Endothelial function and cardiovascular risk in active inflammatory bowel diseases.

BACKGROUND: Endothelial dysfunction has been already reported in inflammatory bowel diseases (IBD). However, case series so far examined were rather heterogeneous as for disease severity and subsets investigated. OBJECTIVE: We evaluated endothelial dysfunction by brachial artery flow-mediated vasodilatation (FMD), and subclinical atherosclerosis by assessment of common carotid intima-media thickness (CCA-IMT) in a cohort of patients with Crohn's disease (CD) or Ulcerative colitis (UC) in active phase compared to healthy control subjects. METHODS: Forty-nine patients (mean age 41±16 years), 25 with CD and 23 with UC, and forty controls (mean age 45±15 years) were enrolled. Diagnosis was based on the standard clinical, endoscopic and histological criteria. Disease activity was assessed by Crohn's Disease Activity Index or Disease Activity Index. All patients, were under medical treatment as appropriate. RESULTS: FMD values were lower in IBD patients than controls (6.1±3.0 vs 8.2±3.4. p=0.003); no difference was seen between UC/CD groups (5.9±3.5 vs 6.3±2.6, p=0.67). No changes in statistical differences occurred after adjustment for age, gender, body mass index and family history of cardiovascular disease. Finally, no differences in IMT values were seen between IBD patients and controls. Disease duration and medical treatment did not affect endothelial function. CONCLUSIONS: Our study showed a lower FMD in IBD patients. Inflammation and immune response could explain endothelial dysfunction, which is the earliest stage of atherosclerotic process. IBD patients in active phase might therefore be at higher risk for atherosclerosis progression.

Alrp, a survival factor that controls the apoptotic process of regenerating liver after partial hepatectomy in rats.

Augmenter of Liver Regeneration (Alrp) enhances, through unknown mechanism/s, hepatocyte proliferation only when administered to partially hepatectomized (PH) rats. Liver resection, besides stimulating hepatocyte proliferation, induces reactive oxygen species (ROS), triggering apoptosis. To clarify the role of Alrp in the process of liver regeneration, hepatocyte proliferation, apoptosis, ROS-induced parameters and morphological findings of regenerating liver were studied from PH rats Alrp-treated for 72 h after the surgery. The same parameters, evaluated on regenerating liver from albumin-treated PH rats, were used as control. The results demonstrated that Alrp administration induces the anti-apoptotic gene expression, inhibits hepatocyte apoptosis and reduces ROS-induced cell damage. These and similar data from in vitro studies and the presence of 'Alrp homologous proteins' in viruses as well as in mammals (i) allow to hypothesize that Alrp activity/ies may not be exclusive for regenerating liver and (ii) suggest the use of Alrp in the treatment of oxidative stress-related diseases.

Estrogens, phytoestrogens and colorectal neoproliferative lesions.

Epidemiological and experimental studies suggest a protective role of estrogens against colorectal cancer. This effect seems to be mediated by their binding to estrogen receptor beta (ER-beta), one of the two estrogen receptors with high affinity for these hormones. Very recently, the demonstration of an involvement of ER-beta in the development of adenomatous polyps of the colon has also been documented, suggesting the use of selective ER-beta agonists in primary colorectal cancer prevention. Phytoestrogens are plant-derived compounds that structurally and functionally act as estrogen-agonists in mammals. They are characterized by a higher binding affinity to ER-beta as compared to estrogen receptor alpha (ER-alpha), the other estrogen receptor subtype. These biological characteristics explain why the administration of phytoestrogens does not produce the classical side effects associated to estrogen administration (cerebro- and cardio-vascular accidents, higher incidence of endometrial and breast cancer) and makes these substances ideal candidates for the prevention of colorectal cancer.