Cyclooxygenase-independent inhibitory effects on T cell activation of novel 4,5-dihydro-3 trifluoromethyl pyrazole cyclooxygenase-2 inhibitors.

Anti-inflammatory efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) has been related to their properties as inhibitors of cyclooxygenase (COX)-mediated prostaglandin (PG) synthesis. However, recent studies have suggested that variations of the in vivo anti-inflammatory actions among different NSAIDs could not be solely explained by COX inhibition. Here, we have analyzed the effects on T cell activation of novel 4,5-dihydro-3 trifluoromethyl pyrazole anti-inflammatory drugs with different potencies as COX-2 inhibitors, namely E-6087, E-6232, E-6231, E-6036 and E-6259 as well as the chemically related COX-2 inhibitor Celecoxib. These drugs inhibited mitogen-mediated T cell proliferation as well as Interleukin (IL)-2, tumor necrosis factor (TNF)-α and Interferon (IFN)-γ synthesis by activated T cells, independently of their ability to inhibit COX-2 enzymatic activity. Immunosuppressive effects of these drugs seem to be due to their interference on transcription factor activation as induced transcription from Nuclear Factor (NF)-κB and Nuclear Factor of Activated T cells (NFAT)-dependent enhancers was inhibited in a dose-dependent manner, being the latter effect the most sensitive to the action of those compounds. Both NFAT dephosphorylation, required for its nuclear translocation, as well as transcriptional activity of a GAL4-NFAT chimera were diminished in the presence of these compounds. These findings provide new insights into the molecular mechanisms involved in the immunomodulatory and anti-inflammatory actions of NSAIDs, which may have important implications in anti-inflammatory therapy, through inhibition of NFAT.

Relationship between metabolic syndrome and ischemic heart disease mortality in Spain.

Morbidity and mortality due to ischemic heart disease (IHD) is subject to wide geographic variation both between and within countries. The aim of this study was to determine whether geographic variations exist in the prevalence of metabolic syndrome in the Spanish working population or in its relationship with IHD mortality. We analyzed clinical and laboratory data obtained during health check-ups carried out in Spanish workers (n=17,837) during 2003. The prevalence of metabolic syndrome was 17% in men and 6.5% in women. However, there was a heterogeneous distribution across the different regions studied. The prevalence in southern and western regions (e.g., in men: 22.15% in Extremadura and 20.6% in Galicia) was double that observed in central and northern zones (e.g., in the Basque Country and Castile and León). This research indicates that there is a significant association between IHD mortality and the prevalence of metabolic syndrome in workers from different Spanish regions.

Relación entre el síndrome metabólico y la mortalidad por cardiopatía isquémica en España / Relationship between metabolic syndrome and ischemic heart disease mortality in Spain

La mortalidad y morbilidad de la cardiopatía isquémica siguen una distribución geográfica heterogénea entre diferentes países e incluso dentro de cada país. El objetivo del presente estudio es analizar si hay diferencias en la distribución geográfica del síndrome metabólico en la población laboral española y su relación con la mortalidad por cardiopatía isquémica. Analizamos datos clínicos y analíticos (n = 17.837) procedentes de los exámenes de salud realizados a trabajadores durante el año 2003. La prevalencia del síndrome metabólico es del 17% en varones y el 6,5% en mujeres. Sin embargo, su distribución es heterogénea en las diferentes comunidades estudiadas. Las regiones del sur y el oeste muestran prevalencias (Extremadura, 22,15%; Galicia, 20,6% en varones) que duplican las de las zonas del centro y el norte: País Vasco y Castilla y León. Nuestro trabajo señala una asociación significativa entre la mortalidad por cardiopatía isquémica y la frecuencia de síndrome metabólico en trabajadores de las diferentes provincias españolas (AU)

Morbidity and mortality due to ischemic heart disease (IHD) is subject to wide geographic variation both between and within countries. The aim of this study was to determine whether geographic variations exist in the prevalence of metabolic syndrome in the Spanish working population or in its relationship with IHD mortality. We analyzed clinical and laboratory data obtained during health check-ups carried out in Spanish workers (n=17,837) during 2003. The prevalence of metabolic syndrome was 17% in men and 6.5% in women. However, there was a heterogeneous distribution across the different regions studied. The prevalence in southern and western regions (e.g., in men: 22.15% in Extremadura and 20.6% in Galicia) was double that observed in central and northern zones (e.g., in the Basque Country and Castile and León). This research indicates that there is a significant association between IHD mortality and the prevalence of metabolic syndrome in workers from different Spanish regions (AU)

Comparison of cardiovascular risk factors in young Spanish men between the 1980s and after the year 2000. Data from the AGEMZA study.

INTRODUCTION AND OBJECTIVES: To investigate the cardiovascular risk profile of a sample of young Spanish men taken in the 1980s, the initial AGEMZA study cohort, and to compare the findings with those in another sample with similar characteristics taken after 2000. METHODS: The two AGEMZA study cohorts comprised young men who were resident at the Zaragoza General Military Academy, where they were studying as aspiring cadets. A descriptive study of each cohort was carried out and the participants' anthropometric characteristics, sporting and dietary habits, exposure to toxins, and biochemical and lipid profiles were analyzed. Data on the prevalence of various risk factors were obtained for each cohort and the coronary disease risk was estimated using the Framingham equation. RESULTS: Comparison of data on 248 subjects from the current cohort with data on 260 from the initial cohort showed the following significant changes: weight (+6.03 kg), body mass index (BMI) (+1.57), cholesterol (+12.46 mg/dL), low-density lipoprotein cholesterol (+15.8 mg/dL), high-density lipoprotein cholesterol (-4.11 mg/dL), triglycerides (+3.64 mg/dL), apolipoprotein B (+24.8 mg/dL), estimated coronary disease risk in the next 10 years (+1/1000 individuals) and estimated coronary disease risk up to the age of 65 years (+23/1000 individuals). There were significant correlations between increases in weight and BMI and lipid profile alterations. CONCLUSIONS: The lipid profile and BMI were worse in the current sample. These findings make it essential that preventive measures for young people should be introduced and that an increased effort should be made to develop programs aimed at either stopping the progressive rise in obesity or even preventing it altogether.

Comparación de los factores de riesgo cardiovascular de jóvenes españoles de los años ochenta y tras el 2000. Datos del estudio AGEMZA / Comparison of cardiovascular risk factors in young spanish men between the 1980s and after the year 2000. Data from the AGEMZA study

Introducción y objetivos. Analizar el perfil de riesgo cardiovascular de una muestra de jóvenes varones españoles de los años ochenta, cohorte inicial del estudio AGEMZA, y compararla con otra muestra de similares características, tras el 2000. Métodos. Las dos muestras de AGEMZA están compuestas por varones jóvenes residentes en la Academia General Militar de Zaragoza, donde estudiaban en calidad de cadetes aspirantes. Realizamos un estudio descriptivo de cada cohorte, analizando datos antropométricos, hábitos deportivos, dietéticos y tóxicos y sus perfiles bioquímico y lipídico. Obtuvimos datos de la prevalencia de los diferentes factores de riesgo en cada una de ellas y estimamos el riesgo coronario para las dos cohortes mediante la ecuación de Framingham. Resultados. Comparamos datos de 260 sujetos de la muestra inicial y de 248 de la muestra actual, de lo que se obtuvo las siguientes variaciones significativas: peso (+6,03 kg), IMC (+1,57), colesterol total (+12,46 mg/dl), colesterol de las lipoproteínas de baja densidad (+15,8 mg/dl), colesterol de las lipoproteínas de alta densidad (-4,11 mg/dl), triglicéridos (+3,64 mg/dl) y apolipoproteína B (+24,8 mg/dl), el riesgo coronario estimado en los próximos 10 años (+1/1.000 sujetos) y el proyectado a los 65 años de edad (+23/1.000 sujetos). Los aumentos de peso y del IMC se correlacionan de forma significativa con los cambios encontrados en el perfil lipídico. Conclusiones. La muestra actual tiene peor perfil lipídico e IMC. Estos resultados nos obligan a tomar medidas preventivas en los jóvenes y extremar el desarrollo de campañas destinadas a frenar este aumento progresivo de la obesidad y para prevenir su aparición (AU)

Introduction and objectives. To investigate the cardiovascular risk profile of a sample of young Spanish men taken in the 1980s, the initial AGEMZA study cohort, and to compare the findings with those in another sample with similar characteristics taken after 2000. Methods. The two AGEMZA study cohorts comprised young men who were resident at the Zaragoza General Military Academy, where they were studying as aspiring cadets. A descriptive study of each cohort was carried out and the participants' anthropometric characteristics, sporting and dietary habits, exposure to toxins, and biochemical and lipid profiles were analyzed. Data on the prevalence of various risk factors were obtained for each cohort and the coronary disease risk was estimated using the Framingham equation. Results. Comparison of data on 248 subjects from the current cohort with data on 260 from the initial cohort showed the following significant changes: weight (+6.03 kg), body mass index (BMI) (+1.57), cholesterol (+12.46 mg/dL), low-density lipoprotein cholesterol (+15.8 mg/dL), high-density lipoprotein cholesterol (-4.11 mg/dL), triglycerides (+3.64 mg/dL), apolipoprotein B (+24.8 mg/dL), estimated coronary disease risk in the next 10 years (+1/1000 individuals) and estimated coronary disease risk up to the age of 65 years (+23/1000 individuals). There were significant correlations between increases in weight and BMI and lipid profile alterations. Conclusions. The lipid profile and BMI were worse in the current sample. These findings make it essential that preventive measures for young people should be introduced and that an increased effort should be made to develop programs aimed at either stopping the progressive rise in obesity or even preventing it altogether (AU)