Assessment of EN-RAGE, sRAGE, and its isoforms: cRAGE, esRAGE in obese patients treated by moderate caloric restriction combined with physical activity conducted in hospital condition.

BACKGROUND: AGEs, their receptor (RAGE), and the extracellular newly identified receptor for AGEs product-binding protein (EN-RAGE) are implicated in the pathogenesis of inflammation. AIM: We analyzed serum EN-RAGE, soluble RAGE (sRAGE), and their isoforms: endogenous secretory - esRAGE and cleaved - cRAGE concentrations in lean controls (n = 74) and in patients with obesity (n = 71) treated for three weeks with moderate calorie restriction (CR) combined with physical activity in a hospital condition. METHODS: Using the ELISA method, serum sRAGE, esRAGE, and EN-RAGE were measured before and after CR. RESULTS: The serum level of sRAGE and esRAGE in patients with obesity was lower than that in non-obese individuals, contrary to cRAGE. EN-RAGE concentration was about three times higher in obese patients. Gradually, a rise in BMI resulted in sRAGE, esRAGE reduction, and EN-RAGE increase. The sRAGE concentration was sex-dependent, indicating a higher value in lean men. A moderate negative correlation was observed between BMI and all RAGE isoforms, whereas EN-RAGE displays a positive correlation. CR resulted in an expected decrease in anthropometric, metabolic, and proinflammatory parameters and EN-RAGE, but no RAGE isoforms. The ratio EN-RAGE/sRAGE was higher in obese humans than in control and was not modified by CR. CONCLUSION: Obesity decreases sRAGE and esRAGE and increases EN-RAGE concentration. Moderate CR and physical activity by decreasing inflammation reduces EN-RAGE but is insufficient to increase sRAGE and esRAGE to the extent observed in lean patients. EN-RAGE instead of sRAGE could be helpful to indicate a better outcome of moderate dietary intervention in obese subjects.

Treatment of ankylosing spondylitis with TNFα inhibitors does not affect serum levels of tryptophan metabolites.

The imbalance between the kynurenine and serotonin pathways can have serious consequences, e.g., depression. One of the factors leading to the imbalance between the pathways of tryptophan metabolism is inflammation. The aim of our study was to assess the impact of treatment with tumor necrosis factor-alpha (TNFα)-inhibitors on tryptophan metabolism in patients with ankylosing spondylitis (AS). Forty patients with AS (twenty-eight males, twelve females; mean age 40 ± 11 years), qualified to receive anti-TNF-α treatment, were prospectively assessed. As a control group, 20 healthy volunteers (7 males and 13 females, mean age 38 ± 5 years) were recruited from the general population. Patients underwent full clinical and biochemical assessment before and after 6 months of therapy. Disease activity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The presence of depressive disorders was assessed with Beck's Depression Inventory (BDI) scale. Serum concentrations of tryptophan, serotonin, kynurenine, and quinolinic acid were measured. The predominance of the kynurenine pathway in AS patients (compared to the control group) was demonstrated (p < 0.001). Surprisingly, no significant changes in serum levels of tryptophan and its metabolites in AS patients after treatment were found, despite clinical improvement. Moreover, the components of tryptophan metabolism did not correlate significantly with the clinical activity of AS, depression nor laboratory inflammatory markers. Probably some other factors influence the pathways of tryptophan metabolism in patients with ankylosing spondylitis.

The intensity of joint pain in relation to changes in serum TNFα during therapy with anti-TNFα inhibitors.

INTRODUCTION: Tumor necrosis factor-alpha (TNFα) inhibitors have significantly improved the outcomes of treatment for rheumatoid arthritis (RA). In the present study, we aimed to determine whether serum levels of TNFα during therapy with TNFα inhibitors do really reflect the disease activity and correspond to the intensity of pain experienced. MATERIALS AND METHODS: Thirty RA patients were examined before and after 12 weeks of routine therapy with TNFα inhibitors. Serum levels of TNFα were measured with a high-sensitivity immunoassay and related to patients' clinical and biochemical status. Disease activity was assessed by the modified disease activity score (DAS28). RESULTS: A median relative change in TNFα was 13%. The patients were stratified according to whether the relative change in serum TNFα after therapy was above or below this median value. The patients from both subgroups did not differ in baseline characteristics and response to therapy. However, the patients in whom serum TNFα increased after therapy above the median value had more tender joints after treatment than patients from the other group. Consequently, the number of tender joints after the treatment correlated with absolute TNFα concentrations at this time (r = 0.37; p = 0.049) and the magnitude of changes in serum TNFα correlated with a change in the number of tender joints (r = - 0.48; p = 0.008). CONCLUSIONS: Circulating TNFα levels did not decrease in RA patients treated with TNFα inhibitors, despite clinical and biochemical improvement. It is possible, that circulating TNFα is responsible for the persistence of joint pain in this group of patients.

Amaranth (Amaranthus cruentus L.) and canola (Brassica napus L.) oil impact on the oxidative metabolism of neutrophils in the obese patients.

CONTEXT: Amaranth and canola oils have been used traditionally. Amaranth has been identified as being of interest because of its outstanding nutritive value. Amaranth oil is a rich source of highly unsaturated fats and so could be a valuable dietary alternative for individuals affected with obesity. Reactive oxygen species (ROS) are postulated to be involved in systemic inflammation and oxidative stress. Activated polymorphonuclear neutrophils (PMNs) generate high amounts of reactive oxygen species. OBJECTIVE: Our study investigates the impact of amaranth and canola oils supplementation on oxidative metabolism in patients with obesity. We hypothesized that, due to its lipid-lowering and antioxidant properties, amaranth and canola oil would protect against oxidative stress. MATERIALS AND METHODS: We tested 19 obese patients [body mass index (BMI) = 41.1 ± 7.8 kg/m2, (mean ± SD)]. The protocol consisted of two stages: a run-in phase of 2 weeks and an experimental stage - canola or amaranth oil supplementation (20 mL/d) with calorie restriction diet for 3 weeks. The neutrophil oxidative burst was expressed by fluorescence intensity (IF). RESULTS: The oxidative burst had increased significantly at the end of treatment in both groups IF: (21.4 ± 11.15 vs. 35.9 ± 20.3; mean ± SD) p < 0.05. The levels of IF were significantly higher in neutrophils of patients who received canola oil (41.05 ± 25.3) compared to those who received amaranth oil (28.4 ± 11.8) p < 0.05. CONCLUSIONS: Canola oil exerts possible effects on oxidative burst activity in neutrophils in vivo conditions.

Diagnostic value of salivary CRP and IL-6 in patients undergoing anti-TNF-alpha therapy for rheumatic disease.

INTRODUCTION: Saliva has been increasingly used as a diagnostic medium for disease detection and monitoring. The aim of this observational, prospective, pilot study was to investigate whether salivary concentrations of CRP and IL-6 correlate with those in serum and with the clinical course of a rheumatic disease. MATERIALS AND METHODS: Nineteen patients with rheumatic disease newly scheduled for anti-TNFα therapy were included. Patients received anti-TNFα treatment (adalimumab, certolizumab, golimumab or infliximab) as per standard protocols. CRP and IL-6 were measured with high-sensitivity immunoassays before and after 12 weeks of therapy, according to standard regimens. The data were analyzed with nonparametric statistics. RESULTS: Concentrations of CRP in saliva correlated significantly with those in serum (R = 0.62; p < 0.0001) and decreased markedly after successful response to treatment. In patients with a limited response to treatment salivary CRP levels increased. In contrast to CRP, the salivary concentrations of IL-6 did not change significantly over the course of therapy and they did not correlate with serum IL-6 concentrations. Salivary levels of neither CRP nor IL-6 corresponded to parameters of oral health and hygiene. CONCLUSIONS: Salivary CRP but not IL-6 could be of potential use for monitoring the rheumatic disease activity.

Anti-inflammatory Activity and Phytochemical Profile of Galinsoga Parviflora Cav.

The objective of this study was to evaluate the usefulness of a hydroalcoholic extract from Galinsoga parviflora herb (GP) in some aspects of the endothelial cell function necessary for anti-inflammatory activity and wound healing and relate these to the GP phytochemical profile. This study demonstrated that the GP extract caused a dose-dependent reduction of IL-6 secretion on IL-1ß-stimulated endothelial cells. The IL-6 release was decreased to 33% ± 9% while this did not influence the IL-6 secretion without stimulation. Additionally, the GP extract exhibited an anti-hyaluronidase activity (IC50 = 0.47 mg/mL), which was evidently stronger than the positive control kaempferol (IC50 = 0.78 mg/mL) as well as a moderate and concentration-dependent, antioxidant activity. The results of the scratch assay showed that exposure of the endothelial cells to GP induced complete healing of the damage after 12 h of the study. The phytochemical profile of the extract was studied by using spectrophotometric (total amount of polyphenols and flavonoids) and UPLC (phenolic acids) methods. The main compound in the GP extract was a chlorogenic acid (2.00 ± 0.01 mg/g by UPLC). The total content of polyphenols was 98.30 ± 0.14 mg of chlorogenic acid equivalent/g of the dry herb and content of flavonoids amounted to 6.15 ± 0.41 mg quercetin equivalent/g of the dry herb. Moreover, the presence of flavonoids in G. parviflora was provided after their isolation and identification by spectroscopic methods. In conclusion, it demonstrated that application of GP in the treatment of skin lesions gives possibility of wound healing based on antioxidant, anti-inflammatory, and hyaluronidase-inhibiting activities of G. parviflora herb extract.

No effect of anti-TNF-α treatment on serum IL-17 in patients with rheumatoid arthritis.

INTRODUCTION: Interleukin 17 (IL-17) and CC-chemokine ligand 20 (CCL20) are increasingly implicated in the pathogenesis of rheumatoid arthritis (RA). A correlation has been reported to exist between serum levels of IL-17 and CCL20 and the disease activity. However, such an effect has not been universally demonstrated. The aim of the present study was to investigate if serum levels of IL-17 and/or CCL20 reflect the disease activity and response to anti-TNF-α therapy in patients with RA. MATERIAL AND METHODS: Twenty-two RA patients qualified to receive anti-TNF-α treatment were prospectively assessed before and after 12 weeks of therapy. Serum concentrations of IL-17 and CCL20 were measured with high-sensitivity immunoassays. Disease activity was assessed by the 28-joint disease activity score (DAS28). RESULTS: Twelve weeks of therapy resulted in a satisfactory therapeutic response in the majority (91%) of patients (reflected both by clinical and standard biochemical criteria). However, serum concentrations of IL-17 and CCL20 did not change significantly over the course of therapy Moreover, they did not correlate with the disease activity, patient characteristics, and their response to therapy. CONCLUSIONS: Serum levels of IL-17 and CCL20 do not reflect changes in the clinical and biochemical status that occur in patients undergoing anti-TNF-α treatment for RA. The lack of such an association indicates that IL-17 signalling is not affected by anti-TNF-α therapy and is thus not critically involved in the disease pathogenesis.

Serum adiponectin as a predictor of laboratory response to anti-TNF-α therapy in rheumatoid arthritis.

INTRODUCTION: While adiponectin is typically viewed as an anti-inflammatory mediator, such an activity of adiponectin in rheumatoid arthritis (RA) is not so obvious. In the present study we examined whether serum levels of adiponectin reflect the clinical phenotype of RA patients and/or correlate with severity of the disease and the response to anti-TNF-α therapy. MATERIAL AND METHODS: Twenty-one female RA patients qualified to receive anti-TNF-α treatment were prospectively assessed before and after 12 weeks of therapy. Patients underwent full clinical and biochemical assessment. Disease activity was assessed by the Modified Disease Activity Scores (DAS28). Serum concentrations of adiponectin were measured with an immunoassay. The individuals were divided into two subgroups according to whether their baseline serum adiponectin was below or above the median value. The subgroups did not differ in basic demographic, anthropometric, and clinical parameters. RESULTS: Anti-TNF-α treatment resulted in a significant clinical (DAS28) improvement in patients from both subgroups, but no significant differences between basal and post-treatment serum adiponectin concentrations were observed. However, patients with higher baseline adiponectin experienced a significant and more pronounced improvement in laboratory parameters of inflammation (ESR, CRP, neutrophil count, neutrophil-to-lymphocyte ratio). CONCLUSIONS: It is possible that adiponectin exerts systemic anti-inflammatory effects independently of the local activity of RA.

Thy-1+/- fibroblast subsets in the human peritoneum.

Fibrotic thickening of the peritoneum develops in patients receiving peritoneal dialysis (PD) for renal failure. For unknown reasons, however, in some patients it progresses to extensive fibrosis that compromises dialysis capacity of the peritoneum. It is increasingly clear that fibroblasts display large heterogeneity not only between but also within tissues. Differential surface expression of thymocyte differentiation antigen 1 (Thy-1) has been shown to identify functionally distinct fibroblast subsets in several organs. Here, we isolated Thy-1+/- subsets of human peritoneal fibroblasts (HPFB) and analyzed them in terms of profibrotic myofibroblast features. In healthy individuals, Thy-1+ cells constituted ~45% of the HPFB population found in the greater omentum but were not detected in the parietal peritoneum. When propagated in culture and compared with Thy-1- cells, omentum-derived Thy-1+ HPFB consistently displayed an increased expression of α-smooth muscle actin, collagen I, and transforming growth factor-ß1. They also showed greater proliferation capacity and enhanced contractile properties. The number of Thy-1+ HPFB increased significantly in PD patients and made up more than 70 and 95% of all HPFB found in the omentum and parietal peritoneum, respectively. These data indicate that the expansion of Thy-1+ fibroblasts may contribute to fibrotic thickening of the peritoneal membrane during PD.

Association of endothelial proliferation with the magnitude of weight loss during calorie restriction.

OBJECTIVES: Substantial weight loss through intense dietary regimens is thought to ameliorate endothelial dysfunction in obesity. It is less clear whether similar improvements can be achieved with modest dietary interventions. This study aimed to identify the parameters of endothelial cell status in obesity that are affected by mild calorie restriction. METHODS: Human umbilical vein endothelial cells (EA.hy926 line) in culture were exposed pairwise to serum from 57 individuals with simple obesity (BMI > 30 kg/m(2)) collected before and after 8-week dietary intervention with energy deficit of 300-500 kcal/day. RESULTS: Analysis of endothelial transcriptome suggested that the intervention could impact on endothelial cell growth. Cell proliferation was measured with the MTT test and verified by [(3)H]-thymidine incorporation. The participants were categorized according to a change in proliferation over time. Significant decrease in endothelial cell proliferation correlated with the extent of weight loss in men, but not in women. This effect corresponded with changes in serum levels of leptin and adiponectin, but was not related to serum concentrations of several known angiogenic mediators (VEGF, MCP-1, TSP-1, MMP-9, angiopoietin-2). CONCLUSION: Direction and magnitude of changes in serum-induced endothelial cell proliferation identifies patients with the greatest weight loss in response to modest calorie restriction.

Seasonal Influence on Salivary Myeloperoxidase Diurnal Variations in Young Healthy Subjects: A Preliminary Study.

BACKGROUND: The interaction between oxidative status markers and biological rhythms is considered particularly important in the pathogenesis of many diseases and more effective therapies. We aimed to determine if the salivary secretion of myeloperoxidase exhibits diurnal variations, and if the potential daily variability differs seasonally. METHODS: The study was performed in Poznan, Poland (52,25°N, 16,58°E) in 10 healthy male volunteers (age median 23.5 years). Whole mixed unstimulated saliva was collected in summer (August) and winter (December) during 36 h at 2-h intervals starting at 6 a.m. on Saturday and ending at 6 p.m. on Sunday, in the domestic setting. The samples were analysed for myeloperoxidase (MPO) and cortisol by immunoassays. The presence of the circadian rhythm of cortisol secretion in saliva confirmed the rhythmicity of the volunteers. RESULTS: For salivary MPO, significantly higher concentrations compared to midnight and noon were observed for 4 a.m. in both summer and winter. Using the cosinor analysis, the variations in salivary MPO levels showed a moderate fit for the 12-h period rhythm (acrophases: in summer 05:37/17:37, in winter 06:16/18:16), without significant differences in the rhythm parameters in summer and winter. However, higher self-reported Global Seasonal Score (which may predispose to seasonal affective disorder) was associated with significantly stronger relative amplitude (RS = 0.811) in winter season only. CONCLUSIONS: In conclusion, our findings suggest the possible ultradian rhythm for MPO in saliva, with two peaks during the day, regardless of the season.

Treatment regimens and disease activity could alter salivary myeloperoxidase levels in patients with inflammatory bowel diseases.

INTRODUCTION: Inflammatory bowel diseases (IBDs) present with alternating periods of exacerbation and remission; therefore, it is necessary to develop noninvasive diagnostic tools to control the disease activity and improve therapeutic effectiveness. Recently, we have found that patients with ulcerative colitis (UC) who qualified for biologic therapy had significantly lower salivary myeloperoxidase (MPO) levels. OBJECTIVES: This cross­sectional study aimed to assess the impact of IBD activity and applied treatment on salivary antioxidant system as reflected by the levels of catalase, total antioxidant status, and MPO. PATIENTS AND METHODS: The study group comprised 99 patients diagnosed with Crohn disease (CD) and 61 patients with UC. The Crohn Disease Activity Index and modified Mayo scale were used to estimate the clinical activity of CD and UC, respectively. Unstimulated whole mixed saliva was collected. Salivary levels of selected markers were measured with enzyme­linked immunosorbent assays and colorimetric assays. RESULTS: The patients with clinically active UC showed significantly decreased median (interquartile range) salivary MPO levels (79.4 [30.1-157.5] vs 94.8 [58.2-274.7] ng/ml) with significant correlations with the endoscopic stage on the Mayo scale (R = 0.423; P = 0.02). Receiver operating characteristic analysis confirmed a potential usefulness of MPO concentrations in predicting clinically active UC (area under the curve = 0.654; P = 0.03; cutoff <210.4 ng/ml). Moreover, in the patients treated with biologics and without steroid therapy, salivary MPO concentrations negatively correlated with neutrophil counts in the individuals with UC and positively with C­reactive protein level in the patients with CD. CONCLUSIONS: Salivary MPO levels changed depending on the disease activity in the patients with UC. Decreased MPO concentration in the saliva could be a predictor of clinically active UC.

Increased Myeloperoxidase Concentrations in Saliva could Reflect Increased Body Mass and Oral Microinflammation.

BACKGROUND: Increased myeloperoxidase (MPO) levels in saliva are thought to reflect ongoing periodontal inflammation. Less clear is whether and to what extent salivary MPO is increased as a result of systemic inflammation. METHODS: In the present study, we aimed to determine which demographic, anthropometric, biochemical, and dental parameters affect the level of MPO in whole mixed saliva in healthy adults with no apparent inflammatory lesions in the oral cavity. Thus, 113 individuals, aged 20-61 years (including 30.1% men and 23.9% smokers), were examined. RESULTS: In the univariate analysis, higher levels of MPO in saliva were found to be associated with age, an increased body mass index (BMI), higher levels of cytokines tumour necrosis factor-α and interleukin-6, as well as poorer oral hygiene, gingival status, and lower saliva flow. Multivariate logistic regression analysis determined that the main predictors of MPO concentration in saliva were BMI and stimulated saliva flow rate. CONCLUSIONS: Overall, an increase in MPO in saliva could be related to an increase in BMI, possibly as a result of subclinical chronic microinflammation, which also involves the gingiva.

Effect of the one-day fasting on cortisol and DHEA daily rhythm regarding sex, chronotype, and age among obese adults.

Introduction: Physiological and biochemical processes in the human body occur in a specific order and show rhythmic variability. Time dependence characterizes the secretion of cortisol and dehydroepiandrosterone (DHEA). One-day fasting implies alternating fasting days and eating days. The study aimed to determine how 24-h fasting affects the daily rhythm of cortisol and DHEA levels in obese people while taking into account gender and chronotype. Methods: Forty-nine obese patients (BMI 32.2-67.1 kg/m2; 25 women and 24 men) underwent a 3-week hospital-controlled calorie restriction diet to reduce body weight. During hospitalization, patients fasted for 1 day, during which only water could be consumed. Samples of whole mixed unstimulated saliva were collected at 2-3-h intervals over a 64-h period and analyzed for cortisol and DHEA by immunoassays. The individual chronotypes were assessed by the morning and evening questionnaire, according to Horne and Östberg. Three components of daily rhythm were evaluated: amplitude, acrophase, and the so-called MESOR. Results: Cortisol rhythm showed differences in amplitude (p = 0.0127) and acrophase (p = 0.0005). The amplitude on the fasting day was 11% higher (p = 0.224) than the day after. The acrophase advanced on the day of fasting, 48 min earlier than the day before (p = 0.0064), and by 39 min to the day after fasting (p = 0.0005). In the rhythm of DHEA, differences were found in the MESOR (p = 0.0381). The MESOR on the fasting day increased. Discussion: Our results obtained during 64 consecutive hours of saliva sampling suggest that one-day fasting may affect three components of cortisol and DHEA daily rhythm. Additionally, no differences were found in the daily rhythm between the morning and evening chronotypes and between females and males. Although aging did not influence daily cortisol rhythm, DHEA amplitude, MESOR, and acrophase changed with age. To the best of our knowledge, this is the first presentation of changes in DHEA rhythm during one-day fasting.

Nailfold Videocapillaroscopy for Non-Invasive Assessment of Microcirculation and Prognostic Correlation with Endothelial Dysfunction, Cardiovascular Risk Factors, and Non-HLA Antibodies in Heart Transplant Recipients: A Pilot Study.

Early identification of allograft vasculopathy and the concomitant elimination of adverse risk factors is essential for improving the long-term prognosis of heart transplant (HTx) recipients with underlying cardiovascular disease (CVD). The major aim of this pilot study was to conduct a non-invasive imaging evaluation of the HTx patient microcirculation by employing nailfold video-capillaroscopy (NVC) in a well-characterized patient and control cohort, and to correlate these data with endothelial cell function, accompanied by studies of traditional cardiovascular risk factors and non-HLA antibodies in HTx recipients. Ten patients undergoing HTx (mean age of 38 ± 14 years) were recruited for the study and compared to a control group of 12 well-matched healthy volunteers (mean age 35 ± 5 years) with normal body mass index (BMI). Detailed medical records were collected from all individuals. NVC was performed using CapillaryScope 200 MEDL4N microscope. For functional readout and correlation analysis, endothelial cell network formation in conjunction with measurements of patient serum levels of vascular endothelial growth factor (VEGF) and non-HLA autoantibodies directed against the angiotensin II type-1-receptor (anti-AT1R-Ab), endothelin-1 type-A-receptor (anti-ETAR-Ab), protease-activated receptor-1 (anti-PAR-1-Ab), and VEGF-A (anti-VEGF-A-Ab) were studied. Our NVC analysis found that the average apical loop diameter of nailfold capillaries was significantly increased in HTx recipients (p = 0.001). In addition, HTx patients with more prominent changes in capillaroscopic patterns were characterized by the presence of traditional cardiovascular risk factors, and HTx patients had increased levels of anti-AT1R-ab, anti-ETAR-ab, and anti-VEGF-A-Ab (p = 0.017, p = 0.025, and p = 0.003, respectively). Capillary diameters most strongly correlated with elevated serum levels of troponin T and triglycerides (R = 0.69, p = 0.028 and R = 0.81, p = 0.004, respectively). In conclusion, we found that an abnormal NVC pattern in HTx patients is associated with traditional CVD risk factors and that NVC is a useful non-invasive tool to conveniently monitor changes in the microvasculature of HTx patients.

Effect of Flaxseed (Linum usitatissimum L.) Supplementation on Vascular Endothelial Cell Morphology and Function in Patients with Dyslipidaemia-A Preliminary Observation.

CONTEXT: Flaxseed has a characteristic fatty acids composition and unique phytonutrient profile that may have health-promoting properties. OBJECTIVE: This study aimed to determine the effects of 10 weeks of supplementation with the flaxseed (28 g/day) on endothelial cells (EC) function, serum lipids and proinflammatory mediators in patients with mild and severe dyslipidaemia. MATERIALS AND METHODS: Eleven lean patients with severe dyslipidaemia treated with apheresis (group 1; 10 weeks treated in four phases: (i) ordinary diet, (ii) ordinary diet + flaxseed, (iii) ordinary diet (wash out), (iv) ordinary diet + placebo) and eleven obese patients with mild dyslipidaemia-not treated with apheresis (group 2; 10 weeks treated in two phases: (i) ordinary diet, (ii) low fat diet + flaxseed). Flaxseed was given blindly. Serum was collected at the end of each phase of the study. ECs were exposed in vitro to the medium supplemented with pooled serum taken from patients from both groups to detect their morphological changes using light and electron microscopy. ECs proliferation was also measured at the end of each study phase. RESULTS: Serum vascular endothelial growth factor was decreased after flaxseed supplementation but only in group 1. ECs proliferation was increased after flaxseed supplementation only in obese patients. ECs exposed to medium supplemented with obese patients' serum revealed the following cellular abnormalities: accumulation of lipid droplets, changes of rough endoplasmic reticulum and mitochondria, and flaxseed did not reverse observed changes. At the same time, flaxseed supplementation decreases total cholesterol in both tested groups, low-density lipoprotein cholesterol in group 1 and triglycerides in group 2. CONCLUSIONS: Our findings support the potential role of flaxseed in treating dyslipidaemia but indicate only a slight impact on endothelial cell function.

Non-HLA Antibodies in Hand Transplant Recipients Are Connected to Multiple Acute Rejection Episodes and Endothelial Activation.

The role of anti-HLA antibodies in transplant rejection is well-known but the injury associated with non-HLA antibodies is now widely discussed. The aim of our study was to investigate a role of non-HLA antibodies in hand allografts rejection. The study was performed on six patients after hand transplantation. The control group consisted of: 12 kidney transplant recipients and 12 healthy volunteers. The following non-HLA antibodies were tested: antibody against angiotensin II type 1 receptor (AT1R-Ab), antibody against endothelin-1 type-A-receptor (ETAR-Ab), antibody against protease-activated receptor 1 (PAR-1-Ab) and anti-VEGF-A antibody (VEGF-A-Ab). Chosen proinflammatory cytokines (Il-1, IL-6, IFNγ) were used to evaluate the post-transplant humoral response. Laboratory markers of endothelial activation (VEGF, sICAM, vWF) were used to assess potential vasculopathy. The patient with the highest number of acute rejections had both positive non-HLA antibodies: AT1R-Ab and ETAR-Ab. The same patient had the highest VEGF-A-Ab and very high PAR1-Ab. All patients after hand transplantation had high levels of laboratory markers of endothelial activation. The existence of non-HLA antibodies together with multiple acute rejections observed in patient after hand transplantation should stimulate to look for potential role of non-HLA antibodies in humoral injury in vascular composite allotransplantation.

Predictors of Early-Recurrence Atrial Fibrillation after Catheter Ablation in Women and Men with Abnormal Body Weight.

Our study aimed to select factors that affect the rate of early recurrence (up to 3 months) of atrial fibrillation (AF) (ERAF) following pulmonary veins isolation (PVI) in obese women and men. The study comprised 114 patients: 54 women (age: 63.8 ± 6.3, BMI 31 ± 4 kg/m2), and 60 men (age: 60.7 ± 6.7; BMI 31 ± 3 kg/m2) with paroxysmal, persistent and long-standing persistent AF. They had been scheduled to undergo cryoballoon (men n = 30; women n = 30) and radiofrequency (RF) ablation (men n = 30; women n = 24) using the CARTO-mapping. The blood was collected at baseline and 24 h after ablation. The rate of ERAF was comparable after cryoballoon and RF ablation and constituted 18% in women and 22% in men. Almost 70 parameters were selected to perform univariate and multivariate analysis and to create a multivariate logistic regression (MLR) model of ERAF in the obese men and women. The MLR analysis was performed by forward stepwise logistic regression with three variables. It was only possible to create the MLR model for the group of obese men. It revealed a poor predictive value with an unsatisfactory sensitivity of 31%. Men with ERAF: smokers (OR 39.25, 95% CI 1.050-1467.8, p = 0.0021), with a higher ST2 elevation (OR 1.68, 95% CI 1.115-2.536, p = 0.0021) who received dihydropyridine calcium channel blockers (OR 0.042, 95% CI 0.002-1.071, p = 0.0021) less frequently. Our results indicate a complex pathogenesis of ERAF dependent on the patients' gender.

Changes in Salivary Parameters of Oral Immunity after Biologic Therapy for Inflammatory Bowel Disease.

We previously observed that inflammatory bowel disease (IBD) may compromise oral host defense, as assessed by decreased salivary levels of immunoglobulin A (IgA) and myeloperoxidase (MPO). Biologic therapy with inhibitors of cytokines or adhesion molecules is increasingly used for patients with IBD. Little is known, however, about how this treatment modality affects the release and properties of saliva. Here, we aimed to determine how biologic therapy in patients who had not responded to previous standard treatment with conventional drugs affected the salivary concentration of IgA and MPO. To this end, unstimulated whole mixed saliva was collected before treatment or after 10-12 weeks of therapy from 27 patients with Crohn's disease (CD) and 24 patients with ulcerative colitis (UC). After the induction phase of therapy with biologics, salivary levels of IgA and MPO increased significantly in UC, but not in CD patients. These increases were approximately 8-fold and 6-fold, for IgA and MPO, respectively. Moreover, these effects occurred in UC patients who responded successfully to therapy, but not in those who failed to improve. Furthermore, the relative increases in salivary IgA and MPO correlated with the relative decrease in UC severity, as assessed by the Mayo scale. These data indicate that the successful therapy with biologics in UC patients results also in improved oral host defense. However, it remains to be determined why such an effect does not occur during therapy for CD.

Potential Salivary Markers for Differential Diagnosis of Crohn's Disease and Ulcerative Colitis.

The properties of the saliva of patients with inflammatory bowel disease (IBD) are poorly recognized. Likewise, the diagnostic potential of saliva for differentiating various forms of IBD is largely unexplored. Therefore, we compared the concentrations of several parameters in unstimulated whole mixed saliva collected in a standardized manner from patients with active IBD unresponsive to conventional therapy. The samples were received from 27 patients with Crohn's disease (CD), 24 patients with ulcerative colitis (UC), and 51 healthy individuals. Compared to the controls, the salivary concentrations of S100A8/calprotectin, myeloperoxidase, and IgA were significantly decreased in both CD and UC patients. In addition, patients with UC had decreased levels of TNF-R1 and decreased catalase activity. Interestingly, the concentrations of myeloperoxidase and TNF-R1 showed a high differentiation potential for CD and UC (AUC = 0.690 and 0.672, respectively). All these findings are discussed in the context of host defense in the oral cavity, patients' prior treatment regimens, and smoking habits.