Matrix Gla Protein involved in elastic fiber calcification in the dermis of pseudoxanthoma elasticum patients.

Mature MGP (Matrix gamma-carboxyglutamic acid protein) is known to inhibit soft connective tissues calcification. We investigated its possible involvement in pseudoxanthoma elasticum (PXE), a genetic disorder whose clinical manifestations are due to mineralization of elastic fibers. PXE patients have lower serum concentration of total MGP compared to controls (P<0.001). Antibodies specific for the noncarboxylated (Glu-MGP) and for the gamma-carboxylated (Gla-MGP) forms of MGP were assayed on ultrathin sections of dermis from controls and PXE patients. Normal elastic fibers in controls and patients were slightly positive for both forms of MGP, whereas Gla-MGP was more abundant within control's than within patient's elastic fibers (P<0.001). In patients' calcified elastic fibers, Glu-MGP intensively colocalized with mineral precipitates, whereas Gla-MGP precisely localized at the mineralization front. Data suggest that MGP is present within elastic fibers and is associated with calcification of dermal elastic fibers in PXE. To investigate whether local cells produce MGP, dermal fibroblasts were cultured in vitro and MGP was assayed at mRNA and protein levels. In spite of very similar MGP mRNA expression, cells from PXE patients produced 30% less of Gla-MGP compared to controls. Data were confirmed by immunocytochemistry on ultrathin sections. Normal fibroblasts in vitro were positive for both forms of MGP. PXE fibroblasts were positive for Glu-MGP and only barely positive for Gla-MGP (P<0.001). In conclusion, MGP is involved in elastic fiber calcification in PXE. The lower ratio of Gla-MGP over Glu-MGP in pathological fibroblasts compared to controls suggests these cells may play an important role in the ectopic calcification in PXE

El oficio de defender los derechos humanos

Son pocas las personas que se dedican a velar por el respeto a las garantías individuales y la defensa los derechos humanos. Este solo hecho ya las hace excepcionales. Por esta misma razón, merecen un mayor reconocimiento debido a las dificultades, el alto costo personal e incluso los peligros que implica este oficio en una cultura donde la actuación del gobierno y otros actores involucrados en este tema es controversial, como es el caso de México. En este libro se presentan los testimonios de 18 personas que han dedicado su vida a defender a escala local, regional, nacional e internacional, los derechos de los demás. Son mujeres y hombres que comparten los motivos que les llevaron a ejercer esta actividad como una opción y estilo de vida, así como su particular forma de llevar a cabo su lucha y el recuento de sus logros y vicisitudes. A partir de estos testimonios, se analizan las características fundamentales de la génesis y práctica del oficio de ombudsman, en aras de entender su peculiar habitus, con la esperanza de impulsar a más hombres y mujeres a adoptar sin temor esta profesión de un gran impacto social que, sí, puede ser de alto riesgo, aunque se olvida ante la gran satisfacción personal que brinda a quien la desempeña.ITESO, A.C

La humanización del “oficio de defender los Derechos Humanos” desde la práctica de las defensoras

El presente artículo analiza la problemática en torno al género y al debate sobre los principios masculinos y femeninos como fuentes de construcción de lo humano. Examina también las alianzas y oposiciones entre los diferentes feminismos y masculinidades. Finalmente expone, desde una perspectiva de género, la cuestión de la vulnerabilidad de los/as defensores de derechos humanos. La tesis principal versa sobre la posibilidad de humanizar la defensa de los derechos humanos al incorporar los principios masculinos y femeninos en la práctica del oficio

Campaña de sensibilización: Plan estratégico para una ciudad amigable con los adultos mayores DIF Guadalajara - ITESO

El siguiente reporte presenta el trabajo desarrollado en el semestre de primavera 2018, en el cual se desarrolló una campaña de sensibilización para dignificar la imagen de los adultos mayores. El objetivo de este proyecto es mostrar una imagen digna e íntegra de los adultos mayores para generar una visión distinta de cómo se vive la vejez. La campaña se enfocó en diseñar estrategias de sensibilización para el proyecto de ciudad amigable con los mayores por el Gobierno de Guadalajara, a través de la investigación etnográfica y análisis de la metodología horizontal. El reporte también muestra los resultados del diagnóstico de medios que sirvió para el diseño de la campaña de sensibilización, la estrategia de redes sociales y el desarrollo de canal de Youtube.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 placenta in pseudoxanthoma elasticum: clinical, structural and immunochemical study.

Pseudoxanthoma elasticum (PXE) is a rare genetic disorder clinically characterized by skin, cardiovascular and eve manifestations, mainly due to calcification and fragmentation of elastic fibres. although infrequent, complications during pregnancy in nomen affected by PXE have been reported. The aim of the present stud! was to compare structural features of placentae at term from 14 control and 15 PXE-affected nomen, in order to better understand if and hen: abnormal mineral and/or matrix accumulation might affect placental function in PSE. In all cases, pregnancy, fetus growth and delivery were normal. Both gross and light microscopy examination did not reveal dramatic differences between placentae of PSE patients and controls, with regard to weight, dimensions, infarcts, thrombi, inflammatory lesions or vessels. However, necrotic changes and mineralization appealed statistically more pronounced in PXE. By electron microscopy the most remarkable differences between PXE and control placentae were observed in the localization and morphology of mineral precipitates; a significant higher deposition of mineral precipitates was observed associated with the \ub4matrix\ub4-type fibrinoid and among collagen fibrils, especially on the maternal side. Immunocytochemistry revealed the presence of vitronectin and fibronectin associated with the PXE-specific mineralizations and the absence of mineralization on the small and scarce elastic fibres in either controls or in PXE

Oxidative stress in fibroblasts from patients with pseudoxanthoma elasticum: possible role in the pathogenesis of clinical manifestations

Pseudoxanthoma elasticum (PXE) is a genetic disease characterized by calcification and fragmentation of elastic fibres of the skin, cardiovascular system and eye, caused by mutations of the ABCC6 gene, which encodes the membrane transporter MRP6. The pathogenesis of the lesions is unknown. Based on studies of similar clinical and histopathological damage present in haemolytic disorders, our working hypothesis is that PXE lesions may result from chronic oxidative stress occurring in PXE cells as a consequence of MRP6 deficiency. Our results show that PXE fibroblasts suffer from mild chronic oxidative stress due to the imbalance between production and degradation of oxidant species. The findings also show that this imbalance results, at least in part, from the loss of mitochondrial membrane potential (Delta Psi(m)) with overproduction of H2O2. Whether mitochondrial dysfunction is the main factor responsible for the oxidative stress in PXE cells remains to be elucidated. However, mild chronic generalized oxidative stress could explain the great majority of structural and biochemical alterations already reported in PXE