Acute and Chronic Effects of Strength Training on Plasma Levels of Adipokines in Man.

Adipose tissue is specialized cells that produce and release adipokines. Exercise may modulate adipokine production in adipocytes. The aim of this longitudinal study was to evaluate the acute and chronic effects of strength training (ST) on plasma levels of adiponectin, leptin, and resistin. Twelve untrained young male participants (23.42±2.67 years) were selected. The training protocol consisted of 3 exercises, with 3 sets of 65% of 1RM (one-repetition maximum) with pause of 90 s between sets with duration of 5 s/repetition (2 s conc/3 s ecc), 3 times a week for 10 weeks. Blood was collected at four time points: before and after the first ST session and before and after the last ST session. The comparisons between adipokine levels before and after the same training session showed acute changes, while the comparisons between levels before or after the first session versus before or after the last session revealed chronic alterations. ST increased adiponectin levels after the first exercise session in comparison to levels before this session [50 952 (46 568-51 894) pg/mL vs. 52 981 (49 901-54 467) pg/mL, p=0.019]. Similar differences were observed for resistin levels, which were higher after the last session compared to before [4 214.4 (±829) pg/mL vs. pre-S30 2 251.3 (±462.2) pg/mL, p=0.0008] and in the comparison between after the last and after the first ST sessions [4 214.4 (±829.0) pg/mL vs. 1 563.7 (±284.8) pg/mL, p=0.004]. Leptin levels acutely changed in the last training session. ST produced acute and chronic changes in plasma adipokines.

Evaluation of New Potential Inflammatory Markers in Patients with Nonvalvular Atrial Fibrillation.

Atrial fibrillation (AF), the most common arrhythmia in clinical practice, is associated with an increase in mortality and morbidity due to its high potential to cause stroke and systemic thromboembolism. Inflammatory mechanisms may play a role in the pathogenesis of AF and its maintenance. We aimed to evaluate a range of inflammatory markers as potentially involved in the pathophysiology of individuals with nonvalvular AF (NVAF). A total of 105 subjects were enrolled and divided into two groups: patients with NVAF (n = 55, mean age 72 ± 8 years) and a control group of individuals in sinus rhythm (n = 50, mean age 71 ± 8 years). Inflammatory-related mediators were quantified in plasma samples by using Cytometric Bead Array and Multiplex immunoassay. Subjects with NVAF presented significantly elevated values of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF), interferon-gamma, growth differentiation factor-15, myeloperoxidase, as well as IL-4, interferon-gamma-induced protein (IP-10), monokine induced by interferon-gamma, neutrophil gelatinase-associated lipocalin, and serum amyloid A in comparison with controls. However, after multivariate regression analysis adjusting for confounding factors, only IL-6, IL-10, TNF, and IP-10 remained significantly associated with AF. We provided a basis for the study of inflammatory markers whose association with AF has not been addressed before, such as IP-10, in addition to supporting evidence about molecules that had previously been associated with the disease. We expect to contribute to the discovery of markers that can be implemented in clinical practice hereafter.

The potential role of renin-angiotensin system in mild traumatic brain injury.

Traumatic brain injury (TBI) is a serious public health problem, affecting 69 million people worldwide annually. Mild TBI (mTBI) comprises the majority of the cases and remains the most neglected TBI severity. Its intricate pathophysiology involves complex cellular and molecular processes that remain uncomprehended. Although the renin-angiotensin system (RAS) has its well-known roles in blood pressure regulation and fluid balance, accumulating evidence demonstrates its active expression and signaling in the central nervous system. Over the past years, pre-clinical studies have been supporting the role of RAS in mTBI. However, particularly for human TBI, evidence is still missing. Herein, we investigated peripheral levels of angiotensin II (Ang II) and angiotensin-converting enzyme (ACE), components of RAS classical axis, as well as angiotensin-(1-7) [Ang-(1-7)] and ACE2, components of RAS counter-regulatory axis, in 28 mTBI patients and 24 healthy controls. In the first 24 h, mTBI patients displayed lower ACE (p = 0.0004) and ACE2 (p = 0.0047) concentrations and an increase in Ang II (p = 0.0234) and Ang-(1-7) (p = 0.0225) levels compared to controls. Interestingly, at 30 days follow-up, mTBI patients increased the levels of ACE (p = 0.0415) and ACE2 (p = 0.0416) along with a decrease in Ang II (p = 0.0039) and Ang-(1-7) (p = 0.0015) concentrations compared with their measures at 24 h after TBI. Also, our receiver operating curve (ROC) analysis demonstrated that ACE concentration was a good predictor of mTBI diagnosis (AUC = 0.798, p < 0.0001). The current study provides the first clinical evidence of RAS molecule's involvement in mTBI and their possible role as discriminating biomarkers.

Sleep, social behaviour and food consumption of schoolchildren of a large Brazilian city.

OBJECTIVE: To explore the impact of inadequate sleep and associated factors on the social behaviour and food consumption of children and adolescents. DESIGN: Cross-sectional study. SETTING: Sleep information, social behaviour (Strengths and Difficulties Questionnaire), food consumption, demography, nutritional status, lifestyle, and biochemical tests were investigated. PARTICIPANTS: School children in the 4th grade of the municipal school system of a large Brazilian city. RESULTS: Of a total of 797 schoolchildren, 50·9 % were female, with a median age of 9·7 (9·5-10·0) years old and an energy consumption of 7613·6 (5982·7-9766·2) kJ. It was determined that 31·6 % were overweight, and 76·8 % reported insufficient weekly practice of physical activity. A median of 9·6 (8·9-10·5) h of sleep (lower values on weekdays: 9·3 v. 10·5 h, P < 0·001) was recorded. In addition, 27 % of the individuals who experienced inadequate sleep (<9 h) engaged in longer screen time daily (≥2 h/d) (P = 0·05), had an inadequate bedtime (> 22 h) or adequate wake-up time (5-7 h), studied in the morning (P < 0·001) and never took a shower before school (P < 0·001). Of the entire sample, 9·9 % had poor or very poor sleep quality and a greater probability of sleep talking regularly, had difficulty falling asleep, and engaged in inadequate social behaviour while experiencing these conditions compared with those with positive sleep quality. There was no association between sleep and the other variables investigated. CONCLUSIONS: Sleep impairment contributed to changes in sleep and social behaviour in schoolchildren. The findings of this study may reinforce the importance of developing actions to promote adequate sleep and a healthy lifestyle at school age.

Renin-angiotensin system molecules are associated with subclinical atherosclerosis and disease activity in rheumatoid arthritis.

OBJECTIVES: To compare serum levels of RAS components in women with RA versus healthy females and to investigate the association between these molecules and subclinical atherosclerosis. METHODS: A cross-sectional study involving female RA patients without ischemic CVD. Disease activity was assessed using the DAS28 and the CDAI. IMT of the common carotid artery was evaluated by ultrasonography. Serum levels of Ang II, Ang-(1-7), ACE and ACE2 were determined by enzyme immunoassay. RESULTS: Fifty women with RA, mean 48.2 (7.3) years, were compared to 30 healthy women, paired by age. RA patients had higher plasma levels of Ang II (p < .01), Ang-(1-7) (p < .01), and ACE (p < .01) than controls. The ratios of ACE to ACE2 were higher in RA patients, whereas Ang II/Ang-(1-7) ratios were lower in RA patients. The presence of hypertension and the treatment with ACE inhibitors did not significantly modify serum levels of Ang II, Ang-(1-7), ACE and ACE2 in patients with RA. Seven RA patients had altered IMT, and eight patients exhibited atherosclerotic plaque. There was a negative correlation between ACE2 levels and IMT (p = .041). IMT positively correlated with age (p = .022), disease duration (p = .012) and overall Framingham risk score (p = .008). Ang II concentrations positively correlated with DAS28 (p = .034) and CDAI (p = .040). CONCLUSION: Patients with RA had an activation of the RAS, suggesting an association with disease activity and cardiovascular risk. Rheumatological key messages Imbalance of both RAS axes may be associated with cardiovascular risk and disease activity in rheumatoid arthritis. Ultrasonography of the carotid arteries can identify early, subclinical atherosclerotic disease in rheumatoid arthritis patients. Angiotensin-converting enzyme inhibition or angiotensin 1 receptor blockade may be beneficial for rheumatoid arthritis patients.

Evidence for interactions between inflammatory markers and renin-angiotensin system molecules in the occurrence of albuminuria in children with sickle cell anemia.

Sickle cell anemia (SCA) is an important cause of chronic kidney disease, but its pathophysiology is not completely understood. The aim of this study was to compare inflammatory biomarkers in urine samples of SCA children with and without albuminuria, and to explore correlations with renin-angiotensin system (RAS) molecules. A cross-sectional study of 213 children selected from the Minas Gerais state cohort were assigned to two groups: Group 1-89 children with SCA who had albuminuria; Group 2-124 children with SCA and normal albuminuria matched by age and sex with group 1. A subset of 89 children was prospectively followed for a median time of 1.1 year. Inflammatory biomarkers (chemokines and cytokines) in urine were measured using cytometric beads array, and RAS molecules were measured by ELISA. Children with albuminuria had significantly higher urinary levels of IP-10/CXCL10, MCP-1/CCL2, MIG/CXCL9, IL-8/CXCL8, IL-12p70, TNF, IL-10, and IL-6 than patients with normal albuminuria. In the correlation analysis, albumin/creatinine ratio was significantly and positively correlated with IP-10/CXCL10, MCP-1/CCL2, MIG/CXCL9, IL-8/CXCL8, TNF, IL-10, and IL-6. Significant correlations were found between inflammatory and RAS molecules. In the prospective analysis, cumulative risk of persistent albuminuria was higher for children with urinary levels of IP-10/CXCL10 or IL-6 above the 50th percentile. Our data showed that inflammatory markers and RAS molecules might contribute to the occurrence of albuminuria in children with SCA, suggesting that both pathways interact in sickle cell nephropathy.

Evaluation of Brain Cytokines and the Level of Brain-Derived Neurotrophic Factor in an Inflammatory Model of Depression.

INTRODUCTION: Major depressive disorder is considered a global public health problem. Inflammatory processes are likely involved in its pathophysiology, but the underlying mechanisms have remained uncertain.Here, we used the model of systemic lipopolysaccharide (LPS) injection to test the hypothesis that depressive-like behaviors occur along with changes in the levels of cytokines and brain-derived neurotrophic factor (BDNF) in the hippocampus (HC), prefrontal cortex (PFC), and hypothalamus (HT), and can be prevented by dexamethasone administration. METHODS: Adult C57Bl/6 male mice were first isolated for 10 days, and thereafter received an injection of dexamethasone (6 mg/kg, intraperitoneal [i.p.]), saline followed by LPS (0.83 mg/kg, i.p.), or saline. After 6 h, animals were subjected to the forced-swim test (FST) and open-field tests. Immediately after the behavioral tests, they were euthanized and their brains were collected for the biochemical analyses. RESULTS: LPS increased the immobility time and reduced the distance travelled in the FST and open-field test, respectively. Dexamethasone increased the immobility time in saline-treated mice but reduced this behavior in the LPS group. LPS increased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and interferon (IFN)-γ in most of the regions evaluated. Dexamethasone prevented LPS-induced IL-6 in the HC, PFC, and HT. Interestingly, dexamethasone increased IL-4 and IL-10 levels in both the LPS- and saline-treated groups. Although dexamethasone reduced BDNF in saline-treated mice, it prevented LPS-induced reduction in this neurotrophic factor. CONCLUSION: In summary, dexamethasone decreased proinflammatory and increased anti-inflammatory levels of cytokines and prevented a reduction in BDNF levels induced by the inflammatory stimulus. Thus, the attenuation of depressive-like behavior induced by dexamethasone may be related to the effects on these parameters.

Peripheral levels of sST2 are increased in patients with temporal lobe epilepsy: Additional evidence of low-grade inflammation.

Inflammation plays a pivotal role in temporal lobe epilepsy (TLE) pathophysiology. IL-33 can act as a transcription factor or as a cytokine, the latter through the transmembrane ST2 receptor or its soluble isoform (sST2), presenting a dual role in neurological diseases. The aim of this study was to determine the plasma levels of IL-33 and sST2 in parallel with clinical features in patients with TLE. Peripheral blood from patients and controls was sampled for the measurement of plasma levels of IL-33 and sST2 by enzyme-linked immunoassay (ELISA). While there were similar levels of IL-33 between controls and patients, sST2 were increased in patients. IL33 and sST2 plasma levels were not associated with TLE-related clinical features. In a subgroup analysis, IL-33 levels correlated with memory performance. In conclusion, our results reinforce the concept of chronic low-grade inflammation in patients with TLE.

Microgliosis is associated with visual memory decline in patients with temporal lobe epilepsy and hippocampal sclerosis: A clinicopathologic study.

Hippocampal sclerosis (HS) is characterized by neuronal loss and gliosis. The intensity and distribution of these histopathological findings over the Cornu Ammonis (CA) subfields are important for the classification of HS and prognostication of patients with temporal lobe epilepsy (TLE). Several studies have associated the neuronal density reduction in the hippocampus with cognitive decline in patients with TLE. The current study aimed at investigating whether the expression of glial proteins in sclerotic hippocampi is associated with presurgical memory performance of patients with TLE. Before amygdalohippocampectomy, patients were submitted to memory tests. Immunohistochemical and morphometric analyses with glial fibrillary acidic protein (GFAP) for astrogliosis and human leucocyte antigen DR (HLA-DR) for microgliosis were performed in paraffin-embedded HS and control hippocampi. Sclerotic hippocampi exhibited increased gliosis in comparison with controls. In patients with TLE, the area and intensity of staining for HLA-DR were associated with worse performance in the memory tests. Glial fibrillary acidic protein was neither associated nor correlated with memory test performance. Our data suggest association between microgliosis, but not astrogliosis, with visual memory decline in patients with TLE.

Stress, anxiety, self-efficacy, and the meanings that physical therapy students attribute to their experience with an objective structured clinical examination.

BACKGROUND: Excessive stress and anxiety can impair learning. The objective structured clinical examination (OSCE) is a valuable tool to assess and promote the acquisition of clinical skills. However, significant OSCE-related stress and anxiety are frequently reported. The aim of this study was to investigate the relationships between physiological stress, self-reported levels of anxiety due to an OSCE, self-efficacy, and the meanings that physical therapy students attribute to their experience with the exam. DESIGN: Concurrent mixed methods study. METHODS: A total of 32 students took part in this study. All were enrolled in the third semester of a 10-semester Physical Therapy Bachelor Program. Salivary cortisol levels, self-reported anxiety (State-Trait Anxiety Inventory, STAI) were measured before the OSCE. Exam scores and self-efficacy ratings were also recorded. Correlations between variables were tested with the Pearson correlation, with ɑ at 0.05. Semi-structured interviews were used to explore the personal perspectives of students. Thematic analysis was used to investigate emergent themes. RESULTS: Trait anxiety scores were significantly higher than normative values (p < 0.001). A high proportion of students showed high (STAI> 49) state anxiety (37.5%) and trait anxiety (65.6%). Salivary cortisol was not associated anxiety (p > 0.05). Neither stress nor anxiety correlated with OSCE scores. A moderate and significant direct correlation was found for self-efficacy scores and OSCE scores (r = 0.475, p = 0.007). Students reported that confidence had a calming effect and led to better self-perceived performance. They also reported that the OSCE can provide meaningful learning experiences despite being stressful. CONCLUSIONS: A high proportion of our students reported a stable/lingering negative affect. However, neither stress nor anxiety related to OSCE scores. Students' confidence in their capabilities was correlated with their performance. Their subjective reports suggest that self-confidence may have protected them from the negative effects of stress and anxiety on academic performance.

Circulating levels of adipokines are altered in patients with temporal lobe epilepsy.

OBJECTIVE: A persistent low-grade inflammatory state has been described in patients with temporal lobe epilepsy (TLE) in the interictal period. Adipokines are cytokines produced by the adipose tissue that can influence inflammatory response. The purpose of this study was to evaluate the plasma levels of adipokines in patients with TLE in comparison with controls. In addition, we sought to investigate whether the levels of adipokines were associated with clinical parameters in TLE. METHODS: Forty patients with TLE and 40 controls were enrolled in this study. All participants were subjected to clinical assessment that included the Mini International Neuropsychiatric Interview (MINI) and the Hamilton Depression Rating Scale (HAM-D). Peripheral blood was drawn, and plasma levels of adipokines (adiponectin, leptin, and resistin) were measured by enzyme-linked immunoassay (ELISA). RESULTS: People with TLE presented higher leptin and lower adiponectin and resistin levels in comparison with controls. The levels of these adipokines correlated negatively with illness length but not with other clinical parameters. In a binary logistic regression model, higher leptin and lower adiponectin levels remained as significant predictors of TLE diagnosis. CONCLUSIONS: These results corroborate the view that TLE is a multisystemic condition associated with low-grade inflammation.

Plasma Levels of Brain-Derived Neurotrophic Factor are Associated with Prognosis in the Acute Phase of Ischemic Stroke.

CONTEXT: Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neuronal survival, differentiation, and maturation. PURPOSE: To evaluate the levels of BDNF in the acute phase of stroke and their potential association with neurological impairment. METHODS: Patients in the acute phase of ischemic stroke were evaluated with the following clinical tools: National Institutes of Health Stroke Scale, modified Rankin scale, Gugging Swallowing Screen and Alberta Stroke Program Early CT Score. Blood samples were collected at 3 different moments of hospital stay. BDNF was measured through enzyme-linked immunosorbent assay. RESULTS: Patients who were discharged after 10 days had worse clinical outcomes and higher levels of BDNF since admission. There was correlation between BDNF levels and clinical parameters. CONCLUSION: BDNF levels were associated with clinical prognosis in the acute phase of ischemic stroke.

Leptin as an obesity marker in rheumatoid arthritis.

The determination of excess of body fat mass provides a more suitable determinant of obesity in rheumatoid arthritis patients; however, body mass index (BMI) may not be accurate for the quantification of adiposity. To identify a marker of excess adiposity in women with rheumatoid arthritis (RA) using different methods for fat mass evaluation. A cross-sectional study was conducted in adult female patients with RA. Disease activity was assessed by DAS28-ESR, and obesity was determined by waist circumference (WC), BMI and dual-energy X-ray absorptiometry (DXA). The Human Bone Metabolism kit (Merck Millipore, Darmstadt, Alemanha) was used to determine the plasma levels of leptin, TNF-α, IL-6, and IL-1ß by quantification of serum proteins by technical microspheres (LUMINEX, TX, USA). Adiponectin was measured by enzyme-linked immunosorbent assay sandwich kit (R&D Systems, Minneapolis, MN, USA). Eighty-nine female patients, median age of 55.4 (± 11.6) years, and median disease duration of 16.4 (± 14.9) years were included. The frequency of obesity was 33.7% according to BMI, 89.9% with WC, and 56.1% with DXA. The median serum leptin concentration was the only marker that correlated with body fat percentage according to the three methods. This correlation was positive and not influenced by DAS28, C-reactive protein, erythrocyte sedimentation rate, or inflammatory cytokines levels (IL-6, TNF-α, IL-1ß). Analysis of ROC curves determined the cut-off point of 10.3 ng/mL of leptin as an obesity marker, with a sensitivity of 96.43% and a specificity of 23.81%. Serum leptin correlates positively with fat mass and is potentially useful in excess fat mass determination in clinical practice.

Neuroprotective effects of intrastriatal injection of rapamycin in a mouse model of excitotoxicity induced by quinolinic acid.

BACKGROUND: The mammalian target of rapamycin (mTOR) is a kinase involved in a variety of physiological and pathological functions. However, the exact role of mTOR in excitotoxicity is poorly understood. Here, we investigated the effects of mTOR inhibition with rapamycin against neurodegeneration, and motor impairment, as well as inflammatory profile caused by an excitotoxic stimulus. METHODS: A single and unilateral striatal injection of quinolinic acid (QA) was used to induce excitotoxicity in mice. Rapamycin (250 nL of 0.2, 2, or 20 µM; intrastriatal route) was administered 15 min before QA injection. Forty-eight hours after QA administration, rotarod test was performed to evaluate motor coordination and balance. Fluoro-Jade C, Iba-1, and GFAP staining were used to evaluate neuronal cell death, microglia morphology, and astrocytes density, respectively, at this time point. Levels of cytokines and neurotrophic factors were measured by ELISA and Cytometric Bead Array 8 h after QA injection. Striatal synaptosomes were used to evaluate the release of glutamate. RESULTS: We first demonstrated that rapamycin prevented the motor impairment induced by QA. Moreover, mTOR inhibition also reduced the neurodegeneration and the production of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α induced by excitotoxic stimulus. The lowest dose of rapamycin also increased the production of IL-10 and prevented the reduction of astrocyte density induced by QA. By using an in vitro approach, we demonstrated that rapamycin differently alters the release of glutamate from striatal synaptosomes induced by QA, reducing or enhancing the release of this neurotransmitter at low or high concentrations, respectively. CONCLUSION: Taken together, these data demonstrated a protective effect of rapamycin against an excitotoxic stimulus. Therefore, this study provides new evidence of the detrimental role of mTOR in neurodegeneration, which might represent an important target for the treatment of neurodegenerative diseases.

Immunophenotype of neutrophils in oral squamous cell carcinoma patients.

BACKGROUND: The aim was to explore the immunophenotype of neutrophils and lymphocytes and the inflammatory mediators in patients with oral squamous cell carcinoma, comparing with controls; and to associate with clinicopathological data. METHODS: Blood was collected from 13 patients and 13 controls. The immunophenotype of neutrophils (CD66b, CD16, CD11a, arginase-1), T lymphocytes (CD4, CD8) and the intracellular cytokine production (IL-10, TNF, IFN-γ) was evaluated by flow cytometry. Plasma concentration of sVCAM-1, sTNF-RI, sTNF-RII, and IL-1ß was measured by ELISA. MPO, Lipocalin-2/NGAL, sICAM-1, and p-selectin were quantified by Luminex assay. The excised tumors were submitted to immunohistochemistry for neutrophils (CD66b) and lymphocytes (CD3, CD4, CD8). Association with clinical data was explored. P values <.05 were considered significant. RESULTS: Patients presented higher percentage of neutrophils and lower lymphocytes, resulting a higher neutrophil/lymphocyte ratio than controls. They also presented higher percentage of neutrophils expressing CD66b+ , CD66b+ Arginase-1+ , CD66b+ IL10+ , CD66b+ TNF+ , CD66b+ Arginase-1+ IL-10+ , and lower CD66b+ CD16+ CD11a+ and CD66b+ Arginase-1+ TNF+ . CD66b+ neutrophils were detected in all tumors, with a CD66b+ /CD3+ ratio of 0.40. Patients showed higher concentration of plasmatic sVCAM-1 and lower Lipocalin-2/NGAL. Patients with good outcome presented lower percentage of neutrophils, higher percentage of lymphocytes, and lower NLR than patients who died. CONCLUSION: The amount and immunophenotype of neutrophils and lymphocytes differ between patients and healthy individuals, with a pro-tumorigenic profile of neutrophils. As these cells also get within tumor microenvironment, they possibly exert systemic and local functions in cancer pathogenesis. The association of neutrophil count with outcome corroborates recent studies and this merits further investigation for applicability as a prognosticator.

Posterior urethral valve in fetuses: evidence for the role of inflammatory molecules.

BACKGROUND: The aim of this cross-sectional study was to investigate inflammatory biomarkers in urine samples of 24 fetuses with posterior urethral valve (PUV) collected at 22 ± 4 weeks of gestation and to compare the findings with measurements in urine samples of 22 male healthy preterm neonates at 23 ± 4 weeks (control group). METHODS: Inflammatory biomarkers in urine were measured using a cytometric bead array [interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ, soluable tumor necrosis factor receptor (TNFR) 1, sTNFR2, monocyte chemoattractant protein-1/chemokine ligand 2 (MCP-1/CCL2), eotaxin/CCL11 and interferon gamma-induced protein/10/C-X-C motif chemokine 10 (IP-10/CXCL10)] and ELISA assays [TNF, IL-8/CXCL8 and transforming growth factor-beta (TGF-ß)]. The Mann-Whitney test was used to compare medians. Markers of glomerular (creatinine) and tubular [beta 2 (ß2)-microglobulin, uromodulin, osmolality] functions were correlated with inflammatory biomarkers (Spearman test). RESULTS: An intense inflammatory profile was identified, with significantly increased concentrations of urinary IL-2, IL-4, IL-6, TNF, sTNFRI, sTNFRII, IFN-γ, MCP-1/CCL2, eotaxin/CCL11 and IL-8/CXCL8 in the PUV group compared to the controls. The same was observed for the anti-inflammatory cytokine IL-10 and for the fibrogenic mediator TGF-ß. In the correlation analysis, ß2-microglobulin positively correlated with the presence of MCP-1/CCL2, sTNFRI and eotaxin/CCL11 and negatively correlated with the presence of creatinine. CONCLUSIONS: This study shows that inflammatory molecules are already increased in fetuses with PUV at the mean gestational age of 22 weeks, suggesting a physiopathological role for inflammation just after the embryological formation of the urethral membrane.

Serum levels of interleukin-33 and its soluble form receptor (sST2) are associated with cognitive performance in patients with schizophrenia.

OBJECTIVE: Changes in immune system have been reported in schizophrenia. This study aimed to evaluate the involvement of IL-33, a member of the IL-1 cytokine family, in schizophrenia and its association with cognitive performance in these patients. METHODS: Forty patients with chronic schizophrenia and 40 healthy subjects participated in the study. Serum levels of IL-33 and sST2 (soluble form of the IL-33 receptor) were measured using enzyme-linked immunosorbent assay (ELISA). Patients were evaluated with the Brief Assessment of Cognition in Schizophrenia (BACS) and the Schizophrenia Cognition Rating Scale (SCoRS). RESULTS: Patients with schizophrenia and controls presented similar serum levels of IL-33 and sST2. Levels of both markers were positively correlated with cognitive performance in patients with schizophrenia. CONCLUSION: We found a significant correlation between IL-33 and sST2 levels and cognition in schizophrenia. Our results might help in the understanding of how immune markers are associated with cognitive impairment in schizophrenia. It remains to be determined whether the association between IL-33/sST2 and cognition is restricted to patients with schizophrenia.

Negative impact of high cumulative glucocorticoid dose on bone metabolism of patients with myasthenia gravis.

This current study aimed to evaluate the frequency of low bone mass, osteopenia, and osteoporosis in patients with myasthenia gravis (MG) and to investigate the possible association between bone mineral density (BMD) and plasma levels of bone metabolism markers. Eighty patients with MG and 62 controls BMD were measured in the right femoral neck and lumbar spine by dual-energy X-ray absorptiometry. Plasma concentrations of osteocalcin, osteopontin, osteoprotegerin, tumor necrosis factor (TNF-α), interleukin (IL)-1ß, IL-6, dickkopf (DKK-1), sclerostin, insulin, leptin, adrenocorticotropic hormone, parathyroid hormone, and fibroblast growth factor (FGF-23) were analyzed by Luminex®. The mean age of patients was 41.9 years, with 13.5 years of length of illness, and a mean cumulative dose of glucocorticoids 38,123 mg. Patients had significant reduction in BMD of the lumbar, the femoral neck, and in the whole body when compared with controls. Fourteen percent MG patients had osteoporosis at the lumbar spine and 2.5% at the femoral neck. In comparison with controls, patients with MG presented lower levels of osteocalcin, adrenocorticotropic hormone, parathyroid hormone, sclerostin, TNF-α, and DKK-1 and higher levels of FGF-23, leptin, and IL-6. There was a significant negative correlation between cumulative glucocorticoid dose and serum calcium, lumbar spine T-score, femoral neck BMD, T-score, and Z-score. After multivariate analysis, higher TNF-α levels increased the likelihood of presenting low bone mass by 2.62. MG patients under corticotherapy presented low BMD and altered levels of bone markers.

Urinary Levels of IL-1ß and GDNF in Preterm Neonates as Potential Biomarkers of Motor Development: A Prospective Study.

Objectives. To evaluate the association between inflammatory biomarkers, neurotrophic factors, birth conditions, and the presence of motor development abnormalities in preterm neonates. Methods. Plasma and urinary levels of cytokines (IL-1ß, IL-6, IL-10, TNF, and IL-12p70), chemokines (CXCL8/IL-8, CCL2/MCP-1, CCL5/RANTES, CXCL10/IP-10, and CXCL9/MIG), and neurotrophic factors (BDNF and GDNF) were evaluated in 40 preterm neonates born between 28 and 32 incomplete weeks of gestation, at four distinct time points: at birth (umbilical cord blood) (T0), at 48 (T1), at 72 hours (T2), and at 3 weeks after birth (T3). Biomarkers levels were compared between different time points and then associated with Test of Infant Motor Performance (TIMP) percentiles. Results. Maternal age, plasma, and urinary concentrations of inflammatory molecules and neurotrophic factors were significantly different between groups with normal versus lower than expected motor development. Higher levels of GDNF were found in the group with lower than expected motor development, while IL-1ß and CXCL8/IL-8 values were higher in the group with typical motor development. Conclusion. Measurements of cytokines and neurotrophic factors in spot urine may be useful in the follow-up of motor development in preterm neonates.

Peripheral leukocyte profile in people with temporal lobe epilepsy reflects the associated proinflammatory state.

INTRODUCTION: Markers of low-grade peripheral inflammation have been reported amongst people with epilepsy. The mechanisms underlying this phenomenon are unknown. We attempted to characterize peripheral immune cells and their activation status in people with temporal lobe epilepsy (TLE) and healthy controls. METHODS AND RESULTS: Twenty people with TLE and 19 controls were recruited, and peripheral blood lymphocyte and monocyte subsets evaluated ex vivo by multi-color flow cytometry. People with TLE had higher expression of HLA-DR, CD69, CTLA-4, CD25, IL-23R, IFN-γ, TNF and IL-17 in CD4(+) lymphocytes than controls. Granzyme A, CTLA-4, IL-23R and IL-17 expression was also elevated in CD8(+) T cells from people with TLE. Frequency of HLA-DR in CD19(+) B cells and regulatory T cells CD4(+)CD25(+)Foxp3(+) producing IL-10 was higher in TLE when compared with controls. A negative correlation between CD4(+) expressing co-stimulatory molecules (CD69, CD25 and CTLA-4) with age at onset of seizures was found. The frequency of CD4(+)CD25(+)Foxp3(+) cells was also positively correlated with age at onset of seizures. CONCLUSION: Immune cells of people with TLE show an activation profile, mainly in effector T cells, in line with the low-grade peripheral inflammation.