Sepsis is one of the major threats for the survival and prognosis of patients in intensive care units. In cases where detailed clinical data and monitoring is available, the diagnosis of sepsis is reliable. But when clinical data are incomplete or missing and sepsis is only suspected based on the autopsy results, the picture is often equivocal. This report describes the gross pathological findings obtained from the autopsy of a 48-year-old woman with Crohn\'s disease after surgical intervention. Macroscopically, we found intestinal perforation and signs of peritonitis. Histologically, the pulmonary/bronchial arteries were lined with E-selectin (CD 62E)-positive endothelial cells, which are an established postmortem histological marker of sepsis. We extended our investigations to the cerebral cortex and subcortical medullary layer. The endothelium of the cortical vessels and those in the cerebral medullary layer were likewise immunopositive for E-selectin. Furthermore, numerous TMEM119-positive, highly ramified microglial cell profiles were found in the grey and white matter. Microglial cells were lining the vascular profiles. In addition, TMEM119-positive microglial profiles were abundant in the cerebrospinal fluid (CSF). Multiorgan E-selectin positivity of the vascular endothelia provides further evidence for the postmortem diagnosis of sepsis.

OBJECTIVE: To evaluate the combination of plasma activated endothelial microparticles (CD62e), serum Copeptin (CPP) and placental growth factor (PlGF) levels at 18-23 weeks of gestation for prediction of preeclampsia (PE) in primigravid women.
METHODS: This was a nested case-control study from a prospective cohort of 1115 primigravid women attending antenatal care clinic. Plasma levels of CD62e and serum Copeptin, PlGF levels were measured by flow cytometry and ELISA, respectively. Data were presented as median (Interquartile range) and biomarker levels were compared between patients and controls using Mann-Whitney Test. Using binary logistic regression, predictive potential of a combination of biomarkers for PE prediction was determined.
RESULTS: Women who developed PE 41 (3.97%) showed significantly increased levels of plasma CD62e [799.33 (546.86-1249.29) versus 384.08 (245.03-576.00), p < 0.0001], serum Copeptin [303.42 (226.01-484.18) versus 207.24 (169.73-276.46), p < 0.0001] and reduced level of PlGF [238.38 (161.36-312.62) versus 947.21 (466.7-1428.56), p < 0.0001] compared to controls at 18-23 weeks of gestation. None of the marker showed statistically significant alteration in levels in fetal growth restriction (FGR) group 68 (6.58%) compared to controls. Using binary logistic regression analysis, AUC, Sensitivity, specificity, PLR, NLR, PPV, and NPV of combination of CD62e, Copeptin and PlGF for prediction of PE at 18-23 weeks of gestation was 0.969, 92.3%, 90.3%, 9.73, 0.08, 79.17%, and 96.94%, respectively.
CONCLUSIONS: At 18-23 weeks, Combination of CD62e microparticles, copeptin, and PlGF levels can effectively identify women at risk of developing PE later in gestation.

BACKGROUND: Hypertension is associated with endothelial cell dysfunction. E-selectin, an endothelial cell adhesion molecule, is specific for endothelial cell activation. Polymorphism in E-selectin gene has recently been identified among which Leu554Phe E-selectin gene polymorphism is least investigated in essential hypertension. This study reports the association of E-selectin gene Leu554Phe polymorphism and the expression of E-selectin gene in patients with essential hypertension.
METHODS: We analysed the Leu554Phe polymorphism and expression of E-selectin gene in 250 patients with essential hypertension and 250 normal healthy controls. Genotyping of Leu554Phe polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the expression of E-selectin gene at mRNA and protein levels were carried out by real-time PCR and Western blot, respectively.
RESULTS: A significant association of E-selectin genotypes (CT + TT) with essential hypertension (P < .0001, Odds ratio = 2.2 [1.58-3.24] at 95% CI) was observed. The expression of mRNA for E-selectin gene in patients with essential hypertension was ~12-fold higher as compared to control. We observed an elevated level of E-selectin protein expression (up to 1.9 times) in patients as compared to controls.
CONCLUSIONS: A significant association of E-selectin (Leu554Phe) gene and increased expression of E-selectin gene at mRNA and protein levels in patients might be related to the genetic predisposition to develop essential hypertension.

BACKGROUND: Familial hypercholesterolaemia (FH) leads to premature coronary artery diseases (CAD) which pathophysiologically can be measured by inflammation, endothelial activation and oxidative stress status. However, the status of these biomarkers among related unaffected relatives of FH cases and whether FH is an independent predictor of these biomarkers have not been well established. Thus, this study aims to (1) compare the biomarkers of inflammation, endothelial activation and oxidative stress between patients with FH, their related unaffected relatives (RUC) and normolipaemic subjects (NC) (2)determine whether FH is an independent predictor of these biomarkers.
METHODS: One hundred thirty-one FH patients, 68 RUC and 214 matched NC were recruited. Fasting lipid profile, biomarkers of inflammation (hsCRP), endothelial activation (sICAM-1 and E-selectin) and oxidative stress [oxidized LDL (oxLDL), malondialdehyde (MDA) and F2-isoprostanes (ISP)] were analyzed and independent predictor was determined using binary logistic regression analysis.
RESULTS: hsCRP was higher in FH and RUC compared to NC (mean ± SD = 1.53 ± 1.24 mg/L and mean ± SD = 2.54 ± 2.30 vs 1.10 ± 0.89 mg/L, p < 0.05). sICAM-1 and E-selectin were higher in FH compared to NC (mean ± SD = 947 ± 742 vs 655 ± 191 ng/mL, p < 0.001 and 175 ± 131 vs 21.6 ± 10.7 ng/mL, p < 0.001 respectively) while sICAM-1 concentration was higher in RUC compared to NC (mean ± SD = 945 ± 379 vs 655 ± 191 ng/mL, p < 0.01). Biomarkers of oxidation (ox-LDL, MDA and ISP) were elevated in FH compared to NC [mean ± SD = (48.2 ± 26.8 vs 27.3 ± 13.2 mU/L, p < 0.001), (2.57 ± 1.3 vs 1.20 ± 0.30 nmol/mL, p < 0.001) and (645 ± 396 vs 398 ± 20.5 pg/L, p < 0.001) respectively], but no significant differences were observed between RUC and NC (p > 0.05). FH was an independent predictor for sICAM-1 (p = 0.007), ox-LDL (p < 0.001) and MDA (p < 0.001) while RUC independently predicted for sICAM-1 (p < 0.001).
CONCLUSIONS: The screening for FH is vital as all biomarkers associated with atherogenesis are higher in these subjects and FH also independently predict biomarkers of endothelial activation and oxidative stress. Furthermore, despite not fulfilling the diagnostic criteria for FH, related unaffected family members that may not phenotypically express the mutation may still be at risk of developing CAD as reflected from the enhanced inflammatory and endothelial activation status observed in this group. This highlights the need to not only conduct family tracing in indexed FH cases, but also assess the coronary risk among family members that do not fulfil the FH diagnostic criteria.

OBJECTIVE: To investigate the relationship between interleukin-6 (IL-6), endothelin-1 (ET-1), E-selectin and the risk of cardio-cerebrovascular events.
METHODS: Based on a cohort study in which 2 589 Mongolians had been followed up for 10 years, a nested case-control study was carried out to analyze the relationship between IL-6, ET-1, E-selectin and the risk of cardio-cerebrovascular events. Logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence intervals (95%CI).
RESULTS: The average level of IL-6 (7.66 vs. 8.77 pg/ml), ET-1 (0.74 vs. 0.75 pg/ml) and E-selectin (17.96 vs. 18.32 ng/ml)were not significantly different between the case and the control groups (P > 0.05). Data from the logistic regression analysis showed that IL-6, ET-1 and E-selectin were not significantly associated with the risk of cardio-cerebrovascular events. The multivariable adjusted ORs (95%CI) on the risk of cardio-cerebrovascular events were 0.69 (0.41-1.16), 1.10 (0.66-1.85) and 1.19 (0.71-2.00) for the participants with IL-6>23.91 pg/ml, ET-1>1.33 pg/ml and E-selectin>24.43 ng/ml, respectively, compared with those having IL-6≤23.91 pg/ml, ET-1≤1.33 pg/ml or E-selectin≤24.43 ng/ml.
CONCLUSIONS: Data from our study indicated that the levels of IL-6, ET-1 and E-selectin at baseline were not significantly associated with the risk of cardio-cerebrovascular events in people from Inner Mongolia.

OBJECTIVE: Sudden sensorineural hearing loss (SSNHL) is strictly related to inner ear vascular injuries and recently to some atherosclerotic risk factors. The pathogenic role of inflammatory molecules in atherosclerosis is well established. However, there is little knowledge about the potential role of inflammatory cytokines and adhesion molecules on SSNHL etiology.
METHODS: The aim of this study was to evaluate the role of proinflammatory genetic polymorphisms of the MCP-1 (CCL2), E-selectin, and interleukin (IL)-6 gene in SSNHL patients.
METHODS: We evaluated the frequency and distribution of selected single nucleotide polymorphisms of the MCP-1 (CCL2), E-selectin, and IL-6 gene in 87 SSNHL patients and 107 healthy controls.
RESULTS: Our results did not show significant difference between the compared groups for MCP-1 and E-selectin genes, whereas a significant difference was reported for the IL-6 gene (P < .0001).
CONCLUSIONS: The main finding of our study is that the 174G/G polymorphism (with a wider distribution of wt/wt genotype in SSNHL patients than in the healthy controls) of the IL-6 gene is significantly associated with the risk of SSNHL, which is consistent with a previous finding on serum levels of IL-6 in SSNHL. It is possible that the variant acts as a triggering agent of different lipidemia-related phenotypes. Both the -174G/G polymorphism and elevated IL-6 levels in SSNHL patients could suggest that IL-6 plays a role in the inner ear involvement by atherosclerotic inflammatory events.

BACKGROUND: The aim of this study was to evaluate the endothelial function, systemic inflammatory biomarkers and subgingival microbial profile associations in patients with and without periodontal disease.
METHODS: Forty-four patients, half with chronic moderate to severe periodontitis (cases) and half gingivitis and incipient periodontitis (controls) were recruited. Anthropometric, clinical, biochemical parameters, endothelial function, subgingival microbiota, and eight plasma biomarkers of cardiovascular disease were assessed in both groups.
RESULTS: Both groups were comparable in anthropometric parameters, blood pressure, and number of positive metabolic syndrome components. Univariate analyses demonstrated significantly higher plasma levels of E-selectin (64.5 ± 30.9 vs 43.8 ± 22.2; P = 0.026) and myeloperoxidase (MPO) (103 ± 114.5 vs 49.1 ± 35.6; P = 0.032) in cases than controls. In addition, significantly higher levels of E-selectin, MPO and ICAM-1 were found in periodontitis patients after adjustment by age and waist circumference. Red complex microorganisms were more frequently detected by culture and polymerase chain reaction in patients with severe to moderate periodontitis.
CONCLUSIONS: Subgingival red complex bacteria and important cardiovascular risk markers were increased in untreated chronic moderate to severe periodontitis cases. Periodontitis seems to be associated with systemic inflammation that could increase the risk of cardiovascular events. The causal relation between periodontal infections and cardiovascular disease requires further research.

BACKGROUND: Coal workers\' pneumoconiosis (CWP) is characterized by chronic pulmonary inflammation and fibrotic nodular lesions that usually lead to progressive fibrosis. Inflammation is the first step in the development of CWP. E-selectin, an adhesion molecule, is involved in the development of various inflammatory diseases.
METHODS: We investigated the association between the functional polymorphisms in SELE and the risk of CWP in Han Chinese population. Three polymorphisms (T1880C/rs5355, T1559C/rs5368, A16089G/rs4786) in SELE were genotyped and analyzed in a case-control study with 697 CWP cases and 694 controls. The genotyping was based on the TaqMan method with the ABI 7900HT Real Time PCR system.
RESULTS: The SELE rs5368 CT genotype was associated with a significantly increased risk of CWP (OR = 1.28, 95% CI = 1.02-1.60, P = 0.03) relative to the CC genotype. The statistical analysis of classification and regression tree (CART) and multifactor dimensionality reduction (MDR) were used to predict the interactions among risk factors of CWP. The MDR analysis found that the best interaction model was the two-factor model that contains pack-years smoked and SELE rs5368 genotypes. For non-smokers, the CART analysis showed an increased risk of CWP for carriers of the SELE rs_5368 variant genotype compared with the common genotype (OR = 1.51; 95% CI = 1.11-2.05, P = 0.0069).
CONCLUSIONS: The results suggest that the T1559C/rs5368 polymorphism and smoking are involved in the susceptibility to CWP. Further studies are warranted to validate these findings.

OBJECTIVE: To evaluate prediagnostic markers of endothelial dysfunction and inflammatory processes in primary open-angle glaucoma (POAG).
METHODS: Blood samples were collected from 1989 to 1990 in the nurses\' health study (women) and from 1993 to 1995 in the health professionals follow-up study (men), and medical-record confirmed incident poag cases were identified (women: 229 cases and 455 controls; men: 116 cases and 228 controls). Controls were matched on cohort, age, race, ethnicity, cancer status, and date of blood collection. Plasma concentrations of ICAM-1, E-selectin, and soluble TNF receptor 2 (sTNF-R2), a marker related to TNF-α, were measured with ELISA assays. Cohort-specific multivariable conditional logistic regression model results were meta-analyzed.
RESULTS: We observed no associations with ICAM-1 or E-selectin. for sTNF-R2, the mean (SD) plasma levels (pg/ml) in cases and controls were 2888 (997) and 2993 (913), respectively, in women; and 2622 (664) and 2569 (688), respectively, in men. pooled multivariable results showed no relation between sTNF-R2 levels and POAG. however, compared with the lowest tertile of sTNF-R2, the highest tertile showed a significant decreased risk of POAG in women (multivariable odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.360.93; P(trend) = 0.03) but not in men (P(trend) = 0.21; P for heterogeneity by sex = 0.03). also, among women, the inverse association with sTNF-R2 was stronger with normal-tension glaucoma (ntg; maximum intraocular pressure 21 mm Hg at diagnosis): highest versus lowest tertile comparison OR = 0.29 (95% CI = 0.12-0.71; Ptrend = 0.007).
CONCLUSIONS: In women, but not in men, higher sTNF-R2 levels at 6 to 8 years before diagnosis were inversely associated with POAG, but more strongly for NTG.

BACKGROUND: Genetic variation is thought to contribute to the etiology of hypertension, and E-selectin is a candidate essential hypertension-associated gene. This study thus sought to investigate possible genetic associations between the T1880C, C602A and T1559C polymorphisms of E-selectin and essential hypertension.
METHODS: Hypertensive patients (n = 490) and healthy normotensive subjects (n = 495) were screened for the genotypes T1880C, C602A and T1559C using real-time quantitative polymerase chain reaction after DNA extraction to identify representative variations in the E-selectin gene. The associations between genotypes and alleles of the three mutations and essential hypertension were then analyzed using a case-control study.
RESULTS: Hypertensive patients and normotensive subjects were significantly different with respect to the genotypes CC, CA and AA (P = 0.005) and the C-allele frequency of C602A (P = 0.001). A comparison of dominant versus recessive models also revealed significant differences between the two groups (P = 0.004 and P = 0.02). When subgrouped by gender, these indexes differed significantly between normotensive and essential hypertensive males, but not in females. The additive model of the T1559C genotype did not differ between essential hypertensive and normotensive groups overall (P = 0.39), but it was different between hypertensive and normotensive males (P = 0.046) and females (P = 0.045). The CC + TC versus TT frequency of T1559C was also different in the recessive model of male hypertensive and normotensive groups (P = 0.02). Further analysis showed that C602A and T1559C were significantly associated with hypertension (C602A: OR = 7.58, 95%CI = 1.53-11.97, P < 0.01; and T1559C: OR = 6.77, 95%CI = 1.07-1.83, P < 0.05). The frequency of the C-C-C haplotype was significantly higher in hypertensive patients than in control individuals as well as in hypertensive and normotensive males (P = 0.008 and 0.01). The frequency of the C-A-T haplotype was higher only in male hypertensives and normotensives (P = 0.015). Furthermore, there was a significant interaction between E-selectin and gender (P = 0.02 for C602A and 0.04 for T1559C).
CONCLUSIONS: C602A and T1559C may be independent risk factors for essential hypertension in the Chinese population, whereas T1880C is not.