Are Overweight and Obesity Risk Factors for Developing Metabolic Syndrome or Hypertension after a Preeclamptic Event?

OBJECTIVE: To identify the determinants and risks associated with developing hypertension and metabolic syndrome in the first year postpartum in women who experienced preeclampsia. METHODS: A cohort study was conducted, involving women who had experienced preeclampsia (PE) recently. The control group was women with the same characteristics but a healthy pregnancy. The variables analyzed were somatometry, disease history, pre-pregnancy body mass index (Pre-BMI), and Third Adult Treatment Panel updated (ATP III) metabolic syndrome (MS) data (blood pressure, obesity, triglycerides, high-density lipoproteins, and fasting glucose). These variables were measured at 3, 6, and 12 months postpartum. RESULTS: Women with a history of PE exhibited higher systolic and diastolic blood pressure than women without PE. The risk of developing isolated diastolic arterial hypertension at 3 and 12 months of follow-up was two to eight times greater in women with a history of PE. Factors associated with having higher blood pressure levels were preeclampsia, insulin resistance, age, and BMI. Neither the pre-BMI index nor gestational weight gain (GWG) had any effect on blood pressure in any of the three assessments. Women with preeclampsia had a 5- to 8-fold increased risk of developing MS (which could be explained not only by the history of preeclampsia but also by the history of pre-pregnancy obesity). However, PE was not identified as a risk factor at the six-month evaluation and was only explained by pre-pregnancy obesity and overweight. CONCLUSIONS: Obesity and overweight, as well as preeclampsia, were strongly associated with the development of hypertension and metabolic syndrome during the first year following childbirth.

High Glucose Promotes Inflammation and Weakens Placental Defenses against E. coli and S. agalactiae Infection: Protective Role of Insulin and Metformin.

Placentas from gestational diabetes mellitus (GDM) patients undergo significant metabolic and immunologic adaptations due to hyperglycemia, which results in an exacerbated synthesis of proinflammatory cytokines and an increased risk for infections. Insulin or metformin are clinically indicated for the treatment of GDM; however, there is limited information about the immunomodulatory activity of these drugs in the human placenta, especially in the context of maternal infections. Our objective was to study the role of insulin and metformin in the placental inflammatory response and innate defense against common etiopathological agents of pregnancy bacterial infections, such as E. coli and S. agalactiae, in a hyperglycemic environment. Term placental explants were cultivated with glucose (10 and 50 mM), insulin (50-500 nM) or metformin (125-500 µM) for 48 h, and then they were challenged with live bacteria (1 × 105 CFU/mL). We evaluated the inflammatory cytokine secretion, beta defensins production, bacterial count and bacterial tissue invasiveness after 4-8 h of infection. Our results showed that a GDM-associated hyperglycemic environment induced an inflammatory response and a decreased beta defensins synthesis unable to restrain bacterial infection. Notably, both insulin and metformin exerted anti-inflammatory effects under hyperglycemic infectious and non-infectious scenarios. Moreover, both drugs fortified placental barrier defenses, resulting in reduced E. coli counts, as well as decreased S. agalactiae and E. coli invasiveness of placental villous trees. Remarkably, the double challenge of high glucose and infection provoked a pathogen-specific attenuated placental inflammatory response in the hyperglycemic condition, mainly denoted by reduced TNF-α and IL-6 secretion after S. agalactiae infection and by IL-1ß after E. coli infection. Altogether, these results suggest that metabolically uncontrolled GDM mothers develop diverse immune placental alterations, which may help to explain their increased vulnerability to bacterial pathogens.

Lysosomal dysfunction induced by changes in albumin's tertiary structure: Potential key factor in protein toxicity during diabetic nephropathy.

AIMS: Increased amounts of protein, in particular albumin within renal tubular cells (TBCs), induce the expression of inflammatory and fibrogenic mediators, which are adverse prognostic factors in tubulointerstitial fibrosis and diabetic nephropathy (DN). We sought to assess the participation of the thiol-linked tertiary structure of albumin in the mechanism of protein toxicity in a model of TBCs. MATERIALS AND METHODS: Cultured human renal proximal tubular cells, HK-2, were exposed to isolated albumin from patients with and without DN (Stages 0, 1 and 4). The magnitude of change of the albumin tertiary structure, cell viability (LDH leakage), apoptosis (Annexin V), transdifferentiation and reticulum endoplasmic stress (Western blot and flow cytometry) and lysosomal enzyme activity were assessed. KEY FINDINGS: We found that albumin from Stage 4 patients presented >50% higher thiol-dependent changes of tertiary structure compared to Stages 0 and 1. Cells incubated with Stage 4 albumin displayed 5 times less viability, accompanied by an increased number of apoptotic cells; evidence of profibrogenic markers E-cadherin and vimentin and higher expression of epithelial-to-mesenchymal transition markers α-SMA and E-cadherin and of endoplasmic reticulum stress protein GRP78 were likewise observed. Moreover, we found that cathepsin B activity in isolated lysosomes showed a significant inhibitory effect on albumin from patients in advanced stages of DN and on albumin that was intentionally modified. SIGNIFICANCE: Overall, this study showed that thiol-dependent changes in albumin's tertiary structure interfere with the lysosomal proteolysis of renal TBCs, inducing molecular changes associated with interstitial fibrosis and DN progression.

Is gestational diabetes mellitus in obese women predicted by oxidative damage in red blood cells?

Obesity in pregnant women has been associated with an increased risk of maternal complications, including gestational diabetes mellitus (GDM), a process that is related to oxidative stress (OS). To evaluate the biomarkers of OS in red blood cells (RBCs), we assigned 80 pregnant women to one of three groups: control (n = 28), overweight (n = 26) and obese (n = 26). Then, we measured in plasma, the levels of glucose, triacylglycerol (TAG), insulin, free fatty acids (FFAs), leptin and cytokines (e.g. interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-alpha]) and OS biomarkers, such as lipohydroperoxides (LHP), malondialdehyde (MDA) and protein carbonylation (PC) in RBCs. We found significant positive correlations between OS biomarkers, body mass index (BMI) and pregnancy progression. Seven (26.9%) obese women who were diagnosed with GDM at 24-28 weeks of pregnancy showed significantly increased concentrations of FFAs, insulin, leptin, TNF-alpha and biomarkers of OS measured at 12-13 weeks of gestation. We propose to quantify LHP, MDA and PC in membranes of erythrocytes as possible markers to diagnose GDM from weeks 12-14.

Estrés oxidativo, función pulmonar y exposición a contaminantes atmosféricos en escolares mexicanos con y sin asma / Oxidative stress, lung function and exposure to air pollutants in Mexican schoolchildren with and without asthma

Resumen: Objetivo: Evaluar la asociación entre la exposición a contaminantes atmosféricos y marcadores de estrés oxidativo, por un lado, y la función pulmonar, por el otro, en escolares, con y sin asma, de las ciudades de Salamanca y León, en Guanajuato, México. Material y métodos: Se realizaron determinaciones de marcadores de estrés oxidativo y pruebas de función pulmonar en 314 escolares, y se obtuvo información sobre contaminantes atmosféricos (ozono, dióxido de azufre, monóxido de carbono y partículas menores de 2.5 µm y menores de 10 µm) de las estaciones de monitoreo correspondientes. Para evaluar la asociación se corrieron modelos de regresión lineal múltiple. Resultados: Con un día de retraso a la exposición a partículas menores de 10 µm (PM10), se observó un incremento de 0.09 pmol en los dienos conjugados entre niños asmáticos de Salamanca (p<0.05). La exposición a ozono durante el mismo día incrementó la concentración de lipo-hidroperóxidos en 4.38 nmol entre asmáticos de Salamanca, así como en 2.31 nmol por la exposición a PM10 para dos días de retraso (p<0.05). La capacidad vital forzada disminuyó 138 y 203 ml en niños sin asma, respectivamente, por la exposición a monóxido de carbono (p<0.05). Conclusiones: La exposición a contaminantes atmosféricos incrementa el estrés oxidativo y disminuye la función pulmonar en escolares con y sin asma.

Abstract: Objective. To assess the association between the air pollutants exposure on markers of oxidative stress and lung function in schoolchildren with and without asthma from Salamanca and Leon Guanajuato, Mexico. Materials and methods: We realized determinations of oxidative stress biomarkers and lung function tests in 314 schoolchildren. Information of air pollutants (O3, SO2, CO, PM2.5 and PM10) were obtained from monitoring stations and multiple linear regression models were run to assess the association. Results: An increase of 0.09 pmol in conjugated dienes was observed by exposure to PM10 lag 1 in asthmatics from Salamanca (p<0.05). The exposure to O3 during the same day increased the concentration of Lipohydroperoxides in 4.38 nmol in asthmatics of Salamanca, as well as in 2.31 nmol by exposure to PM10 lag 2 (p<0.05). The forced vital capacity decreased by 138 and 203 ml in children without asthma, respectively, due to exposure to carbon monoxide (p<0.05). Conclusions: Exposure to air pollutants increase oxidative stress and decreased lung function in schoolchildren, with and without asthma.

[Oxidative stress, lung function and exposure to air pollutants in Mexican schoolchildren with and without asthma]. / Estrés oxidativo, función pulmonar y exposición a contaminantes atmosféricos en escolares mexicanos con y sin asma.

OBJECTIVE.: To assess the association between the air pollutants exposure on markers of oxidative stress and lung function in schoolchildren with and without asthma from Salamanca and Leon Guanajuato, Mexico. MATERIALS AND METHODS: We realized determinations of oxidative stress biomarkers and lung function tests in 314 schoolchildren. Information of air pollutants (O3, SO2, CO, PM2.5 and PM10) were obtained from monitoring stations and multiple linear regression models were run to assess the association. RESULTS: An increase of 0.09 pmol in conjugated dienes was observed by exposure to PM10 lag 1 in asthmatics from Salamanca (p<0.05). The exposure to O3 during the same day increased the concentration of Lipohydroperoxides in 4.38 nmol in asthmatics of Salamanca, as well as in 2.31 nmol by exposure to PM10 lag 2 (p<0.05). The forced vital capacity decreased by 138 and 203 ml in children without asthma, respectively, due to exposure to carbon monoxide (p<0.05). CONCLUSIONS: Exposure to air pollutants increase oxidative stress and decreased lung function in schoolchildren, with and without asthma.

OBJETIVO: Evaluar la asociación entre la exposición a contaminantes atmosféricos y marcadores de estrés oxidativo, por un lado, y la función pulmonar, por el otro, en escolares, con y sin asma, de las ciudades de Salamanca y León, en Guanajuato, México. MATERIAL Y MÉTODOS: Se realizaron determinaciones de marcadores de estrés oxidativo y pruebas de función pulmonar en 314 escolares, y se obtuvo información sobre contaminantes atmosféricos (ozono, dióxido de azufre, monóxido de carbono y partículas menores de 2.5 µm y menores de 10 µm) de las estaciones de monitoreo correspondientes. Para evaluar la asociación se corrieron modelos de regresión lineal múltiple. RESULTADOS: Con un día de retraso a la exposición a partículas menores de 10 µm (PM10), se observó un incremento de 0.09 pmol en los dienos conjugados entre niños asmáticos de Salamanca (p<0.05). La exposición a ozono durante el mismo día incrementó la concentración de lipo-hidroperóxidos en 4.38 nmol entre asmáticos de Salamanca, así como en 2.31 nmol por la exposición a PM10 para dos días de retraso (p<0.05). La capacidad vital forzada disminuyó 138 y 203 ml en niños sin asma, respectivamente, por la exposición a monóxido de carbono (p<0.05). CONCLUSIONES: La exposición a contaminantes atmosféricos incrementa el estrés oxidativo y disminuye la función pulmonar en escolares con y sin asma.

Altered Expression of Natural Cytotoxicity Receptors and NKG2D on Peripheral Blood NK Cell Subsets in Breast Cancer Patients.

Human natural killer (NK) cells are considered professional cytotoxic cells that are integrated into the effector branch of innate immunity during antiviral and antitumoral responses. The purpose of this study was to examine the peripheral distribution and expression of NK cell activation receptors from the fresh peripheral blood mononuclear cells of 30 breast cancer patients prior to any form of treatment (including surgery, chemotherapy, and radiotherapy), 10 benign breast pathology patients, and 24 control individuals. CD3-CD56dimCD16bright NK cells (CD56dim NK) and CD3-CD56brightCD16dim/- NK cells (CD56bright NK) were identified using flow cytometry. The circulating counts of CD56dim and CD56bright NK cells were not significantly different between the groups evaluated, nor were the counts of other leukocyte subsets between the breast cancer patients and benign breast pathology patients. However, in CD56dim NK cells, NKp44 expression was higher in breast cancer patients (P = .0302), whereas NKp30 (P = .0005), NKp46 (P = .0298), and NKG2D (P = .0005) expression was lower with respect to healthy donors. In CD56bright NK cells, NKp30 (P = .0007), NKp46 (P = .0012), and NKG2D (P = .0069) expression was lower in breast cancer patients compared with control group. Only NKG2D in CD56bright NK cells (P = .0208) and CD56dim NK cells (P = .0439) showed difference between benign breast pathology and breast cancer patients. Collectively, the current study showed phenotypic alterations in activation receptors on CD56dim and CD56bright NK cells, suggesting that breast cancer patients have decreased NK cell cytotoxicity.

RBC membrane damage and decreased band 3 phospho-tyrosine phosphatase activity are markers of COPD progression.

Injury to red blood cell (RBC) membrane by oxidative stress is of clinical importance in chronic obstructive pulmonary disease (COPD) which leads to oxidative stress (OE) during disease progression. Here, we studied the impact of this stress on injury to RBC membrane. Blood samples from both healthy volunteers (HV, n = 11) and controlled COPD patients (n=43) were divided according to their GOLD disease stage (I=7, II=21, III=10, IV=5). Plasma levels of paraoxonase (PON) activity, protein carbonyls (PC), conjugate dienes, lipohydroperoxides (LPH) and malondialdehyde (MDA) were determined and the PTPase, and the oxidative parameters were measured in RBC ghosts. Plasma from patients with COPD showed an increased oxidation of lipids and proteins, that correlated with the disease progression. PON activity decreased from GOLD stages II to IV and correlated with an increase in LPH (p less than 0.0001, r = -0.8115). There was evidence of an increase in the oxidative biomarkers in RBCs, while the PTPase activity was diminished in stage III and IV of COPD. In conclusion, OE-induced injury associated with COPD is associated with an oxidative damage to the RBC membrane, with a concomitant decrease in the PTPase activity and altered function of anionic exchanger (AE1).

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.

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.