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1.
Sci Rep ; 9(1): 8581, 2019 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-31189975

RESUMEN

Glucocorticoids (Gcs) are widely prescribed anti-inflammatory compounds, which act through the glucocorticoid receptor (GR). Using an unbiased proteomics screen in lung tissue, we identified the membrane protein caveolin -1 (Cav1) as a direct interaction partner of the GR. In Cav1 knockout mice GR transactivates anti-inflammatory genes, including Dusp1, more than in controls. We therefore determined the role of Cav1 in modulating Gc action in two models of pulmonary inflammation. We first tested innate responses in lung. Loss of Cav1 impaired the inflammatory response to nebulized LPS, increasing cytokine/chemokine secretion from lung, but impairing neutrophil infiltration. Despite these changes to the inflammatory response, there was no Cav1 effect on anti-inflammatory capacity of Gcs. We also tested GR/Cav1 crosstalk in a model of allergic airway inflammation. Cav1 had a very mild effect on the inflammatory response, but no effect on the Gc response - with comparable immune cell infiltrate (macrophage, eosinophils, neutrophils), pathological score and PAS positive cells observed between both genotypes. Pursuing the Th2 adaptive immune response further we demonstrate that Cav1 knockout mice retained their ability to expel the intestinal nematode parasite T.muris, which requires adaptive Th2 immune response for elimination. Therefore, Cav1 regulates innate immune responses in the lung, but does not have an effect on Th2-mediated adaptive immunity in lung or gut. Although we demonstrate that Cav1 regulates GR transactivation of anti-inflammatory genes, this does not translate to an effect on suppression of inflammation in vivo.


Asunto(s)
Caveolina 1/inmunología , Enfermedades Pulmonares Parasitarias/inmunología , Pulmón/inmunología , Receptores de Glucocorticoides/inmunología , Tricuriasis/inmunología , Trichuris/inmunología , Animales , Caveolina 1/genética , Inmunidad Innata , Inflamación , Pulmón/parasitología , Pulmón/patología , Enfermedades Pulmonares Parasitarias/genética , Ratones , Ratones Noqueados , Receptores de Glucocorticoides/genética , Células Th2/inmunología , Tricuriasis/genética , Tricuriasis/patología
2.
Ment Health Prev ; 3(4): 178-184, 2015 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-26682131

RESUMEN

OBJECTIVES: Older adults underutilize mental health services suggesting that significant barriers are operating. This study presents reliability and validity data for a revised version of the self-report Barriers to Mental Health Services Scale (BMHSS) designed to quantify 10 barriers to mental health service use, so that barriers can be examined collectively. METHODS: The Barriers to Mental Health Services Scale Revised (BMHSS-R) was revised to improve its reliability and validity, including adding items, eliminating poor items, and balancing the number of items across subscales. A sample of 100 older adults (M age = 72.1 years, SD = 17.8 years) completed the BMHSS-R, the Beliefs Toward Mental Illness Scale, and the Willingness to Seek Help Questionnaire. RESULTS: Internal consistency for the 10 subscales of the BMHSS-R ranged between .63 and .87, with 8 of the 10 values greater than .70. Correlational analyses indicated that many of the subscales overlap considerably but are still distinct. Convergent validity of the BMHSS-R subscales of help-seeking and stigma was partially supported, although correlations were modest. CONCLUSION: Revisions to the BMHSS resulted in improved reliability estimates for use as a measure of perceived barriers to mental health services. We recommend when using the BMHSS-R to combine results with other information (e.g., service utilization data) to characterize a profile of barriers. We discuss directions for future research and further refinement of the BMHSS-R.

3.
Nat Commun ; 5: 4960, 2014 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-25248305

RESUMEN

Despite its ubiquitous presence in the built environment, concrete's molecular-level properties are only recently being explored using experimental and simulation studies. Increasing societal concerns about concrete's environmental footprint have provided strong motivation to develop new concrete with greater specific stiffness or strength (for structures with less material). Herein, a combinatorial approach is described to optimize properties of cement hydrates. The method entails screening a computationally generated database of atomic structures of calcium-silicate-hydrate, the binding phase of concrete, against a set of three defect attributes: calcium-to-silicon ratio as compositional index and two correlation distances describing medium-range silicon-oxygen and calcium-oxygen environments. Although structural and mechanical properties correlate well with calcium-to-silicon ratio, the cross-correlation between all three defect attributes reveals an indentation modulus-to-hardness ratio extremum, analogous to identifying optimum network connectivity in glass rheology. We also comment on implications of the present findings for a novel route to optimize the nanoscale mechanical properties of cement hydrate.

5.
J Org Chem ; 66(14): 4752-8, 2001 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-11442399

RESUMEN

The synthesis and preliminary photophysical properties of a series of diazatrithia-15-crown-5 and diazatrithia-16-crown-5 ligands containing two 8-hydroxyquinoline sidearms are reported. The ligands were prepared by a two-step process. First, diazatrithiacrown ethers 11 and 12 were prepared by treating bis(alpha-chloroamide) 5 with various dimercaptans followed by reduction using a boron-THF complex. Hydroxymethyl-substituted macrocycle 12 was rearranged to hydroxy-substituted diazatrithia-16-crown-5 in refluxing aqueous HCl. Macrocyclic diamines 11-13 were converted to either 5-chloro-8-hydroxyquinolin-7-ylmethyl-substituted diazatrithiacrown ethers 14-16 by a Mannich aminomethylation reaction or to 8-hydroxyquinolin-2-ylmethyl-substituted diazatrithiacrown ethers 17-19 by reductive amination using 8-hydroxyquinoline-2-carboxaldehyde. Preliminary photophysical studies show that ligands 16 and 19 exhibit increased fluorescence in the presence of Zn(2+), indicating that these ligands could be chemical sensors for Zn(2+).

6.
Neurol Neurochir Pol ; 34(3): 475-86, 2000.
Artículo en Polaco | MEDLINE | ID: mdl-10979542

RESUMEN

The role of mandibular dysfunction in the etiology of headache is still underestimated in the medical literature. For this reason an analysis of own questionnaire investigations published in the years 1983 to 1999 was done. These investigations were carried out in 3915 subjects aged 15-66. In order to determine the prevalence of headache associated with mandibular dysfunction in the analysis mandibular parafunctions and clicking in the temporomandibular joints (TMJs) were selected. The comparison of the prevalence of headache in groups with and without mandibular parafunctions and in groups with and without clicking in the TMJs has shown that the prevalence of headache was significantly higher in groups with mandibular parafunctions and with clicking in the TMJs than in groups without these disturbances. The difference in the prevalence of headache in the investigated groups has shown that headaches noted in the population can be associated with mandibular parafunctions in 18.2% and dependent on the age with clicking in the TMJs in 9.7% to 25%.


Asunto(s)
Cefalea/epidemiología , Cefalea/etiología , Trastornos de la Articulación Temporomandibular/complicaciones , Trastornos de la Articulación Temporomandibular/fisiopatología , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Trastornos de la Articulación Temporomandibular/diagnóstico
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