The Role of MMP-9 in Regulating Degradation of the Splenic Microvascular Basement Membrane Induced by High Altitude Hypoxia / Rol de la MMP-9 en la Regulación de la Degradación de la Membrana Basal Microvascular Esplénica Inducida por Hipoxia de Altura

SUMMARY: To investigate changes of MMP-9 in the rat spleen and hypoxia-induced microvascular basement membrane under high altitude hypoxia. Thirty male specific pathogen-free Sprague Dawley rats were randomly divided into control and hypoxia groups, with 15 rats in each group. The rats in the control group were placed in Dingxi City, Gansu Province (2080 m above sea level) for 30 days. Rats in the hypoxia group were raised in a hypoxic environment in Maduo County, Qinghai Province (4300 m above sea level), for 30 days to establish a hypoxic rat model. Routine blood tests, MMP-9 mRNA, MMP-9 protein, and the spleen microvascular basement membrane were detected. (1) Compared with the control group, the red blood cell count, hemoglobin, and hematocrit levels of the rats in the hypoxia group were all increased; thus, a hypoxia model was successfully established. (2) Compared with the control group, the expression of MMP-9 mRNA and protein was significantly higher in the spleen of rats in the hypoxic group, and the difference was statistically significant (P <0.05). (3) Compared with the control group, the blood vessel basement membrane in the spleen of the hypoxia group was degraded. Under natural low air pressure and high altitude conditions, the expression of MMP-9 in rat spleen tissue increases and participates in the degradation of the microvascular basement membrane.

El objetivo de este trabajo fue investigar los cambios de la MMP-9 en el bazo de la rata y la membrana basal microvascular inducida bajo hipoxia a gran altura. Treinta ratas macho Sprague Dawley, libres de patógenos específicos, se dividieron aleatoriamente en dos grupos de 15 ratas cada uno, un grupo control y un grupo hipoxia. Durante 30 días las ratas del grupo control estuvieron en la ciudad de Dingxi, provincia de Gansu (2080 m sobre el nivel del mar). Las ratas del grupo de hipoxia se criaron en un entorno hipóxico en el condado de Maduo, provincia de Qinghai (4300 m sobre el nivel del mar), durante 30 días para establecer un modelo de rata hipóxica. Se realizaron análisis de sangre de rutina, ARNm de MMP-9, proteína MMP-9 y de la membrana basal microvascular del bazo. En comparación con el grupo control, el recuento de glóbulos rojos, la hemoglobina y los niveles de hematocrito de las ratas del grupo de hipoxia aumentaron; por lo tanto, se estableció con éxito un modelo de hipoxia. En comparación con el grupo control, la expresión de ARNm y proteína de MMP-9 fue significativamente mayor en el bazo de las ratas del grupo hipóxico, siendo la diferencia estadísticamente significativa (P <0,05). En comparación con el grupo control, la membrana basal de los vasos sanguíneos estaba degradada en el bazo del grupo hipoxia. En condiciones naturales de baja presión atmosférica y gran altitud, la expresión de MMP-9 en el tejido del bazo de la rata aumenta y participa en la degradación de la membrana basal microvascular.

Expression of Key Enzymes in Glucose Metabolism in Chronic Mountain Sickness and Its Correlation with Phenotype / 中国实验血液学杂志

OBJECTIVE@#To explore the pathogenesis of erythrocytosis by detecting the key enzymes of glucose metabolism and glucose transporter in bone marrow erythrocytes of chronic mountain sickness (CMS), and analyzing its correlation with hemoglobin.@*METHODS@#Twenty CMS patients hospitalized in Qinghai Provincial People's Hospital from January 2019 to December 2020 were selected as CMS group. Twenty males with leukocyte count > 3.5×109/L who had accepted bone marrow aspiration and had normal result were taken as control group. The mRNA and protein expression of key enzymes and glucose transporter in glucose metabolism in bone marrow CD71+ erythrocytes were detected by real time qPCR and Western blot, respectively. Glucose, lactic acid and 2,3-diphosphoglycerate in the bone marrow supernatant and serum were tested by ELISA. The mRNA and protein expression of key enzymes and glucose transporter, glucose, lactic acid and 2,3-diphosphoglycerate of the two groups were compared. Pearson correlation was used to analyze the correlation between key enzymes, glucose transporter in glucose metabolism in bone marrow CD71+ erythrocytes and hemoglobin.@*RESULTS@#The expression of HK2, GLUT1 and GLUT2 mRNA in the CMS group were higher than those in the control group (P<0.001), while the expression of HK1, OGDH and COX5B mRNA were not different. The expression of HK2, GLUT1 and GLUT2 protein in the CMS group were higher than those in the control group (P<0.05). The levels of glucose and lactic acid in the bone marrow supernatant and serum in the CMS group were not different from those in the control group, while the level of 2,3-diphosphoglycerate was higher (P<0.001). Both HK2 and GLUT2 proteins were positively correlated with hemoglobin (r=0.511, 0.717).@*CONCLUSION@#CMS patients may increase glycolysis by increasing the expression of HK2, and promote the utilization of glucose through high expression of GLUT1 and GLUT2 to meet the need of energy supply.

Fisiología respiratoria. Neumología de altura: saturación de oxígeno, edema pulmonar y pruebas de función pulmonar / Respiratory physiology - High -altitude pneumology: oxygen saturation, pulmonary edema and pulmonary function tests

En las alturas, sobre todo a 2500 metros sobre el nivel del mar, la cantidad absoluta de oxígeno va decreciendo y por lo tanto la cantidad disponible para el intercambio gaseoso disminuye, produciéndose una vasoconstricción hipóxica pulmonar (VHP). La VHP asociada a la hipoxia hipobárica de la altura produce un aumento de la presión pulmonar que es mayor en los lactantes y a mayores alturas. No hay valores únicos de saturación de oxígeno (SatO2) en la altura, porque ésta va disminuyendo según el mayor nivel de altura, aumenta con la edad, y la brecha entre la vigilia y sueño es grande (sobre todo en los primeros meses de vida). El 25% de los niños sanos que viven en altura tienen valores de SatO2 significativamente menores que el 75% restante. Los valores normales de los índices de apnea/hipopnea son distintos a los de nivel del mar. El edema pulmonar de las alturas es una patología frecuente, que se produce por un incremento desproporcionado en la VHP reflejando una hiperactividad del lecho vascular pulmonar ante la exposición aguda a la hipoxia hipobárica. Tiene cuatro fenotipos, es infrecuente en menores de 5 años y rara vez es mortal, la sospecha clínica y el manejo oportuno con oxigeno es la clave. Finalmente, en la altura los valores normales de la función pulmonar de la espirometría, oscilometría de impulso y capacidad de difusión son distintos que a nivel del mar.

At high altitude, especially > 2,500 meters above sea level, the absolute amount of oxygen decreases and therefore the amount available for gas exchange decreases, producing hypoxic pulmonary vasoconstriction (VHP). VHP associated with high-altitude hypobaric hypoxia produces an increase in pulmonary pressure that is greater in infants and at higher altitudes. There are no single values of oxygen saturation (SatO2) at altitude, because it decreases with the highest level of altitude, increases with age, and the gap between wakefulness and sleep is large (especially in the first months of life). Around 25% of healthy children living at altitude have SatO2 values significantly lower than the remaining 75%. The normal values of the apnea/hypopnea indices are different from those at sea level. High altitude pulmonary edema is a frequent pathology that is produced by a disproportionate increase in VHP reflecting hyperactivity of the pulmonary vascular bed in the face of acute exposure to hypobaric hypoxia, it has four phenotypes, it is uncommon in children under 5 years of age, and it is rarely fatal, the clinical suspicion and timely management with oxygen is the key. Finally, at high altitude, the normal values of lung function from spirometry, impulse oscillometry, and diffusing capacity are different from those at sea level.

Bibliometric analysis of main diseases due to exposure to altitude in the world / Análise bibliométrica das principais doenças decorrentes da exposição à altitude no mundo

Introduction: Around 140 million people in the world live-in high-altitude regions; however, there are few bibliometric studies. Objective: Describe the scientific production of the main diseases due to exposure to altitude in the world. Methods: Observational study, bibliometric type. After a systematic search in Scopus, original articles were included, whose main variable was mountain sickness, high-altitude cerebral edema and high-altitude pulmonary edema. Characteristics of each study were manually extracted and analyzed using descriptive statistics. Results: 2305 articles were found on mountain sickness (n=1531), high-altitude pulmonary edema (n=549) and high-altitude cerebral edema (n=225), respectively, in Scopus. Regarding the most influential journal was High Altitude Medicine and Biology in all three diseases, the country with the highest number of articles was the United States (458, 168 and 75), the most used language was English (91.31%, 85.33% and 84.19%), the author with the highest number of publications was Bartsh P. (2.94%, 18.60% and 3.42%) and most of the articles were open access (41.08%, 42.06% and 76.53%), respectively. Conclusion: The scientific production of original articles on mountain sickness, high-altitude pulmonary edema and high-altitude cerebral edema in Scopus has increased in recent years; however, it is still scarce compared to other diseases.

Introdução: Cerca de 140 milhões de pessoas no mundo vivem em regiões de grande altitude, porém, existem poucos estudos bibliométricos. Objetivo: Descrever a produção científica sobre as principais doenças decorrentes da exposição à altitude no mundo. Métodos: Estudo observacional, do tipo bibliométrico. Após busca sistemática no Scopus, foram incluídos artigos originais, cuja variável principal foi mal da montanha, edema cerebral de altitude e edema pulmonar de altitude. As características de cada estudo foram extraídas manualmente e analisadas por meio de estatística descritiva. Resultados: Foram encontrados 2.305 artigos sobre mal da montanha (n=1.531), edema pulmonar de altitude (n=549) e edema cerebral de altitude (n=225), respectivamente no Scopus. Em relação ao periódico mais influente foi High Altitude Medicine and Biology nas três doenças, o país com maior número de artigos foi os Estados Unidos (458, 168 e 75), o idioma mais utilizado foi o inglês (91,31%, 85,33% e 84,19%), o autor com maior número de publicações foi Bartsh P. (2,94%, 18,60% e 3,42%) e a maioria dos artigos foi de acesso aberto (41,08%, 42,06% e 76,53%), respectivamente. Conclusão: A produção científica de artigos originais sobre mal da montanha, edema pulmonar de altitude e edema cerebral de altitude em Scopus tem aumentado nos últimos anos, porém ainda é escassa em comparação com outras doenças

Physical activity in the post-COVID-19: AEROBICOVID project design and perspectives / Atividade física no pós-COVID-19: escopo do projeto AEROBICOVID e suas perspectivas

During the COVID-19 pandemic, several late-onset impairments have been observed, affecting the health and functionality of those involved. On the other hand, lower SARS-CoV-2 infection rates and severity of symptoms were observed in high-altitude cities. In this sense, the AEROBICOVID project was developed with the hypothesis that exercise would be an important opportunity for health improvement and that hypoxia would promote additional benefits in the recovery process. The cohort was about 84 participants with approximately 30 days since the COVID-19 symptoms recovery, 25 in the control group, and 59 divided into three moderate physical training groups. The project had good results in teaching, research, and extension, but also faced difficulties in operationalization. This experience is the basis for future proposals through an extension project at the University of São Paulo and in a Family Health Unit, besides a research project that will develop a new low-cost hypoxia technology (AU)

Durante a pandemia de COVID-19 estão sendo observados vários efeitos tardios, afetando a saúde e a funcionalidade dos acometidos. Por outro lado, foram observadas menores taxas de infecção pelo SARS-CoV-2 e gravidade dos sintomas em cidades de elevada altitude. Neste sentido, o projeto AEROBICOVID foi desenvolvido com a hipótese de que o exercício seria uma proposta importante para a melhoria da saúde e que a hipóxia promoveria benefícios adicionais no processo de recuperação. Participaram 84 pessoas com aproximadamente 30 dias desde a recuperação dos sintomas da COVID-19, 25 no grupo de controle e 59 divididos em três grupos de treinamento físico moderado. O projeto teve bons resultados no ensino, pesquisa e extensão, mas também enfrentou dificuldades na operacionalização. Estas experiências são a base para propostas futuras através de um projeto de extensão na Universidade de São Paulo e em uma Unidade de Saúde da Família, além de um projeto de pesquisa que desenvolverá uma nova tecnologia de hipóxia de baixo custo (AU)

Gene expression signature analysis of peripheral blood mononuclear cells from patients with for high altitude pulmonary hypertension and value for potential drug selection / 中华心血管病杂志

Objective: To investigate the gene expression characteristics of peripheral blood mononuclear cells from patients with high altitude pulmonary hypertension (HAPH) in Naxi residents living in Lijiang, Yunnan, and to explore the underlying pathogenesis and value for potential drug selection. Methods: This is a case-control study. Six patients with HPAH (HPAH group) and 4 normal subjects (control group) were selected from the Naxi residents who originally lived in Lijiang, Yunnan Province. The general clinical data of the two groups were collected, and the related indexes of pulmonary artery pressure were collected. Peripheral blood mononuclear cells of the subjects were collected for RNA sequencing. The differences on gene expression, regulatory network of transcription factors and drug similarity between the two groups were compared. The results were compared with the public data of idiopathic pulmonary arterial hypertension (IPAH). Biological processes and signal pathways were analyzed and compared between HPAH and IPAH patients. Results: The age of 6 patients with HAPH was (68.1±8.3) years old, and there were 2 males (2/6). The age of 4 subjects in the control group was (62.3±10.9) years old, and there were 2 males (2/4). Tricuspid regurgitation velocity, tricuspid pressure gradient and pulmonary systolic pressure in HAPH group were significantly higher than those in control group (all P<0.05). The results of RNA sequencing showed that compared with the control group, 174 genes were significantly upregulated and 169 genes were downregulated in peripheral blood mononuclear cells of HAPH group. These differentially expressed genes were associated with 220 biological processes, 52 molecular functions and 23 cell components. A total of 21 biological processes and 2 signal pathways differed between HPAH and IPAH groups, most of which were related to inflammation and immune response. ZNF384, SP1 and STAT3 were selected as highly correlated transcription factors by transcription factor prediction analysis. Trichostatin A and vorinostat were screened out as potential drugs for the treatment of HAPH by drug similarity analysis. Conclusions: There are significant differences in gene expression in peripheral blood monocytes between HAPH patients and normal population, and inflammation and immune dysfunction are the main pathogenic factors. Trichostatin A and Vorinostat are potential drugs for the treatment of HAPH.

Pharmacodynamic of cilostazol for anti-altitude hypoxia / 中南大学学报(医学版)

OBJECTIVES@#The plateau environment is characterized by low oxygen partial pressure, leading to the reduction of oxygen carrying capacity in alveoli and the reduction of available oxygen in tissues, and thus causing tissue damage. Cilostazol is a phosphodiesterase III inhibitor that has been reported to increase the oxygen release of hemoglobin (Hb) in tissues. This study aims to explore the anti-hypoxic activity of cilostazol and its anti-hypoxic effect.@*METHODS@#A total of 40 male BALB/C mice were randomly divided into a low-dose cilostazol (6.5 mg/kg) group, a medium-dose (13 mg/kg) group, a high-dose (26 mg/kg) group, and a control group. The atmospheric airtight hypoxia experiment was used to investigate the anti-hypoxic activity of cilostazol and to screen the optimal dosage. Twenty-four male Wistar rats were randomly divided into a normoxia control group, a hypoxia model group, an acetazolamide (22.33 mg/kg) group, and a cilostazol (9 mg/kg) group. After 3 days of hypoxia in the 4 010 m high altitude, blood from the abdominal aorta was collected to determine blood gas indicators, the levels of IL-6 and TNF-α in plasma were determined by enzyme-linked immunosorbent assay, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutataione (GSH) were measured. The degree of pathological damage for rat tissues was observed with HE staining.@*RESULTS@#Compared with the control group, the survival time of mice in the low, medium, and high dose group of cilostazol was significantly prolonged, and the survival time of mice in the medium dose group was the longest, with an extension rate at 29.34%, so the medium dose was the best dose. Compared with the hypoxia model group, the P50 (oxygen partial pressure at Hb oxygen saturation of 50%) value of rats in the cilostazol group was significantly increased by 1.03%; Hb and Hct were significantly reduced by 8.46% and 8.43%, and the levels of IL-6 and TNF-α in plasma were reduced by 50.65% and 30.77%. The MDA contents in heart, brain, lung, liver, and kidney tissues were reduced by 37.12%, 29.55%, 25.00%, 39.34%, and 21.47%, respectively. The SOD activities were increased by 94.93%, 9.14%, 9.42%, 13.29%, and 20.80%, respectively. The GSH contents were increased by 95.24%, 28.62%, 28.57%, 20.80%, and 44.00%, respectively. The results of HE staining showed that compared with the hypoxia model group, cilostazol significantly improved the damage of heart, lung, and kidney tissues in rats after hypoxia.@*CONCLUSIONS@#Cilostazol can significantly improve the oxidative stress and inflammatory reaction caused by rapid altitude hypoxia, and it has a significant protective effect on tissue damage caused by hypoxia, suggesting that it has obvious anti-hypoxic activity.

Variaciones fisiológicas y antropométricas en trabajadores según su residencia en tres altitudes geográficas del Perú / Physiological and anthropometric variations in workers due to their residence in three geographic altitudes in Peru

Introducción: El organismo se adapta al lugar donde reside, pero este tema no ha sido estudiado en la población laboral peruana. Objetivo: Determinar las variaciones fisiológicas y antropométricas en trabajadores según su residencia en tres altitudes geográficas del Perú. Métodos: Se realizó una investigación transversal analítica, con los datos fisiológicos (6 parámetros de laboratorio) y antropométricos (peso y talla) de 7500 trabajadores en 3 altitudes diferentes: Lima (nivel del mar), Arequipa (2500 m sobre el nivel del mar) y Cerro de Pasco (4300 m sobre el nivel del mar). Estas mediciones fueron estándares, realizadas por clínicas ocupacionales con certificaciones de calidad. Se obtuvo los coeficientes y valores p para las diferencias según cada altitud y ajustados por el sexo y la edad de cada participante. Resultados: Todos los parámetros fisio-antropométricos variaron según la altitud de residencia (todos los valores p fueron menores a 0,005). Los que se incrementaron a mayor altitud fueron la hemoglobina, el colesterol total y el colesterol HDL; en cambio, disminuyeron a mayor altitud el peso y la glucosa en ayunas. En los hombres aumentaron todas las variables menos en el colesterol HDL (que disminuyó significativamente) y el colesterol LDL (que no tuvo variación estadística), en comparación con las mujeres. Conclusiones: Son evidentes las variaciones en las mediciones de los trabajadores según el lugar donde residían, lo que muestra que no se debe tomar parámetros fijos para su valoración laboral. Esto debe servir a los médicos del trabajo y las autoridades, para tener en cuenta al momento de la valoración de la aptitud médica y luego para la vigilancia ocupacional(AU)

Introduction: The human body adapts to its place of residence, but this topic has not been studied in the Peruvian working population. Objective: Determine physiological and anthropometric variations in workers due to their residence in three geographic altitudes in Peru. Methods: An analytical cross-sectional study was conducted of physiological data (6 laboratory parameters) and anthropometric data (weight and height) of 7 500 workers from three different altitudes: Lima (sea level), Arequipa (2 500 m above sea level) and Cerro de Pasco (4 300 m above sea level). The measures were standard and taken by occupational clinics with quality certifications. Coefficients and p values for differences between the altitudes were obtained and adjusted according to the sex and age of participants. Results: All the physio-anthropometric parameters varied with the altitude of the place of residence (all p values were under 0.005). The parameters which increased at a higher altitude were hemoglobin, total cholesterol and HDL cholesterol, whereas the ones which decreased at a higher altitude were weight and fasting glucose. Among men all variables increased except for HDL cholesterol (which decreased significantly) and LDL cholesterol (which did not show any statistical variation), in comparison with women. Conclusions: Variations in measurements taken from workers from different places of residence are obvious, which shows that fixed parameters should not be used for their labor assessment. This should be taken into account by occupational doctors and authorities for medical attitude assessment and occupational surveillance(AU)

Un ejemplo de respuesta adaptativa integrada: la aclimatación humana a la altitud / An example of integrated adaptive response: human acclimatization to altitude

Se describen las respuestas fisiológicas que el ser humano desarrolla en respuesta a la exposición a la altitud geográfica. Se describen no sólo las alteraciones debidas a una mala coordinación de los ajustes fisiológicos desencadenados durante la aclimatación a la altura sino también sus manifestaciones clínicas más relevantes. Se detallan los mecanismos moleculares subyacentes a tales respuestas y cómo su mejor conocimiento puede permitir aplicar la exposición intermitente a hipoxia como una herramienta útil para la resolución o alivio de determinadas alteraciones y patologías.

We depict the physiological responses developed by the human body in response to the exposure to geographic altitude. The main alterations due to a noncoordinated setup of the physiological adjustments triggered during the acclimatization at altitude are also described, as its most relevant clinical manifestations. The molecular mechanisms underlying such responses are detailed, and how a better knowledge of these processes can allow us to apply intermittent exposure to hypoxia programs as a useful tool for the resolution or relief of certain disorders and pathologies.

Eritrocitosis excesiva y mal de montaña crónico en mujeres residentes a extrema altura (la Rinconada 5200 msnm, Perú) / Excessive erythrocytosis and acute mountain sickness in women living at extreme altitude (La Rinconada, 5200 msnm, Perú)

El objetivo del trabajo fue determinar la prevalencia y el impacto de la eritrocitosis excesiva (EE) y mal de montaña crónico (MMC) en mujeres, y factores asociados en el desarrollo de estas alteraciones, principalmente la edad e índice de masa corporal (IMC). Los resultados mostraron una prevalencia de EE y MMC, de 19,72% y 25,35%, respectivamente. La edad promedio es de 39,79 ± 10,87; el hematocrito promedio fue 51,95 ± 6,85; la saturación de oxígeno fue 79,88 ± 5,24 y el IMC promedio de la participantes es 28,08 ± 3,87. La prevalencia de EE en el sexo femenino es mayor en las mujeres posmenopáusicas, en comparación a las premenopáusicas. Por otro lado, se determinó que un mayor índice de masa corporal se asocia fuertemente a menores valores de saturación de oxígeno. Entonces, así el incremento de la edad y del índice de masa corporal, favorecen el presencia de eritrocitosis excesiva más marcada condicionando un desarrollo de mal de montaña crónico de mayor severidad.

The aim of the work was to determine the prevalence and impact of excessive erytrochytes (EE) and chronic mountain sickness (MMC) in women, and related factors of the development of these alterations, mainly age and body max index (IMC). Results displayed incidence of EE and MMC, by 19.72% and 25.35%, respectively. The average age was 39.79 ± 10.87; the average hematocrit was 51.95 ± 6.85; the oxygen saturation was 79.88 ± 5.24 and the average IMC of the participants was 28.08 ± 3.87. The prevalence of EE on females is greater in postmenopausal women, in comparison to pre menopausals. On the other hand, it was determined that a greater body mass index is strongly associated to lesser oxygen saturation values. Hence, the increase of age and body max index, favor the most marked excesive erytrochytes presence conditioning the most serious acute mountain sickness.

Función ventricular derecha en residentes nativos a gran altura / Right ventricular function in native residents at high altitude

Los adaptados genéticamente a la altura son los tibetanos, sherpas y etíopes; los aymaras y quechuas están aclimatados (Bolivia, Perú y norte de Chile). En Bolivia el mal crónico de montaña afecta 10% de la población masculina. El objetivo fue determinar la función ventricular derecha en residentes sanos y con mal crónico de montaña mediante ecocardiografía transtoráxica. Se utilizaron participantes sanos y con mal crónico de montaña admitidos por el IBBA, desde el año 2012 al 2013. Las variables tomadas son: demográficas, espirometria forzada, gasometría arterial en reposo e hiperoxia, ECG y ECCTT. Los controles (n 40), la edad promedio (44,13±9,69 años), predominio masculino y sobrepeso (IMC 26,27±6,68kg /m2), procedentes de La Paz 3.600 msnm (54%), Potosí 4.000 msnm (22%), El Alto 4.100 msnm (15%) y Oruro 3.800 msnm (9%), el promedio de Hematocrito 51,34±2,91%, hemoglobina 17,15±0,89gr/ dl, Espirometria forzada y Gasometría arterial en reposo e hiperoxia normales, la ECCTT muestra hipertensión pulmonar leve (35,85±3,64mmHg), aumento de grosor del VD (0,51±0,08), TAPSE (2,94±3,85mmHg) y el índice de Tei (0,44±0,22) normales. Los casos (n 40), la edad promedio (48,43±8,08 años), predominio masculino y sobrepeso (IMC 29,54±3,41kg / m2), procedente de La Paz 3.600 msnm (56%), Potosí 4.000 msnm (24%), El Alto 4.100 msnm (13%) y Oruro 3.800 msnm (7%), Hematocrito 63,08±6,2%, Hemoglobina 21,01±2,01gr/dl con eritrotrocitosis, espirometría forzada normal, gasometría arterial en reposo con hipoxemia moderada (PaO2 51,73±4,68mmHg), hipocapnia (PaCO2 27,62±2,04mmHg) y gradiente Alveolo-arterial aumentado (7,61±3,15). Gasometría arterial en hiperoxia descarta shunt (PaO2 308,9±52,58mmHg), el ECG muestra 2 de 11 criterios de crecimiento VD, la ECCTT con hipertensión pulmonar moderada (PSAP 45,22±5,69mmHg), aumento de grosor del VD (0,73±0,22), TAPSE (2,08±0,18cm), normal e índice de Tei (0,51±0,10) ligeramente aumentado. Se concluyó que la función ventricular derecha se encuentra conservada, a pesar de tener hipertensión pulmonar leve (controles) y moderada (casos), con aumento del grosor del ventrículo derecho.

Those genetically adapted to the height are the Tibetans, Sherpas, and Ethiopians; the Aymara and Quechuas are acclimatized (Bolivia, Peru, and northern Chile). In Bolivia, chronic mountain sickness affects 10% of the male population. The objective was to determine the right ventricular function in healthy residents with chronic mountain sickness using transthoracic echocardiography. Use the healthy and chronically ill mountain participants admitted by the IBBA, from 2012 to 2013. The variables taken are demographic, forced spirometry, arterial blood gas at rest and hyperoxia, ECG, and ECCTT. Controls (n 40), average age (44.13 ± 9.69 years), male predominance and overweight (BMI 26.27 ± 6.68kg / m2), frequency from La Paz 3,600 masl (54%), Potosí 4,000 masl (22%), El Alto 4,100 masl (15%) and Oruro 3,800 masl (9%), the average Hematocrit 51.34 ± 2.91%, hemoglobin 17.15 ± 0.89gr / dl, Forced spirometry y Resting arterial blood gas and normal hyperoxia, ECCTT shows mild pulmonary hypertension (35.85 ± 3.64 mmHg), increased RV thickness (0.51 ± 0.08), TAPSE (2.94 ± 3.85 mmHg ) and the Tei index (0.44 ± 0.22) normal. The cases (n 40), the average age (48.43 ± 8.08 years), male predominance and overweight (BMI 29.54 ± 3.41kg / m2), derived from La Paz 3,600 masl (56%), Potosí 4,000 masl (24%), El Alto 4,100 masl (13%) and Oruro 3,800 masl (7%), Hematocrit 63.08 ± 6.2%, Hemoglobin 21.01 ± 2.01gr / dl with erythrocytosis, normal forced spirometry , resting arterial blood gas with moderate hypoxemia (PaO2 51.73 ± 4.68mmHg), hypocapnia (PaCO2 27.62 ± 2.04mmHg) and increased Alveolo-arterial gradient (7.61 ± 3.15). Arterial blood gas in hyperoxia rules out shunt (PaO2 308.9 ± 52.58mmHg), ECG shows 2 of 11 RV growth criteria, ECCTT with moderate pulmonary hypertension (PSAP 45.22 ± 5.69mmHg), increased RV thickness (0.73 ± 0.22), TAPSE (2.08 ± 0.18cm), normal and Tei index (0.51 ± 0.10) slightly increased. It was concluded that the right ventricular function is preserved, a weight of having mild pulmonary hypertension (controls) and moderate (cases), with increased thickness of the right ventricle.

Altitude effect on sleep quality and serum melatonin levels in Chilean mining workers / Efecto de la Altitud en la calidad de sueño y niveles séricos de melatonina en trabajadores mineros en Chile

High altitude (HA) mining operations are a very important business in Chile, but reduced availability of oxygen affects the sleep quality, increasing the risk of accidents. An important regulator of sleep-wake cycle is the hormone Melatonin, produced by pineal gland as a sleep inductor. The aim of this study is to evaluate the effect of high altitude (4,500 m) on the quality of sleep of workers undergoing to Chronic Intermittent Hypobaric Hypoxia (CIHH) using self-reported surveys of sleepiness and sleep quality, measurement of sleep apnea (using nocturnal oximetry) and serum levels of melatonin. The Desaturation index (ID4) results revealed higher HA scores compared to sea level (SL). Regarding melatonin levels, the results show that it is increased in HA versus SL and this increase would be related to oxygen saturation during sleep. These data link sleep quality in HA to its melatonin levels, suggesting that melatonin may be a potential biomarker for sleep quality.

Mal agudo de montaña: pasado, presente y futuro / Acute mountain sickness: past, present and future

Evidencias en textos históricos Chinos de los años 403 AC y de la Conquista Española en 1590, muestran de las condiciones singulares que afectaban tanto a hombres como a animales al ascender por sectores montañosos por sobre 4000 m., y que ahora reconocemos como mal agudo de montaña. Ya desde el siglo XIX, se ha reconocido que es la falta de oxígeno (hipoxia) el factor determinante de la respuesta aclimatatoria como de la desaclimatización a la hipoxia de altura. El objetivo de la actual revisión fue una puesta al día de definiciones, factores que inciden en una mayor incidencia de mal agudo de montaña, mecanismo fisiológico propuesto, el desarrollo de estrategias farmacológicas para la prevención y/o tratamiento y por último, se ha revisado respecto de las distintas estrategias que se han desarrollado para la evaluación de la susceptibilidad individual, conocido comúnmente como test de hipoxia.

Some Chinese historical text from 403 BC and the Spanish Conquest in 1590 indicates unique conditions that affected both men and animals when climbing mountainous areas over 4000 m. and that is currently known as Acute Mountain Sickness (MAM). Since the XIX century, the lack of oxygen (hypoxia), has been recognized as the main factor of the acclimatization and declimatization to the high altitude hypoxia. The aim of the current revision is an update of definitions, factors that contribute the Acute Mountain Sickness, the proposed physiological mechanism, the development of pharmacological strategies for the prevention and/or treatment, and finally, we reviewed the different strategies developed for the individual susceptibility assessment, generally known as hypoxia test.

Edema pulmonar de las alturas. A propósito de un caso / High Altitude Pulmonary Edema: About a Case

El edema pulmonar de las alturas es una condición clínica que se desarrolla en individuos que han estado en regiones a nivel del mar y que posteriormente ascienden rápidamente a altitudes por encima de los 2500 metros. Se describe el caso de un paciente de 26 años con cuadro clínico y hallazgos radiológicos típicos de esta patología, en quién inicialmente se sospechó infección por coronavirus dada la sintomatología y el contexto de pandemia actual

High altitude pulmonary edema is a clinical condition that develops in individuals who have been in regions at sea level and who subsequently have a rapid ascent to altitudes above 2500 meters. We present the case of a 26-year-old male with clinical presentation and radiological findings typical of this entity, in whom coronavirus infection was initially suspected given the signs and symptoms in context of the current pandemic

Ibuprofeno comparado con acetazolamida para prevención de mal agudo de montaña / Ibuprofen versus acetazolamide for prevention of acute mountain sickness

INTRODUCCIÓN: El mal agudo de montaña es una condición frecuente en individuos sanos, sin aclimatación que se exponen a alturas desde 2500 metros sobre el nivel del mar. Clásicamente se ha utilizado acetazolamida para prevenirlo, pero en los últimos años ha surgido evidencia a favor de ibuprofeno. Sin embargo, no está claro cuál de estos tratamientos es más efectivo. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos dos revisiones sistemáticas que en conjunto incluyeron un estudio primario, el cual corresponde a un ensayo aleatorizado. Concluimos que no es posible establecer con claridad si ibuprofeno es mejor o peor que acetazolamida debido a que la certeza de evidencia existente ha sido evaluada como muy baja.

INTRODUCTION: Acute mountain sickness is a common condition occurring in healthy subjects that undergo rapid ascent without prior acclimatization, as low as 2500 meters above sea level. The classic preventive agent has been acetazolamide, although in the last decade there has been evidence favoring ibuprofen. However, it is unclear which method is more efficient. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis) and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified two systematic reviews that included only one primary study, which is a randomized trial. We concluded it is not possible to establish whether ibuprofen is better or worse than acetazolamide because the certainty of evidence has been evaluated as very low.

Edema agudo de pulmón por mal de altura: caso pediátrico / Acute pulmonary edema due to altitude sickness: pediatric case

Resumen: El edema pulmonar por mal de altura es una entidad no cardiogénica que se debe a hipoxia hipobárica y falta de adaptación pulmonar en los pacientes que retornan a altitudes mayores de 2.500 m luego de haber permanecido a nivel del mar por varios días. Esta entidad, frecuente en los niños, debido a sus características anatómicas y fisiológicas, suele ser subdiagnosticada o confundida con otras patologías que cursan con insuficiencia respiratoria. Presentamos el caso de un paciente de sexo masculino, 4 años de edad, atendido en Emergencias por dificultad respiratoria severa por mal de altura.

Abstract: Pulmonary edema by altitude sickness is a non-cardiogenic entity, due to lack of pulmonary adaptation and hypobaric hypoxia in patients who return to altitudes higher than 2,500 meters after staying for several days at sea level. This entity is frequent in children, given their physiological and anatomical characteristics. It tends to be underdiagnosed or confused with other pathologies associated with shortness of breath. We present the case of a four-year-old male patient, who attended the emergency department for severe respiratory distress caused by altitude sickness.

Saturación de oxígeno, frecuencia cardiaca y respiratoria en recién nacidos a término en poblaciones de altura / Oxygen saturation, heart and respiratory frequency of term newborns in high-altitude populations

Introducción: La adaptación a la vida extrauterina de los recién nacidos es importante, especialmente en poblaciones de altura donde las características son diferentes a poblaciones a nivel del mar. Objetivos: Determinar la correlación entre saturación de oxígeno, frecuencia cardiaca y respiratoria durante los primeros 720 minutos de vida en recién nacidos a término a 3 400 metros sobre el nivel del mar. Métodos: Estudio observacional, prospectivo. Se incluyó a recién nacidos de parto eutócico a término del servicio de neonatología de un hospital de Cusco-Perú durante octubre y diciembre del 2016. Se evaluó la saturación de oxígeno, frecuencia cardiaca y respiratoria a los 5, 30, 120, 360, 480 y 720 minutos después del nacimiento. Se realizó un análisis descriptivo y se calcularon las correlaciones entre las variables utilizando el coeficiente de Correlación de Pearson. Se consideró significativos los valores p<0,05. Resultados: La media de saturación de oxígeno, frecuencia cardiaca y frecuencia respiratoria fue estable a las dos horas. Se obtuvo una correlación significativa entre la frecuencia cardiaca y saturación de oxígeno a los 5, 30, 120, 360 y 720 minutos. La frecuencia respiratoria y saturación de oxígeno se correlacionó significativamente a los 5, 30, 480 y 720 minutos. Conclusiones: La correlación entre la saturación de oxígeno, frecuencia cardiaca y frecuencia respiratoria es adecuada en distintos periodos. Este estudio contribuye a conocer mejor la adaptación a la vida extrauterina del recién nacido en esta población de altura(AU)

Introduction: Newborns adaptation to extrauterine life is important, especially in high altitude populations where the characteristics are different from sea level populations. Objectives: To estimate the correlation between oxygen saturation, heart and respiratory frequency during the first 720 minutes of life in term newborns at 3 400 meters above sea level. Methods: An observational, prospective study was performed. Newborns from eutocic delivery at term that were born during October and December 2016 in the neonatology service at Cusco-Peru Hospital were included in the study. Oxygen saturation, heart frequency and respiratory frequency were assessed at 5, 30, 120, 360, 480 and 720 minutes after birth. A descriptive analysis was performed and the correlations among the variables were calculated using Pearson's correlation coefficient test. Values p <0.05 were considered significant. Results: Mean oxygen saturation, heart rate and respiratory rate were stable at two hours. A significant correlation was obtained between heart rate and oxygen saturation at 5, 30, 120, 360 and 720 minutes. Respiratory frequency and oxygen saturation correlated significantly at 5, 30, 480 and 720 minutes. Conclusions: Correlation between oxygen saturation, heart rate and respiratory rate are adequate in different periods. This study contributes to better understand the adaptation of newborns in these high altitude populations(AU)

Phytochemistry and Biological Activities of Werneria and Xenophyllum species / Fitoquímica y actividades biológicas de especies de Werneria y Xenophyllum

Plants of the genera Werneria (Asteraceae) and Xenophyllum (genus extracted from Werneria) are used in traditional medicine of Latin America for the treatment of mountain sickness, hypertension and gastrointestinal disorders. Only a small number of species of these genera have been studied, leading to the isolation of compounds belonging to the classes of benzofurans, chromenes, acetophenones, coumarates, diterpenes and pyrrolizidine alkaloids. Some of the plant extracts and/or compounds have shown antimicrobial, anti-HIV, hypotensive and photoprotective activities.

Las plantas de los géneros Werneria (Asteraceae) y Xenophyllum (género extraido de Werneria) son usadas en la medicina tradicional de América Latina para el tratamiento del mal de montaña, hipertensión y desórdenes gastrointestinales. Solo un pequeño número de especies de estos géneros ha sido investigado, lográndose aislar compuestos que pertenecen a las clases de benzofuranos, cromenos, acetofenonas, cumaratos, diterpenos y alcaloides pirrolizidínicos. Algunos de los extractos y/o compuestos de dichas plantas han mostrado actividades antimicrobianas, anti-HIV, hipotensoras y fotoprotectoras.

Acetazolamida como tratamiento del mal agudo de montaña / Acetazolamide for the treatment of acute mountain sickness

INTRODUCCIÓN El mal agudo de montaña es la patología más prevalente relacionada con la exposición aguda a la altura, secundaria a los efectos de la hipoxia hipobárica en nuestro organismo. La acetazolamida se ha utilizado tradicionalmente para su prevención y tratamiento, sin embargo, aún existe controversia respecto al grado de utilidad que tiene este medicamento como monoterapia. MÉTODOS Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un meta análisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES Identificamos una revisión sistemática que incluyó dos estudios primarios, ambos correspondientes a ensayos aleatorizados. Concluimos que no es posible establecer con claridad si el tratamiento con acetazolamida disminuye los síntomas del mal agudo de montaña ni si aumenta el riesgo de efectos adversos, debido a que la certeza de la evidencia existente ha sido evaluada como muy baja.

INTRODUCTION Acute mountain sickness is the most prevalent illness related to acute exposure to high altitude, secondary to the hypobaric hypoxia effects in our body. Acetazolamide has been traditionally used for its prevention and treatment, however, there is still controversy regarding the degree of usefulness of this medication as monotherapy. METHODS We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS We identified a systematic review that included two primary studies, both corresponding to randomized trials. We conclude that it is not possible to establish clearly whether treatment with acetazolamide reduces the symptoms of acute mountain disease or increases the risk of adverse effects, because the certainty of the existing evidence has been evaluated as very low.