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We have analyzed the role of the thyroid hormone receptors (TRs) in epidermal homeostasis. Reduced keratinocyte proliferation is found in interfollicular epidermis of mice lacking the thyroid hormone binding isoforms TRα1 and TRβ (KO mice). Similar results were obtained in hypothyroid animals, showing the important role of the liganded TRs in epidermal proliferation. In addition, KO and hypothyroid animals display decreased hyperplasia in response to 12-O-tetradecanolyphorbol-13-acetate. Both receptor isoforms play overlapping functional roles in the skin because mice lacking individually TRα1 or TRβ also present a proliferative defect but not as marked as that found in double KO mice. Defective proliferation in KO mice is associated with reduction of cyclin D1 expression and up-regulation of the cyclin-dependent kinase inhibitors p19 and p27. Paradoxically, ERK and AKT activity and expression of downstream targets, such as AP-1 components, are increased in KO mice. Increased p65/NF-κB and STAT3 phosphorylation and, as a consequence, augmented expression of chemokines and proinflammatory cytokines is also found in these animals. These results show that thyroid hormones and their receptors are important mediators of skin proliferation and demonstrate that TRs act as endogenous inhibitors of skin inflammation, most likely due to interference with AP-1, NF-κB, and STAT3 activation., This work was supported by Ministerio de Ciencia e Innovación Grants BFU2007-62402 and SAF2008-00121, Fondo de Investigaciones Sanitarias Grants RD06/0020/0036 and RD06/0020/0029, and European CRESCENDO Grant FP-018652.

This article is distributed under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License., Observations in thyroid patients and experimental animals show that the skin is an important target for the thyroid hormones. We previously showed that deletion in mice of the thyroid hormone nuclear receptors TRα1 and TRβ (the main thyroid hormone-binding isoforms) results in impaired epidermal proliferation, hair growth, and wound healing. Stem cells located at the bulges of the hair follicles are responsible for hair cycling and contribute to the regeneration of the new epidermis after wounding. Therefore a reduction in the number or function of the bulge stem cells could be responsible for this phenotype. Bulge cells show increased levels of epigenetic repressive marks, can retain bromodeoxyuridine labeling for a long time, and have colony-forming efficiency (CFE) in vitro. Here we demonstrate that mice lacking TRs do not have a decrease of the bulge stem cell population. Instead, they show an increase of label-retaining cells (LRCs) in the bulges and enhanced CFE in vitro. Reduced activation of stem cells leading to their accumulation in the bulges is indicated by a strongly reduced response to mobilization by 12-O-tetradecanolyphorbol-13-acetate. Altered function of the bulge stem cells is associated with aberrant activation of Smad signaling, leading to reduced nuclear accumulation of β-catenin, which is crucial for stem cell proliferation and mobilization. LRCs of TR-deficient mice also show increased levels of epigenetic repressive marks. We conclude that thyroid hormone signaling is an important determinant of the mobilization of stem cells out of their niche in the hair bulge. These findings correlate with skin defects observed in mice and alterations found in human thyroid disorders., This work was supported by grants from the Ministerio de Economía y Competitividad (BFU2011-28058 to A.A. and SAF2012-34378 to J.M.P.), the Instituto de Salud Carlos III (RD12 /0036/0030 to A.A. and RD12/0036/0009 to J.M.P.), and the Comunidad de Madrid (S2011/BMD-2328 TIRONET to A.A. and S2010/BMD-2470 to J.M.P.).

The adequate device size selection for left atrial appendage closure is crucial to ensuring adequate implantation and for avoiding the need for multiple attempts that increase the risk of complications. Our aim was to evaluate the information obtained using different imaging techniques to select the size of the closure device in a clinical environment.Thirty-seven patients who consecutively underwent implantation of Amplatzer cardiac plug (ACP) devices were studied. All patients were examined using computed tomography (CT) prior to intervention. Measurements were compared to those obtained using intraoperative transesophageal echocardiography (IOTEE) and angiography. Size was determined by the longest axis of the appendage ostium. The influence of all techniques on the correct selection of final size was assessed.The measurements taken using the three techniques agreed in only 21.6% of the cases, leading to accurate selection of device size. Two techniques coincided as follows: IOTEE-CT in 45.9%, angiography-CT in 35.13%, and angiography-IOTEE in 24.3%. Measurements using CT were definitive for ACP selection in 75.7% of cases, angiography in 48.6%, and echocardiography in 51.4%. Device size was undermeasured with angiography in 35.1% of cases, and with IOTEE in 24.3%; CT overmeasured 21.6% of cases. The combination of angiography-CT was the most accurate for selection of device size.CT most often predicts the appropriate device size. If it fails, it usually overestimates the size. Agreement of measurements with all three techniques is the most accurate situation; when two agree, the most accurate combination is angiography and CT.

La enfermedad renal cronica es un FRCV reconocido. La enfermedad cardiovascular (ECV) es la principal causa de muerte en los pacientes con enfermedad renal cronica en fase terminal (30-40%). Hasta el 80% de los pacientes en lista de espera estan asintomaticos desde el punto de vista cardiovascular, siendo una afeccion caracteristicamente silente desde el punto de vista clinico en estos. La ECV es la causa principal de muerte en el primer ano postrasplante. En pacientes de alto riesgo la mortalidad cardiovascular postrasplante es elevada. Objetivo: Analizar el perfil de riesgo, asi como el estudio cardiovascular pretrasplante renal y su relacion con la incidencia de eventos cardiovasculares postrasplante en nuestra comunidad. Material y metodos: Pacientes trasplantados en Extremadura entre 2000 y 2010 (n = 457). Se analizo el perfil de riesgo cardiovascular, asi como el screening cardiologico pretrasplante y la relacion con los eventos cardiovasculares tempranos y tardios. Resultados: Los factores mas relacionados con los eventos cardiacos peritrasplante fueron la edad (OR 1,1/ano) y la ECV pretrasplante (OR 4). Los eventos postrasplante tardios (despues de una semana) ocurrieron fundamentalmente en la poblacion de alto riesgo cardiovascular, con una supervivencia libre de muerte cardiovascular menor (log rank p 0,001) al igual que en el caso de evento combinado (muerte + evento isquemico log rank p 0,001). Variables predictoras independientes de evento CB en el subgrupo de alto riesgo fueron: enfermedad CV previa OR = 3,2; edad (anos) OR = 1,04; DM OR = 2; tiempo en dialisis (anos) OR = 1,06. No hubo difrencias en la supervivencia libre de eventos cardiovasculares entre el grupo de alto riesgo con o sin estudio cardiovascular. Conclusiones: La mayoria de los pacientes en estudio pretrasplante presentan un alto riesgo cardiovascular. El estudio CV previo al Tx no influyo en el mal pronostico de los pacientes de alto riesgo.

This is an open-access article distributed under the terms of the Creative Commons Attribution License., Both clinical and experimental observations show that the skin is affected by the thyroidal status. In hypothyroid patients the epidermis is thin and alopecia is common, indicating that thyroidal status might influence not only skin proliferation but also hair growth. We demonstrate here that the thyroid hormone receptors (TRs) mediate these effects of the thyroid hormones on the skin. Mice lacking TRα1 and TRβ (the main thyroid hormone binding isoforms) display impaired hair cycling associated to a decrease in follicular hair cell proliferation. This was also observed in hypothyroid mice, indicating the important role of the hormone-bound receptors in hair growth. In contrast, the individual deletion of either TRα1 or TRβ did not impair hair cycling, revealing an overlapping or compensatory role of the receptors in follicular cell proliferation. In support of the role of the receptors in hair growth, TRα1/TRβ-deficient mice developed alopecia after serial depilation. These mice also presented a wound-healing defect, with retarded re-epithelialization and wound gaping, associated to impaired keratinocyte proliferation. These results reinforce the idea that the thyroid hormone nuclear receptors play an important role on skin homeostasis and suggest that they could be targets for the treatment of cutaneous pathologies., This work was supported by Grants BFU2011-28058, RD12/0036/0030 and S2011/BMD-2328 to AA, and SAF2012-34378, RD12/0036/0009 and S2010/BMD-2470 to JMP. MM-F is funded by a ‘Juan de la Cierva’ research fellowship (JCI-2010-06167).