Budd-Chiari syndrome with hepatopulmonary syndrome: a case report and literature review / 中华儿科杂志

Objective: To summarize the clinical features and prognosis of Budd-Chiari syndrome with hepatopulmonary syndrome (HPS) in children. Methods: The clinical data of a child who had Budd-Chiari syndrome with HPS treated at the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University in December 2016 was analyzed retrospectively. Taking "Budd-Chiari syndrome" and "hepatopulmonary syndrome" in Chinese or English as the keywords, literature was searched at CNKI, Wanfang, China Biomedical Literature Database and PubMed up to July 2023. Combined with this case, the clinical characteristics, diagnosis, treatment and prognosis of Budd-Chiari syndrome with HPS in children under the age of 18 were summarized. Results: A 13-year-old boy, presented with cyanosis and chest tightness after activities for 6 months, and yellow staining of the skin for 1 week. Physical examination at admission not only found mild yellow staining of the skin and sclera, but also found cyanosis of the lips, periocular skin, and extremities. Laboratory examination showed abnormal liver function with total bilirubin 53 μmol/L, direct bilirubin 14 μmol/L, and indirect bilirubin 39 μmol/L, and abnormal blood gas analysis with the partial pressure of oxygen of 54 mmHg (1 mmHg=0.133 kPa), the partial pressure of carbon dioxide of 31 mmHg, and the alveolar-arterial oxygen gradient of 57 mmHg. Hepatic vein-type Budd-Chiari syndrome, cirrhosis, and portal hypertension were indicated by abdominal CT venography. Contrast-enhanced transthoracic echocardiography (CE-TTE) was positive. After symptomatic and supportive treatment, this patient was discharged and received oxygen therapy outside the hospital. At follow-up until March 2023, there was no significant improvement in hypoxemia, accompanied by limited daily activities. Based on the literature, there were 3 reports in English while none in Chinese, 3 cases were reported. Among a total of 4 children, the chief complaints were dyspnea, cyanosis, or hypoxemia in 3 cases, and unknown in 1 case. There were 2 cases diagnosed with Budd-Chiari syndrome with HPS at the same time due to respiratory symptoms, and 2 cases developed HPS 1.5 years and 8.0 years after the diagnosis of Budd-Chiari syndrome respectively. CE-TTE was positive in 2 cases and pulmonary perfusion imaging was positive in 2 cases. Liver transplantation was performed in 2 cases and their respiratory function recovered well; 1 case received oxygen therapy, with no improvement in hypoxemia; 1 case was waiting for liver transplantation. Conclusions: The onset of Budd-Chiari syndrome with HPS is insidious. The most common clinical manifestations are dyspnea and cyanosis. It can reduce misdiagnosis to confirm intrapulmonary vascular dilatations with CE-TTE at an early stage. Liver transplantation is helpful in improving the prognosis.

Importance of assessing biomarkers and physiological parameters of anemia-induced tissue hypoxia in the perioperative period

Abstract Anemia is associated with increased risk of Acute Kidney Injury (AKI), stroke and mortality in perioperative patients. We sought to understand the mechanism(s) by assessing the integrative physiological responses to anemia (kidney, brain), the degrees of anemia-induced tissue hypoxia, and associated biomarkers and physiological parameters. Experimental measurements demonstrate a linear relationship between blood Oxygen Content (CaO2) and renal microvascular PO2 (y = 0.30x + 6.9, r2= 0.75), demonstrating that renal hypoxia is proportional to the degree of anemia. This defines the kidney as a potential oxygen sensor during anemia. Further evidence of renal oxygen sensing is demonstrated by proportional increase in serum Erythropoietin (EPO) during anemia (y = 93.806*10−0.02, r2= 0.82). This data implicates systemic EPO levels as a biomarker of anemia-induced renal tissue hypoxia. By contrast, cerebral Oxygen Delivery (DO2) is defended by a profound proportional increase in Cerebral Blood Flow (CBF), minimizing tissue hypoxia in the brain, until more severe levels of anemia occur. We hypothesize that the kidney experiences profound early anemia-induced tissue hypoxia which contributes to adaptive mechanisms to preserve cerebral perfusion. At severe levels of anemia, renal hypoxia intensifies, and cerebral hypoxia occurs, possibly contributing to the mechanism(s) of AKI and stroke when adaptive mechanisms to preserve organ perfusion are overwhelmed. Clinical methods to detect renal tissue hypoxia (an early warning signal) and cerebral hypoxia (a later consequence of severe anemia) may inform clinical practice and support the assessment of clinical biomarkers (i.e., EPO) and physiological parameters (i.e., urinary PO2) of anemia-induced tissue hypoxia. This information may direct targeted treatment strategies to prevent adverse outcomes associated with anemia.

Research progress on the effects of childhood obstructive sleep apnea syndrome on cognition and brain functions / 生理学报

Obstructive sleep apnea syndrome (OSAS), a prevalent sleep disorder in children, is characterized by recurring upper airway obstruction during sleep. OSAS in children can cause intermittent hypoxia and sleep fragmentation, ultimately affect brain development and further lead to cognitive impairment if lack of timely effective intervention. In recent years, magnetic resonance imaging (MRI) and electroencephalogram (EEG) have been employed to investigate brain structure and function abnormalities in children with OSAS. Previous studies have indicated that children with OSAS showed extensive gray and white matter damage, abnormal brain function in regions such as the frontal lobe and hippocampus, as well as a significant decline in general cognitive function and executive function. However, the existing studies mainly focused on the regional activity, and the mechanism of pediatric OSAS affecting brain networks remains unknown. Moreover, it's unclear whether the alterations in brain structure and function are associated with their cognitive impairment. In this review article, we proposed two future research directions: 1) future studies should utilize the multimodal neuroimaging techniques to reveal the alterations of brain networks organization underlying pediatric OSAS; 2) further investigation is necessary to explore the relationship between brain network alteration and cognitive dysfunction in children with OSAS. With these efforts, it will be promising to identify the neuroimaging biomarkers for monitoring the brain development of children with OSAS as well as aiding its clinical diagnosis, and ultimately develop more effective strategies for intervention, diagnosis, and treatment.

Progression in the application of machine learning in acute respiratory distress syndrome / 中华危重病急救医学

Acute respiratory distress syndrome (ARDS) is a clinical syndrome defined by acute onset of hypoxemia and bilateral pulmonary opacities not fully explained by cardiac failure or volume overload. At present, there is no specific drug treatment for ARDS, and the mortality rate is high. The reason may be that ARDS has rapid onset, rapid progression, complex etiology, and great heterogeneity of clinical manifestations and treatment. Compared with traditional data analysis, machine learning algorithms can automatically analyze and obtain rules from complex data and interpret them to assist clinical decision making. This review aims to provide a brief overview of the machine learning progression in ARDS clinical phenotype, onset prediction, prognosis stratification, and interpretable machine learning in recent years, in order to provide reference for clinical.

A new type of artificial airway sealer used between artificial airway and ventilator pipeline / 中华危重病急救医学

The need for mechanical ventilation due to severe hypoxemia and acute respiratory distress syndrome has increased dramatically in the global pandemic of severe respiratory infectious diseases. In clinical scenarios, it is sometimes necessary to briefly disconnect the ventilator pipeline from the artificial airway. Still, this operation can lead to a sharp drop in airway pressure, which is contrary to the protective lung ventilation strategy and increases the risk of environmental exposure to bioaerosol, posing a serious threat to patients and medical workers. At present, there is yet to be a practical solution. A new artificial airway device was designed by the medical staff from the department of critical care medicine of Beijing Tiantan Hospital, Capital Medical University, based on many years of research experience in respiratory support therapy, and recently obtained the National Utility Model Patent of China (ZL 2019 2 0379605.4). The device comprises two connecting pipes, the sealing device body, and the globe valve represented by the iridescent optical ring. It has a simple structure, convenient operation, and low production cost. The device is installed between the artificial airway and the ventilator pipeline and realizes the instantaneous sealing of the artificial airway by adjusting the shut-off valve. Using this device to treat mechanically ventilated patients can minimize the ventilator-induced lung injury caused by the repeated disconnection of pipelines, avoid iatrogenic transmission of bioaerosols, and realize dual protection for patients and medical workers. It has extensive clinical application prospects and high health and economic value.

Efectos biológicos de la exposición a distintas concentraciones de oxígeno: desde la hipoxia hipobárica al oxígeno hiperbárico / Biological effects due to exposure to different concentrations of oxygen from hypo to hyperoxemia

The systemic effects of oxygen deficiency or excess are not thoroughly described. Knowledge is evolving towards the description of beneficial and detrimental effects of both extremes of partial pressure of oxygen (PaO2). The cellular and tissue mediators derived from the modulation of the oxidative tone and the production of reactive oxygen species (ROS) are widely characterized biochemically, but the pathophysiological characterization is lacking. Preclinical models support the use of hypobaric hypoxia preconditioning, based on its beneficial effects on ventricular function or its reduction in infarct size. A very important use of oxygen today is in commercial diving. However, novel clinical indications for oxygen such as the healing of diabetic foot ulcers and bone injury caused by radiotherapy are increasingly used. On the other hand, the modulation of the hypoxic response associated with exposure to high altitude environments (hypobaric), favors Chile and its highlands as a natural laboratory to determine certain cardiovascular, cerebral and metabolic responses in the resident population. Also, the consequences of the intermittent exposure to high altitudes in workers also deserves attention. This review discusses the physiopathological response to hypo and hyperoxemia, associated with environments with different oxygen concentrations, and brings back the concept of oxygen as a pharmacological mediator in extreme environments such as high altitudes and hyperbaric medicine in divers, decompression sickness, osteonecrosis associated with radiotherapy and sudden sensorineural hearing loss.

Efecto de la hipoxia sobre los tejidos de la cavidad oral: revisión de la literatura / Effect of hypoxia on oral tissues: a review of the literature

La exposición a hipoxia es considerada un estímulo estresante, por lo que el organismo desarrolla meca-nismos de aclimatación para asegurar la homeosta-sis. Si bien el efecto de la hipoxia sobre los distintos sistemas de tejidos y órganos ha sido bien documen-tado, el rol de los bajos niveles de O2 en la cavidad oral no ha recibido el mismo análisis. En este trabajo se revisaron los datos bibliográficos disponibles sobre el efecto de la hipoxia sobre el tejido periodontal, las glándulas salivales, la pulpa dental y el hueso mandi-bular y alveolar. De lo analizado en la bibliografía, re-sulta evidente que los bajos niveles de O2 aumentan el número de mediadores inflamatorios que inducen la progresión de la enfermedad periodontal y, a su vez, la inflamación establecida durante dicha enfermedad agrava aún más las condiciones de hipoxia tisular. Las glándulas salivales también se encuentran afectadas durante la exposición a hipoxia, disminuyendo la can-tidad de saliva secretada, observándose alteraciones ultraestructurales en el parénquima glandular. Por otra parte, se ha establecido que la hipoxia puede te-ner efectos deseados para el cultivo de células madre de la pulpa dental, lo cual resulta útil en el campo de la odontología reparativa y también para el movimien-to dental durante los tratamientos ortodónticos. En conclusión, para determinar los efectos de la hipoxia en la cavidad oral se debe analizar no sólo el tipo de tejido involucrado sino también las condiciones de hi-poxia a las cuales éste es sometido, así también como la duración de la exposición y la modalidad de hipoxia (AU)

Exposure to hypoxia is considered a stressful stimulus, therefore the organism develops acclimation mechanisms to try to ensure homeostasis. Although the effect of hypoxia on different tissues and organs has been very well documented, the role of low levels of O2 in the oral cavity has not received the same analysis. In this review, we analyzed the available bibliographic data concerning the effects of hypoxia on periodontal tissue, salivary glands, and dental pulp. The published evidence demonstrates that low O2 levels increase the number of inflammatory mediators that induce the progression of periodontal disease, and, in turn, the inflammation established during the progression of periodontitis aggravates tissue hypoxia conditions. Salivary glands are also affected during hypoxic exposure, decreasing salivary secretion, and leading to ultrastructural alterations in the glandular parenchyma. On the other hand, hypoxia could also be beneficial in some scenarios. It has been established that dental pulp cells grow better in culture under hypoxic conditions than they do in normoxia. Furthermore, mild hypoxia seems to stimulate periodontal ligament cells proliferation and matrix degradation, key events during for orthodontic treatments. In conclusion, to determine the effects of hypoxia in the oral cavity, it is necessary to analyze not only the type of tissue involved but also the hypoxic conditions to which it is subjected, as well as its duration and modality (AU)

Perfil clínico e fatores associados ao óbito de pacientes COVID-19 nos primeiros meses da pandemia / Perfil clínico y factores asociados a la muerte de pacientes COVID-19 en los primeros meses de la pandemia / Clinical profile and factors associated with the death of COVID-19 patients in the first months of the pandemic

RESUMO Objetivo analisar as características individuais, clínicas e os fatores associados à mortalidade de pacientes com COVID-19, em hospital público do estado do Paraná, Brasil. Métodos estudo seccional, retrospectivo, documental (n= 86), com pacientes adultos internados, de março a junho de 2020. Resultados a mortalidade foi de 12,8%, o grupo de maior risco foi de idosos com comorbidades, especialmente, cardiovasculares. A chance de óbito foi 58 vezes maior em idosos, comparada aos adultos, e oito vezes maior naqueles com comorbidades, comparadas aos hígidos. A maioria dos pacientes apresentou sintomatologia respiratória, febre e mialgia. Tratamento à base de antibióticos, anticoagulantes e antivirais, associado ao suporte ventilatório. As principais complicações foram hipóxia, insuficiência renal aguda e infecção secundária. Conclusão e implicações para a prática idosos com comorbidades cardiovasculares que necessitaram de cuidados intensivos apresentaram maior chance de óbito. Os resultados de um dos centros de referência na pandemia possibilitam discutir medidas epidemiológicas adotadas, com ênfase em conceitos restritivos nos primeiros meses.

RESUMEN Objetivo analizar las características individuales, clínicas y los factores asociados a la mortalidad en pacientes con COVID-19 en un hospital público del estado de Paraná. Métodos estudio transversal, retrospectivo, documental (n = 86), con pacientes adultos hospitalizados, de marzo a junio de 2020. Resultados la mortalidad fue del 12,8%, grupo de mayor riesgo para los ancianos con comorbilidades, especialmente enfermedades cardiovasculares. La probabilidad de muerte fue 58 veces mayor en los ancianos en comparación con los adultos y ocho veces mayor en aquellos con comorbilidades en comparación con los sanos. La mayoría de los pacientes presentaban síntomas respiratorios, fiebre y mialgia. Tratamiento a base de antibióticos, anticoagulantes y antivirales, asociado al soporte ventilatorio. Las principales complicaciones fueron hipoxia, insuficiencia renal aguda e infección secundaria. Conclusión e implicaciones para la práctica los ancianos con comorbilidades cardiovasculares que requirieron cuidados intensivos tenían una mayor probabilidad de muerte. Los resultados de uno de los centros de referencia pandémica permiten discutir las medidas epidemiológicas adoptadas, con énfasis en conceptos restrictivos en los primeros meses.

ABSTRACT Objective to analyze the individual and clinical characteristics and the factors associated with mortality in patients with COVID-19, in a public hospital in the state of Paraná, Brazil. Methods a cross-sectional, retrospective, documentary study (n= 86), with adult inpatients, from March to June 2020. Results mortality was 12.8%, the highest risk group was the elderly with comorbidities, especially cardiovascular ones. The chance of death was 58 times higher in the elderly compared to adults, and eight times higher in those with comorbidities compared to the healthy ones. Most patients presented with respiratory symptoms, fever, and myalgia. Treatment was based on antibiotics, anticoagulants and antivirals, associated with ventilatory support. The main complications were hypoxia, acute renal failure, and secondary infection. Conclusion and implications for practice elderly people with cardiovascular comorbidities who required intensive care had a higher chance of death. The results from one of the reference centers in the pandemic make it possible to discuss epidemiological measures adopted, with emphasis on restrictive concepts in the first months.

TRPV4 channel mediates the increase of pulmonary microvascular endothelial permeability in rats with chronic hypoxic pulmonary hypertension / 生理学报

The purpose of the present study was to investigate the effect of transient receptor potential vanilloid 4 (TRPV4) channel on the permeability of pulmonary microvascular endothelial cells (PMVECs) in rats with chronic hypoxia-induced pulmonary hypertension (CHPH), so as to clarify the mechanism of vascular endothelial dysfunction during the occurrence of pulmonary hypertension (PH). CHPH rat model was established by exposure to chronic hypoxia (CH) for 21 days. Primary PMVECs were cultured by adherent tissue blocks at the edge of the lung. The permeability coefficient of primary cultured PMVECs was detected by fluorescein isothiocyanate (FITC)-dextran. The structure of tight junction (TJ) was observed by transmission electron microscope. The expression of TRPV4 and TJ-related proteins, such as, Occludin, Claudin-5, ZO-1 were examined by real-time fluorescence quantitative PCR and Western blotting. The intracellular calcium concentration ([Ca

Chronic Exposure to Hypoxia Inhibits Myelinogenesis and Causes Motor Coordination Deficits in Adult Mice / 神经科学通报·英文版

Exposure to chronic hypoxia is considered to be a risk factor for deficits in brain function in adults, but the underlying mechanisms remain largely unknown. Since active myelinogenesis persists in the adult central nervous system, here we aimed to investigate the impact of chronic hypoxia on myelination and the related functional consequences in adult mice. Using a transgenic approach to label newly-generated myelin sheaths (NG2-CreER

Efectos morfológicos y mecánicos en ratas Sprague Dawley sometidas a ciclos de hipoxia / Morphological and mechanical effects in Sprague Dawley rats subjected to hypoxia cycles

Periodos extensos de hipoxia provocan cambios adaptativos que permiten responder a las demandas impuestas por el ambiente. Sin embargo, existen casos donde esta exposición es intermitente, como es el caso de los trabajadores en zonas andinas. El objetivo de esta comunicación fue comprobar los efectos morfológicos y mecánicos en diafragma y pulmones de ratas sometidas a la hipoxia intermitente. Se utilizaron 4 ratas Sprague Dawley de 6 meses de edad. Dos ratas fueron sometidas a 10 ciclos de hipoxia hipobárica intermitente (HHI) de 96 h (~428 torr; PO2 90 mm Hg), seguidos de 96 h de normoxia normobárica, durante 80 días. Se realizaron pruebas tracción uniaxial y de tinción con HematoxilinaEosina y Picrosirius red de Junqueira. Al comparar las curvas de los diafragmas, los sometidos a hipoxia reducen levemente su esfuerzo respecto a la condición de normoxia, en el tejido pulmonar la hipoxia afecta negativamente su resistencia, estas muestran una pendiente menor respecto a las normóxicas. En el análisis histológico, el parénquima pulmonar presentó menor cantidad de vasos sanguíneos y celularidad, como una mayor fracción de área de los espacios alveolares y cantidad de colágeno total en el grupo HHI. En el diafragma, el grupo HHI presentó menor cantidad de miocitos distribuidos irregularmente y de colágeno total. En conclusión, los principales hallazgos indican que el diafragma y el tejido pulmonar sometido a HHI sufren cambios estructurales, que se traducen en una disminución en su capacidad de resistencia tensil.

Extensive periods of hypoxic cause adaptive changes that make it possible to respond to the demands imposed by the environment. However, there are cases where this exposure is intermittent, as is the case of workers in andean areas. The objective of this communication was to verify the morphological and mechanical effects on diaphragm and lungs of rats subjected to intermittent hypoxic. Four 6-monthold Sprague Dawley rats were used. Two rats were subjected to 10 cycles of intermittent hypobaric hypoxic (IHH) of 96 h (~428 torr, PO2 90 mm Hg), followed by 96 h of normobaric normoxia, for 80 days. Uniaxial traction and staining tests were performed with Hematoxylin-Eosin and Picrosirius red de Junqueira. When comparing the curves of the diaphragms, those subjected to hypoxic slightly reduce their effort with respect to the condition of normoxia, in the lung tissue the hypoxic negatively affects its resistance, these show a lower slope with respect to the normoxics. In the histological analysis, the pulmonary parenchyma had a lower number of blood vessels and cellularity, such as a greater area fraction of alveolar spaces and amount of total collagen in IHH group. In the diaphragm, IHH group had a lower number of irregularly distributed myocytes and a lower amount of total collagen. In conclusion, the main findings indicate that the diaphragm and lung tissue subjected to IHH undergo structural changes, which result in a decrease in tensile strength.

Hepatitis hipóxica en paciente con endomiocardiofibrosis / Hypoxic hepatitis in a patient with endomyocardial fibrosis

La endomiocardiofibrosis es una causa de miocardiopatía restrictiva frecuente en la región de África subsahariana, aunque poco frecuente en nuestra población. Posee estrecha relación con la presencia de hipereosinofilia en sangre y tiene alta morbimortalidad. La hepatitis hipóxica es una afección clínica con un patrón enzimático característico, muy prevalente en unidades de cuidados intensivos y elevada mortalidad. Se reconocen múltiples mecanismos fisiopatológicos, como la isquemia, la congestión venosa y la alteración en la utilización de oxígeno del hepatocito. Describimos el caso de u na paciente de 35 años, consumidora de cocaína, con diagnóstico de endomiocardiofibrosis secundario a síndrome hipereosinofílico idiopático que presentó shock cardiogénico y hepatitis hipóxica asociada. Evolucionó favorablemente con el tratamiento de sostén adecuado.

Endomyocardial fibrosis is a restrictive cardiomyopathy with high morbidity and mortality rates, prevalent in the sub-Saharan Africa region but infrequent in our population. It has a close relation with blood hypereosinophilia. Hypoxic hepatitis is frequently observed in intensive care units and its diagnosis is clinical. It shows a typical enzyme pattern with high mortality too. There are multiple mechanisms responsible for this condition, such as ischemia, passive congestion and dysoxia. We described the case of a 35 year-old cocaine addict woman diagnosed with endomyocardial fibrosis and hypereosinophilic syndrome who developed cardiogenic shock with hypoxic hepatitis. The patient evolved favorably with the appropriate treatment.

Otimização de condições para teste de apneia em paciente hipoxêmico com morte encefálica / Optimization of conditions for apnea testing in a hypoxemic brain dead patient

RESUMO Relatamos o caso de um paciente que evoluiu com suspeita de morte encefálica associada à atelectasia e à hipoxemia moderada a grave, apesar de instituídos ventilação protetora, sistema de aspiração traqueal fechado, pressão positiva ao final da expiração moderada e manobra de recrutamento. Diante da não obtenção de pressão parcial de oxigênio adequada para o teste de apneia, optamos por pronar o paciente, utilizar pressão positiva expiratória final mais elevada, realizar nova manobra de recrutamento e ventilar com volume corrente mais elevado (8mL/kg), sem ultrapassar pressão de platô de 30cmH2O. O teste de apneia foi realizado em posição prona, com válvula de pressão positiva contínua nas vias aéreas acoplada em tubo T. O atraso no diagnóstico foi de 10 horas; a doação de órgãos não foi possível devido à parada circulatória. Este relato demonstra as dificuldades para obtenção de níveis de pressão parcial de oxigênio mais altos para a realização do teste de apneia. Os atrasos que isso pode acarretar ao diagnóstico de morte encefálica e ao processo de doação de órgãos são discutidos, além de potenciais estratégias de otimização da pressão parcial de oxigênio para realização do teste, conforme as recomendações atuais.

ABSTRACT We report the case of a patient in whom brain death was suspected and associated with atelectasis and moderate to severe hypoxemia even though the patient was subjected to protective ventilation, a closed tracheal suction system, positive end-expiratory pressure, and recruitment maneuvers. Faced with the failure to obtain an adequate partial pressure of oxygen for the apnea test, we elected to place the patient in a prone position, use higher positive end-expiratory pressure, perform a new recruitment maneuver, and ventilate with a higher tidal volume (8mL/kg) without exceeding the plateau pressure of 30cmH2O. The apnea test was performed with the patient in a prone position, with continuous positive airway pressure coupled with a T-piece. The delay in diagnosis was 10 hours, and organ donation was not possible due to circulatory arrest. This report demonstrates the difficulties in obtaining higher levels of the partial pressure of oxygen for the apnea test. The delays in the diagnosis of brain death and in the organ donation process are discussed, as well as potential strategies to optimize the partial pressure of oxygen to perform the apnea test according to the current recommendations.

Emodin protects H9c2 cells from hypoxia-induced injury by up-regulating miR-138 expression

Myocardial infarction (MI) is a common presentation for ischemic heart disease, which is a leading cause of death. Emodin is a Chinese herbal anthraquinone used in several diseases. However, the effect of emodin in hypoxia-induced injury in cardiomyocytes has not been clearly elucidated. Our study aimed to clarify the functions of emodin in hypoxia-induced injury in rat cardiomyocytes H9c2 and explore the underlying mechanism. The effects of emodin on cell viability and apoptosis were analyzed by the Cell counting kit-8 assay and flow cytometry assay, respectively. The cell proliferation- and cell apoptosis-related proteins were detected by western blot. qRT-PCR was used to determine the relative expression of miR-138. Cell transfection was performed to alter miR-138 and MLK3 expression. miR-138 target was performed by dual luciferase activity assay. Sirt1/AKT and Wnt/β-catenin pathways-related factors phosphorylation were analyzed by western blot. Emodin inhibited hypoxia-induced injury in H9c2 cells by promoting cell viability and reducing cell apoptosis. miR-138 was down-regulated by hypoxia treatment but up-regulated by emodin. Up-regulation of miR-138 alleviated hypoxia-induced cell injury. Down-regulation of miR-138 attenuated the growth-promoting effect of emodin on hypoxia-induced injury, whereas up-regulation of miR-138 enhanced the growth-promoting effects of emodin. The underlying mechanism might be by inactivating Sirt1/AKT and Wnt/β-catenin pathways. MLK3 was negatively regulated by miR-138 expression and inactivated Sirt1/AKT and Wnt/β-catenin pathways. Emodin alleviated hypoxia-induced injury in H9c2 cells via up-regulation of miR-138 modulated by MLK3, as well as by activating Sirt1/AKT and Wnt/β-catenin pathways.

Intermittent hypoxia, brain glyoxalase-1 and glutathione reductase-1, and anxiety-like behavior in mice

Objective: Sleep apnea has been associated with anxiety, but the mechanisms of the sleep apnea-anxiety relationship are unresolved. Sleep apnea causes oxidative stress, which might enhance anxiety-like behavior in rodents. To clarify the apnea-anxiety connection, we tested the effect of intermittent hypoxia, a model of sleep apnea, on the anxiety behavior of mice. Methods: The rodents were exposed daily to 480 one-minute cycles of intermittent hypoxia to a nadir of 7±1% inspiratory oxygen fraction or to a sham procedure with room air. After 7 days, the mice from both groups were placed in an elevated plus maze and were video recorded for 10 min to allow analysis of latency, frequency, and duration in open and closed arms. Glyoxalase-1 (Glo1) and glutathione reductase-1 (GR1) were measured in the cerebral cortex, hippocampus, and striatum by Western blotting. Results: Compared to controls, the intermittent hypoxia group displayed less anxiety-like behavior, perceived by a statistically significant increase in the number of entries and total time spent in open arms. A higher expression of GR1 in the cortex was also observed. Conclusion: The lack of a clear anxiety response as an outcome of intermittent hypoxia exposure suggests the existence of additional layers in the anxiety mechanism in sleep apnea, possibly represented by sleepiness and irreversible neuronal damage.

Profilaxia do tromboembolismo venoso em viagens aéreas / Venous thromboembolism prophylaxis on flights

A aviação civil vem apresentando aumento progressivo do número de voos regulares nos últimos 10 anos e, em função disso, mais passageiros estão sendo transportados em viagens aéreas (VAs). Associado a isso, há um aumento das doenças relacionadas às VAs, especialmente naquelas de longa duração. Uma das complicações mais temidas dos voos é o tromboembolismo venoso (TEV), mas a sua real incidência é de difícil mensuração devido à falta de consenso sobre, por exemplo, quanto tempo após o pouso podemos considerar que o TEV possa estar relacionado à VA realizada ou mesmo quanto tempo de voo pode ser considerado como de longa duração. Muito tem se discutido sobre os mecanismos fisiopatológicos do TEV relacionado às VAs, quais passageiros são os de maior risco e quais medidas profiláticas podemos adotar com segurança e eficácia. O objetivo desta revisão é esclarecer esses pontos e as condutas consensuais atuais

Civil aviation has seen a steady increase in the number of scheduled flights over the last ten years and, as a result, more passengers are traveling by air. This has been associated with an increase in flight-related diseases, especially on long-haul flights. One of the most feared complications during flights is venous thromboembolism (VTE), but its true incidence is difficult to measure because of a lack of consensus on elements such as the definition of how long after landing a VTE can be considered to be related to a flight and even how long a flight must last to be considered of long duration. There has been much discussion of the pathophysiological mechanisms of flight-related VTE, of which passengers are at greatest risk, and of what prophylactic measures can be adopted safely and effectively. The purpose of this review is to clarify these points and describe current consensual conduct

Normoblastemia multinuclear en un recién nacido secundaria a hipoxia / Multinucleated normoblastemia in a newborn secondary to hypoxia

Es posible detectar normoblastos en los frotis de sangre periférica de los recién nacidos. En general, la cantidad de normoblastos por cada 100 leucocitos está en el intervalo de 0 a 10. Se observan con más frecuencia de lo usual ante una situación de hipoxia porque la hipoxia intrauterina aumenta la producción de eritrocitos. Sin embargo, no se había informado antes un caso de normoblastos multinucleados en un recién nacido a causa de la hipoxia. Presentamos el caso de un recién nacido con normoblastos multinucleados secundarios a hipoxia intrauterina. Este caso es importante porque es la primera vez que se han detectado normoblastos multinucleados en el frotis de sangre periférica de un recién nacido hipóxico.

Normoblasts may be seen in peripheral blood smear of newborns. The number of normoblasts per 100 white blood cells is generally in the range of 0-10.They can be seen more common than usual in hypoxic condition, because intrauterine hypoxia increases the production of red blood cells. However, multinucleated normoblasts in a newborn caused by hypoxia haven't been reported before. We present a newborn with multinucleated normoblasts secondary to intrauterine hypoxia. This case is important; because it is the first time multinucleated normoblasts in peripheral blood smear of a hypoxic newborn has been detected.

Efeitos da Hipóxia na Variabilidade da Frequência Cardíaca em Indivíduos Saudáveis: Uma Revisão Sistemática / Effects of Hypoxia on Heart Rate Variability in Healthy Individuals: A Systematic Review

Fundamento: A hipóxia é uma condição fisiológica que pode influenciar a modulação autonômica cardíaca, qualpode ser avaliada pelas flutuações espontâneas da frequência cardíaca, chamada de variabilidade da frequência cardíaca (VFC). Estudos têm reportado reduções ou manutenção da VFC em situação de hipóxia apresentando efeitos controversos. Há uma lacuna no conhecimento em relação às modificações da VFC durante a hipóxia. Objetivo: Revisar sistematicamente estudos que investigaram os efeitos da hipóxia na VFC em adultos saudáveis e não aclimatados durante o repouso. Métodos: A presente revisão sistemática foi realizada a partir da diretriz PRISMA. Os termos utilizados para a busca nas bases MEDLINE, SCOPUS, LILACS e EUROPE PMC foram: "heart rate variability" OR "cardiac autonomic modulation" OR "cardiac autonomic regulation" AND (hypoxia OR altitude) NOT intermitente NOT sleep. Os registros foram filtrados por espécie, idade e idiomas. Resultados: Ao final da triagem e elegibilidade restaram 13 artigos para a síntese qualitativa. Discussão: Os estudos utilizam protocolos experimentais variados que envolvem diferença na pressão barométrica, no nível de oxigênio, no tempo de exposição à hipóxia e no controle da frequência respiratória. Possivelmente a influência desses fatores e também a variação interindividual à hipóxia podem justificar diferentes respostas na VFC. Conclusão: A partir dos estudos investigados, a hipóxia foi capaz de gerar uma queda na VFC, seja por retirada ou manutenção da modulação vagal, ou por predomínio simpático ou mesmo pela combinação dessas respostas em adultos saudáveis não aclimatados a hipóxia. Este efeito parece ser dependente do nível de altitude e da pressão barométrica

Background: Hypoxia is a physiological condition that may affect the cardiac autonomic modulation, which can be assessed by spontaneous fluctuations in heart rate, know as heart rate variability (HRV). Studies have reported reductions or maintenance of HRV in hypoxic situation presenting controversial effects. There is a knowledge gap in relation to changes in HRV during hypoxia. Objective: The aim of this study was to systematically review the effects of hypoxia on HRV in unacclimatized healthy adults at rest. Methods: This systematic review was performed according to PRISMA guidelines. Search terms used in MEDLINE, SCOPUS, LILACS and EUROPE PMC database were: "heart rate variability" OR "cardiac autonomic modulation" OR "cardiac autonomic regulation" AND NOT intermittent NOT sleep (hypoxia OR altitude). Records were filtered by species, age group and language. Results: At the end of the screening and eligibility, 13 manuscripts remained for qualitative synthesis. Discussion: The studies used different experimental protocols involving difference in barometric pressure, oxygen level, time of exposure to hypoxia and control of respiratory rate. Possibly the influence of these factors and also the interindividual variation to hypoxia may justify different responses in HRV. Conclusion: Based on the investigated studies, hypoxia has been capable of generating a decrease in HRV, either by reduction or maintenance of vagal modulation, or by sympathetic predominance or even the combination of these responses in healthy adults unacclimatized to hypoxia. This effect appears to be dependent on altitude level and barometric pressure

Emissões otoacústicas em recém-nascidos com hipóxia perinatal leve e moderada / Otoacoustic emissions in newborns with mild and moderate perinatal hypoxia

RESUMO Introdução Atualmente, somente a hipóxia neonatal grave (evidenciada pelo valor do Apgar) é considerada risco para a deficiência auditiva. A hipóxia é uma das causas mais comuns de lesão e morte celular. Nos casos de hipóxia leve ou moderada, embora menor, a privação da oxigenação está presente e, dessa forma, algum dano ao sistema auditivo pode ocorrer. Objetivo Investigar as amplitudes das emissões otoacústicas em recém-nascidos a termo sem risco para deficiência auditiva que apresentaram hipóxia leve ou moderada. Métodos Foram selecionados 37 recém-nascidos de ambos os sexos, divididos em dois grupos: 25 do grupo controle, formado por recém-nascidos sem hipóxia, e 12 do grupo estudo, formado por recém-nascidos com hipóxia leve ou moderada. Resultados Foram pesquisadas as EOAT e EOAPD em ambos os grupos e comparados os seus resultados. Nas EOAPD foram encontradas diferenças estatísticas entre as amplitudes nas frequências 1.000, 2.800, 4.000 e 6.000 Hz. Nas EOAT foram encontradas diferenças estatísticas nas bandas de frequência de 1.000, 1.400, 2.000, 2.800 e 4.000 Hz, sendo as EOA do grupo estudo menores que as do grupo controle. Conclusão Embora a ocorrência de hipóxia neonatal leve e moderada não seja considerada risco para perda auditiva, a mínima privação do oxigênio durante o momento de hipóxia neonatal parece interferir no funcionamento das células ciliadas externas e, consequentemente, no nível de respostas das emissões otoacústicas. Dessa forma, faz-se necessário o acompanhamento longitudinal desses lactentes, a fim de identificar o possível impacto desses resultados na aquisição de linguagem e, futuramente, no desempenho escolar.

ABSTRACT Introduction Severe neonatal hypoxia (as evidenced by the Apgar value) is currently considered the only risk for hearing loss. Hypoxia is one of the most common causes of injury and cell death. The deprivation of oxygen in mild or moderate cases of hypoxia, although smaller, occurs and could cause damage to the auditory system. Objective To investigate the amplitude of otoacoustic emissions in neonates at term with mild to moderate hypoxia and no risk for hearing loss. Methods We evaluated 37 newborns, divided into two groups: a control group of 25 newborns without hypoxia and a study group of 12 newborns with mild to moderate hypoxia. TEOAE and DPOAE were investigated in both groups. Results The differences between groups were statistically significant in the amplitude of DPOAE at the frequencies of 1000, 2800, 4000 and 6000 Hz. In TEOAE, statistically significant differences were found in all tested frequency bands. OAE of the study group were lower than those in the control group. Conclusion Although the occurrence of mild and moderate neonatal hypoxia is not considered a risk factor for hearing loss, deprivation of minimum oxygen during neonatal hypoxia seems to interfere in the functioning of the outer hair cells and, consequently, alter the response level of otoacoustic emissions. Thus, hese children need longitudinal follow-up in order to identify the possible impact of these results on language acquisition and future academic performance.

Inactivated Pseudomonas aeruginosa inhibits hypoxia-induced pulmonary hypertension by preventing TGF-beta1/Smad signaling

Pseudomonas aeruginosa is one of the common colonizing bacteria of the human body and is an opportunistic pathogen frequently associated with respiratory infections. Inactivated P. aeruginosa (IPA) have a variety of biological effects against inflammation and allergy. Transforming growth factor-β (TGF-β) signaling plays a critical role in the regulation of cell growth, differentiation, and development in a wide range of biological systems. The present study was designed to investigate the effects of IPA on TGF-β/Smad signaling in vivo, using a hypoxia-induced pulmonary hypertension (PH) rat model. Sprague Dawley rats (n=40) were exposed to 10% oxygen for 21 days to induce PH. At the same time, IPA was administered intravenously from day 1 to day 14. Mean pulmonary artery pressure (mPAP) and the right ventricle (RV) to left ventricle plus the interventricular septum (LV+S) mass ratio were used to evaluate the development of PH. Vessel thickness and density were measured using immunohistochemistry. Primary arterial smooth muscle cells (PASMCs) were isolated and the proliferation of PASMCs was assayed by flow cytometry. The production of TGF-β1 in cultured supernatant of PASMCs was assayed by ELISA. The expression levels of α-smooth muscle actin (α-SMA), TGF-β1 and phospho-Smad 2/3 in PASMCs were assayed by western blot. Our data indicated that IPA attenuated PH, RV hypertrophy and pulmonary vascular remodeling in rats, which was probably mediated by restraining the hypoxia-induced overactive TGF-β1/Smad signaling. In conclusion, IPA is a promising protective treatment in PH due to the inhibiting effects on TGF-β1/Smad 2/3 signaling.