher in the Ang 1-7 groups (Pr>F value 0.05). As a result of our study, the effect of Ang 1-7 on the bones of rats with diabetes was investigated biomechanically. Ang 1-7 has a protective impact on the bones of rats with diabetes.

Se sabe que la diabetes mellitus tiene complicaciones tardías, incluyendo enfermedades microvasculares y macrovasculares. La diabetes puede afectar los huesos a través de los marcadores bioquímicos de la estructura, la densidad y el recambio óseo. Este estudio tuvo como objetivo investigar biomecánicamente los efectos protectores en los huesos de la angiotensina 1-7 (Ang 1-7), uno de los péptidos activos en el sistema renina-angiotensina, en ratas con diabetes. Treinta ratas albinas Wistar macho, de tres meses de edad y con un peso de 250-300 g, se dividieron en cuatro grupos: diabetes, Ang 1-7, diabetes más Ang 1-7 y control. Un mes después, se desarrolló diabetes en ratas; se sacrificaron los animales y se extrajo su fémur derecho. Se realizaron pruebas biomecánicas de flexión de tres puntos en los fémures. El grupo diabéticos tenía una fragilidad ósea significativamente mayor que los otros grupos (Pr > 0,05). La fragilidad ósea fue menor y la flexibilidad ósea fue mayor en los grupos Ang 1-7 (valor Pr>F 0,05). Como resultado de nuestro estudio, se determinó biomecánicamente el efecto de Ang 1-7 en los huesos de ratas con diabetes. Se concluye que Ang 1-7 tiene un impacto protector en los huesos de ratas diabéticas.

Respiratory muscles: structure, function and relationship with the ACE gene: a brief morphofunctional communication / Músculos respiratorios: estructura, función y relación con el gen de la ECA: una breve comunicación morfofuncional

SUMMARY: Pulmonary ventilation is a mechanical process in which the respiratory muscles act in coordination to maintain the oxygenation of the organism. Any alteration in the performance of these muscles may reduce the effectiveness of the process. The respiratory muscles differ from the other skeletal muscles in the vital support that they provide through rhythmiccontractions. The structure and energy system of the muscles are specially adapted to perform this function. The composition of the respiratory muscles is exceptional; they are small, and present an abundant capillary network, endowing them with a high aerobic level and resistance to fatigue. Coordinated regulation of the local renin-angiotensin system provides proper blood flow and energy supply in the myofibrils of the skeletal muscle tissue. Specifically, this performance will depend to a large extent on blood flow and glucose consumption, regulated by the renin-angiotensin system. The angiotensin converting enzyme is responsible for degrading kinins, which finally regulate muscle bioenergy and glucose between the blood vessel and the skeletal muscle. The objective of this review is to describe the structure of the respiratory muscles and their association with the angiotensin converting enzyme gene.

La ventilación pulmonar es un proceso mecánico en el que los músculos respiratorios actúan coordinadamente para mantener la oxigenación en el organismo. Así, cualquier alteración en el desempeño de estos músculos puede reducir la efectividad del proceso. Los músculos respiratorios se diferencian de otros músculos esqueléticos, debido al apoyo vital que brindan a través de sus contracciones rítmicas. La estructura y el sistema energético de estos músculos están especialmente adaptados para realizar esta función. La composición de los músculos respiratorios es especial; son pequeñas y presentan una abundante red capilar, lo que les otorga un alto nivel aeróbico y resistencia a la fatiga. La regulación coordinada del sistema renina-angiotensina local, proporciona un adecuado flujo sanguíneo y suministro de energía a las miofibrillas del músculo esquelético. En concreto, este rendimiento dependerá en gran medida del flujo sanguíneo y del consumo de glucosa, regulado por el sistema renina-angiotensina. Aquí, la enzima convertidora de angiotensina es responsable de degradar las kininas, que finalmente regulan la bioenergía muscular y la glucosa entre el vaso sanguíneo y el músculo esquelético. El objetivo de esta breve comunicación es describir la estructura de los músculos respiratorios y su asociación con el gen de la enzima convertidora de angiotensina.

Role of Brain Angiotensin-II in Development of Experimental Diabetic Nephropathy in Wistar Rats

Abstract The renin-angiotensin-aldosterone system (RAAS) plays a key role in diabetic nephropathy (DN). Angiotensin-II secreted during the RAAS pathway increases nephropathy. It stimulates oxidative stress which can quench nitric oxide. Reduced nitric oxide level aggravates Ang-II-induced vasoconstriction. Ang-II has also emerged as a central mediator of the glomerular hemodynamic changes that are associated with renal injury. Deletion of ACE2 is also noted due to increased Ang-II level which leads to the development of DN. We hypothesize that nephropathy caused by Ang-II in the periphery may be controlled by brain RAAS. ACE inhibitors and ARBs may show the renoprotective effect when administered through ICV without crossing the blood-brain barrier. DN was observed after 8 weeks of diabetes induction through alloxan. Administration of captopril and valsartan once and in combined therapy for 2 weeks, significantly reduced urine output, blood urea nitrogen, total protein in the urine, serum cholesterol, serum creatinine, serum triglycerides, and kidney/body weight ratio as compared to diabetic control rats. Further, combination therapy significantly increased the body weight and serum nitrate level as compared to diabetic control animals. However, increased ACE2 levels in the brain may reduce the sympathetic outflow and might have decreased the peripheral activity of Ang-II which shows beneficial effects in DN.

Can SARS-CoV-2 induce hematologic malignancies in predisposed individuals? A case series and review of the literature

Abstract Introduction Coronavirus disease 2019 (COVID-19) may present with extrapulmonary manifestations, including hematologic changes. Previous studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) can interact with the renin-angiotensin system, ultimately causing increased production of angiotensin II. By reporting the cases of previously healthy young adults diagnosed with a hematologic malignancy after experiencing COVID-19, we raise the hypothesis that the SARS-Cov-2 infection could act as a trigger for leukemogenesis in predisposed individuals. Methods This was a case series performed through extraction of relevant clinical information from the medical records of three patients admitted to our Hematology unit between August 2020 and September 2020. Main Results Considering the relatively rapid development of cytopenias following recovery from COVID-19, it cannot be ruled out that SARS-Cov-2 played a role in leukemogenesis in those patients. Based on previous in vitro studies, the renin-angiotensin system imbalance induced by SARS-CoV-2 could potentially promote in vivo leukemogenesis through several mechanisms. Conclusion Despite the advances in pathophysiological and clinical characterization of COVID-19, the consequences of the pandemic to the incidence of hematologic diseases are still to be elucidated. In this context, future dissection of the status of the local bone marrow renin-angiotensin system in leukemogenesis is a clinically relevant basic research area.

Sistema Renina Angiotensina Aldosterona em mulheres que utilizam contraceptivo hormonal injetável: protocolo de um estudo observacional comparativo de corte transversal / Renin Angiotensin Aldosterone System in women using injectable hormonal contraceptive: protocol of a comparative observational study of cross-sectional

INTRODUÇÃO: Os contraceptivos orais são a forma mais utilizada para o controle de natalidade, chegando a 200 milhões de usuárias desde sua iniciação na década de 1960. Desde 2013, nosso grupo de pesquisa tem apresentado resultados que sugerem que mulheres em uso de Contraceptivos Orais Combinados (COC), e sem outros fatores de risco, apresentam maior valor de proteína C reativa, lipemia pós-prandial, lipoproteína de baixa densidade oxidada e diminuição da sensibilidade insulínica, quando comparadas a suas congêneres sem uso de COC. Recentemente, foi verificado que o uso de COC eleva os valores de renina plasmática em 600%, podendo explicar por que o uso desse fármaco é um fator de risco para o desenvolvimento de hipertensão arterial sistêmica. Apesar de o uso de Contraceptivo Hormonal Injetável (CHI) estar aumentando, não encontramos estudos clínicos que abordassem o tema, demonstrando uma lacuna na literatura científica. OBJETIVO: Comparar os valores de renina plasmática, enzima conversora de angiotensina 1 e aldosterona de mulheres que utilizam CHI com mulheres que não utilizam nenhum contraceptivo à base de hormônio. MÉTODOS: Protocolo de um estudo observacional comparativo de corte transversal, composto por mulheres com idade entre 18 e 30 anos, eutróficas, irregularmente ativas pelo Questionário Internacional de Atividade Física, versão curta, que estão em uso continuado de CHI há pelo menos 6 meses ou que não fazem uso. A amostra será por conveniência, as participantes selecionadas assinarão o termo de consentimento livre e esclarecido. Posteriormente, responderão a um questionário padrão, serão submetidas a um exame físico, e serão encaminhadas para coleta das amostras sanguíneas.

INTRODUCTION: Oral contraceptives are the most widely used form of birth control, reaching 200 million users since its inception in the 1960. Since 2013, our research group has presented results that suggest that women using Combined Oral Contraceptives (COC) and without other risk factors, have a higher value of C-reactive protein, postprandial lipemia, oxidized low-density lipoprotein and decreased insulin sensitivity, when compared to their counterparts without the use of COC. Recently, it was found that the use of COC increases plasma renin values by 600%, which may explain why the use of this drug is a risk factor for the development of systemic arterial hypertension. Although the use of Injectable Hormonal Contraceptives (IHC) is increasing, we have not found clinical studies that addressed the topic, demonstrating a gap in the scientific literature. OBJECTIVE: Compare the values of plasma renin, angiotensin-converting enzyme 1 and aldosterone of women using IHC with women who do not use any hormone-based contraceptives. METHODS: Protocol of a comparative observational cross-sectional study, composed of women aged between 18 and 30 years, eutrophic, irregularly active by the International Physical Activity Questionnaire, short version, who have been in continuous use of IHC for at least 6 months or that do not use. The sample will be for convenience and the selected participants will sign the informed consent form. Subsequently, they will answer a standard questionnaire, undergo a physical examination, and be sent to collect blood samples.

O papel dos inibidores da enzima conversora de angiotensina e dos antagonistas dos receptores de angiotensina em pacientes com Covid-19: uma revisão narrativa / The role of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Antagonists in patients with Covid-19: a narrative review

O objetivo deste trabalho é reunir e discutir os principais achados científicos, opiniões de especialistas e considerações de comunidades médicas a respeito da continuação do tratamento de pacientes hipertensos diagnosticados com Covid-19 em uso de anti-hipertensivos. Trata-se de uma revisão narrativa de literatura, restringida a publicações até abril de 2020, utilizando as bases de dados Medline e Embase e consulta a quatro sociedades científicas de Cardiologia. Um total de 93 publicações foram encontradas nas bases de dados consultadas, e, destas, nove publicações foram elegíveis para análise, sendo que seis publicações se mostraram favoráveis à continuação do tratamento com inibidores da enzima conversora de angiotensina e antagonistas dos receptores de angiotensina, o que foi ao encontro das recomendações das sociedades de Cardiologia; outras três publicações sugeriram que essas classes de anti-hipertensivos podem aumentar a gravidade da infecção. A continuação do tratamento com anti-hipertensivos durante a pandemia de coronavírus ou após o diagnóstico da infecção apresenta um paradoxo entre o potencial aumento da patogenicidade viral e a proteção pulmonar conferida pelo equilíbrio do sistema renina-angiotensina.

The objective of this work is to gather and discuss the main scientific findings, opinions and specialists in medical communities and respect for the continuation of treatment with antihypertensive drugs in hypertensive patients diagnosed with Covid-19. This is a narrative review of the literature, restricted to publications until April 2020, using Medline and Embase as a database and consulting four scientific societies of cardiology. A total of 93 publications were found in the databases consulted and of these, 9 publications were eligible for analysis, with six publications being considered favorable for the continuation of treatment with angiotensin-converting enzyme inhibitors and receptor antagonists angiotensin, which met the decisions of cardiology societies; three other publications suggested that these classes of antihypertensives may increase the severity of the infection. The continuation of treatment with antihypertensive drugs during a coronavirus pandemic or after the diagnosis of infection presents a paradox between the potential increase in viral pathogenicity and the pulmonary protection provided by the balance of the renin-angiotensin system.

Papel do imunometabolismo, receptores Toll-Like e ECA 2 na COVID-19 / Role of immunometabolism, Toll-Like receptors, and ACE-2 in COVID-19

No combate à infecção pelo coronavírus 2 da síndrome respiratória aguda grave (SARS-CoV-2), o organismo se utiliza de mecanismos da imunidade inata, dentre eles os receptores Toll- Like (TLR), responsáveis pela sinalização da inflamação através da liberação de mediadores químicos e recrutamento de células imunitárias. Na patologia causada pela doença do SARS-CoV-2 2019 (COVID-19), ganha especial importância o TLR-4, visto que a sua estimulação exacerbada vem sendo relacionada ao estado hiperinflamatório em fases avançadas da COVID-19. Outro receptor que desempenha um papel primordial na infecção pelo SARS-CoV-2, servindo como porta de entrada para o vírus e progressão da doença, é a enzima conversora de angiotensina 2 (ECA 2), cuja ligação com a proteína S viral causa desregulação de vários sistemas fundamentais para a homeostase, como o sistema renina-angiotensina-aldosterona. Pacientes com doenças cardiometabólicas como obesidade, diabetes, aterosclerose e hipertensão vêm sendo classificados como alto risco para desenvolver as formas graves da COVID-19, visto que o estado inflamatório, já existente nessas doenças, pode ser agravado pelo desequilíbrio metabólico causado pelo SARS-CoV-2. A elucidação desses e de outros mecanismos relacionados à fisiopatologia da COVID-19 é imprescindível para uma melhora na estratificação de risco, nas escolhas terapêuticas e no prognóstico desses pacientes. Desta forma, nesta revisão objetivamos discutir as relações entre TLR-4, ECA 2, doenças cardiometabólicas, infecção pelo SARS-CoV-2 e gravidade da COVID-19.

In the fight against the infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the body uses mechanisms from the innate immune system, such as Toll-Like receptors (TLR), responsible for inflammation signaling through release of chemical mediators and recruitment of immune cells. In the disease caused by SARS-CoV-2 (COVID-19), TLR-4 assumes special importance because its exacerbated stimulation has been related to a hyperinflammatory state in advanced stages of COVID-19. Another receptor that plays a major role in SARS-CoV-2 infection, serving as a gateway to the virus and impacting disease progression, is angiotensin-converting enzyme 2 (ACE-2), whose binding to the viral S protein causes dysregulation of several key systems for homeostasis, such as the renin-angiotensin-aldosterone system. The elucidation of these and other mechanisms related to the pathophysiology of COVID-19 is essential for an improvement in risk stratification, therapeutic choices, and prognosis for these patients. Thus, we aimed to discuss in this review the relationships between TLR-4, ACE-2, cardiometabolic diseases, SARS-CoV-2 infection, and severity of COVID-19.

O uso de inibidores do Sistema Renina-Angiotensina pode aumentar a suscetibilidade à infecção pelo SARS-CoV-2 (COVID-19)? / Can the use of Renin-Angiotensin System inhibitors increase the susceptibility to SARSCoV-2 infection (COVID-19)?

Diante do contexto pandêmico da COVID-19, esforços têm sido direcionados ao desenvolvimento de medidas terapêuticas seguras e eficazes no combate à doença. Entretanto, divergências entre as condutas adotadas nesses pacientes tem sido frequentes. Em especial, fármacos inibidores do Sistema Renina-Angiotensina, como os Inibidores da Enzima Conversora de Angiotensina e Bloqueadores do Receptor da Angiotensina, são foco de grande discussão. Diversos autores questionam uma possível relação de risco aumentado entre o uso de tais medicações e o desenvolvimento de formas mais graves da doença, ao correlacionar a regulação positiva da Enzima Conversora de Angiotensina 2 induzida por esses fármacos com o fato do SARS-CoV-2 usar essa enzima como receptor celular. Enquanto isso, outros autores defendem que essa modulação atue como fator protetor à gravidade da infecção, levando em consideração a promoção de efeitos vasodepressores, anti-fibróticos e anti-inflamatórios. Dada a alta prevalência do uso desses anti-hipertensivos, a presente revisão analisa o funcionamento do Sistema Renina-Angiotensina; aspectos moleculares do novo coronavírus; e a inibição da Angiotensina 2 no contexto dessa infecção, para discutir qual conduta seria mais adequada no manejo da hipertensão arterial e doenças cardiovasculares, dada a pandemia da COVID-19.

In the face of the pandemic context of the COVID-19, efforts have been directed to the development of safe and effective therapeutic actions in combating the disease. However, divergences between management of these patients have been frequent. Especially, Renin-Angiotensin System inhibitors, as Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers, are the focus of great discussion. Several authors question a possible increased risk relation between the use of that medication and the development of the most severe disease form, when correlating AngiotensinConverting Enzyme 2 upregulation induced by those drugs with the fact that SARS-CoV-2 uses this enzyme as its cellular receptor. Meanwhile, other authors defend that the referred modulation acts as a protective factor to infection severity, considering the induction of vasodepressor, antifibrotic and anti-inflammatory effects. Given the high prevalence of the use of those antihypertensive drugs, the present review analyses the Renin-Angiotensin System functionning; molecular aspects of the novel coronavirus; and the Angiotensin 2 inhibition in the context of this infection, in order to discuss which conduct would be more appropriate in the management of arterial hypertension and cardiovascular diseases, given the COVID-19 pandemic.

Cardiovascular damage due to COVID-19: what do we need to know?

SUMMARY Severe Acute Respiratory Syndrome Coronavirus 2 is part of the Cononaviridae family and is the causative agent of the 2019 (Covid-19) Coronavirus pandemic declared by the World Health Organization in March, 2020. This virus has a high rate of transmission, affecting several individuals, and has caused thousands of deaths. The clinical manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 infection are not restricted only to the respiratory tract, and there is an express involvement of the cardiovascular system with a higher risk of death in this group. In such patients there is an overactivation of renin-angiotensin-aldosterone system, which promotes an increase in the expression of angiotensin-converting enzyme - 2 that acts as a receptor for the SPIKE protein expressed by the virus and enables the interaction between the host cell and Severe Acute Respiratory Syndrome Coronavirus 2. This process of infection causes a hyperinflammatory state that increases the inflammatory markers of cardiac injury. Hence, an adequate understanding and clinical guidance regarding the monitoring, and controlling the damage in these patients is essential to avoid worsening of their clinical condition and to prevent death.

Renin-Angiotensin-Aldosterone System Inhibitors in COVID-19: A Review

Among the multiple uncertainties surrounding the novel coronavirus disease (COVID-19) pandemic, a research letter published in The Lancet implicated drugs that antagonize the renin-angiotensin-aldosterone system (RAAS) in an unfavorable prognosis of COVID-19. This report prompted investigations to identify mechanisms by which blocking angiotensin-converting enzyme 2 (ACE2) could lead to serious consequences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The possible association between RAAS inhibitors use and unfavorable prognosis in this disease may have been biased by the presence of underlying cardiovascular diseases. As the number of COVID-19 cases has increased worldwide, it has now become possible to investigate the association between RAAS inhibitors and unfavorable prognosis in larger cohorts. Observational studies and one randomized clinical trial failed to identify any consistent association between the use of these drugs and unfavorable prognosis in COVID-19. In view of the accumulated clinical evidence, several scientific societies recommend that treatment with RAAS inhibitors should not be discontinued in patients diagnosed with COVID-19 (unless contraindicated). This recommendation should be followed by clinicians and patients.

COVID-19 e hipertensión arterial: ¿existe evidencia para suspender antagonistas del sistema renina-angiotensina-aldosterona? / COVID-19 and arterial hypertension: is there evidence to suspend renin-angiotensin-aldosteronesystem blockade?

Resumen El nuevo coronavirus SARS-CoV-2, causante de la enfermedad COVID-19, presenta una alta mortalidad en pacientes con enfermedades cardiovasculares, diabetes e hipertensión, trastornos que comparten la fisiopatología subyacente relacionada con el sistema renina-angiotensina (RAS). El SARS-CoV-2 utiliza la proteína de la membrana angiotensina I y convierte a la enzima convertidora de angiotensina tipo 2 (ACE2) en un receptor de entrada celular; por tanto, el RAS, regulado por ACE y ACE2, puede verse alterado en pacientes con COVID-19. Sin embargo, aún no es claro si el uso de fármacos antihipertensivos inhibidores de la ACE2 y bloqueadores del receptor de angiotensina II podría potencializar el daño ocasionado por el virus o contrarrestar su efecto, sobre todo a nivel pulmonar. El desafío se ve agravado por la información exagerada publicada en diferentes revistas científicas, la cual podría llevar a acciones inapropiadas, por lo que es importante diferenciar rápidamente la verdadera epidemia de hipótesis falsas, que podría llevar a conductas medicas potencialmente dañinas.

Abstract The new coronavirus SARS-CoV-2, which causes the disease COVID-19, has a high mortality in patients with cardiovascular diseases, diabetes and hypertension, disorders that share the underlying pathophysiology related to the renin-angiotensin system (RAS). SARS-CoV-2 uses the membrane protein angiotensin I and converts angiotensin converting enzyme type 2 (ACE2) into a cellular entry receptor, therefore, RAS, regulated by ACE and ACE2, can be altered in COVID-19 patients. However, it is not yet clear whether the use of antihypertensive drugs ACE2 inhibitors and angiotensin II receptor blockers could potentiate the damage caused by the virus or counteract its effect, especially in the lungs. The challenge is compounded by the exaggerated information published in different scientific journals, which could lead to inappropriate actions, so it is important to quickly differentiate the true epidemic from false hypotheses, which could lead to potentially harmful medical behaviors.

Manejo de la Hipertensión en el SARS-CoV2era: conocimiento actual y perspectivas futuras / Management of Hypertension in the SARS-CoV2era: Current Knowledge and Future Perspectives

The new SARS-CoV2 pandemic has ignited research worldwide, regarding its parameters. Hypertension, a comorbidity with high prevalence among patients with COVID-19 infection, is being extensively studied in the setting of the pandemic. Futhermore, RAAS inhibitors, drugs widely used among hypertensive patients, are on the spotlight regarding their safety during the COVID-19 era. In this review, we present current knowledge regarding both these aspects, as well as the new guidelines for the treatment of hypertensive patients during the pandemic

Study of serum and urinary markers of the reninangiotensin-aldosterone system in myelomeningocele patients with renal injury detected by DMSA

ABSTRACT Introduction: The Renin-Angiotensin-Aldosterone System (RAAS) has been suggested as a possible marker of renal injury in chronic diseases. This study proposes to analyze the serum and urinary markers of the RAAS in myelomeningocele patients with renal function abnormalities detected on DMSA. Material and Methods: Seventeen patients followed in our institution that presented with renal injury on DMSA. We review nephrologic and urologic clinical aspects and evaluated ultrassonagraphy, voiding urethrocystography and urodynamics. Urinary and serum samples were collected to evaluate possible correlations of renal lesions with RAAS. Control group urine and serum samples were also sent for analysis. Results: Serum ACE 2 activity means in relation to urodynamic findings were the only values that had a statistically significant difference (p = 0.040). Patients with normal bladder pattern presented higher ACE 2 levels than the high risk group. Statistical analysis showed that the study group (SG) had a significantly higher mean serum ACE than the CG. The means of ACE 2 and urinary ACE of the SG and CG were not statistically different. The ROC curve for serum ACE values had a statistically significant area for case and non-case differentiation, with 100% sensitivity and 53% specificity for values above 60.2 mg/dL. No statistically significant areas were observed in relation to ACE 2 and urinary ACE values between SG and CG. Conclusion: The analysis of serum ACE, ACE 2 and urinary ACE were not significant in patients with myelomeningocele and neurogenic bladder with renal injury previously detected by renal DMSA.

Considerations on the use of antihypertensive blockers of the renin-angiotensin system in adults and children in the face of the COVID-19 pandemic / Consideraciones sobre el uso de antihipertensivos bloqueadores del sistema renina-angiotensina en adultos y niños ante la pandemia de COVID-19

Abstract As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with hypertension and other cardiovascular comorbidities develop more severe coronavirus disease (COVID)-19 and are at high risk of death, a controversy arose about the use of antihypertensives as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs). Such drugs might increase the expression of the fundamental receptor of this new infectious agent: the angiotensin-converting enzyme 2 (ACE2). Preclinical observations indicate that the increase of ACE2 expression or the activity by ACEis and ARBs leads to a greater transformation of angiotensin (Ang)-II to Ang-(1-7), which is associated with positive effects on cardiovascular and pulmonary pathophysiology. This association has been demonstrated in observational studies in patients with cardiovascular pathology and pneumonia. It has not been possible to confirm whether users of ACEis or ARBs are more infected by the new coronavirus, due to methodological issues in studies with patients infected with SARS-CoV-2. However, the use of such antihypertensive treatments in both children and adults might reduce the virulence of infection. Therefore, changes in the antihypertensive therapy of patients at risk of contracting COVID-19 are not recommended.

Resumen Los pacientes con hipertensión y otra comorbilidad cardiovascular infectados con SARS-CoV-2 desarrollan cuadros más graves de COVID-19 y con mayor frecuencia fallecen. Este hecho ha originado una controversia acerca del uso de antihipertensivos inhibidores de la enzima convertidora de la angiotensina (IECA) y de antagonistas de los receptores de la angiotensina II (ARA-II), pues tales medicamentos pueden incrementar la expresión del receptor funcional de este nuevo agente infeccioso: la enzima convertidora de la angiotensina 2 (ECA2). Las observaciones preclínicas indican que el aumento de la expresión o de la actividad de la ECA2 por uso de IECA o ARA-II conduce a una mayor transformación de angiotensina 2 a a angiotensina 1-7, la cual se asocia con efectos positivos sobre la fisiopatología pulmonar y cardiovascular. En estudios observacionales de pacientes con patología cardiovascular y neumonía se ha confirmado esta asociación. La falta de evidencia contundente debida a aspectos metodológicos en estudios con pacientes infectados con SARS-CoV-2 no permite confirmar si los usuarios de IECA o ARA-II se contagian más con el nuevo coronavirus. Sin embargo, continuar con tales medicamentos antihipertensivos, tanto en adultos como en niños, podría reducir la virulencia de la infección. Por ello, no se recomienda cambiar la terapia antihipertensiva en los pacientes susceptibles a la COVID-19.

Uso terapéutico de los inhibidores de la enzima convertidora de angiotensina en pacientes con COVID-19: las «dos caras de la moneda¼ / Therapeutic use of angiotensin converting enzyme inhibitors in patients with COVID-19: the "two sides of the coin"

Resumen La evidencia actual es limitada para determinar el impacto del uso de los inhibidores de la enzima convertidora de angiotensina (IECA) en la predisposición al empeoramiento de la enfermedad del coronavirus 2019 (COVID-19). Inicialmente se reportó que en los pacientes con progresión grave de la COVID-19 existía una mortalidad elevada, los cuales tenían antecedentes de hipertensión arterial, diabetes mellitus, enfermedad cardiovascular y enfermedad renal crónica. Parte de estos pacientes también tenía en común que utilizaban IECA, lo cual alertó a la comunidad médica sobre su riesgo potencial en coexistencia con COVID-19. Sin embargo, estudios más recientes de casos-controles encontraron que los inhibidores del sistema renina-angiotensina, incluyendo los IECA, no incrementan el riesgo de COVID-19 o de requerir admisión hospitalaria por esta causa. Diferentes revistas científicas han facilitado el acceso a reportes preliminares, dejando a discreción de la comunidad médica y científica hacer uso de dicha información para promover el desarrollo de estudios que confirmen experimentalmente dichos hallazgos, preclínicos y epidemiológicos, que finalmente impacten en las decisiones de la práctica clínica para beneficiar a los pacientes con COVID-19. En esta revisión de la literatura se exploran los diferentes efectos mediados por los IECA que podrían estar relacionados con la respuesta inmune durante la infección y la transmisión de COVID-19, compilando evidencia disponible que evalúa si en realidad representan un riesgo o si, por el contrario, confieren un efecto protector.

Abstract There is limited evidence for determining the impact of the use of angiotensin converting enzyme inhibitors (ACE-I) in the tendency to worsening of coronavirus-19 disease (COVID-19). It was initially reported that, in patients with serious progression of COVID-19, there was an increased mortality in those that had a history of suffering arterial hypertension, diabetes mellitus, cardiovascular disease, and chronic kidney disease. A proportion of these patients also had in common that they used ACE-I, which alerted the medical community on the potential risk in coexisting with COVID-19. However, in more recent case-control studies, they found that inhibitors of the renin-angiotensin system, including ACE-I, does not increase the risk of COVID-19 or require hospital admission due to this cause. Several scientific journals have provided access to preliminary reports, leaving the use of such information at the discretion of the medical and scientific community for promoting the development of studies that might confirm these preclinical and epidemiological findings experimentally. These may finally have an impact on the clinical practice decisions, in order to benefit patients with COVID-19. In this literature review, the different effects mediated by ACE-I that could be related to the immune response during the infection and transmission of COVID-19 are examined, gathering available evidence that evaluates whether, in reality, they represent a risk or if on the other hand, they confer a protector effect.

Informe diário de evidências COVID-19: busca realizada em 7 de agosto de 2020 / COVID-19 daily evidence report: search conducted on August 7, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 12 artigos e 4 protocolos.

Informe diário de evidências COVID-19: busca realizada em 15 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 15, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 6 protocolos.