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.

High Plasmatic Levels of Advanced Glycation End Products are Associated with Metabolic Alterations and Insulin Resistance in Preeclamptic Women.

AIMS: The purpose of this study was to investigate the association between plasmatic levels of advanced end glycation products (AGEs) and the metabolic profile in subjects diagnosed with preeclampsia, due to the known relation of these molecules with oxidative stress and inflammation, which in turn are related with PE pathogenesis. BACKGROUND: It has been reported that increased levels of AGEs are observed in patients with preeclampsia as compared with healthy pregnant subjects, which was mainly associated with oxidative stress and inflammation. Besides, in women with preeclampsia, there are metabolic changes such as hyperinsulinemia, glucose intolerance, dyslipidemia, among others, that are associated with an exacerbated insulin resistance. Additionally, some parameters indicate the alteration of hepatic function, such as increased levels of liver enzymes. However, the relationship of levels of AGEs with altered lipidic, hepatic, and glucose metabolism parameters in preeclampsia has not been evaluated. OBJECTIVE: To investigate the association between plasmatic levels of AGEs and hepatic, lipid, and metabolic profiles in women diagnosed with preeclampsia. METHODS: Plasma levels of AGEs were determined by a competitive enzyme-linked immunosorbent assay (ELISA) in 15 patients diagnosed with preeclampsia and 28 normoevolutive pregnant subjects (control group). Hepatic (serum creatinine, gammaglutamyl transpeptidase, aspartate transaminase, alanine transaminase, uric acid, and lactate dehydrogenase), lipid (apolipoprotein A, apolipoprotein B, total cholesterol, triglycerides, low-density lipoproteins, and high-density lipoproteins), and metabolic variables (glucose, insulin, and insulin resistance) were assessed. RESULTS: Plasmatic levels of AGEs were significantly higher in patients with preeclampsia as compared with the control. A positive correlation between circulating levels of AGEs and gamma-glutamyl transpeptidase, uric acid, glucose, insulin, and HOMA-IR levels was found in patients with preeclampsia. In conclusion, circulating levels of AGEs were higher in patients with preeclampsia than those observed in healthy pregnant subjects. Besides, variables of hepatic and metabolic profile, particularly those related to insulin resistance, were higher in preeclampsia as compared with healthy pregnant subjects. Interestingly, there is a positive correlation between AGEs levels and insulin resistance. CONCLUSIONS: Circulating levels of AGEs were higher in patients with preeclampsia than those observed in healthy pregnant subjects. Besides, hepatic and metabolic profiles, particularly those related to insulin resistance, were higher in preeclampsia as compared with healthy pregnant subjects. Interestingly, there is a positive correlation between AGEs levels and insulin resistance, suggesting that excessive glycation and an impaired metabolic profile contribute to the physiopathology of preeclampsia.

Increased systemic and peritoneal oxidative stress biomarkers in endometriosis are not related to retrograde menstruation.

Objetives: The goal of this study was to determine if systemic and peritoneal oxidative stress biomarkers are related to each other and to retrograde menstruation in endometriosis. Methods: Plasma and peritoneal fluid oxidative stress biomarkers and hemoglobin and erythrocytes in peritoneal fluid as retrograde menstruation indicators, were measured in 28 patients with endometriosis and 23 without endometriosis. Results: In the peritoneal fluid, carbonyls and lipohydroperoxides, indicative of protein and lipid oxidative damage, were higher in endometriosis group (21%, p = 0.016 and 46%, p = 0.009, respectively). However, these biomarkers were not different in the blood plasma of both groups, and only protein dityrosine, was increased in the plasma of endometriosis group (31%, p = 0.04). The peritoneal fluid hemoglobin content was not higher in the endometriosis group, nor related to carbonyls and lipohydroperoxides. Additionally, the peritoneal fluid oxidative biomarkers were not correlated with the blood plasma ones, and only malondialdehyde, and ischemia-modified albumin were almost two times higher in peritoneal fluid. Discussion: Our results show a peritoneal and systemic oxidative stress biomarkers increase in endometriosis, but not related to each other, and do not support the hypothesis of an increase in hemoglobin-iron supply towards the peritoneal cavity that causes oxidative damage.

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.

Effects of Physical Rehabilitation in Patients with Spinocerebellar Ataxia Type 7.

Today, neurorehabilitation has become in a widely used therapeutic approach in spinocerebellar ataxias; however, there are scarce powerful clinical studies supporting this notion, and these studies require extension to other specific SCA subtypes in order to be able to form conclusions concerning its beneficial effects. Therefore, in this study, we perform for the first time a case-control pilot randomized, single-blinded, cross-sectional, and observational study to evaluate the effects of physical neurorehabilitation on the clinical and biochemical features of patients with spinocerebellar ataxia type 7 (SCA7) in 18 patients diagnosed with SCA7. In agreement with the exercise regimen, the participants were assigned to groups as follows: (a) the intensive training group, (b) the moderate training group, and (c) the non-training group (control group).We found that both moderate and intensive training groups showed a reduction in SARA scores but not INAS scores, compared with the control group (p < 0.05). Furthermore, trained patients exhibited improvement in the SARA sub-scores in stance, gait, dysarthria, dysmetria, and tremor, as compared with the control group (p < 0.05). No significant improvements were found in daily living activities, as revealed by Barthel and Lawton scales (p > 0.05). Patients under physical training exhibited significantly decreased levels in lipid-damage biomarkers and malondialdehyde, as well as a significant increase in the activity of the antioxidant enzyme PON-1, compared with the control group (p < 0.05). Physical exercise improved some cerebellar characteristics and the oxidative state of patients with SCA7, which suggest a beneficial effect on the general health condition of patients.

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.

Enhanced healing and anti-inflammatory effects of a carbohydrate polymer with zinc oxide in patients with chronic venous leg ulcers: preliminary results.

INTRODUCTION: Insufficient wound healing related to chronic inflammation of chronic venous leg ulcers (CVUs) represents an important public health problem. The aim of this study was to evaluate the effects of a carbohydrate polymer with zinc oxide therapy on CVUs. MATERIAL AND METHODS: Forty patients with CVUs were recruited for this study and were divided into a study group and control group. Patients In the study group were instructed to use venous compression treatment andtopical carbohydrate polymer with zinc oxide twice daily, while patients In the control group were treated with only venous compression treatment. All patients were followed up for 8 weeks. Peripheral blood samples and biosy tissue specimens were obtained at the initiation of treatment and after 8 weeks to assess serum levels of inflammatory cytokines as well as the percentage of leukocytes, T-helper cells, cytotoxic-T cells, macrophages and endothelial cells in the biopsy tissue using flow cytometry. RESULTS: A significantly greater reduction in the mean percentage ulcer area from baseline to eight weeks was observed in the study group (up to 40% for large ulcers). Furthermore, the patients in the study group had reduced systemic levels of the pro-inflammatory cytokines IL-8 (p = 0.0028) and IL-6 (p = 0.0302), fewer total CD45+ cells (p = 0.0038) and more CD31+ cells (p = 0.045) present in ulcer biopsies compared to the control group. CONCLUSIONS: The carbohydrate polymer with zinc oxide treatment with venous compression enhances healing of CVUs and improves quality of life due, in part, to its anti-inflammatory properties.

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 biomarkers and their relationship with cytokine concentrations in overweight/obese pregnant women and their neonates.

BACKGROUND: Oxidative damage present in obese/overweight mothers may lead to further oxidative stress conditions or inflammation in maternal and cord blood samples. Thirty-four pregnant women/newborn pairs were included in this study to assess the presence of oxidative stress biomarkers and their relationship with serum cytokine concentrations. Oxidative stress biomarkers and antioxidant enzymes were compared between the mother/offspring pairs. The presence of 27 cytokines was measured in maternal and cord blood samples. Analyses were initially performed between all mothers and newborns and later between normal weight and mothers with overweight and obesity, and diabetic/non-diabetic women. RESULTS: Significant differences were found in biomarker concentrations between mothers and newborns. Additionally, superoxide-dismutase activity was higher in pre-pregnancy overweight mothers compared to those with normal weight. Activity for this enzyme was higher in neonates born from mothers with normal pregestational weight compared with their mothers. Nitrites in overweight/obese mothers were statistically lower than in their offspring. Maternal free fatty acids, nitrites, carbonylated proteins, malondialdehyde and superoxide dismutase predicted maternal serum concentrations of IL-4, IL-13, IP-10 and MIP-1ß. Arginase activity in maternal plasma was related to decreased concentrations of IL-4 and IL-1ß in cord arterial blood. Increased maternal malondialdehyde plasma was associated with higher levels of IL-6 and IL-7 in the offspring. CONCLUSIONS: Oxidative stress biomarkers differ between mothers and offspring and can predict maternal and newborn cytokine concentrations, indicating a potential role for oxidative stress in foetal metabolic and immunologic programming. Moreover, maternal obesity and diabetes may affect maternal microenvironments, and oxidative stress related to these can have an impact on the placenta and foetal growth.

[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.

Potent anti-inflammatory activity of carbohydrate polymer with oxide of zinc.

Pebisut is a biological adhesive composed of naturally occurring carbohydrates combined with zinc oxide (ZnO) initially used as a coadjutant for healing of anastomoses. Likewise some works demonstrated that carbohydrate complexes exerts anti-inflammatory activity and it is widely known that ZnO modulate inflammation. However, the direct effects of Pebisut on isolated cells and acute inflammatory responses remained to be investigated. The present study evaluated anti-inflammatory effect of Pebisut using lipopolysaccharide (LPS) stimulated human mononuclear cells, chemotaxis, and cell infiltration in vivo in a murine model of peritonitis. Our data show that human cells treated with different dilutions of Pebisut release less IL-6, IL-1 ß , and IL-8 after LPS stimuli compared with the control treated cells. In addition, Pebisut lacked chemotactic activity in human mononuclear cells but was able to reduce chemotaxis towards CCL2, CCL5, and CXCL12 that are representative mononuclear cells chemoattractants. Finally, in a murine model of peritonitis, we found less number of macrophages (F4/80(+)) and T lymphocytes (CD3(+)) in peritoneal lavages from animals treated with Pebisut. Our results suggest that Pebisut has anti-inflammatory activity, which might have a beneficial effect during anastomoses healing or wounds associated with excessive inflammation.

Urban PM2.5 activates GAPDH and induces RBC damage in COPD patients.

During Chronic Obstructive Pulmonary Disease (COPD) progression, the intracellular antioxidant defence in RBCs must preserve the integrity of the plasmalemma through NADPH+ generation to obtain a sufficient number of reduced non-protein SH-groups. Here, we studied the activities of enzymes in RBCs that are related to glutathione metabolism under conditions of increasing oxidative stress, which are associated with COPD progression, by increasing cellular damage in vitro with PM2.5, a ROS generator. The study included 43 patients, who were separated according to their GOLD classification into moderate and severe groups, along with 11 healthy volunteers (HV). Blood samples were analysed for G6PD, GAPDH, GPx, and GR. The results showed significant decreases in the oxidation of the G6PD, GR and GPx proteins, resulting in decreased enzymatic activity. By contrast, an increase (p<0.05) in GAPDH was observed, suggesting a pool of ATP on the membrane. However, it is evident that RBCs are damaged during the progression of COPD, although their integrity is preserved, and they retain limited function, thus allowing patient survival without haemolysis.

Urban PM2.5 induces ROS generation and RBC damage in COPD patients.

Particulate matters (PM) produce adverse effects on the respiratory system and cause COPD. These effects are thought to involve intrinsic generation of ROS which are present in ambient PM (transition metals and aromatic organic compounds). Here, we examined the chemical composition and ultra-microscopic structure of PM2.5. The effect of this PM was studied in red blood cell (RBC) membranes (ghosts) from healthy volunteers (n = 11) and COPD patients (n = 43). These effects were compared with that produced by a Fenton metal-catalytic ROS generator. Oxidative biomarkers and cell damage were singificantly increased in presence of PM2.5 or ROS generator in RBC of COPD patients as compared with those in cells from healthy volunteers. In contrast, total SH groups, band 3 phospho-tyrosine phosphatase (PTPase) and glucose-6 phosphate dehydrogenase (G6PD) activities were all diminished in cells from COPD patients. In conclusion, PM2.5 increases damage to RBCs from COPD patients, decreases the activity of PTPase and G6PD, and alters the function of the anionic exchanger (AE1) and the antioxidant response by decreasing SH groups.

Increased platelet and erythrocyte arginase activity in chronic obstructive pulmonary disease associated with tobacco or wood smoke exposure.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease that is characterized by a progressive and irreversible decline in lung function and is caused primarily by chronic exposure to tobacco and to wood smoke. It is linked to oxidative stress and to an up-regulation of airway arginases and is also associated with alterations in platelets and erythrocytes. In the present study, arginase activity was studied in platelets and erythrocytes of 2 groups of COPD patients: 31 tobacco ex-smokers and 27 patients who had been exposed to wood smoke. A total of 15 healthy controls were also included. METHODS: Plasma, platelets, and erythrocytes were obtained from the blood samples. Levels of the oxidative stress biomarkers, carbonyls and malondialdehyde, were measured in the plasma, and arginase activity was quantified in platelets and erythrocytes. RESULTS: In both groups of COPD patients, an increase in the oxidative stress biomarkers was found. Platelet arginase activity in both COPD groups was 2-fold higher than that in the control group. In the erythrocytes, the arginase activity increased 1.7-fold over the control only in the wood smoke-induced COPD group. DISCUSSION AND CONCLUSIONS: These results suggest that the increase in arginase activity in platelets and erythrocytes participates in the alteration in nitric oxide metabolism in COPD patients and that there may be some differences between the tobacco smoke- and wood smoke-induced COPD.

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).

Correlation of Plasma Protein Carbonyls and C-Reactive Protein with GOLD Stage Progression in COPD Patients.

Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). To investigate the correlation between the progression of COPD and plasma biomarkers of chronic inflammation and oxidative injury, blood samples were obtained from healthy volunteers (HV, n = 14) and stabilized COPD patients. The patients were divided into three groups according to their GOLD stage (II, n = 34; III, n = 18; IV, n = 20). C-reactive protein (CRP), protein carbonyls (PC), malondialdehyde (MDA), susceptible lipoperoxidation of plasma substrates (SLPS), and myeloperoxidase activity (MPO) were measured. The plasma concentration of SLPS was measured as the amount of MDA generated by a metal ion-catalyzed reaction in vitro. PC, SLPS, and CPR were increased significantly (p < 0.001) in COPD patients when compared to HV. MDA concentrations and MPO activities were not significantly different from those of the HV group. In conclusion, increased oxidation of lipids and proteins resulting in a progressive increase in the amount of total plasma carbonyls and oxidative stress the presence of oxidative stress during COPD progression, concomitant with an increased oxidation of lipids and proteins resulting in a progressive and significant increase in the amount of total carbonyls formed from lipid-derived aldehydes and direct amino acid side chain oxidation in plasma, may serve as a biomarker and independent monitor of COPD progression and oxidative stress injury.

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'.