Exploring the Link between Inflammatory Biomarkers and Adipometrics in Healthy Young Adults Aged 20-35 Years.

Obesity and aging are associated with an inflammatory state, which represents the common background for a wide range of diseases. This study aims to explore the correlation between hsCRP, IL-1ß, IL-6, TNF-α, IFN-γ, and white blood cell count (WBC) and adipometrics (arm, waist, and hip circumferences: AC, WC, HC; total body fat mass: TBFM, visceral fat level: VFL, body mass index: BMI; waist/hip ratio: WHR; waist/height ratio: WHtR) in young and healthy adults aged 20-35 years old. The subjects were divided by BMI into the overweight/obesity (OW/OB) group and normal weight (NW) group, and by hsCRP level into Group 1 (<1 mg/L), Group 2 (≥1-2.99 mg/L), and Group 3 (≥3 mg/L). The concentration of all inflammatory biomarkers was significantly higher in the OW/OB group compared to the NW group, with the exception of IL-1ß. Significant positive correlations were found between hsCRP, TNF-α, WBC, and all adipometrics; between IL-6 and WHR, WHtR, BMI, TBFM, and VFL; and between IFN-γ and HC, BMI, and TBFM. IL-1ß correlates positively with WHR and VFL. In Groups 1-3, all the differences between the adipometrics showed significant differences. Subclinical inflammation persists in association with being overweight and obese in healthy young adults aged 20-35 years old.

Serum tau protein and myelin basic protein in pediatric patients with congenital heart defects undergoing cardiac surgery: preliminary assessment as novel neuromarkers of brain injury.

INTRODUCTION: Neurological impairment is a big concern in the development of patients with congenital heart defects (CHD). A number of neuromarkers have been studied in search of a diagnostic or prognostic marker for brain injury during the vulnerable perioperative period. Our aim was to assess two novel neuromarkers, myelin basic protein (MBP) and protein Tau (pTau), as diagnostic markers for brain injury in perioperative period in children with CHD. METHODS: Forty patients were enrolled and dichotomized based on peripheric oxygen saturation in cyanotic and non-cyanotic group. Blood samples were collected preoperative, after the induction of anesthesia, and in postoperative day 1. Neuromarker concentrations were measured using commercially available ELISA kits. RESULTS: Neuromarkers' values were increased postoperative, with statistical significance reached only in non-cyanotic group (p < 0.0001). A significant positive correlation was observed between preoperatory MBP and albumin level, hemoglobin level, height, and weight of patients. Association with cerebral saturations were analyzed by a coefficient defined as ≥ 20% reduction in cerebral saturation measured by near-infrared spectroscopy during perioperative period. An acceptable predicting model was observed with pTau in cyanotic group (AUC = 0.7). CONCLUSION: We evaluated MBP and pTau as potential biomarkers of brain injury in children with CHD undergoing cardiac surgery. Elevated postoperative pTau and MBP concentrations were observed in both groups. Elevated pTau values were associated with perioperative hypoxemia.

Serum Markers of Brain Injury in Pediatric Patients with Congenital Heart Defects Undergoing Cardiac Surgery: Diagnostic and Prognostic Role.

Introduction: The objectives of this study were to assess the role of neuromarkers like glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF), protein S100 (pS100), and neuron-specific enolase (NSE) as diagnostic markers of acute brain injury and also as prognostic markers for short-term neurodevelopmental impairment. Methods: Pediatric patients with congenital heart defects (CHDs) undergoing elective cardiac surgery were included. Neurodevelopmental functioning was assessed preoperatively and 4-6 months postoperatively using the Denver Developmental Screening Test II. Blood samples were collected preoperatively and postoperatively. During surgery, regional cerebral tissue oxygen saturation was monitored using near-infrared spectroscopy (NIRS). Results: Forty-two patients were enrolled and dichotomized into cyanotic and non-cyanotic groups based on peripheric oxygen saturation. Nineteen patients (65.5%) had abnormal developmental scores in the non-cyanotic group and eleven (84.6%) in the cyanotic group. A good diagnostic model was observed between NIRS values and GFAP in the cyanotic CHD group (AUC = 0.7). A good predicting model was observed with GFAP and developmental scores in the cyanotic CHD group (AUC = 0.667). A correlation was found between NSE and developmental quotient scores (r = 0.09, p = 0.046). Conclusions: From all four neuromarkers studied, only GFAP was demonstrated to be a good diagnostic and prognostic factor in cyanotic CHD patients. NSE had only prognostic value.

The peripheral profile of the chitinase 3-like-1 in benign multiple sclerosis - a single centre's experience.

BACKGROUND: A limited subgroup of multiple sclerosis (MS) patients present with a long-term disease evolution characterized by a limited disease progression, known as benign MS (BMS). Chitinase 3-like-1 (CHI3L1) levels are sensitive to inflammatory processes and may play a role in the pathogenesis of MS. In this observational, cross-sectional study, we aimed to evaluate the implications of serum CHI3L1 and inflammatory cytokines in BMS patients treated with interferon ß-1b for over a decade. METHODS: We collected serum samples from 17 BMS patients and 17 healthy controls (HC) to measure serum CHI3L1 levels and a Th17 panel of inflammatory cytokines. Serum levels of CHI3L1 were analysed using the sandwich ELISA method and the Th17 panel was assessed using the multiplex XMap technology on a Flexmap 3D Analyzer. RESULTS: Serum CHI3L1 levels did not differ significantly from HC. We identified a positive correlation between CHI3L1 levels and relapses during treatment. CONCLUSIONS: Our findings suggest that there are no differences in serum CHI3L1 levels between BMS patients and HC. However, serum CHI3L1 levels are sensitive to clinical inflammatory activity and may be associated with relapses in BMS patients.

A Comprehensive Summary of the Current Understanding of the Relationship between Severe Obesity, Metabolic Syndrome, and Inflammatory Status.

At present, obesity, as a part of metabolic syndrome, represents the leading factor for disability, and is correlated with higher inflammation status, morbidity, and mortality. The purpose of our study is to add new insights to the present body of knowledge regarding the correlations between chronic systemic inflammation and severe obesity, which cannot be treated without considering other metabolic syndrome conditions. Biomarkers of high-level chronic inflammation are recognized as important predictors of pro-inflammatory disease. Besides the well-known pro-inflammatory cytokines, such as WBCs (white blood cells), IL-1 (interleukin-1), IL-6 (interleukin-6), TNF-alpha (tumor necrosis factor-alpha), and hsCRP (high-sensitivity C-reactive protein), as well as anti-inflammatory markers, such as adiponectin and systemic inflammation, can be determined by a variety of blood tests as a largely available and inexpensive inflammatory biomarker tool. A few parameters, such as the neutrophil-to-lymphocyte ratio; the level of cholesterol 25-hydroxylase, which is part of the macrophage-enriched metabolic network in adipose tissue; or levels of glutamine, an immune-metabolic regulator in white adipose tissue, are markers that link obesity to inflammation. Through this narrative review, we try to emphasize the influence of the weight-loss process in reducing obesity-related pro-inflammatory status and associated comorbidities. All data from the presented studies report positive results following weight-loss procedures while improving overall health, an effect that lasts over time, as far as the existing research data show.

Cytokine Secretion Dynamics of Isolated PBMC after Cladribine Exposure in RRMS Patients.

Cladribine (CLD) treats multiple sclerosis (MS) by selectively and transiently depleting B and T cells with a secondary long-term reconstruction of the immune system. This study provides evidence of CLD's immunomodulatory role in peripheral blood mononuclear cells (PBMCs) harvested from 40 patients with untreated relapsing-remitting MS (RRMS) exposed to CLD. We quantified cytokine secretion from PBMCs isolated by density gradient centrifugation with Ficoll−Paque using xMAP technology on a FlexMap 3D analyzer with a highly sensitive multiplex immunoassay kit. The PBMC secretory profile was evaluated with and without CLD exposure. PBMCs isolated from patients with RRMS for ≤12 months had significantly higher IL-4 but significantly lower IFN-γ and TNF-α secretion after CLD exposure. PBMCs isolated from patients with RRMS for >12 months had altered inflammatory ratios toward an anti-inflammatory profile and increased IL-4 but decreased TNF-α secretion after CLD exposure. CLD induced nonsignificant changes in IL-17 secretion in both RRMS groups. Our findings reaffirm CLD's immunomodulatory effect that induces an anti-inflammatory phenotype.

Treatment With Cladribine Selects IFNγ+IL17+ T Cells in RRMS Patients - An In Vitro Study.

Background: Multiple sclerosis (MS) is an incurable autoimmune disease mediated by a heterogeneous T cell population (CD3+CD161+CXCR3-CCR6+IFNγ-IL17+, CD3+CXCR3+CCR6+IFNγ+IL17+, and CD3+CXCR3+IFNγ+IL17- phenotypes) that infiltrates the central nervous system, eliciting local inflammation, demyelination and neurodegeneration. Cladribine is a lymphocyte-depleting deoxyadenosine analogue recently introduced for MS therapy as a Disease Modifying Drug (DMD). Our aim was to establish a method for the early identification and prediction of cladribine responsiveness among MS patients. Methods: An experimental model was designed to study the cytotoxic and immunomodulatory effect of cladribine. T cell subsets of naïve relapsing-remitting MS (RRMS) patients were analyzed ex vivo and in vitro comparatively to healthy controls (HC). Surviving cells were stimulated with rh-interleukin-2 for up to 14days. Cell proliferation and immunophenotype changes were analyzed after maximal (phorbol myristate acetate/ionomycin/monensin) and physiological T-cell receptor (CD3/CD28) activation, using multiparametric flow cytometry and xMAP technology. Results: Ex vivo CD161+Th17 cells were increased in RRMS patients. Ex vivo to in vitro phenotype shifts included: decreased CD3+CCR6+ and CD3+CD161+ in all subjects and increased CD3+CXCR3+ in RRMS patients only; Th17.1 showed increased proliferation vs Th17 in all subjects; CD3+IL17+ and CD3+IFNγ+IL17+ continued to proliferate till day 14, CD3+IFNγ+ only till day 7. Regarding cladribine exposure: RRMS CD3+ cells were more resistant compared to HC; treated CD3+ cells proliferated continuously for up to 14 days, while untreated cells only up to 7 days; both HC/RRMS CD3+CXCR3+ populations increased from baseline till day 14; in RRMS patients vs HC, IL17 secretion from cladribine-treated cells increased significantly, in line with the observed proliferation of CD3+IL17+ and CD3+IFNγ+IL17+ cells; in both HC/RRMS, cladribine led to a significant increase in CD3+IFNγ+ cells at day 7 only, having no further effect at day14. IFNγ and IL17 secreted in culture media decreased significantly from ex vivo to in vitro. Conclusions: CD3+ subtypes showed different responsiveness due to selectivity of cladribine action, in most patients leading to in vitro survival/proliferation of lymphocyte subsets known as pathogenic in MS. This in vitro experimental model is a promising tool for the prediction of individual responsiveness of MS patients to cladribine and other DMDs.

Fascin-1 and its role as a serological marker in prostate cancer: a prospective case-control study.

AIM: This study aims to investigate any modification of serological FSCN1 in prostate cancer patients compared with patients without neoplasia. MATERIAL & METHODS: Clinical data and blood specimens from patients with and without prostate cancer were obtained. A quantitative sandwich ELISA method was used to determine serological values of FSCN1. RESULTS: Although serum values of FSCN1 were dissimilar in the two cohorts of patients (6.90 vs 7.33 ng/ml), the difference was not statistically significant (p = 0.20). Serum values of FSCN1 stratified for Gleason score groups were not significantly distinguishable (p = 0.65). A negative correlation (rho = -0.331; p = 0.009) was reported between FSCN1 and age. CONCLUSION: Further studies are required to evaluate a possible diagnostic role of FSCN1 in prostate cancer.

Extended lipid profile in Romanian ischemic stroke patients in relation to stroke severity and outcome: a path analysis model.

INTRODUCTION: Our aim was to evaluate the extended lipid profile in ischemic stroke patients and the relationship with stroke type, severity and outcome. MATERIAL AND METHODS: We prospectively enrolled 124 ischemic stroke patients and 40 healthy controls; baseline plasma and erythrocyte membrane fatty acids concentrations and common lipid profile were analysed. Stroke severity was evaluated by NIHSS on admission, while the functional outcome was defined by mRS at discharge and after 3 months. RESULTS: Total cholesterol, triglycerides, HDL-cholesterol, DHA, adrenic, stearic and lauric acid were all lower in patients, taking into account that 87.7% of patients did not receive statins before admission. There was a different pattern in plasma and erythrocyte membrane of fatty acids between patients and controls, also omega-3 index was significantly lower in patients. Patients with poor outcome without statins had significantly lower triglyceride (p = 0.028), while the total cholesterol levels were significantly lower in patients with poor outcome (p = 0.03) but with treatment initiated after admission. Bivariate analysis revealed that patients with poor outcome had significantly lower triglyceride levels regardless the statins use, while the total cholesterol and HDL-cholesterol levels were significantly lower in patients with poor outcome under statin treatment. The long-term outcome were positively influenced by age (ß̂ = 0.22, p = 0.001), and NIHSS score at admission (ß̂ = 0.55, p < 0.001), and negatively by cholesterol levels (ß̂ = -0.17, p = 0.031). CONCLUSIONS: DHA, adrenic, stearic and lauric acid were lower in stroke patients; plasma adrenic acid was consumed during the acute phase. The most important predictors for long-term outcome was NIHSS at admission followed by age and total cholesterol.

Gestational obesity and subclinical inflammation: The pathway from simple assessment to complex outcome (STROBE-compliant article).

ABSTRACT: Maternal obesity and excessive gestational weight gain (GWG) are associated with pregnancy-related complications, poor birth outcomes, and increased birth weight (BW).The aims of this study were to assess the relationship between excessive GWG and gestational inflammatory status in terms of blood parameters, as well as its influence on newborn's outcomes.We performed a prospective study on 176 pregnant women divided into 2 groups depending on the GWG: group 1-normal GWG, 80 cases; and group 2-high GWG, 96 cases. The statistical analysis was performed using the GraphPad Prism program, trial variant. We performed a thorough anamnesis and clinical examination in all mothers and their newborns, as well as an assessment of multiple laboratory parameters.The levels of both platelets and triglycerides were significantly higher in pregnant women from high GWG group (P = .0165/P = .0247). The newborns whose mothers presented an excessive GWG were found with a significantly higher BW as compared to those with normal GWG mothers (P = .0023). We obtained a positive correlation between the mothers' and newborns' values for hemoglobin, high-density lipoprotein, leucocytes, and platelets/lymphocytes ratio (P = .0002/P = .0313/P = .0137). Moreover, a significant positive correlation was found between GWG and BW (r = 0.2049, 95% CI: 0.0588-0.3425, P = .0064).Our findings sustain the hypothesis that maternal obesity is a risk factor for macrosomia and childhood obesity since we found a positive correlation between GWG and BW. Women with high GWG expressed significantly higher levels of platelets and triglycerides suggesting a subclinical inflammation associated to excessive fat accumulation. The inflammation transfer from mother to fetus in our study was suggested by the positive correlations between maternal and neonatal leukocytes and platelets/lymphocytes ratio.

The gap between overweight and obesity status in children - (STROBE-compliant article).

ABSTRACT: Overweight might represent only the early stage of obesity or it might act as a trigger of self-awareness turning into an ideal chance for preventing further obesity development.The aim of this study was to assess the differences between overweight and obese children in terms of anthropometric, low-grade systemic inflammation, liver impairment and atherosclerotic risk.We performed a study on 132 children aged between 5 and 18 years, divided according to the BMI into 2 groups: group 1 to 76 obese children, and group 2 to 56 overweight children, assessing anthropometric, laboratory and elastography parameters.We obtained significantly higher values of anthropometric parameters in obese children versus overweight ones. We found higher levels of leukocytes, lymphocytes, AST, ALT, and E median (P = .0345, P = .0103, P < .0001, P = .0008 and P < .0001) in the obese group as compared to the overweight one. BMI was positively correlated with neutrophils, NLR, ESR, glycemia, anthropometric parameters, and E median (P = .0007/<.0001/.0018/.0044/<.0001/<.0001/<.0001/<.0001/<.0001/.0204); and negatively with lymphocytes and HDL-cholesterol (r = -0.2747/-0.2181, P = .0116/.0120).Our study underlined significant differences between overweight and obese children in terms of inflammatory status and liver impairment suggesting that the risk is directly related to the increase in BMI.

Systemic inflammatory status - a bridge between gestational weight gain and neonatal outcomes (STROBE-compliant article).

ABSTRACT: Pregnant women with excessive gestational weight gain express an inflammatory status with multiple negative effects on birth outcomes.The aim of this study was to identify the relationship between gestational weight gain at different gestational ages and inflammatory status in pregnant women and their newborns assessing both interleukin 6 and 8, as well as hepcidin in these couples.Our study included 170 pregnant women and their newborns. Pregnant women were clinically assessed at the end of the 1st trimester and at term, whereas the newborns were assessed over the first 3 days of life. The levels of interleukin 6, 8 and hepcidin were measured in both pregnant women and their newborns.We noticed higher levels of interleukin 6, interleukin 8 and hepcidin in pregnant women at the time of delivery as compared to the end of the 1st trimester. We observed a direct significant correlation between gestational weight gain at the time of delivery and interleukin 8 in both mothers [r = 0.1834, 95% CI: 0.0293-0.3290, (P = .0167)] and newborns [r = 0.1790, 95% CI: 0.0248-0.3249, (P = .0195)]. Our study underlined that a higher gestational weight gain resulted in a significantly higher birth weight [r = 0.2190, 95% CI: 0.0663-0.3617, (P = .0041)].Our findings suggest that interleukin 8 might be an important indicator of inflammatory status in both mothers and newborns. Moreover, excessive gestational weight gain was associated with an increase in birth weight.

Plasma RBP4 Level in Association with Body Composition, Metabolic Profile, STRA6 and RBP4 Gene Polymorphisms in Obese Romanian Children.

BACKGROUND: Pediatric obesity continues to remain a serious health concern which has significantly increased the morbidity risk in adulthood. Recent studies have analyzed the impact of the two adipokines, RBP4 (retinol binding protein 4) and STRA6 (stimulated by retinoic acid 6) in pediatric obese subjects with contradictory results. METHODS: An observational study was conducted in the Pediatric and Endocrinology Departments, Targu-Mures, Romania, including 213 children between 5-17 years of age, divided into two groups according to body mass index (BMI) standard deviation score (SDS): case (overweight or obese) and control (normal SDS). Age, sex, basic anthropometric and biochemical measurements and genotype of rs3758539, and rs10882280 for RBP4 gene and rs974456 and rs351224 of STRA6 gene were analyzed. Statistical analysis used SPSS v. 25.0, with a level of significance α = 0.05. RESULTS: There is no association between the two gene's polymorphisms and obesity in our pediatric population. In regression analysis, with HOMA IR (homeostatic model assessment of insulin resistance) as the outcome, the plasmatic level of RBP4 and fat mass percentage are significant predictors, with the model explaining 42% of the HOMA variability. Hypercholesterolemia was significantly associated with male sex, carrying variant allele and heterozygote status of rs10882280 RBP4 gene and wild-type allele rs351224 of STRA6 gene. CONCLUSION: There is no significant association between obesity and SNPs of the RBP4 and STRA6 in our population, but they seem to play a role in insulin resistance and hypercholesterolemia.

Clinical Immunological Correlations in Patients with Multiple Sclerosis Treated with Natalizumab.

Natalizumab (NAT) was the first disease modifying therapy used for the treatment of relapsing-remitting multiple sclerosis (MS) that was designed with a specific mechanism of action that targets an important step of the MS immunopathology, directly blocking the T lymphocyte intrusion in the central nervous system. Initially, it was considered that NAT carried no biological effects on the peripheral immune response. The purpose of our study was to assess the effects of NAT on the peripheral pro and anti-inflammatory cytokines and to reveal possible correlations between them and the clinical activity of the disease. We noticed a significant decrease in interleukin (IL)-17, tumor necrosis factor-alpha (TNF-α) and IL-31 serum levels in treated patients. The lack of relapses during the study was associated with low baseline IL-17 level. The patients that had an increase in the disability score during the study had significantly lower IL-17 and higher IL-1ß baseline levels. IL-17 can be used as a biomarker for disease activity but also for progression assessment in NAT treated patients. NAT has a far more complex mechanism compared to what was initially believed, besides modulating lymphocyte trafficking through the blood-brain barrier, it also changes the peripheral levels of pro and anti-inflammatory cytokines in MS patients.

Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression.

BACKGROUND: The goal of the study was to evaluate a potential role for tumor necrosis factor alpha (TNF-α) genetic variability as biomarker in sepsis. In particular, we aimed to determine if single nucleotide polymorphisms (SNPs) of TNF-α gene are associated with sepsis in terms of risk, severity and outcome. METHODS: We performed a prospective study on 163 adult critically ill septic patients (septic shock 65, sepsis 98, further divided in 40 survivors and 123 deceased) and 232 healthy controls. Genotyping of TNF-α SNPs (-308G/A, -238G/A, -376G/A and +489G/A) was performed for all patients and controls and plasma cytokine levels were measured during the first 24 h after sepsis onset. RESULTS: TNF-α +489G/A A-allele carriage was associated with significantly lower risk of developing sepsis and sepsis shock (AA+AG vs GG: OR = 0.53; p = 0.004; 95% CI = 0.34-0.82 and OR = 0.39; p = 0.003; 95% CI = 0.21-0.74, respectively) but not with sepsis-related outcomes. There was no significant association between any of the other TNF-α promoter SNPs, or their haplotype frequencies and sepsis or septic shock risk. Circulating TNF-α levels were higher in septic shock; they were not correlated with SNP genotype distribution; GG homozygosity for each polymorphism was correlated with higher TNF-α levels in septic shock. CONCLUSIONS: TNF-α +489G/A SNP A-allele carriage may confer protection against sepsis and septic shock development but apparently does not influence sepsis-related mortality. Promoter TNF-α SNPs did not affect transcription and were not associated with distinct sepsis, septic shock risk or outcomes.

Correlations of serum leptin and leptin resistance with depression and anxiety in patients with type 2 diabetes.

AIM: The associations of serum leptin/soluble leptin receptor (sObR) and leptin resistance with symptoms of depression and anxiety were investigated in patients with type 2 diabetes (T2D). METHODS: We report the results of two cross-sectional studies, performed 2 years apart, that included 216 and 237 T2D patients, respectively. Symptoms of depression and anxiety were assessed with specific questionnaires (Patient Health Questionnaire-9, Center for Epidemiologic Studies Depression Scale, and Generalized Anxiety Disorder-7, respectively). Laboratory data (including leptin and sObR) were collected, and free leptin index (FLI), as an estimate of leptin resistance, was calculated. One hundred forty patients had laboratory data available on both occasions, and were evaluated longitudinally. Simple and multiple correlations between depression/anxiety and parameters of interest were performed. RESULTS: In both studies, serum leptin levels were higher, whereas resting energy expenditure/leptin ratios were lower in T2D patients with depressive and moderate-severe anxiety symptoms. In the second study, patients with depressive symptoms had higher FLI and lower sObR levels, while those with moderate-severe anxiety only had higher FLI. Depression scores correlated with serum leptin (r = 0.29, [95%CI: 0.14-0.42]; r = 0.32, [95%CI: 0.18-0.45]) and FLI (r = 0.30, [95%CI: 0.15-0.43]; r = 0.32, [95%CI: 0.17-0.45]; P < 0.0001 for all). Multiple regression analyses identified leptin (ß = 0.167; t ratio = 1.98) and FLI (ß = 2.935, t ratio = 2.44) (P < 0.05 for both) as variables that significantly contributed to depressive symptoms. Depressive symptoms were present in significantly more patients with leptin levels in the highest versus the lowest quartiles on both evaluations (odds ratio: 5.98, 95%CI [1.76-20.32], P < 0.01). CONCLUSION: Depressive and moderate-severe anxiety symptoms were associated with high leptin concentrations and leptin resistance in T2D patients.

The role of interleukin-6 as an early predictor of sepsis in a murine sepsis model.

AIM: Evaluating the role of interleukin-6 (IL-6) as an early predictor of sepsis in a murine model. MATERIALS AND METHODS: The study divided 26 Wistar rats into two experimental groups in which sepsis was induced through the intraperitoneal injection of different Escherichia coli cultures [Group 1: Extended-spectrum beta-lactamase (ESBL)-producing culture and Group 2: Standardized ATCC35218 culture] and a control group. IL-6 levels were determined at 5 and 24 hours post-inoculation and immunohistochemistry (IHC) was performed on tissue samples from the sacrificed animals. RESULTS: Mean plasma IL-6 levels in Group 1 peaked at 5 hours [37.4 pg∕mL; standard deviation (SD) = 2.4 pg∕mL] and decreased at 24 hours (34 pg∕mL; SD=3.2 pg∕mL) after inoculation. IL-6 levels in Group 1 were elevated compared to Group 2, at 5 hours (33.7 pg∕mL; SD=3.3 pg∕mL; p=0.019) and non-significantly so at 24 hours (32.5 pg∕mL; SD=2.4 pg∕mL; p=0.233). The results did not show an increase over control levels at either 5 hours (37.6 pg∕mL; SD=3.4 pg∕mL) or 24 hours (40.8 pg∕mL; SD=2.9 pg∕mL) after inoculation. The IHC shows a varying degree of IL-6 expression across all organ types studied. No statistically significant correlations were found between the tissue level quantification of IL-6 and serum values at 24 hours in either group. CONCLUSIONS: For an early stage of infection/inflammation, serum levels of IL-6 are not correlated with tissue-level inflammation disproving a potential role of IL-6 as a very precocious diagnostic and predictor test. Accumulation of IL-6 in lung, kidney and spleen tissue can be observed from the beginning of inflammation.

The influence of Visfatin, RBP-4 and insulin resistance on bone mineral density in women with treated primary osteoporosis.

INTRODUCTION: The impact of the two adipokines, visfatin and retinol-binding protein 4 (RBP-4) on bone mineral density (BMD) has been analysed in various studies with conflicting results. Visfatin is highly expressed in visceral fat with stimulatory effect on osteoblast proliferation and inhibition on osteoclast formation, while RBP-4 acts as a transporter protein for retinol, associated with changes in insulin sensitivity, independent of obesity, with no consensus on its effect on bone metabolism. We evaluated the relationship between serum concentrations of visfatin, RBP-4, markers of insulin resistance and current BMD in treated postmenopausal osteoporosis (PO). METHODS: Demographics, previous treatment, metabolic status, anthropometry, serum Alkaline phosphatise (ALP), visfatin, RBP-4, the HOMA IR (homeostatic model assessment of insulin resistance) index and BMD were evaluated in 61 subjects with PO. Statistical analysis used SPSS v. 25.0, with a level of significance α = 0.05. Regression models were constructed to evaluate the relationship between adipokines and BMD, adjusting for covariates. RESULTS: In multilinear regression analysis, the strongest predictor for current BMD was a previous BMD, followed by ALP and age. RBP4 and HOMA IR were significant predictors, while visfatin had no significant effect. A significant correlation between body mass index (BMI) and BMD at the femoral neck was observed. ALP was negatively correlated with BMD and visfatin positively with RBP4. CONCLUSIONS: Data indicate a positive relationship between BMD and RBP-4, an inverse relationship between markers of insulin resistance, bone turn-over and current BMD. No significant effect of visfatin on BMD was observed.

Atrial electrical remodeling induced by chronic ischemia and inflammation in patients with stable coronary artery disease.

The pathophysiology of coronary artery disease (CAD) includes low-grade chronic inflammation. At its turn, inflammation is known to promote myocardial structural remodeling and to increase vulnerability to atrial arrhythmias. Meanwhile, the impact of chronic inflammation on the electrophysiological properties of the atria remains unknown. We aimed to evaluate the impact of low-grade chronic inflammation on atrial electrophysiology in patients with stable CAD undergoing elective coronary artery bypass grafting (CABG). Circulating levels of several inflammatory, angiogenesis, and endothelial dysfunction markers were determined 1 day before CABG in 30 consecutive CAD patients. Right atrial appendage samples were collected during the CABG procedure; action potential recordings were performed in six study patients using the microelectrode technique. Interleukin (IL)-1b (r = 1.00, P = 0.01), IL-6 (r = 0.98, P < 0.01), vascular endothelial growth factor (VEGF) (r = 0.98, P < 0.01), and hemoglobin (r = 0.98, P < 0.01) levels significantly positively correlated with the duration of atrial depolarization. Consequently, IL-6, VEGF, and hemoglobin (r = -0.86, P = 0.03 for all) levels significantly negatively correlated with the velocity of atrial depolarization. There was no significant correlation between any of the studied markers levels and any of the other parameters of the action potential (all P > 0.05). The present study is the first to demonstrate that in patients with stable CAD, chronic inflammation and ischemia are associated with pro-arrhythmic atrial electrical remodeling. These changes may contribute to the increased propensity to postoperative atrial arrhythmias seen in some of the patients undergoing CABG.