IMPLICAZIONI CLINICHE DEI POLIMORFISMI GENETICI NELLE ULCERE VENOSE DEGLI ARTI INFERIORI:UN MODELLO DI DANNO E RIPARAZIONE TISSUTALE

Introduction. Tissue injury and reparative processes are multi-factorial and complex mechanisms, where genetics has a role and gene-gene and gene-environment interactions play pivotal functions. Several gene variants (SNPs, single nucleotide polymorphism) have a definite role in etiopathogenesis, diagnosis and prognosis of venous leg ulcers (VLU), thus, the SNPs’s identification in patients is basic for the diagnosis and prognosis of this disease. We had already demonstrated that some gene polymorphisms aid to ulcer onset and other polymorphisms influence the ulcer extension and healing after superficial venous surgery. With the present study, we would like to verify if some gene polymorphisms interfer in ulcer healing with the same medical treatment. Materials and Methods. From February 2007 to October 2008 we enrolled in our study 45 consecutive patients with VLU, 18 male e 27 female, with a median age of 72.9 years (range 20-95 years). The median initial ulcer size was 8.8 cm2 (range 0.3-62.3 cm2with a wide spectrum of disease duration, from 30 days to 20 years. We draw blood to any patient to determine the gene polymorphisms of our interest (HFE, FXIII, MMP12) and we did weekly dressing changes with the same therapeutic strategy (advanced dressing, plus multilayer elastic bandaging) made up by the same physician, to riduce the “human variability” and so catch the real role of gene and molecular variants. The study lasted 12 weeks. The study endpoints were: 1) to establish the healing rate after 12 weeks of treatment; 2) to determine tha risponders in function of Margolis Index (reduction of ulcer size of at least 50% after 4 weeks of treatment); 3) to verify if exist a correlation between gene variants, healing, responders. Results. For FXIII gene polymorphisms (VV,VL, LL) we did not find statistically significant differences neither for healing rate at week 12th, nor for Margolis Index (P=ns). Same conclusions for HFE gene polymorphisms (HD e HH). For matrix metalloprotease 12 (MMP12) gene polymorphisms (AA, AG, GG), we found that the homozygous AA genotype increases 2.27 times the healing probability (OR= 2.27, CI 0.5-10.25), instead the –G carriers are 3.28 times more responders (OR=3.28, CI 0.58-18.36). Discussione. What we noted in this study, seems to be contradictory with what we demonstrated before for the MMP12 gene variants, that means the association with –G allele and smaller ulcer size. Really, also for patient population –G carrier has a smaller ulcer and moreover a greater probability to reduce ulcer size of at least 50% after 4 weeks of treatment. So, the only discrepancy, seems to be the greater probability to heal for the homozygous aa carriers, but, we can explain that, examinig the tissue injury and reparative process. This is extremely complex, dynamic, multi-fasic and multi-factorial, thus it is possible that enzymes traditionally considered of tissue injury like MMPs, could play a role in different phases of tissue remodelling in reparative process, maybe with different functions in reparative phases according to the specific MMMP family, or, in the same family, according to the different gene polymorphisms

Exploitation and Dissemination Report

This Exploitation and Dissemination report is the final document that summarizes Dissemination, Communication and Exploitation carried out in the Project RESOLVE

Treatment and prognosis of endocrine tumors of gastrointestinal tract and pancreas: A retrospective study about 16 cases.

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Inflammation in venous disease.

Chronic venous disease (CVD), mainly due to venous reflux or, sometimes, to venous outflow obstruction, produces a microcirculatory overload leading to the impairment of venous drainage. Venous drainage depends primarily on a major hemodynamic parameter called trans-mural pressure (TMP). TMP is increased in patients affected by CVD, leading to impaired tissue drainage, and, consequently, facilitating the beginning of the inflammatory cascade. Increased TMP determines red blood cell extravasation and either dermal hemosiderin deposits or iron laden-phagocytes. Iron deposits are readily visible in the legs of all patients affected by severe CVD. Local iron overload could generate free radicals or activate a proteolytic hyperactivity of metalloproteinases (MMPs) and/or downregulate tissue inhibitors of MMPs. These negative effects are particularly evident in carriers of the common HFE gene's mutations C282Y and H63D, because intracellular iron deposits of mutated macrophages have less stability than those of the wild type, inducing a significant oxidative stress. It has been demonstrated that such genetic variants increase the risk of ulcers and advance the age of ulcer onset, respectively. The iron-dependent vision of inflammation in CVD paves the way to new therapeutic strategies including the deliberate induction of iron deficiency as a treatment modality for non-healing and/or recurrent venous leg ulcers. The inflammatory cascade in CVD shares several aspects with that activated in the course of multiple sclerosis, an inflammatory and neurodegenerative disease of unknown origin in which the impairment of cerebral venous outflow mechanisms has been recently demonstrated

Radiolabelled somatostatin analogs for diagnosis and radio-guided surgery of neuroendocrine breast cancer undetectable with conventional imaging procedures

Some neoplasms are classified as primary neuroendocrine tumours (NETs) because of their positivity for neuroendocrine markers [chromogranins A and B (CgA, CgB) and neuron-specific enolase (NSE)]. Neuroendocrine differentiation has been reported, for example, in both "in situ" and infiltrating breast cancer. Diagnosis of NET is bio-humoral (CgA, NSE, synaptophysin) and instrumental. Even if the final diagnosis is made by open biopsy, radionuclide imaging using radiolabelled somatostatin analogs, such as In-111 pentetreotide, may detect neuroendocrine primary tumours and metastases before they become detectable using traditional and advanced imaging modalities [mammography (MX), ultrasound (US) and magnetic resonance imaging (MRI)]. When neuroendocrine breast lesions are not detectable, radio-guided surgery (RGS) is able to localise cancer. We report a case of a woman with a palpable lymph node in the left axilla. She underwent a US-guided lymph node biopsy, which was positive for massive metastases, probably of neuroendocrine breast origin. Mammary plus axillary US showed only lymphadenopathy in the left axilla. MX and breast MRI were negative. Neoplastic markers (CEA, CA 15.3, CA 125 and CA 19.9) were negative too. On the other hand, neuroendocrine markers (NSE and CgA) were positive. A whole body scintigraphic scan plus thorax and abdomen single photon emission computed tomography (SPECT) with In-111 pentetreotide (222 MBq; 6 mCi) showed an uptake in the left mammary gland. No other pathological localisations were observed. The day after the intravenous injection of In-111 pentetreotide, the patient underwent RGS breast tumour resection and left axillary lymphadenectomy. In conclusion, we would like to emphasise: (1) the role of radionuclide imaging for the detection of breast NETs in relation to conventional diagnostic procedures; (2) the role of RGS in localising and removing a non-palpable breast NET that was undetectable with the use of conventional imaging techniques

Use of preoperative lymphoscintigraphy and intraoperative gamma-probe detection for identification of the sentinel lymph node in patients with papillary thyroid carcinoma

AIMS: Lymph node metastases for papillary thyroid carcinoma are associated with an increased incidence of locoregional recurrence. The use of preoperative lymphoscintigraphy and intraoperative gamma probe detection to localize the sentinel lymph node in papillary thyroid carcinoma was investigated. METHODS: From February 2004 to December 2005 the sentinel lymph node technique was studied in 64 consecutive patients with cytological evidence of papillary thyroid carcinoma. The day before surgery, patients were submitted to US-guided peri-tumoural injection of the radiotracer and a lymphoscintigraphy was performed. In the operating room a total thyroidectomy was done, and thanks to a hand-held gamma probe the sentinel lymph node and all lymph nodes, belonging to the sentinel node compartment, were removed. RESULTS: The gamma probe identified the sentinel lymph node in 62 patients (96.8%). We found 48 (77.5%) sentinel lymph node without metastases; 12 (19.3%) with metastases and 2 (3.2%) with micrometastases. In 7 cases (11.3%), with a negative sentinel lymph node, metastases in other nodes of the same region were recorded. In 22 cases (34.3%) the ultrasound give an erroneous indication (P=0.004). Five patients (8.0%), 4 with multifocal cancer, had a positive postoperative lymphoscintigraphy. CONCLUSION: This study shows that the sentinel lymph node technique for papillary thyroid carcinoma is feasible, repeatable, and more accurate than preoperative ultrasound. In cases of multifocal thyroid lesions more patients should be enrolled to establish the utility of the radio-guided technique

Euphorion et les mythes

Ce volume constitue les actes d’un colloque organisé à l’ENS de Lyon (19-20 janvier 2012) pour mettre à l’honneur ce poète oublié, dans des échanges pluridisciplinaires autour de cette œuvre très peu lue en dehors d’un cercle restreint de spécialistes. En réunissant les contributions de philologues, historiens de l’art et historiens des idées, ce volume s’efforce d’enrichir le commentaire des fragments et tente de comprendre les usages que ce poète a faits de la matière mythologique dans une perspective politique ou pour rendre compte du monde dans lequel il évoluait. La première partie de l’ouvrage propose deux parcours géographiques pour donner une idée du traitement du mythe par Euphorion, allant d’abord au sein de la Grèce traditionnelle d’Eubée en Béotie et de l’Attique en Corinthie, puis parcourant l’Asie mineure et le Proche-Orient où Euphorion a fait lui-même une partie de sa carrière. La seconde partie plus littéraire essaie de mettre en lumière certains aspects propres de la poétique d’Euphorion au sein d’un ensemble de poètes qui recherchent l’obscurité, l’étrange ou la rareté et dans l’art spécifique de la malédiction

A polymorphism in the 5' UTR of the DEFB1 gene is associated with the lung phenotype in F508del homozygous Italian cystic fibrosis patients

BACKGROUND: The identification of cystic fibrosis (CF) patients who are at greater risk of lung damage could be clinically valuable. Thus, we attempted to replicate previous findings and verify the possible association between three single nucleotide polymorphisms (SNPs c.-52G>A, c.-44C>G and c.-20G>A) in the 5' untranslated region (5' UTR) of the β defensin 1 (DEFB1) gene and the CF pulmonary phenotype. METHODS: Genomic DNA from 92 Italian CF patients enrolled in different regional CF centres was extracted from peripheral blood and genotyped for DEFB1 SNPs using TaqMan(®) allele specific probes. In order to avoid genetic confounding causes that can account for CF phenotype variability, all patients were homozygous for the F508del CFTR mutation, and were then classified on the basis of clinical and functional data as mild lung phenotype (Mp, n=50) or severe lung phenotype patients (Sp, n=42). RESULTS: For the c.-20G>A SNP, the frequency of the A allele, as well as the AA genotype, were significantly more frequent in Mp than in Sp patients, and thus this was associated with a protective effect against severe pulmonary disease (OR=0.48 and 0.28, respectively). The effect of the c.-20G>A A allele is consistent with a recessive model, and the protective effect against Sp is exerted only when it is present in homozygosis. For the other two SNPs, no differences were observed as allelic and genotypic frequency in the two subgroups of CF patients. CONCLUSIONS: Our results, although necessary to be confirmed in larger and multiethnic populations, reinforce DEFB1 as a candidate modifier gene of the CF pulmonary phenotype

A polymorphism in the 5' UTR of the DEFB1 gene is associated with the lung phenotype in F508del homozygous Italian cystic fibrosis patients

The identification of cystic fibrosis (CF) patients who are at greater risk of lung damage could be clinically valuable. Thus, we attempted to replicate previous findings and verify the possible association between three single nucleotide polymorphisms (SNPs c.-52G>A, c.-44C>G and c.-20G>A) in the 5' untranslated region (5' UTR) of the \u3b2 defensin 1 (DEFB1) gene and the CF pulmonary phenotype

Maternal Stress and Coping Strategies in Developmental Dyslexia: An Italian Multicenter Study

BackgroundStudies about the impact of developmental dyslexia (DD) on parenting are scarce. Our investigation aimed to assess maternal stress levels and mothers’ copying styles in a population of dyslexic children.MethodsA total of 874 children (500 boys, 374 girls; mean age 8.32 ± 2.33 years) affected by DD was included in the study. A total of 1,421 typically developing children (789 boys, 632 girls; mean age 8.25 ± 3.19 years) were recruited from local schools of participating Italian Regions (Abruzzo, Calabria, Campania, Puglia, Umbria, Sicily) and used as control-children group. All mothers (of both DD and typically developing children) filled out an evaluation for parental stress (Parenting Stress Index—Short Form) and coping strategies [Coping Inventory for Stressful Situations (CISS)].ResultsNo statistical differences for mean age (p = 0.456) and gender (p = 0.577) were found between DD and control children. Mothers of children affected by DD showed an higher rate of all parental stress indexes (Parental Distress domain p < 0.001, Difficult Child p < 0.001, Parent–Child Dysfunctional Interaction p < 0.001, and Total Stress subscale score p < 0.001) than controls mothers. According to the CISS evaluation, mothers of DD children reported a significantly higher rate of emotion-oriented (p < 0.001) and avoidance-oriented (p < 0.001) coping styles than mothers of typical developing children. On the other hand, a lower representation of task-oriented coping style was found in mothers of DD children (p < 0.001) in comparison to mothers of control-children.ConclusionOur study shows the clinical relevance of the burden carried by the mothers of children affected by DD and suggests the importance to assess parents, particularly mothers, to improve family compliance and clinical management of this disorder