Alterations of specific biomarkers of metabolic pathways in vascular tree from patients with Type 2 diabetes.

The aims of this study were to check whether different biomarkers of inflammatory, apoptotic, immunological or lipid pathways had altered their expression in the occluded popliteal artery (OPA) compared with the internal mammary artery (IMA) and femoral vein (FV) and to examine whether glycemic control influenced the expression of these genes. The study included 20 patients with advanced atherosclerosis and type 2 diabetes mellitus, 15 of whom had peripheral arterial occlusive disease (PAOD), from whom samples of OPA and FV were collected. PAOD patients were classified based on their HbA1c as well (HbA1c ≤ 6.5) or poorly (HbA1c > 6.5) controlled patients. Controls for arteries without atherosclerosis comprised 5 IMA from patients with ischemic cardiomyopathy (ICM). mRNA, protein expression and histological studies were analyzed in IMA, OPA and FV. After analyzing 46 genes, OPA showed higher expression levels than IMA or FV for genes involved in thrombosis (F3), apoptosis (MMP2, MMP9, TIMP1 and TIM3), lipid metabolism (LRP1 and NDUFA), immune response (TLR2) and monocytes adhesion (CD83). Remarkably, MMP-9 expression was lower in OPA from well-controlled patients. In FV from diabetic patients with HbA1c ≤6.5, gene expression levels of BCL2, CDKN1A, COX2, NDUFA and SREBP2 were higher than in FV from those with HbA1c >6.5. The atherosclerotic process in OPA from diabetic patients was associated with high expression levels of inflammatory, lipid metabolism and apoptotic biomarkers. The degree of glycemic control was associated with gene expression markers of apoptosis, lipid metabolism and antioxidants in FV. However, the effect of glycemic control on pro-atherosclerotic gene expression was very low in arteries with established atherosclerosis.

Consumption and portion sizes of tree nuts, peanuts and seeds in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts from 10 European countries

Tree nuts, peanuts and seeds are nutrient dense foods whose intake has been shown to be associated with reduced risk of some chronic diseases. They are regularly consumed in European diets either as whole, in spreads or from hidden sources (e.g. commercial products). However, little is known about their intake profiles or differences in consumption between European countries or geographic regions. The objective of this study was to analyse the population mean intake and average portion sizes in subjects reporting intake of nuts and seeds consumed as whole, derived from hidden sources or from spreads. Data was obtained from standardised 24-hour dietary recalls collected from 36 994 subjects in 10 different countries that are part of the European Prospective Investigation into Cancer and Nutrition (EPIC). Overall, for nuts and seeds consumed as whole, the percentage of subjects reporting intake on the day of the recall was: tree nuts = 4. 4%, peanuts = 2.3 % and seeds = 1.3 %. The data show a clear northern (Sweden: mean intake = 0.15 g/d, average portion size = 15.1 g/d) to southern (Spain: mean intake = 2.99 g/d, average portion size = 34.7 g/d) European gradient of whole tree nut intake. The three most popular tree nuts were walnuts, almonds and hazelnuts, respectively. In general, tree nuts were more widely consumed than peanuts or seeds. In subjects reporting intake, men consumed a significantly higher average portion size of tree nuts (28.5 v. 23.1 g/d, P<0.01) and peanuts (46.1 v. 35.1 g/d, P<0.01) per day than women. These data may be useful in devising research initiatives and health policy strategies based on the intake of this food group.

Genetic diversity of Toscana virus

Distribution of Toscana virus (TOSV) is evolving with climate change, and pathogenicity may be higher in nonexposed populations outside areas of current prevalence (Mediterranean Basin). To characterize genetic diversity of TOSV, we determined the coding sequences of isolates from Spain and France. TOSV is more diverse than other well-studied phleboviruses (e.g.,Rift Valley fever virus).

El implante de condrocitos autólogos en la red sanitaria pública de Andalucía. Resultados tras 6 años de circuito asistencial.

Objective: To asses the results of Autologous Chondrocyte Implantation (ACI) whith periosteal patch and To propagate the care circuits existing about in Andalusia. Material and Methods: From its of ficial licence in 2005, the tissue bank and the Virgen de la Victoria Hospital from Málaga, performed the ACI in the Andalusian public health system. 16 patients has been operated between 2006-2013, whith medium follow-up 47,6 months (6 months-6 years), from public hos- pitals throughout Andalucia, managed by hospital admission source and destination. Physiologically younger patients were selected (<50 años), with singles, > 2cm2 symptomatics chondral lesions, in stables and well aligned knees. ACI was used as res- cue procedure after microfracture ́s failure except osteochondritis dissecans. To assess the results the Concinnati score and the Short Form 36 (SF-36) score were used. A descriptive analysis was performed and non-parametric tests were used to establish correlations and compare results. Results: In 15 patients with more than one year of follow-up: 14 men(87.5%) and 2women (14.5%), medium age 28.2 years old (min 17 max 43), the lesion was located into de femoral condyle, mostly in the internal one (81,2%) with medium size 2,7cm2(2-4,2). We founded significant improvement (p<0,001), both daily activities ( 89,3% preop. limitatión - 9% postop), as in the sports (90,2% preop limitatión - 38% postop) and the exploration of the knee (67,7% hpatological findings preop- 13,3%postop). The SF-36 score improved in all categories, over all in mental health (p> 0,01). The patient satisfaction was high or very high in 12 of the 15 patients ( 80%), and low in 3 patients. Conclusions: ACI improve quality of life and knee function in femoral condyle chondral lesions. The case ́s selection and the collaboration with Tissue Bank, allows us to create care circuits for treatment of patients from other provinces in the Public Sanitary Health System in Andalucia. It is necessary to increase the experience with this type of therapy, consolidating multicenter workgroups that provide strength to the conclusions.

Regulation of cell death receptor S-nitrosylation and apoptotic signaling by Sorafenib in hepatoblastoma cells.

Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells.