Inflammatory cytokine, adipokine and adhesion molecules are known to play a key role in pathogenesis of diabetic kidney disease (DKD). In this study, our aim was to investigate the role of fetuin-A in relation with pro-inflammatory cytokines (IL-6, IL-18), adipokines (adiponectin, leptin), chemokine (MCP-1), and adhesion molecules (ICAM-1, VCAM-1) in control and DKD subjects. We recruited a total of 224 type 2 diabetic (T2D) subjects. The control subjects were T2D with a normal albumin excrete (albumin-to-creatinine ratio-ACR ≤ 30 mg/g creatinine) and estimated glomerular filtration rate (eGFR) ≥ 60 (ml/min/1.73 m2), while cases were T2D subjects with albumin excrete (ACR ≥ 30 mg/g creatinine) and eGFR ≤ 60 (ml/min/1.73 m2). FBS, HbA1c, lipid profile (TC, LDL, HDL, triglyceride), ALT, AST, GGT, serum creatinine, BMI, blood pressure was evaluated in all the study subjects. Randox evidence biochip analyzer was used for measuring inflammatory cytokines, adipokines, and adhesion molecules by chemiluminescent assay. Serum fetuin-A and IL-18 were measured by ELISA kits. Serum fetuin-A levels were significantly decreased in DKD cases compare to control group [456.8 (299.2-649.0) µg/ml versus 670.6 (573.0-726.1) µg/ml; p < 0.001)]. Serum fetuin-A levels correlates significantly with IL-6, IL-18, TNF-α, PAI-1, leptin, resistin and ACR (p < 0.001). This study concludes that serum fetuin-A and pro-inflammatory markers (IL-18, IL-6, IL-1α and TNF-α) might play an important role in the pathophysiology and inflammatory process of DKD.

The presence of neopterin in gingival crevicular fluid (GCF) is a marker for local and acute immune activation, and the presence of vascular cell adhesion molecule (VCAM-1) in GCF is accepted as a marker for chronic vascular inflammation.
OBJECTIVE: This study aimed to evaluate effects of periodontal treatment on GCF levels of neopterin and VCAM-1 in patients with chronic periodontitis (CP) with acute myocardial infarction (AMI) compared with systemically healthy CP patients.
METHODS: Sixty subjects (20 CP patients with AMI, 20 healthy CP patients, and 20 healthy controls) were included. GCF samples were analyzed at baseline and after 3 and 6 months, and the probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing, gingival (GI) and plaque (PI) indices were recorded. We determined neopterin and VCAM-1 levels (concentration and total amount) using enzyme-linked immunosorbent assay (ELISA). No significant differences were seen between the AMI+CP and CP groups for PI, GI, GCF levels of neopterin and VCAM-1 at baseline.
RESULTS: The number of teeth with 5 mm≤CAL<7 mm and CAL≥7 mm were significantly increased in the AMI+CP group at baseline. There were no significant differences between the AMI+CP and CP for PI, CAL, GCF volumes, and the AMI+CP group had the highest clinical improvement in the number of teeth with 5 mm≤CAL<7 mm at the sixth month. There were significant positive correlations between clinical periodontal inflammation and the presence of neopterin and VCAM-1 in GCF prior to and following periodontal treatment, and between the GCF volume and clinical parameters.
CONCLUSIONS: Data suggest that the total amount and concentration of neopterin and VCAM-1 in GCF seemed to be closely associated with periodontal disease severity in CP patients with AMI. Moreover, the results of our study demonstrate that the past periodontal status is potentially correlated between groups, with similar periodontal disease severity.

Reducing death due to neonatal sepsis is a global health priority, however there are limited tools to facilitate early recognition and treatment. We hypothesized that measuring circulating biomarkers of endothelial function and integrity (i.e. Angiopoietin-Tie2 axis) would identify young infants with sepsis and predict their clinical outcome.
We conducted a matched case-control (1:3) study of 98 young infants aged 0-59 days of life presenting to a referral hospital in Bangladesh with suspected sepsis. Plasma levels of Ang-1, Ang-2, sICAM-1, and sVCAM-1 concentrations were measured at admission. The primary outcome was mortality (n = 18); the secondary outcome was bacteremia (n = 10).
Ang-2 concentrations at presentation were higher among infants who subsequently died of sepsis compared to survivors (aOR 2.50, p = 0.024). Compared to surviving control infants, the Ang-2:Ang-1 ratio was higher among infants who died (aOR 2.29, p = 0.016) and in infants with bacteremia (aOR 5.72, p = 0.041), and there was an increased odds of death across Ang-2:Ang-1 ratio tertiles (aOR 4.82, p = 0.013).
This study provides new evidence linking the Angiopoietin-Tie2 pathway with mortality and bacteremia in young infants with suspected sepsis. If validated in additional studies, markers of the angiopoietin-Tie2 axis may have clinical utility in risk stratification of infants with suspected sepsis.

The pathogenic basis of abnormal placentation and dysfunction in preeclampsia (PE) is highly complex and incompletely understood. Secretory sphyngomyelinase activity (S-ASM) was analyzed in plasma samples from 158 pregnant women developing PE and 112 healthy pregnant controls. Serum PlGF, sFlt-1, s-Endoglin and sVCAM were measured. Results showed S-ASM activity to be higher in women who later developed PE than in those with uncomplicated pregnancies (40.6% and 28.8% higher in the late- and early-onset groups, respectively). Plasma S-ASM activity correlated significantly with circulating markers of endothelial damage in the late-PE group (endoglin and sVCAM-1), with plasma cholesterol and total lipid levels. However, these significant associations were not observed in the early-PE or control groups. This work provides the first evidence of significantly elevated circulating S-ASM activity in the first trimester of pregnancy in women who go on to develop PE; thus, it may be deduced that the circulating form of ASM is biologically active in PE and could contribute to promoting endothelial dysfunction and cardiovascular programming. Plasma S-ASM measurement may have clinical relevance as a further potential biomarker contributing to the earliest identification of women at risk of developing preeclampsia.

BACKGROUND: Epidemiologic data on genetic susceptibility to cardiovascular effects of arsenic exposure from drinking water are limited.
OBJECTIVE: We investigated whether the association between well-water arsenic and cardiovascular disease (CVD) differed by 170 single nucleotide polymorphisms (SNPs) in 17 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction.
METHODS: We conducted a prospective case-cohort study nested in the Health Effects of Arsenic Longitudinal Study, with a random subcohort of 1,375 subjects and 447 incident fatal and nonfatal cases of CVD. Well-water arsenic was measured in 2000 at baseline. The CVD cases, 56 of which occurred in the subcohort, included 238 coronary heart disease cases, 165 stroke cases, and 44 deaths due to other CVD identified during follow-up from 2000 to 2012.
RESULTS: Of the 170 SNPs tested, multiplicative interactions between well-water arsenic and two SNPs, rs281432 in ICAM1 (padj = 0.0002) and rs3176867 in VCAM1 (padj = 0.035), were significant for CVD after adjustment for multiple testing. Compared with those with GC or CC genotype in rs281432 and lower well-water arsenic, the adjusted hazard ratio (aHR) for CVD was 1.82 (95% CI: 1.31, 2.54) for a 1-SD increase in well-water arsenic combined with the GG genotype, which was greater than expected given aHRs of 1.08 and 0.96 for separate effects of arsenic and the genotype alone, respectively. Similarly, the joint aHR for arsenic and the rs3176867 CC genotype was 1.34 (95% CI: 0.95, 1.87), greater than expected given aHRs for their separate effects of 1.02 and 0.84, respectively.
CONCLUSIONS: Associations between CVD and arsenic exposure may be modified by genetic variants related to endothelial dysfunction.

BACKGROUND: Cytoadherence of infected red blood cells to brain endothelium is causally implicated in malarial coma, one of the severe manifestations of falciparum malaria. Cytoadherence is mediated by specific binding of variant parasite antigens, expressed on the surface of infected erythrocytes, to endothelial receptors including, ICAM-1, VCAM and CD36. In fatal cases of severe falciparum malaria with coma, blood vessels in the brain are characteristically congested with infected erythrocytes. Brain sections from a fatal case of knowlesi malaria, but without coma, were similarly congested with infected erythrocytes. The objective of this study was to determine the binding phenotype of Plasmodium knowlesi infected human erythrocytes to recombinant human ICAM-1, VCAM and CD36.
METHODS: Five patients with PCR-confirmed P. knowlesi malaria were recruited into the study with consent between April and August 2010. Pre-treatment venous blood was washed and cultured ex vivo to increase the proportion of schizont-infected erythrocytes. Cultured blood was seeded into Petri dishes with triplicate areas coated with ICAM-1, VCAM and CD36. Following incubation at 37°C for one hour the dishes were washed and the number of infected erythrocytes bound/mm2 to PBS control areas and to recombinant human ICAM-1 VCAM and CD36 coated areas were recorded. Each assay was performed in duplicate. Assay performance was monitored with the Plasmodium falciparum clone HB3.
RESULTS: Blood samples were cultured ex vivo for up to 14.5 h (mean 11.3 ± 1.9 h) to increase the relative proportion of mature trophozoite and schizont-infected red blood cells to at least 50% (mean 65.8 ± 17.51%). Three (60%) isolates bound significantly to ICAM-1 and VCAM, one (20%) isolate bound to VCAM and none of the five bound significantly to CD36.
CONCLUSIONS: Plasmodium knowlesi infected erythrocytes from human subjects bind in a specific but variable manner to the inducible endothelial receptors ICAM-1 and VCAM. Binding to the constitutively-expressed endothelial receptor CD36 was not detected. Further work will be required to define the pathological consequences of these interactions.

BACKGROUND: Acute kidney injury (AKI) following cardiac surgery with cardiopulmonary bypass (CPB) causes increased morbidity and mortality.
OBJECTIVE: To evaluate the plasma profile of biomarkers potentially involved in AKI development following CPB.
METHODS: In a nested case-control study, plasma levels of 27 biomarkers in 11 AKI cases were compared with 25 controls.
RESULTS: Pre-CPB, plasma levels of epidermal growth factor and macrophage inflammatory protein-1beta, 2 h following CPB, soluble vascular cell adhesion molecule-1 (sVCAM-1), fractalkine and macrophage inflammatory protein-1alpha, and at later time points, sVCAM-1 and interleukin-6 were associated with AKI.
CONCLUSIONS: Biomarkers associated with AKI following CPB may merit further study.

OBJECTIVE: There is evidence that inflammation plays a role in the pathogenesis of atherosclerosis. We compared levels of inflammatory markers between patients undergoing carotid endarterectomy (CEA) and controls, and between patients with symptomatic and asymptomatic internal carotid artery (ICA) stenosis.
METHODS: A total of 180 patients with ICA stenosis were compared with 180 age-matched and sex-matched controls. The biomarkers evaluated were high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1 (sVCAM-1), and interleukin-6 (IL-6).
RESULTS: The levels of hs-CRP, sVCAM-1, and IL-6 in the CEA group were significantly higher than in the control group (1.87 mg/mL vs 1.44 mg/mL, P = .011; 1408 ng/dL vs 672 ng/dL, P < .001; 11.9 pg/mL vs 6.3 pg/mL, P < .001). Multivariate linear regression analysis, adjusted for all clinical and physiologic parameters, showed a significant association between ICA stenosis and hs-CRP, sVCAM-1, and IL-6 concentrations. Analysis of symptomatic (n = 101) and asymptomatic (n = 79) ICA stenosis did not detect a difference in levels of these markers.
CONCLUSIONS: Our study suggests that inflammatory markers could serve as markers for ICA atherosclerosis but are not useful to identify carotid plaque at risk for symptomatic conversion.

OBJECTIVE: The aim of this study was to study the inflammatory response to open revascularization of an ischemic leg in terms of activation of white blood cells (WBC), platelets and endothelial cells.
METHODS: prospective study.
METHODS: Venous samples from 21 patients suffering critical limb ischemia (CLI) were drawn before, and 4 weeks after (20 patients) revascularization. Total WBC, differentiated WBC, and platelets were counted. Expression of CD11b/CD18 on granulocytes and monocytes and CD41 on platelets was measured by flow cytometry. Soluble endothelial markers (sICAM-1, sVCAM-1, sE-selectin and sP-selectin) were analysed with ELISA.
RESULTS: WBC and granulocyte count decreased in the subgroup of patients with ulcer and gangrene but no change in activation of WBC was recorded. The endothelial marker sICAM-1 decreased while VCAM-1 increased following surgery, most evident in the subgroup with ulcers and gangrene.
CONCLUSIONS: This study shows that revascularization of CLI does not significantly influence the inflammatory response in patients with rest pain only, but a limited response of down regulation was found in the ulcer/gangrene patients probably as an effect of healing ulcers.

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