Hepatic gene expression in morbidly obese women: implications for disease susceptibility.

The objective of this study was to determine the molecular bases of disordered hepatic function and disease susceptibility in obesity. We compared global gene expression in liver biopsies from morbidly obese (MO) women undergoing gastric bypass (GBP) surgery with that of women undergoing ventral hernia repair who had experienced massive weight loss (MWL) following prior GBP. Metabolic and hormonal profiles were examined in MO vs.

A hyperactive pulmonary vasculature in response to chronic mitral regurgitation.

A subset of patients with mitral valve disease has a marked rise in pulmonary vascular resistance (PVR) that is disproportionate to elevations in pulmonary venous pressure. Termed a "hyperactive" pulmonary vasculature, the elevation in PVR falls promptly and dramatically in response to mitral valve replacement. We report a 55-year-old man with progressive, exertional dyspnea of several months' duration who had signs of congestive heart failure (CHF) with moderate mitral valvular regurgitation and aortic stenosis by echocardiographic interrogation.

Toward a broader understanding of aldosterone in congestive heart failure.

Discovered some 50 years ago, aldosterone (ALDO) has come to be recognised as a mineralocorticoid hormone with well-known endocrine properties in epithelial cells that contribute to the pathophysiology of congestive heart failure. This includes Na+ resorption at the expense of K+ excretion in classic target tissues: kidneys, colon, sweat and salivary glands. Though less well known, Mg2+ excretion is likewise enhanced by ALDO, while adrenal ALDO secretion is regulated by extracellular Mg2+ ([Mg2+]o).

Aldosteronism and peripheral blood mononuclear cell activation: a neuroendocrine-immune interface.

Aldosteronism eventuates in a proinflammatory/fibrogenic vascular phenotype of the heart and systemic organs. It remains uncertain whether peripheral blood mononuclear cells (PBMCs) are activated before tissue invasion by monocytes/macrophages and lymphocytes, as is the case for responsible pathogenic mechanisms. Uninephrectomized rats treated for 4 weeks with dietary 1% NaCl and aldosterone (ALDOST, 0.

Aldosteronism: an immunostimulatory state precedes proinflammatory/fibrogenic cardiac phenotype.

Chronic inappropriate (relative to dietary Na+ intake) elevations in circulating aldosterone (ALDO), termed aldosteronism, are associated with remodeling of intramural arteries of the right and left heart. Lesions appear at week 4 of treatment with ALDO and 1% dietary NaCl in uninephrectomized rats (ALDOST) and include invading monocytes, macrophages and lymphocytes with intracellular evidence of oxidative and nitrosative stress, myofibroblasts, and perivascular fibrosis. In this study, we tested the hypothesis that an immunostimulatory state with activated circulating peripheral blood mononuclear cells (PBMCs) precedes this proinflammatory and profibrogenic cardiac phenotype and is initiated by reduction in the cytosolic free Mg2+ concentration ([Mg2+]i).