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.

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.