Thoracic aorta shows with advancing age various changes and a progressive deterioration in structure and function. As a result, vascular remodeling (VR) and medial degeneration (MD) occur as pathological entities responsible principally for the sporadic TAA onset. Little is known about their genetic, molecular, and cellular mechanisms. Recent evidence is proposing the strong role of a chronic immune/inflammatory process in their evocation and progression. Thus, we evaluated the potential role of Toll like receptor- (TLR-) 4-mediated signaling pathway and its polymorphisms in sporadic TAA. Genetic, immunohistochemical, and biochemical analyses were assessed. Interestingly, the rs4986790 TLR4 polymorphism confers a higher susceptibility for sporadic TAA (OR = 14.4, P = 0.0008) and it represents, together with rs1799752 ACE, rs3918242 MMP-9, and rs2285053 MMP-2 SNPs, an independent sporadic TAA risk factor. In consistency with these data, a significant association was observed between their combined risk genotype and sporadic TAA. Cases bearing this risk genotype showed higher systemic inflammatory mediator levels, significant inflammatory/immune infiltrate, a typical MD phenotype, lower telomere length, and positive correlations with histopatological abnormalities, hypertension, smoking, and ageing. Thus, TLR4 pathway should seem to have a key role in sporadic TAA. It might represent a potential useful tool for preventing and monitoring sporadic TAA and developing personalized treatments.

Food intolerance-related constipation is characterized by proctitis with eosinophil infiltrate of the rectal mucosa. A reduced mucus gel layer can be considered a contributory factor in the pathogenesis of the constipation.

Background Chronic constipation in children can be caused by cows' milk intolerance (CMI), but its pathogenesis is unknown.Aims To evaluate the histology and manometry pattern in patients with food intolerance-related constipation.Patients and methods Thirty-six consecutive children with chronic constipation were enrolled. All underwent an elimination diet and successive double-blind food challenge. All underwent rectal biopsy and anorectal manometry.Results A total of 14 patients were found to be suffering from CMI and three from multiple food intolerance. They had a normal stool frequency on elimination diet, whereas constipation recurred on food challenge. The patients with food intolerance showed a significantly higher frequency of erosions of the mucosa, and the number of intra-epithelial lymphocytes and eosinophils. The rectal mucous gel layer showed that the food-intolerant patients had a significantly lower thickness of mucous than the other subjects studied. Manometry showed a higher anal sphincter resting pressure and a lower critical volume in food intolerance patients than in the others suffering from constipation unrelated to food intolerance. Both histology and manometry abnormalities disappeared on the elimination diet.Conclusions Food intolerance-related constipation is characterized by proctitis. Increased anal resting pressure and a reduced mucous gel layer can be considered to be contributory factors in the pathogenesis of constipation. Eur

Objective: Oral Lichen Planus (OLP) is a chronic inflammatory disease with an autoimmune inflammatory pathogenesis. The aim of the research is to compare the vascular endothelial growth factor (VEGF) and adhesion of molecules in the biopsy samples of patients affected by OLP, in order to research the presence of the angiogenetic phenomenon and to understand its pathogenetic mechanism. Materials and Methods: Thirty OLP patients and thirty healthy subjects were enrolled in a study. The immunohistochemical analysis of the VEGF and vascularendothelial adhesion molecules was carried out by means of primary antibodies and anti-CD34, anti-VEGF, anti-CD106 antigen (VCAM-1) and anti-CD54 antigen (ICAM-1). The statistical significance of the differences was checked with the Mann-Whitney test (MW test). The level of significance was set to P<0.001. Data analysis was carried out with StatView 5.0.1 (SAS Institute Inc., Cary, NC). Results: The results reveal the presence of a significant angiogenesis in OLP patients for the VEGF, CD34, CD106 and CD54 (P < 0.001).. The number of vessels in the biopsies of the patients with OLP (mean±SD: 21.27±4.85), compared with the healthy subjects (mean±SD: 4.74±0.97) was significantly more (Mann-Whitney test, P < 0.001). The positive expression rate of VEGF, CD34, VCAM-1 and ICAM-1 in oral lichen samples was 64.2%, 54.3%, 32.5% and 29.7%, respectively. Isolated endothelial cells and newly-formed micro-vessels and endothelial cells with high-immune-positivity to the antibodies anti-ICAM-1 and anti-VCAM-1 were observed. Conclusions: The results of our immunohistochemical research show that a significant neoangiogenesis occurs in oral lichen planus.

Based on our histological and genetic data, we underline that a surgical approach in patients with BAV, ascending aortic aneurysm and normal root, should consider not only the diameter of the aneurysmatic aortic portion but also the histological features of the whole ascending aorta and the genetic risk profile.