Gal-1 and LAT1 as regulatory molecules in skin inflammatory diseases

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina. Departamento de Bioquímica. Fecha de Lectura: 15-07-2021Skin diseases are common disorders with a high prevalence among occupational diseases. Allergic contact dermatitis (ACD) and psoriasis are complex and frequent inflammatory skin pathologies in which the immune system and epithelial alterations play an important role in their development. ACD, also known as contact hypersensitivity (CHS), is a frequent T-cell mediated inflammatory skin disease characterized by red, itchy, swollen and cracked skin. It is caused by the direct contact with an allergen and/or irritant. Galectin-1 (Gal-1) is a β-galactoside-binding lectin which is highly expressed in several types of immune cells. The role of endogenous Gal-1 in CHS is not known. We found that Gal-1-deficient mice display more sustained and prolonged skin inflammation than wild-type mice after oxazolone treatment. Gal-1-deficient mice have increased CD8+ T cells and neutrophilic infiltration in the skin. After the sensitization phase, Gal-1-depleted mice showed increased frequency of central memory CD8+ T cells and IFNγ secretion by CD8+ T cells. The absence of Gal-1 does not affect migration of transferred CD4+ and CD8+ T cells from the blood to the lymph nodes or to the skin. Depletion of CD4+ T lymphocytes as well as adoptive transfer experiments demonstrated that endogenous expression of Gal-1 on CD8+ T lymphocytes exerts a major role in the control of CHS model. These data underscore the protective role of endogenous Gal-1 in CD8+ but not CD4+ T cells in the development of CHS disease. Psoriasis is a common chronic skin disorder characterized by a thickened epidermis caused by keratinocyte (KC) proliferation and dermal inflammatory infiltrate. The main clinical manifestation is the presence of raised, squamous, erythematous oval plaques. The progress of this pathology can be affected by diverse causes such as immune system, genetic, autoantigens and environmental factors. It is mainly mediated by IL-23, IL-1β, and IL-17. Although psoriasis is a hyperproliferative skin disorder, the possible role of amino acid transporters has remained unexplored. Thus, we sought to investigate the role of the essential amino acid transporter L-type amino acid transporter 1 (LAT1) in psoriasis. We found that LAT1 expression is increased in KCs and skin-infiltrating lymphocytes of psoriatic lesions in human subjects and mice. LAT1 deletion in KCs does not dampen the inflammatory response or their proliferation, which could be maintained by increased expression of the alternative amino acid transporters LAT2 and LAT3. Specific deletion of LAT1 in γδ and CD4+ T cells controls the inflammatory response induced by imiquimod (IMQ). LAT1 deletion or inhibition by JPH203 blocks expansion of IL-17-secreting γ4+δ4+ and CD4+ T cells and dampens the release of IL-1β, IL-17, and IL-22 in the IMQ-induced model. Moreover, inhibition of LAT1 blocks expansion of human γδ T cells and IL-17 secretion by human CD4+ T cells. IL-23 and IL-1β stimulation upregulates LAT1 expression and induces mTOR activation in IL-17+ γδ and Th17 cells. Deletion or inhibition of LAT1 efficiently controls IL-23-and IL-1β-induced phosphatidylinositol 3-kinase/AKT/mTOR activation independent of T-cell receptor signaling. Overall, this thesis work underscores the protective role of endogenous Gal-1 in CD8+ T cells in the development of CHS and the novel strategy to control skin inflammation in psoriasis mediated by the IL23/IL-1β/IL-17 axis through targeting LAT1-mediated amino acid upta

Medidas generales en la prevención y el control del contagio hospitalario

Cartel presentado en la Segunda Conferencia Internacional de Comunicación en Salud, celebrada el 23 de octubre de 2015 en la Universidad Carlos III de MadridLa frecuencia de las infecciones hospitalarias oscila entre un 5-10% de los pacientes hospitalizados, por lo que, constituye uno de los problemas de salud pública más graves y de gran importancia epidemiológica porque aumentan las tasas de mortalidad y morbilidad, aumentan la estancia hospitalaria del paciente y con ello, los costes económicos. El objetivo de este trabajo es analizar las medidas preventivas actuales y las actuaciones para el control de dichas infecciones mediante una revisión bibliográfica. Las bases de datos requeridas para la búsqueda bibliográfica fueron: IME, SciELO, Cuiden y Dialnet, limitándose la búsqueda a publicaciones desde el año 2005 hasta la actualidad con los descriptores “infección y hospitalaria y prevención” y “infección y hospitalaria y control”. Los resultados obtenidos indican que las medidas de prevención se adecuan a la infección que se pretende evitar, pero existen métodos generales aplicables a todos los casos, como son: Correcta asepsia de las manos del personal sanitario antes y después de toda intervención realizada con el paciente; Uso de guantes propios al procedimiento; Asepsia del material en toda actuación realizada sobre el paciente; Control de los procedimientos que se le realizan a los pacientes, como: sondaje vesical, sondaje nasogástrico,…Correcta distribución, control y contacto con los pacientes; Asepsia de las dependencias hospitalarias donde están internados los pacientes. En base a los resultados obtenidos podemos concluir que para evitar las infecciones en los servicios sanitarios se cuentan con medidas que reducen satisfactoriamente la frecuencia de las mismas y que éstas deberían ser cumplidas con estricto control. La primera y más importante es la medida de prevención y la segunda es el control de la misma cuando ya está instaurada

Therapeutic Applications and Effects of Lupinus angustifolius (Blue Lupin) and Its Components: A Systematic Review and Meta-Analysis

Lupinus angustifolius has a unique nutrient profile among legumes and may have beneficial health effects when included in the diet. The aim of this study was to investigate the biological properties of blue lupin (Lupinus angustifolius), its chemical components, and their relevance for monitoring biological and anthropometric health markers, including triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), BMI, weight, and glycemia, compared with control groups with other kinds of diets. PubMed,Web of Science, and Scopus databases, updated to December 2023, were searched. Out of the 194 studies identified, a total of 7 randomized controlled trials (RCTs) comprising 302 participants met the eligibility criteria. The results of our study indicated that the blue lupin diet has a direct relationship with parameters such as blood glucose, weight, and LDL-C but not with TGs or BMI. In conclusion, the research described in this review clearly indicates that L. angustifolius may play an important role in the dietary prevention of hyperlipidemia and hypertension. Therefore, it would be highly advisable to increase its consumption in diets. However, further studies, ideally in humans, are required to truly establish L. angustifolius’s health-promoting properties

Study of weight and body mass index on graft loss after transplant over 5 years of evolution

Antonio Liñán González conceived paper, oversaw data collection, conducted data analysis, wrote manuscript and approved final version. Raquel García Pérez participated in study design, data analysis and interpretation, critically revised manuscript and approved final version. Juan Bravo Soto participated in study design, data analysis, and interpretation of data and revision of manuscript and approved final version. Rafael Fernández Castillo participated in study design, interpretation of data and revision of manuscript and approved final version.Patients frequently experience a weight gain after organ transplantation. This increase in weight is the result of multiple factors, and is usually intensified by glucocorticoids and immunosuppressive drugs. It can also delay graft function and cause serious health problems. The objective of this study was to study the obesity as well as its causes and consequences in kidney transplant patients. The sample population consisted of 282 renal transplant patients, 170 men and 112 women, 18-74 years of age, who were monitored over a period of five years. For the purposes of our research, the patients were divided into two groups: (1) normal weight 18.5 ≤ BMI <25; (2) overweight 25 ≤ BMI ≤30. The association between BMI as an independent variable and graft survival was determined by means of a Cox regression analysis. Overweight patients were characterized by a higher comorbidity prevalence. In the Cox multivariate analysis, the initial BMI, evaluated as a continuous variable continued to be an independent predictor of delayed graft function and chronic nephropathy. This study evaluated the BMI as a continuous value instead of a categorical value. In conclusion, our results suggest that an increase in BMI without categorical variation can be an independent risk factor for graft loss. Consequently, obesity prevention for renal transplant patients should include dietary counseling and management, moderate physical activity, and steroid minimization

Reactions to synthetic membranes dialyzers: Is there an increase in incidence?

Background: Reactions to dialyzers used in dialysis have been reported more frequently in recent years. Evidence, however, shows that the reaction rate has remained stable for years. Summary: One explanation for the apparent increase in publication frequency could be the lack of knowledge that dialyzer reactions may well occur with biocompatible membranes. Studies showed that the cause of these reactions is very diverse and varied, involving multiple materials. However, polyvinylpyrrolidone continues to be the main suspect, but without conclusive results. There are no differences between the different fibers, and although polysulfone is the most described, it is also the most used. Key Messages: The change to cellulose triacetate continues to be the most appropriate form of treatment. The classification of these reactions into type A and B complicates the diagnosis, and its true usefulness is in doubtThe research presented in this article is supported by the grants from the Spanish Ministry of Economy and Competitiveness and European Regional Development Funds (ERDF/FEDER) through ISCIII/FIS grants PI16/01298, PI17/01495, CIBERDEM and REDINREN RD016/0019 and through the Madrid Renal Society (SOMANE) grant

Internet y conducta sexual de riesgo para VIH/SIDA en jóvenes

Objective: To determine whether the use of online sexual material influences sexual risk behavior for HIV / AIDS in young university students. Concepts of Social Cognitive Theory were used.Enfermería Global Nº 38 Abril 2015 Página 138Methods: A descriptive correlational design, involving 200 university students selected by systematic random sampling (k = 11).Results: Young people who used sexual material online rich media to masturbation (rs =.34), arousal (rs = 29), stimulation (rs = 29), adventure (rs = 30), meeting people (rs =.27), images (rs =.17) and cybersex (rs =.25) showed greater sexual risk behavior for HIV / AIDS (p &lt;.01). The use of sexual material online for masturbation (R2 = 6.4%, F [1,189] = 12.80, p &lt;.001), seeking adventures (R2 = 4.8%, F [1,189] = 9.56, p &lt;.01), meeting people (R2 = 5.9%, F [1,189] = 11.88, p &lt;.01) and have cybersex (R2 = 4.1%, F [1,189] = 8.07, p &lt;.01) had a significant positive effect on behavior sexual risk for HIV/AIDS.Conclusions: The use of online sexual material influences sexual risk behavior for HIV/AIDS.Objetivo: Determinar si el uso de material sexual en línea influye en la conducta sexual de riesgo para VIH/SIDA en los jóvenes universitarios. Se utilizaron conceptos de la Teoría Cognitiva Social.Método: Diseño descriptivo correlacional, participaron 200 jóvenes universitarios, seleccionados por muestreo aleatorio sistemático (k = 11).Resultados: Los jóvenes que usaron material sexual en línea en medios ricos para masturbarse (rs = .34), excitarse (rs = .29), estimularse (rs = .29), buscar una aventura (rs = .30), conocer gente (rs = .27), imágenes (rs = .14) y cibersexo (rs = .25) mostraron mayor conducta sexual de riesgo para VIH/SIDA (p &lt; .01). El uso de material sexual en línea para masturbarse (R2 = 6.4%, F [1,189] = 12.80, p &lt; .001), buscar una aventura (R2 = 4.8%, F [1,189] = 9.56, p &lt; .01), conocer gente (R2 = 5.9%, F [1,189] = 11.88, p &lt; .01) y tener cibersexo (R2 = 4.1%, F [1,189] = 8.07, p &lt; .01) presentó un efecto positivo y significativo en la conducta sexual de riesgo para VIH/SIDA.Conclusiones: El uso de material sexual en línea influye en la conducta sexual de riesgo para VIH/SIDA

Estudio de prefactibilidad para el cambio de energía convencional por energía fotovoltaica del sistema de bombeo de agua potable de la comunidad Sacaclí, municipio de San Rafael del Norte

Presenta un estudio de pre factibilidad donde se analiza la alternativa de solución de instalar un sistema solar fotovoltaico para el bombeo de un pozo de agua potable en la comunidad de Sacaclí donde los miembros del comité de agua potable y saneamiento de la comunidad ha detectado un incremento dela facturación de la energía eléctrica lo que afecta la sostenibilidad del sistema de bombeo de agua potable actual

The Minor Allele of rs7574865 in the STAT4 Gene Is Associated with Increased mRNA and Protein Expression

We studied 201 patients (80% female; median age, 54 years; median disease duration, 5.4 months) from PEARL study. Demographic, clinical, laboratory and therapeutic data were collected at each visit. IL-6 serum levels were measured by enzyme immune assay. The rs7574865 was genotyped using TaqMan probes. The expression levels of STAT4 mRNA were determined at 182 visits from 69 patients using quantitative real-time polymerase chain reaction. STAT4 protein was assessed by western blot in 62 samples from 34 patients. To determine the effect of different variables on the expression of STAT4 mRNA and protein, we performed multivariate longitudinal analyses using generalized linear models.This work was supported by grants awarded to IGA from the RETICS Program (RD08/0075/0004 and RD12/0009/0017 [RIER]) and FIS Program (PI11/0551) and to JM from RETICS Program (RD08/0075/0011 and RD12/0009/0004 [RIER]) from the Instituto de Salud Carlos III (www.isciii.es). Measurement of IL-6 levels described in this article was supported by different research grants from Roche to IGA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

QT variability unrelated to RR variability during stress testing for identification of coronary artery disease

Stress test electrocardiogram (ECG) analysis is widely used for coronary artery disease (CAD) diagnosis despite its limited accuracy. Alterations in autonomic modulation of cardiac electrical activity have been reported in CAD patients during acute ischemia. We hypothesized that those alterations could be reflected in changes in ventricular repolarization dynamics during stress testing that could be measured through QT interval variability (QTV). However, QTV is largely dependent on RR interval variability (RRV), which might hinder intrinsic ventricular repolarization dynamics. In this study, we investigated whether different markers accounting for low-frequency (LF) oscillations of QTV unrelated to RRV during stress testing could be used to separate patients with and without CAD. Power spectral density of QTV unrelated to RRV was obtained based on time-frequency coherence estimation. Instantaneous LF power of QTV and QTV unrelated to RRV were obtained. LF power of QTV unrelated to RRV normalized by LF power of QTV was also studied. Stress test ECG of 100 patients were analysed. Patients referred to coronary angiography were classified into non-CAD or CAD group. LF oscillations in QTV did not show significant differences between CAD and non-CAD groups. However, LF oscillations in QTV unrelated to RRV were significantly higher in the CAD group as compared with the non-CAD group when measured during the first phases of exercise and last phases of recovery. ROC analysis of these indices revealed area under the curve values ranging from 61 to 73%. Binomial logistic regression analysis revealed LF power of QTV unrelated to RRV, both during the first phase of exercise and last phase of recovery, as independent predictors of CAD. In conclusion, this study highlights the importance of removing the influence of RRV when measuring QTV during stress testing for CAD identification and supports the added value of LF oscillations of QTV unrelated to RRV to diagnose CAD from the first minutes of exercise. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'

Habilidades comunicativas del personal sanitario con el paciente con discapacidad en la comunicación

Cartel presentado en el 3er Congreso Internacional de Comunicación en Salud (3ICHC), celebrado los días 19 y 20 de octubre de 2017 en la Universidad Carlos III de Madrid.El objetivo de esta revisión sistemática ha sido analizar las repercusiones sociales y sanitarias de los pacientes con afasia, así como describir unas normas que faciliten el proceso comunicativo sanitario-paciente. Para ello se ha llevado a cabo una pesquisa en las bases de datos de SciELO, Pubmed y Dialnet entre 2010-2017 empleando como fórmulas de búsqueda: [afasia y repercusiones sociales-sanitarias] y [afasia y sanitarios y normas comunicativas]