Is "Attenuation of Oxidative Stress" Helpful to Understand the Mechanism of Remote Ischemic Preconditioning in Cardiac Surgery?

OBJECTIVES: The aim of this study was to determine the effect of remote ischemic preconditioning (RIPC) on markers of cardiac ischemia and response to oxidative stress in patients undergoing coronary artery bypass grafting (CABG) surgery. DESIGN: A prospective, randomized, and blinded study. SETTING: A single-center university hospital. PARTICIPANTS: This study included patients who underwent isolated CABG surgery with cardiopulmonary bypass who were selected carefully to prevent confounding with factors known to affect markers of ischemia-reperfusion and response to oxidative stress. INTERVENTIONS: The authors randomly assigned patients to RIPC to the left lower extremity using a blood pressure cuff (study group) or a cuff that was applied but not inflated or deflated (control group). MEASUREMENTS AND MAIN RESULTS: At 6 hours after CABG surgery, high-sensitivity cardiac troponin T levels were significantly lower in the study group than in the control group. Levels of superoxide dismutase, an antioxidant enzyme, were significantly greater 15 minutes after release of the cross-clamp in the study group, whereas malondialdehyde levels were lower (not significantly) at 1 and 15 minutes after release of the cross-clamp. Hemodynamic parameters were not significantly different at any time point during the study. CONCLUSIONS: The authors' method of RIPC before CABG surgery resulted in less myocardial ischemia, as indicated by lower troponin levels. Changes in levels of endogenous antioxidant enzymes supported the hypothesis that this protection from ischemia-reperfusion injury was related to scavenging of free oxygen radicals. Future studies might include a more heterogeneous population and medications that lower the body's response to oxidative stress.

Maternal Serum S100-B, PAPP-A and IL-6 levels in severe preeclampsia.

AIM: We aimed to investigate the relationship of maternal serum levels of S100-B, PAPP-A and IL-6 with severe preeclampsia. MATERIALS AND METHODS: This prospective case-control study consisted of 27 severe preeclamptic and 36 healthy singleton pregnancies. The groups were matched for parity, maternal age and body mass index. Maternal blood sampling for S100B, PAPP-A and IL-6 was performed at the morning after an overnight fasting. RESULTS: S100-B concentrations were significantly higher in severe preeclampsia group (0.09 ± 0.05 vs. 0.13 ± 0.01 µg/L; p = 0.025). PAPP-A levels were higher (196.54 ± 21.56 vs. 208.80 ± 23.97 mIU/ml; p = 0.707) and IL-6 levels were lower in severe preeclamptic group (68.79 ± 29.89 vs. 37.30 ± 6.46 pg/ml; p = 0.372). AUC value for S100-B was calculated as 0.712. When cutoff level for serum S100-B for predicting severe preeclampsia was regarded as 0.0975 µg/L, sensitivity and specificity were found to be 81.4 % and 58.3 %, respectively. Pregnancies with ≥0.0975 µg/L S100-B levels had 12.75-fold increased risk for having CNS symptoms (OR 12.75; 95 % CI 2.69-60.28) and 3.27-fold increased risk for having HELLP syndrome (OR 3.27; 95 % CI 0.62-17.36). CONCLUSION: Our results suggest that serum S100B levels may be a potential marker in severe preeclampsia for the severity of hypoperfusion both in placenta and brain pointing at subsequent risk of organ failure.

Metoclopramide use to induce lactation can alter DRD2 and BDNF in the prefrontal cortex of offspring.

Metoclopramide, used as an anti-emetic drug in clinical practice, has recently also begun being used to establish hyperprolactinemic effects in breastfeeding. The purpose of this study was to investigate the potential side-effects of metoclopramide applied in the lactation period in the central nervous system of offspring rats. Eighteen female albino Wistar rats that had just given birth were divided into three groups together with their pups, healthy controls, low-dose metoclopramide (10 mg/kg, twice per day i.p.) and a high-dose metoclopramide group (45 mg/kg, twice per day i.p.). Brain tissues from six pups from each mother were harvested at the end of the 21st day. Immunohistochemical and ELISA techniques were performed using dopamine D2 receptor (DRD2), brain derived neurotrophic factor (BDNF) and neural growth factor (NGF), markers of extrapyramidal reaction in the brain, as signal molecules. Based on biochemical levels and immunohistochemical results, DRD2 expression decreased only in the external pyramidal layer neurons in the high-dose offspring group. Strong BDNF reaction was determined in pyramidal neurons in all layers in the control offspring group, and decreased reaction was observed in the high- and low-dose groups. No significant difference was observed in NGF expression between the three groups. Since high-dose metoclopramide caused a decrease in DRD2 expression in the external pyramidal layer in the prefrontal cortex, and since both high and low doses reduced BDNF expression, care needs to be taken with the use of metoclopramide in the lactation period due to the possibility of extrapyramidal reactions in offsprings.

Relationship of neutrophil gelatinase-associated lipocalin (NGAL) and procalcitonin levels with the presence and severity of the preeclampsia.

OBJECTIVE: The aim of the present study was to evaluate changes in maternal serum neutrophil gelatinase-associated lipocalin (NGAL) and procalcitonin (PCT) concentrations in preeclampsia. MATERIAL AND METHOD: This case-control study consisted of 40 preeclamptic and 40 healthy singleton pregnancies matched for age and body mass index. Serum NGAL and PCT levels were compared between the groups. Diagnostic performance and clinical association of these markers were evaluated. RESULTS: NGAL and PCT concentrations were significantly higher in preeclamptic group (p < 0.0001 and p = 0.001, respectively) and their levels were correlated with the severity of the preeclampsia. There were significant positive correlation between these markers and mean arterial pressure (MAP) and spot urine protein excretion. There was negative correlation between NGAL and apgar scores and fetal birth weight. Pregnancies with higher NGAL (OR: 4.89; 95% CI: 1.81-13.21) and higher PCT (OR: 6.67; 95% CI: 2.44-18.21) concentrations had higher risk for preeclampsia. CONCLUSION: NGAL and PCT may be potential biomarkers for preeclampsia. Their levels increase significantly in preeclampsia and they are related to the severity of the disease. These results are in agreement with the generalized endothelial damage and persistant inflammatory status in preeclampsia. NGAL may also be an indicator for adverse neonatal outcomes with decreased placental hypoperfusion.

IL-5, IL-8 and MMP -9 levels in exhaled breath condensate of atopic and nonatopic asthmatic children.

RATIONALE: Asthma is a heterogeneous disease, and a great majority of pediatric patients with asthma demonstrate atopic characteristics and develop a Th2 type cytokine response. Nonatopic asthma, on the other hand, is seen more rarely. METHODS: In this study, levels of IL-5, IL-8 and MMP-9 were measured in exhaled breath condensate (EBC) of the subjects to demonstrate the extent of tissue damage as well as eosinophilic and neutrophilic inflammation in children with atopic and nonatopic asthma. A total of 37 children with atopic asthma and 37 children with nonatopic asthma were enrolled in the study. Patients who exhibited protease positive aeroallergen (House dust mite, mould mix, olea, grass mix) sensitivity in allergen skin prick test were included in the atopic asthma group. To evaluate the EBC, the fluid content of the breath was collected by having the patients exhale into an EBC device, after which the IL-5, IL-8 and MMP-9 levels were assayed using the ELISA method. RESULTS: The atopic asthmatics exhibited significantly higher IL-5 levels in their EBC samples than the nonatopic asthmatics (0.271 [0.198-0.489] pg/ml and 0.198 [0.125-0.344] pg/ml, respectively, p = 0.04), while no significant differences were observed in the levels of IL-8 and MMP-9 in the EBC samples of the atopic and nonatopic asthmatics. CONCLUSIONS: IL-5 levels, as a marker of eosinophilic inflammation, were demonstrated to be higher in the children with atopic asthma when compared to those with nonatopic asthma in EBC. The fact that no significant difference was apparent in the IL-8 levels between the groups suggests that it is the severity of the disease rather than the atopic state that plays an important role in IL-8 levels. Since no difference was recorded between the groups in terms of MMP-9 levels, lung damage in asthma sufferers seems to develop independent of atopia.

E-cadherin as an epithelial barrier protein in exhaled breath condensate.

Airway epithelium plays an important role as a physical barrier and a modulator of allergic response. Junctions between cells provide epithelial integrity and barrier function. The aim of this study was to investigate the influence of atopy on airway epithelial integrity in asthma and to measure E-cadherin levels in exhaled breath condensate as an indicator epithelial damage. A total of 74 patients with asthma (35 atopic and 39 non-atopic) and 39 healthy children were enrolled in this case-control study. Sociodemographic characteristics and asthma severity parameters in the last three-month period were recorded and pulmonary function tests were performed. Blood samples were obtained to measure serum immunoglobulin E (IgE) levels and peripheral blood eosinophil count, and exhaled breath condensate (EBC) was obtained to measure E-cadherin.EBC E-cadherin levels were significantly lower in the asthmatics when compared to non-atopic controls (0.109 (0.076) versus 0.191 (0.184) ng mL(-1) respectively, p = 0.01). Atopic and non-atopic asthmatic groups had lower EBC E-cadherin levels compared to the control group. (0.112 (0.060) ng ml(-1), 0.106 (0.089) ng ml(-1) and 0.191 (0.184) ng ml(-1), p = 0.02 and p < 0.01 respectively). However, EBC E-cadherin levels were not different between atopic and non-atopic asthmatics. The results of our study support the role of E-cadherin in the pathogenesis of asthma. However, the absence of difference in E-cadherin levels between atopic and non-atopic asthmatics suggests that allergic sensitization is not the primary factor for development of epithelial barrier dysfunction in asthma.