sVCAM-1 Levels Research Articles

CD34+ and CD34+VEGFR2+ cells in poorly controlled hypertensive patients.

CD34+ and CD34+VEGFR2+ cells participate in the repair of damaged endothelium and vascular remodelling. As their number and activity change due to the development of cardiovascular diseases, they are recognised as useful markers of cardiovascular health. As ineffective blood pressure control concerns high percentage of hypertensive patients, the purpose of our study was to investigate if proportions of various CD34+ and CD34+VEGFR2+ populations change due to hypertension occurrence and the effectiveness of the therapy. We also wanted to establish which factors impact these cells. Circulating populations of CD34+ and CD34+VEGFR2+ cells were analysed in peripheral blood samples by flow cytometry. Serum/plasma levels of sICAM-1, sVCAM-1 and vWF were determined using immunoenzymatic assay. We did not observe differences in CD34+ populations, but proportions of CD34+VEGFR2+ (p = 0.006), CD34+VEGFR2+CD133+ (p = 0.002) and CD34+VEGFR2+c-Kit+ (p = 0.003) cells were reduced in patients with poorly controlled blood pressure. We have also established that these cells exhibit connections with age, blood pressure and sICAM-1 serum levels. However, multiparametric regression analyses did not indicate any of the analysed variables as independent factors affecting CD34+VEGFR2+ populations. CD34+VEGFR2+, CD34+VEGFR2+CD133+ and CD34+VEGFR2+c-Kit+ cells are reduced in poorly controlled hypertensive patients, which may be partially connected with increased cardiovascular complications and mortality observed in this group.

Spirulina maxima Decreases Endothelial Damage and Oxidative Stress Indicators in Patients with Systemic Arterial Hypertension: Results from Exploratory Controlled Clinical Trial.

(1) Background: Spirulina (Arthrospira) maxima has shown beneficial effects such as being anti-dyslipidemic, antiviral, antioxidant and antihypertensive. However, there are few and limited clinical studies. (2) Methods: a prospective, randomized, parallel pilot study of 4.5 g administration of Spirulina maxima or placebo for 12 weeks in 16 patients with systemic arterial hypertension (SAH) undergoing treatment with angiotensin-converting enzyme (ACE) inhibitors was performed to assess the effects on endothelial damage and oxidative stress indicators. The blood levels of sICAM-1, sVCAM-1, endothelin-1, and sE-selectin were quantified; the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and concentrations of reduced glutathione, oxidized glutathione, and thiobarbituric acid reactive substances, were also quantified before and after the treatment period. (3) Results: There were statistically significant (p < 0.05) decreases in systolic blood pressure, sVCAM-1, sE-selectin and endothelin-1 levels, and increases in glutathione peroxidase activity and oxidized glutathione levels. (4) Conclusion: The effects found in the present study agree with antihypertensive and antioxidant effects previously reported for Spirulina maxima. However, this is the first report about the effects on indicators of endothelial damage. More research in this field is necessary to gain an insight into the effects of Spirulina on these indicators.

Assessment of soluble cytotoxic T lymphocyte-associated antigen-4, transforming growth factor β1, and platelet-derived microparticles during dasatinib therapy for patients with chronic myelogenous leukemia.

BackgroundThe outcome for chronic myelogenous leukemia (CML) patients presented in the chronic phase has changed dramatically since the introduction of tyrosine kinase inhibitor (TKI) therapy. Notably, an increased incidence of large granular lymphocytes (LGLs), which is related to immunological conditions, appears to be predictive of a favorable outcome for dasatinib therapy. We therefore examined the immunological characteristics of CML patients during dasatinib therapy by determining the plasma concentrations of five different biomarkers.MethodsThe plasma levels of biomarkers, specifically interleukin-6, platelet-derived microparticles (PDMPs), soluble vascular cell adhesion molecule 1 (sVCAM-1), transforming growth factor (TGF) β1, and soluble cytotoxic T lymphocyte-associated antigen-4 (sCTLA-4), were measured by ELISA at baseline and after 2 and 6 months of TKI treatment. The incidence of LGLs was estimated by microscopic examination.ResultsThe levels of PDMPs, sVCAM-1, and TGFβ1 were significantly elevated in patients with CML. Dasatinib treatment was associated with a significant reduction in the levels of these markers and with an increased incidence of LGLs compared with imatinib or nilotinib treatment. In addition, an increased incidence of LGLs was significantly correlated with a decreased sCTLA-4 level during dasatinib therapy.ConclusionThe assessment of the levels of specific biomarkers may be beneficial to understand the immunological conditions of patients with CML during dasatinib treatment.

Elevated Levels of Hepatokine Angiopoietin-like 3 Correlate Paradoxically with Hypocholesterolemia and Hemolysis in Sickle Cell Anemia

Sickle cell disease (SCD) is characterized by chronic hemolytic anemia and vaso-occlusion. Hypocholesterolemia has been long recognized in SCD patients, and while it has been postulated that it is secondary to increased erythropoiesis, these mechanisms are not fully understood. Despite their name, angiopoietin-like proteins (ANGPTLs) are family of regulators of angiogenesis unable to bind to receptors classically targeted by angiopoetins. ANGPTL3 and ANGPTL4 are also inhibitors of lipoprotein lipase (LPL), and have become pharmacological targets in the treatment of dyslipidemia. We hypothesized that ANGPTL levels would be abnormal in SCD and could contribute to the understanding of lipid dysregulation. We aimed to determine, compare and correlate the circulating concentrations of ANGPTL3 and ANGPTL4 with hemolysis, lipid metabolism and endothelial dysfunction biomarkers in patients with sickle cell anemia (HbSS), hemoglobin SC disease (HbSC), and healthy individuals (HbAA). Thirty-six HbSS patients (age range 18-55, 21 men), 19 HbSC patients (HbSC) (age range 29-68, 8 men), and 31 HbAA controls (age range 18-66, 23 men) were enrolled in this study. Exclusion criteria were pregnancy, history of blood transfusion or sickle cell pain crisis in the past 3 months. Peripheral blood samples were collected for complete blood counts, biochemistry tests (lactate dehydrogenase [LDH], bilirubin, cholesterol and low and high density fractions, oxidized LDL [oxLDL], hemopexin), and determination of ANGPTL3, ANGPTL4, and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels as marker of endothelial dysfunction. Differences in the intensity of hemolytic anemia between the two groups of SCD were confirmed, as well as decrease in total cholesterol (AA 176±32, SC 141±28 and SS 124±33mg/dL, p<0.0001), HDL (AA 46±11, SC 45±9, SS 37±11mg/dL, p<0.001) and LDL (AA 97±30, SC 76±34 or SS 63±27mg/dL, p<0.0001), as expected. Levels of both ANGPTL3 and ANGPTL4 were significantly higher in both SCD groups than in controls (ANGPTL3: AA 106±30, SC 147±37 and SS 155±58ng/mL, p<0.0001; ANGPTL4: AA 29±23ng/mL, SC 49±52ng/mL, SS 52±39ng/mL, p=0.04). While ANGPTL4 correlated only with LDH and HDL, ANGPTL3 correlated positively with reticulocyte count, LDH, total bilirubin, sVCAM-1, and the degree of LDL oxidation as estimated by oxLDL/LDL ratio, and negatively with hemoglobin, hemopexin, total cholesterol, and LDL levels. Our findings are surprising because the increase in AGPTLs should enhance inhibition of lipoprotein lipase, which is expected to cause hypercholesterolemia. It is therefore possible that hemolytic stimulus is able to override a feedback controlled by the liver between the amount of circulating lipoproteins and the need for LPL inhibition. This may also at least partially support the assumption that the plasma cholesterol pool is consumed for the synthesis of new red blood cells, so inhibition of LPL in this setting could be a compensatory mechanism. Nevertheless, the lack of significant differences between HbSS and HbSC suggests that erythropoietic drive is not the only determining factor. ANGPTL3 has been reported to be elevated in atherosclerosis and in rheumatic disease, so low grade chronic inflammation affecting the endothelium, along with a tendency towards more LDL oxidation could explain the positive correlation between sVCAM-1 and ANGPTL3. It is most remarkable that only ANGPTL3 correlated with hemolysis. ANGPTL3 is exclusively produced by the liver, while ANGPTL4 can be synthesized by adipose tissue, muscle, kidney, heart and thyroid, suggesting the stimulus for its overproduction generated by hemolysis is mostly sensed by hepatocytes. Considering the negative correlation with hemopexin, one possibility is that heme-hemopexin complexes taken up by liver cells and subsequent heme oxygenase induction may be involved in upregulation of ANGPTL3. Our data reveal that the production of lipoprotein lipase inhibitors is dysregulated in SCD-associated hypocholesterolemia, with a paradoxical increase in ANGPTLs which is most likely due to a liver response to hemolysis. Further studies should determine whether this mechanism is compensatory or driven by excessive heme production. DisclosuresFertrin:Alexion Pharmaceuticals Brasil: Speakers Bureau; Apopharma Inc.: Honoraria.

Clinical characteristics and prognosis of serous body cavity effusions in patients with sepsis: a retrospective observational study

BackgroundCavity effusion is common in patients with infectious diseases. However, the incidence rate and characteristics of serous cavity effusions (SCE) in septic patients are not clear to date. The objective of this study was to investigate the incidence and characteristics of SCE in septic patients and to explore the correlations between the bloody effusions and the illness severity/prognosis in septic patients.MethodsFrom January 2010 to January 2015, a total of 214 patients with severe sepsis and septic shock were enrolled in this retrospective observational study. Thoracentesis or abdominal paracentesis was performed in 45 septic patients because of massive pleural effusions or ascites. The serum concentrations of VEGF, VEGFR, Ang, sICAM-1, sVCAM-1, E-selectin, Serpine1 and VE-cadherin in 45 septic patients underwent paracentesis were measured by enzyme-linked immunosorbent assay (ELISA).ResultsOf the 214 septic patients, 155 (72.4%) had SCE according to imaging or ultrasound manifestations. 45 subjects with SCE underwent therapeutic thoracentesis or abdominal paracentesis. Effusion laboratory analysis showed that exudates were predominant when compared with transudates (95.6% vs. 4.4%), and 16 (35.6%) patients suffered bloody effusions. Compared with patients with non-bloody effusions, those with bloody effusions showed higher critical illness scores (13 vs. 17 for APACHE II; 7 vs. 9 for SOFA), and higher mortality (6.9% vs. 62.5%). Moreover, patients with bloody effusions had delayed TT and APTT, increased D-dimer concentration, and higher serum levels of CRP and PCT (P < 0.05). In addition, the serum levels of Ang2, sVCAM-1 and E-selectin were significantly higher in patients with bloody effusions than in those with non-bloody effusions (P < 0.05). However, the serum level of VEGFR2 was lower in patients with bloody fluids (P = 0.025).ConclusionsThe incidence of serous cavity effusion is high in patients with sepsis. The septic patients with bloody effusions suffer a more inflammatory burden and a worse prognosis compared to septic patients with non-bloody effusions.

Endothelial Function in Children with Acute Lymphoblastic Leukemia (ALL) May Reflect the Clinical Outcome.

Endothelial dysfunction is a common feature of early complications of hemato-oncologic therapy. The aim of our study was to assess the profile of endothelial function at diagnosis time, then during initial treatment phase of acute lymphoblastic leukemia (ALL), and to verify the presence of its correlation with early clinical outcome (ECO). 28 ALL children and 18 healthy age-matched control ones were recruited. Study group was examined at baseline and at 33rd and 78th day of treatment. At each protocol step the endothelial function was assessed by measurement of sP-selectin (CD62-P), PAI-1(serpinE1), sE-selectin (CD62E), sICAM-1(sCD54), sVCAM-1(sCD106), and VEGF concentrations. Higher baseline sICAM-1 and sVCAM-1 levels and lower sP-selectin and VEGF were observed in children with ALL. sICAM-1, sVCAM-1, and sE-selectin levels were decreasing following the treatment with protocol I. Higher sE-selectin and lower baseline sICAM-1 levels were observed in children treated unsuccessfully. Lower PAI-1 levels were observed in children who survived. Higher baseline sE-selectin levels and lower sICAM-1 and VEGF were observed in children treated unsuccessfully. A decrease in sE-selectin and lower PAI-1 at the 78th day of therapy were associated with better ECO. High baseline VEGF and sE-selectin levels, significant increase in PAI-1, and low initial sICAM-1 levels are prognostics for poorer prognosis in the ALL children.

Enhanced expression of TACE contributes to elevated levels of sVCAM-1 in endometriosis.

Are increased sVCAM-1 and sICAM-1 levels associated with tumor necrosis factor-alpha-converting enzyme (TACE) activity in endometriosis? Here we provide the first functional evidence that induced TACE activity in human endometriotic epithelial cells is at least in part responsible for the enhanced release of sVCAM-1 from these cells. We and others have shown that serum-soluble (s)VCAM-1 levels are significantly higher in women with endometriosis, compared to disease-free controls. Experimental evidence exists suggesting a role of sICAM-1 and sVCAM-1 in the pathogenesis of endometriosis. TACE was identified as the protease responsible for phorbol 12-myristate 13-acetate (PMA)-induced VCAM-1 release in murine endothelial cells. Additionally, it has recently been shown that TACE is upregulated in the endometrial luminal epithelium of the mid-secretory phase in infertile women. This study was conducted at the Tertiary Endometriosis Referral Center of the Medical University of Vienna. Samples from a total number of 97 women were collected between July 2013 and September 2014. After complete surgical exploration of the abdominopelvic cavity, 49 women with histologically proven endometriosis and 48 endometriosis-free control women were enrolled. Each participating woman contributed only one sample of eutopic endometrium and normal peritoneum, and some of the women with endometriosis contributed samples of diverse types of endometriotic lesions (in total 52 ectopic samples). Among the 49 women with endometriosis, 36 matched samples of endometriotic lesions and corresponding eutopic endometrium were collected. In order to detect sVCAM-1 and TACE protein by ELISA, peritoneal fluid (PF) samples were collected from 44 cases and 32 controls during surgery. Expression of TACE mRNA was analyzed by qRT-PCR in 111 endometrium tissue samples (28 eutopic control samples, 33 eutopic samples from women with endometriosis, 50 ectopic samples from lesions) and 37 healthy peritoneum samples. Immunohistochemistry was performed in 123 tissue samples (39 eutopic control samples, 42 eutopic samples from women with endometriosis, 42 ectopic samples from lesions) and the relation between tissue TACE protein levels and sVCAM-1 secretion was examined. PMA-induced sVCAM-1 release, and TACE- and VCAM-1-transcripts or proteins were measured in an immortalized endometriotic epithelial cell line (11Z) pre-incubated either with TACE inhibitors or following TACE siRNA knockdown. Here, we demonstrate that TACE protein is overexpressed in epithelium of tissue samples of both eutopic endometrium and ectopic lesions of women with endometriosis compared to disease-free controls (P < 0.001 both) and that the overexpression of the protein in the lesions is due to activation of TACE gene transcription (P < 0.001). Moreover, epithelial TACE protein was significantly higher in ectopic samples than in corresponding eutopic tissue of women with the disease (P < 0.001). High endometrial tissue TACE protein expression correlated with higher serum sVCAM-1 levels (P < 0.05) but not with sICAM-1 levels. Inhibition of TACE either by TACE inhibitors or by TACE siRNA knockdown resulted in decreased PMA-induced shedding of sVCAM-1 in vitro (P < 0.005 or P < 0.01, respectively), but the TACE inhibitors did not affect transcription of TACE or VCAM-1. Additionally, we observed an upregulation of TACE in proliferative endometrial epithelium of infertile (P < 0.005), compared to fertile women. TACE was increased in infertile women with endometriosis (P = 0.051) but not in infertile women without endometriosis. Albeit well characterized, our control population included women with other gynecologic diseases, which may have impacted the levels of sVCAM-1 and tissue TACE expression levels, e.g. benign ovarian cysts or uterine fibroids. Thus, the results of our analysis have to be interpreted carefully and in the context of the current experimental settings. The dysregulation of TACE substrate shedding represents a promising yet relatively unexplored area of endometriosis progression and could serve as a basis for the development of new treatments of the disease. This work was supported by the Ingrid Flick Foundation. The authors have no competing interests to declare.

Plasma levels of soluble NCAM in multiple sclerosis

In multiple sclerosis (MS), several adhesion molecules are involved within the central nervous system in inflammatory and neurodegenerative processes that are associated to progressive disability and increasing brain atrophy. The neural cell adhesion molecule (NCAM) has been suggested to participate in the reparative mechanisms and in the remyelination processes, key issues in MS pathology. We aimed at investigating plasma levels of the seldom investigated soluble (s)NCAM, and as comparison those of intercellular adhesion molecule-1 (sICAM-1) and vascular adhesion molecule-1 (sVCAM-1), and their association with clinical and MRI measures of lesion volumes and of global and regional atrophy. The cross-sectional study was conducted in 85 relapsing-remitting (RR)-MS, 53 progressive (P)-MS patients, and 42 healthy individuals (HI).Correlation of MRI measures with plasma levels of these adhesion molecules were not observed.In the MS and HI groups, sNCAM levels were significantly and positively associated with sVCAM-1 levels. Differently, the correlation between sICAM-1 and sVCAM-1 was observed only in MS patients. sNCAM and sVCAM-1 levels were higher in P-MS compared to HI (P = 0.05 and P = 0.028 respectively). The sVCAM-1 levels differed (P < 0.001) among DMTs groups and HI.The association of sNCAM plasma levels with MS disease, as well as differences in sVCAM-1 levels in patients receiving different DMTs, deserve further investigation.

The role of biomarkers of endothelial activation in predicting morbidity and mortality in patients with severe sepsis and septic shock in intensive care: A prospective observational study

IntroductionEndothelial dysfunction plays an essential role in the pathogenesis of sepsis. The study aimed to illustrate the associations between the dynamic change (from day 1 to day 7) in biomarker concentration of endothelial dysfunction and outcomes in severe sepsis and septic shock in the intensive care unit (ICU). Materials and methodsWe studied 102 patients enrolled in the Beijing Chao-yang Hospital affiliated with the Capital Medical University. A receiver operating characteristic (ROC) curve were used to assess the prognostic values of the circulating adhesion Angiopoietin-2/Angiopoietin-1 ratio (Ang-2/Ang-1) and Angiopoietin-1/Tie-2 ratio (Ang-1/Tie-2), intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and thrombomodulin (TM). Spearman's rank correlation and a multiple regression analysis were used to assess the relationship between the change in sequential organ failure assessment (Δ SOFA) score (SOFA score at day 7 minus SOFA score at day 1) and the levels of Δ Ang-2/Ang-1 and Δ Ang-1/Tie-2 ratios, ΔsICAM-1, ΔsVCAM-1 and Δ sTM. ResultsThe Ang-2/Ang-1 ratio, sICAM-1, sVCAM-1 and sTM levels significantly increased from day 1 to day 7 (all p = 0.045), and the Ang-1/Tie-2 ratio level markedly decreased from day 1 and day 7 (p = 0.027) in non-survivors. The biomarkers at Days 1 and 7 had significant prognostic value for 90-day mortality in severe sepsis and septic shock in ICU. The difference in biomarkers for endothelial dysfunction were suggested to be effective, independent predictors of changes in Δ SOFA. ConclusionsEndothelial dysfunction may constitute an independent contributor to sepsis-associated outcomes in ICU.

ASSOCIATION OF COAGULATION FACTORS WITH THE PRESENCE OF UNSTABLE ATHEROSCLEROTIC PLAQUES IN THE CORONARY ARTERIES

Objective. This study was devoted to examinationof some factors of blood coagulation (factor II, factor VII, factor XII, antithrombin III) in order to find their associations with biomarkers of endothelial dysfunction (endothelin 1, monocyticchemoattractant protein type 1, MCP-1, lipoprotein (a), LP (a), adhesive molecules sVCAM-1, asymmetric dimethylarginin, ADMA, homocysteine), inflammation (interleukins, IL-6, IL - 8, C-reactive protein, CRP) and with unstable atherosclerotic plaques in the coronary arteries in men with coronary atherosclerosis.Material and methods. In 93 men with coronary atherosclerosis without acute coronary syndrome, blood coagulation factors concentrations (factor II, factor VII, factor XII, antithrombin III) were studied in the blood with goal to find their associations with biomarkers of endothelial dysfunction (endothelin 1, MCP-1, LP(a), adhesion molecules sVCAM-1, ADMA, homocysteine), of inflammation (IL-6, IL-8, CRP) and with the presence of unstable plaques in the coronary arteries.Results. In men with unstable atherosclerotic plaques in the coronary arteries, the blood levels of factor VII and factor XII were 1.3 and 1.3 times higher, respectively, compared to men who had stable plaques in the coronary arteries. Correlation links between the blood levels of factor II and factor XII and the presence of unstable atherosclerotic plaques in the coronary arteries (r=0.239 and r=0.250, p &lt;0.05, respectively) have been revealed, as well as between coagulation factors and blood levels of LP(a), sVCAM-1, IL-6 and CRP. Results of logistic regression analysis showed that the relative risk of present of unstable atherosclerotic plaques in the coronary arteries is associated with an elevated blood level of factor XII (OR=1.008, 95 % CI 1.000-1.017, p=0.048).Conclusion. Our results indicate that elevated blood levels of the Hageman factor may be a new biomarker of probability of unstable atherosclerotic plaques presence in the coronary arteries.

Linking systemic angiogenic markers to synovial vascularization in rheumatoid arthritis.

BackgroundNeoangiogenesis is a crucial event to promote the development of the hyperplasic proliferative pathologic synovium in Rheumatoid arthritis (RA). Ultrasound (US) is sensitive for detection of power Doppler (PD) vascularization.ObjectiveTo explore the associations between a set of complementary circulating angiogenic markers and a comprehensive US assessment in patients with RA.Patients and methodsSerum levels of eight angiogenic markers were measured by quantitative ELISAs in a total of 125 patients with RA, who were all systematically assessed in parallel by PDUS, performed on 32 joints.ResultsSerum levels of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and Tie-2 were more likely to be increased in patients with synovial hyperemia detected on at least one joint (Power Doppler grade ≥1). sVCAM-1, Tie-2 and Angiostatin concentrations gradually increased together with the grade of the semiquantitative PDUS scale and concentrations of these three markers were markedly increased in patients with moderate to marked hyperemia (Power Doppler grade 2 and 3). Levels of sVCAM-1, Tie-2, and Angiostatin correlated with a global arthritis sum score, defined by the sum of the semiquantitative PDUS scores for all joints examined. Levels of Tie-2 and Placenta Growth Factor (PlGF) were associated with PDUS features indicating residual disease activity.ConclusionOur results support the relevance of measuring serum levels of vascular markers to evaluate the intensity and extent of synovial vascularization. Angiogenic markers, and particularly Tie-2, could be a valuable surrogate of active synovitis and their place in relation to PDUS in clinical practice deserve further investigation.

Effect of severe hyperemesis gravidarum on maternal vascular endothelial health: evaluation of soluble adhesion molecules

Purpose: This study aimed to clarify the effect of severe hyperemesis gravidarum (sHG) on maternal vascular endothelial health with evaluation of soluble adhesion molecules.Method: The study population consisted of two groups of pregnant participants between 18 and 35 years of age who were between 5 and 13 weeks of gestation: sHG group and a healthy control group. A group of 26 participants whose pregnancies were complicated by sHG was compared with 26 healthy participants regarding serum levels of the soluble adhesion molecules such as E-selectin, soluble intracellular cell adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule one (sVCAM-1), as well as other biochemical markers. The two groups had similar baseline characteristics.Results: Maternal baseline characteristics were similar in both groups. Serum levels of E-selectin (p < .001), sICAM-1 (p < .001), and sVCAM-1 (p < .001) were higher in the sHG group compared with the control group. Higher blood urea nitrogen, creatinine, and sodium levels, serum osmolarity, and urine density (p < .001, < .001, .006, .041, and .001, respectively) were also observed in the sHG group compared with the control group.Conclusions: The findings of this study indicated that sHG could impact endothelial cell function and these changes represented hypovolemia and dehydration caused by severe vomiting. Large-scale studies are required to understand the clinical importance of this finding regarding the long-term consequences and underlying mechanisms of elevated sICAM-1, sVCAM-1, and sE-selectin synthesis.

Effect of daily intake of a low-alcohol orange beverage on cardiovascular risk factors in hypercholesterolemic humans

Oxidative stress, inflammation status, endothelial dysfunction, and imbalanced lipid metabolism play a major role in cardiovascular disease. Bioactive compounds and moderate alcohol consumption have been associated with decreased cardiovascular risk. This study aimed to evaluate the effect on cardiovascular risk factors of a low-alcohol beverage derived from the alcoholic fermentation of orange juice. Eighteen individuals with moderately high cholesterol levels were randomly assigned to an experimental group (n = 9) who drank 500 mL/day of the orange beverage for 2 weeks or a control group (n = 9) who drank no orange beverage. Blood samples were drawn at the beginning and end of the study period. Consumption of the beverage significantly decreased plasma levels of total cholesterol (−15.6%), LDL-cholesterol (−17.8%), LDL-cholesterol/HDL-cholesterol ratio (−21.4%), catalase (−25.5%), TBARS (−42.6%), and sVCAM-1 (−5.8%). This orange beverage would have a potential capacity to improve cardiovascular risk in hypercholesterolemic humans, supporting its future consideration as a functional beverage.

Clinical effect of Shenqi-Tongmai decoction in stable angina pectoris patients with Qi-deficiency-blood-stasis syndrome and the influence on levels of serum associated adhesion factors

Objective To investigate the effect of Shenqi-Tongmai decoction in Stable Angina pectoris Patients with Qi-deficiency-blood-stasis syndrome and the influence on serum associated adhesion factors. Methods A total of 110 patients with stable angina pectoris treated in the department of cardiology of traditional Chinese medicine hospital of Xinle city from Feb. 2015 to Feb. 2017 were divided into 2 groups according to the number random table method, with 55 in each group. All the patients were given the standardized treatment with western medicine, and the treatment group were aditionally treated with the Shenqi-Tongmai decoction. All the patients were treated for a course of 4 weeks. The TCM syndrome score, Seattle angina questionnaire (SAQ) score, electrocardiographic examination index and serum soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1) level of the two groups before and after treatment were compared, and the clinical curative effect of the two groups was compared. Results The TCM syndrome score (7.1 ± 2.2 vs. 11.4 ± 3.0, t=8.590), serum sICAM-1 (227.69 ± 42.81 ng/ml vs. 275.33 ± 48.62 ng/ml, t=5.454) level, serum sVCAM-1 (272.04 ± 39.87 ng/ml vs. 296.58 ± 42.60 ng/ml, t=3.127) level and lead ecg ST segment down number (2.7 ± 0.6 vs. 3.2 ± 0.6, t=4.067), T wave of low lead numbers (1.7 ± 0.3 vs. 2.1 ± 0.3, t=6.807), numbers of T wave inversion lead (1.7 ± 0.3 vs. 2.1 ± 0.2, t=9.908) of the treatment group were significantly lower than those of the control group (P<0.01). The SAQ scores (76.8 ± 10.5 vs. 67.4 ± 10.1, t=4.805) was higher than that of the control group (P<0.01). The curative effect of angina pectoris and electrocardiogram of the treatment group were 91.0% (50/55) and 92.7% (51/55), and the control group were 76.4% (42/55) and 78.2% (43/55). The difference was statistically significant between the two groups (χ2=4.251, 4.681, P<0.05). Conclusions Traditional Chinese medicine Shenqi-Tongmai decoction can effectively improve the SAQ scores and TCM syndrome score and electrocardiogram examination index, improve the clinical curative effect in the treatment of Stable Angina pectoris based on the western medicine (Qi-deficiency-blood-stasis syndrome) and its mechanism may be related to improving of the serum levels of sICAM 1, sVCAM 1. Key words: Angina, stable; Qi-deficiency blood stasis; Shenqi-Tongmai decoction; Soluble intercellular adhesion molecule-1; Soluble vascular cell adhesion molecule-1

Psychosocial stress and inflammation driving tryptophan breakdown in children and adolescents: A cross-sectional analysis of two cohorts

BackgroundTryptophan breakdown is an important mechanism in several diseases e.g. inflammation and stress-induced inflammation have been associated with the development of depression via enhanced tryptophan breakdown. Depression is a major public health problem which commonly starts during adolescence, thus identifying underlying mechanisms during early life is crucial in prevention. The aim of this work was to verify whether independent and interacting associations of psychosocial stress and inflammation on tryptophan breakdown already exist in children and adolescents as a vulnerable age group. MethodsTwo cross-sectional population-based samples of children/adolescents (8–18 y) were available: 315 from the European HELENA study and 164 from the Belgian ChiBS study. In fasting serum samples, tryptophan, kynurenine, kynurenic acid, C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-ɣ, soluble vascular adhesion molecule 1 (sVCAM1) and soluble intercellular adhesion molecule 1 (sICAM1) were measured. Psychological stress was measured by stress reports (subjective) and cortisol (objective – awakening salivary cortisol or hair cortisol). Linear regressions with stress or inflammation as predictor were adjusted for age, sex, body mass index, puberty, socio-economic status and country. ResultsIn both cohorts, inflammation as measured by higher levels of CRP, sVCAM1 and sICAM1 was associated with kynurenine/tryptophan ratio and thus enhanced tryptophan breakdown (beta: 0.145–0.429). Psychological stress was only associated with tryptophan breakdown in the presence of higher inflammatory levels (TNF-α in both populations). ConclusionsInflammatory levels were replicable key in enhancing tryptophan breakdown along the kynurenine pathway, even at young age and in a non-clinical sample. The stress-inflammation interaction indicated that only the stress exposures inducing higher inflammatory levels (or in an already existing inflammatory status) were associated with more tryptophan breakdown. This data further contributes to our understanding of pathways to disease development, and may help identifying those more likely to develop stress or inflammation-related illnesses.

Low-level laser irradiation modifies the effect of hyperglycemia on adhesion molecule levels.

Endothelium plays a key role in maintaining vascular homeostasis by secreting active factors involved in many biological processes such as hemostasis, angiogenesis, and inflammation. Hyperglycemia in diabetic patients causes dysfunction of endothelial cells. Soluble fractions of adhesion molecules like sE-selectin and vascular cell adhesion molecule (sVCAM) are considered as markers of endothelial damage. The low-level laser therapy (LLLT) effectively supports the conventional treatment of vascular complications in diabetes, for example hard-to-heal wounds in patients with diabetic foot syndrome. The aim of our study was to evaluate the effect of low-energy laser at the wavelength of 635nm (visible light) and 830nm (infrared) on the concentration of adhesion molecules: sE-selectin and sVCAM in the supernatant of endothelial cell culture of HUVEC line. Cells were cultured under high-glucose conditions of 30mM/L. We have found an increase in sE-selectin and sVCAM levels in the supernatant of cells cultured under hyperglycemic conditions. This fact confirms detrimental influence of hyperglycemia on vascular endothelial cell cultures. LLLT can modulate the inflammation process. It leads to a decrease in sE-selectin and sVCAM concentration in the supernatant and an increase in the number of endothelial cells cultured under hyperglycemic conditions. The influence of LLLT is greater at the wavelength of 830nm.

Liraglutide suppresses non-esterified free fatty acids and soluble vascular cell adhesion molecule-1 compared with metformin in patients with recent-onset type 2 diabetes

BackgroundIt has been suggested that liraglutide could have an impact on glucose and lipid metabolism disorder and adhesion molecule activation, which may play important roles in the vascular damage of diabetes. In this study, we examined the effects of liraglutide versus metformin on non-esterified free fatty acids, beta-cell insulin secretion, and adhesion molecule levels in patients with recent-onset type 2 diabetes mellitus.MethodsIn this study, 60 patients newly diagnosed with type 2 diabetes mellitus (mean age 33.97 ± 5.67 years) were randomly assigned to receive once-daily subcutaneous liraglutide or oral metformin. Before the study and after the 8-week treatment period, a 75 g oral glucose tolerance test was performed. Plasma glucose, lipids and lipoprotein, plasma insulin, glycaemic and insulin responses, non-esterified free fatty acids (NEFA), and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were evaluated.ResultsAfter 8 weeks, 120 min of NEFA (155 ± 125 vs 99 ± 73 µmol/L, P = 0.026) and the levels of sVCAM-1 (465 ± 136 vs 382 ± 131 ng/ml, P = 0.013) significantly decreased, while the early phase insulin secretion index (24.94 [7.78, 38.89] vs. 31.13 [17.67, 59.09], P = 0.031), fasting plasma insulin (104 [51, 123] vs 113 [54, 171] mIU/L, P = 0.015), 60 min plasma insulin (326 [165, 441] vs 471 [334, 717] mIU/L, P = 0.005), 120 min plasma insulin (401 [193, 560] vs 500 [367, 960] mIU/L, P = 0.047), and insulin area under the curve (AUCins) (648 [321, 742] vs 738 [451, 1118] mIU/L, P = 0.005) remarkably increased for patients in the liraglutide treatment group. The levels of sVCAM-1 dramatically decreased after 8 weeks of liraglutide treatment (503 ± 182 vs 382 ± 131 ng/ml, P = 0.046) compared to that of the metformin treatment group. At the same time, the differences before and after liraglutide treatment in 120 min of NEFA (− 32 [− 96, − 5] vs 5 [− 35, 38] µmol/L, P = 0.033) and AUCins (738 [451, 1118] vs 594 [357, 1216] mIU/L, P = 0.014) were remarkably enhanced compared to that of the metformin therapy. Nevertheless, there were no significant differences in fasting NEFA after liraglutide or metformin treatment. The reduction of 120 min NEFA (ΔNEFA) was positively correlated with the decrease of sVCAM-1 (ΔsVCAM-1) after 8 weeks of liraglutide treatment (r = 0.523, P = 0.003).ConclusionsOur results demonstrate that liraglutide administration is more effective than metformin in reducing 120 min NEFA and suppressing sVCAM-1 levels for recent-onset type 2 diabetes mellitus. We suggest that this outcome may be because liraglutide is associated with potentiating insulin secretion capacity, inhibiting vascular inflammatory cytokines, and antagonizing atherosclerosis.

Adhesion molecules in patients with severe atherothrombotic stroke

Abstract Introduction . Atherothrombotic stroke represents 34% of stroke cases among all the subtypes of ischemic stroke. Adhesion molecules are proteins associated with the basal membrane. They contribute to the intensification of adhesion processes, hyperaggregation of blood cells and microcirculation disorders. Objective. To investigate the blood levels of adhesion molecules in patients with severe atherothrombotic stroke. Materials and methods. For the study, we recruited 21 patients (mean age, 67 [61; 73] years) with atherothrombotic stroke in the carotid system who were observed for the initial 48 hours since the development of neurological symptoms. The patients were categorized as severe stroke based on the total NIHSS score (Me 15 [14; 18]) at the time of admission. The spectrum of soluble cellular adhesion molecules as immunological markers of endothelial dysfunction was studied. Results. Increased levels of sICAM-1, sPECAM-1, sР-selectin, sЕ-selectin and sVCAM-1 were revealed at the beginning of the acute period of atherothrombotic stroke. By the day 21, a decrease of sPselectin, sE-selectin and sVCAM-1 was seen, and this phenomenon was probably caused by effects of blood antiplatelet therapy and statins on cellular adhesion. Positive correlation was established between the VCAM-1 during the first 48 hours of atherothrombotic stroke and the severity of neurologic deficit by the day 21. In the subgroup of patients with lethal outcomes, sICAM-1 and sVCAM-1 levels were higher in comparison with patients with severe disability. Conclusion. Elevated expression of sVCAM-1 in the first 48 hours of atherothrombotic stroke is associated with severe neurologic deficit by the day 21 of stroke. The high levels of sICAM-1 and sVCAM-1 upon admission may be regarded as risk factors for lethal outcomes.

Effect of cerebrospinal fluid drainage after aneurysm clipping on hydrocephalus, cerebral vasospasm and serum IGF-1, sVCAM-1

Objective To investigate the value of cerebrospinal fluid drainage after aneurysm clipping in patients with intracranial aneurysm complicated with subarachnoid hemorrhage. Methods 84 intracranial aneurysms patients with subarachnoid hemorrhage were selected, and they were randomly divided into study group (n=42) and control group (n=42). The control group used simple suture after aneurysm clipping, the study group was given lumbar cistern drainage by implementation of the dural suture tube after aneurysm clipping.Before and after hydrocephalus and cerebral vasospasm, treatment changes of serum insulin-like growth factor 1 (IGF-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were compared between the two groups. Results The incidence rate of hydrocephalus of the study gruop was 4.8%, which was significantly lower than the 14.3% of the control group (χ2=9.743, P 0.05). The serum levels of IGF-1 and sVCAM-1 between the two groups had no statistically significant differences before operation (t=0.417, 0.603, all P>0.05). At the 8th day after operation, the serum levels of sVCAM-1 and IGF-1 of the study group were significantly lower than those of the control group (t=7.335, 6.856, all P<0.05). Conclusion After aneurysm clipping, the lumbar cistern drainage tube drainage is beneficial to reduce hydrocephalus and cerebral vasospasm incidence, inhibit the expression of serum IGF-1, sVCAM-1, with less adverse reactions, it is worthy of application. Key words: Aneurysm clipping; Subarachnoid hemorrhage; Cerebrospinal fluid drainage; Hydrocephalus; Cerebral vasospasm

High levels of an endothelial dysfunction marker (sVCAM-1) are associated with injurious and recurrent falls and mortality over a 5-year interval in an older population

We investigated the association between elevated plasma concentrations of circulating soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and injurious falls and mortality over a 5-year period. We studied the prospective relationship between levels of circulating adhesion molecules and falls in 680 community-dwelling participants in the MOBILIZE Boston Study. The mean sVCAM-1 (±SD) concentration was 1192 ± 428 ng/mL. Over 5-years of follow-up, 10.2% of participants died. The baseline sVCAM-1 (±SD) concentration was 1434 ± 511 ng/mL in those who died vs. 1162 ± 402 ng/mL in those who survived (P < 0.0001). sVCAM-1 level was associated with recurrent falls (P < 0.01); compared to the lowest quintile, the highest quintile of sVCAM-1 was associated with increased risk of injurious falls [multivariable adjusted Incidence Rate Ratio = 1.9, 95% CI (1.2–2.9), P = 0.009]. On survival analysis, the highest sVCAM-1 quintile was associated with the greatest mortality over 5 years (log-rank test, P < 0.0001). The adjusted hazard ratio was 2.4 [95% CI (2.1–2.7), P = 0.002]. High sVCAM-1 blood concentration was strongly associated with recurrent falls, injurious falls, and mortality in older adults.