Elguezabal N.,Neiker Instituto Vasco Of Investigacian Y Desarrollo Agrario |
Chamorro S.,Neiker Instituto Vasco Of Investigacian Y Desarrollo Agrario |
Molina E.,Neiker Instituto Vasco Of Investigacian Y Desarrollo Agrario |
Garrido J.M.,Neiker Instituto Vasco Of Investigacian Y Desarrollo Agrario |
And 3 more authors.
Gut Pathogens | Year: 2012
Background: Inflammatory Bowel Disease (IBD), which includes both Crohns disease (CD) and ulcerative colitis (UC), is caused by a complex interplay involving genetic predisposition, environmental factors and an infectious agent. Mycobacterium avium subsp. paratuberculosis (MAP) is a promising pathogen candidate since it produces a chronic intestinal inflammatory disease in ruminants that resembles CD in humans. MAP is a ubiquitous microorganism, although its presence in the food chain, especially in milk from infected animals, is what made us think that there could be an association between lactase persistence (LP) and IBD. The LCT mutation has brought adaptation to dairy farming which in turn would have increased exposure of the population to infection by MAP. NOD2 gene mutations are highly associated to CD. Methods: In our study, CD and UC patients and controls from the North of Spain were genotyped for the lactase gene (LCT) and for three NOD-2 variants, R702W, G908R and Cins1007fs. MAP PCR was carried out in order to assess MAP infection status and these results were correlated with LCT and NOD2 genotypes. Results: As for LP, no association was found with IBD, although UC patients were less likely to present the T/T -13910 variant compared to controls, showing a higher C-allele frequency and a tendency to lactase non-persistence (LNP). NOD2 mutations were associated to CD being the per-allele risk higher for the Cins1007fs variant. MAP infection was more extended among the healthy controls (45.2%) compared to CD patients (21.38%) and UC patients (19.04%) and this was attributed to therapy. The Asturian CD cohort presented higher levels of MAP prevalence (38.6%) compared to the Basque CD cohort (15.5%), differences also attributed to therapy. No interaction was found between MAP infection and LCT or NOD2 status. Conclusions: We conclude that LP is not significantly associated with IBD, but that MAP infection and NOD2 do show not mutually interacting associations with IBD. © 2012 Elguezabal et al.; licensee BioMed Central Ltd.
Monfort A.,Fundacion Inbiomed |
Soriano-Navarro M.,CIBER ISCIII |
Garcia-Verdugo J.M.,CIBER ISCIII |
Izeta A.,Fundacion Inbiomed |
Izeta A.,Instituto Biodonostia
Journal of Tissue Engineering and Regenerative Medicine | Year: 2013
Full thickness wounds require a dermal component to achieve functional permanent skin restoration. Currently available tissue-engineered skin substitutes lack a subcutaneous fat layer that would functionally contribute some of the mechanical and thermoregulatory properties of normal skin. To generate a trilayer engineered skin equivalent, we included bone marrow mesenchymal (BM-MSC) or adipose tissue-derived (ASC) stromal cells in a human plasma hydrogel exposed to adipogenic clues for three weeks. Approximately half of the cells differentiated under these conditions into mature adipocytes that survived for two years in culture with minimal medium change. In vitro generation of bona fide fully differentiated adipocytes was assessed by leptin secretion and ultrastructurally demonstrated through semithin to ultrathin sectioning and lipid staining with osmium tetroxide. Furthermore, presence of BM-MSCs or ASCs within the subcutaneous layer contributed to the epidermal differentiation program, with more proliferating basal cells depositing basal membrane proteins and differentiating into mature keratinocytes that were able to generate a pluristratified epithelium. In conclusion, we engineered a fully differentiated human skin trilayer that could present multiple applications such as use for in vitro drug absorption tests and regenerative therapies. © 2012 John Wiley & Sons, Ltd.
Jimenez F.,Clinica Dr. Jimenez Acosta |
Izeta A.,Instituto Biodonostia |
Poblet E.,University of Castilla - La Mancha
Dermatologic Surgery | Year: 2011
Background The bulge stem cell region is a structure important for the regeneration of the pilosebaceous unit. Measurements of the different compartments of a hair follicle may have implications in hair transplantation and hair regeneration studies. Objective To measure the length of the different portions of the occipital scalp hair and to estimate at what depth they are located. METHODS AND MATERIAL Hair follicles from the occipital scalp were obtained from 29 individuals. Measurements were performed on digital pictures using a software imaging system. Antibody anticytokeratin (CK), 15 was used as a bulge stem cell marker. RESULTS The mean length of a scalp hair follicle is 4.16 mm. The infundibulum measures 0.76 mm, the isthmus 0.89 mm, and the inferior portion 2.5 mm. The insertion of the arrector pili muscle is located 1.65 mm deep. CK15 immunoreactivity starts at a depth of 1 mm and extends down to 1.8 mm. CONCLUSION The ideal depth for the trichophytic procedure is to cut the wound edge at a depth of less than 1 mm to avoid the bulge zone. The data provided can serve as an objective anatomical reference in hair regeneration studies using horizontally transected follicles. The authors have indicated no significant interest with commercial supporters. © 2010 by the American Society for Dermatologic Surgery, Inc.
Bravo-San Pedro J.M.,University of Extremadura |
Niso-Santano M.,University of Extremadura |
Gomez-Sanchez R.,University of Extremadura |
Pizarro-Estrella E.,University of Extremadura |
And 8 more authors.
Cellular and Molecular Life Sciences | Year: 2013
Mutations in leucine-rich repeat kinase 2 (LRRK2) are a major cause of familial Parkinsonism, and the G2019S mutation of LRRK2 is one of the most prevalent mutations. The deregulation of autophagic processes in nerve cells is thought to be a possible cause of Parkinson's disease (PD). In this study, we observed that G2019S mutant fibroblasts exhibited higher autophagic activity levels than control fibroblasts. Elevated levels of autophagic activity can trigger cell death, and in our study, G2019S mutant cells exhibited increased apoptosis hallmarks compared to control cells. LRRK2 is able to induce the phosphorylation of MAPK/ERK kinases (MEK). The use of 1,4-diamino-2,3-dicyano-1, 4-bis[2-aminophenylthio]butadiene (U0126), a highly selective inhibitor of MEK1/2, reduced the enhanced autophagy and sensibility observed in G2019S LRRK2 mutation cells. These data suggest that the G2019S mutation induces autophagy via MEK/ERK pathway and that the inhibition of this exacerbated autophagy reduces the sensitivity observed in G2019S mutant cells. © 2012 Springer Basel AG.
Anasagasti A.,Instituto Biodonostia |
Irigoyen C.,Hospital Universitario Donostia |
Barandika O.,Instituto Biodonostia |
Lopez de Munain A.,Instituto Biodonostia |
And 4 more authors.
Vision Research | Year: 2013
With a worldwide prevalence of about 1 in 3500-5000 individuals, Retinitis Pigmentosa (RP) is the most common form of hereditary retinal degeneration. It is an extremely heterogeneous group of genetically determined retinal diseases leading to progressive loss of vision due to impairment of rod and cone photoreceptors. RP can be inherited as an autosomal-recessive, autosomal-dominant, or X-linked trait. Non-Mendelian inheritance patterns such as digenic, maternal (mitochondrial) or compound heterozygosity have also been reported. To date, more than 65 genes have been implicated in syndromic and non-syndromic forms of RP, which account for only about 60% of all RP cases. Due to this high heterogeneity and diversity of inheritance patterns, the molecular diagnosis of syndromic and non-syndromic RP is very challenging, and the heritability of 40% of total RP cases worldwide remains unknown. However new sequencing methodologies, boosted by the human genome project, have contributed to exponential plummeting in sequencing costs, thereby making it feasible to include molecular testing for RP patients in routine clinical practice within the coming years. Here, we summarize the most widely used state-of-the-art technologies currently applied for the molecular diagnosis of RP, and address their strengths and weaknesses for the molecular diagnosis of such a complex genetic disease. © 2012 Elsevier Ltd.