Biomarkers of inflammation and innate immunity in atrophic nonunion fracture.

Background: Nonunion is a failure of healing following a bone fracture. Its physiopathology remains partially unclear and the discovery of new mediators could promote the understanding of bone healing.

Methods: Thirty-three atrophic nonunion (NU) patients that failed to demonstrate any radiographic improvement for 6 consecutive months were recruited for providing serum samples.

Decreased pool of mesenchymal stem cells is associated with altered chemokines serum levels in atrophic nonunion fractures.

Nonunion fractures can cause severe dysfunction and are often difficult to treat mainly due to a poor understanding of their physiopathology. Although many aspects of impaired fracture healing have been extensively studied, little is known about the cellular and molecular mechanisms leading to atrophic nonunion. Therefore, the aim of the present study was to assess the pools and biological functions of bone marrow-derived mesenchymal stem cells (hMSCs) and circulating endothelial progenitor cells (EPCs) in atrophic nonunion patients compared to healthy subjects, and the systemic levels of growth factors involved in the recruitment, proliferation and differentiation of these cells.

Dipeptidyl peptidase IV inhibition improves cardiorenal function in overpacing-induced heart failure.

Aims: Recent studies indicate that brain natriuretic peptide (BNP(1-32)) may be truncated into BNP(3-32) by dipeptidyl peptidase IV (DPP4) and that BNP(3-32) has reduced biological activities compared with BNP(1-32). We investigated if DPP4 contributes to the cardiorenal alterations and to the attenuated response to BNP seen in heart failure.

Methods And Results: Haemodynamic and renal assessment was performed in 12 pigs at baseline, 4 weeks after pacing-induced heart failure, and during BNP infusion.

Evaluation of the influence of age on pulmonary arterial pressure by use of right ventricular catheterization, pulsed-wave Doppler echocardiography, and pulsed-wave tissue Doppler imaging in healthy Beagles.

Objective: To assess the influence of age on pulmonary hemodynamics and hemorheological properties in healthy dogs.

Animals: 14 healthy Beagles.

Procedures: Dogs were placed in 2 age groups as follows: young dogs (or= 8 years old; 6).

Ventricular-arterial uncoupling in heart failure with preserved ejection fraction after myocardial infarction in dogs - invasive versus echocardiographic evaluation.

Background: Heart failure with preserved left ventricular ejection fraction and abnormal diastolic function is commonly observed after recovery from an acute myocardial infarction. The aim of this study was to investigate the physiopathology of heart failure with preserved ejection fraction in a model of healed myocardial infarction in dogs.

Methods: Echocardiography, levels of neurohormones and conductance catheter measurements of left ventricular pressure-volume relationships were obtained in 17 beagle dogs 2 months after a coronary artery ligation, and in 6 controls.

Cardiac insulin-like growth factor-1 and cyclins gene expression in canine models of ischemic or overpacing cardiomyopathy.

Background: Insulin-like growth factor-1 (IGF-1), transforming growth factor beta (TGFbeta) and cyclins are thought to play a role in myocardial hypertrophic response to insults. We investigated these signaling pathways in canine models of ischemic or overpacing-induced cardiomyopathy.

Methods: Echocardiographic recordings and myocardial sampling for measurements of gene expressions of IGF-1, its receptor (IGF-1R), TGFbeta and of cyclins A, B, D1, D2, D3 and E, were obtained in 8 dogs with a healed myocardial infarction, 8 dogs after 7 weeks of overpacing and in 7 healthy control dogs.

Cell therapy with autologous bone marrow mononuclear stem cells is associated with superior cardiac recovery compared with use of nonmodified mesenchymal stem cells in a canine model of chronic myocardial infarction.

Objective: Stem cell therapy can facilitate cardiac repair in infarcted myocardium, but the optimal cell type remains uncertain. We conducted a randomized, blind, and placebo-controlled comparison of autologous bone marrow mononuclear cell and mesenchymal stem cell therapy in a large-animal model of chronic myocardial infarction.

Methods: Eleven weeks after coronary ligation, 24 dogs received intramyocardial injections of mononuclear cells (227.

Ventricular ErbB2/ErbB4 activation and downstream signaling in pacing-induced heart failure.

The neuregulin-1 (NRG-1)/ErbB system has emerged as a cardioprotective system that becomes activated during myocardial stress, most convincingly shown in response to cardiotoxic chemotherapy. Direct evidence of increased ventricular ErbB receptor activity in heart failure unrelated to cardiotoxic drugs is, however, limited. We investigated changes in NRG-1 expression, ErbB receptor phosphorylation and downstream activation of intracellular ErbB targets during rapid pacing and progressive ventricular dysfunction in the dog.

Activin-A, transforming growth factor-beta, and myostatin signaling pathway in experimental dilated cardiomyopathy.

Background: The pathogenic mechanisms of dilated cardiomyopathy are still uncertain. A number of cytokines and growth factors participate in the remodeling process of the disease.

Methods: We investigated the cardiac myostatin, transforming growth factor (TGF)beta, and activin-A/Smad growth inhibitory signaling pathway in experimental dilated cardiomyopathy.

Pretreatment of adult bone marrow mesenchymal stem cells with cardiomyogenic growth factors and repair of the chronically infarcted myocardium.

The in vivo cardiac differentiation and functional effects of unmodified adult bone marrow mesenchymal stem cells (MSCs) after myocardial infarction (MI) is controversial. We postulated that ex vivo pretreatment of autologous MSCs using cardiomyogenic growth factors will lead to cardiomyogenic specification and will result in superior biological and functional effects on cardiac regeneration of chronically infarcted myocardium. We used a chronic dog MI model generated by ligation of the coronary artery (n = 30).

Effects of ramipril on renal function during progressive overpacing-induced heart failure in dogs.

Objective: To investigate the effects of preventive angiotensin converting enzyme inhibitor treatment with ramipril in dogs with progressively severe experimentally induced heart failure.

Animals: 20 dogs.

Procedures: Dogs were randomly allocated to receive no treatment (control) or ramipril (0.

Respiratory-related heart rate variability in progressive experimental heart failure.

Heart failure is associated with autonomic imbalance, and this can be evaluated by a spectral analysis of heart rate variability. However, the time course of low-frequency (LF) and high-frequency (HF) heart rate variability changes, and their functional correlates during progression of the disease are not exactly known. Progressive heart failure was induced in 16 beagle dogs over a 7-wk period by rapid ventricular pacing.

Early activation of cardiac and renal endothelin systems in experimental heart failure.

We investigated the time course of the expression of cardiac and renal endothelin systems in tachycardia-induced heart failure in dogs. Eleven beagles underwent rapid pacing at a progressively increased rate over a period of 5 wk, with a weekly clinical examination, echocardiography, measurement of circulating and urinary endothelin-1 (ET-1), and myocardial and renal tissue biopsies. Real-time quantitative PCR was used for determinations of tissue prepro-ET-1 (ppET-1), ET-1-converting enzyme (ECE-1), and ETA and ETB receptor mRNA.