Serum Soluble Vascular Cell Adhesion Research Articles

The Role of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Predicting Complicated Appendicitis in Children.

Acute appendicitis is a common abdominal emergency observed in emergency departments (ED). Distinguishing between uncomplicated and complicated appendicitis is important in determining a treatment strategy. Serum soluble vascular cell adhesion molecule-1 (VCAM-1) is an inflammatory biomarker. We aimed to determine the role of VCAM-1 in predicting complicated appendicitis in children. Pediatric patients with suspected appendicitis admitted to the ED were enrolled in this prospective study. Pre-surgical serum VCAM-1 was tested in children with acute appendicitis within 72 h of symptoms (from day 1 to day 3). Serum VCAM-1 levels were further analyzed and compared between patients with and without complicated appendicitis. Among the 226 pediatric appendicitis patients, 70 had uncomplicated appendicitis, 138 had complicated appendicitis, and 18 had normal appendices. The mean serum VCAM-1 levels in patients with perforated appendicitis were higher than in those with simple appendicitis (p < 0.001). On day 1 to day 3, the mean VCAM-1 levels in patients with complicated appendicitis were all significantly higher than in those with uncomplicated appendicitis (all p < 0.001). Serum VCAM-1 levels may be helpful in differentiating uncomplicated and complicated appendicitis in children and could predict appendiceal perforation.

Soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and Natalizumab Serum Concentration as Potential Biomarkers for Pharmacodynamics and Treatment Response of Patients with Multiple Sclerosis Receiving Natalizumab.

Natalizumab (NTZ) is an established treatment for highly active, relapsing-remitting multiple sclerosis. In the context of rare progressive multifocal leukoencephalopathy and extended interval dosing as a treatment option, biomarkers for treatment monitoring are required. Natalizumab serum concentration (NTZ SC) and soluble vascular cell adhesion molecule 1 (sVCAM-1) concentrationwere shown to change on treatment with NTZ. We aimed to investigate whether NTZ SC and sVCAM-1 could be suitable pharmacodynamic markers and whether they could predict disease activity on NTZ, improving the concept of personalized multiple sclerosis treatment. In a retrospective study at the Medical University of Innsbruck, Austria, we identified patients treated with NTZ and chose samples longitudinally collected during routine follow-ups for the measurement of NTZ SC and sVCAM-1 by an enzyme-linked immunosorbent assay. We correlated these with clinical and demographic variables and clinical outcomes. Furthermore, we analyzed the stability of NTZ SC and sVCAM-1 during treatment. One hundred and thirty-seven patients were included. We found a strong negative correlation between NTZ SC and sVCAM-1. Both showed significant associations with body mass index, infusion interval, sample age, and anti-drug-antibodies. Natalizumab serum concentration was reduced in extended interval dosing, but not sVCAM-1. Only sVCAM-1 showed a weak association with relapses during treatment, while there was no association with disease progression. Both NTZ SC and sVCAM-1 showed a wide inter-individual distribution while levels in single patients were stable on treatment. Soluble vascular cell adhesion molecule 1 is a suitable pharmacodynamic marker during treatment with NTZ, which is significantly reduced already after the first dose, remains stable in individual patients even on extended interval dosing, and strongly correlates with NTZ SC. Because of the high inter-individual range, absolute levels of sVCAM-1 and NTZ SC are difficult to introduce as treatment monitoring biomarkers in order to predict disease activity in single patients.

Resveratrol attenuates atherosclerotic endothelial injury through the Pin1/Notch1 pathway

The present study investigates whether resveratrol could modulate the endothelial dysfunction of atherosclerosis via the Pin1/Notch1 signaling pathway. To assess the vascular endothelial cell (VECs) injury in mice, the levels of serum soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin), soluble thrombomodulin (sTM), and von Willebrand factor (vWF) were measured. Expressions of Pin1 and Notch1 intracellular domain (NICD1), both mRNA and protein, were also measured. Human umbilical vein endothelial cells (HUVECs) treated with 100 μg/mL oxidized low-density lipoprotein (ox-LDL) were incubated with resveratrol at doses from 10 μM to 40 μM. Cell function was evaluated by measuring apoptosis, cell viability, lipid accumulation, and adherent human myeloid leukemia mononuclear (THP-1) cells. Resveratrol intervention in AS mice decreased the expression of serum sVCAM-1, sICAM-1, sE-selectin, sTM, and vWF and dose-dependently down-regulated Pin1 and NICD1 mRNA and protein expression in endothelial cells. Resveratrol intervention reversed ox-LDL-induced cell dysfunction by increasing viability and decreasing apoptosis, lipid accumulation, and the adhesion of THP-1 cells. These beneficial effects were reversed by the overexpression of Pin1. Resveratrol regulates endothelial cell injury of atherosclerosis by inhibiting the Pin1/Notch1 signaling pathway, suggesting novel therapeutic targets for atherosclerosis treatment.

Effect of Shuxuening combined with edaravone on neurological function, serum VEGF and serum sVCAM-1 in patients with cerebral infarction

Objective To investigate the effects of Shuxuening injection combined with edaravone on neurological function, serum vascular endothelial growth factor (VEGF) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with cerebral infarction. Methods A total of 112 patients with cerebral infarction admitted to Zhejiang Provincial Armed Police Hospital from August 2016 to August 2018 were enrolled in the study.They were divided into observation group and control group according to the digital table, with 56 patients in each group.The two groups were given routine symptomatic treatment.On the basis of this, the control group was given edaravone treatment, and the observation group was given Shuxuening injection combined with edaravone.The changes of NIHSS, GCS score, serum NSE, NGF, NTF, VEGF and sVCAM-1 levels before and after treatment were compared between the two groups, and the clinical efficacy was compared. Results After treatment, the effective rate of the observation group was 92.86%(52/56), which was higher than that of the control group 73.21%(41/56), the difference was statistically significant (χ2=7.669, P<0.05). After treatment, the NIHSS score, NSE, sVCAM-1 of the two groups were decreased, which of the observation group were lower than those of the control group[(3.27±1.16)points vs.(6.32±2.12)points, (13.15±1.14)μg/L vs.(17.64±1.89)μg/L, (648.56±134.67)ng/mL vs.(1 078.36±131.23)ng/mL], while the GCS score, NGF, NTF, VEGF levels of the two groups were elevated, which of the observation group were higher than those of the control group[(13.64±3.86)points vs.(11.89±3.41)points, (76.13±8.72)μg/L vs.(68.24±7.25)μg/L, (5.14±0.36)μg/L vs.(3.74±0.29)μg/L, (831.51±91.67)ng/L vs.(752.83±91.24)ng/L], the differences were statistically significant (t=9.414, 2.543, 15.223, 5.205, 22.663, 4.552, 15.672, all P<0.05). Conclusion Shuxuening injection combined with edaravone can improve the curative effect of patients with cerebral infarction, improve neurological function, effectively improve serum VEGF level and decrease sVCAM-1 level.It is worthy of clinical application. Key words: Infarction, middle cerebral artery; Central nervous system; Vascular endothelial growth factors; Shuxuening; Edaravone

Bitter melon (Momordica charantia) attenuates atherosclerosis in apo-E knock-out mice possibly through reducing triglyceride and anti-inflammation

BackgroundBitter melon (BM, Momordica charantia) has been accepted as an effective complementary treatment of metabolic disorders such as diabetes, hypertension, dyslipidemia and etc. However it is unclear whether BM can prevent the progression of atherosclerosis. To confirm the effects of BM on atherosclerosis and explore its underlying mechanisms, we design this study.MethodsTwenty four male apolipoprotein E knock-out (ApoE-/-) mice aged 8 weeks were randomly divided into control group fed with high fat diet (HFD) only and BM group fed with HFD mixed with 1.2%w/w BM. After 16 weeks, body weight, food intake, blood glucose, serum lipids were measured and the atherosclerotic plaque area and its histological composition were analyzed. The expression of vascular cell adhesive molecules and inflammatory cytokines in the aortas were determined using quantitative polymerase chain reaction.ResultsBody weight gain and serum triglycerides (TG) significantly decreased in BM group. BM reduced not only the atherosclerotic plaque area and the contents of collagen fibers in atherosclerotic plaques but also the serum soluble vascular cell adhesion molecule (VCAM)-1 and P-selectin levels, as well as the expressions of monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-6 in aortas.ConclusionOur study indicates that dietary BM can attenuate the development of atherosclerosis in ApoeE-/- mice possibly through reducing triglyceride and anti-inflammation mechanism.

Relationship between serum vascular cell adhesion molecule-1 and endothelin-1 levels with organ involvement and disease activity in systemic lupus erythematosus patients.

Background Endothelial dysfunction plays an important role in pathogenesis of systemic lupus erythematosus (SLE). Considering the importance of serum soluble vascular cell adhesion molecule-1 as the most abundant of the circulating adhesion molecules increased as a result of endothelial dysfunction and the role of endothelin-1 in pathophysiology of SLE, this study aimed to evaluate serum soluble vascular cell adhesion molecule-1 and endothelin-1 levels in SLE patients compared to healthy subjects. Methods In this cross-sectional study, 60 SLE patients according to the Systemic Lupus International Collaborating Clinics classification criteria for SLE and 40 age and sex-matched healthy controls were included. In patients, clinical examination was performed and SLE disease activity index was assessed. Serum endothelin-1 and soluble vascular cell adhesion molecule-1 levels were measured using ELISA kits. Results The mean ± standard deviation age of patients and controls was 31.91 ± 7.66 and 33.20 ± 10.08 years, respectively. Compared to healthy controls, serum soluble vascular cell adhesion molecule-1 (1023.8 ± 352.96 vs. 866.06 ± 109.91) and endothelin-1 (77.83 ± 16.27 vs. 54.45 ± 12.01) was significantly higher in SLE patients ( P = 0.003 and P < 0.001, respectively). The most common organs involved in patients were skin, joint and kidney. There were no significant differences in serum soluble vascular cell adhesion molecule-1 and endothelin-1 levels according to organ involvement, activity of disease and the conventional serum markers of disease activity ( P > 0.05). There was no significant correlation between disease activity, organ involvement and negative or positivity of autoantibodies as well as serum complement with endothelin-1 and vascular cell adhesion molecule-1 levels ( P > 0.05). Conclusions Although our study revealed higher serum soluble vascular cell adhesion molecule-1 and endothelin-1 levels in SLE patients compared to healthy controls, there were no significant correlations between their serum levels with organ involvement and disease activity.

Serum Soluble Vascular Cell Adhesion Molecule-1 Overexpression Is a Disease Marker in Patients with First-Time Diagnosed Antinuclear Antibodies: A Prospective, Observational Pilot Study.

Objective Antinuclear antibodies (ANA) serve as screening tests for connective tissue diseases but have low specificity. In this pilot study, we aimed to identify patients with first-time positive ANA and musculoskeletal complaints and correlate serum soluble vascular adhesion molecules as biomarkers. Methods Prospective, observational study with 100 ANA-positive patients, comparing them to age- and gender-matched healthy controls (HC, n = 75), was conducted. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), endothelial-leukocyte adhesion molecule-1 (sELAM-1), and vascular cell adhesion molecule-1 (sVCAM-1) were measured. A subgroup of patients with systemic sclerosis (SSc) treated with immunosuppressants was followed over 10 months. Results Patients belonged to three main entities: rheumatoid arthritis (RA, n = 32), collagen diseases (CD, n = 56) also including systemic sclerosis (SSc, n = 11), and other autoimmune diseases (n = 12). sICAM-1 was similar among groups. sELAM-1 was elevated by 1.9-fold in only in SSc. sVCAM-1 was elevated by 3.1-fold in RA and by 3.3-fold in CD and in other autoimmune diseases by 3.4-fold. Seven SSc patients with immunosuppression had a 2.7-fold increased sVCAM-1 at baseline and reached the levels of healthy controls after 5 months, while CRP, ESR, and clinical parameters remained unchanged. Conclusion Our study suggests that sVCAM-1 is a disease marker independent of standard serum parameters in several rheumatic diseases. This study is registered with EU PAS Register number: EUPAS22154.

Pre-operative serum VCAM-1 as a biomarker of atrial fibrillation after coronary artery bypass grafting

ObjectiveSystemic inflammation is a recognised contributory factor in the pathogenesis of de novo post-operative atrial fibrillation after cardiac surgery. This study aims to determine whether serum soluble vascular endothelial cell adhesion molecule (sVCAM-1) may predict the onset of POAF in patients under going coronary artery bypass grafting.Methods34 patients undergoing non-emergent, on-pump CABG were prospectively recruited. Plasma was obtained at 24 h pre-operatively and at 48 and 96 h post-operatively. POAF was defined by continuous Holter recording. Inter-group comparisons were performed using student t-test or ANOVA as appropriate.ResultsThirteen (13/34) patients developed POAF at a mean of 2.5 days post-operatively. Serum sVCAM-1 was significantly increased in the pre-operative serum of POAF when compared to non-POAF patients (p = 0.022). No significant difference was observed between the groups at 48 h (p = 0.073) or 96 h (p = 0.135) post-operatively. sVCAM-1 had a sensitivity of 60.0% and specificity of 77.27%, with an overall diagnostic accuracy of 75.2% in predicting POAF.ConclusionssVCAM-1 concentration in the pre-operative serum of patients undergoing CABG may accurately predict the onset of de novo POAF. As such, serum sVCAM-1 may be used as a predictive biomarker for this common arrhythmia. Further work must now perform prospective, targeted validation of these results in a larger patient cohort.

Acute effects of post-absorptive and postprandial moderate exercise on markers of inflammation in hyperglycemic individuals.

Systemic inflammation is involved in the development of several diseases, including cardiovascular disease and type 2 diabetes. It is known that vigorous exercise affects systemic inflammation, but less is known about exercise at lower intensities. Hyperglycemia can also entail pro-inflammatory responses; however, postprandial hyperglycemia is blunted if the meal is followed by exercise. Hypotheses were: (1) moderate physical exercise acutely affects levels of C-reactive protein (CRP) and serum soluble vascular cell adhesion molecule 1 (sVCAM-1) in hyperglycemic individuals and (2) the effect depends on whether the activity is performed in a post-absorptive or postprandial state. Twelve participants diagnosed with hyperglycemia, but not using anti-diabetic medication, underwent three test days in a randomized cross-over study; 1 control day without exercise, 1 day with 60min of treadmill walking ending 30min before breakfast, and 1 day with an identical bout of activity 30min after the start of breakfast. Food intake was strictly standardized and venous blood for CRP, and sVCAM-1 analysis was sampled at standardized timepoints during the first 3.5h after breakfast and once 24h later. Merged data from the two exercise days showed that sVCAM-1 increased from baseline (4 ± 16ng/mL) compared to the control condition (-28 ± 47ng/mL, ES = 0.7, p = 0.024). There was no statistically significant difference in changes in sVCAM-1 levels between the two exercise test days. Exercise did not affect CRP values. Moderate exercise increases sVCAM-1 in hyperglycemic individuals, whereas it does not affect CRP.

Soluble adhesion molecules as markers of native arteriovenous fistula thrombosis in children on uremia.

Vascular access represents a lifeline for children undergoing hemodialysis. A failure of vascular access among patients receiving regular hemodialysis is associated with increased morbidity, mortality and costs. We assessed the possibility of using soluble adhesion molecules as reliable predictors of vascular access failure in children on hemodialysis. Moreover, we evaluated whether there is an association among the different studied adhesion molecules in hemodialysis patients with thrombosed and non-thrombosed arteriovenous fistula fistulas (AVFs). This study included 55 hemodialysis children, 36 with good access and 19 with access failure, and 20 healthy volunteers. Forty-four patients had native AVFs and 11 patients had tunneled permanent catheter (11with thrombosed and 33 with non-thrombosed AVFs). Serum-soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin) and soluble P-selectin (sP-selectin) were measured using ELISA technique. A significant increase was found in the levels of sVCAM-1, sICAM-1, sE-selectin and sP-selectin versus controls and all hemodialysis patients, hemodialysis patients with good access and hemodialysis patients with access failure (P=0.001 for sVCAM-1 and sICAM-1 and P=0.0001 for sE-selectin and sP-selectin). A significant increase was found in the levels of sVCAM-1, sE-selectin and sP-selectin in both chronic hemodialysis patients with thrombosed and non-thrombosed native AVFs versus controls (P=0.0001 for all parameters). There was significant difference between both chronic hemodialysis patients with thrombosed and non-thrombosed native AVFs as regard to sVCAM-1 (54.64±30.82 versus 25.69±27.96ng/ml, P=0.04). Both sICAM-1 and sP-selectin were positively correlated with the erythropoietin (EPO) dose in hemodialysis children (r=0.31, P=0.04 and r=0.32, P=0.04, respectively). A significant positive association was found between E-selectin and sP-selectin in hemodialysis patients with thrombosed AVFs (r=0.83, P=0.04). There was a significant correlation between sVCAM-1 and EPO dose in thrombosed AVF group (r=0.84, P=0.01). The assessment of serum sVCAM-1 might be useful for the identification of the chronic hemodialysis patients at an increased risk for native AVFs thrombosis. The role of EPO in vascular access failure should be taken into consideration. The clinical relevance of these observations warrants further investigations.

Pentosan polysulfate treatment ameliorates motor function with increased serum soluble vascular cell adhesion molecule-1 in HTLV-1-associated neurologic disease

The main therapeutic strategy against human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) characterized by lower extremity motor dysfunction is immunomodulatory treatment, with drugs such as corticosteroid hormone and interferon-α, at present. However, there are many issues in long-term treatment with these drugs, such as insufficient effects and various side effects. We now urgently need to develop other therapeutic strategies. The heparinoid, pentosan polysulfate sodium (PPS), has been safely used in Europe for the past 50 years as a thrombosis prophylaxis and for the treatment of phlebitis. We conducted a clinical trial to test the effect of subcutaneous administration of PPS in 12 patients with HAM/TSP in an open-labeled design. There was a marked improvement in lower extremity motor function, based on reduced spasticity, such as a reduced time required for walking 10 m and descending a flight of stairs. There were no significant changes in HTLV-I proviral copy numbers in peripheral blood contrary to the inhibitory effect of PPS in vitro for intercellular spread of HTLV-I. However, serum soluble vascular cell adhesion molecule (sVCAM)-1 was significantly increased without significant changes of serum level of chemokines (CXCL10 and CCL2). There was a positive correlation between increased sVCAM-1and reduced time required for walking 10 m. PPS might induce neurological improvement by inhibition of chronic inflammation in the spinal cord, through blocking the adhesion cascade by increasing serum sVCAM-1, in addition to rheological improvement of the microcirculation. PPS has the potential to be a new therapeutic tool for HAM/TSP.

Effects of Metformin or an Oral Contraceptive Containing Cyproterone Acetate on Serum C-reactive Protein, Interleukin-6 and Soluble Vascular Cell Adhesion Molecule-1 Concentrations in Women with Polycystic Ovary Syndrome

The aim of the present study was to evaluate the effects of commonly used treatment regimens such as metformin (MET) or an oral contraceptive pill (OC) containing ethynyloestradiol and cyproterone acetate (EE-CPA) on surrogate serum CVD risk factors and markers of endothelial dysfunction (CRP, IL-6, sVCAM) in women with PCOS.This study was conducted in a crossover design in order to compare the effects of 2 different treatment regimens in the same subject and has been registered under the number NCT01798875 in the ClinicalTrials.gov registry.42 women with PCOS (age range 18-36 years, median BMI 24.9) were randomly assigned to treatment with MET (850 mg bid) or EE-CPA containing OC for 4 months. After 2 months washout period, treatments were crossed over.Treatment with and OC increased significantly serum CRP concentrations (from 0.77 mg/l [95% CI: 0.70; 2.18] to 1.70 mg/l [95% CI: 1.65; 3.69], P<0.001). Treatment with MET slightly reduced serum CRP levels, but this difference did not reach statistical significance (P=0.08). 4 months treatment with MET or EE-CPA had no effect on serum IL-6 and sVCAM-1 concentrations (P>0.05).Treatment with EE-CPA containing OC for 4 months in women with PCOS significantly raises serum CRP. Since this rise was not accompanied by the increase in serum concentrations of IL-6, which is the most potent and effective stimulant of hepatic CRP production, we can speculate that this effect is caused by the liver first-pass effect of oral oestrogen administration. If this in turn can confer, cardiovascular risk among these women warrants further -studies.

Prevalence and risk factors for pulmonary hypertension in patients with hemoglobin E/β‐thalassemia disease

To find the prevalence and risk factors of pulmonary hypertension (PHT) in adult patients with hemoglobin E/β-thalassemia disease (E/β-Thal). One hundred and ten clinically stable E/β-Thal outpatients, sixty-one of whom had undergone splenectomy, were prospectively studied using their clinical profiles, selected blood tests, chest roentgenogram, and transthoracic echocardiogram. Based on the pulmonary artery systolic pressure (PASP) values estimated by the echocardiogram of ≥36mmHg, they were dichotomized into those with (PHT+) and without (PHT-) PHT. PHT was found in 41 (37.3%) patients without gender preponderance. It was not due to the left heart and was not severe (PASP=46.3±10.4mmHg). PASP was higher in splenectomized patients (48.0±11 vs. 40.3±4.7mmHg (P=0.004)). PHT was found in 32 of 61 (52.5%) splenectomized patients, mostly (53%) in the second decade, and rarely (6.3%) during the first 5yr after splenectomy. PHT+ patients had more hemolysis (P=0.001-0.04 depending on the parameters), more asplenic cases (P<0.001), and higher serum soluble vascular cell adhesion molecule-1 (sVCAM-1) and high-sensitivity C-reactive protein levels (P=0.004 and 0.008, respectively). Strong risk factors by univariate analysis were serum sVCAM-1 levels ≥1600ng/mL, serum cell-free Hb≥3mg/dL, asplenia, and amount of NRBCs/100 WBCs >40. Prevalence of PHT in E/β-Thal patients was 37.3% without gender preponderance. Those with severe hemolysis and asplenia invariably had severer PHT. Strong risk factors were asplenia and associated markedly elevated values of sVCAM-1, cell-free Hb, and NRBCs in blood.

Features Associated With Pulmonary Hypertension In Splenectomized Patients With Hemoglobin E/β-Thalassemia Disease

IntroductionPulmonary hypertension (PHT) associated with thalassemia hemoglobinopathy is now an accepted clinical entity. Due to a high prevalence of thalassemia hemoglobinpathy worldwide, it is the most common entity of PHT. Despite the commonness, its pathogenesis is not yet completely understood. Although asplenia is a known risk factor, PHT does not develop in all splenectomized patients. The present study was therefore done to search for other associated features. Patients and MethodsSixty-one clinically stable splenectomized hemoglobin E/β-thalassemia disease (E/β-Thal) adult outpatients, on no medication aside from folic acid and who received no blood transfusion in the preceding 4 weeks, were prospectively studied. All gave written informed consent, and study protocol was approved by the institution ethics committee on studies in humans (#0774/2548). Transthoracic echocardiogram was used to evaluate cardiac function and to estimate pulmonary artery systolic pressure (PASP). PHT was defined as an estimated PASP ≥36 mmHg. Clinical features and laboratory data were dichotomized according to the presence (PHT+) or absence (PHT-) of PHT, and statistical analysis was done by STATA version 10 (Stata Corp, Texas), considering a P value<0.05 as statistically significant. ResultsOf the 61 patients, 32 (52.5%) were PHT+, 14 of whom were female. There was no gender difference between the 2 groups (p=0.246). All had normal left ventricular ejection fraction, and none had positive serology for human immunodeficiency virus. Results expressed in mean ± SD or median (range) of the various measured parameters and their statistically significant differences are shown in the following table. ConclusionsPHT was found in 52.5% of the 61 splenectomized E/β-Thal patients with no gender preponderance. Although PHT was found mostly after the first decade of splenectomy, its prevalence did not correlate with time elapsed since the procedure. Features associated with PHT in splenectomized E/β-Thal patients were greater transfusion requirement, lower RBC counts, higher serum lactate dehydrogenase (LDH) and lower serum cholesterol levels, as a reflection of more severe disease and more severe ineffective erythropoiesis; together with a higher serum soluble vascular cell adhesion molecule-1 (VCAM-1) levels, likely from chronic hypoxemia. Disclosures:No relevant conflicts of interest to declare.PHT+ (n=32)PHT- (n=29)P-valueAge (yrs)28.54 ± 10.1629.83 ± 10.940.635Duration post splenectomy (yrs)15.08 (0.92 – 39.42)14.92 (1.92 – 40.33)0.718Total PRBC transfusion (units)40 (3 - 452)21 (5 - 247)0.005RBC (x 106 /uL)2.98 ± 0.443.38 ± 0.620.008Corrected reticulocyte (%)5.8 (1.0 – 8.1)5.2 (0.9 – 16.9)0.692NRBC/100 WBC715.5 (120 – 2,510)435 (4 – 1,330)0.056Corrected WBC (x 103/uL)10.10 ± 3.999.28 ± 4.450.455Platelet (x 103/uL)751.16 ± 235.06697.96 ± 190.410.347Albumin (g/dL)4.26 ± 0.554.49 ± 0.360.087Globulin (g/dL)4.78 ± 1.174.09 ± 0.730.021Cholesterol (mg/dL)88.38 ± 23.36110.27 ± 24.060.003LDH (U/L)345.06 ± 130.80231.52 ± 106.080.006Serum cell-free Hb (mg/dL)4.68 (2.39 - 29.4)3.44 (1.01 – 13.93)0.067C-reactive protein (high sens) (mg/L)3.12 (0.67 – 41.31)1.83 (0.32 – 9.61)0.068Thrombin-antithrombin complexes (ug/L)4.20 (2.07 – 14.72)3.30 (1.20 – 11.31)0.490Soluble VCAM-1 (ng/mL)1,920.32 ± 600.601,325.33 ± 365.430.001NT pro BNP (pmol/L)9.27 (2.55 - 112.80)5.89 (2.00 – 21.60)0.086

SCM-198 attenuates early atherosclerotic lesions in hypercholesterolemic rabbits via modulation of the inflammatory and oxidative stress pathways

ObjectiveTo investigate SCM-198 (also known as “leonurine”), a compound in Herba leonuri, as well as its effect on the progression of atherosclerosis in hypercholesterolemic rabbits and underlying mechanisms. MethodsThirty New Zealand male White rabbits (5 groups, n = 6) were fed either a normal diet or a high-cholesterol diet (1%). The rabbits on the high-cholesterol diet received treatments of low, moderate, and high doses of SCM-198 and placebo concurrently. Eight weeks later, the animals underwent ultrasonographic imaging. They were then sacrificed for further pathological and molecular biological analysis. ResultsSCM-198-treated rabbits showed a significant alleviation in the development of atherosclerosis in a dose-dependent manner. The lesions were smaller after the SCM-198 treatments. In addition, the elasticity of the arteries and hemodynamic status improved, accompanied with a decrease in smooth muscle cell migration and, macrophage infiltration, as well as the expression of platelet-endothelial cell adhesion molecule-1 (PECAM-1) in the aortas. Marginal changes in the lipid parameters were found in the SCM-198-treated rabbits, with high-density lipid cholesterol (HDL-C) elevation and triglyceride (TG) reduction at the high dose. SCM-198 treatment dose-dependently reduced levels of serum soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as well as the mRNA levels of VCAM-1, IL-6, TNF-α, monocyte chemoattractant protein-1 (MCP-1), iNOS and MMP-9 in the aorta. In addition, SCM-198 also dose-dependently increased the total antioxidant capacities and in parallel decreased the lipid peroxidation levels in the serum and liver. The antioxidant effects of SCM-198 were implicated by the enhanced activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and levels of glutathione (GSH) in the liver, as well as the mRNA levels of CAT, SOD-1 and GPx in the aorta. ConclusionsIn a rabbit atherosclerotic model, SCM-198 dose-dependently ameliorated the progression of atherosclerotic lesions and vascular dysfunction accompanied by the suppression of inflammatory factors and oxidative stress. These findings suggested that SCM-198 might be a potential agent for the treatment of atherosclerosis.

RESTORE Study: Effects of a 24-Week Natalizumab Treatment Interruption on Immune Parameters and Multiple Sclerosis Magnetic Resonance Imaging Disease Activity (P06.168)

RESTORE Study: Effects of a 24-Week Natalizumab Treatment Interruption on Immune Parameters and Multiple Sclerosis Magnetic Resonance Imaging Disease Activity (P06.168)

Effect of Keishibukuryogan on Endothelial Function in Patients with at Least One Component of the Diagnostic Criteria for Metabolic Syndrome: A Controlled Clinical Trial with Crossover Design

We evaluated the effect of keishibukuryogan (KBG; Guizhi-Fuling-Wan), a traditional Japanese (Kampo) formula, on endothelial function assessed by reactive hyperemia peripheral arterial tonometry (Endo-PAT2000) in patients with metabolic syndrome-related factors by controlled clinical trial with crossover design. Ninety-two patients were assigned to group A (first KBG-treatment period, then control period; each lasting 4 weeks, with about one-year interval) or group B (first control, then KBG-treatment). In forty-nine (27, group A; 22, group B) patients completing all tests, the mean value of the natural logarithmic-scaled reactive hyperemia index (L_RHI) increased and those of serum nonesterified fatty acid (NEFA), malondialdehyde, and soluble vascular cell adhesion molecule 1 decreased significantly during the KBG-treatment period, but not during the control period, and 4-week changes of L_RHI, NEFA, and malondialdehyde between the 2 periods showed significance. These results suggest that KBG has beneficial effect on endothelial function in patients with metabolic syndrome-related factors.

Effects of Marine Omega-3 Fatty Acids on Serum Systemic and Vascular Inflammation Markers and Oxidative Stress in Hemodialysis Patients

Background and Aims: High concentrations of serum inflammation markers, especially vascular inflammation markers, are an important risk factor for cardiovascular diseases in hemodialysis patients. The present study was designed to investigate the effects of marine omega-3 fatty acids on serum systemic and vascular inflammation markers and oxidative stress in hemodialysis patients. Methods: Thirty-four hemodialysis patients were randomly assigned to either the marine omega-3 fatty acid or the placebo group. Patients in the omega-3 fatty acid group received 2,080 mg marine omega-3 fatty acids daily for 10 weeks, whereas the placebo group received a corresponding placebo.At baseline and the end of week 10, 5 ml blood was collected after a 12- to 14-hour fast. Results: Mean serum soluble intercellular adhesion molecule type 1 (sICAM-1) decreased significantly in the omega-3 fatty acid group at the end of week 10 compared to baseline (p < 0.05) and this reduction was significant in comparison with the placebo group (p < 0.05). No significant differences were observed between the two groups in mean changes in serum soluble vascular cell adhesion molecule type 1, sE-selectin, sP-selectin, C-reactive protein, interleukin-6, tumor necrosis factor-α, malondialdehyde and total antioxidant capacity. Conclusion: The results of the present study indicate that marine omega-3 fatty acids can reduce serum sICAM-1, a risk factor for cardiovascular diseases, but it has no effect on serum systemic inflammation markers and oxidative stress in hemodialysis patients.

Study of Serum Soluble Vascular Cell Adhesion Molecule-1 Level in Type 2 Diabetic Patients with Diabetic Retinopathy

Objective To study the change and the correlation of serum soluble vascular cell adhesion molecuh-1(sVCAM-1)level with diabetic retinopathy in type 2 diabetic patients.Methods 60 type 2 diabetic patients were selected for the study through the examination of ophthalmoscope and/or fundus fluorescence angiography by ophthalmologist.Diabetic patients were divided into three main groups:No signs of diabetic retinopathy(NDR)(n=20);Background DR(BDR)(n=20)Proliferative DR(PDR)(n=20).Healthy individuals matching sex and age of the patients were used as controls(n=20);Serum sVCAM-1 level was measured by ELISA,compared in diabetes without DR,with BDR,with PDR.These levels were compared with those of 20 controls.Results The serum level of sVCAM-1 in the DM patients with PDR or BDR and those without DR were significantly higher than those in healthy controls(all P＜0.001);Serum level of sVCAM-1 in PDR groups were higherthan those in DM patients with BDR or patients without DR(all P＜0.001);There was no difference between the patients with BDR and those without DR (P＞0.05).(4)In the DM patients,there was a positive correlation between serum sVCAM-1 and the course of diseases(r=0.338,P＜0.05),but no relationship with HbA1C,FBG,CHO,TG,LDL and INS.Conclusion Increased serum level of sVCAM-1 in different stage of DR patients suggested that they hagbe play an important role in the development of DR,and may assess the severity of diabetic retinopathy.The measuremem of serum sVCAM-1 levels in type 2 diabetic patients could be clinically useful for early diagnosis or treatment of diabetic retinopathy. Key words: Diabetic Retinopathy; Vascular cell adhesion molecule-1

Serum soluble vascular cell adhesion molecule-1 (sVCAM-1) in scleroderma patients and its relation to pulmonary involvement and disease activity

IntroductionPulmonary compromise in systemic sclerosis (SSc) includes pulmonary hypertension (PHT) and interstitial lung disease (ILD) which reflect specific pathological insults, namely, obliterative vasculopathy and fibrosis, respectively. Vascular (endothelial cell) injury and activation are the earliest and possibly primary events in the pathogenesis of SSc. Being one of the endothelium-related indices, serum soluble vascular cell adhesion molecule-1 (sVCAM-1) could be a useful parameter in vascular assessment. Aim of the workThe aim of this study was to (1) assess the serum level of sVCAM-1 in SSc patients and (2) investigate any correlation of sVCAM-1 with pulmonary involvement (PHT and ILD) and disease activity. Patients and methodsThis study was carried out on 15 SSc patients and 10 control subjects of matched age and sex. Each patient was subjected to history taking, full clinical examination, assessment of skin involvement by the modified Rodnan skin score (mRSS), routine laboratory investigations, assay of VCAM-1 by the use of ELISA test and multislice CT for assessment of PHT and ILD. ResultsThere was a statistically significant increase of serum sVCAM-1 in SSc patients compared to controls (p=0.0069). There were no statistically significant differences between sVCAM-1 levels in patients with and without PHT, patients with mild ILD and those with moderate to severe ILD as well as patients with limited and diffuse SSc. No significant correlation could be found in SSc patients between sVCAM-1 levels and mRSS (r=0.186, p=0.661), serum creatinine (r=−0.379, p=0.191) and different grades of ILD (r=−0.154, p=0.609). There was a statistically significant correlation between serum sVCAM-1 level and CRP (r=0.852, p=0.001). ConclusionThe increased level of sVCAM-1 among the studied SSc patients could not be strictly attributed to pulmonary endothelial cell activation/damage and its pathologic role could not be verified in this respect by this study. The pattern of its correlation with selected disease activity indices pointed out to its link to the inflammatory stage of SS. Consequently, it could be considered as a non specific marker of inflammation irrespective to the type and extent of systemic organ involvement.