89 research outputs found
Inflammatory Disturbances in Preeclampsia: Relationship between Maternal and Umbilical Cord Blood
Preeclampsia (PE) is one of the main causes of maternal and fetal mortality and morbidity. PE is associated with an inflammatory state and with oxidative stress, in maternal circulation. Our aim was to evaluate and compare the levels of oxidative stress and inflammatory markers in maternal and umbilical cord blood (UCB), in normal and PE pregnancies. We measured acute-phase proteins (CRP and α1-antitrypsin), proinflammatory cytokines (IL-6 and TNF-α), leukocyte activation (elastase, lactoferrin, sL-selectin, sVCAM, sPECAM), total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS), and uric acid levels. We studied 42 healthy pregnant women, 46 PE women, and their neonates. The concentrations of IL-6, TNF-α, α1-antitrypsin, CRP, sVCAM, uric acid, and TBARS were significantly higher, and sL-selectin was significantly lower in PE pregnant women as compared with normotensive pregnant women. In newborns uric acid, α1-antitrypsin, and CRP values were significantly higher in PE; leukocyte count, sL-selectin, lactoferrin, and the ratio elastase/α1-antitrypsin were significantly lower. Our data suggest that PE pregnancy is associated with an enhanced maternal inflammatory condition, which is reflected in fetal circulation. This enhanced inflammatory state seems to be related to endothelial dysfunction and increased cytokine synthesis, rather than with neutrophil activation
Bilirubin dependent on UGT1A1 polymorphisms, hemoglobin, fasting time and body mass index
In PressIn humans, bilirubin levels are influenced by different
factors. This study aims to evaluate the influence of several nongenetic
factors (hematologic data, smoking status, alcohol intake, fasting time,
physical activity, oral contraceptive therapy and caloric intake) and the
genetic contribution of UGT1A1 polymorphisms for the bilirubin levels,
in a cohort of young women. Hematologic data, bilirubin and
screening of TA duplication in the TATA box region of the UGT1A1
gene were performed in 146 young white women. Body mass index
(BMI) and body fat were determined, and a questionnaire about fasting
time, smoking habits, oral contraceptive therapy, caloric intake and
physical activity was performed. Participants were divided into 3
groups according to the tertiles of bilirubin levels. Subjects from the
second and third tertile had significant increases in hemoglobin (Hb)
concentration, hematocrit, mean cell Hb and mean cell Hb concentration
compared with those in the first tertile. Red blood cell count was
significantly increased in subjects in the third tertile. A significant
increased frequency was found for the c.-41_-40dupTA allele in homozygosity
for both second and third tertiles. Multiple linear regression
analysis showed that the c.-41_-40dupTA allele, Hb, BMI and fasting
hours were independent variables associated with bilirubin serum
levels. Hb concentration, fasting time and BMI were identified as
nongenetic causes, together with the genetic UGT1A1 polymorphisms,
as the main factors associated with variations in bilirubin levels in a
healthy female population.Bolsa de doutoramento SFRH/BD/42791/2007 da Fundação para a Ciência e Tecnologia (FCT) e Fundo Social Europeu
Linkage of cytosolic peroxiredoxin 2 to erythrocyte membrane imposed by hydrogen peroxide-induced oxidative stress
Human erythrocyte peroxiredoxin 2 (Prx2) is a typical 2-cys cytosolic peroxiredoxin with thiol-dependent hydrogen peroxide scavenger activity. In a previous work, we reported Prx2 erythrocyte membrane linkage in some Hereditary Spherocytosis patients and that it seemed to be related to oxidative stress. The aim of the present work was to determine if Prx2 linkage to erythrocyte membrane could be induced by oxidative stress
mediated by H2O2 and to further understand how and why this process occurs. We performed in vitro assays in which catalase or both Hb autoxidation and catalase were inhibited, under H2O2-induced oxidative stress conditions. Erythrocyte membrane linked Prx2 was detected by immunoblotting and quantified by densitometry. As oxidative stress markers, we determined membrane bound hemoglobin and lipid peroxidation, and we found that their values increased with H2O2 concentration. Prx2 linkage to the
membrane also rose with increasing H2O2 concentration, and was only observed when the oxidized form of the enzyme was present in the cytosol. Oxidized Hb and Prx2 membrane linkages appear to be independent
processes, although, both result from oxidative stress and may be useful as oxidative stress and/or erythrocyte damage/senescence markers
Changes in red blood cells membrane protein composition during hemodialysis procedure
Our aim was to evaluate the influence of the hemodialysis (HD) procedure in red blood cells (RBC) membrane protein composition. We evaluated hematological data (RBC count,
hemoglobin concentration, and hematimetric indices) and RBC membrane protein composition (linear and exponential gradient
polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate [SDS-PAGE] followed by densitometry analysis of RBC membrane proteins) before and immediately after the HD procedure in 20 patients (10 responders and 10 non-responders to recombinant human erythropoietin therapy [rhEPO]) and 26 healthy controls. Before HD, patients presented anaemia and significant changes in membrane protein composition, namely, a statistically significant reduction in spectrin associated with a
significant increase in bands 6, as well as an altered membrane protein interaction (protein 4.1/spectrin, protein 4.1/band 3, protein 4.2/band 3 and spectrin/band 3). After HD, we found that patients showed a statistically significant increase in RBC count and hemoglobin, a further and statistically significant decrease in
spectrin, an increase in band 3, and an altered spectrin/band 3 ratio. When comparing responders and non-responders patients after HD, we found that the non-responders presented a trend to a higher reduction in spectrin. Our data suggest that HD procedure seems to contribute to a reduction in spectrin, which is normally
associated with a reduction in RBC deformability, being that reduction in spectrin is higher in non-responder patients
Cardiovascular risk factors in Portuguese obese children and adolescents: impact of small reductions in body mass index imposed by lifestyle modifications
Objectives: Evaluate cardiovascular risk factors in Portuguese obese children and adolescents and the long-term effects of lifestyle modifications on such risk factors. Design: Transversal cohort study and longitudinal study. Setting: University Hospital S. João and Children's Hospital Maria Pia, Porto. Patients/Participants: 148 obese children and adolescents [81 females (54.7%); mean age of 11.0 years]and 33 controls (sex and age matched) participated in a cross-sectional study. Sixty obese patients agreed to participate in an one year longitudinal study after medical and nutritionist appointments to improve lifestyle modification; a substantial body mass index (BMI) reduction was defined by a decrease in BMI z-score (BMI z-sc) of 0.3 or more over the studied period. Main Outcome measures: Lipid profile (triglycerides, cholesterol, HDLc, LDLc, lipoprotein (a), apolipoproteins A and B) and circulating levels of C-reactive protein (CRP), adiponectin, glucose, and insulin. Results: Compared with the lean children, obese patients demonstrated statistically significantly higher insulin resistance index [Homeostasis model assessment (HOMA)], and triglycerides, LDLc, apolipoprotein (apo) B, insulin and CRP concentrations, whereas their HDLc and apo A levels were significantly lower (cross-sectional study). In the longitudinal study (n=60), a substantial BMI reduction occurred in 17 (28.3%) obese patients which led to a significant reduction in triglycerides, cholesterol, LDLc, apo B, glucose and insulin levels and in HOMA. The ΔBMI values over the studied period correlated inversely and significantly with BMI (P<0.001) and HOMA (P=0.026) values observed at baseline. In multiple linear regression analysis, BMI at baseline remained associated to changes in BMI over the studied period (standardised Beta: -0.271, P=0.05). Conclusion: Our data demonstrates that small reductions in BMI-zc, imposed by lifestyle modifications in obese children and adolescents, improve the cardiovascular risk profile of such patients. Furthermore, patients with higher BMI and/or insulin resistance seem to experience a greater relative reduction in their BMI after lifestyle improvements.info:eu-repo/semantics/publishedVersio
Neutrophil activation and resistance to recombinant human erythropoietin therapy in Hemodialysis Patients
The aim of this work was to evaluate the neutrophil activation state in chronic kidney disease (CKD) patients under hemodialysis, and its linkage with resistance to recombinant human erythropoietin (rhEPO) therapy. Methods: We studied 63 CKD patients under hemodialysis and rhEPO treatment (32 responders and 31 non-responders to rhEPO therapy). In 20 of the CKD patients (10 responders and 10 non-responders to rhEPO therapy), blood samples were also collected immediately after dialysis. Twenty-six healthy volunteers were included in a control group. Hemoglobin levels, total and differential leukocyte counts, and circulating levels of C-reactive protein (CRP), elastase and lactoferrin were measured in all patients and controls. Results: Compared with controls, CKD patients presented with significantly higher CRP, neutrophil and elastase levels. When we compared the 2 groups of patients, we found that non-responders presented statistically significantly higher elastase plasma levels. A positive significant correlation was found between elastase levels and weekly rhEPO dose and CRP serum levels. After the hemodialysis procedure, a statistically significant rise in elastase, lactoferrin and, elastase/neutrophil and lactoferrin/neutrophil ratios were found. Conclusions: Our data show that CKD patients under hemodialysis present higher elastase levels (particularly in non-responding patients), which could be related to the rise in neutrophils, and to be part of the enhanced inflammatory process found in these patient
Band 3 profile as a marker of erythrocyte changes in chronic kidney disease patients
Our aim was to study changes in red blood cell (RBC) membrane band 3 profile, as a cumulative marker of RBC changes, in chronic kidney disease (CKD) patients under haemodialysis and recombinant human erythropoietin (rhEPO) therapy and its linkage with resistance to this therapy.
We studied 63 CKD patients, 32 responders and 31 non-responders to rhEPO therapy, and 26 healthy individuals. We evaluated the band 3 profile [% of band 3 monomer, high molecular weight aggregates (HMWAg), and proteolytic fragments (Pfrag)], membrane-bound haemoglobin (MBH), haematological data, total serum bilirubin, glutathione peroxidase (GPx) and superoxide dismutase activities, total antioxidant status (TAS) and plasma lipid peroxidation (TBA). Compared
to controls, band 3 profile presented by CKD patients showed statistically significant lower HMWAg and Pfrag values and a significant higher value in band 3 monomer. GPx, TBA and TAS activities, and TBA/TAS ratio were also significantly higher in CKD patients. Comparing responders to non-responders CKD patients, significantly lower value in Pfrag and a trend for a higher value in MBH were found in non-responders.
Our data suggest that CKD patients present younger RBC population, which could be related to the rhEPO therapy. The adverse plasma environment associated to CKD patients under hemodialysis imposes changes in band 3 profile, particularly in non-responders, suggesting that resistance to rhEPO therapy in CKD patients seems to be associated to an increase in RBC damage
Higher fibrinolytic and inflammatory markers are associated with central venous catheters use in chronic kidney disease patients under haemodialysis
Interruption of blood supply to the heart is a leading cause of death and disability. However, the molecular events that occur during heart ischemia, and how these changes prime consequent cell death upon reperfusion, are poorly understood. Protein SUMOylation is a post-translational modification that has been strongly implicated in the protection of cells against a variety of stressors, including ischemia-reperfusion. In particular, the SUMO2/3-specific protease SENP3 has emerged as an important determinant of cell survival after ischemic infarct. Here, we used the Langendorff perfusion model to examine changes in the levels and localisation of SUMOylated target proteins and SENP3 in whole heart. We observed a 50% loss of SENP3 from the cytosolic fraction of hearts after preconditioning, a 90% loss after ischemia and an 80% loss after ischemia-reperfusion. To examine these effects further, we performed ischemia and ischemia-reperfusion experiments in the cardiomyocyte H9C2 cell line. Similar to whole hearts, ischemia induced a decrease in cytosolic SENP3. Furthermore, shRNA-mediated knockdown of SENP3 led to an increase in the rate of cell death upon reperfusion. Together, our results indicate that cardiac ischemia dramatically alter levels of SENP3 and suggest that this may a mechanism to promote cell survival after ischemia-reperfusion in heart
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