Biomarkers of extracellular matrix metabolism (MMP-9 and TIMP-1) and risk of stroke, myocardial infarction and cause-specific mortality : cohort study

Objective: Turnover of the extracellular matrix in all solid organs is governed mainly by a balance between the degrading matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). An altered extracellular matrix metabolism has been implicated in a variety of diseases. We investigated relations of serum levels of MMP-9 and TIMP-1 to mortality risk from an etiological perspective. Design: The prospective Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, followed from 1991–1995 for up to 18.1 years. A random population-based sample of 1,082 71-year-old men, no loss to follow-up. Endpoints were all-cause (n = 628), cardiovascular (n = 230), non-cardiovascular (n = 398) and cancer mortality (n = 178), and fatal or non-fatal myocardial infarction (n = 138) or stroke (n = 163). Results: Serum MMP-9 and TIMP-1 levels were associated with risk of all-cause mortality (Cox proportional hazard ratio [HR] per standard deviation 1.10, 95% confidence interval [CI] 1.03–1.19; and 1.11, 1.02–1.20; respectively). TIMP-1 levels were mainly related to risks of cardiovascular mortality and stroke (HR per standard deviation 1.22, 95% CI 1.09–1.37; and 1.18, 1.04–1.35; respectively). All relations except those of TIMP-1 to stroke risk were attenuated by adjustment for cardiovascular disease risk factors. Relations in a subsample without cardiovascular disease or cancer were similar to those in the total sample. Conclusion: In this community-based cohort of elderly men, serum MMP-9 and TIMP-1 levels were related to mortality risk. An altered extracellular matrix metabolism may be involved in several detrimental pathways, and circulating MMP-9 or TIMP-1 levels may be relevant markers thereof.

El sentimiento trágico en San Manuel Bueno, mártir : Una lucha contra la razón en búsqueda de la fe

Este trabajo de investigación tiene como fin analizar el pensamiento del autor Miguel de Unamuno para poder relacionarlo con los pensamientos del personaje del cura de la novela San Manuel Bueno, mártir. El objetivo es buscar la relación que existe entre el autor y el cura en lo que se refiere a los temas relacionados con la religión. Para este estudio se utilizará la metodología hermenéutica donde se analizará el pensamiento del autor en relación con el personaje San Manuel, basándose principalmente en el libro Del sentimiento trágico de la vida, uno de los libros más destacados sobre el pensamiento filosófico del autor. Al final, como una pequeña aportación a la tesis, se hablará de la posible misión profética que tuvo Unamuno en sus últimos años de vida que a través de sus obras quiso despertar la conciencia de sus lectores para que se unieran a la búsqueda de la verdadera fe.