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 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.

Antiangiogenic, Anti-Inflammatory and Antioxidant Properties of Bidens tripartite Herb, Galium verum Herb and Rumex hydrolapathum Root.

Plants are commonly used in folk medicine. Research indicates that the mechanisms of biological activity of plant extracts may be essential in the treatment of various diseases. In this respect, we decided to test the ethanolic extracts of Bidens tripartita herb (BTH), Galium verum herb (GVH), and Rumicis hydrolapathum root (RHR) on angiogenic, anti-inflammatory, and antioxidant properties and their total polyphenols content. In vitro studies using endothelial cells were used to see tested extracts' angiogenic/angiostatic and anti-inflammatory properties. The DPPH assay and FRAP analysis were used to detect antioxidant properties of extracts. The Folin-Ciocalteu analysis was used to determine the content of total polyphenols. The results of gas chromatography-mass spectrometry analysis was also presented. In vitro study demonstrated that BTH, GVH, and RHR ethanolic extracts significantly increased cell invasiveness, compared with the control group. Increased endothelial proangiogenic invasiveness was accompanied by reduced metalloproteinase inhibitor 1 (TIMP-1) and raised in metalloproteinase 9 (MMP-9). Only BTH and GVH significantly reduced cell proliferation, while BTH and RHR facilitated migration. Additionally, tested extracts reduced the production of proangiogenic platelet-derived growth factor (PDGF) and hepatocyte growth factor (HGF). The most potent anti-inflammatory capacity showed BTH and GVH, reducing proinflammatory interleukin 8 (CXCL8) and interleukin 6 (Il-6), compared to RHR extract that has slightly less inhibited CXCL8 production without affecting IL-6 production. Moreover, we confirmed the antioxidant properties of all examined extracts. The highest activity was characterized by RHR, which has been correlated with the high content of polyphenols. In conclusion, the modifying influence of examined extracts can be promising in disorders with pathogenesis related to angiogenesis, inflammation and free radicals formation. BTH is the best choice among the three tested extracts with its antiangiogenic and anti-inflammatory properties.

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 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.

Pleiotropic Potential of Evernia prunastri Extracts and Their Main Compounds Evernic Acid and Atranorin: In Vitro and In Silico Studies.

Evernia prunastri is a lichen widely distributed in the Northern Hemisphere. Its biological properties still need to be discovered. Therefore, our paper focuses on studies of E. prunastri extracts, including its main metabolites evernic acid (EA) or atranorin (ATR). Phytochemical profiles using chromatographic analysis were confirmed. The antioxidant activity was evaluated using in vitro chemical tests and in vitro enzymatic cells-free tests, namely superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT). The anti-inflammatory potential using cyclooxygenase-2 (COX-2) and hyaluronidase were determined. The neuroprotective potential using acetylcholinesterase, (AChE), butyrylcholinesterase (BChE), and tyrosinase (Tyr) was estimated. The hypoglycemic activity was also confirmed (α-glucosidase). Principal component analysis was performed to determine the relationship between the biological activity of extracts. The inhibitory effect of EA and ATR on COX-2 AChE, BChE, Tyr, and α-glucosidase was evaluated using molecular docking techniques and confirmed for EA and ATR (besides α-glucosidase). The penetration of EA and ATR from extracts through the blood-brain barrier was confirmed using the parallel artificial membrane permeability assay blood-brain barrier test. In conclusion, depending on chemical surroundings and the concentration, the E. prunastri extracts, EA or ATR, showed attractive pleiotropic properties, which should be further investigated.

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.

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.

No Significant Effect of the Individual Chronotype on the Result of Moderate Calorie Restriction for Obesity-A Pilot Study.

BACKGROUND: Chronotype is the pattern of the circadian rhythm that allows an individual to optimize times of sleep and activity. It has been observed that chronotypes may associate with some conditions and diseases, including obesity. It is not known, however, whether chronotypes determine the effectiveness of weight loss regimens. Therefore, in the present study, we compared the outcomes of a 3-week moderate calorie restriction undertaken by individuals with obesity under the same controlled hospital conditions. METHODS: A total of 131 participants with obesity (median BMI 40.0) were studied. The subjects underwent the same dietary intervention over 3 weeks, with a 30% reduction in daily caloric intake. The individual chronotypes were assessed by the morning and evening questionnaire (MEQ) according to Horne and Östberg. Anthropometric and biochemical parameters were assessed by routine methods. RESULTS: Of all patients examined, 75% had the morning (lark) chronotype and 25% had the evening (owl) chronotype. These patient sub-groups did not differ in terms of demographic, anthropometric and biochemical characteristics at baseline. After 3 weeks of calorie restriction, both groups experienced a similar loss of weight and BMI (Body Mass Index) (3.4 ± 0.38% for larks vs. 4.1 ± 0.47% for owls, p = 0.45), with owls exhibiting a marginally greater loss of body fat (3.1 ± 0.79%) compared with larks (2.6 ± 0.64%), p = 0.02. On the other hand, the larks had a more discernable, but not statistically significant from owls, decrease in glycated haemoglobin and CRP (C Reactive Protein). CONCLUSIONS: The chronotype of individuals with obesity does not have a significant effect on the magnitude of the body weight loss, but there is a tendency observed towards the reduction in body fat content in owls through changing their meal and sleep timing to earlier hours, in response to moderate calorie restriction applied under the same controlled conditions.

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.

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.

Moderate Caloric Restriction Partially Improved Oxidative Stress Markers in Obese Humans.

Oxidative stress and inflammation are implicated in obesity. Therefore, we investigated whether moderate and short-term calorie restriction (CR) reflects a real-life situation, mediates weight loss, and improves oxidative stress markers. We analyzed oxidative stress markers in patients with obesity undergoing moderate CR. Serum oxidative stress markers (myeloperoxidase (MPO), superoxide dismutase (SOD), catalase, total antioxidant status (TAS), and reactive oxygen species (ROS) (generation by endothelial cells in vitro)) were measured in 53 subjects (mean BMI 37.8 ± 5.9 kg/m2) who underwent 8 weeks of CR, which included a reduction of 300-500 kcal/day. MPO was the most CR-sensitive parameter. The mean level of serum MPO in patients with obesity was 20% higher than that in post CR intervention (p < 0.001). SOD increased by 12% after CR (p < 0.05), which was largely due to the improvement in glucose tolerance and the reduction in insulin resistance after CR. Other tested parameters were not modified during the treatment. CR resulted in an expected decrease in body weight (by 5.9 ± 4.6 kg, p < 0.0001) and other anthropometric parameters. Additionally, it was accompanied by a significant change in hsCRP, hsTNF alpha, hsIL-6, leptin (all p < 0.0001), and HOMA-IR (p < 0.05). Cardiovascular and metabolic parameters were also partially improved. Short-term, moderate CR partially improves antioxidant capacity but is enough to substantially change anthropometric parameters in obese patients. Our observations indicate that mimicking real-life situations and low-cost dietary intervention can be successfully implemented in obesity treatment with a simultaneous moderate effect on antioxidant status.

Transcriptional Regulation of Thrombin-Induced Endothelial VEGF Induction and Proangiogenic Response.

Thrombin, the ligand of the protease-activated receptor 1 (PAR1), is a well-known stimulator of proangiogenic responses in vascular endothelial cells (ECs), which are mediated through the induction of vascular endothelial growth factor (VEGF). However, the transcriptional events underlying this thrombin-induced VEGF induction and angiogenic response are less well understood at present. As reported here, we conducted detailed promotor activation and signal transduction pathway studies in human microvascular ECs, to decipher the transcription factors and the intracellular signaling events underlying the thrombin and PAR-1-induced endothelial VEGF induction. We found that c-FOS is a key transcription factor controlling thrombin-induced EC VEGF synthesis and angiogenesis. Upon the binding and internalization of its G-protein-coupled PAR-1 receptor, thrombin triggers ERK1/2 signaling and activation of the nuclear AP-1/c-FOS transcription factor complex, which then leads to VEGF transcription, extracellular secretion, and concomitant proangiogenic responses of ECs. In conclusion, exposure of human microvascular ECs to thrombin triggers signaling through the PAR-1-ERK1/2-AP-1/c-FOS axis to control VEGF gene transcription and VEGF-induced angiogenesis. These observations offer a greater understanding of endothelial responses to thromboinflammation, which may help to interpret the results of clinical trials tackling the conditions associated with endothelial injury and thrombosis.

Abnormal Nailfold Capillaries in Patients after Hand Transplantation.

BACKGROUND: The development of graft vasculopathy may play a role in the long-term deterioration of hand grafts. The aim of study was to examine the patterns of the nailfold capillaries in hand transplant recipients. METHODS: the study was performed on six patients who received hand transplantation. To normalize for the effect of immunosuppression an age- and sex-matched group of 12 patients with active kidney transplant was selected. As an additional control group, 12 healthy volunteers were recruited. Nailfold videocapillaroscopy was performed in all participants. Additionally, serum concentrations of vascular endothelial growth factor (VEGF) were measured. RESULTS: Videocapillaroscopic examination of the hand allografts revealed significant abnormalities: including capillary disorganization and microhaemorrhages. The number of capillaries was reduced, the vessels were enlarged and branched. Surprisingly, similar, albeit slightly less pronounced, changes were seen in the nailfolds of healthy hands of the limb transplant recipients. In kidney transplant recipients the capillaroscopic pattern was general normal and comparable to healthy individuals. Moreover, serum concentrations of VEGF in all participants correlated with average capillary diameter in capillaroscopy. CONCLUSIONS: in hand transplant recipients advanced microvascular abnormalities are found in nailfold capillaroscopic pattern in both transplanted and own extremities connected with elevated levels of VEGF.

Poor Oral Hygiene and High Levels of Inflammatory Cytokines in Saliva Predict the Risk of Overweight and Obesity.

The study aimed to determine if oral hygiene influences not only oral health but also potentially metabolic disorders such as overweight or obesity. Participants were 94 patients: 40 with increased body mass and 54 with normal body mass. The methods included dental examination, a questionnaire concerning hygienic habits and an assessment of selected salivary inflammatory markers. The new parameter named "cleaning index" (describing the interaction between average time of tooth brushing in minutes and its frequency per day) significantly correlated with Body Mass Index (RSpearman = 0.300). The multivariate regression model incorporating cleaning index, approximal plaque index, receptor 1 for tumor necrosis factor-alpha (TNFα-R1) and interleukin-15 (IL-15) had a high power to predict overweight or obesity (AUC = 0.894). Patients with poor oral hygiene (approximal plaque index >40%) were more than eight times more likely to suffer from obesity than patients with good oral hygiene. Cleaning index higher than 4 decreased the odds by about 85%. Oral hygiene habits, adjusted by salivary concentrations of selected inflammatory markers may allow predicting effectively overweight or obesity risk. Early proper dental prophylaxis and treatment could lead to the better prevention of metabolic disorders.

Flaxseed (Linum Usitatissimum L.) Supplementation in Patients Undergoing Lipoprotein Apheresis for Severe Hyperlipidemia-A Pilot Study.

Being rich in polyunsaturated fatty acids, flaxseed (Linum usitatissimum L.) is thought to be able to decrease lipid levels and dampen inflammation. In this pilot study, we aimed to determine whether flaxseed supplementation could improve the profiles of lipids and inflammatory mediators in patients with severe hyperlipidemia resistant to conventional lipid-lowering pharmacotherapy and requiring lipoprotein apheresis. To this end, six patients received, blindly-in addition to their normal lipoprotein apheresis regimen-a 10-week dietary supplementation with flaxseed (28 g/d) administered in biscuits. This was followed by a 10-week washed out-period and a 10-week supplementation phase with whole wheat placebo. Blood samples were collected at the end of each phase, before the lipoprotein apheresis session. The primary endpoint was the lipid profile and the secondary endpoints were the concentrations of inflammatory mediators and tolerability. Flaxseed supplementation was well-tolerated and resulted in a consistent and significant decrease in total cholesterol and low-density lipoprotein (LDL) levels. The median (and range) percentage decrease was 11.5% (0-18.8) and 7.3% (4.4-26.6), for cholesterol (p = 0.015) and LDL-C (p = 0.003), respectively. On the other hand, there was no significant effect of flaxseed on lipoprotein(a) (Lp(a)), C-reactive protein (CRP), and interleukin 6 (IL-6) concentrations. These observations indicate that flaxseed can produce a cholesterol- and LDL-lowering effect in patients treated with lipoprotein apheresis. Thus, flaxseed supplementation may help to control cholesterol in this patient population. The flaxseed supplementation protocol applied may be of use for further adequately-powered studies to validate and extend our findings.

Preeclampsia with Intrauterine Growth Restriction Generates Morphological Changes in Endothelial Cells Associated with Mitochondrial Swelling-An In Vitro Study.

Pregnancy complicated by preeclampsia (PE) and intrauterine growth restriction (IUGR) promotes endothelial cell (EC) dysfunction. Our in vitro study aimed to evaluate the endothelial cell morphology after acute and chronic exposition to medium supplemented with serum taken from healthy pregnant women and women with IUGR and IUGR with PE. In the same condition, ECs viability, proliferation, reactive oxygen species (ROS) production, and serum concentration of vascular endothelial growth factor (VEGF) were also measured. Pregnant women with IUGR and IUGR with PE-delivered babies with reduced body mass and were characterized in elevated blood pressure, urine protein loss, and reduced level of VEGF. The 24 hours of exposition did not exert any morphological changes in ECs, except the reduction in cell viability, but prolonged exposition resulted in significant morphological changes concerning mostly the swelling of mitochondria with accompanying ROS production, cell autophagy, reduced cell viability, and proliferation only in complicated pregnancies. In conclusion, the sera taken from women with IUGR and IUGR with PE show a detrimental effect on ECs, reducing their viability, proliferation, and generating oxidative stress due to dysfunctional mitochondria. This multidirectional effect might have an adverse impact on the cardiovascular system in women with IUGR and PE.

Predictors of atrial fibrillation early recurrence following cryoballoon ablation of pulmonary veins using statistical assessment and machine learning algorithms.

Inflammation, oxidative stress, myocardial injury biomarkers and clinical parameters (longer AF duration, left atrial enlargement, the metabolic syndrome) are factors commonly related to AF recurrence. This study aims to assess the predictive value of laboratory and clinical parameters responsible for early recurrence of atrial fibrillation (ERAF) following cryoballoon ablation (CBA) using statistical assessment and machine learning algorithms. This study group comprised 118 consecutive patients (mean age, 62.5 ± 7.8 years; women 36%) with paroxysmal (54.1%) and persistent (45.9%) AF who underwent their first pulmonary vein isolation (PVI) performed by CBA (Arctic Front Advance 2nd generation 28 mm). The biomarker concentrations were measured at baseline and after CBA in a 24-h follow-up. ERAF was defined as at least a 30-s episode of arrhythmia registered by a 24 h-Holter monitor within the 3 months following the procedure. 56 clinical, laboratory and procedural variables were collected from each patient. We used two classification algorithms: support vector machines, gradient boosted tree. The synthetic minority over-sampling technique (SMOTE) was used to provide a balanced training data set. Within a period of 3 months 21 patients (17.8%) experienced ERAF. The statistical analysis indicated that the lowered levels of post-ablation TnT (p = 0.043) and CK-MB (p = 0.010) with the TnT elevation (p = 0.044) were the predictors of ERAF following CBA. In addition, diabetes and statin treatment were significantly associated with ERAF after CBA (p < 0.05). The machine learning algorithms confirmed the results obtained in the univariate analysis.