Upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in renal tissue in severe dengue in humans: Effects on endothelial activation/dysfunction

Abstract INTRODUCTION: Dengue is an important mosquito-borne disease in tropical and subtropical regions. Adhesion molecules have not been systematically characterized in the renal tissue of patients with severe dengue (SD). The objective of this study was to detect viral antigens in samples from patients that evolved with SD, correlating with the expression of ICAM-1, VCAM-1, VE-cadherin, and E-selectin to contribute to a better understanding of the pathophysiology of SD. METHODS: Kidney specimens from patients with SD were selected according to clinical and laboratorial data and submitted to histological and immunohistochemistry analysis. A semiquantitative evaluation was performed considering positive immunostaining in 20 glomeruli. RESULTS: Viral antigens were mainly detected in distal tubules. The intense immunostaining of VCAM-1 and ICAM-1 was observed. The expression of E-selectin was discrete, and VE-cadherin expression varied from mild to moderate. VCAM-1 was slightly intense in the glomerular capsule; the expression of ICAM-1 was diffuse. E-selectin was diffuse, and VE-cadherin varied from mild to moderate. The most frequent histological findings were glomerular congestion, mild glomerulitis, acute renal injury, and glomerular atrophy. CONCLUSIONS: The results appear to demonstrate an imbalance between vascular endothelial permeability regulating events in renal lesions in SD. The increase in the expression of ICAM-1 and VCAM-1 is an in-situ indicator of higher permeability with a consequent influx of cells favoring the inflammation of the endothelium. These molecules are important in the pathophysiology of the disease and provide the possibility of developing new markers for the evaluation, clinical follow-up, and therapeutic response of patients with SD.

Relationship between circulating VCAM-1, ICAM-1, E-selectin and MMP9 and the extent of coronary lesions

OBJECTIVES: Inflammatory molecules play a role in the development of atherosclerosis, which is the primary origin of cardiovascular disorders. However, to the best of our knowledge, no study has attempted to investigate the relationship between these circulating molecules and the prediction of cardiovascular risk. The present study aimed to investigate the relationships of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 serum concentrations with the extent of coronary lesions. METHODS: Seventy-four individuals who were undergoing coronary angiography for the first time for diagnostic purposes were enrolled in this study. The extent of the coronary lesion was assessed using the Friesinger Index, and subjects were classified into four groups: no lesions, minor lesions, intermediate lesions and major lesions. Serum biochemical parameters and serum concentrations of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 were analyzed. RESULTS: The vascular cell adhesion molecule-1 concentration was higher than 876 ng/mL in individuals with intermediate and major lesions (p<0.001 and p=0.020, respectively). Moreover, logistic regression analysis showed that these patients had an increased risk of having an intermediate lesion (p=0.007). Interestingly, all individuals with major lesions had vascular cell adhesion molecule-1 concentrations higher than 876 ng/mL. No association was found between the concentrations of the other proteins and the Friesinger Index. CONCLUSIONS: Serum vascular cell adhesion molecule-1 may be associated with the extent of coronary lesions. Moreover, it may represent an alternative to improve the cardiovascular risk classification in patients without acute coronary syndrome.

Circulating early biomarkers of atherogenesis in participants of the Longitudinal Study of Adult Health (ELSA-Brasil) without diabetes or cardiovascular disease

ABSTRACT Objective Our aim was to describe the distribution of selected biomarkers according to age and sex, adjusted for HOMA-IR and adiposity, in a subset of middle-aged individuals of Brazilian Longitudinal Study of Adult Health-ELSA without diabetes mellitus or CVD. Subjects and methods This cross-sectional study was conducted in 998 participants of the ELSA-Brasil without diabetes and/or cardiovascular disease. In addition to the traditional risk factors, several biomarkers concentrations were compared according to sex, age groups (35-44; 45-54 yrs) and HOMA-IR tertiles. Linear regression was used to examine independent associations of sex and age with selected novel biomarkers, adjusted for body adiposity and HOMA-IR. Results Fifty-five percent were women. Men had higher mean values of body mass index, waist circumference, blood pressure, plasma glucose, HOMA-IR, worse lipid profile and higher E-selectin and lower leptin concentrations than women; while women had higher levels of HDL-cholesterol and leptin than men. Mean values of waist circumference, systolic BP, plasma glucose and apolipoprotein B (Apo B) increased with age in both sexes. Leptin and E-selectin concentrations increased across HOMA-IR tertiles. Independent associations of Apo B with age were found only in male sex, while of leptin with body mass index and HOMA-IR, and of E-selectin with HOMA-IR in both sexes. Conclusions In conclusion, our data indicate age, sex, adiposity and, consequently, insulin resistance, influence circulating levels of Apo B, leptin and E-selectin, suggesting that those aspects should be taken into consideration when assessing these parameters for research or clinical purposes in individuals at relatively low cardiometabolic risk.

Arterial stiffness and endothelial inflammation in prediabetes and newly diagnosed diabetes patients

ObjectiveThere is a growing body of data supporting the association between diabetes and microcirculatory disfunction. We aimed to study e-selectin levels, and their associations with serum markers of inflammation and arterial stiffness in prediabetes and newly diagnosed diabetes patients in this study.Subjects and methodsSixty patients (25 females) with a newly established elevated fasting serum glucose [20 impaired fasting glucose (IFG), 20 impaired glucose tolerance (IGT), 20 newly diagnosed diabetes (T2DM)] and 17 healthy controls (13 females) were included in the study. Serum e-selectin and hs-CRP levels, and arterial stiffness parameters of the patients were studied.ResultsFasting serum glucose was the most important predictor of serum e-selectin levels. Pulse wave velocity and central aortic pressures were significantly higher in IFG, IGT and T2DM groups, compared to controls (p = 0.001, < 0.001, 0.013 and 0.015, 0.002, 0.009, respectively). The mean arterial pressure did not show any significant association with serum e-selectin and hs-CRP levels (β coefficient: 0.092, p = 0.358; and β coefficient: 0.189, p = 0.362, respectively).ConclusionPrediabetes patients have increasing e-selectin levels through the diagnosis of T2DM. E-selectin is associated with serum glucose levels. Prediabetic and newly diagnosed diabetics have higher arterial stiffness measurements. Serum e-selectin may be a good marker of endothelial inflammation and dysfunction increasing in parallel with serum glucose levels, predicting future cardiovascular events.

Circulating E-selectin levels and insulin resistance are associated with early stages of atherosclerosis in nonfunctional adrenal incidentaloma

Objective To evaluate circulating E-selectin levels in patients with nonfunctional adrenal incidentaloma (NFA) in relation to insulin resistance and early atherosclerosis.Subjects and methods A total of 40 patients with NFA (mean [SD] age: 55.6 [10.7] years; 70% were females) and 35 controls (mean [SD] age: 51.5 [8.1] years; 71.4% were females) selected from age-, gender- and body mass index (BMI)- matched healthy subjects were enrolled. Serum hsCRP, lipid profile, insulin levels and the homeostasis model assessment of insulin resistance (HOMA-IR) were evaluated. High-resolution B-mode ultrasonography was performed. Serum levels of E-selectin were evaluated by enzyme-linked immunosorbent assay.Results Patients with NFA had significantly higher values for E-selectin (14.9 (4.8) vs. 12.2 (4.1) ng/mL, p < 0.01) and CIMT (0.6 (0.1) vs. 0.5 (0.1) mm, p < 0.05) than controls. Serum E-selectin levels showed a statistically significant association with hsCRP (r = 0.751, p < 0.001), HOMA-IR (r = 0.575, p < 0.001) and CIMT (r = 0.762, p < 0.001). CIMT (Carotid intima media thickness) was increased in patients with NFA patients with NFA were more insulin resistant than controls and statistically significant relationship was found between size of tumor and HOMA-IR (r = 0.361, p < 0.001).Conclusion In conclusion, based on significantly higher values for E-selectin, CIMT and HOMA-IR in patients with NFA than controls along with significant correlation of E-selectin levels to CIMT, HOMA-IR and hs-CRP, our findings seems to indicate an increased risk of early atherosclerosis and impaired endothelial function in NFA patients, particularly in case of insulin resistance.

Relationship between deep venous thrombosis and inflammatory cytokines in postoperative patients with malignant abdominal tumors

Deep venous thrombosis (DVT) is a common surgical complication in cancer patients and evidence that inflammation plays a role in the occurrence of DVT is increasing. We studied a population of cancer patients with abdominal malignancies with the aim of investigating whether the levels of circulating inflammatory cytokines were associated with postoperative DVT, and to determine the levels in DVT diagnoses. The serum levels of C-reactive protein (CRP), interleukins (IL)-6 and IL-10, nuclear transcription factor-κB (NF-κB) and E-selectin (E-Sel) were determined in 120 individuals, who were divided into 3 groups: healthy controls, patients with and patients without DVT after surgery for an abdominal malignancy. Data were analyzed by ANOVA, Dunnet's T3 test, chi-square test, and univariate and multivariate logistic regression as needed. The CRP, IL-6, NF-κB, and E-Sel levels in patients with DVT were significantly higher than those in the other groups (P<0.05). The IL-10 level was higher in patients with DVT than in controls but lower than in patients without DVT. Univariate analysis revealed that CRP, IL-6, NF-κB, and E-Sel were statistically associated with the risk of DVT (OR=1.98, P=0.002; OR=1.17, P=0.000; OR=1.03, P=0.042; and OR=1.38, P=0.003; respectively), whereas IL-10 had a protective effect (OR=0.94, P=0.011). Multivariate analysis showed that E-Sel was an independent risk factor (OR=1.41, P=0.000). Thus, this study indicated that an increased serum level of E-Sel was associated with increased DVT risk in postoperative patients with abdominal malignancy, indicating that E-Sel may be a useful predictor of diagnosis of DVT.

Study of prognostic values of soluble selectins E and P in successfully resuscitated children after cardiopulmonary arrest

Successful resuscitation of children with cardiopulmonary arrest [CPA] is often complicated by postresuscitation state related to ischemiaireperfusion injury. Studies demonstrated increase in release of soluble intercellular adhesion molecules including soluble E- and soluble P-selectins [sE- and sPselectins] during and after cardiopulmonary resuscitation [CPR]. Therefore, this study was carried out to analyze the relationship between plasma levels of sE- and sP-selectins in successfully resuscitated children after CPA and their outcome. Plasma levels of sE-and sP-selectin were measured 24 hrs after successful resuscitation of 65 children with CPA. Forty five [69.23%] patients out of 65 developed SIRS in the second day after CPR. Patients with SIRS had non significantly higher sE-selectin levels [95.58 +/- 32.38 ng/ml] than patients without SIRS [88.17 +/- 28.25 ng/ml] [p =0.67]. The mean value of sE-selectin was not significantly higher in patients with sepsis [96.53 +/- 30.62 ng/ml] than in patients without sepsis [89.39 +/- 27.57 ng/ml] [p = 0.48]. The mean value of sE-selectin was significantly higher in non survivors [147.65 +/- 43.64 ng/ml] than in survivors [87.63 +/- 25.89 ng/ml] [p <0.01]. Patients with SIRS had significantly higher sP-selectin levels [187. 12 +/- 64. 75 ng/ml] than patients without SIRS [100.42 +/- 33.70 ng/ml] [p =0.005]. The mean value of sP-selectin was significantly higher in patients with sepsis [172.40 +/- 54.43 ng/ml] than in patients without sepsis [105.60 +/- 34.35 ng/ml] [p =0.015]. The mean value of sP-selectin was not significantly higher in survivors [217.75 +/- 72.08 ng/ml] than in non survivors [175.69 +/- 51.43 ng/ml] [p = 0.175]. The total non survival was 57 [87.69%] patients. Cerebral performance at hospital discharge was good in 3 out-of 8 patients [37.5%] and unfavorable in 5 [62.5%] patients. sE-selectin had higher sensitivity [94.87%] and specificity [85.33%] in the prediction of non survival with an area under the ROC curve [95% CI] of 0.95 [0.84-0.99] and a cut-off value of 136 ng/ml. sP-selectin had higher sensitivity [87.50%] and specificity [96.55%] in the prediction of sepsis with an area under the ROC curve [95% CI] of 0.96 [0.86-0.99] and a cut-off value of 159 ng/ml. Successful CPR after cardiac arrest is associated with increase in sE- and sP-selectin and high incidence of SIRS. Estimation of sE-selectin may help detection of patients with high risk of poor outcome while estimation of sP-selectin may predict those with high risk for sepsis

Biochemical study on some adipocyto-kines in chronic renal failure: their relationship to endothelial dysfunction and inflammation

Chronic renal failure has been associated with impaired immunity and subclinical inflammation involving cytokines derived from adipose tissue - adipocytokines. Deteriorating renal function may increase overall inflammatory responses because of the decreased renal clearance of factors that are directly or indirectly involved in inflammation. Declining renal function may also affect the levels of additional inflammatory molecules such as C-reactive protein [CRP] and interleukin-6.The aim of the study was to assess visfatin and apelin in correlation with markers of endothelial cell injury and inflammation in 20 patients with CRF and 20 age- and sex-matched healthy controls.We assessed visfatin and apelin, markers of: coagulation: TAT [thrombin-antithrombin complexes]; fibrinolysis: tPA [tissue plasminogen activator] and PAI-1 [plasminogen activator inhibitor-1]; endothelial function/injury: 1CAM [intracellular adhesion molecule], VCAM [vascular cell adhesion molecule], CD40L and E-selectin and inflammation: hsCRP andIL-lbeta. Visfatin, apelin, TAT, ICAM, VCAM, CD40L, PAI-1, E-selectin, hsCRP, IL-lbeta and triglycerides were elevated while serum albumin and t-PA were decreased in CRF patients when compared with the control group.Significant positive correlations were found between visfatin on one hand and each of apelin, t-PA, PAI-1, E-selectin, ICAM, VCAM, hsCRP, LL-lbeta, CD40L and triglycerides on the other hand in patients with CRF.Also, Significant positive correlations were found between Apelin and each of EL-lbeta, E-selectin, ICAM, VCAM, creatinine and triglycerides in CRF

Marcadores de inflamación y disfunción endotelial en niños con diabetes tipo 1 / Inflammation markers and endothelial disfunction in children with type 1 diabetes

Se ha hallado un estado inflamatorio subclínico ha sido informado en la fase temprana de la diabetes, el cual incrementa los niveles séricos de citoquinas que inducen la síntesis de proteínas de fase aguda como la proteína C reactiva (PCR) y el fibrinógeno (Fg), y estimula la expresión endotelial de moléculas de adhesión. Se estudiaron 30 pacientes (15 varones y 15 mujeres) con diabetes tipo 1 (DT1), de 11.8 ± 2.1 años de edad y 3.9 ± 3.2 años de evolución de la enfermedad, sin complicaciones vasculares. Se realizó recuento de leucocitos, velocidad de sedimentación globular (VSG), glucemia en ayunas, hemoglobina glicosilada (HbA1c), Fg, PCR ultrasensible (uPCR), determinación E-selectina soluble (sE-S), molécula de adhesión vascular celular 1 (VCAM-1) y microalbuminuria. Se encontraron niveles aumentados de uPCR, sE-S y VCAM-1 en los pacientes diabéticos comparados con el grupo control [0.60 (0.30-1.25) vs. 0.20 (0.20-0.65) mg/l, p = 0.013], [108 (60-150) vs. 68 (56-82) ng/ml, p = 0.0031] y [750 (708-826) vs. 721 (674-751) ng/ml, p = 0.039] respectivamente. Al agrupar a los diabéticos de acuerdo a la duración de la enfermedad (= 3 y > de 3 años), los valores de uPCR fueron mayores en el segundo grupo. La uPCR se correlacionó con sE-S (r = 0.44, p = 0.03) y con VCAM-1 (r = 0.49, p = 0.02). Estos resultados sugieren la presencia de un estado proinflamatorio y de activación endotelial estrechamente asociados en la DT1.

A subclinical inflammation state was detected in the early step of diabetes, which increases the serum levels of cytokines that induce acute-phase protein synthesis as C-reactive protein (PCR) and fibrinogen (Fg), stimulating the endothelial disfunction of adhesion molecules. Thirty patients (15 boys, 15 girls) with type 1 diabetes (DT1), without vascular complications, were studied. Their mean age and duration of diabetes were 11.8 ± 2.1 and 3.9 ± 3.2 years, respectively. The laboratory parameters evaluated were: blood leukocytes count, globular sedimentation velocity, fasting glycemia, glycosylated hemoglobin (HbA1c), high sensitivity PCR (uPCR), plasma soluble E-selectin (sE-S), sVCAM-1 and microalbuminuria. Increased levels of uPCR, sE-S and VCAM-1 were found, compared with the control group control [0.60 (0.30-1.25) vs. 0.20 (0.20-0.65) mg/l, p = 0.013], [108 (60- 150) vs. 68 (56-82) ng/ml, p = 0.0031] y [750 (708-826) vs. 721 (674-751) ng/ml, p = 0.039] respectively. When diabetic patients were grouped according to duration of disease (= 3 and > de 3 years), uPCR values were higher in the second group. uPCR levels were better correlated with sE-S (r = 0.44, p = 0.03) and VCAM-1 (r = 0.49, p = 0.02). These results suggest the presence of pro-inflammatory and endothelial activation states, which are strongly associated with DT1.

Soluble cell adhesion molecules and parameters of lipoprotein metabolism in patients with severe burns / Moléculas de adhesión celular soluble y parámetros del metabolismo de la lipoproteína en pacientes con quemaduras severas

BACKGROUND: The role of leukocyte adhesion molecules in patients with burns and their relationship to other parameters of inflammation and lipid metabolism is only recently beginning to be explored. Therefore, we investigated the temporal changes in the levels of soluble cell adhesion molecules and other parameters of inflammation and lipoprotein metabolism in patients with thermal injury. MATERIALS AND METHODS: The serum levels of soluble adhesion molecules, intercellular cell adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin, C-reactive protein (CRP) and fibrinogen in seven patients with severe burns over a 30- day period were measured to determine the involvement of these factors in the pathophysiology of severe burns. Serum levels of sICAM-1, sVCAM-1 and sE-selectin were determined by ELISA. Furthermore, total cholesterol, high-density lipoprotein cholesterol (HDL chol), low-density lipoprotein cholesterol (LDL chol) and triglycerides (TG) were measured. RESULTS: Blood levels of sICAM-1, sVCAM-1, CRP and fibrinogen increased with maximum values six days after thermal injury. In contrast, serum levels of sE-selectin were elevated two days after thermal injury. The sICAM-1, sVCAM-1 and sE-selectin levels correlated significantly with both the CRP and the fibrinogen levels. Plasma total cholesterol, HDL cholesterol and LDL cholesterol decreased with minimum values four days after thermal injury. Furthermore, an increase of triglyceride levels was observed. CONCLUSION: The observed inflammatory response of soluble cell adhesion molecules could be useful in monitoring endothelial activation immediately following thermal injury. Further studies involving a larger number of patients with burns should help to clarify the extent to which measured parameters, especially the temporal changes of sCAMs, could be relevant in assessing the morbidity of patients with thermal injury.

ANTECEDENTES: El papel de las moléculas de adhesión leucocitaria en pacientes con quemaduras y su relación con otros parámetros de inflamación y metabolismo de lípidos ha comenzado a ser explorados sólo recientemente. Por lo tanto, investigamos los cambios temporales en los niveles de las moléculas de adhesión celular solubles y otros parámetros de inflamación y metabolismo de las lipoproteínas en pacientes con daños térmicos. MATERIALES Y MÉTODOS: Los niveles de suero de las moléculas de adhesión solubles, las moléculas 1 de adhesión intracelular (sICAM-1), las moléculas 1 de adhesión celular vascular (sVCAM-1) y sE-selectina, la proteína reactiva C (CRP), y el fibrinógeno en siete pacientes con quemaduras severas en un período de 30 días, fueron medidas a fin de determinar la participación de estos factores en la patofisiología de las quemaduras severas. Los niveles séricos de sICAM-1, sVCAM-1 y sE-selectina fueron determinados mediante ELISA. Además, se midieron el colesterol total, el colesterol de lipoproteína de alta densidad (HDL col), el colesterol de lipoproteína de baja densidad (LDL col), y los triglicéridos. RESULTADOS: Los niveles de sangre de sICAM-1, sVCAM-1, CRP y fibrinógeno aumentaron a valores máximos, seis días después del daño térmico. Los niveles de sICAM-1, sVCAM-1 y sE-selectina tuvieron una correlación significativa tanto con la CRP como con los niveles de fibrinógeno. El colesterol total de plasma, el colesterol HDL y el colesterol LDL disminuyeron a valores mínimos cuatro días después del daño térmico. Además, se observó un aumento en los niveles de triglicéridos. CONCLUSIÓN: La respuesta inflamatoria observada de las moléculas de adhesión celular soluble puede ser útil para monitorear la activación endotelial inmediatamente luego del daño térmico. Estudios ulteriores que comprendan un gran número de pacientes con quemaduras deben ayudar a aclarar hasta que punto los parámetros medidos, especialmente los cambios temporales de sCAMs, pudieran ser relevantes a la hora de evaluar la morbilidad de los pacientes con heridas térmicas.

Genetic predisposition of E-selectin gene (S128R) polymorphism in patients with coronary artery disease (CAD).

Background & objectives: A surface glycoprotein molecule, E-selectin is involved in adhesion of circulating leukocyte to the activated endothelium and plays a fundamental role in pathogenesis of atherosclerosis. The present study was undertaken to document the status of S128R polymorphism of E-selectin gene in angiographically proven coronary artery disease (CAD) patients from Uttar Pradesh. Methods: Genotype of the S128R polymorphism was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 329 angiographically proven CAD patients [n=83 acute myocardial infarction (AMI) and n= 246 AMI-free] and 331 age and sex matched control individuals (angiographically proven not to have CAD). Results: This pilot study revealed a significant association of R allele in coronary artery disease patients in univariate analysis [allele frequency 9.6% in patients vs. 5.6% in control (P = 0.031, OR = 1.57, 95% CI = 1.05 – 2.47)]. However, after binomial logistic regression the significant determinants of CAD were: presence of diabetes (OR: 2.26, P=0.001) hypertension (OR = 2.61, P=0.001), smoking habit (OR=2.038, P=0.001), elevated serum triglycerides (OR=1.967, P=0.001) and low HDL-C (high density lipoprotein cholesterol) (OR=1.107, P=0.001). Interpretation & conclusions: The interaction of classical risk factors for CAD with S128R polymorphism in our study population showed that the significant determinants of coronary artery disease were presence of diabetes, hypertension, smoking habit, elevated serum triglycerides and low HDL. S128R polymorphism in E-selectin gene was not an independent predictor of CAD in our population.

Endothelial and platelet activation markers in early and convalescent phases of ischemic stroke: correlation with clinical and functional disability

The soluble form of selectins in the blood may play an important role in the pathophysiology of atherosclerotic ischemic stroke. To determine whether blood concentrations of the soluble form of selectins are elevated among patients with atherosclerotic ischemic stroke, whether their concentrations in blood correlate with clinical and functional disability and to estimate differences in their levels between lacunar and territorial strokes. We measured the serum levels of soluble E-selectin [sE-selectin] and soluble P-selectin [sP-selectin] during the early and convalescent phases of 37 patients with ischemic stroke compared to controls. We, also did correlation analysis between their levels at baseline and after 3 months with clinical and functional disability scores [National Institutes of Health Stroke Scale-NIHSS-and Barthel Index-BI-respectively]. Levels of sE-selectin and sP-selectin in stroke patients were significantly elevated compared with controls during the early phase, with significant fall in their levels below baseline measurements and below those in controls after three months. sE-selectin levels after 3 months correlated with a better functional status as measured by BI, while sP-selectin levels didn't show any correlation with clinical or functional scores. No significant differences were found in the course of sE-selectin, sP-selectin levels between lacunar and territorial strokes. The evaluation of endothelial and platelet markers would represent the pathophysiological status of stroke. This may offer the possibility of researching the application of antagonists and/ or activity modulators of some of them in ischemic brain disease therapy

Relationship of SICAM-1 and SE-selectin to obesity measures in an Egyptian female sample

To evaluate circulating levels of sICAM-1, and sE-Selectin as indices of endothelial activation in a sample of obese young Egyptian females. Thirty obese and 30 non-obese premenopausal females were included in the study. They were subjected to complete clinical examination, and measurement of body mass index [BMI] and waist/hip ratio [W/H ratio]. Laboratory measurements included serum cholesterol [TC], serum LDL and HDL cholesterol, serum triglycerides [TG] and body fat%. Serum sICAM-1 and sE-Selectin concentrations were measured with ELISA technique. The treatment program included balanced low calorie food regimen and daily exercise therapy for 45-60 minutes at the intensity of 70-85% of maximum heart rate. Obese patients were reassessed after 3 months. Results: Obese females had significantly higher DM1, TC, LDL cholesterol, TG, body fat% and plasma levels of sE-Selectin and sICAM-1. HDL cholesterol was significantly lower in the obese group. Highly significant correlations were found between sE-Selectin and BMI, W/H ratio, TC, LDL cholesterol and body fat%. There was a significant correlation with TG, while sICAM-1 significantly correlated with BMI, TC and LDL cholesterol. A negative significant correlation was found between HDL cholesterol and CAMs. After treatment program, serum levels of sE-Selectin, sICAM-1 were significantly lowered with significant reductions in BMI, TC, LDL cholesterol, and TG and body fat%. Circulating levels of sE-Selectin and sICAM-1 are related to anthropometric and metabolic measures f obesity. sE-Selectin showed the strongest association with central obesity. Combined weight reduction, physical activity resulted in decrease in sE-Selectin and sICAM-1 levels

E-selectina soluble en una población infanto-juvenil con diabetes tipo 1 / Soluble E- selectin in children and adolescents with type 1 diabetes

El estado de hiperglucemia crónica en los pacientes diabéticos produce una agresión al endotelio vascular, conduciendo al desarrollo prematuro de ateroesclerosis. El objetivo de este trabajo fue determinar niveles de E-selectina soluble (sE-S) en una población infanto-juvenil con diabetes tipo1 (DT1) y su relación con el control glucémico y el perfil lipídico. Se estudiaron 30 pacientes con DT1 (16 mujeres y 14 varones), de edades comprendidas entre 6 y 15 años, comparados con 20 sujetos controles. Se determinaron: sE-S, glucemia en ayunas, hemoglobina glicosilada (HbA1c), colesterol total (CT), HDL-C, LDL-C, no HDL-C y triglicéridos (TG). Los niveles de sE-S fueron 66% más altos en los diabéticos que en los sujetos controles (p = 0.0001). Los pacientes fueron agrupados en: diabéticos con buen control glucémico (DBCG, HbA1c < 8%) y diabéticos con pobre control glucémico (DPCG, HbA1c > 8%). La concentración de sE-S en DPCG y en DBCG fue: 111.3 ± 40.5 vs. 68.0 ± 11.3 ng/ml, respectivamente p = 0.02. En los diabéticos la incidencia de valores no deseables en el perfil lipídico fue: CT: 50%; HDL-C 14%; LDL-C 52%, no HDL-C 26.7% y TG 14%. La sE-S se correlacionó mejor con HbA1c (r = 0.53, p = 0.0001) que con la glucemia en ayunas (r = 0.36, p = 0.008) y CT (r = 0.36, p = 0.009). De los resultados obtenidos se sugiere que la sE-S es un marcador temprano de disfunción endotelial y de probable riesgo de aterosclerosis en pacientes infanto-juveniles con DT1.

The chronic hyperglycemic state in diabetic patients produces an aggression to the vascular endothelium leading to a premature development of atherosclerosis. The objective of this paper was to determine the soluble E-selectin (sE-S) levels in children with type 1 diabetes (DT1) and its relationship with glycemic control and lipid profile. Thirty patients with DT1, (16 girls and 14 boys), age between 6 and 15 years were studied, whose data were compared with 20 control subjects. In both groups sE-S was determined as well as fasting glycemia, glycosylated hemoglobin (HbA1c), total cholesterol (TC), HDL-C, LDL-C, non-HDL-C and triglycerides (TG). sE-S values were 66% higher in diabetics than in control subjects (p = 0.001). Patients were grouped in: good glycemic control diabetics (GGCD, HbA1c < 8%) and poor glycemic control diabetics (PGCD, HbA1c > 8%). sE-S concentratios were in PGCD an GGCD respectively. 111.3 ± 40.5 vs 68.0 ± 11.3 ng/ml, p = 0.02. In the diabetic group, the incidence of non desirable values in the lipid profile parameters were: TC 50%; HDL-C 14%; LDL-C 52%, non-HDL-C 26.7% and TG 14%. sE-S values were better correlated with HbA1c (r = 0.53, p = 0.0001) than fasting glycemia (r = 0.36, p = 0.008), and CT (r = 0.36, p = 0.009). These results suggest that sE-S is an early marker of endothelial dysfunction and a probable risk marker of atherosclerosis in children with DT1.

Niveles de moléculas de adhesión solubles en pacientes diabéticos tipo 2 normotensos e hipertensos / Levels of soluble adhesion molecules among normal and hypertensive type 2 diabetic patients

Antecedentes: La diabetes mellitus tipo 2 y la hipertensión arterial cursan con disfunción endotelial, lo que condiciona inflamación vascular, expresión de moléculas de adhesión que favorecen la migración celular subendotelial y el desarrollo de aterosclerosis. El objetivo de este estudio fue valorar los niveles circulantes de moléculas de adhesión solubles en pacientes diabéticos tipo 2 normotensos e hipertensos. Material y métodos: Las concentraciones en suero de VCAM1, ICAM1 y E-selectina fueron determinados por ELISA (RyDSystems Minneapolis), en 80 pacientes diabéticos tipo 2, (40 normotensos y 40 hipertensos), así como en 40 sujetos normotensos no diabéticos; el método estadístico empleado fue ANOVA. Resultados: Los pacientes diabéticos presentaron niveles significativamente mayores de moléculas de adhesión celular que los no diabéticos (p<0.001 para las tres moléculas). A su vez, entre los pacientes diabéticos, los sujetos hipertensos mostraron niveles significativamente mayores de ICAM que los normotensos (316±17 versus. 295±16 ng/ml p<0.01), mientras que en VCAM y E-selectina no hubo diferencia significativa. Conclusiones: Los pacientes diabéticos muestran niveles significativamente mayores de moléculas de adhesión solubles que los no diabéticos. La coexistencia de hipertensión aumenta significativamente los valores de ICAM, esto podría explicar la mayor frecuencia de complicaciones en los pacientes que cursan con las dos patologías.

BACKGROUND: Hypertension and type-2 diabetes affect endothelial function, which in turn increases the expression of soluble adhesion molecules and lead to the development of vascular damage. The aim of this study was to assess soluble adhesion molecule levels among normotensive and hypertensive diabetic patients. MATERIAL AND METHODS: Serum levels of soluble VCAM1, ICAM1 and e-selectin were measured in 80 type-2 diabetic patients, (40 normotensive and 40 hypertensive), and in 40 normotensive non-diabetic subjects by ELISA (RyDSystems Minneapolis). Statistical analysis was performed with ANOVA. RESULTS: Among diabetic patients, levels of all three soluble adhesion molecules were significantly increased when compared with non-diabetic patients (p < 0.001 for all three molecules), In diabetic hypertensive patients, higher levels of ICAM1 were detected in comparison to normotensive diabetic patients (316 vs. 295 ng/ml p < 0.01), VCAM1 and e-selectin levels were not different between diabetic patients with and without hypertension. CONCLUSIONS: Diabetes is associated with increased levels of soluble adhesion molecules, suggesting a role of these molecules may play in endothelial damage. ICAM1 is further increased when hypertension and diabetes are present. The latter may explain why diabetic-hypertensive patients displayed more complications than normotensive patients.

Biochemical markers and lipoprotein profile levels in childhood type I diabetes mellitus: early prediction of vascular complications

Diabetes mellitus is the most common endocrine and metabolic disorder in childhood and adolescents, with no cure. In this work, we studied the serum levels of the soluble leucocyte adhesion molecules, vascular adhesion molecules -1 [sVCAM-1], intercellular adhesion molecules -1 [Svcam-1], intercellular adhesion molecules [sICAM-1, sICAM-2], and sE-selectin. Also, we studied the lipoprotein phenotype including: serum triglyceride, serum cholesterol, HDL. VLDL, LDL, apoA, and apoB in the serum of 27 children [13 male 14 female] with type 1 diabetes mellitus with and without vascular complications. Their ages ranged from [2.25-20 years] with a mean 15.6 +/- 5.2 years. They were divided into two groups, group [Ia]comprised 14 patients without vascular complications and group [Ib], 13 patients with vascular complications [microalbuminuria, neuropathy, hypertension and retinopahy] presenting with vaying degrees of metabolic control and disease duration and were compared with age, sex matched healthy subjects [n=22, 10 male, 12 female] mean age 14.9 +/- 4.8 yeas. There were significantly higher concentration of soluble sVCAM-1 [mean 1866.7 +/- 631.6ng/mL], sICAM-1 [mean 581.6 +/- 387.1ng/mL], sICAM-2 [mean 425.1 +/- 215.6ng/mL] in type 1 diabetic patients versus age, sex matched control [mean 947.3 +/- 469.6. 184.8 +/- 62.3, and 193.1 +/- 66.6 ng/mL] respectively, p<0.001. As regards sE-selectin there was no significant differences in the concentration in both diabetic and control groups. Significant positive correlations were found between [sICAM-1, sICAM-2] and HbAlc [r=0.44, r=0.37] respectively p<0.05, but no correlations were found between sVCAM-1 or sE selectin and glycosylated hemoglobin. There was a significant increase in sVCAM-1 serum of diabetic children with vascular complications as compared to diabetic children without vascular complications [mean 2183.6 +/- 600.3 versus 1590.4 +/- 584.2ng/mL] [p<0.05]. In diabetic children with positive microalbuminuria there were significant higher levels of sVCAM-1 concentration when compared with the normoalbuminuric diabetic patients [mean 2343.2 +/- 572.7 versus 1709.4 +/- 576.7 ng/mL] p<0.05. While no significant difference were found in the levels of sICAM-1, sICAM-2 and sE-selectin between both groups of diabetic children with and without vasacular complications. As regard lipid profile there were significant increase in serum triglycerides [mean 140.6 +/- 40.9, p<0.01], serum cholesterol [mean 190.6 +/- 25.7, p<0.001], VLDL [mean 26.2 +/- 7.9, p<0.05], LDL [mean 121.8 +/- 29.6 p<0.001], apoA [mean 208.1 +/- 47.4, p<0.001 and apoB [mean 175.9 +/- 54.8, p<0.001] in diabetic patients as compared with control group [mean 100.7 +/- 32.5, 152.5 +/- 26.7, 20.1 +/- 6.5, 78.7 +/- 29.9, 148.5 +/- 42.9 and 84.53 +/- 33.2] respectively. There was a decrease in HDL in diabetic patients as compared to control group but it was not statistically significant. Correlations between circulating adhesion molecules and lipid profile revealed that there was a significant correlations between sVCAM-1 and serum triglyceride, serum cholesterol, HDL. LDL in diabetic children with vascular complications [r=0.56, r=0.53 p<0.01, r=0.43, r=0.46 p<0.05] respectively. In diabetic children without complication there was a significant correlation between sVCAM-1 and cholesterol. VLDL [r=0.37, r=0.39 respectively p<0.05]. Also, there was a significant positive correlation between sICAM-1 and VLDL [r=0.46, p<0.05], and there was a significant correlation between sICAM-2 and LDL [r=0.37, p<0.05] in diabetic children with vascular complications. But there was no significant correlation between sVCAM-1 and sICAM-1, sICAM-2 and sE-sellectin levels in both groups of diabetic patients and their age, disease duration, mean blood glucose, insulin dose, or frequency of diabetic ketoacidosis or hypoglycemic attack which reflect extreme variation in the glycemic control. In patient with microalbujminuria, there was a significant positive correlation between sVCAM-1 and serum triglycerides, serum cholesterol, LDL [r=0.45, p<0.05, r=0.48 p<0.01, r=0.37 p<0.05] respectively. Also a significant positive correlation was found between intercellular adhesion molecules sICAM-2 and LDL [r=0.39, p<0.05]. sICAM-1 has a positive correlation with triglyceride [r=0.39, p<0.05] and a significant negative correlation with HDL [r=0.4, p<0.05], was identified as well. We concluded that in respective of actual metabolic control, serum concentration of sVCAM-1 sICAM-1 and sICAM-2 but not sE-selection are elevated in patients with type I diabetes mellitus, reflecting ongoing endothelial cell stimulation and leucocyte activation even in the absence of clinically detectable angiopathy. Our results suggest an important role of sVCAM-1 in micro and macrovascular complications which may serve as the basic for further evaluation of circulating sVCAM-1 as a potential serum marker for vascular complications. Also sICAM-1, sICAM-2, seem to be good and reliable indicators of glycemic control. Our finding proved an important relationship between adhesion molecules and dyslipidemia exists in type 1 diabetic patients with vascular complications. It is recommended to screen diabetic children regularly for sole adhesion molecules, lipid profile and microalbuminurea levels for early detection of diabetic vascular complications

Association between en dothelial selectin [E-selectin] gene polymorphisms and E-selectin level with visceral leishmaniais, in an ARMS-PCR based study

In the visceral leishmaniasis [VL], parasites reside in reticuluendothelial system, mainly in macrophages. Endothelial Selectin [E-selectin] might play an important role in leukocyte-endothelium interactions and inflammatory cell recruitment. The aim of this study was determining E-selectin level and its polymorphism in three groups, patients, seropositive and healthy individuals. Serum soluble E-selectin levels as well as 2 polymorphisms of E-selectin [Ser 128 Arg and Leu 554 Phe] were measured in a cohort of patients with documented VL [n=64], a healthy control group [n=74] and a seropositive for VL but without any symptoms [n=81]. Circulation concentration of E-selectin levels was measured by ELIS. The amplification refractory mutation system [ARMS]-PCR procedure was used for detecting polymorphisms. The mean of E-selectin levels significantly differed between three groups [P<0.026], and were increased in patients in comparison with other groups. Difference was more considerable between two groups of patients and healthy ones [patients 92.8 ng/ml; healthy individuals 71.9 ng/ml]. Polymorphisms were associated with soluble E-selectin levels and altogether explained 14.4%, 7.2%, and 8.7% in patients, seropositive and seronegative healthy individuals, respectively. Distribution of polymorphisms of 128 Ser/Arg and 554 Leu/Phe among three groups was not different significantly; however, there was a considerable arrangement in distribution of Ser 128 Arg polymorphism and 128 Arg allele in healthy group was more than two fold of patients [55% against 20%]. The association between soluble E-selectin levels and visceral leishmaniasis suggests that this molecule might have significant role in the inflammatory process in VL. Moreover, frequency of 128 Arg allele in healthy group was higher than patients

Polimorfismos de nucleótido simple en moléculas de adhesión y parámetros clínicos en artritis reumatoide / Single nucleotid polymorphisms of adhesion molecules and clinical parameters in rheumatoid arthritis

Se investigó la relación entre los polimorfismos de E-selectina, la molécula de adhesión vascular-1 (VCAM1) y la molécula de adhesión intercelular-1 (ICAM1) con el perfil de lípidos y marcadores clínicos de inflamación en artritis reumatoide (AR). Se incluyeron 60 pacientes con AR clasificados de acuerdo a los criterios del American College of Rheumatology (ACR, 1987) y 60 controles clínicamente sanos (CCS), no relacionados entre sí, definidos como población de mestizos mexicanos. Los genotipos se caracterizaron por la técnica de PCR-RFLP. La velocidad de sedimentación globular (VSG), factor reumatoideo (FR), concentración de fibrinógeno (FB), proteína C reactiva (PCR) y perfil de lípidos, se realizaron por métodos convencionales. El análisis estadístico se efectuó con SPSS v10.0. La VSG correlacionó con PCR, FR, FB y cHDL, (r=0,507; 0,296; 0,475 y -0,308, respectivamente); PCR con FB (r=0,613), p<0,05. El alelo 1238G se asoció con FR y Apo-B; y el alelo 721A, con cHDL y cLDL (p<0,05). Los datos muestran que los niveles de FB, cHDL, y los alelos 721A de ICAM1 y 1238G de VCAM1 se asocian con los marcadores clínicos de inflamación. Existen diferencias entre la distribución de los polimorfismos en este estudio y las reportadas para población oriental, caucásica y turca.

The genotypes were characterized using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) technique. The ESR (erythrocyte sedimentation rate), RF (rheumatoid factor), fibrinogen (FB), C-reactive protein (CRP) and lipid profile were measured by routine methods. Statistical analysis was performed using SPSS v10.0. The significant Pearson´s correlations were: ESR with CRP, RF, FB and HDLc, (r=0.507, 0.296, 0.475, and -0.308, respectively); CRP with FB (r=0.613), p<0.05. The results showed an association with A allele of ICAM1 polymorphism and serum levels of HDLc and LDLc; and Apo-B and FR showed an association with C allele of VCAM1 polymorphism (p<0.05). Data shows that FB and HDLc levels, and ICAM1 polymorphism allele 721A and VCAM1 polymorphism allele 1238G are associated with clinical inflammation markers in RA. Our Mexican-mestizo population showed differences with many reports (from English, American, Turkish, Japanese, Chinese, Italian, and Korean populations).

Vascular cell adhesion molecule-1, E-selectin and von willebrand factor: Role as surrogate markers of angiogenesis in breast cancer

Angiogenesis, the development of new blood vessels from pre-existing vasculature, is a prerequisite for tumor growth and metastasis in breast cancer. Surrogate markers for angiogenesis would be useful for studying the effectiveness of antiangiogenesis drugs. We examined the potential of three glycoproteins: vascular cell adhesion molecule-1 [VCAM-1], endothelial selectin [E-Selectin], and von Will brand factor [vWF], to serve as markers for angiogenesis. Serum levels of VCAM-1, E-selectin and plasma vWF levels were measured by enzyme-linked immunosorbent assay in 54 women with different stages [1-IV] of breast cancer [12 women in stage 1, 16 in stage 11, I4 in stage III and 12 in stage IV]. Their ages ranged from 25-70 years. To investigate whether the concentration of these activated endothelial cell molecules are associated with breast cancer, the serum levels of soluble VCAM-1, E-selectin and plasma levels of vWF in women with breast cancer were compared with those of22 healthy age-matched control women, we also examined whether levels of VCAM-1, E-selectin or vWF are associated with tumor progression and stage of breast cancer [early and advanced breast cancer]. The results revealed that levels of VCAM-1, E-selectin and vWF are elevated in breast cancer women, even in early stages when compared with control women. Although plasma vWF and serum VCAM-1 levels were significantly elevated in advanced stages than early stages of breast cancer with a positive correlation with disease stage, E-selectin did not show a statistical difference between different stages of breast cancer. vWF, which is released by all endothelial cells, would be a pan-endothelial marker that would not accurately report angiogenesis and Serum soluble VCAM-1 can, be considered as an accurate marker of tumor angiogenesis in breast cancer

Serum and cerebrospinal fluid concentrations of E-selectin in patients with aneurysmal subarachnoid hemorrhage

The goal of the present study was to determine concentrations of E-selectin in both cerebrospinal fluid (CSF) and serum of patients with aneurysmal subarachnoid hemorrhage (SAH) and to evaluate the correlation between the clinical parameters and E-selectin levels. Both CSF and serum samples obtained from 12 patients with aneurysmal SAH and 8 patients with hydrocephalus (control group) without any other known central nervous system disease were assayed for E-selectin by quantitative enzyme-linked immunosorbent assay and the results were compared between the two groups. Mean levels of soluble forms of E-selectin within the first 3 days and on the 5th and 7th days of SAH were 4.0 ± 7.9, 2.8 ± 5.2, and 3.1 ± 4.9 ng/ml in the patient's CSF, and 33.7 ± 9.2, 35.1 ± 7.0, and 35.2 ± 8.7 ng/ml in serum, respectively. In contrast, mean E-selectin levels were 0.1 ± 0.2 ng/ml in CSF and 8.7 ± 5.0 ng/ml in serum of control patients. The difference between groups was statistically significant regarding both CSF and serum E-selectin levels (P < 0.05). Thus, we have demonstrated a marked increase of E-selectin concentration in both CSF and serum of patients with aneurysmal SAH compared with control and suggest that blocking the interaction between E-selectin and vascular endothelium may have a beneficial effect on vasospasms.