Hyperoxia: Effective Mechanism of Hyperbaric Treatment at Mild-Pressure.

HBOT increases the proportion of dissolved oxygen in the blood, generating hyperoxia. This increased oxygen diffuses into the mitochondria, which consume the majority of inhaled oxygen and constitute the epicenter of HBOT effects. In this way, the oxygen entering the mitochondria can reverse tissue hypoxia, activating the electron transport chain to generate energy. Furthermore, intermittent HBOT is sensed by the cell as relative hypoxia, inducing cellular responses such as the activation of the HIF-1α pathway, which in turn, activates numerous cellular processes, including angiogenesis and inflammation, among others. These effects are harnessed for the treatment of various pathologies. This review summarizes the evidence indicating that the use of medium-pressure HBOT generates hyperoxia and activates cellular pathways capable of producing the mentioned effects. The possibility of using medium-pressure HBOT as a direct or adjunctive treatment in different pathologies may yield benefits, potentially leading to transformative therapeutic advancements in the future.

Altitude Diving on a Closed Circuit Oxygen Rebreather.

Closed-circuit rebreather diving is becoming more common. Rebreathers are complicated, adding to the stress of diving. Also adding to this complexity in the presented case is diving at a high-altitude, cold-water reservoir in Colorado. One diver experienced an oxygen-induced seizure at depth. The other diver had a rapid ascent with loss of consciousness. In this case, two experienced divers recovered from a possible devastating dive. Fortunately, they both returned to their pre-dive baseline health. Dive plan- ning is important, but as in this case, dive execution is paramount. This is a clinical case for an uncommon event presenting to an emergency department.

One-Pot Synthesis and in Silico Molecular Docking Studies of Arylselanyl Hydrazides as Potential Antituberculosis Agents.

The present study reports a simple two-step method for the synthesis of arylselanyl hydrazide derivatives using hypophosphorous acid and polyethylene glycol (H3 PO2 /PEG-400) as an alternative reducing system and hydrazine hydrate (NH2 NH2 ⋅xH2 O/50-60 %). This single-vessel procedure was employed with methyl acrylate 2a and methyl bromoacetate 2b using diaryl diselenides to generate the nucleophile species to produce, respectively, 3-(arylselanyl)propane-hydrazides 4a-e and 2-(arylselanyl)acetohydrazides 5a-e with good yields by accelerating the reduction of -Se-Se- bond, when compared to available methods. The synthesized molecules are structurally similar to the isoniazid (INH). Therefore, we perform in silico molecular docking studies, using the lactoperoxidase enzyme, in order to verify whether the INH Se derivatives could interact in a similar way to INH at the active site of the mammalian enzyme. The in silico results indicated a similar type of interaction of the arylselanyl hydrazide derivatives with that of INH. In view of the similar in silico interaction of the selenium derivatives of INH, the arylselanyl hydrazide derivatives reported here should be tested against Mycobacterium tuberculosis in vitro.

Correlación de índice PO2/FiO2 con parámetros inflamatorios y de coagulación en pacientes críticos con covid-19. Lombardía, 2020 / PO2/FiO2 index correlation with inflammatory and coagulation parameters in critically-ill patients with COVID-19 in Lombardy, 2020

RESUMEN Introducción: el conocimiento de la fisiopatología de la enfermedad ha revolucionado el enfoque tradicional en el tratamiento de las enfermedades causadas por virus respiratorios. Actualmente, se utilizan marcadores de la respuesta inflamatoria para diagnosticar, estratificar y predecir en muchos casos el comportamiento futuro del enfermo de covid-19. Objetivo: caracterizar la naturaleza de la relación entre el índice PO2/FiO2 y los parámetros inflamatorios y de coagulación en pacientes graves por la covid-19, en la región de Lombardía, Italia. Materiales y métodos: se realizó un estudio analítico, longitudinal, retrospectivo con 191 pacientes graves y críticos, que ingresaron con diagnóstico de covid-19 del 1 de abril al 20 mayo de 2020, en el Hospital Mayor de Crema, en la región de Lombardía, Italia. Resultados: las correlaciones evidenciadas fueron las siguientes: proteína C reactiva (-0,417) p = 0; procalcitonina (-0,152) p = 0,018; dímero D (-0,112) p = 0,061; fibrinógeno (-0,272) p = 0,000; creatinina plasmática (-0,320) p = 0,000; conteo de linfocitos (0,028) p = 0,000; troponina (-0,028) p = 0,142, y lactato (-0,191) p = 0,288. Conclusiones: los marcadores inflamatorios en la patogenia de la enfermedad juegan un rol capital, y el enfoque hacia este renglón del tratamiento médico antiinflamatorio de cualquier tipo es mandatorio. Se debe realizar un correcto monitoreo de la coagulación, usar heparinas de bajo peso molecular, así como mantener un adecuado soporte hemodinámico capaz de evitar las disoxias celulares que progresen al fallo multiorgánico (AU).

ABSTRACT Introduction: the knowledge of disease physiopathology has revolutionized the traditional approach in the treatment of diseases caused by respiratory viruses. Currently, the markers of inflammatory answer are used to diagnose, stratify and predict in many cases the future behavior of COVID-19 patients. Objective: to characterize the nature of the relationship between PO2/FiO2 (PAFI, Spanish acronym of PA= presión arterial [arterial pressure], FI=fracción inspirada [inspired fraction]) and coagulation and inflammatory parameters in seriously-ill patients with COVID-19, in the region of Lombardy, Italy. Materials and methods: a retrospective, longitudinal, analytic study was carried out in 191 severe and critical patients who were admitted in Hospadale Maggiori di Crema, in the region of Lombardy, Italy, with the diagnosis of COVID-19, in the period April 1st-May 20, 2020. Results: the evidenced correlations were the following: reactive C protein (-0.417) p=0; procalcitonin (PCT) (-0.152) p=0.018. D dimer (-0.112) p=0.061; Fibrinogen (-0.272) p=0.000; Plasma creatinine (-0.320) p=0.000; lymphocytes count (0,028) p=0,000; troponin (-0.028) p=0.142; and lactate (-0.191) p=0.288. Conclusions: inflammatory markers play a capital role in the disease pathogenesis, and approaching this item of the medical anti-inflammatory treatment is mandatory. It is useful to keep a correct coagulation screening, using low molecular weight heparins, and also keeping an adequate hemodynamic support able to avoid cell dysoxia progressing to multiorgan failure (AU).

Modelo temporal del comportamiento de pacientes críticos con covid-19 durante su estadía en cuidados intensivos. Lombardía, Italia / Temporal model of the behavior of critically ill patients with COVID-19 during their staying in intensive care. Lombardy, Italy

RESUMEN Introducción: una serie temporal es el producto de la observación de una variable en el tiempo. Es una herramienta matemática que se aplica con frecuencia en la salud. No se han elaborado modelos temporales que predigan el comportamiento de los pacientes durante su ingreso en la Unidad de Cuidados Intensivos. Objetivos: crear una serie temporal que permita predecir el comportamiento, durante su ingreso en la Unidad de Cuidados Intensivos, de pacientes graves producto de la covid-19 en la región de Lombardía, Italia. Materiales y métodos: analítico, longitudinal prospectivo con un grupo de pacientes críticos que ingresaron del 1 de abril al 1 de mayo de 2020, con diagnóstico de covid-19, en el Hospital Mayor de Crema, en la región de Lombardía, Italia. El universo estuvo constituido por 28 pacientes y se trabajó con el total de ellos. Resultados: composición por sexo: 48 % masculino. Media de edad: 83 años. Serie temporal: Modelo 1 que ajusta (Hold) PO2/FiO2 p = 0,251; Modelo 2 (ARIMA) SatO2/FiO2 p = 0,674 (en los dos primeros modelos el resultado se incrementó con los días, siguiendo un comportamiento predecible); Modelo 3 (ARIMA) p = 0,406 (en este caso, el resultado esperado decreció a medida que transcurrió el tiempo). Las funciones obtenidas permiten calcular el valor esperado según el día desde el ingreso. Conclusiones: predecir la evolución del paciente en la Unidad de Cuidados Intensivos permitió detectar tempranamente aquellos con una curva inesperada y dirigir hacia a ellos las terapéuticas más agresivas (AU).

ABSTRACT Introduction: a time series is the product of the observation of a variable in time. It is a mathematical tool frequently applied in health. No temporal models have been developed to predict patients' behavior during their staying in the Intensive Care Unit. Objectives: to create a time series allowing to predict the behavior of seriously-ill patients due to COVID-19, during their staying in the Intensive Care Unit in the region of Lombardy, Italy. Materials and methods: analytic, longitudinal prospective study with a group of critical patients who were admitted from April 1st to May 1st, with COVID-19 diagnosis, to Ospedale Maggiore di Crema, in the Lombardy region, Italy. The universe was formed by 28 patients and all of them were worked on. Results: 48% of patients were male. Average age: 83 years; Time series: Model 1 holding PO2/FiO2 p = 0.251; Model 2 (ARIMA) SatO2/FiO2 p = 0.674 (in the two first models the result increased with the days, following a predictable behavior=; Model 3 (ARIMA) p = 0.406 (in this case the expected result decreased as time passed). The obtained functions allow to calculate the expected value according to the day from the admission. Conclusions: predicting patient's evolution in the Intensive Care Unit allowed early detecting those with unexpected curves and targeting more aggressive therapies toward them (AU).

Pharmacological safety of Plinia cauliflora (Mart.) Kausel in rabbits.

Fruit peels of Plinia cauliflora (Mart.) Kausel are widely used in Brazilian traditional medicine, but no studies have proved the safety of its pharmacological effects on the respiratory, cardiovascular, and central nervous systems. The present study assessed the safety pharmacology of P. cauliflora in New Zealand rabbits. First, an ethanol extract (EEPC) was selected for the pharmacological experiments and chemical characterization. Then, different groups of rabbits were orally treated with EEPC (200 and 2000 mg/kg) or vehicle. Acute behavioral and physiological alterations in the modified Irwin test, respiratory rate, arterial blood gas, and various cardiovascular parameters (i.e., heart rate, blood pressure, and electrocardiography) were evaluated. The main secondary metabolites that were identified in EEPC were ellagic acid, gallic acid, O-deoxyhexosyl quercetin, and the anthocyanin O-hexosyl cyanidin. No significant behavioral or physiological changes were observed in any of the groups. None of the doses of EEPC affected respiratory rate or arterial blood gas, with no changes on blood pressure or electrocardiographic parameters. The present study showed that EEPC did not cause any significant changes in respiratory, cardiovascular, or central nervous system function. These data provide scientific evidence of the effects of this species and important safety data for its clinical use.

Validation protocol for multiple blood gas analyzers in accordance with laboratory accreditation programs / Protocolo de validação de múltiplos equipamentos para análise de gases sanguíneos em conformidade com os programas de acreditação laboratorial

ABSTRACTIntroduction:The results of blood gas analysis using different instrumentation can vary widely due to the methodological differences, the calibration procedures and the use of different configurations for each type of instrument.Objective:The objective of this study was to evaluate multiple analytical systems for measurement of blood gases, electrolytes and metabolites in accordance with the accreditation program (PALC) of Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial (SBPC/ML).Materials and methods:20 samples were evaluated in three ABL800 Flex (Radiometer Medical ApS, Denmark) blood gas analyzers, and the results were compared with those of the device in use, which was considered the reference. The analysis of variance (Anova) was applied for statistical purposes, as well as the calculation of mean, standard deviation and coefficient of variation.Results:The p values obtained in the statistical analysis were: pH = 0.983, pO2 = 0.991, pCO2 = 0.353, lactate = 0.584, glucose = 0.995, ionized calcium = 0.983, sodium = 0.991, potassium = 0.926, chlorine = 0.029.Conclusion:The evaluation of multiple analytical systems is an essential procedure in the clinical laboratory for quality assurance and accuracy of the results.

RESUMOIntrodução:Os resultados da análise dos gases sanguíneos utilizando diferentes equipamentos podem apresentar grandes variações decorrentes das diferenças metodológicas, dos procedimentos de calibração e da aplicação de configurações distintas para cada tipo de instrumento.Objetivo:O objetivo deste trabalho foi avaliar múltiplos sistemas analíticos para teste de gases sanguíneos, eletrólitos e metabólitos, em conformidade com o Programa de Acreditação de Laboratórios Clínicos (PALC) da Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial (SBPC/ML).Materiais e métodos:Foram avaliadas 20 amostras em três analisadores de gases sanguíneos ABL800 Flex (Radiometer Medical ApS, Dinamarca) em relação ao equipamento em uso, que foi considerado referência. A análise de variância (Anova) foi aplicada para fins de estudo estatístico dos resultados obtidos nos quatro equipamentos, bem como o cálculo da média, do desvio padrão e do coeficiente de variação.Resultados:Os valores de p obtidos na análise estatística foram: pH = 0,983, pO2 = 0,991, pCO2 = 0,353, lactato = 0,584, glicose = 0,995, cálcio ionizado = 0,983, sódio = 0,991, potássio = 0,926 e cloro = 0,029.Conclusão:A avaliação de múltiplos sistemas analíticos é procedimento essencial no laboratório clínico para garantia da qualidade e da exatidão dos resultados.

Valores de referencia de gases arteriales y de electrolitos en caninos de la sabana de Bogotá / Reference Values of Arterial Gases and Electrolytes in Canines from the Bogotá Savanna / Valores de referência de gases arteriais e de eletrólitos em caninos da savana de Bogotá

Debido a la ausencia de valores de gasometría arterial que se ajusten a nuestras condiciones ambientales y a la amplia variedad de datos no actualizados en la literatura y utilizados en la práctica diaria, obtenidos con alturas, razas y equipos diferentes a los disponibles en nuestro medio, es necesario generar conocimiento propio ajustado a nuestra realidad. Se realizó una medición sistemática al azar de sangre arterial y venosa en 100 caninos sanos a la altura de la sabana de Bogotá (Chía: 2652 msnm; Cajicá: 2558 msnm; Sopó: 2650 msnm; La Calera: 2718 msnm y Bogotá: 2630 msnm), utilizando el analizador I-STAT® con cartucho EG7+. Se encontraron valores de referencia de gasometría, electrolitos, bases efectivas y pH. Los valores fueron comparados entre cuatro grupos por peso. Para cada parámetro se realizó estadística descriptiva basada en promedio, desviación estándar, error estándar, y se hallaron los límites de confianza (95%) y los intervalos con desviación estándar (una y dos desviaciones). Se evidenció disminución de PCO2, PO2, SO2, bicarbonato, BE. El pH se encontró levemente aumentado, similar a lo reportado por autores a grandes alturas y diferentes (no corroborado estadísticamente) a reportes en literatura, en los que la altura no fue una variable. Aun así son usados frecuentemente como referencia en la práctica de pequeños animales; solo la presentó diferencias estadísticas por grupos de peso. Como conclusión, se evidenció una regulación del pH sanguíneo eficaz a 2600 msnm, con diferentes valores de bicarbonato, PCO2, PO2, BE, que indican la necesidad de obtener y utilizar valores de referencia acordes con condiciones locales.

Due to the lack of arterial gas values that meet our environmental conditions and the wide variety of out-of-date data in literature and used in everyday practice, obtained with different heights, breeds and equipment to the ones available in our context, it becomes necessary to generate our own knowledge adjusted to our reality. A random systematic measurement of arterial and venous blood was made on 100 healthy canines in the Bogotá Savanna (Chia: 2652 m.a.s.l.; Cajica: 2558 m.a.s.l.; Sopo: 2650 m.a.s.l.; La Calera: 2718 m.a.s.l.; and Bogotá: 2630 m.a.s.l.;), using the I-STAT® analyzer with EG7+ cartridge. Reference values were found for gasometry, electrolytes, effective basis and pH. The values were compared between four groups by weight. Descriptive statistics were made for each parameter based on average, standard deviation and standard error, and the trust limits (95%) and the intervals with standard deviation (one and two deviations) were found. A decrease on PCO2, PO2, SO2, bicarbonate and BE was evident. The pH was found to be slightly increased, similar to the one reported by authors at great heights and different (not statistically confirmed) from reports in literature, where height was not a variable. Even so, they are frequently used as reference in the practice of small animals; only PO2 presented statistical differences by groups of weight. As a conclusion, effective regulation of blood pH was evident at 2600 m.a.s.l., with different bicarbonate values, PCO2, PO2, BE, which suggest the need to obtain and use reference values consistent with local conditions.

Devido à ausência de valores de gasometria arterial que se ajuste a nossas condições ambientais e à ampla variedade de dados não atualizados na literatura e utilizados na prática diária, obtidos com alturas, raças e equipes diferentes aos disponíveis em nosso meio, é necessário gerar conhecimento próprio ajustado a nossa realidade. Realizou-se uma medição sistemática ao azar de sangue arterial e venoso em 100 caninos sãos à altura da savana de Bogotá (Chia: 2652 msnm; Cajicá: 2558 msnm; Sopó: 2650 msnm; a Calera: 2718 msnm e Bogotá: 2630 msnm), utilizando o analisador I-STAT® com cartucho EG7+. Encontraram-se valores de referência de gasometria, eletrólitos, bases efetivas e pH. Os valores foram comparados entre quatro grupos por peso. Para cada parâmetro se realizou estatística descritiva baseada na média, no padrão de desvio, erro padrão, e se encontrou os limites de confiança (95%) e os intervalos com desvio padrão (um e dois desvios). Evidenciou-se diminuição de PCO2, PO2, SO2, bicarbonato, BE. O pH se encontrou levemente aumentado, similar ao reportado por autores a grandes alturas e diferentes (não corroborado estatisticamente) a relatórios em literatura, onde que a altura não foi uma variável.. Ainda assim são usados frequentemente como referência na prática de pequenos animais; só a PO2 apresentou diferenças estatísticas por grupos de peso. Como conclusão, se evidenciou uma regulação do pH sanguíneo eficaz a 2600 msnm, com diferentes valores de bicarbonato, PCO2, PO2, BE, que indicam a necessidade de obter e utilizar valores de referência acordes com condições locais.

Uso de sangue arterial e venoso no exame do equilíbrio ácido-básico de novilhos normais ou com acidose metabólica

Twelve steers were used to compare the blood gas and acid-base status. The animals were randomly divided in three equal groups according to the following diets: 1- adequate, for gaining 600g/head/d ; 2- protein and energy levels to meet the maintenence; 3- protein and energy 20% below the maintenance levels. One hundred thirty-two arterial blood (caudal auricular artery) or venous blood (jugular vein) were continuously sampled for 11 fortnights. At the end of the experiment steers from groups 2 and principally 3 presented a moderate level of metabolic acidosis. Higher pH and pO2 levels were found in arterial blood; conversely, higher level of bicarbonate, TCO2, BE and pO2 levels were found in the venous blood. High correlation was found in the pH (r = 0.81), bicarbonate and TCO2 (r = 0.94) between venous and arterial blood; median correlation but significant in the pCO2 (r = 0.56) and lack of correlation in the pO2 (r = -0.06). The higher the pCO2, the higher the bicarbonate (r = 0.54) and TCO2 (r = 0.56) concentration. In spite of the small differences of pH, bicarbonate, TCO2 and even pCO2 between venous and arterial blood the values of arterial blood can be predicted adequately from the venous blood either in healthy steers or steers with moderate metabolic acidosis. When respiratory changes are concerned arterial blood must be collected for evaluating pO2. It was easier to sample venous blood than arterial blood.

Doze novilhos foram utilizados para comparar os resultados hemogasométricos de sangue arterial e venoso. Esses animais foram divididos em três grupos idênticos, recebendo: 1- dieta balanceada, proporcionando ganho de peso de 600g/d; 2- dieta de mantença em proteína e energia e 3- dieta com teores 20% abaixo da mantença. Amostras de sangue arterial (artéria auricular caudal) e venoso (veia jugular) foram colhidas por 11 quinzenas consecutivas, num total de 132 amostras. Ao término do experimento, os animais dos grupos 2 e principalmente 3 apresentaram acidose metabólica moderada. Maiores valores de pH e de pO2 foram constatados no sangue arterial enquanto os teores de bicarbonato, TCO2, BE e pCO2 foram superiores no sangue venoso. Existiram altas correlações entre os valores do sangue arterial e venoso para o pH (r = 0,81), bicarbonato e TCO2 (r = 0,94), sendo esta correlação média, mas significativa, no caso da pCO2 (r = 0,56) e inexistente na pO2 (r= -0,06). Quanto maiores foram os valores de pCO2 maiores foram os teores de bicarbonato (r = 0,54) e TCO2 (r =0,56). Apesar das discrepâncias de pH, das concentrações de bicarbonato, TCO2, e mesmo de pCO2 obtidos no sangue venoso e arterial, é possível estimar, adequadamente, a partir do primeiro esses valores nas amostras arteriais em novilhos normais e com moderado grau de acidose metabólica. Nos casos de alterações respiratórias, amostras de sangue arterial devem ser colhidas para determinação de pO2. A colheita de sangue venoso foi mais facilmente realizada que do sangue arterial.

Uso de sangue arterial e venoso no exame do equilíbrio ácido-básico de novilhos normais ou com acidose metabólica

Twelve steers were used to compare the blood gas and acid-base status. The animals were randomly divided in three equal groups according to the following diets: 1- adequate, for gaining 600g/head/d ; 2- protein and energy levels to meet the maintenence; 3- protein and energy 20% below the maintenance levels. One hundred thirty-two arterial blood (caudal auricular artery) or venous blood (jugular vein) were continuously sampled for 11 fortnights. At the end of the experiment steers from groups 2 and principally 3 presented a moderate level of metabolic acidosis. Higher pH and pO2 levels were found in arterial blood; conversely, higher level of bicarbonate, TCO2, BE and pO2 levels were found in the venous blood. High correlation was found in the pH (r = 0.81), bicarbonate and TCO2 (r = 0.94) between venous and arterial blood; median correlation but significant in the pCO2 (r = 0.56) and lack of correlation in the pO2 (r = -0.06). The higher the pCO2, the higher the bicarbonate (r = 0.54) and TCO2 (r = 0.56) concentration. In spite of the small differences of pH, bicarbonate, TCO2 and even pCO2 between venous and arterial blood the values of arterial blood can be predicted adequately from the venous blood either in healthy steers or steers with moderate metabolic acidosis. When respiratory changes are concerned arterial blood must be collected for evaluating pO2. It was easier to sample venous blood than arterial blood.

Doze novilhos foram utilizados para comparar os resultados hemogasométricos de sangue arterial e venoso. Esses animais foram divididos em três grupos idênticos, recebendo: 1- dieta balanceada, proporcionando ganho de peso de 600g/d; 2- dieta de mantença em proteína e energia e 3- dieta com teores 20% abaixo da mantença. Amostras de sangue arterial (artéria auricular caudal) e venoso (veia jugular) foram colhidas por 11 quinzenas consecutivas, num total de 132 amostras. Ao término do experimento, os animais dos grupos 2 e principalmente 3 apresentaram acidose metabólica moderada. Maiores valores de pH e de pO2 foram constatados no sangue arterial enquanto os teores de bicarbonato, TCO2, BE e pCO2 foram superiores no sangue venoso. Existiram altas correlações entre os valores do sangue arterial e venoso para o pH (r = 0,81), bicarbonato e TCO2 (r = 0,94), sendo esta correlação média, mas significativa, no caso da pCO2 (r = 0,56) e inexistente na pO2 (r= -0,06). Quanto maiores foram os valores de pCO2 maiores foram os teores de bicarbonato (r = 0,54) e TCO2 (r =0,56). Apesar das discrepâncias de pH, das concentrações de bicarbonato, TCO2, e mesmo de pCO2 obtidos no sangue venoso e arterial, é possível estimar, adequadamente, a partir do primeiro esses valores nas amostras arteriais em novilhos normais e com moderado grau de acidose metabólica. Nos casos de alterações respiratórias, amostras de sangue arterial devem ser colhidas para determinação de pO2. A colheita de sangue venoso foi mais facilmente realizada que do sangue arterial.