Peripheral artery disease and oxidative stress in patients in a program for preventing complications of diabetes mellitus and dyslipidemia / Enfermedad arterial periférica y estrés oxidativo en pacientes del programa para la prevención de complicaciones de diabetes mellitus y dislipidemias

Abstract Introduction: Peripheral artery disease (PAD) is mainly caused by atherosclerosis but also involves hyperglycemia and dyslipidemia, which trigger oxidative stress and lead to vascular damage. Objectives: To determine the prevalence of PAD in patients with type 2 diabetes mellitus (DM2) and/or prediabetes and/or dyslipidemia, to identify some risk factors and to establish whether urinary levels of 8-isoprostane-f2α (an oxidative stress marker) are elevated in patients with PAD. Design: A cross-sectional, nonprobabilistic, convenience sampling study Materials and methods: The sample included 146 patients with DM2 and/or prediabetes and/ or dyslipidemias from the Universidad Nacional de Colombia. Risk factors, symptoms related to PAD, ankle-brachial index measurement and biochemical variables (HbA1c%, fasting blood glucose, lipid profile, creatinine and albuminuria) were recorded. Urine levels of 8-isoprostane-f2α were determined by ELISA. The 8-iso-PGF2α/creatine concentration were analyzed using the statistical package R. Risk factors were compared using ANOVA/ Kruskal-Wallis. ROC curves were generated to analyze the discriminant power of the biomarkers. The joint analysis of laboratory results and risk factors was performed using multivariate logistic regressions. Results: PAD was identified in 10 diabetic patients. Risk factors were smoking, dyslipidemia, poor metabolic control, overweight or obesity. There was no evidence of increased urinary 8-isoprostane-f2α in these subjects. Conclusions: A low prevalence of PAD was found in subjects with DM2. There was no evidence of increased 8-isoprostane-f2α measured by ELISA in patients with PAD. The extension of the study with different markers of oxidative stress and the use of other techniques is recommended (Acta Med Colomb 2019; 44. DOI: https://doi.org/10.36104/amc.2019.1257).

Resumen Introducción: la enfermedad arterial periférica (EAP) es causada principalmente por aterosclerosis e intervienen la hiperglucemia y dislipidemia que desencadenan estrés oxidativo y daño vascular. Objetivo: determinar la prevalencia de EAP en pacientes con diabetes mellitus tipo 2 (DM2) y/o prediabetes y/o dislipidemias, así como algunos factores de riesgo; también, establecer si los niveles urinarios de 8-isoprostano-f2α (marcador de estrés oxidativo) están elevados en pacientes con EAP. Diseño: estudio de tipo transversal, no probabilístico, de conveniencia. Material y métodos: la muestra comprendió 146 pacientes con DM2 y/o prediabetes y/o dislipidemias de la Universidad Nacional de Colombia. Se registraron factores de riesgo, síntomas relacionados con EAP, medida índice tobillo-brazo y variables bioquímicas (HbA1c%, glucemia basal, perfil lipídico, creatinina y albuminuria). Se determinaron niveles en orina de 8-isoprostano-f2α por ELISA. Los resultados de la concentración de 8-iso-PGF2α/creatinuria se analizaron mediante el paquete estadístico R. La comparación de factores de riesgo se analizó mediante ANOVA/Kruskal-Wallis. Se generaron curvas ROC para analizar el poder discriminante del biomarcador. El análisis conjunto de resultados de laboratorios y de factores de riesgo se realizó mediante regresiones logísticas multivariantes. Resultados: se evidenció prevalencia de EAP en 10 pacientes diabéticos. Como factores de riesgo se encontraron: fumar, dislipidemia, mal control metabólico, sobrepeso u obesidad. No se evidenció aumento del 8-isoprostano-f2α urinario en estos sujetos. Conclusiones: se encontró baja prevalencia de EAP en los sujetos con DM2. No se evidenció aumento del 8-isoprostano-f2α medido por ELISA en pacientes con EAP. Se recomienda ampliar el estudio con diferentes marcadores de estrés oxidativo y uso de otras técnicas. (Acta Med Colomb 2019; 44. DOI: https://doi.org/10.36104/amc.2019.1257).

Cysteinyl leukotriene and 8-isoprostane in exhaled breath condensate of asthmatic children / 国际儿科学杂志

Objective To analyze the change of cysteinyl leukotriene ( Cys-LTs) levels and 8-Isopros-tane (8-iso-PG) levels in the exhaled breath condensate (EBC) of asthmatic children from acute exacerbation to clinical remission, and investigate the role of the detection of Cys-LTs and 8-iso-PG in EBC in its severity and pathogenesis , and explore the relationship between the Cys-LTs and 8-iso-PG through measuring Cys-LTs levels and 8-iso-PG levels in the EBC of asthmatic children. Methods The outpatient or inpatient asthmatic children of the pediatrics and a group of healthy children were studied. All subjects′ EBC were collected by the R-Tube produced by American Respiratory Research. The concentration of Cys-LTs and 8-iso-PG in EBC were measured by enzyme-linked immunosorbent assay (ELISA), and compared among children in asthmatic exacerbation, asthmatic remission, and healthy condition. The relevance of their change would be explored at the same time. Results (1) Cys-LTs levels in EBC were higher in asthma exacerbation, compared to healthy controls (P0. 05 ) . ( 2 ) 8-iso-PG levels was higher in asthmatic exacerbation compared to asth-matic remission ( P<0. 05 ) . Moreover, the 8-iso-PG levels were significantly higher in asthmatic remission than in healthy controls (P<0. 05). (3) Through the relevance analysis of the Cys-LTs and 8-iso-PG levels in EBC among the three groups, Cys-LTs levels in EBC of asthmatic exacerbation significantly were correlated with 8-iso-PG levels (n1 =35, r1 =0. 61, P<0. 05), while there was no significant correlation between 8-iso-PG levels and Cys-LTs levels in asthmatic remission. Conclusion The increase of 8-iso-PG levels in EBC of bronchial asthmatic patients correlates with the disease and its control. Therefore, 8-iso-PG can be an objective indicator for asthmatic diagnosis and healing efficacy. Cy-LTs levels increase in the EBC of bronchial asthmatic according to disease severity. The two levels correlate during asthmatic exacerbation, indicating that a link be-tween airway oxidative stress and inflammation among asthmatics.

Exhaled breath condensate analysis in chronic obstructive pulmonary disease.

The increasing focus on airway inflammation in the pathogenesis of chronic obstructive pulmonary disease (COPD) has led to development and evolution of tools to measure it. Direct assessment of airway inflammation requires invasive procedures, and hence, has obvious limitations. Non-invasive methods to sample airway secretions and fluids offer exciting prospects. Analysis of exhaled breath condensate (EBC) is rapidly emerging as a novel non-invasive approach for sampling airway epithelial lining fluid and offers a convenient tool to provide biomarkers of inflammation. It has definite advantages that make it an attractive and a feasible option. It is a source of mediators and molecules that are the causes or consequences of the inflammatory process. Measurement of such markers is increasingly being explored for studying airway inflammation qualitatively and quantitatively in research studies and for potential clinical applications. These biomarkers also have the potential to develop into powerful research tools in COPD for identifying various pathways of pathogenesis of COPD that may ultimately provide specific targets for therapeutic intervention. The EBC analysis is still an evolving noninvasive method for monitoring of inflammation and oxidative stress in the airways. The limited number of studies available on EBC analysis in COPD have provided useful information although definite clinical uses are yet to be defined. Evolving technologies of genomics, proteomics, and metabonomics may provide deeper and newer insights into the molecular mechanisms underlying the pathogenesis of COPD.

The Effect of Repetitive Hypoxia on Production of Lipid Peroxidation in Newborn Rat Brain

PURPOSE: Among many pathophysiologic mechanisms of hypoxic-ischemic brain injury, reactive oxygen species (ROS) cause or contribute to brain damage relates to their ability to attack the fatty acid moiety of plasma and subcellular membranes. Because ROS are generated by hypoxia-ischemia especially during reperfusion period of recovery, repetitive hypoxia-reoxygenation in newborn brain may result in more severe damage than a similar single insult. It is to determine whether repetitive hypoxia-reoxygenation may produce more ROS than a similar single insult in newborn rat brain. METHODS: We compared the production of lipid peroxidation in 3 days old rat brain following normoxia, repetitive hypoxia-reoxygenation and an equal duration of sustained hypoxia-reoxygenation by measuring 8-isoprostane-F2alpha. 8-isoprostane-F2alpha is free radical catalyzed metabolites of arachidonic acid, which is produced independent of cyclooxygenase. RESULTS: Compared to a single duration hypoxia-reoxygenation, repetitive hypoxia- reoxygenation produce more ROS (8-isoprostane-F2alpha) in newborn rat brain (P < 0.005). CONCLUSION: It can be speculated that repetitive hypoxia is more detrimental than equal duration of single insult in new born rat brain. Relations between increased ROS production and brain injury following repetitive hypoxia-reoxygenation should be evaluated.

Efficacy of midtrimester amniotic fluid 8-isoprostane measurement in the prediction of severe preeclampsia / 대한산부인과학회잡지

OBJECTIVE: The objective of this study is to investigate whether the amniotic fluid 8-isoprostane levels at the time of genetic amniocentesis is a marker for severe preeclampsia. METHODS: A case-control study was conducted to compare mid-trimester concentrations of amniotic fluid 8-isoprostane in women with normal pregnancies (n=22) and in those who subsequently developed severe preeclampsia (n=22). Amniotic fluid was also obtained by amniocentesis from another women who already developed severe preeclampsia (n=22) after 20 weeks of gestation. The 8-isoprostane levels were measured by enzyme-linked immunoassay. For statistical analysis, nonparametric tests and receiver-operating characteristic curves were used where appropriate. Statistical significance was considered when probability was <0.05. RESULTS: The levels of midtrimester amniotic fluid 8-isoprostane were found to be significantly decreased in the women who subsequently developed severe preeclampsia in comparison with those who underwent normal pregnancies (P<0.05). The levels of 8-isoprostane in preeclamptic amniotic fluid were found to be significantly decreased with respect to that in midtrimester amniotic fluid (P<0.05). No relationship was found between the midtrimester amniotic fluid 8-isoprostane levels and preeclampsia with small-for- gestational-age. After the onset of severe preeclampsia, however, the amniotic fluid 8-isoprostane levels were significantly decreased in women with small-for-gestational-age. The midtrimester amniotic fluid 8-isoprostane level of 170 pg/ml had a sensitivity of 72.7% and a specificity of 63.6% in the prediction of severe preeclampsia. CONCLUSION: The midtrimester amniotic fluid 8-isoprostane levels may predict the later occurrence of severe preeclampsia. This study not only presents a new information that 8-isoprostane is detected in human amniotic fluid, but also provides a convincing evidence that a subclinical process from faulty placentation in early gestation is important for the occurrence of preeclampsia. Further studies are warranted to determine which mechanism causes such decrease in amniotic fluid 8-isoprostane in preeclampsia.