Protective effect of trans-nerolidol on vascular endothelial cell injury induced by lipopolysaccharides / Efectos protectores del trans-nerolidol en lesiones inducidas por lipopolisacáridos en células endoteliales vasculares

This article aimed to discuss the protection of trans - nerolidol on vascular endothelial cells (ECs) injured by lipopolysac charides. ECs were divided into four groups: normal, model, low and high dose trans - nerolidol treatment groups. The cell survival rate and the contents of NO in the cell culture supernatant were determined. The protein expression and transcript level of pe roxisome proliferator - activated receptor - γ (PPARγ), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) were determined by western blotting and RT - PCR respectively. Compared with the normal group, cell livability, protein e xpression and mRNA transcript level of PPARγ and eNOS decreased, NO contents, protein expression and mRNA transcript tlevel of iNOS increased in model group significantly. Compared with model group, all the changes recovered in different degree in treatmen t groups. Hence, it was concluded that trans - nerolidol can alleviate the ECs injuryby the regulation of iNOS/eNOS through activating PPARγ in a dose - dependent manner

Este artículo tiene como objetivo discutir la protección del trans - nerolidol en las células endoteliales vasculares (CE) dañadas por lipopolisacáridos. Las CE se di vidieron en cuatro grupos: normal, modelo, grupos de tratamiento con trans - nerolidol de baja y alta dosis. Se determinó la tasa de supervivencia de las células y los contenidos de óxido nítrico (NO) en el sobrenadante del cultivo celular. La expresión de p roteínas y el nivel de transcripción del receptor activado por proliferadores de peroxisomas - γ (PPARγ), el óxido nítrico sint et asa endotelial (eNOS) y el óxido nítrico sint et asa inducible (iNOS) se determinaron mediante western blot y RT - PCR, respectivamen te. En comparación con el grupo normal, la viabilidad celular, la expresión de proteínas y el nivel de transcripción de PPARγ y eNOS disminuyeron, los contenidos de NO, la expresión de proteínas y el nivel de transcripción de iNOS aumentaron significativam ente en el grupo modelo. En comparación con el grupo modelo, todos los cambios se recuperaron en diferentes grados en los grupos de tratamiento. Por lo tanto, se concluyó que el trans - nerolidol puede aliviar el daño en las CE regulando iNOS/eNOS a través d e la activación de PPARγ de manera dependiente de la dosis.

Desempenho do óxido nítrico na sepse: uma revisão de escopo / Desempeño del óxido nítrico en la sepsis: una revisión de alcance / Performance of nitric oxide in sepsis: a scoping review

Resumo Objetivo Mapear as evidências disponíveis sobre as ações do óxido nítrico na fisiopatologia da sepse e sua relação com a gravidade de pacientes sépticos. Método Revisão de escopo de acordo com a metodologia do Joanna Briggs Institute. Realizou-se busca por estudos que evidenciaram as ações do óxido nítrico na sepse e se o seu aumento está associado à gravidade de pacientes sépticos. Dois revisores independentes fizeram o mapeamento das informações utilizando um instrumento de extração de dados previamente elaborado. Os dados foram analisados quanto à sua relevância, sendo posteriormente extraídos e sintetizados. Resultados De 1342 estudos, 11 foram incluídos na revisão. O primeiro foi publicado em 2017 e o último, em 2022. A maioria foi desenvolvida nos Estados Unidos, na China e na Alemanha. Os estudos apresentaram informações referentes as ações do óxido nítrico, sintetizando sua biodisponibilidade e os inibidores endógenos relacionados a sua produção, além de abordarem a relação do óxido nítrico com a gravidade da sepse. Conclusão A produção de óxido nítrico fisiológico durante a sepse atua como protetor vascular, principalmente na microcirculação, porém, em altas concentrações, contribui para a disfunção vascular, que subverte a fisiologia da regulação da pressão arterial, causando profunda vasodilatação e hipotensão refratária e aumentando a gravidade de pacientes sépticos.

Resumen Objetivo Mapear las evidencias disponibles sobre las acciones del óxido nítrico en la fisiopatología de la sepsis y su relación con la gravedad de pacientes sépticos. Métodos Revisión de alcance de acuerdo con la metodología del Joanna Briggs Institute. Se realizó una búsqueda de estudios que evidenciaron las acciones del óxido nítrico en la sepsis y si su aumento estaba asociado a la gravedad de pacientes sépticos. Dos revisores independientes hicieron el mapeo de la información utilizando un instrumento de extracción de datos previamente elaborado. Los datos se analizaron respecto a su relevancia, para luego extraerlos y sintetizarlos. Resultados De 1342 estudios, se incluyeron 11 en la revisión. El primero fue publicado en 2017 y el último en 2022. La mayoría se realizó en Estados Unidos, China y Alemania. Los estudios presentaron información referente a las acciones del óxido nítrico, sintetizando su biodisponibilidad y los inhibidores endógenos relacionados con su producción, además de abordar la relación del óxido nítrico con la gravedad de la sepsis. Conclusión La producción de óxido nítrico fisiológico durante la sepsis actúa como protector vascular, principalmente en la microcirculación. Sin embargo, en altas concentraciones, contribuye a la disfunción vascular, que subvierte la fisiología de la regulación de la presión arterial, causa una profunda vasodilatación e hipotensión refractaria y aumenta la gravedad de pacientes sépticos. Registro da revisão de escopo no Open Science Framework: https://doi.org/10.17605/OSF.IO/MXDK2

Abstract Objective Map the available evidence on the actions of nitric oxide in the pathophysiology of sepsis and its relationship with the severity of sepsis in patients. Method Scoping review following the Joanna Briggs Institute methodology. A search was carried out for studies that highlighted the actions of nitric oxide in sepsis, informing whether its increase is associated with the severity of sepsis in patients. Two independent reviewers mapped the information using a previously designed data extraction instrument. The data was analyzed for its relevance and then extracted and synthesized. Results Eleven of 1342 studies were included in the review. The first of them was published in 2017 and the last in 2022. Most of them were developed in the USA, China, and Germany. Studies have reported the actions and bioavailability of nitric oxide and endogenous inhibitors related to its production, and related nitric oxide to the severity of sepsis. Conclusion The physiological production of nitric oxide during sepsis acts as a vascular protector, mainly in the microcirculation but contributes to vascular dysfunction in high concentrations, subverting the regulation of blood pressure, causing deep vasodilation and refractory hypotension, and increasing the severity of sepsis in patients. Registration of the scoping review in the Open Science Framework: https://doi.org/10.17605/OSF.IO/MXDK2

Tratamientos coadyuvantes a la ventilación mecánica invasiva en el manejo del síndrome de distrés respiratorio agudo secundario a covid-19 / Adjuvant treatments to invasive mechanical ventilation in the management of acute respiratory distress syndrome secondary to COVID-19

Introducción: La presente revisión bibliográfica está realizada con el fin de obtener respuestas acerca de aspectos relacionados con las técnicas y tratamientos, así como cuidados asociados al paciente crítico diagnosticado con covid-19. Objetivo: Analizar la evidencia científica disponible sobre la efectividad de la utilización de la ventilación mecánica invasiva junto con otras técnicas coadyuvantes, en la reducción de la tasa de mortalidad en pacientes con síndrome de distrés respiratorio agudo y juicio clínico de covid-19 atendidos en unidades de cuidados intensivos. Metodología: Se realizó una revisión bibliográfica sistematizada en las bases de datos PubMed, CUIDEN, LILACS, Medline, CINAHL y Google Scholar, utilizando términos MeSH (adult respiratory distress syndrome, mechanical ventilation, prone position, nitric oxide, extracorporeal membrane oxygenation, nursing care) y los operadores booleanos correspondientes. Los estudios seleccionados se sometieron a una lectura crítica realizada entre el 6 de diciembre de 2020 y el 27 de marzo de 2021 utilizando la herramienta Critical Appraisal Skills Programme en español y un instrumento de evaluación de estudios epidemiológicos transversales. Resultados: Se seleccionaron un total de 85 artículos. Tras realizar la lectura crítica se incluyeron en la revisión un total de 7 artículos, consistiendo en 6 estudios descriptivos y un estudio de cohortes. Tras el análisis de dichos estudios, se desprende que la técnica que mejor resultados ha obtenido es la oxigenación por membrana extracorpórea, siendo importantes los cuidados proporcionados por el personal de enfermería cualificado y capacitado. Conclusión: La mortalidad por covid-19 aumenta en pacientes tratados con ventilación mecánica invasiva respecto a los pacientes tratados con oxigenación por membrana extracorpórea. Los cuidados de enfermería y la especialización pueden repercutir en una mejora de los resultados en los pacientes.(AU)

Introduction: This bibliographic review is carried out in order to obtain answers about aspects related to techniques and treatments, as well as care associated with the critically ill patient diagnosed with COVID-19. Objective: To analyze the available scientific evidence on the effectiveness of the use of invasive mechanical ventilation together with other adjuvant techniques, in reducing the mortality rate in patients with acute respiratory distress syndrome and clinical trial of COVID-19 treated in intensive care units. Methodology: A systematized bibliographic review was carried out in the PubMed, CUIDEN, LILACS, Medline, CINAHL and Google Scholar databases, using MeSH terms (adult respiratory distress syndrome, mechanical ventilation, prone position, nitric oxide, extracorporeal membrane oxygenation, nursing care) and the corresponding Boolean operators. The selected studies underwent a critical reading carried out between December 6, 2020 and March 27, 2021 using the Critical Appraisal Skills Program tool in Spanish and a cross-sectional epidemiological studies evaluation instrument. Results: A total of 85 articles were selected. After performing the critical reading, a total of 7 articles were included in the review, 6 being descriptive studies and one a cohort study. After analyzing these studies, it appears that the technique that has obtained the best results is extracorporeal membrane oxygenation, with the care provided by qualified and trained nursing staff being very important. Conclusion: Mortality from COVID-19 increases in patients treated with invasive mechanical ventilation compared to patients treated with extracorporeal membrane oxygenation. Nursing care and specialization can have an impact on improving patient outcomes.(AU)

Adjuvant treatments to invasive mechanical ventilation in the management of acute respiratory distress syndrome secondary to COVID-19.

INTRODUCTION: This bibliographic review is carried out in order to obtain answers about aspects related to techniques and treatments, as well as care associated with the critically ill patient diagnosed with Covid-19. OBJECTIVE: To analyze the available scientific evidence on the effectiveness of the use of invasive mechanical ventilation together with other adjuvant techniques, in reducing the mortality rate in patients with Acute Respiratory Distress Syndrome and clinical trial of Covid-19 treated in intensive care units. METHODOLOGY: A systematized bibliographic review was carried out in the Pubmed, Cuiden, Lilacs, Medline, Cinahl and Google Scholar databases, using MeSH terms (Adult Respiratory Distress Syndrome, Mechanical Ventilation, Prone Position, Nitric Oxide, Extracorporeal Membrane Oxygenation, Nursing Care) and the corresponding Boolean operators. The selected studies underwent a critical reading carried out between December 6, 2020 and March 27, 2021 using the Critical Appraisal Skills Program tool in Spanish and a cross-sectional epidemiological studies evaluation instrument. RESULTS: A total of 85 articles were selected. After performing the critical reading, a total of 7 articles were included in the review, 6 being descriptive studies and 1 cohort study. After analyzing these studies, it appears that the technique that has obtained the best results is ECMO, with the care provided by qualified and trained nursing staff being very important. CONCLUSION: Mortality from Covid-19 increases in patients treated with invasive mechanical ventilation compared to patients treated with extracorporeal membrane oxygenation. Nursing care and specialization can have an impact on improving patient outcomes.

The effect of dexmedetomidine on expression of neuronal nitric oxide synthase in spinal dorsal cord in a rat model with chronic neuropathic pain / O efeito da dexmedetomidina na expressão do óxido nítrico sintase neuronal na medula espinhal dorsal em um modelo rato com dor neuropática crônica

Abstract Background Neuropathic pain typically refers to the pain caused by somatosensory system injury or diseases, which is usually characterized by ambulatory pain, allodynia, and hyperalgesia. Nitric oxide produced by neuronal nitric oxide synthase (nNOS) in the spinal dorsal cord might serve a predominant role in regulating the algesia of neuropathic pain. The high efficacy and safety, as well as the plausible ability in providing comfort, entitle dexmedetomidine (DEX) to an effective anesthetic adjuvant. The aim of this study was to investigate the effect of DEX on the expression of nNOS in spinal dorsal cord in a rat model with chronic neuropathic pain. Methods Male Sprague Dawley (SD) rats were randomly assigned into three groups: sham operation group (sham), (of the sciatic nerve) operation (CCI) group, and dexmedetomidine (DEX) group. Chronic neuropathic pain models in the CCI and DEX groups were established by sciatic nerve ligation. The thermal withdrawal latency (TWL) was measured on day 1 before operation and on day 1, 3, 7 and 14 after operation. Six animals were sacrificed after TWL measurement on day 7, and 14 days after operation, in each group, the L4-6 segment of the spinal cords was extracted for determination of nNOS expression by immunohistochemistry. Results Compared with the sham group, the TWL threshold was significantly decreased and the expression of nNOS was up-regulated after operation in the CCI and DEX groups. Compared with the CCI grou[, the TWL threshold was significantly increased and the expression of nNOS was significantly down-regulated on day 7 and 14 days after operation in the DEX group. Conclusion Down-regulated nNOS in the spinal dorsal cord is involved in the attenuation of neuropathic pain by DEX.

Resumo Antecedentes A dor neuropática refere-se tipicamente à dor causada por lesões ou doenças do sistema somatossensorial. De modo geral, é caracterizada por dor à ambulação, alodinia e hiperalgesia. O óxido nítrico produzido pela enzima óxido nítrico sintase neuronal (nNOS) na medula espinhal dorsal pode ter um papel predominante na regulação da dor neuropática. A alta eficácia e segurança, bem como a plausível capacidade de proporcionar conforto, faz com que a dexmedetomidina (DEX) seja um adjuvante anestésico eficaz. O objetivo deste estudo foi investigar o efeito da DEX na expressão de nNOS na medula espinhal dorsal em um modelo de ratos com dor neuropática crônica. Métodos Ratos Sprague Dawley (SD) machos foram distribuídos aleatoriamente em três grupos: grupo de cirurgia simulada (sham), grupo de cirurgia (do nervo ciático; CCI) e grupo dexmedetomidina (DEX). Os modelos de dor neuropática crônica nos grupos CCI e DEX foram estabelecidos por ligadura do nervo ciático. A latência de retirada térmica (TWL) foi medida no dia 1 antes da cirurgia e nos dias 1, 3, 7 e 14 após o procedimento. Seis animais de cada grupo foram eutanasiados após a medida de TWL nos dias 7 e 14 após a cirurgia e o segmento L4-6 da medula espinhal foi extraído para determinação da expressão de nNOS por imuno-histoquímica. Resultados Em comparação ao grupo sham, o limiar de TWL diminuiu significativamente e a expressão de nNOS foi regulada de maneira positiva após a cirurgia nos grupos CCI e DEX. Comparado ao grupo CCI, o limiar de TWL aumentou de forma significativa e a expressão de nNOS caiu significativamente diminuída nos dia 7 e 14 após a cirurgia no grupo DEX. Conclusão A regulação negativa de nNOS na medula espinhal dorsal está envolvida na atenuação da dor neuropática pela DEX.

Serum nitric oxide concentration in generalized chronic and aggressive periodontitis in the Mexican population is not related to the severity of the disease / La concentración de óxido nítrico en suero de pacientes con periodontitis agresiva y crónica generalizada no está relacionada con la gravedad de la enfermedad

Introduction: Periodontitis is an inflammatory disease that affects the supporting tissues of teeth, the effects of excess of nitric oxide, may contribute to the symptoms of periodontitis. Objective: To determine the serum nitric oxide concentration in generalized chronic and aggressive periodontitis patients and to compare it with a healthy subject group from the Mexican population. Materials and methods: A case and control study was performed. Sixty-nine individuals were recruited from the Clínica de Posgrado de Periodoncia of the Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, México. Patients with clinical features of generalized chronic periodontitis (GCP group, n=19), generalized aggressive periodontitis (GAP group, n=11), and a group of healthy subjects (HS group, n=39) were included in the study. Informed consent was obtained from each subject, and serum nitric oxide concentration was measured by an enzyme-linked immunosorbent assay. Results: Nitric oxide concentration in the study groups was greater in the GCP group (462.57 ± 16.57 µmol/L) than in the GAP group (433.84 ± 18.61 µmol/L) and the HS group (422.46 ± 12.07 µmol/L). A comparison using Student's t-test (one-tailed) between healthy subjects and generalized chronic periodontitis showed borderline significance (p<0.04), whereas no significant differences were observed in HS and GAP groups, with a p-value of 0.64, and the GAP vs. GCP p-value was 0.33. Conclusion: The serum nitric oxide concentration observed in the present study suggests that nitric oxide plays a major role in the inflammatory process, which cannot necessarily be linked to the severity of the disease and periodontal tissue destruction.

Introducción. La periodontitis es una enfermedad inflamatoria que afecta los tejidos de soporte dental; los efectos del exceso de óxido nítrico pueden contribuir a los síntomas de la periodontitis. Objetivo. Determinar la concentración de óxido nítrico en el suero de los pacientes con periodontitis agresiva y crónica generalizada, y compararla con la de individuos sanos de población mexicana. Materiales y métodos. Se trata de un estudio de casos y controles. Se incluyeron 69 individuos de la Clínica de Posgrado de Periodoncia del Centro Universitario de Ciencias de la Salud de la Universidad de Guadalajara. Se dividieron en tres grupos: pacientes con periodontitis crónica generalizada (GCP, n=19), pacientes con periodontitis agresiva generalizada (GAP, n=11) e individuos sanos periodontalmente (HS, n=39). Se obtuvo el consentimiento informado de todos los participantes. Se utililizó la prueba ELISA para medir la concentración de óxido nítrico en suero. Resultados. Las concentraciones de óxido nítrico observadas fueron mayores en el grupo GCP (462,57 ± 16,57 µmol/L) que en los grupos GAP (433,84 ± 18,61 µmol/L) y HS (422,46 ± 12,07 µmol/L). La comparación entre HS y GCP mediante la prueba estadística t de Student (una cola), mostró diferencias significativas (p<0,04), y no se observaron diferencias entre los grupos HS y GAP (p=0,64), ni entre GAP y GCP (p=0,33). Conclusiones. La concentración de óxido nítrico en suero, observada en el presente estudio, sugiere que el óxido nítrico desempeña un importante papel en el proceso inflamatorio, lo que no necesariamente está ligado a la gravedad de la enfermedad ni a la destrucción del tejido periodontal.

The relationship between reduced choroidal thickness due to high plasma asymmetrical dimethylarginine level and increased severity of diabetic retinopathy / Altos níveis de dimetil-arginina assimétrica no plasma podem aumentar a gravidade da retinopatia diabética através da redução da espessura da coroide

ABSTRACT Purpose: To evaluate the relationship between subfoveal choroidal thickness and plasma asymmetrical dimethylarginine level and the severity of diabetic retinopathy in patients with type 2 diabetes mellitus. Methods: A total of 68 cases, including 15 patients without diabetic retinopathy, 17 patients with nonproliferative diabetic retinopathy, 16 patients with type 2 diabetes mellitus and proliferative diabetic retinopathy, and 20 healthy patients (control group), were enrolled in this study. Subfoveal choroidal thickness was measured manually using the enhanced depth imaging optical coherence tomography scanning program, and plasma asymmetrical dimethylarginine level was measured using a commercial micro enzyme-linked immunosorbent assay kit. Results: The subfoveal choroidal thickness values and plasma asymmetrical dimethylarginine levels were significantly different between the four groups (p<0.001 and p<0.001). The subfoveal choroidal thickness values were significantly lower in the proliferative diabetic retinopathy group than in the other three groups (no diabetic retinopathy, nonproliferative diabetic retinopathy, and control groups; p<0.001, p=0.045, and p<0.001, respectively). The plasma asymmetrical dimethylarginine levels were significantly higher in the proliferative diabetic retinopathy group than in the other three groups (p<0.001, p<0.04, and p<0.001, respectively). In addition, a significant negative correlation was also found between plasma asymmetrical dimethylarginine level and subfoveal choroidal thickness (p<0.001, r=-0.479). Conclusion: Asymmetrical dimethylarginine is an important marker of endothelial dysfunction and endogenous endothelial nitric oxide synthase inhibitor. The severity of diabetic retinopathy was related to increased plasma asymmetrical dimethylarginine level and reduced subfoveal choroidal thickness in type 2 diabetic patients with diabetic retinopathy.

RESUMO Objetivo: Avaliar a relação da espessura subfoveal da coroide e dos níveis plasmáticos de dimetil-arginina assimétrica com a gravidade da retinopatia diabética em pacientes com diabetes mellitus tipo 2. Métodos: Foram incluídos 68 casos, compreendendo 15 pacientes sem retinopatia diabética, 17 pacientes com retinopatia diabética não proliferativa, 16 pacientes com retinopatia diabética proliferativa, e 20 casos saudáveis (grupo de controle). A espessura subfoveal da coroide foi medida manualmente, usando o programa de varredura com tomografia computadorizada óptica com imagem profunda aprimorada, e os níveis plasmáticos de dimetil-arginina assimétrica foram medidos usando um kit microELISA comercial. Resultados: Os valores da espessura subfoveal da coroide e os níveis plasmáticos de dimetil-arginina assimétrica foram significativamente diferentes nos quatro grupos (p<0,001 para ambos os parâmetros). Os valores da espessura subfoveal da coroide foram significativamente menores no grupo com retinopatia diabética proliferativa do que nos outros três grupos (sem retinopatia diabética, retinopatia diabética não proliferativa e grupo de controle, com p<0,001, p=0,045 e p<0,001, respectivamente). Já os níveis plasmáticos de dimetil-arginina assimétrica foram significativamente maiores no grupo com retinopatia diabética proliferativa do que nos outros três grupos (p<0,001, p=0,04 e p<0,001, respectivamente). Além disso, também foi encontrada uma correlação negativa significativa entre os níveis plasmáticos de dimetil-arginina assimétrica e a espessura subfoveal da coroide (p<0,001, r=-0,479). Conclusão: A dimetil-arginina assimétrica é um importante marcador de disfunção endotelial e um inibidor endógeno da óxido nítrico sintase. Foi encontrada uma relação da gravidade da retinopatia diabética e de níveis elevados de dimetil-arginina assimétrica no plasma com a redução da espessura subfoveal da coroide em pacientes diabéticos tipo 2 com retinopatia diabética.

Sex Differences in Baseline Risk Factors for Asthma Between Early Adolescence and Young Adulthood

Background: Several studies have shown sex differences in the prevalence of asthma and an association with age. The aim of the present study was to prospectively investigate the development of asthma, wheeze, rhinitis, and allergic symptoms in adolescence and adulthood. We also aimed to determine whether sex modifies the association between baseline risk factors and incidence of asthma in early adulthood. Methods: In the Screening Project Asthma in Schools (SPAIS) study, adolescents aged 12-15 years completed a standardized respiratory questionnaire (International Study of Asthma and Allergies in Childhood) and underwent measurements of fractional exhaled nitric oxide (FeNO) and lung function (FEV1) at baseline. Two follow-up assessments with similar questionnaires were performed after 4 and 16 years, with a total of 491 participants in all 3 examinations. Results: The prevalence of asthma and wheeze were unchanged after 4 years but had increased after 16 years. However, the increase was significant only for females. The prevalence of rhinitis and allergy symptoms increased steadily, albeit with no differences between the sexes. The sex interaction analysis showed that higher FeNO (P=.01) and a family history of asthma (P=.02) increased the risk of incident asthma for males but not for females. Conclusions: An increased prevalence of respiratory symptoms was seen primarily between late adolescence and young adulthood; the difference was significant for females but not for males. Allergic risk factors in early adolescence for incident asthma in early adulthood were confirmed in males but not in females. Awareness of these sex differences in the development of symptoms and of the associated risk factors is important in clinical practice (AU)

Antecedentes: Varios estudios han mostrado diferencias por sexo en la prevalencia del asma y una relación de la misma con la edad. El objetivo del presente estudio fue investigar prospectivamente el desarrollo de asma, sibilancias, rinitis y síntomas alérgicos, entre la adolescencia y la edad adulta. Más aún, determinar si el sexo modifica las asociaciones entre los factores de riesgo iniciales y la incidencia de asma en la edad adulta temprana. Métodos: En el estudio "Screening Project Asthma in Schools" (SPAIS), los adolescentes de 12 a 15 años respondieron un cuestionario respiratorio estandarizado (ISAAC) y se sometieron a mediciones de óxido nítrico exhalado (FeNO) y función pulmonar (FEV1) al inicio del estudio. Se realizaron dos seguimientos con cuestionarios similares después de 4 y 16 años, con 491 sujetos que participaron en los tres exámenes. Resultados: La prevalencia de asma y sibilancias se mantuvo sin cambios después de 4 años, pero aumentó a los 16 años. Sin embargo, el aumento fue significativo sólo para las mujeres. Un aumento más continuo de la rinitis y los síntomas alérgicos no mostró diferencias entre los sexos. El análisis de interacción sexual mostró que un FeNO más alto (p=0,01) y los antecedentes familiares de asma (p=0,02) aumentaron el riesgo de asma incidente para los hombres, pero no para las mujeres. Conclusiones: Se observó una mayor prevalencia de síntomas respiratorios principalmente entre la adolescencia tardía y la edad adulta temprana, que fue significativa para las mujeres pero no para los hombres. Los factores de riesgo alérgico en la adolescencia temprana para el asma incidente en la edad adulta temprana se confirmaron en hombres, pero no en mujeres. El conocimiento de estas diferencias por género en el desarrollo de los síntomas y los factores de riesgo asociados son importantes en la práctica clínica (AU)

Very Rapid Improvement in Extended Nitric Oxide Parameters Is Associated With Clinical and Functional Improvement in Patients With Chronic Rhinosinusitis With Nasal Polyps Treated With Dupilumab

Background: Dupilumab, an anti–IL-4 receptor a monoclonal antibody, was recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate-to-severe asthma. Onset of its clinical effects is rapid. CRSwNP is characterized by extended type 2 inflammatory involvement that can be assessed using extended nitric oxide analysis. Objectives: We investigated whether dupilumab was associated with a rapid improvement in extended nitric oxide parameters, lung function, and clinical outcomes in patients with CRSwNP. Methods: Consecutive patients with CRSwNP and an indication for dupilumab were evaluated for extended nitric oxide analysis (exhaled, FeNO; bronchial, JawNO; alveolar, CalvNO; nasal, nNO) and lung function 15 and 30 days after initiation of treatment and for clinical outcomes (nasal polyps score [NPS], quality of life questionnaires, visual analog scale [VAS] for the main symptoms, and the Asthma Control Test [ACT]) 30 days after initiation of treatment. Results: We enrolled 33 patients. All extended nitric oxide and lung function parameters improved significantly after 15 days of treatment, remaining stable at 30 days. Scores on the NPS, VAS for the main CRSwNP symptoms, quality of life questionnaires, and the ACT improved significantly 30 days after initiation of treatment. Conclusions: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway areas. This is associated with improved lung function and clinical parameters in patients with CRSwNP. (AU)

Antecedentes: El dupilumab, un anticuerpo monoclonal anti-IL-4 receptor alfa, ha sido aprobado recientemente para el tratamiento de la rinosinusitis crónica con pólipos nasales (CRSwNP) y asma de moderada a grave, demostrando un inicio rápido de los efectos clínicos. La CRSwNP se caracteriza por un infiltrado extenso inflamatorio de tipo 2 que puede evaluarse mediante el análisis de óxido nítrico exhalado extendido. Objetivos: En este estudio, investigamos si dupilumab se asocia con una mejora rápida en los parámetros de óxido nítrico extendido, la función pulmonar y los resultados clínicos en pacientes con CRSwNP. Métodos: Se incluyeron pacientes consecutivos con CRSwNP e indicación para ser tratados con dupilumab y fueron evaluados mediante el análisis de óxido nítrico extendido (exhalado, FENO; bronquial, JawNO y alveolar, componentes CalvNO; nasal, nNO) y función pulmonar, 15 y 30 días después del inicio del tratamiento; y en el caso de las variables clínicas (puntuación del tamaño de los pólipos nasales [NPS]; cuestionarios de calidad de vida; escalas analógicas visuales [EVA] para los principales síntomas principales, prueba de control del asma [ACT]) solo después de 30 días de iniciado el tratamiento. Resultados: Se incluyeron 33 pacientes. Todos los parámetros del análisis extendido del óxido nítrico y la función pulmonar mejoraron significativamente después de 15 días de tratamiento, permaneciendo estables a los 30 días de tratamiento. El NPS, las EVA para los principales síntomas de CRSwNP, el cuestionario de calidad de vida y el ACT mejoraron significativamente después de 30 días de inicio del tratamiento. Conclusiones: En pacientes con CRSwNP, el tratamiento con dupilumab se asocia con una mejoría muy rápida en la inflamación tipo 2 en todos los compartimentos de las vías respiratorias y esto se asocia con una mejor función pulmonar y los parámetros clínicos. (AU)

Why does ingestion of watermelon trigger headache attacks in patients with migraine? / Por que a ingestão de melancia desencadeia crises de dor de cabeça em pacientes com enxaqueca?

Several triggers can trigger a migraine attack, including food. By the way, food only triggers headache in migraine sufferers. The foods that most trigger headache attacks are these: cheese, chocolate, citrus fruits and some sweet fruits, such as watermelon.

Vários gatilhos podem desencadear uma crise de enxaqueca, incluindo alimentos. Aliás, a comida só provoca dor de cabeça em quem sofre de enxaqueca. Os alimentos que mais desencadeiam as crises de dor de cabeça são estes: queijo, chocolate, frutas cítricas e algumas frutas doces, como a melancia.

Efeitos Agudos do Nitrato Dietético na Pressão Central e Desempenho Cardíaco em Hipertensos: Estudo Cruzado, Randomizado e Placebo-Controlado / Acute Effects of Dietary Nitrate on Central Pressure and Endothelial Function in Hypertensive Patients: A Randomized, Placebo-Controlled Crossover Study

Resumo Fundamento O nitrato inorgânico (NO3-) da dieta pode fornecer substrato fisiológico para reduzir o nitrito (NO2-) a óxido nítrico (NO) independente do endotélio. Estudos sugerem que o NO3- inorgânico tem efeitos benéficos na saúde cardiovascular. Objetivos Este estudo avaliou os efeitos agudos de 500 mL de suco de beterraba rico em nitrato (SB; contendo 11,5mmol NO3-) na pressão arterial e na função endotelial em pacientes hipertensos tratados. Métodos Estudo cruzado, randomizado, controlado por placebo foi realizado em pacientes hipertensos tratados (n=37; mulheres=62%) que foram submetidos à avaliação clínica e nutricional, avaliação dos parâmetros hemodinâmicos centrais e reatividade microvascular. O nível de significância foi p<0,05. Resultados A média de idade foi 59±7 anos e das pressões sistólica e diastólica foi de 142±10/83±9 mmHg. Houve aumento significativo na taxa de viabilidade subendocárdica (RVSE; 149±25 vs. 165±30%, p<0,001) e redução na duração da ejeção (DE; 37±4 vs. 34±4%, p<0,001) na fase beterraba, mas nenhuma diferença significativa de RVSE na fase controle. O % de aumento na perfusão (155 vs. 159%, p=0,042) cresceu significativamente na fase beterraba, o que não foi observado na fase controle. Na fase beterraba, a alteração da RVSE apresentou correlação significativa com a alteração da área sob a curva de hiperemia reativa pós-oclusiva (ASC-HRPO) (r=0,45, p=0,012). A mudança na DE mostrou uma correlação significativa com pico de perfusão pós-intervenção (r=-0,37, p=0,031) e ASC-HRPO (r=-0,36, p=0,046). Conclusão A ingestão aguda de SB por pacientes hipertensos resultou em melhora da função endotelial, que foi associada à maior viabilidade subendocárdica e desempenho na contração miocárdica.

Abstract Background The diet's inorganic nitrate (NO3-) may provide a physiological substrate for reducing nitrate (NO2-) to NO independent of the endothelium. Studies suggest that inorganic NO3- has beneficial effects on cardiovascular health. Objective This study evaluated the acute effects of 500 mL nitrate-rich beetroot juice (BRJ; containing 11.5mmol NO3-) on blood pressure and endothelial function in treated hypertensive patients. Methods A randomized, placebo-controlled, crossover study was conducted in treated hypertensive patients (n=37; women=62%) who underwent clinical and nutritional evaluation and assessment of central hemodynamic parameters and microvascular reactivity. The significance level was p<0.05. Results The mean age was 59±7 years, and mean systolic and diastolic blood pressures were 142±10/83±9mmHg. There was a significant increase in the subendocardial viability ratio (SEVR; 149±25 vs. 165±30%, p<0.001) and reduction in ejection duration (ED; 37±4 vs. 34±4%, p<0.001) in the beetroot phase but no significant SEVR difference in the control phase. The % increase in perfusion (155 vs. 159 %, p=0.042) was significantly increased in the beetroot phase, which was not observed in the control phase. In the beetroot phase, the change in SEVR showed a significant correlation with the change in the area under the curve of post-occlusive reactive hyperemia (AUC-PORH) (r=0.45, p=0.012). The change in ED showed a significant correlation with the post-intervention perfusion peak (r=-0.37, p=0.031) and AUC-PORH (r=-0.36, p=0.046). Conclusions The acute ingestion of BRJ by hypertensive patients resulted in an improvement of endothelial function, which was associated with higher subendocardial viability and performance in myocardial contraction.

Revisión Sistemática Exploratoria sobre Uso de Óxido Nítrico Inhalado para Evaluación de Reactividad Vascular Pulmonar en Laboratorio de Hemodinamia en Sujetos Pediátricos con Hipertensión Pulmonar / Exploratory Systematic Review on the Use of Inhaled Nitric Oxide for Evaluation of Pulmonary Vascular Reactivity in Hemodynamics Laboratory in Pediatric Subjects with Pulmonary Hypertension

Introducción. La hipertensión arterial pulmonar (HAP) es una enfermedad que presenta un elevado índice de mortalidad en la población pediátrica. Para su diagnóstico, el gold standard es la prueba de reactividad vascular pulmonar (PRVP), debido a que permite medir la respuesta vasodilatadora del lecho vascular pulmonar frente a la administración de moléculas con acción terapéutica, como el óxido nítrico inhalado (iNO). Esta prueba al ser positiva se asocia a un mejor pronóstico. En la actualidad existe incertidumbre y falta de consenso sobre la indicación y administración de iNO durante la PRVP. Objetivo. Describir el uso reportado en la literatura sobre iNO en PRVP en sujetos pediátricos con HAP. Métodos. Revisión sistemática exploratoria sensible en bases de datos PubMed, Epistemonikos, Cochrane, Scopus, Lilacs y Scielo, que describen el uso de iNO durante la PRVP en sujetos pediátricos con HAP. Resultados. se identificaron 8.906 artículos, de los cuales se seleccionaron 5 para la revisión cualitativa. La PRVP se realizó durante el cateterismo cardiaco derecho (CCD) en sujetosentre 2 semanas y 18 años de edad. Los diagnósticos fueron HAP primaria, idiopática y asociada a patología cardiaca congénita, cardiomiopatía y enfermedad pulmonar. Esta prueba fue realizada en sujetos sólo con soporte de oxígeno o con sedación profunda en ventilación mecánica invasiva, con dosis variables de oxígeno (21 y 100%) e iNO (3 y 80 ppm), o asociado a otras moléculas como iloprostol®, dilitiazem, sildenafil y/o epoprostenol. La administración de iNO disminuyó presión de arteria pulmonar y la resistencia vascular pulmonar, con mantención de presión arterial sistémica y gasto cardiaco y sin complicaciones asociadas a su uso. Conclusiones. Existen escasos estudios sobre iNO en PRVP pediátrica y con calidad metodológica limitada. El iNO se utiliza como método diagnóstico de vaso reactividad en sujetos pediátricos con HAP asociada a cardiopatía congénita, primaria o secundaria. Los protocolos para su uso son variables con dosis entre 20 y 40 ppm, con o sin uso de oxigeno adicional, con tiempos poco precisos y sin consenso en equipos de administración.

Background. Pulmonary arterial hypertension (PAH) is a disease that has a high mortality rate among the pediatric population. For its diagnosis, the pulmonary vascular reactivity test (PVRT) is considered the "Gold Standard", because it allows to measure the vasodilator response of pulmonary vascular circulation with the administration of molecules with therapeutic action, such as inhaled nitric oxide (iNO). This test, when positive, is associated with a better prognosis of the disease. Currently, there's uncertainty and lack of consensus on the indication and administration of iNO during the PVRT. Objetives. to describe use of iNO in PVRT in pediatric users with PAH reported in the literature. Methods. Scoping review of studies published between 1992 and 2021 in PubMed, Epistemonikos, Cochrane, Scopus, Lilacs and Scielo databases, which describe the use of iNO during PVRT in pediatric users with PAH, in English and Spanish. Primary and secondary studies with a sensitive search strategy were considered. Results. 8,906 articles were identified, 40 were selected by title, 8 by full text, and 5 for final qualitative review. Of the total of articles selected, 3 were primary and 2 secondary studies. PVRT was performed during right heart catheterization (RHC) in a population between 2 weeks and 18 years old. Diagnoses were primary PAH, idiopathic PAH and PAH associated with congenital heart disease, cardiomyopathy and pulmonary disease. This test was carried out in subjects on spontaneous ventilation with oxygen support or with deep sedation in invasive mechanical ventilation, with variable oxygen doses between 21 and 100%, with exclusive use of iNO between 3 and 80 ppm, being more used between 20 and 40 ppm, or associated with other molecules such as iloprostol®, dilithiazim, sildenafil and / or epoprostenol. In all selected studies, administration of iNO decreased PAP (pulmonary artery pressure) and PVR (pulmonary vascular resistance), with maintenance of SBP (systemic arterial blood pressure) and cardiac output. The primary studies were made up of pre and post-test of serial or parallel interventions. The selected studies of iNO in PVRT did not report complications associated with its use. Conclusions. studies on iNO in pediatric PVRT are scarce in number of publications and methodological quality. iNO is used as a diagnostic method of vasoreactivity in pediatric users with PAH associated with congenital, primary, or secondary heart disease. The protocols for its use are variable with recommended doses between 20 and 40 ppm, with or without the use of additional O2, with imprecise times and without consensus in administration equipment. The response to PVRT serves as a guide for the treatment and prognosis of pediatric users with PAH.

Assessing the nitric oxide and asymmetric dimethylarginine levels in lifelong premature ejaculation: A prospective study / Evaluación de los niveles de óxido nítrico y dimetilarginina asimétrica en la eyaculación precoz de por vida, un estudio prospectivo

Objective: To evaluate nitric oxide (NO) and asymmetric dimethylarginine (ADMA) levels in men with premature ejaculation (PE), which is a common condition that adversely affects quality of life. Material and method: Of the 20–50-year old men presenting to the urology clinic, who were married or had regular sexual intercourse, 40 that were diagnosed with lifelong PE according to the Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculation latency time (IELT) measured by a stopwatch were included in the study. The results of the PE group were compared to those of the control group formed with 40 healthy hospital personnel. Venous blood samples were centrifuged and stored at −80°C. The NO and ADMA values were compared between the individuals with and without PE. Results: There was no statistically significant difference between the groups in terms of age, body mass index (BMI), and The International Erectile Dysfunction Index-5 (IIEF-5) questionnaire scores. The NO and ADMA values were significantly lower in the PE group than in the control group (29.76±13.26μmol/L vs. 48.27±22.71μmol/L; p<0.001 and 1.01±0.49nmol/ml vs. 1.83±1.06nmol/ml; p<0.001, respectively). There was a significant correlation between IELT and NO levels (r=0.407, p=0.001). Conclusion: Our study can contribute to the explanation of the pathophysiology of PE having unclear etiology and treatment. Further studies on these molecules with larger case series are required for the diagnosis and treatment of PE. (AU)

Objetivo: Evaluar los niveles de óxido nítrico (NO) y dimetilarginina asimétrica en hombres con eyaculación precoz (EP), que es una afección común que afecta negativamente la calidad de vida. Material y método: De los hombres de 20 a 50 años que acudieron a la clínica de urología, que estaban casados o tenían relaciones sexuales regulares, se incluyeron en el estudio 40 que fueron diagnosticados con EP de por vida según la Herramienta de Diagnóstico de la Eyaculación Precoz y el tiempo de latencia de la eyaculación intravaginal medidos por un cronómetro. Se compararon los resultados del grupo de EP con los del grupo control formado por 40 personas sanas del hospital. Las muestras de sangre venosa se centrifugaron y almacenaron a −80°C. Se compararon los valores de NO y dimetilarginina asimétrica entre los individuos con y sin EP. Resultados: No hubo diferencias estadísticamente significativas entre los grupos en términos de edad, índice de masa corporal y puntajes del cuestionario International Erectile Dysfunction Index-5. Los valores de NO y dimetilarginina asimétrica fueron significativamente más bajos en el grupo de EP que en el grupo control (29,76±13,26 frente a 48,27±22,71μmol/l [p<0,001] y 1,01±0,49 frente a 1,83±1,06nmol/ml [p<0,001], respectivamente). Hubo una correlación significativa entre los niveles de tiempo de latencia de la eyaculación intravaginal y NO (r=0,407, p=0,001). Conclusión: Nuestro estudio puede contribuir a la explicación de la fisiopatología de la EP de etiología y tratamiento poco claros. Se requieren más estudios sobre estas moléculas con series de casos más grandes para el diagnóstico y tratamiento de la EP. (AU)

Relationship between exhaled nitric oxide and biomarkers of atopy in children and adolescents with allergic rhinitis.

INTRODUCTION: Measurement of the exhaled nitric oxide fraction (FeNO) has been proposed as an indirect and non-invasive method to detect eosinophilic airway inflammation. Allergic rhinitis (AR) is frequently associated with high levels of FeNO. Allergic sensitization can contribute to the recruitment of eosinophils in the airway and the consequent increase in FeNO. OBJECTIVE: To correlate FeNO values with inflammatory and atopic sensitization biomarkers in patients with AR. PATIENTS AND METHODS: Observational, analytical, cross-sectional study. Children and adolescents with AR without asthma were included. FeNO, blood eosinophil count, total serum IgE were determined and skin tests with aeroallergens were performed by calculating the scores for PPC1 (number of positive allergens), STS2 (sum of millimeters of positive papules) and the atopy index (ratio between STS2/STS1). Spearman's correlation test was used between FeNO and variables of inflammation and atopy. RESULTS: Twenty-eight patients between 6 and 17 years old were included. There was a significant positive correlation between FeNO and blood eosinophils (r=.38; p=.047) and between FeNO and the atopy index (r=.40; p=.03). No correlation was found between FeNO and total serum IgE (r=.24; p=.21), STS1 (r=.20; p=.32) and STS2 (r=.34; p=.08). CONCLUSION: In children and adolescents with AR, FeNO was correlated with the atopy index and the blood eosinophil count. These last biomarkers could be used as alternatives for FeNO as biomarkers of lower airway inflammation in patients with AR.

Relationship between exhaled nitric oxide and biomarkers of atopy in children and adolescents with allergic rhinitis

Introduction: Measurement of the exhaled nitric oxide fraction (FeNO) has been proposed as an indirect and non-invasive method to detect eosinophilic airway inflammation. Allergic rhinitis (AR) is frequently associated with high levels of FeNO. Allergic sensitization can contribute to the recruitment of eosinophils in the airway and the consequent increase in FeNO.ObjectiveTo correlate FeNO values with inflammatory and atopic sensitization biomarkers in patients with AR.Patients and methodsObservational, analytical, cross-sectional study. Children and adolescents with AR without asthma were included. FeNO, blood eosinophil count, total serum IgE were determined and skin tests with aeroallergens were performed by calculating the scores for PPC1 (number of positive allergens), STS2 (sum of millimeters of positive papules) and the atopy index (ratio between STS2/STS1). Spearman's correlation test was used between FeNO and variables of inflammation and atopy.ResultsTwenty-eight patients between 6 and 17 years old were included. There was a significant positive correlation between FeNO and blood eosinophils (r=.38; p=.047) and between FeNO and the atopy index (r=.40; p=.03). No correlation was found between FeNO and total serum IgE (r=.24; p=.21), STS1 (r=.20; p=.32) and STS2 (r=.34; p=.08).ConclusionIn children and adolescents with AR, FeNO was correlated with the atopy index and the blood eosinophil count. These last biomarkers could be used as alternatives for FeNO as biomarkers of lower airway inflammation in patients with AR. (AU)

Antecedentes: La determinación de la fracción exhalada de óxido nítrico (FeNO) ha sido propuesta como un método indirecto no invasivo para detectar la inflamación eosinofílica de la vía aérea. La rinitis alérgica (RA) se asocia frecuentemente con la FeNO elevada. La sensibilización a alérgenos puede contribuir al reclutamiento de eosinófilos en la vía aérea y el consiguiente incremento de la FeNO.ObjetivosCorrelacionar los valores de la FeNO con los biomarcadores inflamatorios y de sensibilización atópica en los pacientes con RA.Pacientes y métodosEstudio observacional, analítico y transversal. Se incluyeron niños y adolescentes con RA, sin asma. Se determinó la FeNO, el recuento de eosinófilos en sangre, la IgE sérica total, y se realizaron pruebas cutáneas con aeroalérgenos calificando los puntajes PPC1 (número de alérgenos positivos), PPC2 (suma de los milímetros de las pápulas positivas) y el índice de atopia (cociente entre milímetros de pápulas positivas/número de antígenos positivos). Se utilizó la prueba de correlación de Spearman entre la FeNO y las variables de inflamación y atopia.ResultadosSe incluyeron 28 pacientes entre 6 y 17 años. Se comprobó una correlación positiva significativa entre la FeNO y los eosinófilos en sangre (r=0,38; p=0,047), y el índice de atopia (r=0,40; p=0,03). No hubo correlación entre la FeNO con IgE sérica total (r=0,24; p=0,21) y con PPC1 (r=0,20; p=0,32) y PPC2 (r=0,34; p=0,08).ConclusionesEn niños y adolescentes con RA, la FeNO se correlacionó con el recuento de eosinófilos hemáticos y el índice de atopia. Estos últimos podrían utilizarse como sustitutos de la FeNO como biomarcadores de inflamación bronquial en pacientes con RA. (AU)

Efecto del óxido nítrico inhalado en la mecánica ventilatoria y oxigenación de pacientes con hipoxemia grave refractaria a prono prolongado y bloqueo neuromuscular secundario a infección por SARS-CoV-2 / Effect of inhaled nitric oxide on ventilatory mechanics and oxygenation of patients with severe hypoxemia refractory to prolonged prone and neuromuscular blockade secondary to SARS-CoV-2 / Efeito do óxido nítrico inalado na mecânica ventilatória e oxigenação de pacientes com hipoxemia grave refratária a pronação prolongada e bloqueio neuromuscular secundário à infecção por SARS-CoV-2

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Abstract: Introduction: Among the patients infected with SARS-CoV-2, 14.6% were admitted to intensive care unit. this 29 to 75% required invasive mechanical ventilation with an associated mortality of 12 to 81%. Acute respiratory distress syndrome (ARDS) is the most serious form of presentation. The pathophysiology of ARDS secondary to SARS-CoV-2 differs from conventional causes. It presents dysregulation in hypoxic pulmonary vasoconstriction, secondary acute pulmonary hypertension and microthrombotic phenomena. The development of refractory severe hypoxemia (PaO2 < 60 mmHg or PaO2/FiO2 < 100 mmHg, with FiO2 80 to 100%, with PEEP > 10 to 20 cmH2O for at least 10 to 12 hours) constitutes the scenario of maximum severity with an associated mortality of 71 to 94%. The use of rescue strategies that impact on the specific pathophysiology of this entity such as the use of inhaled nitric oxide, neuromuscular blockade and prone ventilation have emerged as therapeutic targets of interest. Protective mechanical ventilation (plateau pressure [Pplat] < 27 cmH2O and driving pressure [DP] < 15 cmH2O) continues to be the cornerstone of the management. Objectives: To determine whether there is an association between the use of inhaled nitric oxide and prone ventilation with ventilatory mechanics in patients with severe refractory hypoxemia secondary to SARS-CoV-2 infection. Material and methods: A historical, retrospective, descriptive, comparative and retrolective cohort study was carried out. Data from the records of patients admitted to the Respiratory ICU of the ABC Medical Center with a diagnosis of ARDS secondary to SARS-CoV-2 infection who required iNO and mechanical ventilation in prone from April 1 to December 31, 2020 were analyzed. A univariate analysis was performed, the statistical analysis was performed in SPSS v 21, measures of trend, dispersion were analyzed as well as the analysis of risk factors with Student's t test and χ2. Results: A total of 108 patients were analyzed, of which 54 received iNO, neuromuscular blockade and prone and 54 only neuromuscular blockade and prone ventilation. 81.5% (n = 88) were men. The most common comorbidity was diabetes mellitus in 51.9% (n = 56). The increase in oxygenation (delta PaO2/FiO2) was with a median of 31.9 ± 15.2 mmHg in the iNO group and 52.9 ± 16.74 mmHg in the control group (p = 0.001). The postintervention Pplat in the iNO group was 26.3 ± 3 and 34.5 ± 1.9 cmH2O in the control group (p = 0.792). The preintervention DP in the iNO group was 17.2 ± 3.9 and 13.4 ± 2.8 cmH2O in control group vs 13.1 ± 1.29 and 12 ± 1.92 cmH2O after the intervention (p = 0.001). Conclusions: The use of iNO in patients with severe hypoxemia refractory to prone ventilation and neuromuscular blockade did not produce a statistically significant improvement in oxygenation, however it allowed to reprogram the ventilatory support to keep the patient in goals of alveolar protection.

Resumo: Introdução: 14.6% dos pacientes infectados com SARS-CoV-2 são internados em terapia intensiva. Destes, 29 a 75% necessitam de ventilação mecânica invasiva com mortalidade associada de 12 a 81%. A síndrome do desconforto respiratório agudo (SDRA) é a forma mais grave de apresentação. A fisiopatologia da SDRA secundária ao SARS-CoV-2 difere das causas convencionais. Apresenta desregulação na vasoconstrição pulmonar hipóxica, hipertensão pulmonar aguda secundária e fenômenos microtrombóticos. O desenvolvimento de hipoxemia grave refratária (PaO2 < 60 mmHg ou PaO2/FiO2 < 100 mmHg, com FiO2 de 80 a 100%, PEEP > 10 a 20 cmH2O por pelo menos 10 a 12 horas) constitui o cenário mais grave com mortalidade associada de 71 a 94%. O uso de estratégias de resgate que impactam na fisiopatologia específica dessa entidade, como o uso de óxido nítrico inalatório (NOi), bloqueio neuromuscular e ventilação prona, surgiram como alvos terapêuticos de interesse. A ventilação mecânica protetora (Pressão de Platô [PPLAT] < 27 cmH2O e Pressão de Condução [CP] < 15 cmH2O) continua sendo a base de seu manejo. Objetivo: Determinar se existe associação entre o uso de óxido nítrico inalatório e ventilação prona prolongada com mecânica ventilatória em pacientes com hipoxemia refratária grave secundária à infecção por SARS-CoV-2. Material e métodos: Realizou-se um estudo de coorte histórico, retrospectivo, descritivo, comparativo e retroletivo. Analisaram-se dados dos prontuários de pacientes internados na UTI Respiratória do Centro Médico ABC com diagnóstico de SDRA secundária à infecção por SARS-CoV-2 que necessitaram de óxido nítrico inalatório e ventilação mecânica prona no período de 1o de abril a 31 de dezembro de 2020. Realizou-se uma análise univariada , a análise estatística foi realizada no SPSS v 21, foram analisadas as medidas de tendência e dispersão, assim como a análise dos fatores de risco com teste t de Student e χ2. Resultados: Analisaram-se 108 pacientes, dos quais 54 receberam NOi, bloqueio neuromuscular e prono e 54 apenas bloqueio neuromuscular e ventilação prona. 81.5% (n = 88) eram homens. A comorbidade mais comum foi diabetes mellitus em 51.9% (n = 56). O aumento da oxigenação (Delta PaO2/FiO2) foi com mediana de 31.9 ± 15.2 mmHg no grupo NOi e 52.9 ± 16.74 mmHg no grupo controle (p = 0.001). A PPLAT após a intervenção no grupo NOi foi de 26.3 ± 3 e 34.5 ± 1.9 cmH2O no grupo controle (p = 0.792). A PC antes da intervenção no grupo NOi foi de 17.2 ± 3.9 e 13.4 ± 2.8 cmH2O no grupo controle vs 13.1 ± 1.29 e 12 ± 1.92 cmH2O após a intervenção (p = 0.001). Conclusões: O uso de NOi em pacientes com hipoxemia grave refratária à ventilação em pronação e bloqueio neuromuscular não produziu melhora estatisticamente significativa na oxigenação, porém permitiu que o suporte ventilatório fosse reprogramado para manter as metas de proteção alveolar do paciente.

Assessing the nitric oxide and asymmetric dimethylarginine levels in lifelong premature ejaculation: A prospective study.

OBJECTIVE: To evaluate nitric oxide (NO) and asymmetric dimethylarginine (ADMA) levels in men with premature ejaculation (PE), which is a common condition that adversely affects quality of life. MATERIAL AND METHOD: Of the 20-50-year old men presenting to the urology clinic, who were married or had regular sexual intercourse, 40 that were diagnosed with lifelong PE according to the Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculation latency time (IELT) measured by a stopwatch were included in the study. The results of the PE group were compared to those of the control group formed with 40 healthy hospital personnel. Venous blood samples were centrifuged and stored at -80°C. The NO and ADMA values were compared between the individuals with and without PE. RESULTS: There was no statistically significant difference between the groups in terms of age, body mass index (BMI), and The International Erectile Dysfunction Index-5 (IIEF-5) questionnaire scores. The NO and ADMA values were significantly lower in the PE group than in the control group (29.76±13.26µmol/L vs. 48.27±22.71µmol/L; p<0.001 and 1.01±0.49nmol/ml vs. 1.83±1.06nmol/ml; p<0.001, respectively). There was a significant correlation between IELT and NO levels (r=0.407, p=0.001). CONCLUSION: Our study can contribute to the explanation of the pathophysiology of PE having unclear etiology and treatment. Further studies on these molecules with larger case series are required for the diagnosis and treatment of PE.

Vericiguat en insuficiencia cardíaca: de la evidencia científica a la práctica clínica / Vericiguat in heart failure: from scientific evidence to clinical practice

A pesar de los tratamientos actuales, el riesgo de muerte y hospitalizaciones en pacientes con insuficiencia cardíaca con fracción de eyección reducida (IC-FEr) sigue siendo elevado. La fisiopatología de la IC-FEr incluye activación neurohormonal caracterizada por la estimulación de las vías deletéreas (sistemas simpático y renina-angiotensina-aldosterona) y la supresión de las vías protectoras como las dependientes del óxido nítrico. La inhibición o estimulación de algunas de estas vías, pero no de todas, es insuficiente. En la IC-FEr existe una menor actividad de óxido nítrico, guanilato ciclasa soluble y GMPc que provoca efectos deletéreos a nivel miocárdico, vascular y renal. Vericiguat estimula la actividad de esta vía protectora. El estudio VICTORIA demostró, en pacientes con IC-FEr y descompensación reciente, que la adición de vericiguat al tratamiento médico óptimo reducía de forma significativa la incidencia del objetivo primario compuesto de muerte cardiovascular u hospitalización por IC, con un número de 24 pacientes que es necesario tratar, y una excelente tolerabilidad (AU)

Despite currently available treatments, risk of death and hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF) remains high. The pathophysiology of HFrEF includes neurohormonal activation characterized by stimulation of deleterious pathways (i.e., sympathetic nervous and renin-angiotensin-aldosterone systems) and suppression of protective pathways such as nitric oxide-dependent pathways. Inhibition or stimulation of some, but not all, of these pathways is insufficient. In HFrEF, there is reduced nitric oxide, soluble guanylate cyclase, and cGMP activity, leading to deleterious effects in the myocardial, vascular, and renal systems. Vericiguat is able to stimulate the activity of this protective pathway. The VICTORIA study demonstrated that the addition of vericiguat to optimal medical treatment in patients with HFrEF and recent decompensation significantly reduced the incidence of the primary endpoint, a composite of cardiovascular death or HF hospitalization, with a number needed to treat of 24 patients and excellent tolerability (AU)

P2X7 receptor-nitric oxide interaction mediates apoptosis in mouse immortalized mesangial cells exposed to high glucose / A interação do receptor P2X7 com o óxido nítrico medeia a apoptose em células mesangiais imortalizadas de camundongos expostas a níveis elevados de glicose

Abstract Introduction: Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia that leads to diabetic nephropathy (DN). We showed that P2X7, a purinergic receptor, was highly expressed in DM; however, when oxidative stress was controlled, renal NO recovered, and the activation of this receptor remained significantly reduced. The aim of this study was to assess the influence of NO on the P2X7 and apoptosis in mouse immortalized mesangial cells (MiMC) cultured in high glucose (HG) medium. Methods: MiMCs were cultured with DMEM and exposed to normal glucose (NG), mannitol (MA), or HG. Cell viability was assessed by an automated counter. Supernatants were collected for NO quantification, and proteins were extracted for analysis of NO synthases (iNOS and eNOS), caspase-3, and P2X7. Results: Cell viability remained above 90% in all groups. There was a significant increase in the proliferation of cells in HG compared to MA and NG. NO, iNOS, caspase-3, and P2X7 were significantly increased in HG compared to NG and MA, with no changes in eNOS. We observed that there was a strong and significant correlation between P2X7 and NO. Discussion: The main finding was that the production of NO by iNOS was positively correlated with the increase of P2X7 in MCs under HG conditions, showing that there is a common stimulus between them and that NO interacts with the P2X7 pathway, contributing to apoptosis in experimental DM. These findings could be relevant to studies of therapeutic targets for the prevention and/or treatment of hyperglycemia-induced kidney damage to delay DN progression.

Resumo Introdução: Diabetes mellitus (DM) é uma doença crônica caracterizada por hiperglicemia levando à nefropatia diabética (ND). Mostramos que P2X7, um receptor purinérgico, foi altamente expresso na DM; entretanto, quando o estresse oxidativo foi controlado, o NO renal recuperou-se, e a ativação deste receptor permaneceu significativamente reduzida. Este estudo objetivou avaliar a influência do NO no P2X7 e a apoptose em células mesangiais imortalizadas de camundongos (CMiC) cultivadas em meio de glicose elevada (GE). Métodos: CMiCs foram cultivadas em meio DMEM e expostas à glicose normal (GN), manitol (MA), ou GE. A viabilidade celular foi avaliada por contador automático. Sobrenadantes foram coletados para quantificação de NO, e foram extraídas proteínas para análise de NO sintases (iNOS e eNOS), caspase-3, e P2X7. Resultados: A viabilidade celular permaneceu acima de 90% em todos os grupos. Houve aumento significativo na proliferação de células na GE comparado com MA e GN. NO, iNOS, caspase-3 e P2X7 foram significativamente aumentados na GE comparados com GN e MA, sem alterações na eNOS. Observamos que houve correlação forte e significativa entre P2X7 e NO. Discussão: O principal achado foi que a produção de NO pela iNOS foi positivamente correlacionada com aumento de P2X7 em CMs sob condições de GE, mostrando que existe um estímulo comum entre eles e que o NO interage com a via do P2X7, contribuindo para apoptose na DM experimental. Estes achados podem ser relevantes para estudos de alvos terapêuticos para a prevenção e/ou tratamento de danos renais induzidos por hiperglicemia para retardar a progressão da ND.