ABSTRACT
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.
Subject(s)
Humans , Respiratory Muscles/anatomy & histology , Respiratory Muscles/enzymology , Respiratory Muscles/physiology , Polymorphism, Genetic , Renin-Angiotensin System , Respiratory Muscles/embryology , Peptidyl-Dipeptidase A/geneticsABSTRACT
Coronaviruses are single-stranded RNA viruses that are common in animals. In the past 20 years, there have been three large-scale epidemics of coronaviruses, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease (COVID). Heart disease is an independent risk factor for severe COVID. At the same time, SARS-CoV-2 infection is often complicated with myocardial injury, which is closely related to poor prognosis. The receptors of SARS coronavirus are angiotensin-converting enzyme 2 (ACE2) and CD209L, among which ACE2 is the main receptor, and ACE2 is abundant in the heart. The receptor of MERS-coronavirus is dipeptide peptidase 4 (DPP4), which is not expressed in myocardial cells, but existed in vascular endothelial cells and blood. These receptors are important factors for the myocardial injury caused by coronavirus infection.
Subject(s)
Animals , COVID-19 , Angiotensin-Converting Enzyme 2 , SARS-CoV-2 , Endothelial Cells , Peptidyl-Dipeptidase A/geneticsABSTRACT
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.
Subject(s)
Animals , Male , Female , Rats , Renin-Angiotensin System/immunology , Angiotensin II/analysis , Diabetic Nephropathies/pathology , Wounds and Injuries/classification , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Peptidyl-Dipeptidase A/administration & dosageABSTRACT
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)
Subject(s)
Humans , Animals , Biological Products/therapeutic use , Biological Therapy/methods , Adrenal Cortex Hormones/therapeutic use , SARS-CoV-2/drug effects , COVID-19/drug therapy , Antiviral Agents/therapeutic use , Antiviral Agents/pharmacology , Biological Therapy/classification , Biological Therapy/standards , Biotechnology , Clinical Trials as Topic , Peptidyl-Dipeptidase A/drug effects , Angiotensin-Converting Enzyme 2/drug effects , Immunomodulating Agents/therapeutic use , COVID-19 Serotherapy , Horses , Immune Sera/biosynthesis , Antibodies, Monoclonal/therapeutic useABSTRACT
Abstract Introduction: Sickle cell nephropathy begins in childhood and presents early increases in glomerular filtration, which, over the long term, can lead to chronic renal failure. Several diseases have increased circulating and urinary angiotensin-converting enzyme (ACE) activity, but there is little information about changes in ACEs activity in children with sickle cell disease (SCD). Objective: We examined circulating and urinary ACE 1 activity in children with SCD. Methods: This cross-sectional study compared children who were carriers of SCD with children who comprised a control group (CG). Serum and urinary activities of ACE were evaluated, as were biochemical factors, urinary album/creatinine rates, and estimated glomerular filtration rate. Results: Urinary ACE activity was significantly higher in patients with SCD than in healthy children (median 0.01; range 0.00-0.07 vs median 0.00; range 0.00-0.01 mU/mL·creatinine, p < 0.001. No significant difference in serum ACE activities between the SCD and CG groups was observed (median 32.25; range 16.2-59.3 vs median 40.9; range 18.0-53.4) mU/m`L·creatinine, p < 0.05. Conclusion: Our data revealed a high urinary ACE 1 activity, different than plasmatic level, in SCD patients suggesting a dissociation between the intrarenal and systemic RAAS. The increase of urinary ACE 1 activity in SCD patients suggests higher levels of Ang II with a predominance of classical RAAS axis, that can induce kidney damage.
Resumo Introdução: A nefropatia falciforme começa na infância e apresenta aumentos precoces na filtração glomerular, que, em longo prazo, podem levar à insuficiência renal crônica. Várias doenças têm aumentado a atividade da enzima conversora da angiotensina (ECA) urinária e circulante, mas há pouca informação sobre alterações na atividade das ECAs em crianças com doença falciforme (DF). Objetivo: Examinamos a atividade da ECA-1 circulante e urinária em crianças com DF. Métodos: Este estudo transversal comparou crianças que eram portadoras de DF com crianças que compunham um Grupo Controle (GC). As atividades séricas e urinárias da ECA foram avaliadas, assim como os fatores bioquímicos, a relação albumina/creatinina urinária e a taxa de filtração glomerular estimada. Resultados: A atividade urinária da ECA foi significativamente maior em pacientes com DF do que em crianças saudáveis (mediana 0,01; intervalo 0,00-0,07 vs mediana 0,00; intervalo 0,00-0,01 mU/mL·creatinina, p < 0,001. Não foi observada diferença significativa nas atividades séricas da ECA entre os grupos DF e GC (mediana 32,25; intervalo 16,2-59,3 vs mediana 40,9; intervalo 18,0-53,4) mU/mL·creatinina, p < 0,05. Conclusão: Nossos dados revelaram uma alta atividade urinária da ECA-1, diferente do nível plasmático, em pacientes com DF, sugerindo uma dissociação entre o Sistema Renina Angiotensina Aldosterona (SRAA) intra-renal e sistêmico. O aumento da atividade urinária da ECA-1 em pacientes com DF sugere níveis mais elevados de Ang II com predominância do eixo clássico do SRAA, que pode induzir lesão renal.
Subject(s)
Humans , Child , Renal Insufficiency, Chronic , Anemia, Sickle Cell , Angiotensins , Cross-Sectional Studies , Peptidyl-Dipeptidase A , Angiotensin-Converting Enzyme 2ABSTRACT
La actual pandemia de COVID-19 provocada por el virus SARS-CoV-2 es un problema de salud que afecta a la población globalmente. Su desarrollo puede ser asintomático o exhibir manifestaciones clínicas moderadas o severas dependiendo en gran medida de la respuesta inmune de quien la padece. Esta enfermedad afecta principalmente a los pulmones a través del desarrollo del síndrome respiratorio agudo severo (SRAS), tanto como por la «tormenta de citocinas¼, una respuesta inflamatoria exacerbada que podría provocar una falla multisistémica y, en casos severos, la muerte. Se conoce que la enzima convertidora de angiotensina 2 (ECA-2), presente en diversos tejidos del cuerpo, actúa como receptor funcional del virus SARS-CoV-2 facilitando la entrada de éste a las células. Se ha demostrado la presencia de dicho receptor en varios tejidos orales, por lo que se puede considerar a la cavidad bucal como una vía latente de infección por dicho coronavirus, ya que su mecanismo de transmisión es a través de la inhalación de partículas virales, ya sea por vía nasal u oral. Así mismo, la presencia de carga vírica en la saliva y algunos de los síntomas de la COVID-19, por ejemplo la ageusia, pueden indicar la presencia de contagio viral en etapas tempranas. La presente revisión muestra evidencia que sugiere que diversos tejidos en la cavidad oral podrían ser considerados sitios potenciales de contagio por el SARS-CoV-2, teniendo un papel importante en el mecanismo de transmisión y en el desarrollo de coinfecciones (AU)
The COVID-19 pandemic caused by the SARS-CoV-2 virus is currently a global healthcare problem. The onset of this disease can exhibit several clinical manifestations ranging from mild to severe symptoms, depending on the individual's immune response. COVID-19 primarily affects the lungs by developing the Severe Acute Respiratory Syndrome (SARS) and the «cytokine storm¼, an exacerbated inflammatory reaction that can lead to multiorgan failure and consequently death. The angiotensin-converting enzyme 2 (ACE-2), present in several tissues in the human body, is known to act as the functional receptor of the SARS-CoV-2 germ facilitating its entrance into the cells. Such receptor is also present in diverse oral cavity tissues, indicating a latent route of infection due to its influence in the transmission mechanism by inhalation, either oral or nasal, of virus particles. Also, viral load in saliva and taste disorder symptoms like ageusia could indicate a viral infection in its early stages. This article presents evidence suggesting that several tissues in the oral cavity can be considered potential sites of SARS-CoV-2 infection, thus playing an essential role in the transmission mechanism and development of co-infections (AU)
Subject(s)
Humans , SARS-CoV-2 , COVID-19 , Mouth Mucosa/pathology , Oral Manifestations , Signs and Symptoms , Taste Disorders , Peptidyl-Dipeptidase A , Viral Load , InflammationABSTRACT
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.
Subject(s)
Humans , Coronavirus , COVID-19 , Renin-Angiotensin System , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Randomized Controlled Trials as Topic , Peptidyl-Dipeptidase A/metabolism , Angiotensin Receptor Antagonists/adverse effects , SARS-CoV-2ABSTRACT
An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%-18.5% of hospitalized adults, calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection. Here, we show that cigarette smoke extract (CSE) and carcinogen benzo(a)pyrene (BaP) increase ACE2 mRNA but trigger ACE2 protein catabolism. BaP induces an aryl hydrocarbon receptor (AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination. ACE2 in lung tissues of non-smokers is higher than in smokers, consistent with the findings that tobacco carcinogens downregulate ACE2 in mice. Tobacco carcinogens inhibit SARS-CoV-2 spike protein pseudovirions infection of the cells. Given that tobacco smoke accounts for 8 million deaths including 2.1 million cancer deaths annually and Skp2 is an oncoprotein, tobacco use should not be recommended and cessation plan should be prepared for smokers in COVID-19 pandemic.
Subject(s)
Adult , Animals , Humans , Mice , COVID-19 , Epithelial Cells , Lung , Pandemics , Peptidyl-Dipeptidase A , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Ubiquitin-Protein Ligases/geneticsABSTRACT
Resumen Introducción: La enfermedad renal aguda es una patología relativamente frecuente en pacientes con infección por COVID-19, en especial en el grupo de pacientes que se encuentran críticamente enfermos; los pacientes con enfermedad renal crónica se consideran un grupo de riesgo durante la pandemia debido a la inmunosupresión asociada por lo cual es importante la detección de infección por SARS CoV-2 en estos pacientes además de quienes están en diálisis y pacientes con trasplante renal. Es de suma importancia la identificación de enfermedad renal al ingreso de pacientes con COVID-19 pues se ha demostrado que representa un indicador para valorar supervivencia y pronóstico; varios estudios han establecido que la falla renal aguda se relaciona directamente con peor pronóstico y mortalidad. Debido al impacto positivo en la supervivencia que significa el manejo oportuno de la falla renal en pacientes positivos para COVID-19. Objetivo: Presentar la información científica actual sobre la fisiopatología de falla renal en contexto de COVID-19, diagnóstico, tratamiento, estrategias de seguimiento de la función renal durante la hospitalización, manejo de unidades de diálisis, indicación de líquidos intravenosos y manejo de shock en pacientes con enfermedad renal. Métodos: Se realizó una revisión de la literatura utilizando las bases de datos PubMed, Google Scholar y Embase; los criterios de selección incluían artículos que registraran el abordaje general y específico de complicaciones en el contexto de enfermedad renal, no se usaron filtros en la búsqueda. Conclusión: La falla renal en el contexto de la infección por COVID-19 representa un aspecto importante a estudiar dentro del desarrollo de la enfermedad y requiere consideraciones especiales para su manejo.
Abstract Introduction: Acute kidney disease is relatively frequent in COVID-19 patients, especially in critically ill patients; chronic kidney disease patients are consider as a risk group during COVID-19 pandemic because of immunosuppression associated with their condition, that's why it is important to detect SARS CoV-2 in this group of patients as in dialysis patients and kidney transplant patients. It is important to identify kidney disease at admission of COVID-19 patients because it has been shown that AKI or kidney disease represent an indicator to value survival and prognosis; literature have established that acute kidney injury is related with worst prognosis and mortality. Because of positive impact in survival that means timely and early treatment and follow up of kidney disease in COVID-19 patients. Objective: To presents actual scientific information about acute kidney injury physiopathology in COVID-19 patients, diagnosis, treatment, follow up strategies during hospitalization, management of dialysis units, intravenous liquids indications and shock management in patients with kidney disease. Methods: A literature review was performed using PubMed, Google Scholar and Embase databases; the selection criteria include articles that record the general and specific approach to complications in the context of kidney disease, no filters are used in the search. Conclusion: Renal failure in the context of COVID-19 infection represents an important aspect to study during development of COVID-19 infection and requires special considerations for its correct management.
Subject(s)
Humans , Male , Female , COVID-19 , Kidney Diseases , Patients , Renal Dialysis , Colombia , Peptidyl-Dipeptidase A , Acute Kidney Injury , HospitalizationABSTRACT
Resumen Introducción: el SARS-COV-2 es un nuevo virus que ha traído nuevos retos a los sistemas de salud a nivel mundial y que ha generado controversia en la continuidad en el uso de bloqueadores del receptor de angiotensina por su correlación fisiopatológica con el SARS-COV-2. Objetivo: presentar la evidencia disponible y las actuales recomendaciones sobre el uso de receptores de la enzima convertidora de angiotensina en el tratamiento para COVID-19. Materiales y métodos: se realizó una búsqueda narrativa en la base de datos PubMed sobre artículos que hablaran acerca del receptor de la enzima convertidora de angiotensina asociado a la pandemia actual por COVID-19. El límite de publicación fue el 13 de abril de 2020 y se incluyeron artículos en todos los idiomas. Resultados: se encontraron 14 artículos con contenido científico significativo para el objetivo de la presente revisión. Conclusión: la fisiopatología del SARS-COV-2 aún es desconocida, así como la efectividad de diferentes fármacos de uso cotidiano para su tratamiento. Dentro de los diferentes medicamentos que se han probado para detener el contagio y sus efectos están aquellos con efecto sobre el receptor de la enzima convertidora de angiotensina.
Abstract Introduction: As a new disease, SARS-COV-2 is a new challenge for healthcare system worldwide, with physiopathology under study and controversy about Angiotensin Converting Enzyme Blockers use because of It's physiopatological correlation with SARS-Cov-2. Objetive: Search for novel literature and recent recomendations about use of Angiotensin Converting Enzyme Blockers during Covid-19 illness. Materials and Methods: We look for narrative literature at PubMed Database for articles about Angiotensin Converting Enzyme and Covid-19 pandemic. Searching limit was April 13 of2.020, we included all languages. Results. We included 14 articles with significative scientific content for review objetive. Conclusion: SARS-Cov-2 Physiopatology is still unclear, also, pharmacology effectiveness in it's treatment. One of these pharmacology groups are the Angiotensin Converting Enzyme Blockers with uncertainty about it's safety during COVID-19 illness.
Subject(s)
Humans , Male , Female , Peptidyl-Dipeptidase A , COVID-19 , Respiratory Distress Syndrome, Newborn , Receptors, Angiotensin , Colombia , Severe acute respiratory syndrome-related coronavirusABSTRACT
RESUMEN: El virus SARS-CoV-2 ingresa al organismo de un individuo susceptible a través de la cavidad oral, nasal o de la mucosa conjuntival; busca ensamblarse por medio de su glicoproteína de superficie o espiga con los receptores de la enzima convertidora de angiotensina 2 que en boca los encontramos con mayor expresión en las células escamosas que recubren el epitelio lingual y las glándulas salivales, una vez que ingresa por medio de la activación de proteasas ingresa a la célula huésped para denudar su RNA viral, a diferencia de otros virus no necesita ir hasta el núcleo de tal forma que en el citoplasma inicia su replicación y utiliza los ribosomas del huésped para formar una gran cantidad de proteínas virales tanto estructurales como accesorias que le permita formar nuevos viriones potencialmente infecciosos; los estomatólogos deben tomar en cuenta esta vía de infección y extremar las medidas para disminuir su carga viral local en la cavidad oral y las barreras físicas de protección para el operador, el paciente y la ergonomía del consultorio.
ABSTRACT: SARS-CoV-2 virus enters the body of a susceptible individual through oral, nasal or conjunctival mucosa, seeking to bind to the spike glycoprotein surface through angiotensin-converting enzyme 2 receptors. These are found in the mouth with a higher expression in oral squamous cells that cover the lingual epithelium and salivary glands. Once proteolytic activation begins, it enters the host cell to denudate its viral RNA. In contrast with other viruses, it does not require nucleus access, and therefore replicates in the cytoplasm using the host's ribosomes to produce great amounts of both structural and accessory viral proteins. Since this generates new and potentially infectious virions, dentists must consider this route of infection and take extreme measures to decrease their viral load in the oral cavity. Physical protection barriers for the operator, the patient and the health and safety of the work place are critical in these cases.
Subject(s)
Humans , Pneumonia, Viral , Coronavirus Infections , Pandemics , Betacoronavirus , Salivary Glands/virology , Virology/methods , Peptidyl-Dipeptidase A , Host-Pathogen Interactions/genetics , MouthABSTRACT
RESUMEN: Un nuevo coronavirus (SARS-CoV-2) ha sido reconocido como el agente etiológico de una misteriosa neumonía originada en Wuhan, China. La OMS ha nombrado a la nueva enfermedad como COVID-19 y, además, la ha declarado pandemia. Taxonómicamente, SARS-CoV-2 pertenece al género de los betacoronavirus junto con SARS-CoV y MERS-CoV. SARS-CoV-2 utiliza la enzima convertidora de la angiotensina 2 (ACE2) como el receptor objetivo para el ingreso en una célula huésped. La expresión de ACE2 en células de tejidos humanos podría indicar un potencial riesgo de reconocimiento por parte del virus y, por ende, ser susceptibles a la infección. Mediante algunas técnicas de laboratorio y de bioinformática, se ha visto una alta presencia de ACE2 en células epiteliales alveolares tipo II de pulmón y en enterocitos del intestino delgado. En la cavidad oral, se ha podido identificar la presencia de ACE2, principalmente, en células epiteliale s de glándulas salivales y células epiteliales de la lengua. Además, se ha reportado la manifestación de algunos síntomas, como sequedad bucal y ambligeustia, los que podrían estar relacionadas con una infección de SARS-CoV-2 en estos órganos. Sin embargo, son necesarios mayores estudios que evidencien esta situación.
ABSTRACT: A novel coronavirus (SARS-CoV-2) has been recognized as a etiologic agent of a mysterious pneumonia originating in Wuhan, China. WHO has named the new disease as COVID-19 and, in addition, has declared it a pandemic. Taxonomically, SARS-CoV-2 belongs to the betacoronavirus genus along with SARS-CoV and MERS-CoV. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as the target receptor for entry into a host cell. The expression of ACE2 in cells of human tissues could indicate a potential risk of recognition by the virus and, therefore, be susceptible to infection. Through some laboratory and bioinformatics techniques, high presence of ACE2 has been seen in type II alveolar epithelial cells of the lung and enterocytes of the small intestine. In oral cavity, mainly presence of ACE2 has been identified in epithelial cells of salivary glands and epithelial cells of tongue. In addition, manifestation of some symptoms, such as dry mouth and amblygeustia, have been reported, which could be related to a SARS-CoV-2 infection in these organs. However, further studies are needed to prove this situation.
Subject(s)
Humans , Angiotensin-Converting Enzyme Inhibitors , Coronavirus Infections/epidemiology , Peptidyl-Dipeptidase A/chemistry , Betacoronavirus/chemistry , Tissue Culture Techniques/methods , Alveolar Epithelial Cells/cytology , Alveolar Epithelial Cells/virology , Mouth/virologySubject(s)
Humans , Pneumonia, Viral/genetics , Coronavirus Infections/genetics , Epigenesis, Genetic , Pandemics , Betacoronavirus/genetics , Pneumonia, Viral/epidemiology , Receptors, Virus/genetics , Genetic Variation , Haplotypes , RNA, Viral/genetics , HLA-B Antigens/genetics , Genome, Human , Genome, Viral , Coronavirus Infections/epidemiology , Peptidyl-Dipeptidase A/genetics , Genetic Predisposition to Disease/genetics , Disease Resistance/genetics , Angiotensin-Converting Enzyme 2 , SARS-CoV-2 , COVID-19 , GenotypeABSTRACT
RESUMEN: El objetivo de este estudio fue describir la frecuencia genotípica y alélica del ACTN3 R577X y ECA I/D en atletas ciegos de fútbol 5. Se incluyó una metodología descriptiva con una muestra de 63 deportistas ciegos (28,0±5,8 años), todos varones, de equipos de fútbol 5 de alto rendimiento. El polimorfismo se determinó mediante la reacción en cadena de la polimerasa en tiempo real (RT-PCR). La estadística fue descriptiva realizada a partir de las medidas de frecuencia de genotipos y alelos. La frecuencia genotípica de la ACTN3 en los deportistas presentó la siguiente distribución: el 28,6 % con genotipo RR, el 54 % con RX y el 17,4 % con XX y frecuencia alélica del 55,6 % para el alelo R y del 44,4 % para el alelo X. En cuanto a la ECA I/D, la frecuencia genotípica fue del 63,5 % para el genotipo ID, del 22,2 % para el DD y del 14,3 % para el II. La frecuencia alélica presentó prevalencia del alelo D con el 53,9 %. El estudio constató una predominancia de los genotipos y alelos representativos de las modalidades de fuerza y velocidad para ACTN3 R577X y ECA I/D de atletas de fútbol 5.
SUMMARY: The aim of this study was to describe the genotypic and allele frequency of ACTN3 R577X and ACE I/D in blind athletes of 5-a-side football performance. A descriptive methodology was included with a sample of 63 blind male athletes (28.0 ±5.8 years) of football teams with a 5-a-side performance rating. The polymorphism was determined by means by of real-time Polymerase Chain Reaction (rt-PCR). Statistics were descriptive based on the measures of frequency of genotypes and alleles. The genotypic frequency of ACTN3 by the athletes presented the following distribution: 28.6 % with RR genotype, 54 % with RX and 17.4 % XX and allele frequency of 55.6 % for the R allele and 44.4 % for the X allele. As for ACE I/D, the genotype frequency was 63.5 % for genotype ID, 22.2 % for DD and 14.3 % for II. The allele frequency showed a predominance of the D allele with 53.9 %. The study found for ACTN3 R577X and ACE I/ D of blind athletes of 5-a-side football, a predominance of genotypes and alleles representative of strength and speed modalities.
Subject(s)
Humans , Male , Adult , Soccer , Vision Disorders/genetics , Para-Athletes , Polymorphism, Genetic , Actinin/genetics , Blindness/genetics , Polymerase Chain Reaction , Peptidyl-Dipeptidase A/genetics , Gene Frequency , GenotypeABSTRACT
Abstract In the efforts to explain COVID-19 pathophysiology, studies are being carried out on the correspondence between the expression of SARS-CoV-2 cell receptors and viral sequences. ACE2, CD147 and TMPRSS2 receptors expression could indicate poorly explored potential infection targets. For the genomic analysis of SARS-CoV-2 receptors, using BioGPS information was decided, which is a portal that centralizes genetic annotation resources, in combination with that of The Human Protein Atlas, the largest portal of human transcriptome and proteome data. We also reviewed the most recent articles on the subject. RNA and viral receptor proteins expression was observed in numerous anatomical sites, which partially coincides with the information reported in the literature. High expression in testicular cells markedly stood out, and it would be therefore important ruling out whether this anatomical site is a SARS-CoV-2 reservoir; otherwise, germ cell damage, as it is observed in infections with other RNA viruses, should be determined.
Resumen En el afán por explicar la fisiopatogenia de COVID-19 se están realizando estudios en torno a la correspondencia entre la expresión de receptores celulares de SARS-CoV-2 y las secuencias virales. La expresión de los receptores ACE2, CD147 y TMPRSS2 podría indicar blancos de infección poco explorados. Para el análisis genómico de los receptores de SARS-CoV-2 se optó por utilizar la información del BioGPS, un portal que centraliza los recursos de anotación genética, en combinación con la de The Human Protein Atlas, el portal más grande de datos del transcriptoma y proteoma humanos. También se revisaron los artículos más recientemente respecto al tema. En numerosos sitios anatómicos se observó la expresión de ARN y proteínas de los receptores del virus, que coinciden parcialmente con la información reportada en la literatura. Resaltó la alta expresión en las células de los testículos, por lo que sería importante descartar si este sitio anatómico es un reservorio de SARS-CoV-2; de no ser así, determinar el daño en las células germinales, tal como sucede en infecciones por otros virus ARN.
Subject(s)
Humans , Pneumonia, Viral/virology , Testis/virology , Coronavirus Infections/virology , Betacoronavirus/isolation & purification , Pneumonia, Viral/physiopathology , Serine Endopeptidases/genetics , Gene Expression Regulation , Virus Latency , Coronavirus Infections/physiopathology , Peptidyl-Dipeptidase A/genetics , Basigin/genetics , Pandemics , Angiotensin-Converting Enzyme 2 , SARS-CoV-2 , COVID-19ABSTRACT
Abstract Introduction: Reports of dermatological manifestations in patients with COVID-19 suggest a possible cutaneous tropism of SARS-CoV-2; however, the capacity of this virus to infect the skin is unknown. Objective: To determine the susceptibility of the skin to SARS-CoV-2 infection based on the expression of viral entry factors ACE2 and TMPRSS2 in this organ. Method: A comprehensive analysis of human tissue gene expression databases was carried out looking for the presence of the ACE2 and TMPRSS2 genes in the skin. mRNA expression of these genes in skin-derived human cell lines was also assessed. Results: The analyses showed high co-expression of ACE2 and TMPRSS2 in the gastrointestinal tract and kidney, but not in the skin. Only the human immortalized keratinocyte HaCaT cell line expressed detectable levels of ACE2, and no cell line originating in the skin expressed TMPRSS2. Conclusions: Our results suggest that cutaneous manifestations in patients with COVID-19 cannot be directly attributed to the virus. It is possible that cutaneous blood vessels endothelial damage, as well as the effect of circulating inflammatory mediators produced in response to the virus, are the cause of skin involvement.
Resumen Introducción: Reportes de manifestaciones dermatológicas en pacientes con COVID-19 sugieren un posible tropismo cutáneo del virus SARS-CoV-2; sin embargo, se desconoce la capacidad de este virus para infectar la piel. Objetivo: Determinar la susceptibilidad de la piel a la infección por SARS-CoV-2 con base en la expresión de los factores de entrada viral ACE2 y TMPRSS2 en dicho órgano. Método: Se buscaron los genes ACE2 y TMPRSS2 en la piel, para lo cual se realizó un análisis extenso de las bases de datos de expresión genética en tejidos humanos. Asimismo, se evaluó la expresión de dichos genes en líneas celulares humanas derivadas de la piel. Resultados: Los análisis mostraron alta expresión conjunta de ACE2 y TMPRSS2 en el tracto gastrointestinal y en los riñones, pero no en la piel. Solo la línea celular de queratinocitos humanos inmortalizados HaCaT expresó niveles detectables de ACE2 y ninguna línea celular de origen cutáneo expresó TMPRSS2. Conclusiones: Los resultados sugieren que las manifestaciones dermatológicas en pacientes con COVID-19 no pueden ser atribuidas directamente al virus; es posible que sean originadas por el daño endotelial a los vasos sanguíneos cutáneos y el efecto de los mediadores inflamatorios circulantes producidos en respuesta al virus.
Subject(s)
Humans , Pneumonia, Viral/complications , Serine Endopeptidases/genetics , Skin Diseases, Viral/virology , Coronavirus Infections/complications , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , Skin/virology , Cell Line , Gene Expression Regulation , Coronavirus Infections/genetics , Genetic Predisposition to Disease , Virus Internalization , Viral Tropism/physiology , Pandemics , Betacoronavirus/isolation & purification , Angiotensin-Converting Enzyme 2 , SARS-CoV-2 , COVID-19ABSTRACT
Resumen: La enfermedad por coronavirus ha extendido su compromiso más allá del sistema respiratorio con reportes crecientes de compromiso en diferentes sistemas, uno de ellos, el Sistema Nervioso. El potencial neuroinvasivo de este agente patógeno se explicaría por su neurotropismo dada la presencia de receptores de ACE2 a nivel de encéfalo y médula espinal, además del importante com promiso inflamatorio sistémico. El compromiso neurológico debido a la infección se ha dividido en Sistema Nervioso Central, destacando síntomas inespecíficos y leves como mareos y cefalea, así como cuadros graves con encefalitis y patología cerebrovascular, y Sistema Nervioso Periférico en donde la mayor relevancia guarda relación con la anosmia, ageusia y miositis. A nivel pediátrico el compromiso parece ser menor que en adultos, pero existe un reporte creciente en la literatura respecto a estos hallazgos. Es de gran importancia de contar con un adecuado registro y anamnesis que permita identificar precozmente el compromiso neurológico.
Abstract: Coronavirus disease has extended its involvement beyond the respiratory system, with increasing reports of involving different systems, such as Nervous System. The neuroinvasive potential of this pathogen would be explained by its neurotropism given the presence of ACE2 receptors in the brain and spinal cord, in addition to the important systemic inflammatory involvement. The neu rological involvement due to infection is divided between the central nervous system, highlighting non-specific and mild symptoms such as dizziness and headache, as well as severe symptoms with encephalitis and cerebrovascular pathology, and the peripheral nervous system, which mainly pre sents anosmia, ageusia, and myositis. Clinical symptomatology in pediatric patients seems to be less than in adults, but there is a growing report in the literature regarding these findings. There fore, it is very important to have an adequate registry and anamnesis that allow early identification of neurological involvement.