Development of a novel 1 receptor biosensor based on its heterodimerization with binding immunoglobulin protein in living cells

The σ1 receptor (S1R) is a ligand-regulated non-opioid intracellular receptor involved in several pathological conditions. The development of S1R-based drugs as therapeutic agents is a challenge due to the lack of simple functional assays to identify and classify S1R ligands. We have developed a novel nanoluciferase binary technology (NanoBiT) assay based on the ability of S1R to heteromerize with the binding immunoglobulin protein (BiP) in living cells. The S1R-BiP heterodimerization biosensor allows for rapid and accurate identification of S1R ligands by monitoring the dynamics of association-dissociation of S1R and BiP. Acute treatment of cells with the S1R agonist PRE-084 produced rapid and transient dissociation of the S1R-BiP heterodimer, which was blocked by haloperidol. The effect of PRE-084 was enhanced by calcium depletion, leading to a higher reduction in heterodimerization even in the presence of haloperidol. Prolonged incubation of cells with S1R antagonists (haloperidol, NE-100, BD-1047, and PD-144418) increased the formation of S1R-BiP heteromers, while agonists (PRE-084, 4-IBP, and pentazocine) did not alter heterodimerization under the same experimental conditions. The newly developed S1R-BiP biosensor is a simple and effective tool for exploring S1R pharmacology in an easy cellular setting. This biosensor is suitable for high-throughput applications and a valuable resource in the researcher's toolkit

Variaciones en la actividad antitripsinica de la fracción fibrilar de la secreción bronquial en diferentes enfermedades pulmonares

Tesis doctoral inédita leída el 27 de Junio de 1974 en la Universidad Autónoma de Madrid, Facultad de Medicin

EPOC y estado nutricional

Las alteraciones nutricionales, entendidas como pérdida de peso o desnutrición, son una complicación muy frecuente en los pacientes con enfermedad pulmonar obstructiva crónica (EPOC) y afectan principalmente a su capacidad funcional y calidad de vida, además de constituir un indicador pronóstico de morbilidad y mortalidad independientes. Los factores que contribuyen a la desnutrición son múltiples; entre ellos cabe mencionar el aumento del gasto energético en reposo, el descenso de la ingesta, el efecto de determinados fármacos y, quizá el más importante, una elevada respuesta inflamatoria sistémica. En este artículo se pretende revisar los aspectos más importantes sobre la prevalencia, etiopatogenia y efectos de la desnutrición en la EPOC, además de discutir los parámetros de valoración nutricional más adecuados en la práctica clínica diaria y la estrategia para que estos pacientes mantengan un correcto estado nutricional

Validity and reproducibility of a Spanish dietary history.

To assess the validity and reproducibility of food and nutrient intake estimated with the electronic diet history of ENRICA (DH-E), which collects information on numerous aspects of the Spanish diet.The validity of food and nutrient intake was estimated using Pearson correlation coefficients between the DH-E and the mean of seven 24-hour recalls collected every 2 months over the previous year. The reproducibility was estimated using intraclass correlation coefficients between two DH-E made one year apart.The correlations coefficients between the DH-E and the mean of seven 24-hour recalls for the main food groups were cereals (r = 0.66), meat (r = 0.66), fish (r = 0.42), vegetables (r = 0.62) and fruits (r = 0.44). The mean correlation coefficient for all 15 food groups considered was 0.53. The correlations for macronutrients were: energy (r = 0.76), proteins (r= 0.58), lipids (r = 0.73), saturated fat (r = 0.73), monounsaturated fat (r = 0.59), polyunsaturated fat (r = 0.57), and carbohydrates (r = 0.66). The mean correlation coefficient for all 41 nutrients studied was 0.55. The intraclass correlation coefficient between the two DH-E was greater than 0.40 for most foods and nutrients.The DH-E shows good validity and reproducibility for estimating usual intake of foods and nutrients

Validity of intake of some nutrients with DH-E2 (at 12 months from baseline) versus biomarkers (mean of measurements at 0, 6 and 12 months).

<p>Validity of intake of some nutrients with DH-E2 (at 12 months from baseline) versus biomarkers (mean of measurements at 0, 6 and 12 months).</p

Baseline characteristics of study participants (N = 101).

<p>SD: Standard deviation.</p

Design of validation study of diet history-ENRICA (DH-E).

<p>Footnote: 24hR: 24-hour recall.</p

Cross-classification of subjects by food and nutrient intake estimated with DH-E2 (at 12 months from baseline) and mean of seven 24-hour recalls during one year.

<p>Cross-classification of subjects by food and nutrient intake estimated with DH-E2 (at 12 months from baseline) and mean of seven 24-hour recalls during one year.</p

Food and nutrient intake according to DH-E1 (at study baseline), mean of seven 24-hour recalls during one year, and DH-E2 (at 12 months from baseline). (N = 101).

<p>SD: Standard deviation.</p