Inflammation markers are associated with Cardiovascular diseases risk in adolescents The Young Hearts Project 2000

Purose: The traditional approach for identifying subjects at risk from cardiovascular diseases (CVD) is to determine the extent of clustering of biological risk factors adjusted for lifestyle. Recently, markers of endothelial dysfunction and low grade inflammation, including high sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecules (sICAM), and soluble vascular adhesion molecules (sVCAM), have been included in the detection for high risk individuals. However, the relationship of these novel biomarkers with CVD risk in adolescents remains unclear. The purpose of this study, therefore, was to establish the association of hsCRP, sICAM, and sVCAM with CVD risk in an adolescent population.
Methods: Data from the Young Hearts 2000 cross-sectional cohort study, carried out in 1999-2001, were used. From a total of 2,017 male and female participants, 95 obese subjects were identified and matched according to age, sex, and cigarette smoking, with 95 overweight and 95 normal-weight adolescents. Clustered CVD risk was computed using a sum of Z-scores of biological risk factors. The relationship was described using multiple linear regression analyses.
Results: hsCRP, sICAM, and sVCAM showed significant associations with CVD risk. hsCRP and sICAM had a positive relation with CVD risk, whereas sVCAM showed an inverse relationship. In this study, lifestyle factors showed no relation with CVD risk.
Conclusion: The results fit the hypothesized role of low grade inflammation and endothelial dysfunction in CVD risk in asymptomatic adolescents. The inverse relationship of VCAM, however, is hard to explain and indicates the complex mechanisms underlying CVD. Further research is needed to draw firm conclusions on the biomarkers used.

New microsatellite markers for Ulva intestinalis (Chlorophyta) and the transferability of markers across species of Ulvaceae

Macroalgal blooms are a growing environmental problem in eutrophicated coastal ecosystems. Members of the green algal genus Ulva are significant contributors to blooms, which are typically dominated by only one of several co-occurring opportunistic species. Our understanding of bloom dynamics, such as the importance of clonality, is limited because previously used genetic markers such as internal transcribed spacer sequences have shown very little resolution. Microsatellites are the marker of choice for such studies, but to date, only five primer pairs have been developed for a single member of this genus, Ulva intestinalis. We have now developed four new microsatellite markers for U. intestinalis using genome screening and restriction-ligation and tested them on individuals from six populations in the Gulf of Finland, Finland. All new markers exhibited polymorphism in U. intestinalis, with the numbers of alleles ranging from 6 to 10. On the basis of assignment tests, F-ST estimates and analysis of molecular variance, there was genetic differentiation among populations. Where significantly different, expected heterozygosity (HE) was higher than observed heterozygosity (Ho), indicating a trend toward heterozygote deficiency. This may indicate that although Ulva spores can disperse relatively efficiently, asexual reproduction can result in genetic differentiation among populations. We also tested the cross-species amplification of our primers and the five primer pairs reported previously on seven species of Ulva, Ulvaria obscura and Unbraulva olivascens (all members of the Ulvaceae). In each species, from five to nine of the loci produced an amplification product, and one to four alleles were discovered at each locus. These markers therefore have great potential for testing hypotheses about the formation and maintenance of multispecies macroalgal blooms.

Hyperglycaemia-induced pro-inflammatory responses by retinal Müller glia are regulated by the receptor for advanced glycation end-products (RAGE)

Aims/hypothesis: Up-regulation of the receptor for AGEs (RAGE) and its ligands in diabetes has been observed in various tissues. Here, we sought to determine levels of RAGE and one of its most important ligands, S100B, in diabetic retina, and to investigate the regulatory role of S100B and RAGE in Müller glia.

Methods: Streptozotocin-diabetes was induced in Sprague-Dawley rats. RAGE, S100B and glial fibrillary acidic protein (GFAP) were detected in retinal cryosections. In parallel, the human retinal Müller cell line, MIO-M1, was maintained in normal glucose (5.5 mmol/l) or high glucose (25 mmol/l). RAGE knockdown was achieved using small interfering RNA (siRNA), while soluble RAGE was used as a competitive inhibitor of RAGE ligand binding. RAGE, S100B and cytokines were detected using quantitative RT-PCR, western blotting, cytokine protein arrays or ELISA. Activation of mitogen-activated protein kinase (MAPK) by RAGE was determined by western blotting.

Results: Compared with non-diabetic controls, RAGE and S100B were significantly elevated in the diabetic retina with apparent localisation in the Müller glia, occurring concomitantly with upregulation of GFAP. Exposure of MIO-M1 cells to high glucose induced increased production of RAGE and S100B. RAGE signalling via MAPK pathway was linked to cytokine production. Blockade of RAGE prevented cytokine responses induced by high glucose and S100B in Müller glia.

Conclusions/interpretation: Hyperglycaemia in vivo and in vitro exposure to high glucose induce upregulation of RAGE and its ligands, leading to RAGE signalling, which links to pro-inflammatory responses by retinal Müller glia. These data shed light on the potential clinical application of RAGE blockade to inhibit the progression of diabetic retinopathy.

Intrinsic variability in the detection of micrometastases in lymph nodes for re-staging of colorectal cancer: effect of individual markers and tissue samples

In this study, we investigated whether (a) carcinoembryonic antigen (CEA), cytokeratin-20 (CK-20) and guanylyl cyclase C (GCC) are clinically useful markers for the molecular detection of submicroscopic metastases in colorectal cancer (CRC) and (b) whether overexpression of CEA, CK-20 and GCC can be reliably detected in formalin-fixed, paraffin-embedded tissues as well as frozen lymph nodes. We studied 175 frozen lymph nodes and 158 formalin-fixed, paraffin-embedded lymph nodes from 28 cases of CRC. CEA or CK-20 or GCC-specific polymerase chain reaction (PCR) was carried out on mRNA transcripts extracted from the nodal tissues. Ten out of I I Dukes' B CRC cases had detectable CEA and CK-20 while 6 out of 11 Dukes' B CRC cases had detectable GCC. In general, the difference of re-staged cases when comparing frozen and paraffin-embedded samples was marked; the only statistically significant correlation between frozen and paraffin tissue was for the CEA marker. Our results indicated a high incidence (>50%) of detecting micrometastases in histologically-negative lymph nodes at the molecular level. (C) 2003 Elsevier Science Ltd. All rights reserved.

A20 Regulation of NF-{kappa}B: Perspectives for Inflammatory Lung Disease.

Persistent activation of NF-B is central to the pathogenesis of many inflammatory lung disorders including Cystic Fibrosis, Asthma and Chronic Obstructive Pulmonary Disease. A20 is an endogenous negative regulator of NF-B signalling which has been widely described in autoimmune and inflammatory disorders including Diabetes and Crohn’s disease, but which has received little attention in terms of chronic lung disorders. This review examines the existing body of research on A20 regulation of NF-B signalling and details the mechanism and regulation of A20 action focusing, where possible, on pulmonary inflammation. A20 and its associated signalling molecules are highlighted as being of potential therapeutic interest for the treatment of inflammatory disorders and a proposed model of A20 activity in inflammatory lung disease is provided.

Iron intake and markers of iron status and risk of Barrett's esophagus and esophageal adenocarcinoma

Objective To investigate the association between iron intake and iron status with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC).