Volteo digital

ITESO, A.C

Volteo digital

ITESO, A.C

Elastin haploinsufficiency induces alternative aging processes in the aorta

Elastin, the main component of elastic fibers, is synthesized only in early life and provides the blood vessels with their elastic properties. With aging, elastin is progressively degraded, leading to arterial enlargement, stiffening, and dysfunction. Also, elastin is a key regulator of vascular smooth muscle cell proliferation and migration during development since heterozygous mutations in its gene (Eln) are responsible for a severe obstructive vascular disease, supravalvular aortic stenosis, isolated or associated to Williams syndrome. Here, we have studied whether early elastin synthesis could also influence the aging processes, by comparing the structure and function of ascending aorta from 6- and 24-month-old Eln+/- and Eln+/+ mice. Eln+/- animals have high blood pressure and arteries with smaller diameters and more rigid walls containing additional although thinner elastic lamellas. Nevertheless, longevity of these animals is unaffected. In young adult Eln+/- mice, some features resemble vascular aging of wild-type animals: cardiac hypertrophy, loss of elasticity of the arterial wall through enhanced fragmentation of the elastic fibers, and extracellular matrix accumulation in the aortic wall, in particular in the intima. In Eln+/- animals, we also observed an age-dependent alteration of endothelial vasorelaxant function. On the contrary, Eln+/- mice were protected from several classical consequences of aging visible in aged Eln+/+ mice, such as arterial wall thickening and alteration of alpha(1)-adrenoceptor-mediated vasoconstriction. Our results suggest that early elastin expression and organization modify arterial aging through their impact on both vascular cell physiology and structure and mechanics of blood vessels

Tensiones y transiciones en las relaciones internacionales

Este libro reúne 12 textos en torno a la realidad internacional con­temporánea, que se presentan a modo de reflexiones, investigacio­nes empíricas y análisis conceptuales, elaborados por académicos y egresados de la Licenciatura de Relaciones Internacionales del ITESO, en el marco de la celebración del 20 aniversario de esta espe­cialidad, que nació en 1997 con el fin de formar profesionales capa­ces de analizar el panorama mundial y de establecer puentes entre las esferas local, nacional y global, para contribuir a la construcción de una sociedad más justa y equitativa. Dividida en cuatro apartados, esta obra busca mostrar una radio­grafía del complicado entramado que enfrentan las relaciones inter­nacionales en el dinámico y desafiante entorno mundial, lo que le convierte en un material de consulta de interés para todo estudiante y profesional en la materia, así como para todo aquel lector que busque conocer mejor los elementos, el funcionamiento, las interac­ciones y transiciones de las estructuras que rigen al mundo.ITESO, A.C

Evaluación del mercado alemán para la distribución de licores de La Casa de las Once Letras

ITESO, A.C

High levels of desmosines in urine and plasma pf patients with pseudoxanthoma elasticum.

BACKGROUND: Pseudoxanthoma elasticum (PXE), a rare heritable disorder caused by mutations of the ABCC6 gene, is characterized by fragmentation and mineralization of elastic fibres. We determined the extent of degradation of elastin by measuring and comparing the amount of desmosines in plasma and urine of PXE patients, healthy carriers and normal subjects. METHODS: Using capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) we measured the amount of desmosines in the urine of 46 individuals (14 PXE patients, 17 healthy carriers and 15 controls) and in the plasma of 56 subjects (18 PXE patients, 23 healthy carriers and 15 controls). Pseudoxanthoma elasticum patients and carriers were identified by clinical, structural and molecular biology analyses. RESULTS: The urinary excretion of desmosines was two-fold higher in PXE patients than in controls (P < 0.01); the values for healthy carriers were intermediate between those of PXE patients and controls. A very similar trend between patients and their relatives was observed for plasma desmosines. There was a significant correlation between the amount of the desmosines in plasma and urine. Moreover, a positive correlation was observed between urinary desmosine content and age of the patients as well as between urinary desmosine content and severity of clinical manifestations. CONCLUSIONS: Both the urinary and plasma desmosine concentrations indicate that elastin degradation is higher in PXE patients and, to a lesser extent, in healthy carriers than in normal subjects. Data seem to indicate that the amount of elastin breakdown products correlates with the age of patients as well as with the severity of the disease

The skin equivalent model: developments and perspectives.

Three-dimensional culture systems have been developed to mimic natural interactions among cells and between cells and the extracellular matrix. The “skin equivalent ” is a 3-D co-culture system of fibroblasts and keratinocytes used as a covering surface in extended wounds, and as a model for studying the influence of each cell type on the synthesis of the extracellular matrix. In the present study, a three-dimensional scaffold made of chitosan, glycosaminoglycans and collagen has been colonised by keratinocytes from newborn foreskin an by fibroblasts isolated from donors of different ages. In the skin equivalent, the neo-synthesized connective tissue is characterized by the presence of amorphous elastic fibers, strengthening the usefulness of this three-dimensional model as a powerful tool for investigating connective tissue metabolism in different physiological (i.e. aging) and pathological conditions. Interestingly, when fibroblasts isolated from aged donors were cultured in vitro, even though in the presence of abundant nutrients and growth factors, their old phenotype appeared not to be completely overcome, indicating that aging is the result of a continuous remodelling controlled by epigenetic as well as genetic factors. Finally, the aged phenotype of fibroblasts seems to exert a stronger influence on keratinocytes compared to that of keratinocytes on fibroblasts

Parameters of oxidative stress are present in the circulation of PXE patients

Pseudoxanthoma elasticum (PXE) is an inherited disorder characterized by calcification of elastic fibres leading to dermatological and vascular alterations associated to premature aged features and to life threatening clinical manifestations. The severity of the disease is independent from the type of mutation in the ABCC6 gene, and it has been suggested that local and/or systemic factors may contribute to the occurrence of clinical phenotype. The redox balance in the circulation of 27 PXE patients and of 50 healthy subjects of comparable age was evaluated by measuring the advanced oxidation protein products (AOPP), the lipid peroxidation derivatives (LOOH), the circulating total antioxidant status (TAS), the thiol content and the extracellular superoxide dismutase activity (EC-SOD). Patients were diagnosed by clinical, ultrastructural and molecular findings. Compared to control subjects, PXE patients exhibited significantly lower antioxidant potential, namely circulating TAS and free thiol groups, and higher levels of parameters of oxidative damage, as LOOH and of AOPP, and of circulating EC-SOD activity. Interestingly, the ratio between oxidant and antioxidant parameters was significantly altered in PXE patients and related to various score indices. This study demonstrates, for the first time, that several parameters of oxidative stress are modified in the blood of PXE patients and that the redox balance is significantly altered compared to control subjects of comparable age. Therefore, in PXE patients the circulating impaired redox balance may contribute to the occurrence of several clinical manifestations in PXE patients, and/or to the severity of disease, thus opening new perspectives for their management