Matrix Metalloproteinases and TIMP-1 production by peripheral blood granulocytes from COPD patients and asthmatics

Both asthmatic and COPD patients were found to have increased amounts of granulocytes and matrix metalloproteinase-9 (MMP-9) in their sputum. The present study was conducted to investigate whether the elevated amounts of MMP-9 and TIMP-1 found in such patients' airways may be linked to an enhanced secretion by granulocytes. Blood granulocytes from asthmatics (n = 10), COPD patients (n = 11), and healthy controls (n = 11) were isolated and cultured under basal conditions or after stimulation by phorbol 12-myristate 13-acetate (PMA) or N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). MMP-9 activity was detected by zymography while MMP-8 and TIMP-1 levels were measured by ELISA. In zymography, pro- and activated forms of MMP-9 were present in each group (healthy subjects, asthmatics, and COPD patients). Spontaneous release was not different between the three groups. Stimulation by fMLP and PMA increased to a similar extent the release of MMP-9 by granulocytes in all the three groups. TIMP-1 levels were also increased after stimulation by PMA and fMLP only in healthy subjects and COPD patients. MMP-8 levels were barely detectable. We conclude that circulating granulocytes from COPD patients and asthmatics do not display an abnormal secretion of MMP-9, and that granulocytes from asthmatics have an impaired ability to release TIMP-1 upon stimulation

Improving inter-observer variability in the evaluation of ultrasonographic features of polycystic ovaries

<p>Abstract</p> <p>Background</p> <p>We recently reported poor inter-observer agreement in identifying and quantifying individual ultrasonographic features of polycystic ovaries. Our objective was to determine the effect of a training workshop on reducing inter-observer variation in the ultrasonographic evaluation of polycystic ovaries.</p> <p>Methods</p> <p>Transvaginal ultrasound recordings from thirty women with polycystic ovary syndrome (PCOS) were evaluated by three radiologists and three reproductive endocrinologists both before and after an ultrasound workshop. The following endpoints were assessed: 1) follicle number per ovary (FNPO), 2) follicle number per single cross-section (FNPS), 3) largest follicle diameter, 4) ovarian volume, 5) follicle distribution pattern and 6) presence of a corpus luteum (CL). Lin's concordance correlation coefficients (rho) and kappa statistics for multiple raters (kappa) were used to assess level of inter-observer agreement (>0.80 good, 0.60 – 0.80 moderate/fair, <0.60 poor).</p> <p>Results</p> <p>Following the workshop, inter-observer agreement improved for the evaluation of FNPS (rho = 0.70, delta rho = +0.11), largest follicle diameter (rho = 0.77, delta rho = +0.10), ovarian volume (rho = 0.84, delta rho = +0.12), follicle distribution pattern (kappa = 0.80, delta kappa = +0.21) and presence of a CL (kappa = 0.87, delta kappa = +0.05). No improvement was evident for FNPO (rho = 0.54, delta rho = -0.01). Both radiologists and reproductive endocrinologists demonstrated improvement in scores (p < 0.001).</p> <p>Conclusion</p> <p>Reliability in evaluating ultrasonographic features of polycystic ovaries can be significantly improved following participation in a training workshop. If ultrasonographic evidence of polycystic ovaries is to be used as an objective measure in the diagnosis of PCOS, then standardized training modules should be implemented to unify the approach to evaluating polycystic ovarian morphology.</p

Extracellular Matrix Biomarkers of Adverse Remodeling after Myocardial Infarction

Approximately every minute, someone will die from a myocardial infarction (MI). A MI is the result of an obstruction of blood supply causing the heart to undergo complex structural and functional changes in the left ventricular wall, known as ventricular remodeling. Cardiomyocytes undergo necrosis rapidly after the onset of injury, leading to early accumulation of neutrophils, activation of metalloproteinases, and degradation of the stromal tissue, eventually leading to formation of a collagen scar. Circulating factors related to inflammatory and fibrotic responses are key predictors of extracellular matrix (ECM) changes that occur after MI. Changes in the collagen network of the ECM can alter myocardial stiffness, consequently leading to cardiac hypertrophy, fibrosis, and LV dysfunction. Proteins and peptides of the ECM are promising biomarkers for MI. This book chapter provides an overview of key ECM biomarkers involved in adverse remodeling post-MI and their practical applications