Background-Postinfarction cardiac repair is regulated through timely activation and repression of inflammatory pathways, followed by transition to fibrous tissue deposition and formation of a scar. The transforming growth factor-␤/Smad3 pathway is activated in healing infarcts and may regulate cellular events critical for the inflammatory and the fibrotic responses. Methods and Results-We examined the effects of Smad3 gene disruption on infarct healing and the pathogenesis of cardiac remodeling. In the absence of injury, Smad3-null hearts had comparable function to and similar morphology as wild-type hearts. Smad3-null animals had suppressed peak chemokine expression and decreased neutrophil recruitment in the infarcted myocardium but showed timely repression of inflammatory gene synthesis and resolution of the inflammatory infiltrate. Although myofibroblast density was higher in Smad3-null infarcts, interstitial deposition of collagen and tenascin-C in the remodeling myocardium was markedly reduced. Compared with wild-type animals, Smad3 Ϫ/Ϫ mice exhibited decreased dilative remodeling and attenuated diastolic dysfunction; however, infarct size was comparable between groups. Transforming growth factor-␤-mediated induction of procollagen type III and tenascin-C in isolated cardiac fibroblasts was dependent on Smad3, which suggests that decreased fibrotic remodeling in infarcted Smad3-null hearts may be due to abrogation of the profibrotic transforming growth factor-␤ responses. Conclusions-Smad3 loss does not alter the time course of resolution of inflammation in healing infarcts, but it prevents interstitial fibrosis in the noninfarcted myocardium and attenuates cardiac remodeling. Thus, the Smad3 cascade may be a promising therapeutic target for the treatment of myocardial infarction.

Although young mice exhibit a robust post-infarction inflammatory response and form dense collagenous scars, senescent mice show suppressed inflammation, delayed granulation tissue formation, and markedly reduced collagen deposition. These defects might contribute to adverse remodeling. These observations suggest that caution is necessary when attempting to therapeutically target the post-infarction inflammatory response in patients with reperfused MI. The injurious potential of inflammatory mediators might have been overstated, owing to extrapolation of experimental findings from young animals to older human patients.

BackgroundPrescription of inappropriate medicine to elderly patients is a major public health care concern. The Beers criteria have been commonly employed as a screening tool to identify the use of potentially inappropriate medications (PIMs). The present study investigated the prevalence of PIM use according to the Beers criteria as well as factors related to PIM use.MethodsData obtained from a retrospective survey included 25,810 outpatients aged ≥65 years from a university medical center in Seoul, Korea. PIMs were defined using the Beers criteria. Factors associated with PIM use were evaluated using multiple regression analysis.ResultsOf all participants, 7,132 (27.6%) were prescribed at least one PIM. The most commonly prescribed PIMs were alprazolam (11.2%), clonazepam (10.8%), zolpidem (8.7%), quetiapine (8.4%), and hydroxyzine (5.4%). In multivariate logistic regression analysis, having five or more prescription medicines (odds ratio [OR], 11.32; 95% confidence interval [CI], 9.38 to 13.66) and five or more prescribing doctors (OR, 4.40; 95% CI, 3.59 to 5.39) were strongly associated with PIM. In a likelihood ratio test for trend, an increasing number of medications and prescribing doctors were both significantly associated with PIM.ConclusionAt a university medical center, the number of medications and the number of prescribing doctors was associated with PIM in older outpatients.

BackgroundNon-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) share common pathogenic mechanisms and many risk factors, and both are linked to an increased risk of cardiovascular diseases. The aim of this study was to assess the association between NAFLD and CKD according to the presence of hypertension and diabetes mellitus in Koreans aged 50 years or older.MethodsA cross-sectional study of 1,706 subjects who received their routine health examination was conducted between May 2008 and April 2010 at Konkuk University medical center. Biochemical tests for liver and abdominal ultrasonography were performed. CKD was defined as either proteinuria or glomerular filtration rate ≤60 mL/min per 1.73 m2.ResultsAmong the 1,706 subjects, There were 545 (31.9%) with non-alcoholic fatty liver disease and 424 (24.9%) with chronic kidney disease. In univariate logistic regression analysis, NAFLD was significantly associated with CKD (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.34 to 2.12). In multivariate logistic regression analysis adjusted for age, sex, current smoking, abdominal obesity, aspartate aminotransferases, alanine aminotransferases, γ-glutamyltransferase, hypertension, diabetes mellitus, hypertriglyceridemia, and low high-density lipoprotein cholesterol, NAFLD was associated with CKD (adjusted OR, 1.68; 95% CI, 1.27 to 2.24). This relationship remained significant after classification according to the presence of hypertension or diabetes mellitus.ConclusionNAFLD diagnosed by ultrasonography was significantly associated with CKD in Koreans aged 50 years or older.

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