Concentrations Of Soluble Adhesion Molecules Research Articles

Association Between Soluble Cell Adhesion Molecules (sP-Selectin, sE-Selectin, and sICAM-1) and Antibodies Against the Antigens of Proteus mirabilis in Rheumatoid Arthritis Patients.

Objective The purpose of this study was to examine the association between the serum concentration of soluble cell adhesion molecules (CAMs) and antibodies against antigens of Proteus mirabilis (P. mirabilis) in rheumatoid arthritis (RA) patients, taking into consideration the implication of P. mirabilis in the etiopathogenesis of RA. Methods The serum levels of soluble P-selectin (sP-selectin), soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 (sICAM-1) were determined by sandwich enzyme-linked immunosorbent assay (ELISA) in 59 RA patients and 36 healthy controls. Using the same ELISA method, the serum levels of class-specific antibodies against hemolysin (HpmB), urease C (UreC), and urease F (UreF) enzymes of P. mirabilis were also measured. Results In this study, increased levels of sP-selectin and sICAM-1 were observed in RA patients, while the levels of sE-selectin were increased in comparison with healthy controls but did not present a statistically significant difference. Moreover, increased levels of antibodies against HpmB, UreC, and UreF of P. mirabilis were found. Additionally, it was observed that the sE-selectin levels presented a significant correlation with IgG antibodies against the UreF antigen (there is no corresponding antigen in human tissue) in all the RA patients. A statistically significant correlation was observed between levels of soluble CAMs and antibodies against P. mirabilis in the different subgroups. Conclusion The observed correlation between soluble CAMs and antibodies against antigens of P. mirabilis, specifically in the subgroup of biologic therapy, indicates that P. mirabilis exists and provokes refractory in the treatment of RA.

Elevated indoleamine 2,3-dioxygenase activity is associated with endothelial dysfunction in people living with HIV and ROS production in human aortic endothelial cells in vitro.

The precise role of indoleamine 2,3-dioxygenase (IDO) in cardiovascular diseases (CVD) among people living with HIV (PLWH) is still under debate, despite recognized links. This study aimed to investigate the impact of elevated IDO activity on endothelial dysfunction in PLWH. A total of 38 PLWH, who had not previously received anti-retroviral therapy (ART), were enrolled in the study. These participants were monitored for 36 months following the initiation of ART. Measurements including plasma levels of IDO activity, markers of endothelial dysfunction, inflammatory factors, and lipids. In vitro, human aortic endothelial cells (HAEC) were exposed to interferon-γ, an IDO inhibitor, a kynurenine 3-hydroxylase (KMO) inhibitor, as well as different concentrations of kynurenine. Pre-ART, PLWH demonstrated notably elevated plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1(sVCAM-1), and IDO activity in comparison to healthy controls. Post-ART, both IDO activity and sICAM-1 levels experienced a significant decrease, with IDO activity reaching levels comparable to those observed in healthy controls. Furthermore, a positive correlation was observed between IDO activity and sICAM-1 (p = 0.0002), as well as sVCAM-1 (p < 0.0001) before ART. In vitro, the augmentation of kynurenine concentration in the medium and the induction of IDO expression in HAEC resulted in increased production of reactive oxygen species (ROS), with minimal impact on endothelial dysfunction. From these findings, it can be concluded that long-term ART has the potential to restore the heightened IDO activity observed in PLWH. The overexpression of IDO primarily influences the expression of ROS in HAEC.

Göttingen pigs as a potential model for natalizumab pharmacokinetics, pharmacodynamics, and immunogenicity evaluation

Natalizumab is a recombinant, humanized form of a monoclonal antibody that binds to CD49d. The presented study was conducted to explore the suitability of Göttingen pigs as a pharmacokinetic/pharmacodynamic model in the preclinical phase of biosimilar natalizumab development. The minipigs were treated with 1.286 or 3.0 mg of natalizumab (Tysabri®) per kg of body weight by a single 1-hour intravenous infusion. Six days before (baseline) and 30 days after administration of the single dose of natalizumab, blood samples were taken for analysis. No signs of local or general intolerance were observed. The pharmacokinetics plot shows a biphasic profile dependent on anti-drug antibody (ADA) levels. A dose-related increase in the CD49d saturation was observed immediately after the end of the infusion. The soluble vascular cell adhesion molecule (sVCAM) concentrations of the female animals were moderately decreased immediately after the end of infusion compared to the predose levels. The soluble mucosal addressin cell adhesion molecule (sMAdCAM) concentrations were slightly decreased compared to the predose levels starting immediately after the end of infusion and lasting for the next 30 days. All animals treated appeared to produce ADA. The concentrations of the ADA ranged from 15.8 to 16,748 ng/mL Göttingen pigs represent a suitable model for pharmacokinetic analysis and mechanism of action evaluation related to saturation of CD49d.

SVCAM-1, and TGFβ1 in chronic phase, chronic myeloid leukemia patients treated with tyrosine kinase inhibitors

The outcome for chronic phase (CP) chronic myelogenous leukemia (CML) patients has changed dramatically since the introduction of tyrosine kinase inhibitor (TKI) therapy. We examined the characteristics of CML patients during TKI therapy by determining the plasma concentrations of soluble vascular cell adhesion molecule 1 (sVCAM-1), and transforming growth factor (TGFβ1) biomarkers. The plasma levels of sVCAM-1 and TGFβ1 were measured by ELISA at baseline and after 3 months of TKI treatment. The levels of sVCAM-1, and TGFβ1 were significantly elevated in patients with CML (P< 0.01). Dasatinib treatment was associated with a significant reduction in the levels of these biomarkers (P< 0.01). In conclusion, plasma levels of sVCAM-1 and TGFβ1 could have a role in the pathogenesis of CML and may be used as predictors of hematological and molecular responses to TKIs. A favorable outcome for Dasatinib therapy was observed.

Biomarkers of Airway Immune Homeostasis Differ Significantly with Generation of E-Cigarettes.

Rationale: Numerous studies have demonstrated that e-cigarettes can impact respiratory immune homeostasis; however, the extent of these effects remains an active area of investigation, and most previous studies were conducted with model systems or subjects exposed to third-generation e-cigarettes, such as vape pens and box mods. Objectives: Given the rise in popularity of nicotine-salt-containing pods and disposable e-cigarettes (fourth generation), we set out to better understand the respiratory effects of these newer e-cigarettes and compare their effects to early-generation devices. Methods: We collected induced sputum samples from a cohort of nonsmokers, smokers, third-generation e-cigarette users, and fourth-generation e-cigarette users (n = 20-30 per group) and evaluated the cellular and fluid-phase composition for markers of inflammation, host defense, and lung injury. Measurements and Main Results: Fourth-generation e-cigarette users had significantly more bronchial epithelial cells in the sputum, suggestive of airway injury. Concentrations of soluble intercellular adhesion molecule 1 (sICAM1) and soluble vascular cell adhesion molecule 1 (sVCAM1) were significantly lower in fourth-generation e-cigarette users in comparison with all other groups, and CRP (C-reactive protein), IFN-γ, MCP-1 (monocyte chemoattractant protein-1), MMP-2 (matrix metalloproteinase 2), uteroglobin, and VEGF (vascular endothelial growth factor) were significantly lower in fourth- versus third-generation e-cigarette users, suggestive of overall immune suppression in fourth-generation e-cigarette users. Predictive modeling also demonstrated clear separation between exposure groups, indicating that the overall mediator milieu is different between groups, particularly fourth-generation e-cigarette users. Conclusions: Our results indicate disrupted immune homeostasis in fourth-generation e-cigarette users and demonstrate that the biological effects of fourth-generation e-cigarette use are unique compared with those associated with previous-generation e-cigarettes.

THE MAIN EPIDEMIOLOGICAL AND DIAGNOSTICAL FEATURES OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE IN SERVICEMEN OF THE ARMED FORCES OF UKRAINE IN THE CONDITIONS OF JOINT FORCES OPERATION

The aim: The aim of the work was to determine the leading epidemiological, diagnostical features, disturbance of spirometric indices, changes in the immune system in servicemen with COPD, who take part in Joint Forces Operation (JFO). Materials and methods: 89 male patients were examined, who sought medical help for COPD, group B. They were divided into two groups. 1 group (42 patients) − with COPD, who took part in the JFO not more than 6 month, the 2 group consisted of 47 patients with COPD, who took part in the JFO during the period more than 6 month. Results: The patients in the group 2 had veraciously more points of cough and sputum expectoration in daily amount of 30 and more ml. The type of sputum in 53.2% patients was predominantly mucus-pus. There were also more percentage of patients with feeling short of breath and the high point, achieved at CAT. There were significant differences in systolic and diastolic blood pressure levels, LV mass index between two groups. Conclusions: It was found that servicemen who took part in JFO for more than 6 months had a more severe course of COPD with a higher score in the CAT and probably lower obstructive ventilatory indices, in a probably higher percentage of cases there were detected such a concomitant pathology as AH stage II and GERD. They had Th17 immune response predomination with significant elevation of IL-17, TGF-β, IL-6 concentrations in serum and high concentration of soluble adhesion molecules. KEY WORDS: Obstructive ventilatory defects, immune, external respiration function, fuel combustion products

Randomized Clinical Trial to Evaluate the Morphological Changes in the Adventitial Vasa Vasorum Density and Biological Markers of Endothelial Dysfunction in Subjects with Moderate Obesity Undergoing a Very Low-Calorie Ketogenic Diet.

Weight loss after bariatric surgery decreases the earlier expansion of the adventitial vasa vasorum (VV), a biomarker of early atheromatous disease. However, no data are available regarding weight loss achieved by very low calorie ketogenic diets (VLCKD) on VV and lipid-based atherogenic indices. A randomized clinical trial was performed to examine changes in adventitial VV density in 20 patients with moderate obesity who underwent a 6-month very low calorie ketogenic diet (VLCKD, 600–800 kcal/day), and 10 participants with hypocaloric diet based on the Mediterranean Diet (MedDiet, estimated reduction of 500 kcal on the usual intake). Contrast-enhanced carotid ultrasound was used to assess the VV. Body composition analysis was also used. The atherogenic index of plasma (log (triglycerides to high-density lipoprotein cholesterol ratio)) and the triglyceride-glucose index were calculated. Serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured. The impact of weight on quality of life-lite (IWQOL-Lite) questionnaire was administered. Participants of intervention groups displayed a similar VV values. Significant improvements of BMI (−5.3 [−6.9 to −3.6] kg/m2, p < 0.001), total body fat (−7.0 [−10.7 to −3.3] %, p = 0.003), and IWQOL-Lite score (−41.4 [−75.2 to −7.6], p = 0.027) were observed in VLCKD group in comparison with MedDiet group. Although after a 6-months follow-up period VV density (mean, right and left sides) did not change significantly in any group, participants in the VLCKD exhibited a significantly decrease both in their atherogenic index of plasma and serum concentration of sICAM-1. A 6-month intervention with VLCKD do not impact in the density of the adventitial VV in subjects with moderate obesity, but induces significant changes in markers of endothelial dysfunction and CV risk.

Association of markers of endothelial activation and dysfunction with occurrence and outcome of pulmonary hemorrhage in dogs with leptospirosis.

BackgroundEndothelial dysfunction might contribute to the development of leptospiral pulmonary hemorrhage syndrome (LPHS).HypothesisSerum concentrations of markers of endothelial activation and dysfunction are higher in dogs with leptospirosis and correlate with the occurrence of LPHS and a higher case fatality rate.AnimalsClinically healthy dogs (n = 31; 10/31 dogs confirmed healthy based on no detected abnormalities on blood work), dogs with leptospirosis with LPHS (n = 17) and without LPHS (n = 15), dogs with acute kidney injury not due to leptospirosis (AKI‐nL, n = 34).MethodsObservational study. Serum concentrations of soluble intercellular adhesion molecule 1 (sICAM‐1), vascular endothelial growth factor (VEGF), and angiopoietin‐2 (Ang‐2) at admission were compared between groups. Correlations with outcome and the accuracy to predict LPHS were examined.ResultsSoluble intercellular adhesion molecule (sICAM‐1), VEGF, and Ang‐2 concentrations were higher in dogs with AKI‐nL (sICAM‐1 34.7 ng/mL, interquartile range [IQR] = 24.4‐75.5; VEGF 43.1 pg/mL, IQR = 12.3‐79.2; Ang‐2 8.5 ng/mL, IQR = 6.2‐12.3), leptospirosis without LPHS (sICAM‐1 45.1 ng/mL, IQR = 30.6‐59.0; VEGF 32.4 pg/mL, IQR = 12.5‐62.6; Ang‐2 9.6 ng/mL, IQR = 6.9‐19.3), and LPHS (sICAM‐1 69.7 ng/mL, IQR = 42.1‐89.1; VEGF 51.8 pg/mL, IQR = 26.3‐96.7; Ang‐2 8.0 ng/mL, IQR = 5.6‐12.2) compared to controls (P < .001). In dogs with leptospirosis, VEGF and sICAM‐1 were higher in nonsurvivors (sICAM‐1 89.4 ng/mL, IQR = 76.5‐101.0; VEGF 117.0 pg/mL, IQR = 90.3‐232.4) than survivors (P = .004) and sICAM‐1 predicted the development of LPHS.ConclusionsSoluble intercellular adhesion molecule 1, VEGF, and Ang‐2 do not discriminate leptospirosis from AKI‐nL. In dogs with leptospirosis, sICAM‐1 and VEGF predict outcome and sICAM‐1 might identify dogs at risk for LPHS.

Plasma Biomarkers of Risk of Tuberculosis Recurrence in HIV Co-Infected Patients From South Africa.

There is an urgent need to identify immunological markers of tuberculosis (TB) risk in HIV co-infected individuals. Previously we have shown that TB recurrence in HIV co-infected individuals on ART was associated with markers of systemic inflammation (IL-6, IL1β and IL-1Rα). Here we examined the effect of additional acute inflammation and microbial translocation marker expression on risk of TB recurrence. Stored plasma samples were drawn from the TB Recurrence upon Treatment with HAART (TRuTH) study, in which individuals with previously treated pulmonary TB were screened for recurrence quarterly for up to 4 years. Recurrent TB cases (n = 37) were matched to controls (n = 102) by original trial study arm assignment and ART start date. Additional subsets of HIV infected (n = 41) and HIV uninfected (n = 37) individuals from Improving Recurrence Success (IMPRESS) study were sampled at active TB and post successful treatment completion. Plasma concentrations of soluble adhesion molecules (sMAdCAM, sICAM and sVCAM), lipopolysaccharide binding protein (LBP) and transforming growth factor-beta (TGF-β1, TGF-β2, TGF-β3) were measured by multiplex immunoassays and ELISA. Cytokine data was square root transformed in order to reduce variability. Multivariable analysis adjusted for a number of potential confounders measured at sample time-point: age, BMI, CD4 count, viral load (VL) and measured at baseline: presence or absence of lung cavities, previous history of TB, and WHO disease stage (4 vs 3). The following analytes were associated with increased risk of TB recurrence in the multivariable model: sICAM (aOR 1.06, 95% CI: 1.02-1.12, p = 0.009), LBP (aOR 8.78, 95% CI: 1.23-62.66, p = 0.030) and TGF-β3 (aOR 1.44, 95% CI 1.01-2.05, p = 0.044). Additionally, we observed a positive correlation between LBP and sICAM (r= 0.347, p<0.0001), and LBP and IL-6, identified to be one of the strongest predictors of TB risk in our previous study (r=0.623, p=0.03). These data show that increased risk of TB recurrence in HIV infected individuals on ART is likely associated with HIV mediated translocation of microbial products and the resulting chronic immune activation.

Baseline and overtime variations of soluble adhesion molecule plasma concentrations are associated with mobility recovery after rehabilitation in multiple sclerosis patients

Rehabilitative exercise outcomes and plasma concentrations of soluble adhesion molecules (sEndoglin, sE-Selectin, sL-Selectin, sICAM-1, sNCAM, sNCAM-1, sVCAM-1, sPECAM-1, sVAP-1) were evaluated in 60 severely disabled progressive multiple sclerosis (MS) patients at 4-time points. Changes of sE-Selectin, sL-Selectin, and sPECAM-1 concentrations were observed over time, and their variations were significantly correlated with rehabilitative outcome variations. Baseline sVAP-1 concentrations were able to predict functional mobility recovery. Our data suggest that the evaluation of adhesion molecules in plasma provides useful information to interpret rehabilitative exercise processes and to identify potential predictors of the rehabilitation-induced changes in mobility outcomes in MS patients.

Soluble intercellular adhesion molecule (ICAM)-1 detects invasive fungal infections in patients following liver transplantation

Purpose Despite antifungal prophylaxis, liver transplanted patients are endangered by invasive fungal infections (IFI). Routinely used microbiological procedures are hallmarked by significant weaknesses, which may lead to a delay in antifungal treatment. Methods Culture-based fungal findings, routinely used biomarkers of infection/inflammation (e.g., procalcitonin or C-reactive protein), as well as corresponding plasma concentrations of soluble Intercellular Adhesion Molecule (ICAM)-1 were analysed in 93 patients during a period of 28 days following liver transplantation (LTX). Results Plasmatic sICAM-1 was significantly elevated in patients affected by an IFI within the first 28 days in comparison to fungally colonised or unobtrusive LTX patients. sICAM-1 might therefore be helpful for the identification of IFI patients after LTX (e.g., Receiver Operating Characteristic (ROC)-Area Under the Curve (AUC): 0.714 at 14d after LTX). The diagnostic performance of sICAM-1 was further improved by its combined use with different other IFI biomarkers (e.g., midregional proadrenomedullin). Conclusion The diagnostic deficiencies of routinely used microbiological procedures for IFI detection in patients after LTX may be reduced by plasmatic sICAM-1 measurements. Clinical Trial Notation. German Clinical Trials Register: DRKS00005480

Dietary stearic acid and palmitic acid do not differently affect ABCA1-mediated cholesterol efflux capacity in healthy men and postmenopausal women: A randomized controlled trial

The saturated fatty acid stearic acid (C18:0) lowers HDL cholesterol compared with palmitic acid (C16:0). However, the ability of HDL particles to promote cholesterol efflux from macrophages (cholesterol efflux capacity; CEC) may better predict coronary heart disease (CHD) risk than HDL cholesterol concentrations. We examined effects of exchanging dietary palmitic acid for stearic acid on ATP-binding cassette transporter A1 (ABCA1)-mediated CEC, and other conventional and emerging cardiometabolic risk makers. In a double-blind, randomized, crossover study with two 4-week isocaloric intervention periods, 34 healthy men and postmenopausal women (61.5±5.7 years, BMI: 25.4±2.5kg/m2) followed diets rich in palmitic acids or stearic acids. Difference in intakes was 6% of daily energy. ABCA1-mediated CEC was measured from J774 macrophages to apolipoprotein (apo)B-depleted serum. Compared with the palmitic-acid diet, the stearic-acid diet lowered serum LDL cholesterol (-0.14mmol/L; p=0.010), HDL cholesterol (-0.09mmol/L; p=<0.001), and apoA1 (-0.05g/L; p<0.001). ABCA1-mediated CEC did not differ between diets (p=0.280). Cholesteryl ester transfer protein (CETP) mass was higher on stearic acid (0.11mg/L; p=0.003), but CETP activity was comparable. ApoB100 did not differ, but triacylglycerol concentrations tended to be higher on stearic acid (p=0.100). Glucose concentrations were comparable. Effects on insulin and C-peptide were sex-dependent. In women, the stearic-acid diet increased insulin concentrations (1.57 μU/mL; p=0.002), while in men, C-peptide concentrations were lower (-0.15ng/mL; p=0.037). Interleukin 6 (0.15pg/mL; p=0.039) and tumor necrosis factor alpha (0.18pg/mL; p=0.005), but not high-sensitivity C-reactive protein, were higher on stearic acid. Soluble intracellular adhesion molecule (9ng/mL; p=0.033), but not soluble vascular cell adhesion molecule and endothelial-selectin concentrations decreased after stearic-acid consumption. As expected, stearic-acid intake lowered LDL cholesterol, HDL cholesterol, and apoA1. Insulin sensitivity in women and low-grade inflammation might be unfavorably affected by stearic-acid intake. However, palmitic-acid and stearic-acid intakes did not differently affect ABCA1-mediated CEC. This trial was registered at clinicaltrials.gov as NCT02835651.

Soluble forms of adhesive molecules in blood serum as a marker of endothelial dysfunction in chronic generalized parodontitis.

An important factor in the pathogenesis of chronic inflammation in periodontitis is endothelial dysfunction (ED). Adhesion molecules are markers of impaired barrier function, adhesive properties and vascular permeability. The study of the concentration of soluble adhesion molecules is very promising in the diagnosis of ED. The purpose of this research was to study changes in the concentration of soluble forms of adhesive molecules of the selectin family and the immunoglobulin superfamily when used as markers of systemic manifestations of ED in the dynamics of the treatment of chronic generalized periodontitis (CP) using surgical and therapeutic schemes. 60 patients with CP (33 women and 27 men) and 20 clinically healthy volunteers (10 men and 10 women) were examined. The state of the endothelium was assessed by the content in the serum of soluble forms of adhesive molecules - sP- and sE-selectins, intercellular adhesive molecules of type 1 (sICAM-1), vascular molecules of cell adhesion of type 1 (VCAM-1) by ELISA. The short-term results of non-surgical treatment of CP are more effective in correction of vascular wall adhesive properties disorders compared with surgical treatment. Conservative treatment of chronic hepatitis C effectively adjusted the blood content of adherent endothelium molecules in women than in men. The long-term results of applying this scheme were characterized by partial preservation of a positive effect on the adhesive properties of the endothelium, however, long-term results were inferior to short-term ones. Surgical treatment of CP in women in the early postoperative period was accompanied by reactive impairment of the adhesive properties of the endothelium. The long-term results of this treatment regimen testified to its greater effectiveness. In women, the effectiveness of treatment of CP in restoring the adhesive properties of the endothelium was higher than in men. The results obtained allow us to conclude that the systemic manifestations of ED in CP were characterized by an increase in the concentration in the blood of soluble forms of adhesion molecules. The dynamics of the concentration of adhesive molecules during the treatment of СР testified to the dependence of the sex of patients on the effectiveness of the influence of therapeutic and surgical treatment regimens on the systemic manifestations of ED.

P872Activity of nonspecific systemic inflammation and biochemical markers of endothelial dysfunction as the criteria of coronary heart disease destabilization

Abstract Introduction Nonspecific systemic inflammation (NSSI) as well as endothelial dysfunction (EDF) plays an important role in the development and progression of coronary heart disease (CHD). Its exacerbation can cause the atherosclerotic plaque damage and the CHD progression with development of atherothrombotic complications. Purpose To evaluate the activity of nonspecific systemic inflammation and biochemical markers of endothelial dysfunction and their diagnostic significance in CHD patients as the criteria of disease destabilization. Methods The study included 173 CHD patients (the average age was 57.24±5.12 years). 92 patients were with stable angina (45 with 2nd and 47 with 3rd functional classes) and 81 patients were with acute coronary syndromes (ACS) (43 with unstable (progressive) angina and 38 – with acute myocardial infarction). The study excluded patients with severe chronic heart failure, liver and kidney dysfunction, acute or chronic inflammatory diseases, diabetes mellitus, severe obesity, infectious diseases. The control group included 30 healthy subjects (average age was 55.37±4.82 years). Activity of NSSI was assessed by the concentration of high sensitive C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α) and pregnancy-associated plasma protein A (PAPP-A) as a marker of endogenic destruction, which were determined by ELISA. EDF was assessed by the concentration of endothelin-1 (ET-1) and soluble vascular cell adhesion molecules (sVCAM) using ELISA method. Results CHD patients were characterized by significant increasing of hsCRP, TNF-α, PAPP-A levels regarding to control group (5.29±0.19 and 0.87±0.04 mg/L for hsCRP, respectively, p&lt;0.001; 4.28±0.18 and 1.18±0.07 ng/mL for TNF-α, respectively, p&lt;0.001; 9.81±0.16 and 3.12±0.42 mIU/L for PAPP-A, respectively, p&lt;0.01), which was the evidence of NSSI activation. Levels of both ET-1 and sVCAM-1 in CHD patients were more than twice higher than in the control group (9.89±0.28 and 4.01±0.36 ng/mL for ET-1, respectively p&lt;0.001; 1442.9±25.3 and 626.0±34.1 ng/mL for sVCAM, respectively, p&lt;0.001). Levels of biochemical markers of both NSSI and EDF increased with an increase in disease severity (p&lt;0.01) and the most severe changes were in patients with ACS, especially in patients with acute myocardial infarction. Significant relationships were between levels of both ET-1 and sVCAM with both hsCRP and TNF-α. Significant relationships were between PAPP-A level with both hsCRP and TNF-α, but were absent with both ET-1 and sVCAM levels. Therefore, we believe that the endogenic destruction of plaque is more related with activation of NSSI than with progression of EDF. Conclusion The severity of the CHD is associated with the degree of both activation of nonspecific systemic inflammation and dysfunction of vascular endothelium. Elevated production of these markers can be considered as the indicator of both atherosclerotic plaque damage and the possibility of ACS development.

Correlation Between Soluble Endothelial Adhesion Molecules and Nitric Oxide Metabolites in Sickle Cell Disease.

Nitric Oxide (NO) and soluble adhesion molecules are promising biomarkers, which predict endothelial dysfunction in sickle cell disease (SCD). Several studies have investigated the relationship between NO (as well as its metabolites) and endothelial adhesion molecules in SCD. However, these studies were done mainly in the developed world, and it is difficult to extrapolate the findings to SCD populations in other geographical regions such as Africa due to significant disparities in the results. The aim of the current study was to determine the correlation between levels of nitric oxide metabolites (NOx) and adhesion molecules in SCD patients in a tertiary hospital in Ghana. A case control cross-sectional study involving 100 SCD (made up of HbSS and HbSC patients) and 60 healthy controls was conducted. Concentrations of NOx and soluble endothelial adhesion molecules (ICAM-1, VCAM-1 and E-selectin) were measured in all the study participants (n = 160) by the Griess reagent system and enzyme-linked immunosorbent assay (ELISA). Correlation analysis was performed to determine a possible link between the variables. Levels of soluble adhesion molecules were higher in the HbSS patients. Correlation of NOx with ICAM-1 almost approached significance (r = 0.565, p = 0.058) in the HbSS patients. There were no correlations between NOx and E-selectin in both HbSS and HbSC patients. There were no significant correlations between NOx and VCAM-1 in all the study participants (p > 0.05). Of the soluble adhesion molecules, ICAM-1 showed a significant positive correlation with VCAM-1 in the HbSC patients. There were no significant differences between the adhesion molecules and the age of participants in the various study groups. Whether or not a significant correlation exists between NOx and soluble adhesion molecules may not depend on the sickle cell genotype. The expression of adhesion molecules may not depend on age.

Diet-induced weight loss improves not only cardiometabolic risk markers but also markers of vascular function: a randomized controlled trial in abdominally obese men

Background: Many trials assessing effects of dietary weight loss on vascular function have been performed without no–weight loss control groups and in individuals with obesity-related morbidities. Usually a limited set of vascular function markers has been investigated.Objective: The objective of this study was to examine effects of diet-induced weight loss on various vascular function markers and differences between normal-weight and abdominally obese men at baseline and after weight reduction.Design: Twenty-five healthy, normal-weight men (waist circumference: <94 cm) and 54 abdominally obese men (waist circumference: 102–110 cm) participated. Abdominally obese participants were randomly allocated to a dietary weight-loss or a no–weight loss control group. Individuals from the weight-loss group followed a calorie-restricted diet for 6 wk to obtain a waist circumference <102 cm followed by a weight-maintenance period of 2 wk. The control group maintained their habitual diet and physical activity levels. The primary outcome was the change in brachial artery flow-mediated vasodilation (FMD).Results: Compared with the control group, FMD did not change in the weight-loss group, but carotid-to-femoral pulse wave velocity tended to decrease by 0.5 m/s (P = 0.065). The retinal arteriolar caliber increased by 5 μm (P < 0.001) and the arteriolar-to-venular ratio by 0.02 (P < 0.01). Soluble endothelial selectin and soluble intercellular adhesion molecule concentrations decreased (P < 0.001). Also, total cholesterol, low–density lipoprotein cholesterol, triacylglycerol, glucose, insulin, C-peptide, homeostasis model assessment of insulin resistance, and blood pressure improved (P < 0.05 for all variables). Except for FMD, these markers differed at baseline between normal-weight and abdominally obese men but became comparable after weight loss.Conclusions: In abdominally obese men, dietary weight loss targeting a waist circumference of <102 cm improved retinal microvascular caliber, plasma biomarkers of microvascular endothelial function, and the more conventional cardiometabolic risk markers. Aortic stiffness tended to decrease, but FMD was not changed. This trial was registered at clinicaltrials.gov as NCT01675401.

Vitamin D status and circulating biomarkers of endothelial dysfunction and inflammation in non-diabetic obese individuals: a pilot study.

IntroductionObesity and inadequate vitamin D status are associated with endothelial dysfunction and cardiovascular disease. We evaluated the associations between vitamin D status (i.e. serum levels of 25-hydroxyvitamin D (25(OH)D)), biomarkers of endothelial dysfunction (i.e. serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble E-selectin (sE-selectin)), inflammatory markers (i.e. high-sensitivity C-reactive protein (hsCRP) and fibrinogen) and cardiometabolic risk factors.Material and methodsFifty obese (body mass index (BMI) ≥ 30 kg/m2) non-diabetic adults (mean age: 36.2 ±5.4 years) without pre-existing cardiovascular abnormalities and 25 clinically healthy, normal weight and age-matched individuals were included. Anthropometric parameters, markers of glucose and lipid metabolism, and serum levels of inflammatory and endothelial dysfunction biomarkers were assessed in all subjects.ResultsThe mean serum 25(OH)D level was significantly lower in the obese group than in controls (33.5 ±15.2 vs. 60.1 ±23.1 nmol/l; p < 0.001). In the obese group, sE-selectin (36.4 (32.1–47.2) vs. 32.4 (24.6–35.5) ng/ml, p < 0.05) and hsCRP (6.0 ±3.4 vs. 3.5 ±1.0 mg/l, p < 0.05) were significantly higher in individuals with lower than median vitamin D levels (i.e. 31 nmol/l) compared with those with higher vitamin D levels. In multivariable linear regression analysis, hsCRP (β = –0.43; p < 0.001) and sE-selectin (β = –0.30; p = 0.03) were independently and significantly associated with serum 25(OH)D levels in the obese group.ConclusionsVitamin D levels may be related to increased levels of biomarkers of endothelial dysfunction and inflammation in obese non-diabetic individuals.

Validation of a Biomarker Panel and Longitudinal Biomarker Performance for Early Detection of Ovarian Cancer.

Longitudinal multimarker combinations have the potential to improve sensitivity while maintaining the high specificity required for the early detection of ovarian cancer. The use of multiple markers to improve sensitivity over cancer antigen 125 (CA125) in longitudinal algorithms for early ovarian cancer detection requires the selection of markers with optimal discriminatory power and low longitudinal variance relative to disease-initiated changes. Our objective was to identify a multimarker panel suitable for ovarian cancer, where each individual marker has its own baseline, permitting longitudinal algorithm development. In this retrospective study, we measured CA125, human epididymis protein 4 (HE4), matrix metalloproteinase-7 (MMP-7), CA72-4, CA19-9, CA15-3, carcinoembryonic antigen, and soluble vascular cell adhesion molecule (sVCAM) concentrations using immunoassays in pretreatment sera from 142 stage I ovarian cancer cases and 5 annual samples each from 217 healthy controls. After random division into training and validation sets, all possible biomarker combinations were explored exhaustively using linear classifiers to identify the panel with the greatest sensitivity for stage I disease at a high specificity of 98%. To evaluate longitudinal performance of the individual markers, the within-person over time and the between-person coefficient of variation (CV) were estimated. Hierarchical modeling across women of log-concentrations enabled the borrowing of information across subjects to moderate variance estimates given the small number of observations per subject. The 4-marker panel comprising CA125, HE4, MMP-7, and CA72-4 performed with the highest sensitivity (83.2%) at 98% specificity. The within-person CVs were lower for CA125, HE4, MMP-7, and CA72-4 (15%, 25%, 25%, and 21%, respectively) compared with their corresponding between-person CV (49%, 20%, 35%, and 84%, respectively) indicating baselines in healthy volunteers. After simple log-transformations, the within-volunteer variation across volunteers was modeled with a normal distribution permitting parsimonious hierarchical modeling. The multiplex panel chosen is suitable for the early detection of ovarian cancer and the individual markers have their own baseline permitting longitudinal algorithm development.

Concentration of soluble adhesion molecules in cerebrospinal fluid and serum of epilepsy patients.

Mounting evidence supports the involvement of brain inflammation and the associated blood-brain barrier damage from which spontaneous and recurrent seizures originate. Detection of the soluble form of adhesion molecules (AM) has also been proven to predict outcomes in central nervous system (CNS) disorders. A recent study has shown that expression of AM in brain vessels was upregulated 24h after kainic acid (KA) induced seizures. The aim of the present study was to investigate soluble AM levels in the cerebrospinal fluid (CSF) and serum of epilepsy patients. Paired CSF and serum samples were analyzed by sandwich enzyme-linked immunosorbent assay (ELISA) to determine the concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1). Increased serum concentrations of sICAM-1 were present in epileptic patients (41 localization-related of unknown etiology, 19 idiopathic generalized). Serum sICAM-1 level in drug-refractory epilepsy was elevated as compared to new diagnosis epilepsy and drug-responsive epilepsy. CSF sVCAM-1 and serum sVCAM-1 concentrations in the epilepsy group were higher as compared to the neurosis group. Moreover, CSF sVCAM-1 and serum sVCAM-1 concentrations in drug-refractory epilepsy were raised as compared to drug-responsive epilepsy and new diagnosis epilepsy. However, there were no significant differences in concentrations of CSF sICAM-1 between the epilepsy and neurosis groups. Our results suggest that sVCAM-1 and sICAM-1 could play an important role in the drug-refractory epilepsy.

THU0236 Brachial Artery Vasodilator Function and Adhesion Molecules in Rheumatoid Arthritis

BackgroundCardiovascular (CV) event rates are increased in Rheumatoid Arthritis (RA). Traditional cardiovascular risk factors do not adequately account for the extent of cardiovascular disease in RA1. The relation among biomarkers...