Meirav Rozenblat

Gender difference in C-reactive protein concentrations in individuals with atherothrombotic risk factors and apparently healthy ones

Recent studies have shown that C-reactive proteins have a pathogenetic role in atherothrombosis and concentrations of these substances could be used as a marker for future vascular events. The objective of this study was to determine gender differences in highly sensitive C-reactive protein (hs-CRP) in individuals with atherothrombotic risk factors and apparently healthy ones. We have presently matched 469 females and 469 males having the same age and body mass index (BMI). Of these, 210 men and 210 women had no atherothrombotic risk factors. In this group the hs-CRP concentrations were 1.6±3.4 mg l−1 in women and 1.0±2.7 mg l−1 in men (p<0.0005). These values were 2.1±3.4 mg l−1 and 1.5±2.8 mg l−1, respectively, in the entire cohort (p<0.0005), which included also individuals with atherothrombotic risk factors. We conclude that significant gender differences exist in hs-CRP concentrations despite perfect matching for age and BMI. These differences should be reflected in guidelines that suggest hs-CRP cut-off points for the stratification of vascular risk.

Correlated Expression of High-Sensitivity C-Reactive Protein in Relation to Disease Activity in Inflammatory Bowel Disease: Lack of Differences between Crohn’s Disease and Ulcerative Colitis

Background/Aims: As opposed to regular C-reactive protein (CRP) assays, the introduction of high-sensitivity ones has enabled us to detect low grade inflammation in patients with inflammatory bowel disease (IBD). We addressed the subject of the degree of correlation between the concentration of high-sensitivity CRP (hs-CRP) and the inflammatory IBD activity score. Methods: Included were 90 patients with Crohn’s disease (CD), 70 with ulcerative colitis (UC) and 160 controls. Disease activity was determined using CD activity index (CDAI) for CD and Mayo score for UC. The Dade Boering BNII Nephelometer was used to determine the hs-CRP concentrations. Results: The coefficient of correlation between hs-CRP and the disease activity score was similar for both UC (0.26) and CD (0.36). Conclusions: These findings are relevant for therapeutic intervention in which a greater absolute reduction in the hs-CRP concentration in CD patients (who generally present higher CRP concentrations than those found in UC) might be interpreted as a better response compared to the same absolute reduction in UC patients. This information is needed for clinicians using the hs-CRP assay to estimate IBD disease activity in daily practice.

The appearance of aggregated erythrocytes in the peripheral blood of individuals with insulin resistance

Insulin resistance is associated with low‐grade inflammatory response. The probability that the acute‐phase response is associated with enhanced erythrocyte adhesiveness/aggregation was not explored.

Inhibition of cell growth by a beta-catenin responsive element

Background: Many colon cancers harbor mutations in the APC/beta-catenin pathway, leading to actwation of downstream genes with beta-catenin/T-cell factor (Tci)responsive promoters. The ultimate therapy of cancer is by targeting neoplastic cells without damaging normal cells. Aim: To selectively kill beta catenin transformed cells by up-regulation of lethal genes using a mutated signal transduction pathway. Materials & Methods: A Xbal fragment contains the TOP/FOP-cFos sequence was cut out from the TOP/FOP flash plasmids (a gift from Hans Clevers) and then cloned to the pGL3-basic vector (Promega), into the Nhel site. The resultant plasmid was designated as pGL3-TOP/FOP. Then, the Luc gene was cut out from this plasmid by Hindlll-Xbal digestion and a cloning site linker was inserted instead of the Luc gene to make the plasmid pGL3-TOP/FOP-HX. The TOP/FOP-HX was used to construct 3 separate genes: Bax, caspase 8 and PKG. The new plasmids were designated as TOP/ FOP-Bax, TOP/FOP-Cas8, and TOP/FOP-PKG. Exponentially growing SW 480 cells, with increased expression of beta~catenin, were transiently transfected with these constructs and then treated for 48 and 72hr with different dosages of a specific COX 2 inhibitor (Celecoxib, 0-50uM). Results: The growth of SW 480 cells was not hampered by the transfection with the FOP plasmids. The TOP-PKG and TOP-Bax plasmids inhibited cell growth by approximatly 20-35%, respectively, while the plasmid TOP-cas8 did not inhibit cell growth. The growth inhibition was associated with induction of apoptosis.Celecoxib inhibited the growth of SW480 ceils The addition of celecoxib to the TOP-Bax/cas8/PKG transfected cells, augmented the growth inhibition in a time and dose dependent manner. Conclusions: 1. This approach may be used to develop therapies to target tumor cells that have defects in the Wnt/beta-catenin/Tcf signal transduction pathway. 2. Selective over-expression of some pro-apoptotic genes, in beta-catenin transformed cells increase their sensitivity to celeco:db. 3. In this model Bax and PKG but not caspase 8 could serve as potential targets, to selectively induce turner cell death.