Interleukin-6 and adhesion molecules VCAM-1 and ICAM-1 as biomarkers of post-acute myocardial infarction heart failure

Acute coronary syndromes are associated with a high prevalence of complications including heart failure (HF). The aim of this study was to investigate the association of novel biomarkers with the occurrence of post-acute myocardial infarction (AMI) HF. A prospective study was conducted with patients admitted to the emergency department with ST-segment elevation myocardial infarction (STEMI). Blood and urine samples were collected for analysis of traditional and novel biomarkers, including interleukin-6, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). We compared the levels of these biomarkers between patients with and without post-STEMI HF. A total of 48 patients were assessed, with a prevalence of males. Fifteen patients (31.2%) had post-STEMI HF. Patients with HF had higher mean values of IL-6, VCAM-1, and ICAM-1 compared to those who did not develop HF (57.06 vs 14.03 pg/mL, P=0.001; 1719.58 vs 1304.34 ng/mL, P=0.001; and 1594.20 vs 1158.74 ng/mL, P<0.001, respectively). The three biomarkers were shown to be good predictors of post-STEMI HF (IL-6: AUC 0.786, P=0.002; VCAM-1: AUC 0.797, P=0.001; and ICAM-1: AUC 0.825, P<0.0001), with the respective cutoff points being calculated based on the best sensitivity and specificity indexes (IL-6: 8.67 pg/mL; VCAM-1: 1501.42 ng/mL; and ICAM-1: 1262.38 ng/mL). Of the three biomarkers, only VCAM-1 and ICAM-1 had a direct linear association between them (r=0.470, P<0.0001). IL-6, VCAM-1, and ICAM-1 were associated with the development of new post-AMI HF symptoms, but only VCAM-1 and ICAM-1 correlated with each other, possibly because they have the same pathophysiological mechanism of action.

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.

Fluxo mediado pela dilatação e espessura da íntima-média da carótida em pacientes com gastrite crônica associada com infecção por Helicobacter pylori / Flow mediated dilation and carotid intima media thickness in patients with chronic gastritis associated with helicobacter pylori infection

ABSTRACT BACKGROUND: Endothelial dysfunction is one of the early stages of vascular diseases. OBJECTIVE: The aim of this study was to investigate the endothelial dysfunction markers in patients with chronic gastritis associated with Helicobacter pylori (H. pylori) infection. METHODS: By a cross sectional study, basic and clinical information of 120 participants (40 patients with positive H. pylori infection, 40 patients with negative H. pylori infection and 40 healthy people) were analyzed. Carotid intima media thickness and flow-mediated dilation levels were measured in all patients and controls. Soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were measured with Elisa for all subjects. IgG level was assessed in chronic gastritis patients. RESULTS: The flow-mediated dilation level in patients with positive H. pylori infection (0.17%±0.09) was significantly lower than those with negative H. pylori infection (0.21% ±0.10, P<0.05) and compared to the control group (0.27% ±0.11, P<0.05). Carotid intima media thickness level in patients with positive H. pylori infection (0.58±0.13 mm) was significantly higher than those with negative H. pylori infection (0.48±0.32 mm, P<0.05) and compared to the control group (0.36±0.44mm, P<0.05). The mean level of sICAM-1 in positive H. pylori infection group (352.16±7.54 pg/mL) was higher than negative H. pylori infection group (332.64±8.75 pg/mL =0.75) and compared to the control group (236.32±12.43 pg/mL, P<0.05). A direct relationship was revealed between flow-mediated dilation and carotid intima media thickness changes and between sICAM-1 and sVCAM-1 associated with the level of H. pylori IgG in chronic gastritis. CONCLUSION: The levels of flow-mediated dilation, carotid intima media thickness and sICAM-1 were higher among patients with positive H. pylori infection. Patients with chronic gastritis associated with H. pylori infection are at risk of endothelial dysfunction due to flow-mediated dilation and carotid intima media thickness abnormalities and increased level of sICAM-1 and sVCAM-1.

RESUMO CONTEXTO: A disfunção endotelial é um dos estágios iniciais de doenças vasculares. OBJETIVO: O objetivo deste estudo foi investigar os marcadores de disfunção endotelial em pacientes com gastrite crônica associada com infecção por Helicobacter pylori (H. pylori). MÉTODOS: Através de estudo cruzado seccional, foram analisadas informações básicas e clínicas de 120 participantes (40 pacientes com infecção pelo H. pylori, 40 pacientes sem infecção pelo H. pylori e 40 pessoas saudáveis). A espessura da camada íntima-média da carótida e níveis de dilatação mediada por fluxo foram medidos em todos os pacientes e controles. A adesão da molécula-1 solúvel (sVCAM-1) à célula vascular e da molécula de adesão intercelular-1 (ICAM-1) foram medidas pelo método Elisa para todas os indivíduos. O nível de H. pylori IgG foi avaliado em pacientes de gastrite crônica. RESULTADOS: O nível de dilatação mediada por fluxo em pacientes com infecção positiva pelo H. pylori foi significativamente menor do que em aqueles com infecção negativa (0,17% ±0, 09) X (0,21% ±0,10) P<0,05 e em relação ao grupo controle (0,27% ±0,11) P<0,05). O nível da espessura da íntima-média da carótida em pacientes com infecção positiva pelo H. pylori foi significativamente maior (0,58±0,13 mm) do que aqueles com negativa (0,48±0,32 mm) P<0,05) e em relação ao grupo controle (0,36±0,44 mm) P<0,05). O nível médio de sICAM-1 grupo de infecção H. pylori positiva (352,16±7,54 pg/mL) foi maior do que o grupo de infecção negativa (332,64±8,75 pg/mL = 0,75) e em relação ao grupo controle (236,32±12,43 pg/mL) P<0,05). Revelou-se uma relação direta entre a dilatação mediada por fluxo e alterações da espessura da íntima-média da carótida e sICAM-1 e sVCAM-1, associada com o nível de H. pylori IgG em gastrite crônica. CONCLUSÃO: Os níveis de dilatação mediada por fluxo, da espessura da íntima-média da carótida e sICAM-1 foram maiores entre os pacientes com infecção positiva pelo H. pylori. Pacientes com gastrite crônica associada a infecção por H. pylori correm o risco de disfunção endotelial, devido à dilatação mediada por fluxo e anormalidades da espessura da íntima-média da carótida e aumento do nível de sICAM-1 e sVCAM-1.

Evaluation of biochemical and clinical markers of endothelial dysfunction and their correlation with urinary albumin excretion in patients with type 1 diabetes mellitus

ABSTRACT Objective Endothelial dysfunction (ED) plays an important role in the pathogenesis of diabetic nephropathy. The purpose of the study was to determine flow mediated endothelial dependent vasodilatation (FMD) measurements and serum soluble (s) endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) levels in patients with type 1 diabetes mellitus (T1DM) with or without increased urinary albumin excretion (UAE) and compare them with the healthy controls. Subjects and methods Seventy three patients with T1DM were enrolled. Patients were divided into two subgroups according to microalbumin measurements in 24-hr urine collections. The diabetic patients without microalbuminuria (41 patients) were defined as Group I and those with microalbuminuria (32 patients) were defined as group II. A hundred age and sex matched healthy subjects participated as the control group (Group III). Serum sET-1, sICAM-1, sVCAM-1 levels and FMD measurements were determined in all participants. Results Median FMD measurement was significantly lower in the diabetic groups compared with the control group (6.6, 6.4 and 7.8% in Group I, II and III, respectively) (p < 0.05). FMD was negatively correlated with age (p = 0.042). Median serum sICAM-1 level was higher in the patient groups compared to the control group (p < 0.05). Median serum sVCAM-1 level was higher in the group of patients with increased albuminuria compared to the normoalbuinuric and the control group (p < 0.05). Serum sVCAM-1 level was found to be positively correlated with degree of urinary albumin excretion (p < 0.001). Conclusion We assume that sVCAM-1 may be used as a predictive marker for risk stratification for nephropathy development and progression.

Study of endothelial dysfunction and vascular inflammation in sleep apnea, obesity and aged humans

Obstructive sleep apnea [OSA] has been associated with cardiovascular complications. The overnight repetitive hypoxia represents a form of oxidative stress in the vasculature which may activate the oxidant-sensitive, proinflammatory transcription factor nuclear factor kjB [NF-kjB], affecting endothelial function and atherosclerosis. We investigated whether the endothelial alterations attributed to OSA rather than to other confounding factors. Also, the production of inflammatory cytokine nuclear factor-kappa beta [NFKbeta] was investigated as the molecular mechanism involved in vascular endothelial dysfunction with OSA. Sixty subjects underwent attended nocturnal polysomnography were grouped by apnea hypopnea index: control [AHI<5/h] and OSA cases [AHI>5/h] the cases were further classified according to age and BMI into subgroup IIA: OSA, non-obese, middle age [35-52 y], subgroup IIB: OSA, non-obese, older age group [55-68 y], subgroup IIIA: OSA, obese, middle age group [35-52 y] and subgroup IIIB: OSA, obese, older age group [55-68 y]. A morning venous blood sample was obtained. Neutrophils were isolated, and NF-kjB activity was determined. Plasma sVCAM-1 was assayed by enzyme-linked immunosorbent assay and flow-mediated dilation [FMD] was performed. NF-jB activation and plasma level of sVCAM-1 were significantly increased in OSA patients as compared to the control group and there was no significant difference between the obese and non-obese cases also no significant difference between the middle and old age cases. The degree of NF-kjB activation was positively correlated with indices of apnea severity[r = 0.938; p< 0.001]. FMD was significantly decreased in OSA patients as compared to the control group. These findings suggested that OSA is an independent risk factor for cardiovascular morbidity also that OSA leads to NF-kjB activation, which may constitute an important pathway linking OSA with systemic inflammation and cardiovascular disease

Inflammation and endothelial activation in benign prostatic hyperplasia and prostate cancer

PURPOSE: Emerging insights underline a link among chronic inflammation and endothelial activation with benign prostatic hyperplasia (BPH) and prostate cancer (PCa). We aim to investigate whether specific plasma markers of inflammation and endothelial activation allow to discriminate BPH and PCa. MATERIALS AND METHODS: Fifteen patients affected by BPH, 15 by PCa and 15 controls, were enrolled. Interleukin-6 (IL-6), CD40 ligand (CD40L), endothelial-selectin (E-selectin), platelet-selectin (P-selectin), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were measured. RESULTS: In systemic blood samples, IL-6 has been found increased in patients affected by BPH (4.25 ± 0. pg/mL) and PCa (5.08 ± 0.24) respect to controls (2.62 ± 0.34; p < 0.05). CD40L was higher in BPH (4.25 ± 0.65 ng/mL; p < 0.05) than in control (2.31 ± 0.20) and PCa group (2.60 ± 0.56). E-selectin, P-selectin and VCAM-1 did not show any significant difference. Higher levels of ICAM-1 were detected in patients with PCa (573.04 ± 52.23) and BPH (564.40 ± 74.67) than in the controls (215.30 ± 11.53 ng/mL; p < 0.05). In local blood samples, IL-6 has been found significantly increased in PCa in comparison with patients with BPH; there was no difference in CD40L, E-selectin, P-selectin, VCAM-1 ed ICAM-1. CONCLUSIONS: Changes in inflammation and endothelial activation markers may be not considered to be of value in discriminating BPH and PCa.

common mutation in methylene tetrahydrofolate reductase gene, inflammation and atherosclerosis in chronic renal failure

Accelerated atherosclerosis is the major cause of mortality in patients on chronic haemodialysis [HD]. Inflammation and endothelial activation or dysfunction might be the major factors leading to high cardiovascular mortality rate in HD patients. Also, C667T mutation of methyltetrahydrofolate reductase [MTHFR] might be associated with accelerated athcrosclerosis. The present study was designed to clarify the role of inflammation, endothelial activation or dysfunction and genotyping of MTHFR enzyme which affect the level or homocysteine and their relation to carotid artery intima-media thickness [CIMT] as an indicator of atherosclerosis. Forty four [44] chronic haemodialysis [HD] patients and 40 healthy subjects were included in the study. Serum highly sensitive C reactive protein [hs-CRP] and IL-6 were measured as inflammatory markers, soluble vascular cell adhesion molecule-1 [sVCAM-1] was measured as a marker of endothelial activation and dysfunction. Common carotid intimal media thickness [CC-IMT] was assessed by carotid artery ultrasonography. genotyping of MTHFR enzyme which affect the level of homocysteine was analyzed by PCR RFLIP technique. Chronic HD patients had elevated levels of inflammatory markers [hs-CRP and IL-6], enhanced endothelial activation or dysfunction demonstrated by elevated VCAM-1 as compared by healthy controls. Haemodialysis patients had significantly higher CC-IMT levels. There is a significant positive correlation between inflammatory cytokines [hs-CRP and IL-6], and each with VCAM-1 and CC-IMT There is no difference in the genotype of C667T MTHFR found between patients and controls, but this mutation especially the TT genotype is associated with development of atherosclerosis as indicated by the increase of CC-IMT

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

Pulmonary 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. The 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. This 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. There 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]. The 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

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.

Correlation between blood levels of adhesion molecules ICAM-1 and VCAM-1 and thrombomodulin with coronary artery disease

The results of studies on coronary artery disease risk factors have demonstrated that some adhesion molecules could be risk factors for coronary artery disease. ICAM-1 and VACM-1 are the most important adhesion molecules. On the other hand, thrombomodulin is an anti-inflammatory factor and can reduce the risk for coronary artery disease. In this study, as well as evaluating these factors, we also studies the effect of the interaction between these factors on coronary artery disease. One hundred twenty-three patients between the ages of 45 and 70 years old who were admitted for coronary angiography in the cardiovascular center and met the inclusion criteria for the research, were selected in the first half of 2008. After recording their personal information and medical history in the questionnaires, blood samples were collected and after routine examination, the blood levels of these factors were measured. WE then entered the acquired results of the blood examination and the angiography in the patients' charts and analyzed the results using statistical methods. The angiography results in patient showed that 18 [14.7%] had normal coronary arteries, 5 [4%] had minimal coronary artery disease, 40 [32.5%] had single-vessel disease, 25 [20.3%] had two-vessel disease, and 35 [28.5%] had three-vessel disease. In laboratory tests, the mean soluble ICAM-1 level in patients with normal coronary arteries was 236 ngr/mL; however, in patients with coronary artery disease, the mean level was 274 ngr/mL. The average amount of VCAM-1 in patients with normal coronary arteries was 697 ngr/mL, whereas patients with coronary artery disase had an average of 108 ngr/mL. Thrombomodulin in the normal coronary artery group was 42 ngr/mL, but in patients with coronary artery disease the average level was 30 ngr/mL. The results in this research showed that increased levels of soluble ICAM-1 and also decreased levels of soluble thrombomodulin increased the risk and intensity of coronary artery disease, with statistical significance. The increase in soluble VCMA-1 also increased the risk of coronary artery disease; this was, however, not statistically significant. The important point is that increased levels of soluble ICAM-1 is a risk factor when the level of thrombomodulin is normal or below normal. When the levels of thrombomodulin and ICAM-1 have both increased, the increased risk and intensity of coronary disease is not statistically important

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.

Circulating adhesion molecules in patients with Keshan disease and their relationship with Coxsackie B virus infection / 华中科技大学学报（医学）（英德文版）

This study determined the levels of serum soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecular-1 (sVCAM-1) in patients with different types of Keshan disease (KD), examined the relationship between Coxsackie B virus-specific IgM antibody (CBV-IgM) and sICAM-1 or sVCAM-1 in KD patients, and investigated the role of these adhesion molecules in the pathogenesis of KD and their clinical implications. The levels of serum sICAM-1, sVCAM-1 and CBV-IgM were measured by using enzyme-linked immunosorbent assay in 22 patients with chronic Keshan disease (CKD), 27 with latent Keshan disease (LKD) and 28 healthy controls. The subjects in different groups were adjusted for sex and age. Echocardiography was adopted to determine left ventricular ejection fraction (LVEF) in 22 patients with CKD. The results showed that CKD patients had significantly higher levels of sICAM-1 and sVCAM-1 than LKD patients and healthy controls (P<0.01 for all). And there was significant difference in the levels of the 2 adhesion molecules between LKD patients and healthy controls (P<0.05). A negative correlation was found between LVEF and sICAM-1 or sVCAM-1 in CKD patients. The percentage of CBV-specific IgM positive individuals in KD patients was significantly higher than that of healthy controls. In CVB-specific IgM positive patients, the levels of serum sICAM-1 and sVCAM-1 were significantly greater than those in CBV-specific IgM negative counterpart. It was concluded that the increase in the levels of sICAM-1 and sVCAM-1 suggests the progression of inflammation in KD. sICAM-1 and sVCAM-1 can promote the development of myocardial pathology and lead to poor myocardial function. The increased serum sICAM-1 and sVCAM-1 in KD patients may be related to CBV infection.

Study of serum and urinary vascular cell adhesion molecule-1 in patients with lupus nephritis

Systemic lupus erythenwtosus [SLE] is a chronic multisystem autoimmune disease. Renal involvement [lupus nephritis; LN] is a frequent and potentially serious complication that worsens morbidity and mortality. LN is a chronic disease with remissions and relapses, and this is important to predict aiming for optimal management. However, a consistent approach still has not been adopted. To study serum and urinary' soluble vascular cell adhesion molecule-I [sVCAM-1] levels in patients with lupus nephr itis and their correlation with the disease activity, laboratory data and renal pathology. Twenty three patients with lupus nephritis and twenty age, sex and ethnic matched healthy controls were subjected to physical examination, abdominal ultrasound, laboratory investigations including: Complete blood cell count, eiythrocyte sedimentation rate [ESR], renal functions, urine analysis, 24-hour urinary protein excretion, liver functions, serum antinuclear antibody [ANA], anti-double stranded deoxyribonucleic acid [anti-dsDNA], serum and urinaly soluble VCAM-1 [sVCAM-1] and other necessary investigations. Percutaneous renal biopsy, with histopathological assessment and determination of activity and chronicity indices, was done for all patients. LN patients had a statistically sign[ficantly higher serum [S] and urinary sVCAM-1, S. ANA, S. antidsDNA, ESR, blood urea, S.creatinine, S.uric acid, 24-hour urinary protein excretion and S. alanine and aspartate aminotransferases, and a statistically significantly lower hemoglobin concentration, S. albumin and creatinine clearance tjian healthy controls. Renal biopsy assessment showed World Health Organization [WHO] class 11 LN in 3 patients, class iii in 4 patients, class IV in 13 patients and class V in 3 patients. S. sVCAM-1 was statistically significantly higher in classes III, IV and V LN than controls and in class IV LN than class II. Urinary sVCAM-1 was statistically signficantly higher in classes II, III, IV and V LN than controls and in classes III and IV LN than class II. Anti-dsDNA was statistically significantly higher in classes III and IV LN than controls, with no statistically significant differences in between the WHO classes. S. and urinary sVCAM-1 showed a statistically wreianon with the total SLEDAI score, pathologic activity index and urinary protein excretion, with a significantly positive correlation between S. and urinary sVCAM-1. A significantly negative correlation was present between S. sVCAM-1 and hemoglobin concentration, and between urinary sVCAM-1 and S. albumin. As regards anti-dsDNA, no statistically significant correlations were observed. In patients with LN, serum and urinary sVCAM-1 are positively correlated with the total SLEDAI score, pathologic activity index and urinary protein excretion. Measurement of their levels, specially urinary sVCAM-1, seems to be valuable in evaluating LNpatients. Further studies are recommended to assess the role of repeated measurements. Whether a blockade of soluble VCAM-1 could have a therapeutic implication in LN remains to be investigated

Hepatoprotective effects of rolipram on experimental murine model of immune-mediated fulminant hepatitis

Autoimmune fulminant hepatic failure has a specific clinical and social importance. However, it still lacks its effective and targeting medication. Herein, we investigated the influence of rolipram, a selective PDE-IV inhibitor, on D-galactosamine/lipopolysaccharide [DGalN/ LPS]-induced immune-mediated and dose-dependent fulminant hepatitis and acute lethality in mice; in which tumor necrosis factor-alpha [TNF-alpha] plays a pivotal role. Two complementary sets of experiments were conducted in this work. Firstly, we assessed the distinct hepatoprotective effects of rolipram on this model. After an intraperitoneal [i.p.] injection of a single sub-lethal dose of D-GalN/LPS [0.2 mg/g + 5 microg/g] into mice a serious destructive hepatic injury was developed over a period of 4 days, and it was associated with abundant increases in the serum levels of liver enzymes [AST and ALT] and the concentrations of TNF-alpha in serum and hepatic tissues, as well as an over-production of vascular cellular adhesion mlocule-1 [VCAM-1] on liver tissues. Additionally, the histopathological findings showed the features of severely injured liver. Interestingly, treatment with rolipram [3 mg/kg, i.p.; at days +0, +1, +2, and +3] remarkably reversed all the aforementioned biochemical, immunological, and histopathological hallmarks of D-GalN/ LPS-induced hepatitis. Secondly, the prophylactic administration of rolipram [10 mg/kg, i.p.; at -24, -12, and -1 h] efficiently prevented the severe acute deaths and massive systemic TNF-alpha production that induced by a lethal dose of D-GalN/LPS [0.6 mg/g + 15 microg/g; i.p.] over 24-h period. The results reveal that rolipram; via, at least in part, inhibition of TNF-alpha production and VCAM-1 over-expression, has obvious hepatoprotective effects on D-GalN/LPS-induced lethal destructive hepatitis in mice. In addition, the beneficial role of rolipram in suppressing the progression of human hepatitis in which TNF-alpha is markedly involved could be considered

Serum adhesion molecule levels in acute coronary syndrome among Indonesian patients.

AIM: to observe whether the VCAM and ICAM level in ACS patients were higher than those in coronary heart disease (CHD) patients. In addition, we would like to observe the cut off point of VCAM and ICAM level in ACS patients. METHODS: in observational study, as many as 146 subjects were analyzed, consisting of 84 ACS patients, and 62 coronary heart disease (CHD) patients. This study were conducted at Dr. Cipto Mangunkusumo General Hospital (RSUPN-CM), Persahabatan Hospital, MMC Hospital and Medistra Hospital, Jakarta. The study was carried out from May 2005 to May 2006. RESULTS: the VCAM level was higher in the group of ACS patients (mean 981.06 ng/mL, SD 319.28, CI 95%: 911.77-1050.35) than in that in the group of CHD (mean 915.23 ng/mL, SD 283.05, CI 95%: 843.35-987.11), but the difference is not significant. At cut-off point of VCAM level >or= 920.8 ng/mL, the highest sensitivity (57.14%) and highest specificity (67.74%) were found with ROC of 0.58. The ICAM level was higher in the group of ACS patients (mean 268.08 ng/mL, SD 72.75, CI 95%: 252.29/283.87) than that in the group of CHD (mean 245.18 ng/mL, SD 87.37, CI 95%: 222.99-267.37), but the difference is not significant. At cut-off point of ICAM level 248.6 ng/mL, the highest sensitivity (54.76%) and highest specificity (66.13%) were found with ROC of 0.62. CONCLUSION: it could be concluded that VCAM and ICAM level in ACS were higher than in CHD, but the difference is not significant. The VCAM and ICAM level are not the best parameter to differentiate between acute (ACS) and stable (CHD) condition.

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.

Correlation between old and new immuno-inflammatory markers and disease activity in systemic lupus erythematosus

To compare new SLE activity inflammatory markers with traditional ones. In addition, to correlate those with disease activity index of SLE. Forty-three patients fulfilling the American College of Rheumatology criteria for diagnosis of SLE and 20 apparently healthy controls were subjects for study. Neopterin, soluble intercellular adhesion molecule [sICAM-1] and soluble vascular cell adhesion molecule [sVCAM-1] were measured as well as anti-dsDNA antibodies, C3, C4 and CRP. The British Isles Lupus Assessment Group [BILAG] disease activity index was used to measure disease activity. Twenty-four [55.8%] patients had active SLE [total BILAG score > 5], involving more than one system in nine [37.5%]. Activity was more in musculoskeletal, mucocutaneous, and hematological systems. All markers showed significant differences between SLE patients and controls. Neopterin, sVCAM and CRP were highest when compared to controls [p>0.001] as well as to inactive subgroup. The level of sICAM-1 in active was insignificantly higher than inactive group. Significant correlations were found between total BILAG score and CRP, neopterin, sVCAM. No positive correlation was found between any marker and disease activity of different BILAG organ systems. All tests were done for 22 patients on 3 occasions over 6 months. Highest levels of sVCAM-1 were in active subgroup with flares during the first measurement. Significant decrease between first and third measurement was observed within all subgroups. Neopterin and sVCAM-1 appear to be clinically useful for isolated and serial concentrations assessments of SLE disease activity scored using the BIIAG index. Anti-dsDNA and sVCAM-1 are good markers to predict remission

role of angiogenesis assessment in the prognosis of breast carcinoma and in the evaluation of the therapeutic effect of "shark care" drug as an angiogenesis inhibitor

There is still uncertainty about angiogenesis as a prognostic factor in breast cancer. To evaluate the prognostic value of microvascular density [MVD] in breast carcinoma and soluble vascular cell adhesion molecule-1 [sVCAM-1], leptin, estradiol and total testosterone as angiogenic markers. Efficacy of shark care drug was assessed by patient's overall survival. 30 premenopausal breast cancer patients [group II] and 15 controls [group I]. Group II was subgrouped into 15 patients receiving chemotherapy alone [IIA] and 15 patients receiving chemotherapy + shark care drug [IIB]. After modified radical mastectomy, microvessels were counted by staining tissues for factor VIII. For surrogate markers, enzyme-linked immunosorbant assay or radiommunoassay kits were used. A high MVD was found only in areas of carcinoma. MVD and sVCAM-1 correlated significantly with each other and with lymph node involvement. After the follow-up, all subgroup IIB patients were alive compared to 66.6% of subgroup IIA [p=0.02]. A high MVD may be a poor prognostic marker of breast carcinoma and a target for antiangiogenic therapy sVCAM-1 is useful for diagnosis and for monitoring response to therapy. Chemotherapy + shark care drug seem to ameliorate the outcome of these patients