Effects of donor age and proliferative aging on the phenotype stability of rat aortic smooth muscle cells

Age-related effects of the vascular wall have been associated with several hemodynamic dysfunctions, including medial vascular calcification. Vascular aging has been traditionally addressed using proliferative senescence of vascu- lar smooth muscle cells (VSMC) in vitro, which induces osteoblastic transition and favors calcification in vitro. In this work, we have analyzed the relation- ship between organismal aging and proliferative senescence by comparing the proliferative aging of VSMC obtained from young, mature, and old rats (2-, 12-, and 24-month cell lines [CL], respectively). VSMC proliferated to more than 100 cumulative population doublings (CPD) without evidence of prolif- erative senescence, most likely as a consequence of telomerase induction. The apoptosis rate increased with CPD in all three CL, but the oxidation status of the cells was not modified. The magnitude of all gene expression changes caused by CPD was higher than the magnitude of the changes caused by donor age: the expressions of VSMC markers a-actin and SM22a decreased, while the expressions of transcription factors Msx2 and Runx2 and of bone morphogenetic protein-2 increased. Treatment of the cells with 2 mmol/L Pi revealed that the intensity of the effect of CPD on calcium deposition was greater than the effect of donor age. In conclusion, the proliferative lifespan of VSMC magnifies the effect of donor age on the osteoblastic transition of VSMC, therefore suggesting that in vivo vascular aging changes can be less dramatic than what is shown by in vitro aging

Análisis de la importancia del Plan Nacional de Investigación de Residuos en producción primaria en España

El Plan Nacional de Investigación de Residuos (PNIR) es el instrumento de control de presenciade determinadas sustancias y sus metabolitos, así como de residuos de ciertos fármacos enanimales vivos y sus productos. Se encuentra en vigor en España desde 1989. PNIR enproducción primaria implica el muestreo de explotaciones ganaderas, y en fases posteriores serealiza en establecimientos alimentarios. Los controles pueden ser muestreos dirigidos osospechosos y, según los criterios de riesgo, se establece el nivel de inspección. Tanto la tomade muestras como su posterior análisis se someten a los protocolos publicados por el Ministeriode Agricultura, Pesca y Alimentación. Anualmente el Ministerio publica un informe de resultadosdel PNIR en producción primaria, que recoge, entre otros datos, el número de controlesrealizados, la distribución de muestras según especie y productos analizados, grupo desustancias buscadas en las muestras y resultados positivos, por especie y grupo de sustancia.También recoge las actuaciones realizadas ante resultados no conformes y su evolución en losúltimos años. El objetivo es, tras definir y conocer el PNIR, analizar los datos publicados en losinformes anuales del Ministerio para demostrar la utilidad del plan, estudiando la evolución enlos últimos años de la presencia de este tipo de sustancias, si se ha incrementado el número decontroles y si existe relación entre los resultados y el tipo de explotación. <br /

Study of the correlation between columnar aerosol burden, suspended matter at ground and chemical components in a background European environment

Although routinely monitored by ground based air quality networks, the particulate matter distribution could be eventually better described with remote sensing techniques. However, valid relationships between ground level and columnar ground based quantities should be known beforehand. In this study we have performed a comparison between particulate matter measurements at ground level at different cut sizes (10, 2.5 and 1.0 mm), and the aerosol optical depth obtained by means of a ground based sunphotometer during a multiinstrumental field campaign held in El Arenosillo (Huelva, Spain) from 28 June to 4 July 2006. All the PM fractions were very well correlated with AOD with correlation coefficients that ranged from 0.71 to 0.81 for PM10, PM2.5 and PM1. Furthermore, the influence of the mixing layer height in the correlations was explored. The improvement in the correlation when the vertical distribution is taken into account was significant for days with a homogeneous mixing layer. Moreover, the chemical analysis of the individual size fractions allowed us to study the origin of the particulate matter. Secondary components were the most abundant and also well correlated in the three size fractions; but for PM10 fraction, chemical species related to marine origin were best correlated. Finally, we obtained a relationship between MODIS L3 AOD from collection 5.1 and the three PM cut sizes. In spite of being a relatively clean environment, all the techniques were able to capture similar day to day variations during this field campaign.Peer ReviewedPostprint (published version

Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet

The physicochemical deposition of calcium-phosphate in the arterial wall is prevented by calcification inhibitors. Studies in cohorts of patients with rare genetic diseases have shed light on the consequences of loss-of-function mutations for different calcification inhibitors, and genetic targeting of these pathways in mice have generated a clearer picture on the mechanisms involved. For example, generalized arterial calcification of infancy (GACI) is caused by mutations in the enzyme ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (eNPP1), preventing the hydrolysis of ATP into pyrophosphate (PPi). The importance of PPi for inhibiting arterial calcification has been reinforced by the protective effects of PPi in various mouse models displaying ectopic calcifications. Besides PPi, Matrix Gla Protein (MGP) has been shown to be another potent calcification inhibitor as Keutel patients carrying a mutation in the encoding gene or Mgp-deficient mice develop spontaneous calcification of the arterial media. Whereas PPi and MGP represent locally produced calcification inhibitors, also systemic factors contribute to protection against arterial calcification. One such example is Fetuin-A, which is mainly produced in the liver and which forms calciprotein particles (CPPs), inhibiting growth of calcium-phosphate crystals in the blood and thereby preventing their soft tissue deposition. Other calcification inhibitors with potential importance for arterial calcification include osteoprotegerin, osteopontin, and klotho. The aim of the present review is to outline the latest insights into how different calcification inhibitors prevent arterial calcification both under physiological conditions and in the case of disturbed calcium-phosphate balance, and to provide a consensus statement on their potential therapeutic role for arterial calcification

HEMATOMA SUBDURAL CRÓNICO EN PACIENTE CON QUISTE ARACNOIDEO GIGANTE

Varón  de  38  años  atendido  en  Urgencias  por  cefalea.  Refiere   traumatismo craneoencefálico 6 meses antes. Asintomático en todo ese tiempo, acude por presentar cefalea holocraneal e inestabilidad de horas de evolución sin nuevo evento traumático. A su llegada, Glasgow 4-5-6, sin signos de focalidad neurológica. Se realiza tomografía computarizada (TC) craneal (Figura 1) objetivando amplio hematoma subdural crónico frontoparietal izquierdo con desplazamiento de línea media e imagen compatible con quiste aracnoideo gigante de fosa temporal y cisura silviana izquierda. El paciente fue valorado por el Servicio de Neurocirugía, donde ingresó para completar estudio. Dada la estabilidad que mostraba, sin focalidad neurológica y adecuado control clínico con analgesia, se realizó, de forma programada, resonancia magnética cerebral (RM) (Figura 2) y tratamiento quirúrgico mediante drenaje parcial del quiste y la colección  subdural, con óptimos resultados.

Mechanisms of phosphate transport

Over the past 25 years, successive cloning of SLC34A1, SLC34A2 and SLC34A3, which encode the sodium-dependent inorganic phosphate (P$_{i}$) cotransport proteins 2a-2c, has facilitated the identification of molecular mechanisms that underlie the regulation of renal and intestinal P$_{i}$ transport. P$_{i}$ and various hormones, including parathyroid hormone and phosphatonins, such as fibroblast growth factor 23, regulate the activity of these P$_{i}$ transporters through transcriptional, translational and post-translational mechanisms involving interactions with PDZ domain-containing proteins, lipid microdomains and acute trafficking of the transporters via endocytosis and exocytosis. In humans and rodents, mutations in any of the three transporters lead to dysregulation of epithelial P$_{i}$ transport with effects on serum P$_{i}$ levels and can cause cardiovascular and musculoskeletal damage, illustrating the importance of these transporters in the maintenance of local and systemic P$_{i}$ homeostasis. Functional and structural studies have provided insights into the mechanism by which these proteins transport P$_{i}$, whereas in vivo and ex vivo cell culture studies have identified several small molecules that can modify their transport function. These small molecules represent potential new drugs to help maintain P$_{i}$ homeostasis in patients with chronic kidney disease - a condition that is associated with hyperphosphataemia and severe cardiovascular and skeletal consequences

Disección espontanea del tronco celiaco

Mujer de 63 años con antecedentes de hipertensión arterial que acude a Urgencias por dolor abdominal epigástrico irradiado en cinturón. El cuadro clínico comenzó, de manera súbita, 2 días antes, siendo valorada en Urgencias y dada de alta con analgesia tras realización de analítica de sangre y radiografía simple de abdomen, que resultaron normales

METAHEMOGLOBINEMIA ADQUIRIDA, A PROPÓSITO DE UN CASO

La metahemoglobinemia es un aumento de la metahemoglobina en el interior del eritrocito imposibilitándose el  transporte eficaz de oxigeno a los tejidos. Puede ser secundaria a la aplicación de anestésicos locales como Emla® crema (lidocaína 25 mg/g, Prilocaína 25 mg/g) cuando alcanzan altas concentraciones en circulación sistémica, provocándose una hipoxemia que no responde a la oxigenoterapia de alto flujo.El tratamiento de elecciónpara los casos graves es el azul de metileno intravenoso.Debido al incremento progresivo en nuestro medio de la depilación con láser, con aplicación previa de anestésicos locales, la incidencia de esta patología, a pesar de tener una baja incidencia, ha sufrido un importante incremento. Debemos sospechar esta entidad en pacientes con clínica sugestiva, ya que se trata de una enfermedad potencialmente mortal y para la cual se dispone de tratamiento específico

Expression of rat renal sulfate transport systems in Xenopus laevis oocytes: functional characterization and molecular identification

Renal proximal tubular sulfate reabsorption is mediated by brush border membrane Na+/sulfate-cotransport and basolateral Na(+)-independent sulfate transport. Injection of rat kidney cortex mRNA into Xenopus laevis oocytes induced Na(+)-dependent as well as Na(+)-independent sulfate transport. The inhibition pattern of Na(+)-dependent uptake coincided with that known for the brush border membrane; the inhibition pattern of Na(+)-independent uptake suggested that this activity could be related to the basolateral cell surface. By Northern blot hybridization of size-fractionated mRNA, we provide evidence that the Na(+)-dependent uptake is induced by an mRNA species related to a recently cloned cDNA encoding rat renal cortex Na+/SO4 cotransport (NaSi-1; Markovich, D., Forgo, J., Stange, G., Biber, J., and Murer, H. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 8073-8077); the Na(+)-independent sulfate transport activity seems to be related to an mRNA species encoding a rat liver Na(+)-independent sulfate transporter (Bissig, M., Hagenbuch, B., Stieger, B., Koller, T., and Meier, P. J. (1994) J. Biol. Chem. 269, 3017-3021). Hybrid depletion experiments using antisense oligonucleotides provided further evidence for the association of the expressed transport activities to NaSi-1 and sat-1, respectively

DISEMINACIÓN MESTATÁSICA DE UNA ULCERA DE MARJOLIN

La úlcera de Marjolin es la degeneración maligna de una lesión crónica traumática. En la mayoría de las ocasiones ocurre sobre cicatrices de quemaduras. Frente a una úlcera crónica de apariencia atípica que no reacciona favorablemente a los tratamientos habituales, se debe sospechar una degeneración maligna y es esencial la realización de una biopsia para llegar al diagnóstico correcto. El tratamiento de la úlcera de Marjolin consiste en la exéresis quirúrgica con amplios márgenes de seguridad, siendo, a veces, necesaria la amputación de la extremidad. Las neoplasias que se asocian con más frecuencia son  los carcinomas espinocelulares. Alrededor del 5% de estos casos tendrán  metástasis locales y a distancia, lo que se relaciona con determinados  factores denominados de alto riesgo. Se expone el caso de un paciente de 65 años con carcinoma epidermoide cutáneo originado de una úlcera de Marjolin, tratado con cirugía y radioterapia, con diseminación metastásica posterior