Does remote ischemic preconditioning affect the systemic inflammatory response by modulating presepsin levels?

OBJECTIVE: We investigated the effect of Remote Ischemic Preconditioning (RIPC) on the inflammatory response during CPB by means of serum presepsin levels at preoperative and postoperative 1st and 24th h. METHODS: In this prospective, randomized, cross-sectional study we included 81 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). Patients were randomized and RIPC was applied to 40 patients in the study group before anesthesia. The remaining 41 patients were determined as the control group. The relationships between RIPC and factors such as presepsin, C-reactive protein (CRP), and leukocyte levels were investigated. RESULTS: There was no significant difference between the groups in postoperative leukocyte and CRP values (p = 0.52, p = 0.13, respectively). When the preoperative and postoperative first hour presepsin values of the patients were compared, no significant difference was found in the control group (p = 0.17), but a significant difference was found in the study group (p < 0.05). When the presepsin values were compared between the groups, a significant difference was found only in the postoperative first hour value (p < 0.05). CONCLUSIONS: It was observed that RIPC application caused to increase the presepsin levels in the postoperative first hour significantly in the study group (p < 0.05).

The relationship between ultrasonographically measured testicular volumes and cord blood inhibin B concentrations in healthy term male neonates.

Serum inhibin B (INHB) concentrations are associated with testicular volumes (TV) in all periods of childhood. The aim of the study was to investigate the relationship between TV measured by ultrasonography (US) and cord blood inhibin B and total testosterone (TT) concentrations, stratified by mode of delivery. In total 90 male infants were included. Testes of healthy, term newborns were evaluated by US on the third day after delivery. TV were calculated using two formulae: The ellipsoid formula [length (mm) × width (mm2) × π/6] and Lambert formula [length (mm) x width (mm) x height (mm) x 0.71]. Cord blood was taken for the determination of total testosterone (TT) and INHB. TT and INHB concentrations were evaluated according to TV percentiles (<10th, 10th-90th, >90th). There was a strong positive correlation between mean TV calculated with both formulae by percentile group (r = 0.777, r = 0.804, r = 0.846; p < 0.001). Cord blood INHB, but not TT were significantly lower in newborns with TV < 10th percentile compared to those with TV between 10 and 90th percentile and > 90th percentile (p < 0.05). There was a positive correlation between left and right TV calculated by either formula, and cord blood INHB (r = 0.212, 0.313, 0.320, 0.246,p < 0.05), not TT. There was no significant difference between hormones and TV when grouped by mode of delivery (p > 0.05). The Lambert and ellipsoid formulas are equally reliable in calculating neonatal testicular by ultrasound. INHB concentration is high in cord blood and positively correlated with neonatal TV. Cord blood INHB concentration may be an indicator for early detection of testicular structure and function disorders in neonates.

Immunohistochemical determination of mTOR pathway molecules in ovaries and uterus in rat estrous cycle stages.

mTOR is a member of the PI3K/Akt/mTOR signaling pathway that participates in cell growth, proliferation, protein synthesis, transcription, angiogenesis, apoptosis and autophagy. mTOR and MAPK pahways are two important key signal pathways which are related to each other. We investigated the role of mTOR and other signaling molecules in rat ovaries and uteruses in stages of the estrous cycle. Young adult female rats were divided into four groups as proestrous, estrous, metestrous and diestrous according to vaginal smears. Immunohistochemical staining of mTORC1, IGF1, PI3K, pAKT1/2/3, ERK1 and pERK1/2 was performed and pAKT1/2/3 and ERK1 were also analyzed using western blotting on ovarian and uterine tissue samples. According to our results, PI3K/Akt/mTOR and ERK/pERK showed an increase in the rat ovulation period. When all the groups were evaluated the immunoreactivities for all of the antibodies were detected in the oocytes, granulosa and theca cells, corpus luteum and stroma of ovary and lamina propria, surface and glandular epithelium of uterus with the strongest observed with anti-ERK1 antibody and then with a decreasing trend with anti-mTORC1, anti-pAkt1/2/3, anti-IGF1, anti-PI3K and anti-pERK1/2 antibodies in the proestrus and estrus stages. Differently from other parts of the ovary, highest antibody expression in the corpus luteum was observed in the metestrous stage. Moreover, the existence of pAKT1/2/3 and ERK1 proteins was confirmed with the Western blotting technique. We suggest that mTOR and mTOR-related ERK signaling molecules may participate in the rat ovulation process.

Examination of plasma zonulin levels in bipolar I disorder: a case-control study with follow-up.

There is an accumulation in studies which strive to reveal zonulin's potential role in mental disorders. To date, one cross-sectional recent study examined zonulin in patients with bipolar disorders (BDs); however, its role still remains vague due to high fluctuation. Our aims are to determine plasma zonulin levels in exacerbation and treatment response periods, and to examine the associations between zonulin and symptom severity in BD. 30 patients with BD type I and 29 healthy controls participated in the current study. Socio-demographic form, Young Mania Rating Scale (YMRS), and Hamilton Depression Rating Scale (HAM-D) were administered. Enzyme-linked immune assay (ELISA) method was used to measure the plasma zonulin levels of the participants. The groups did not differ in plasma zonulin-level comparisons. Plasma zonulin did not alter between the exacerbation and treatment response periods of the patients. Besides, no associations were found between plasma zonulin-level and disease symptoms. Intestinal barrier integrity was not found to be altered among patients with BD type I. The lack of alterations in plasma zonulin level between different periods may be attributable to several factors. One possible factor might be the ELISA method which can detect other proteins (e.g., properdin) rather than zonulin. Therefore, it might fail to indicate direct observation of intestinal permeability. However, future study designs with more accurate estimation of zonulin in a larger sample may provide a different perspective on intestinal permeability's possible role in BD etiology.

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.

The evaluation of pretreatment neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio in patients with laryngeal neoplasms / Avaliação da relação neutrófilo-linfócito e relação neutrófilo-linfócito derivadano pré-tratamento em pacientes com neoplasias laríngeas

Abstract Introduction: Systemic inflammatory biomarkers are promising predictive and prognostic factors for solid cancers. The neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio are used to predict inflammation and used as biomarker in several malignancies. Objective: The purpose of this study was to demonstrate the diagnostic, predictive and prognostic role of neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio in patients with laryngeal neoplasms. Methods: A retrospective study was conducted on medical records involving 229 patients with benign, premalignant and malignant laryngeal neoplasms between 2002 and 2015. The diagnostic, predictive and prognostic role of neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio were evaluated using uni- and multivariate analysis. Results: The neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio were not statistically different between patients with benign, premalignant and malignant laryngeal neoplasms. Both neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio were predictive factors for stage, lymph node metastasis, and distant metastasis. Patients with high neutrophil-lymphocyte ratio value (≥4) had a poor prognosis when compared with patients with low neutrophil-lymphocyte ratio value (5 year, Overall Survival: 69.0% vs. 31.1%, p < 0.001; 5 year, disease free survival: 70.0% vs. 32.7%, p ˂ 0.001; 5 year, locoregional recurrence free survival: 69.7% vs. 32.0%, p < 0.001). Furthermore, neutrophil-lymphocyte ratio was an independent prognostic factor for 5 year: Overall survival (HR = 2.396; 95% CI 1.408-4.077; p = 0.001), Disease free survival (HR = 2.246; 95% CI 1.322-3.816; p = 0.006) and locoregional recurrence free survival (HR = 2.210; 95% CI 1.301-3.753; p = 0.003). Conclusion: Pretreatment neutrophil-lymphocyte ratio is a useful and reliable predictive and prognostic biomarker for patients with laryngeal carcinoma.

Resumo Introdução: Biomarcadores inflamatórios sistêmicos são fatores preditivos e prognósticos promissores para cânceres sólidos. A relação neutrófilo-linfócito e a relação neutrófilo-linfócito derivada são utilizadas para predizer a inflamação e como biomarcadores em várias malignidades. Objetivo: O objetivo deste estudo foi demonstrar o papel diagnóstico, preditivo e prognóstico da relação neutrófilo-linfócito e relação neutrófilo-linfócito derivada em pacientes com neoplasias laríngeas. Método: Foi realizado um estudo retrospectivo em prontuários médicos de 229 pacientes com neoplasias laríngeas benignas, pré-malignas e malignas entre 2002 e 2015. O papel diagnóstico, preditivo e prognóstico da relação neutrófilo-linfócito e relação neutrófilo-linfócito derivada foi avaliado por meio de análise uni- e multivariada. Resultados: A relação neutrófilo-linfócito e a relação neutrófilo-linfócito derivada não foram estatisticamente diferentes entre pacientes com neoplasias laríngeas benignas, pré-malignas e malignas. Ambas as relação neutrófilo-linfócito e relação neutrófilo-linfócito derivada foram fatores preditivos para o estágio, metástase linfonodal e metástase a distância. Pacientes com valor alto da relação neutrófilo-linfócito (≥ 4) apresentaram pior prognóstico quando comparados com pacientes com valor mais baixo da relação neutrófilo-linfócito (5 anos, Sobrevida Global: 69,0% vs. 31,1%, p < 0,001; 5 anos, sobrevida livre de doença: 70,0% vs. 32,7%, p < 0,001; 5 anos, sobrevida livre de recorrência loco-regional: 69,7% vs. 32,0%, p < 0,001). Além disso, a relação neutrófilo-linfócito foi um fator prognóstico independente para 5 anos: Sobrevida global (HR = 2,396; IC95% 1,408-4,077; p = 0,001), sobrevida livre de doença (HR = 2,246; IC95%: 1,322-3,816; p = 0,006) e sobrevida livre de recorrência loco-regional (HR = 2,210; IC95%: 1,301-3,753; p = 0,003). Conclusão: A relação neutrófilo-linfócito no pré-tratamento é um biomarcador preditivo e de prognóstico útil e confiável para pacientes com carcinoma de laringe.

The evaluation of pretreatment neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio in patients with laryngeal neoplasms.

INTRODUCTION: Systemic inflammatory biomarkers are promising predictive and prognostic factors for solid cancers. The neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio are used to predict inflammation and used as biomarker in several malignancies. OBJECTIVE: The purpose of this study was to demonstrate the diagnostic, predictive and prognostic role of neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio in patients with laryngeal neoplasms. METHODS: A retrospective study was conducted on medical records involving 229 patients with benign, premalignant and malignant laryngeal neoplasms between 2002 and 2015. The diagnostic, predictive and prognostic role of neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio were evaluated using uni- and multivariate analysis. RESULTS: The neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio were not statistically different between patients with benign, premalignant and malignant laryngeal neoplasms. Both neutrophil-lymphocyte ratio and derived neutrophil-lymphocyte ratio were predictive factors for stage, lymph node metastasis, and distant metastasis. Patients with high neutrophil-lymphocyte ratio value (≥4) had a poor prognosis when compared with patients with low neutrophil-lymphocyte ratio value (5 year, Overall Survival: 69.0% vs. 31.1%, p<0.001; 5 year, disease free survival: 70.0% vs. 32.7%, p˂0.001; 5 year, locoregional recurrence free survival: 69.7% vs. 32.0%, p<0.001). Furthermore, neutrophil-lymphocyte ratio was an independent prognostic factor for 5 year: Overall survival (HR=2.396; 95% CI 1.408-4.077; p=0.001), Disease free survival (HR=2.246; 95% CI 1.322-3.816; p=0.006) and locoregional recurrence free survival (HR=2.210; 95% CI 1.301-3.753; p=0.003). CONCLUSION: Pretreatment neutrophil-lymphocyte ratio is a useful and reliable predictive and prognostic biomarker for patients with laryngeal carcinoma.

Asymmetric dimethylarginine levels and diabetes duration: Relationship with measures of subclinical atherosclerosis and cardiac function in children and adolescents with Type 1 diabetes.

AIMS: We aimed to evaluate asymmetric dimethylarginine levels in young patients with Type 1 diabetes mellitus according to diabetes duration and to examine the relationship between these levels and measures of atherosclerosis and myocardial function. MATERIALS AND METHODS: In total, 83 patients (8.5-22 years) with Type 1 diabetes mellitus were stratified by diabetes duration: 12-60 months (Group 1, n = 27), >60-120 months (Group 2, n = 29) and >120 months (Group 3, n = 27). Asymmetric dimethylarginine levels were assessed. Carotid intima-media thickness was measured. Myocardial function was assessed by M-mode, conventional Doppler and tissue Doppler echocardiography. RESULTS: Asymmetric dimethylarginine level was significantly higher in Group 1, while carotid intima-media thickness was significantly greater in Group 3 ( p < 0.05). Tissue Doppler echocardiography showed the ratio of peak early to peak late diastolic myocardial annular velocity decreased significantly in Groups 2 and 3 with a negative correlation with duration (r: -0.310, p = 0.004) and HBA1c levels (r = -0.391, p < 0.001). Myocardial performance index in all groups and isovolumic relaxation time in Group 3 increased significantly. Asymmetric dimethylarginine levels were negatively correlated with carotid intima-media thickness and isovolumic relaxation time ( p < 0.05). CONCLUSION: In contrast to adult diabetics, asymmetric dimethylarginine concentration decreases as diabetes duration increases in young Type 1 diabetic patients and is associated with worsening measures of cardiovascular risk and poorer diastolic function.

Secondhand tobacco smoke and severity in wheezing children: Nasal oxidant stress and inflammation.

OBJECTIVES: Prenatal and postnatal smoke exposures are associated with many lung diseases in children due to impaired lung function, increased inflammation, and oxidative stress. We aimed to determine the influence of secondhand tobacco smoke exposure on the levels of nasal glutathione, IL-8, IL-17, MMP-9, and TIMP-1, as well as serum surfactant protein-D (SP-D) in wheezy children. METHODS: We enrolled 150 children with recurrent wheezing and recorded wheezing characteristics at enrollment. We measured the levels of serum cotinine, SP-D, nasal glutathione, IL-8, IL-17, MMP-9, and TIMP-1. Serum cotinine levels between 3 and 12 ng/mL, and above 12 ng/mL were defined as lower and higher level secondhand tobacco smoke exposure, respectively. The ANOVA test, Pearson's correlation analysis and multivariate analysis with a linear regression test were used for the statistical analysis. RESULTS: Ninety-one children had been exposed to lower level secondhand tobacco smoke, while 24 children were exposed to higher level secondhand tobacco smoke. Thirty-five children were not exposed to cigarette smoke. Wheezing symptom scores were higher in exposed children (p = 0.03). Levels of other biomarkers showed no significant difference. CONCLUSIONS: Secondhand tobacco smoke exposure is associated with more severe respiratory symptoms in wheezing children. However, levels of nasal or serum inflammatory markers fail to explain this association, either because of different mechanical factors in the process or due to low levels of the biomarkers especially in nasal secretions.

Evidence of associations between brain-derived neurotrophic factor (BDNF) serum levels and gene polymorphisms with tinnitus.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) gene polymorphisms are associated with abnormalities in regulation of BDNF secretion. Studies also linked BDNF polymorphisms with changes in brainstem auditory-evoked response test results. Furthermore, BDNF levels are reduced in tinnitus, psychiatric disorders, depression, dysthymic disorder that may be associated with stress, conversion disorder, and suicide attempts due to crises of life. For this purpose, we investigated whether there is any role of BDNF changes in the pathophysiology of tinnitus. MATERIALS AND METHODS: In this study, we examined the possible effects of BDNF variants in individuals diagnosed with tinnitus for more than 3 months. Fifty-two tinnitus subjects between the ages of 18 and 55, and 42 years healthy control subjects in the same age group, who were free of any otorhinolaryngology and systemic disease, were selected for examination. The intensity of tinnitus and depression was measured using the tinnitus handicap inventory, and the differential diagnosis of psychiatric diagnoses made using the Structured Clinical Interview for Fourth Edition of Mental Disorders. BDNF gene polymorphism was analyzed in the genomic deoxyribonucleic acid (DNA) samples extracted from the venous blood, and the serum levels of BDNF were measured. One-way analysis of variance and Chi-squared tests were applied. RESULTS: Serum BDNF level was found lower in the tinnitus patients than controls, and it appeared that there is no correlation between BDNF gene polymorphism and tinnitus. CONCLUSIONS: This study suggests neurotrophic factors such as BDNF may have a role in tinnitus etiology. Future studies with larger sample size may be required to further confirm our results.

Analysis of the association of chronic spontaneous urticaria with interlekin-4, -10, transforming growth factor-ß1, interferon-γ, interleukin-17A and -23 by autologous serum skin test.

AIM: To contribute to the understanding of the pathogenesis of chronic spontaneous urticaria (CSU) by identifying its relationship with autoimmunity and cytokines using the autologous serum skin test (ASST) and peripheral blood mononuclear cell culture (PBMC) method. MATERIAL AND METHODS: Interleukins (IL)-4, IL-10, transforming growth factor (TGF-ß1), interferon (IFN)-γ, IL-17A, and IL-23 levels in cell supernatants obtained by the PBMC method were measured using ELISA. Disease activity was assessed by determining the urticaria activity score (UAS). RESULTS: A total of 40 patients diagnosed with CSU participated in this study. Twenty patients had positive ASST results, and 20 had negative results. The control group included 20 healthy volunteers. We found that the IL-23 (p = 0.01), IL-10 (p = 0.04) and IL-4 (p = 0.04) levels of the patient groups were significantly lower compared with those of the control group. The IL-23 (p = 0.009), IL-10 (p = 0.009), IL-4 (p = 0.001), and IL-17 (p = 0.05) levels of the ASST(-) patient group were significantly lower compared with those of the control group. In addition, the IL-4 (p = 0.03) and IFN-γ (p = 0.05) levels of the ASST(+) patient group were significantly lower compared with those of the control group, and the ASST(+) patients had a significantly higher UAS than the ASST(-) patients (p = 0.021). CONCLUSIONS: These results, when considered together with current reports in the literature, indicate that immune dysregulation occurs in the pathogenesis of CSU, causing cytokine imbalance.

Immune and inflammatory role of hydroxyethyl starch 130/0.4 and fluid gelatin in patients undergoing coronary surgery.

OBJECTIVES: Compare the effects on inflammatory (TNF-α, IL-6, IL-8 and IL-10) and immunologic (CD3(+), CD4(+), CD8(+), CD11b(+), CD16(+)/56(+) T cells and total lymphocyte concentration) variables of hydroxyethyl starch 130/0.4, 4% modified fluid gelatin, or crystalloid when used as volume replacement fluids for acute normovolemic hemodilution (a blood conservation technique) in coronary artery bypass graft patients. METHODS: Thirty patients undergoing coronary artery bypass graft surgery were randomized to receive Isolyte S® (Group ISO), 6% hydroxyethyl starch 130/0.4 (Group HES) or 4% modified gelatin solution (Group GEL) for acute normovolemic hemodilution. Blood samples were taken immediately after induction of anaesthesia (T0), and 2 h (T1), 12 h (T2), 24 h (T3), and 48 h (T4) after separation from cardiopulmonary bypass. TNF-α, IL-6, IL-8 and IL-10 levels were determined with commercially available ELISA kits. CD3(+) (mature T cells), CD4(+) (T helper cells), CD8(+) (suppressor cytotoxic T cells), CD16(+)/56(+) (natural killer lymphocytes), and CD11b(+) (Mac-1, adhesion receptor) levels were measured using flow-cytometry reagents. The CD4(+):CD8(+) ratio was calculated. RESULTS: Between-group comparisons showed significantly higher levels of TNF-α at T1 (2 h after weaning from cardiopulmonary bypass) in Group HES compared to Group ISO (p=0.003). IL-8 was significantly lower in Group HES than Group GEL at T1 (p=0.0005). IL-10 was significantly higher in Group HES than in Group GEL at T1 (p=0.0001). The CD4(+):CD8(+) ratio in Group ISO was significantly lower than that in Group HES at T2 (p=0.003). CD11b(+) levels in Group HES were also higher than those in Group GEL and group ISO at T2, but not significantly. CD16/56(+) levels in Group HES were higher than those in Group GEL at T2 (p<0.003). No excessive hemorrhage occurred in any patient. Mediastinal drainage during the first 24 h after surgery in Group HES (347±207 mL) was not significantly different from that of Group GEL (272±177 mL) or Group ISO (247±109) (p>0.05). CONCLUSION: Hydroxyethyl starch 130/0.4 reduced pro-inflammatory responses and increased anti-inflammatory responses to a greater degree than gelatin solution and isolyte S®. The use of hydroxyethyl starch, compared to gelatin solution and isolyte S®, resulted in less decrease in the CD4(+):CD8(+) ratio, suggesting less immunosuppression.

Oxidative stress markers, cognitive functions, and psychosocial functioning in bipolar disorder: an empirical cross-sectional study

Objective: This study aimed to evaluate the relationship between oxidative stress markers and cognitive functions and domains of psychosocial functioning in bipolar disorder. Methods: Oxidative stress markers, cognitive functions, and domains of psychosocial functioning were evaluated in 51 patients with bipolar disorder who were in remission. Correlation analyses between these parameters were calculated with data controlled for duration of illness and number of episodes. Results: There was no statistically significant correlation between oxidative stress markers and cognitive functions. In terms of psychosocial functioning, significant correlations were found between malondialdehyde and sense of stigmatization (r = -0.502); household activities and superoxide dismutase (r = 0.501); participation in social activities and nitric oxide (r = 0.414); hobbies and leisure time activities and total glutathione (r = -0.567), superoxide dismutase (r = 0.667), and neurotrophin 4 (r = 0.450); and taking initiative and self-sufficiency and superoxide dismutase (r = 0.597). There was no correlation between other domains of psychosocial functioning and oxidative stress markers. Conclusion: These results imply that oxidative stress markers do not appear to correlate clearly with cognitive impairment and reduced psychosocial functioning. However, there were some associations between selected oxidative markers and activity-oriented functional markers. This may represent a true negative association, or may be an artifact of oxidative stress being a state rather than a trait marker. .

Oxidative stress in schizophrenia: a case-control study on the effects on social cognition and neurocognition.

BACKGROUND: Schizophrenia is a debilitating mental disorder that presents impairments in neurocognition and social cognition. Several studies have suggested that the etiology of schizophrenia can be partly explained by oxidative stress. However, our knowledge about the implications of oxidative stress on illness-related cognitive deficits is still far from being clear. The aim of this work was to study the role of oxidative stress molecules on social cognition and neurocognition in patients with schizophrenia. METHODS: We assessed the peripheral levels of several molecules associated with oxidative stress, namely nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), homocysteine, superoxide dismutase (SOD) and neurotrophin 4/5 (NT4/5), in forty-one patients with schizophrenia and forty-three healthy participants. A battery of tests to measure neurocognition and social cognition was also administered to the schizophrenia group. RESULTS: We found that the schizophrenia group presented substantially higher levels of oxidative stress than the control group, as revealed by elevated quantities of the pro-oxidants NO and MDA, and decreased levels of the antioxidants GSH, SOD and NT4/5. Interestingly, the levels of NT4/5, which have been shown to have antioxidant effects, correlated with executive functioning, as measured by two distinct tests (WCST and TMT). However, social cognition and symptom severity were not found to be associated with oxidative stress. CONCLUSIONS: We propose a protective role of NT4/5 against oxidative stress, which appears to have a potentially beneficial impact on neurocognition in schizophrenia.

Oxidative stress markers, cognitive functions, and psychosocial functioning in bipolar disorder: an empirical cross-sectional study.

OBJECTIVE: This study aimed to evaluate the relationship between oxidative stress markers and cognitive functions and domains of psychosocial functioning in bipolar disorder. METHODS: Oxidative stress markers, cognitive functions, and domains of psychosocial functioning were evaluated in 51 patients with bipolar disorder who were in remission. Correlation analyses between these parameters were calculated with data controlled for duration of illness and number of episodes. RESULTS: There was no statistically significant correlation between oxidative stress markers and cognitive functions. In terms of psychosocial functioning, significant correlations were found between malondialdehyde and sense of stigmatization (r = -0.502); household activities and superoxide dismutase (r = 0.501); participation in social activities and nitric oxide (r = 0.414); hobbies and leisure time activities and total glutathione (r = -0.567), superoxide dismutase (r = 0.667), and neurotrophin 4 (r = 0.450); and taking initiative and self-sufficiency and superoxide dismutase (r = 0.597). There was no correlation between other domains of psychosocial functioning and oxidative stress markers. CONCLUSION: These results imply that oxidative stress markers do not appear to correlate clearly with cognitive impairment and reduced psychosocial functioning. However, there were some associations between selected oxidative markers and activity-oriented functional markers. This may represent a true negative association, or may be an artifact of oxidative stress being a state rather than a trait marker.

Peripheral Mononuclear Response to Antigenic Stimulation in Children with Obese Asthma Phenotype.

An investigation of immunopathogenetic mechanisms of obesity-associated asthma may demonstrate novel therapeutic targets. The aim of this study was to compare levels of T-helper lymphocyte (Th)1, Th2, regulatory T lymphocyte (Treg), and Th17 cytokines secreted by peripheral blood mononuclear cell culture (PBMC) in response to nonspecific stimulation in obese and nonobese children with asthma. Obese and nonobese children with asthma aged 5-16 were enrolled into this case-control study consecutively. Age at asthma diagnosis and clinical severity were recorded. A skin prick test was performed. Serum adipokine levels and PBMC supernatant interleukin (IL)-4, IL-10, IL-17, IL-23, interferon (IFN)γ, and transforming growth factor (TGF)-ß levels were measured. Mean (±standard deviation) ages of obese (n=28) and nonobese (n=39) children with asthma were 8.7±2.9 and 10.5±3.2, respectively. Asthma symptom score was higher, and age at asthma diagnosis was lower in obese compared with nonobese children with asthma (P=0.03 and P=0.004, respectively). Leptin levels were significantly higher in obese than in nonobese asthma group (P<0.001). IL-10 and IL-17 levels in obese group were significantly lower than in nonobese group (P=0.005 and P=0.017, respectively). On the other hand, TGF-ß levels were significantly higher in obese compared with nonobese children with asthma (P=0.015). IL-4, IL-23, and IFNγ levels were not significantly different between the groups (P<0.05 for all). Low IL-10 and high TGF-ß levels in obese compared with nonobese children with asthma might indicate lower anti-inflammatory cytokine secretion and Treg function as well as a higher remodeling process in obesity-associated asthma in children.

Elevated glucose level at 30 minutes during an oral glucose tolerance test in obese adolescents: a new disorder of glucose tolerance.

We observed glucose levels >140 mg/dL measured at 30 minutes (min) during an oral glucose tolerance test (OGTT) in some obese patients. We aimed to investigate the significance of this finding by comparing lipid profiles, insulin resistance indices, and systemic inflammatory mediators between obese adolescents with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and elevated glucose levels at 30 min. The study involved 80 obese (body mass index >95(th) percentile for age and sex) adolescents (48 female, 32 male) between 11 and 16 years of age. Depending on OGTT results, patients were divided into NGT and IGT groups. The third group was recruited from the NGT group as having glucose levels > 140 mg/dL at 30 minutes. Lipid profiles, [interleukin-6 (IL-6)], neopterin, and lipoprotein associated phospholipase A2 (Lp-PLA2)] were assessed. Neopterin and Lp-PLA2 levels were significantly higher in obese adolescents with elevated glucose levels at 30 min. compared with those in both NGT and IGT groups (p=0.013, and 0.004, respectively). In these adolescents, IL-6 levels were significantly higher only than the NGT group (p=0.01). In logistic regression analysis, IL-6, neopterin and Lp-PLA2 levels were detected to be related to high blood glucose levels at 30 min (OR 1.11, p=0.01; OR 9.03, p=0.013; OR 1.01, p=0.004 respectively). Obese adolescents with elevated glucose levels at 30 min. demonstrated higher inflammatory mediators levels, which were atherosclerotic indicators, than obese adolescents with NGT and IGT. These results suggest that glucose levels >140 mg/dL measured at 30 min during an OGTT may be a new disorder of glucose tolerance in obesity.

Serum homocysteine, vitamin B12, folic acid levels and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in vitiligo.

The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy) levels as well as MTHFR (C677, A1298C) gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C) do not seem to create susceptibility for vitiligo.

Role of adipokines and hormones of obesity in childhood asthma.

PURPOSE: The aim of this study was to evaluate serum levels of leptin, ghrelin, and adiponectin in obese and non-obese children with asthma and in healthy non-asthmatic children, and analyze their relationships with clinical outcomes. METHODS: This study enrolled 40 obese and 51 non-obese children with asthma and 20 healthy children. Body mass index and serum leptin, ghrelin, and adiponectin levels were determined in all children. Asthma symptom scores and lung function test results were recorded for subjects with asthma. RESULTS: Serum leptin levels (11.8±7.9, 5.3±6.8, and 2.1±2.4 ng/mL in the obese asthmatic, non-obese asthmatic, and control groups, respectively) and adiponectin levels (12,586.2±3,724.1; 18,089.3±6,452.3; and 20,297.5±3,680.7 ng/mL, respectively) differed significantly among the groups (P<0.001 for all). Mean ghrelin levels were 196.1±96.8 and 311.9±352.8 pg/mL in the obese and non-obese asthmatic groups, respectively, and 348.8±146.4 pg/mL in the control group (P=0.001). The asthma symptom score was significantly higher in the obese children with asthma than in the non-obese children with asthma (P<0.001). Leptin and adiponectin levels were correlated with the asthma symptom score in non-obese children with asthma (r=0.34 and r=-0.62, respectively). CONCLUSIONS: Obesity leads to more severe asthma symptoms in children. Moreover, leptin, adiponectin, and ghrelin may play important roles in the inflammatory pathogenesis of asthma and obesity co-morbidity.

Effects of physical exercise on lung injury and oxidant stress in children with asthma

Background The aim of this study was to investigate the influence of exercise training on oxidative stress and markers of lung inflammation in children with asthma. Methods Thirty children aged 8-13 years diagnosed with asthma were enrolled in the study as well as 13 healthy children. One group received only pharmacological treatment and the other group was also enrolled in an exercise programme. Venous blood and 24-hour urine samples were obtained from the children enrolled in the study at the beginning and end of the study. Leukotriene E4 and creatinine levels were measured in the urine and matrix metallopeptidase (MMP-9), endothelin-1(ET-1), malnodialdehyde (MDA), IgE and specific IgE levels were measured in blood samples. Results Leukotriene E4, MDA and MMP9 levels decreased significantly with treatment in both groups (p<0.001). However, ET-1 levels decreased significant only in the exercise group (26.5±3.6 vs 21.3±2.4pg/ml respectively, p=0.001). Moreover, ET-1 levels were found to be significantly lower in the exercise group compared to the only pharmacotherapy group (24.2±3.1 vs 21.3±2.4pg/ml, p=0.007). Conclusions Positive influences of exercise training in children with asthma may be mediated by decrease in ET-1 levels(AU)