Endothelial biomarkers (Von willebrand factor, BDCA3, urokinase) as predictors of mortality in COVID-19 patients: cohort study.

BACKGROUND: SARS-CoV-2 is a systemic disease that affects endothelial function and leads to coagulation disorders, increasing the risk of mortality. Blood levels of endothelial biomarkers such as Von Willebrand Factor (VWF), Thrombomodulin or Blood Dendritic Cell Antigen-3 (BDCA3), and uUokinase (uPA) increase in patients with severe disease and can be prognostic indicators for mortality. Therefore, the aim of this study was to determine the effect of VWF, BDCA3, and uPA levels on mortality. METHODS: From May 2020 to January 2021, we studied a prospective cohort of hospitalized adult patients with polymerase chain reaction (PCR)-confirmed COVID-19 with a SaO2 ≤ 93% and a PaO2/FiO2 ratio < 300. In-hospital survival was evaluated from admission to death or to a maximum of 60 days of follow-up with Kaplan-Meier survival curves and Cox proportional hazard models as independent predictor measures of endothelial dysfunction. RESULTS: We recruited a total of 165 subjects (73% men) with a median age of 57.3 ± 12.9 years. The most common comorbidities were obesity (39.7%), hypertension (35.4%) and diabetes (30.3%). Endothelial biomarkers were increased in non-survivors compared to survivors. According to the multivariate Cox proportional hazard model, those with an elevated VWF concentration ≥ 4870 pg/ml had a hazard ratio (HR) of 4.06 (95% CI: 1.32-12.5) compared to those with a lower VWF concentration adjusted for age, cerebrovascular events, enoxaparin dose, lactate dehydrogenase (LDH) level, and bilirubin level. uPA and BDCA3 also increased mortality in patients with levels ≥ 460 pg/ml and ≥ 3600 pg/ml, respectively. CONCLUSION: The risk of mortality in those with elevated levels of endothelial biomarkers was observable in this study.

Oxidative Stress and Air Pollution: Its Impact on Chronic Respiratory Diseases.

Redox regulation participates in the control of various aspects of metabolism. Reactive oxygen and nitrogen species participate in many reactions under physiological conditions. When these species overcome the antioxidant defense system, a distressed status emerges, increasing biomolecular damage and leading to functional alterations. Air pollution is one of the exogenous sources of reactive oxygen and nitrogen species. Ambient airborne particulate matter (PM) is important because of its complex composition, which includes transition metals and organic compounds. Once in contact with the lungs' epithelium, PM components initiate the synthesis of inflammatory mediators, macrophage activation, modulation of gene expression, and the activation of transcription factors, which are all related to the physiopathology of chronic respiratory diseases, including cancer. Even though the pathophysiological pathways that give rise to the development of distress and biological damage are not fully understood, scientific evidence indicates that redox-dependent signaling pathways are involved. This article presents an overview of the redox interaction of air pollution inside the human body and the courses related to chronic respiratory diseases.

Seasonal and Spatial Variability of PM2.5 Concentration, and Associated Metal(loid) Content in the Toluca Valley, Mexico.

This study provides evidence of the seasonal and spatial variation of metal(lloid)s in particulate matter minor to 2.5 microns (PM2.5) in the Toluca Valley Metropolitan Area (TVMA), the fifth largest urban center in Mexico. Four sites were sampled between 2013 and 2014, which included urban and industrial areas, in the dry-cold (November-February) and dry-hot (March-May) seasons; PM2.5 was collected using high- and medium-volume samplers. Metal(lloid) concentrations in PM2.5 were analyzed using inductively coupled plasma‒mass spectrometry (ICP‒MS). The highest 24-hour PM2.5 concentration in the northern area was observed, and the PM2.5 concentrations were independent of the season. Five metal(lloid)s with a recovery percentage above 80% were considered to be reported (Co, Cr, Cu, Mn, and Sb). The maximum concentrations of metal(lloid)s were observed during the dry-cold season, and concentrations were up to one hundred or thousand fold with respect to the dry-hot season. The 24-hour PM2.5 and metal(lloid) concentrations exceeded national and international guidelines to protect population health.

Obesity and pro-inflammatory mediators are associated with acute kidney injury in patients with A/H1N1 influenza and acute respiratory distress syndrome.

BACKGROUND: The obesity has been shown to increase the severity of A/H1N1 infection and the development of acute respiratory distress syndrome (ARDS) and organ involvement. METHODS: Circulating levels of C-peptide, insulin, glucagon, leptin, acute phase reactants (procalcitonin, C-reactive protein, tissue plasminogen activator, and serum amyloids A and P), were measured in samples from 32 critically ill patients with A/H1N1 virus infection, 17 of whom had ARDS complicated by acute kidney injury (AKI) and 15 of whom had ARDS but did not develop AKI. RESULTS: Patients with ARDS and AKI (ARDS/AKI) had higher BMI and higher levels of C-peptide, insulin, leptin, procalcitonin and serum amyloid A compared to those ARDS patient who did not develop AKI. Adjusting for confounding variables using logistic regression analysis, higher levels of C-peptide (>0.75 ng/mL) (OR=64.8, 95% CI = 2.1-1980, p = 0.0006) and BMI>30 Kg/m(2) (OR = 42.0, 95% CI = 1.2-1478, p = 0.04) were significantly associated with the development of AKI in ARDS patients. CONCLUSION: High levels of C-peptide and BMI>30 kg/m(2) were associated with the development of AKI in ARDS patients due to A/H1N1 infection. These metabolic/obesity indicators, together with the profiles of pro-inflammatory acute phase proteins, may be important links between obesity and poor outcomes in A/H1N1 09 infection.

Regulation of Cancer-Associated miRNAs Expression under Hypoxic Conditions.

Solid tumors frequently experience hypoxia or low O2 levels. In these conditions, hypoxia-inducible factor 1 alpha (HIF-1α) is activated and acts as a transcription factor that regulates cancer cell adaptation to O2 and nutrient deprivation. HIF-1α controls gene expression associated with various signaling pathways that promote cancer cell proliferation and survival. MicroRNAs (miRNAs) are 22-nucleotide noncoding RNAs that play a role in various biological processes essential for cancer progression. This review presents an overview of how hypoxia regulates the expression of multiple miRNAs in the progression of cancer cells.

Effect of smoking on the redox status of knee osteoarthritis: A preliminary study.

Even though smoking has been scarcely studied in osteoarthritis (OA) etiology, it is considered a controversial risk factor for the disease. Exposure to tobacco smoke has been reported to promote oxidative stress (OS) as part of the damage mechanism. The aim of this study was to assess whether smoking increases cartilage damage through the generation of OS. Peripheral blood (PB) and synovial fluid (SF) samples from patients with OA were analyzed. The samples were stratified according to smoking habit, Kellgren-Lawrence score, pain, and cotinine concentrations in PB. Malondialdehyde (MDA), methylglyoxal (MGO), advanced protein oxidation products (APOPs), and myeloperoxidase (MPO) were assessed; the activity of antioxidant enzymes such as gamma-glutamyl transferase (GGT), glutathione S-transferase (GST) and catalase (CAT), as well as the activity of arginase, which favors the destruction of cartilage, was determined. When stratified by age, for individuals <60 years, the levels of MDA and APOPs and the activity of MPO and GST were higher, as well as antioxidant system activity in the smoking group (OA-S). A greater degree of pain in the OA-S group increased the concentrations of APOPs and arginase activity (P < 0.01 and P < 0.05, respectively). Arginase activity increased significantly with a higher degree of pain (P < 0.01). Active smoking can be an important risk factor for the development of OA by inducing systemic OS in young adults, in addition to reducing antioxidant enzymes in older adults and enhancing the degree of pain and loss of cartilage.

Air pollution: impact and prevention.

Air pollution is becoming a major health problem that affects millions of people worldwide. In support of this observation, the World Health Organization estimates that every year, 2.4 million people die because of the effects of air pollution on health. Mitigation strategies such as changes in diesel engine technology could result in fewer premature mortalities, as suggested by the US Environmental Protection Agency. This review: (i) discusses the impact of air pollution on respiratory disease; (ii) provides evidence that reducing air pollution may have a positive impact on the prevention of disease; and (iii) demonstrates the impact concerted polices may have on population health when governments take actions to reduce air pollution.

Plasma Endothelial and Oxidative Stress Biomarkers Associated with Late Mortality in Hospitalized COVID-19 Patients.

BACKGROUND: Coronavirus infectious disease 2019 (COVID-19) is a significant public health problem worldwide. COVID-19 increases the risk of non-pulmonary complications such as acute myocardial injury, renal failure, thromboembolic events, and multi-organic damage. Several studies have documented increased inflammation molecules, endothelial dysfunction biomarkers, and dysregulation of coagulation factors in COVID-19 patients. In addition, endothelium dysfunction is exacerbated by the oxidative stress (OxS) promoted by endocrine and cardiovascular molecules. Our objective was to evaluate whether endothelial and OxS biomarkers were associated with mortality in hospitalized COVID-19 patients. METHODS: A prospective cohort study was performed. Patients ≥18 years old with confirmed COVID-19 that required hospitalization were included in a prospective cohort study. Endothelium and oxidative stress biomarkers were collected between 3 and 5 days after admission. RESULTS: A total of 165 patients were evaluated; 56 patients succumbed. The median follow-up was 71 days [23-129]. Regarding endothelial dysfunction and OxS biomarkers, patients who did not survive had higher levels of nitrates (0.4564 [0.1817-0.6761] vs. 0.2817 [0.0517-0.5], p = 0.014), total nitrates (0.0507 [-0.0342-0.1809] vs. -0.0041 [-0.0887-0.0909], p = 0.016), sE-Selectin (1.095 [0.86-1.495] vs. 0.94 [0.71-1.19], p = 0.004), and malondialdehyde (MDA) (0.50 [0.26-0.72] vs. 0.36 [0.23-0.52], p = 0.010) compared to patients who survived. Endothelial and OxS biomarkers independently associated with mortality were sE-selectin (HR:2.54, CI95%; from 1.11 to 5.81, p = 0.027), nitrates (HR:4.92, CI95%; from 1.23 to 19.63, p = 0.024), and MDA (HR: 3.05, CI95%; from 1.14 to 8.15, p = 0.025). CONCLUSIONS: Endothelial dysfunction (sE-selectin and nitrates) and OxS (MDA) are independent indicators of a worse prognosis in COVID-19 patients requiring hospitalization.

Effect of Hypoxia in the Transcriptomic Profile of Lung Fibroblasts from Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease characterized by exacerbated extracellular matrix deposition that disrupts oxygen exchange. Hypoxia and its transcription factors (HIF-1α and 2α) influence numerous circuits that could perpetuate fibrosis by increasing myofibroblasts differentiation and by promoting extracellular matrix accumulation. Therefore, this work aimed to elucidate the signature of hypoxia in the transcriptomic circuitry of IPF-derived fibroblasts. To determine this transcriptomic signature, a gene expression analysis with six lines of lung fibroblasts under normoxia or hypoxia was performed: three cell lines were derived from patients with IPF, and three were from healthy donors, a total of 36 replicates. We used the Clariom D platform, which allows us to evaluate a huge number of transcripts, to analyze the response to hypoxia in both controls and IPF. The control's response is greater by the number of genes and complexity. In the search for specific genes responsible for the IPF fibroblast phenotype, nineteen dysregulated genes were found in lung fibroblasts from IPF patients in hypoxia (nine upregulated and ten downregulated). In this sense, the signaling pathways revealed to be affected in the pulmonary fibroblasts of patients with IPF may represent an adaptation to chronic hypoxia.

Osteopontin's relationship with malnutrition and oxidative stress in adolescents. A pilot study.

Osteopontin (OPN) is a protein involved in inflammatory illnesses such as fibrosis and cancer; its overexpression in cardiovascular diseases promotes the biomineralization of blood vessels and other soft tissues. Moreover, there is an active component of oxidative stress related with those diseases. The present study relates serum OPN levels with nutritional condition and oxidative stress in a group of adolescents. Anthropometric measurements were performed, and fasting blood samples were analyzed to determine OPN concentrations, blood chemistry parameters (glucose, triglycerides, total cholesterol, urea, uric acid, and creatinine) and oxidative stress biomarkers (Paraoxonase-1, Glutathione S-Transferase, Catalase, NAD(P)H Quinone Oxidoreductase, free carbonyl groups and malondialdehyde). Adolescents were categorized according to body mass index (BMI) and metabolic syndrome (MetS) criteria. We found increased OPN serum concentrations in overweight and obese adolescents, as well as in adolescents with MetS. Rises in OPN correlated with arm circumference and biomarkers of lipid peroxidation; with regard to serum glucose there was a trend to positive correlation. Our results suggest that serum OPN is associated to nutritional status and could be considered as an early biomarker of low-grade inflammation and probably the early biomineralization of soft tissues in adolescence.

Physiological Network From Anthropometric and Blood Test Biomarkers.

Currently, research in physiology focuses on molecular mechanisms underlying the functioning of living organisms. Reductionist strategies are used to decompose systems into their components and to measure changes of physiological variables between experimental conditions. However, how these isolated physiological variables translate into the emergence -and collapse- of biological functions of the organism as a whole is often a less tractable question. To generate a useful representation of physiology as a system, known and unknown interactions between heterogeneous physiological components must be taken into account. In this work we use a Complex Inference Networks approach to build physiological networks from biomarkers. We employ two unrelated databases to generate Spearman correlation matrices of 81 and 54 physiological variables, respectively, including endocrine, mechanic, biochemical, anthropometric, physiological, and cellular variables. From these correlation matrices we generated physiological networks by selecting a p-value threshold indicating statistically significant links. We compared the networks from both samples to show which features are robust and representative for physiology in health. We found that although network topology is sensitive to the p-value threshold, an optimal value may be defined by combining criteria of stability of topological features and network connectedness. Unsupervised community detection algorithms allowed to obtain functional clusters that correlate well with current medical knowledge. Finally, we describe the topology of the physiological networks, which lie between random and ordered structural features, and may reflect system robustness and adaptability. Modularity of physiological networks allows to explore functional clusters that are consistent even when considering different physiological variables. Altogether Complex Inference Networks from biomarkers provide an efficient implementation of a systems biology approach that is visually understandable and robust. We hypothesize that physiological networks allow to translate concepts such as homeostasis into quantifiable properties of biological systems useful for determination and quantification of health and disease.

Airborne particulate matter PM2.5 from Mexico City affects the generation of reactive oxygen species by blood neutrophils from asthmatics: an in vitro approach.

BACKGROUND: The Mexico City Metropolitan Area is densely populated, and toxic air pollutants are generated and concentrated at a higher rate because of its geographic characteristics. It is well known that exposure to particulate matter, especially to fine and ultra-fine particles, enhances the risk of cardio-respiratory diseases, especially in populations susceptible to oxidative stress. The aim of this study was to evaluate the effect of fine particles on the respiratory burst of circulating neutrophils from asthmatic patients living in Mexico City. METHODS: In total, 6 subjects diagnosed with mild asthma and 11 healthy volunteers were asked to participate. Neutrophils were isolated from peripheral venous blood and incubated with fine particles, and the generation of reactive oxygen species was recorded by chemiluminescence. We also measured plasma lipoperoxidation susceptibility and plasma myeloperoxidase and paraoxonase activities by spectrophotometry. RESULTS: Asthmatic patients showed significantly lower plasma paraoxonase activity, higher susceptibility to plasma lipoperoxidation and an increase in myeloperoxidase activity that differed significantly from the control group. In the presence of fine particles, neutrophils from asthmatic patients showed an increased tendency to generate reactive oxygen species after stimulation with fine particles (PM2.5). CONCLUSION: These findings suggest that asthmatic patients have higher oxidation of plasmatic lipids due to reduced antioxidant defense. Furthermore, fine particles tended to increase the respiratory burst of blood human neutrophils from the asthmatic group.On the whole, increased myeloperoxidase activity and susceptibility to lipoperoxidation with a concomitant decrease in paraoxonase activity in asthmatic patients could favor lung infection and hence disrupt the control of asthmatic crises.

Correlación directa entre FEF25-75 y la actividad de la paraoxonasa plasmática en pacientes asmáticos adultos / Direct correlation between FEF25-75 and plasmatic paraoxonase activity in adult patients with asthma

Introducción: El incremento en la actividad de mieloperoxidasa (AAPO) (EC 1.11.1.7) plasmática ha sido relacionada con la evolución de diferentes patologías destacando las enfermedades crónico-degenerativas que tienen en común el cursar con un estado de estrés oxidativo (EO) concomitante a un proceso inflamatorio persistente. Este es el caso del asma. La enzima paraoxonasa (PON-1) (EC 3.1.1.2), es una arilesterasa que forma parte de la APO A-I de laa HDL. Su función catalítica le permite hidrolizar hidroperóxidos formados durante la lipoperoxídación de lipoproteínas y membranas como consecuencia de un EO. A la PON-1 se ha considerado como protectora de las lipoproteínas al interrumpir la oxidación de las LDL y disminuir el daño a estructuras celulares. Es una actividad enzimática que representa a la defensa antiestrés oxidativo. Objetivos: Demostrar que el estrés oxidativo del paciente asmático puede ser evaluado por el incremento de MPO como marcador de daño oxidante y que la función respiratoria adecuada puede ser relacionada con la capacidad de defensa antioxidante representada por la actividad de la PON-1. Métodos: La actividad de ambas enzimas fue determinada en el plasma de un grupo de pacientes con asma leve a moderada comparado con un grupo control formado por individuos clínicamente sanos. Resultados: En el grupo de pacientes con asma, la actividad de MPO se incrementó en un 42% (57.31 ± 7.2 U vs 33.34 ± 4.7 U p<0.05), mientras que se observó un decremento del 52% (0.09 ±0.1 nmol p-nitrofenol/mg prot vs 0.05 ± 0.01 nmol p-nitrofenol/mg prot p<0.01) en la actividad de la PON-1. La actividad de la MPO mostró una correlación inversamente proporcional con el FEV1 con una r de Spearman de -0.57 y la PON-1 mostró una correlación directamente proporcional con el FEF25-75 con una r de Spearman de 0.64. Conclusiones: Se demuestra por primera vez que los pacientes con asma, en los que se presenta un estado de estrés oxidativo que afecta ...

Introduction: Plasma myeloperoxidase activity (MPO) (EC 1.11.1.7) has been related to several chronic-degenerative diseases such as asthma, which have in common a chronic inflammatory process. Paraoxonase (PON-1) (EC 3.1.1.2), is an arylesterase enzyme that has a hydroperoxide catalytic function. This enzyme is a component of APO A-l located in HDL. PON1 is has been considered to protect lipoproteins, because it interrupts the oxidation process of LDL, conducive to the atherosclerotic process. Objectives: To demonstrate that, a) oxidative stress in asthmatic patients correlates with the MPO activity, and b) demonstrate the role of PON 1 activity as a biomarker of their pulmonary function. Methods: The activity of both enzymes was measured in plasma of patients with asthma and compared to a control group of healthy subjects. Results: In the group of patients with asthma, MPO activity increased 42% (57.31 ± 7.2 U vs 33.34 ± 4.7 U p<0.05), while PON-1 activity decreased 52% (0.09 ±0.1 nmol p-nitrophenol/mg prot vs 0.05 ± 0.01 nmol p-nitrophenol/mg prot p<0.01). MPO activity showed an inverse correlation with FEV, with a Spearman r of -0.57, while PON-1 activiy showed a direct correlation with FEF25-75, Spearman r of0.64. Conclusions: In this study we show, for the first time, that asthma patients, in whom there is a state of oxidative stress that affects the pulmonary function, PON-1 determination can be useful as a predictor of a better pulmonary function, whereas an increment in MPO activity could be associated to an acute inflammatory process, implicating cellular damage. * U = U/mg of protein'.

Marcadores plasmáticos de estrés oxidante en población mexicana sana de 31 a 60 años de edad / Plasma markers of oxidative stress in healthy 31-60 year old mexican population

Introducción: Patologías como asma, enfermedad pulmonar obstructiva crónica, diabetes mellitus, neuropatías y el síndrome de Alzheimer, entre otros, están asociados al estrés oxidante, condición metabóllca por la cual las personas que sufren estos padecimientos presentan modificaciones y rompimiento de biomoléculas en plasma; es importante conocer sus valores básales en personas sanas para poder interpretarlos adecuadamente. Objetivo: Determinar las concentraciones básales de algunos marcadores de estrés oxidante en adultos sanos (31-60 años). Método: A 67 personas sanas, divididas en tres grupos. Grupo 1 (31-40 años); grupo 2 (41-50 años) y grupo 3 (51-60 años), se les evaluaron los siguientes marcadores de estrés oxidante: Compuestos reactivos al ácido tiobarbitúrico (CRAT), predisposición al daño oxidante, determinación de grupos carbonilo, capacidad antioxidante total de plasma (CATP), y actividad enzimática de paraoxonasa. Los resultados se sometieron a pruebas estadísticas de ANOVA de una vía y post-hoc de Bonferroni, considerando una significancia de 0.05. Resultados: Se encontró un aumento significativo en CRAT en el grupo 2 y en el grupo 3 (8.462 ± 0.571 vs 10.34 ± 1.23µM CRAT, respectivamente). En la predisposición a la lipoperoxidación, el grupo 3 fue el más susceptible al daño, debido a que hubo un incremento en los niveles de CRAT (477.0 ± 16.71 µM) en comparación al grupo 2 (432.3 ± 25.71 µM) y al grupo 1 (320.6 ± 28.95µM). En la determinación de grupos carbonilo no existieron diferencias entre los grupos. La CATP disminuyó en el grupo 2 con respecto al grupo 1 (0.950 ± 0.071 vs 0.69 ± 0.068 unidades, respectivamente). La actividad de paraoxonasa presentó un aumento en el grupo 3 con respecto al grupo 1 (0.119 ± 0.004 vs 0.072 ± 0.007 nmol p-nitrofenol/ mg proteína, respectivamente). Conclusión: Las concentraciones de los marcadores de daño por estrés oxidante se ven modificadas por la edad del individuo. En el proceso natural de envejecimiento, el principal daño es a Iípidos.

Introduction: Patients with asthma, COPD, diabetes mellitus, kidney diseases and Alzheimer syndrome, conditions associated to oxidative stress, have modifications and rupture of certain plasma biomolecules. In order to explain properly this findings, basal values in normal individuals of such biomolecules should be known. Objective: To determine the basal values of some markers of oxidative stress in healthy 31 to 60 year old individuals. Method: Seventy seven healthy volunteers were classified into group 1, 31 to 40 years, group 2, 41 to 50 years and group 3, 51 to 60 years; the following oxidative stress markers were measured: reactive compounds to tiobarbituric acid (TBARs), predisposition to oxidative stress, determination of carbonil groups, total antioxidative capacity of plasma (TACP) and enzymatic activity of paraoxonase. ANOVA and Bonferroni tests were used; a level of 0.05 was considered significant. Results: Croup 2 and 3 showed significant increment in TBARs (8.462 ± 0.571 vs 10.34 ± 1.23µM TBARs, respectively). In the predisposition to lipoper oxidation, group 3 was more susceptible, due to an increase in RCTA levels (477.0 ± 16.71 µM) in comparison to group 2 (432.3 ± 25.71 µM) and 1 (320.6 ± 28.95 µM). There was no difference in the determination of carbonil groups between the groups. TACP is significantly diminished in group 2 in relation to group 1 (0.950 ± 0.071 vs 0.69 ± 0.068 units, respectively). Paraoxonase's activity showed a significant increase in group 3 in relation to group 1 (0.119 ± 0.004 vs 0.072 ± 0.007 nmol p-nitrophenol/mg protein, respectively). Conclusion: Advancing age modifies biomolecular markers of oxidative stress; during the natural aging process, the main damage is to lipids.

Incremento de la actividad de mieloperoxidasa plasmática en pacientes con asma asociada a diabetes mellitus tipo 2. Indicador de mayor desequilibrio homeostático / Increase of myeloperoxidase activity in patients with asthma associated to diabetes mellitus type 2. An indicator of homeostatic disequilibrium

Antecedentes: La actividad de mieloperoxidasa (MPO, EC 1.11.1.7) plasmática ha sido relacionada con diferentes enfermedades crónico-degenerativas, que tienen en común cursar con un proceso inflamatorio crónico, como son los casos de asma y diabetes mellitus. Durante el proceso inflamatorio se generan especies reactivas del oxígeno (ERO) incluyendo al ácido hipocloroso (HCIO-) que es el producto de la MPO. Objetivos: Demostrar que el asma y la diabetes mellitus, que cursan con estrés oxidante, presentan una respuesta metabólica acumulativa que puede ser evaluada por el incremento de MPO como marcador de daño oxidante. Métodos: La actividad de la enzima fue determinada en el plasma de un grupo control formado por 36 individuos clínicamente sanos y en tres grupos de pacientes: a) 13 asmáticos, b) 29 diabéticos y c) 6 con coexistencia de ambos padecimientos. Resultados: En los pacientes con ambos padecimientos, la actividad de MPO se incrementó significativamente (65.1 ± 11.2 U*; p < 0.05). El grupo control presentó una actividad similar (37.6 ±3.2 U*) a la de los pacientes con asma (35.9 ± 5.2 U*) y a los diabéticos (32.6 ± 3.3 U*). Conclusiones: Se demuestra que la coexistencia de dos padecimientos crónico-degenerativos incrementa la posibilidad de daño tisular debido a la generación de ERO, que supera a las defensas antioxidantes del organismo, incrementando el estrés oxidante con el consecuente daño tisular y desequilibrio homeostático. *U = U/mg de proteína:¹.

Background: The activity of the enzyme myeloperoxidase (MPO, EC 1.11.1.7), in plasma has been related to several chronic-degenerative diseases such as asthma and diabetes mellitus which have in common a chronic inflammatory condition. Several reactive species of oxygen are generated during inflammation, including hypochlorous acid, which is a product of MPO. Objective: To prove that asthma and diabetes mellitus, in which there is oxidative stress, present a cumulative metabolic response that can be measured by an increase of MPO, as a marker of oxidative damage. Methods: The activity of MPO was measured in the plasma of a control group of 31 healthy volunteers and in three groups of patients: a) 13 asthmatics, b) 29 diabetics, c) 6 asthmatics and diabetics. Results: In patients with both diseases, asthma and diabetes mellitus, there was a significant increase in the activity of the enzyme MPO (65.1 ± 11.2 U*; p < 0.05). The activity of MPO was similar in the control group (37.6 ± 3.2 U*), the asthma group (35.9 ± 5.2 U*) and the diabetics (32.6 ± 3.3 U*). Conclusions: The coexistence of asthma and diabetes mellitus, both chronic-degenerative diseases, increases the possibility of tissue damage due to the generation of oxygen reactive species that overwhelms the antioxidant defenses of the body, augmenting the oxidative stress and inducing secondary tissue damage and homeostatic disequilibrium. *U= U/mg of protein.

Perspectivas del uso de antioxidantes como coadyuvantes en el tratamiento del asma / Perspectives in the use of antioxidants for the treatment of asthma

Al tratarse de un proceso inflamatorio, en el asma hay participación e incremento en la generación de especies reactivas del oxígeno, dando lugar a un desequilibrio oxidante/antioxidante, fenómeno que se ha descrito como estrés oxidante, que causa daño a diferentes biomoléculas. La utilización de agentes antioxidantes exógenos o activadores de antioxidantes endógenos como coadyuvantes de la terapéutica del paciente asmático, es una posibilidad a discutir.

Oxidative stress seen in bronchial asthma can damage different kinds of biomolecules; this oxidant/antioxidant imbalance results from an increment in the production of oxygen reactive species. The utilization of exogenous antioxidant agents or promoters of endogenous antioxidants can be seen as an alternative therapy for asthma that is worth discussing.

Estrés oxidante en asma / Oxidative stress in asthma

El asma es una enfermedad inflamatoria crónica del tracto respiratorio de etiología aún desconocida; sin embargo, nuevas evidencias han involucrado al estrés oxidante, en el que la participación e incremento en la generación de especies reactivas del oxígeno por diferentes sistemas bioquímicos, superan a los mecanismos antioxidantes en el ambiente de las vías respiratorias del asmático, lo cual es acompañado de alteraciones inducidas por radicales libres que involucran daño estructural y modificaciones metabólicas presentes, a nivel sistémico y en el tracto respiratorio.

Asthma is a chronic inflammatory disease of the airways: its precise etiology is still unknown. New evidence points to oxydative stress, in which the participation and increment of reactive species of oxygen by several biochemical systems overwhelms the anti oxidant mechanisms of the airways; this, in conjunction with changes induced by free radicals involving systemic and local respiratory structural damage and metabolic changes.

Participación d las especies reactivas del oxígeno en las enfermedades pulmonares

Las especies reactivas de oxígeno son moléculas (O2•-, HO • , NO • ), muy reactivas debido a que en el último orbital tienen un electrón no pareado (radical libre), lo cual confiere inestabilidad física. Se incluyen en las especies reactivas de oxígeno a moléculas precursoras de los radicales libres (H2O2, HONO2-). Estas especies participan en procesos fisiológicos en el organismo. Cuando la generación de especies reactivas de oxígeno supera a los mecanismos de inactivación, se presenta el estado metabólico de estrés oxidante que se caracteriza por daños moleculares y celulares que conducen a predisposición o modificación de diversos padecimientos crónico-degenerativos. Entre las enfermedades pulmonares en que se ha demostrado la participación de las especies reactivas de oxígeno, destacan el síndrome de insuficiencia respiratoria progresiva, la enfermedad pulmonar obstructiva crónica y el asma. Se analizan las características del estrés oxidante en estos padecimientos.

Reactive Oxygen Species (ROS) are very reactive molecules (O2•-, HO•, NO• ) since they have a single and unpaired electron in the last orbital (free radical) which confers them physical instability. Free radical precursors such as H2O2 , HONO2- are considered ROS. These species are important in the physiological processes. When ROS production exceeds the inactivation mechanisms, oxidative stress takes place. This stress is characterized by molecular and cellular damage which predisposes to or modifies chronic-degenerative diseases. Among pulmonary diseases in which ROS participation has been proved are ARDS, COPD and asthma. The aim of this paper was to analyze the mechanisms of oxidative stress that lead to those illnesses.

Panorama epidemiológico de las infecciones respiratorias agudas en niños menores de cinco años de los Estados Unidos Mexicanos. Comparación con cinco países del continente americano / Epidemic panorama of acute respiratory infections in children under five years of age in Mexico. Compared to five other countries of the American continent

Introducción. En el contexto de la transición epidemiológica, las infecciones respiratorias agudas han disminuido su importancia como causa de muerte en la población general, aunque todavía representan un problema importante de salud pública debido a la incapacidad, secuela y muerte que producen en los grupos etarios extremos de la vida. Esta característica es compartida con países latinoamericanos en condiciones de desarrollo similares al de México. Objetivo. El propósito de este ensayo es decribir la epidemiología de las infecciones respiratorias agudas en México y en cinco países del continente americano para destacar su magnitud actual y la necesidad de mejorar estrategias para su control y prevención. Conclusión. El análisis de la situación existente en los países de América Latina muestra la heterogenidad epidemiológica que existe entre estas naciones. En nuestro país el perfil epidemiológico de las infecciones respiratorias agudas ha mostrado mejoría con respecto a la mortalidad. Para poder abatir las tasas de morbilidad y mortalidad por infecciones respiratorias agudas es necesario conocer con mayor detalle las características que se encuentran asociadas a la enfermedad en las áreas y grupos de mayor riesgo y así proponer alternativas preventivas adecuadas a los niveles local, regional y nacional