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J. bras. nefrol ; 43(3): 303-310, July-Sept. 2021. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1340129


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.

Humans , Child , Renal Insufficiency, Chronic , Anemia, Sickle Cell , Angiotensins , Cross-Sectional Studies , Peptidyl-Dipeptidase A , Angiotensin-Converting Enzyme 2
Rev. ADM ; 78(3): 167-175, mayo-jun. 2021. ilus
Article in Spanish | LILACS | ID: biblio-1254949


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)

Humans , SARS-CoV-2 , COVID-19 , Mouth Mucosa/pathology , Oral Manifestations , Signs and Symptoms , Taste Disorders , Peptidyl-Dipeptidase A , Viral Load , Inflammation
Frontiers of Medicine ; (4): 252-263, 2021.
Article in English | WPRIM | ID: wpr-880970


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.

Adult , Animals , COVID-19 , Epithelial Cells , Humans , Lung , Mice , Pandemics , Peptidyl-Dipeptidase A , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Ubiquitin-Protein Ligases/genetics
Clinics ; 76: e2342, 2021. tab, graf
Article in English | LILACS | ID: biblio-1286087


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.

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-2
Int. j. odontostomatol. (Print) ; 14(4): 495-500, dic. 2020. tab, graf
Article in Spanish | LILACS | ID: biblio-1134526


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.

Humans , Pneumonia, Viral , Coronavirus Infections , Pandemics , Betacoronavirus , Salivary Glands/virology , Virology/methods , Peptidyl-Dipeptidase A , Host-Pathogen Interactions/genetics , Mouth
Int. j. odontostomatol. (Print) ; 14(4): 501-507, dic. 2020. graf
Article in Spanish | LILACS | ID: biblio-1134527


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.

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/virology
Rev. colomb. nefrol. (En línea) ; 7(supl.2): 280-284, jul.-dic. 2020. graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1251591


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.

Humans , Male , Female , Peptidyl-Dipeptidase A , COVID-19 , Respiratory Distress Syndrome, Newborn , Receptors, Angiotensin , Colombia , SARS Virus
Rev. colomb. nefrol. (En línea) ; 7(supl.2): 221-248, jul.-dic. 2020. tab, graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1251587


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.

Humans , Male , Female , COVID-19 , Kidney Diseases , Patients , Renal Dialysis , Colombia , Peptidyl-Dipeptidase A , Acute Kidney Injury , Hospitalization
Int. j. morphol ; 38(5): 1336-1340, oct. 2020. tab
Article in Spanish | LILACS | ID: biblio-1134445


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.

Humans , Male , Adult , Soccer , Vision Disorders/genetics , Para-Athletes , Polymorphism, Genetic , Actinin/genetics , Blindness/genetics , Polymerase Chain Reaction , Peptidyl-Dipeptidase A/genetics , Gene Frequency , Genotype
Rev. chil. pediatr ; 91(4): 614-619, ago. 2020.
Article in Spanish | LILACS | ID: biblio-1138679


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.

Humans , Child , Pneumonia, Viral/complications , Coronavirus Infections/complications , Peptidyl-Dipeptidase A/metabolism , Nervous System Diseases/virology , Pediatrics , Age Factors , Encephalitis/virology , Headache/virology , Nervous System Diseases/physiopathology
Rev. chil. pediatr ; 91(4): 623-630, ago. 2020.
Article in Spanish | LILACS | ID: biblio-1138681


Resumen: SARS-CoV-2 es un virus de alta estabilidad ambiental. Es principalmente un patógeno respiratorio que también afecta el tracto gastrointestinal. El receptor ACE2 es el principal receptor de SARS- CoV-2, hay evidencia de su elevada presencia en intestino, colon y colangiocitos; igualmente se en cuentra expresado en hepatocitos pero en menor proporción. SARS-CoV-2 tiene un tropismo gas trointestinal que explica los síntomas digestivos y la diseminación viral en deposiciones. Las caracte rísticas de SARS-CoV-2 incluyen a la proteína S (Spike o Espícula) que se une de forma muy estable al receptor ACE2. La infección por SARS-CoV-2 produce disbiosis y alteraciones en el eje pulmón- intestino. A nivel intestinal y hepático produce una respuesta Linfocitos T evidente y una respuesta de citocinas que producirían daño intestinal inflamatorio. Las manifestaciones a nivel intestinal en orden de frecuencia son pérdida de apetito, diarrea, náuseas, vómitos y dolor abdominal. Éste último podría ser un marcador de gravedad. En niños la diarrea es habitualmente leve y autolimitada. A nivel hepático la hipertransaminasemia ocurre en 40-60% de los pacientes graves. SARS-CoV-2 puede per manecer en deposiciones un tiempo más prolongado que en secreciones respiratorias, este hallazgo influiría en la diseminación de enfermedad. En esta revisión se destaca la importancia de efectuar un reconocimiento precoz de las manifestaciones gastrointestinales y hepáticas, aumentar el índice de sospecha, efectuar un diagnóstico oportuno y reconocer eventuales complicaciones de la enferme dad. La potencial transmisión fecal oral puede influir en la diseminación de enfermedad. Reconocer este hallazgo es importante para definir aislamiento.

Abstract: SARS-CoV-2 is a high environmental stable virus. It is predominantly a respiratory pathogen that also affects the gastrointestinal tract. The ACE 2 receptor is the main receptor of SARS-CoV-2, with evidence of its high presence in the intestine, colon and cholangiocytes, and, in smaller proportion, in hepatocytes. SARS-CoV-2 has a gastrointestinal tropism that explains digestive symptoms and viral spread in stools. The characteristics of this virus include the S (Spike) protein that binds very stably to the ACE-2 receptor and, at the same time, SARS-CoV-2 produces dysbiosis and alterations in the gut-lung axis. It produces a clear T-cell response and a cytokines storm in the intestine and liver that would produce inflammatory bowel damage. Intestinal manifestations by order of frequency are loss of appetite, diarrhea, nausea and vomiting, and abdominal pain, where the latter could be a severity marker. In children, diarrhea is the most frequent symptom, usually mild and self-limiting. In the liver, hypertransaminasemia occurs in severe patients ranging from 40 to 60%. SARS-CoV-2 can re main in stools longer than in respiratory secretions, which would influence the spread of disease. This article highlights the importance of an early diagnosis of gastrointestinal and hepatic manifestations, increase the index of suspicion, make a timely diagnosis, and recognize eventual complications of the disease. The potential oral-fecal route of transmission may influence the disease spread. Recognizing this finding is important to define isolation.

Humans , Child , Pneumonia, Viral/complications , Coronavirus Infections/complications , Gastrointestinal Diseases/virology , Liver Diseases/virology , Pneumonia, Viral/diagnosis , Severity of Illness Index , Cytokines/metabolism , Coronavirus Infections/diagnosis , Peptidyl-Dipeptidase A/metabolism , Clinical Laboratory Techniques , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/physiopathology , Liver Diseases/diagnosis , Liver Diseases/physiopathology
Gac. méd. Méx ; 156(4): 348-351, Jul.-Aug. 2020. graf
Article in English | LILACS | ID: biblio-1249923


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.

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-19
Gac. méd. Méx ; 156(4): 324-329, Jul.-Aug. 2020. graf
Article in English | LILACS | ID: biblio-1249919


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.

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-19
Brasília; s.n; 20 jul.2020.
Non-conventional in Portuguese | LILACS, BRISA, PIE | ID: biblio-1117679


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.

Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Betacoronavirus/drug effects , Ribavirin/therapeutic use , Technology Assessment, Biomedical , Vitamin D/therapeutic use , Immunoglobulins/therapeutic use , Dexamethasone/therapeutic use , Methylprednisolone/therapeutic use , Prednisone/therapeutic use , Roxithromycin/therapeutic use , Cross-Sectional Studies/instrumentation , Cohort Studies , Interferons/therapeutic use , Azithromycin/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Peptidyl-Dipeptidase A/therapeutic use , Ritonavir/therapeutic use , Oseltamivir/therapeutic use , Lopinavir/therapeutic use , Amoxicillin/therapeutic use , Hydroxychloroquine/therapeutic use
Brasília; s.n; 15 jul.2020.
Non-conventional in Portuguese | LILACS, BRISA, PIE | ID: biblio-1117674


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.

Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Betacoronavirus/drug effects , Renin-Angiotensin System , Technology Assessment, Biomedical , Omeprazole/therapeutic use , Dexamethasone/therapeutic use , Extracorporeal Membrane Oxygenation/instrumentation , Cohort Effect , Enoxaparin/therapeutic use , Peptidyl-Dipeptidase A/therapeutic use , Ritonavir/therapeutic use , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Lopinavir/therapeutic use , Fibrinolytic Agents/therapeutic use , Esomeprazole/therapeutic use , Darunavir/therapeutic use , Rituximab/therapeutic use , Pantoprazole/therapeutic use , Hydroxychloroquine/therapeutic use , Anticoagulants/therapeutic use
CorSalud ; 12(2): 171-183, graf
Article in Spanish | LILACS | ID: biblio-1133607


RESUMEN Desde los primeros informes de pacientes infectados con el SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) en la provincia China de Wuhan, la infección por el nuevo coronavirus ha contagiado a más de 4,7 millones de personas y los fallecidos superan los 315000, hasta el 18 de mayo del 2020. La lesión o daño miocárdico queda definido, como la detección de un valor de las troponinas cardíacas (T o I) por encima del percentil 99 del límite superior de referencia. El mecanismo exacto a partir del cual esta infección por el nuevo coronavirus le infringe un daño a las células del corazón no ha quedado totalmente esclarecido; no obstante, numerosos podrían ser los factores a tener en cuenta: desequilibrio entre el aporte y la demanda, la respuesta inflamatoria sistémica, hipoxia, disfunción microvascular y el daño miocárdico directo ocasionado por el virus.

ABSTRACT Since the first reports of patients infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) appeared in the Chinese province of Wuhan, the infection by the new coronavirus has infected more than 4.7 millions of people, and the amount of deaths is greater than 315,000, until May 18, 2020. The myocardial injury or damage is defined as the detection of a value of cardiac troponins (T or I) above the 99th percentile of the upper reference limit. The exact mechanism, from which this infection by the new coronavirus causes damage to the heart cells, has not been completely clarified; however, numerous factors could be taken into account: imbalance between the supply and the demand, systemic inflammatory response, hypoxia, microvascular dysfunction and the direct myocardial injury caused by the virus.

Myocardial Reperfusion Injury , Coronavirus Infections , Peptidyl-Dipeptidase A
Rev. chil. pediatr ; 91(3): 330-338, jun. 2020. graf
Article in Spanish | LILACS | ID: biblio-1126169


Resumen: El sistema renina angiotensina aldosterona (SRAA) es el principal regulador del volumen plasmático, manteniendo la homeostasis cardiovascular e hidrosalina. En la vía clásica, la enzima convertidora de angiotensina (ECA) genera Angiotensina II (AngII), de potente efecto inflamatorio y vasoconstrictor. Esta vía clásica es a su vez regulada por la ECA2, que convierte AngII a Ang 1-7, cuyas acciones vaso dilatadoras y antiinflamatorias dan balance a los efectos de AngII. La ECA2 se ha relacionado con la patogenia de infecciones respiratorias como el virus respiratorio sincicial y el síndrome respiratorio agudo grave por coronavirus (SARS-CoV y SARS-CoV-2). Estudios recientes han demostrado que la ECA2 corresponde al principal receptor del SARS-CoV-2, que en conjunto con otros receptores como la serin proteasa TMPRSS2, permiten la fijación, fusión y entrada del virus a la célula huésped. En animales infectados por SARS-CoV se produce una caída de la concentración tisular de ECA2 y Ang 1-7, con la consiguiente sobreexpresión de AngII, y sus efectos vasoconstrictores e inflamatorios. Experimentos con ECA2 recombinante han mostrado un efecto protector frente a la sobreexpresión del SRAA en animales infectados por SARS-CoV, efecto similar al demostrado con el uso de bloquea- dores del receptor de AngII, AT1. La evidencia sobre el rol protector de ECA2 parece respaldar las recomendaciones respecto a no suspender estos medicamentos en la infección SARS-CoV-2. En este artículo presentamos el conocimiento actual sobre el rol del SRAA en la infección por SARS-CoV, a partir de conceptos fisiopatológicos, bases moleculares, y evidencia experimental y clínica.

Abstract: The renin-angiotensin-aldosterone system (RAAS) is the main plasma volume regulator, which maintains cardiovascular and hydrosaline homeostasis. In the classical pathway, the angiotensin converting enzyme (ACE) generates Angiotensin II (AngII), which is powerfully inflammatory and vasoconstrictive. This classical pathway is also regulated by ACE2, which converts AngI to Ang 1-9, and degrades AngII to Ang 1-7, whose vasodilatory and anti-inflammatory functions balance out the effects of AngII. ACE2 has been associated with the pathogenesis of respiratory infections such as RSV and severe acute respiratory syndrome coronavirus (SARS-CoV and SARS-CoV-2). Recent studies have shown that ACE2 corresponds to the main SARS-CoV-2 receptor, which together with other receptors such as the TMPRSS2, allows the virus to attach, fuse, and enter the host cell. These studies have shown that in animals infected with coronavirus there is a drop in tissue concentration of ACE2 and Ang 1-7, leading to overexpression of AngII and its vasoconstrictive and inflammatory effects. Experiments with recombinant ACE2 have shown a protective effect against overexpression of RAAS in coronavirus-infected animals, which is similar to that demonstrated with the use of AnglI receptor blockers (AT1). Evidence on the protective role of ACE2 seems to support the recommendations re garding not discontinuing these drugs in COVID-19 infection. In this article, we present the current knowledge about the role of RAAS in coronavirus infection, based on physiopathological concepts, molecular bases, and experimental and clinical evidence.

Humans , Animals , Pneumonia, Viral/virology , Coronavirus Infections/virology , Peptidyl-Dipeptidase A/metabolism , Betacoronavirus/isolation & purification , Pneumonia, Viral/physiopathology , Renin-Angiotensin System/physiology , Coronavirus Infections/physiopathology , Angiotensin Receptor Antagonists/pharmacology , Pandemics , Angiotensin-Converting Enzyme 2 , SARS-CoV-2 , COVID-19