Losartan reduces trinitrobenzene sulphonic acid-induced colorectal fibrosis in rats.

Background: Intestinal fibrosis is a challenging clinical condition in several fibrostenosing enteropathies, particularly Crohn's disease. Currently, no effective preventive measures or medical therapies are available for intestinal fibrosis. Fibrosis, due to an abnormal accumulation of extracellular matrix proteins, is a chronic and progressive process mediated by cell⁄matrix⁄cytokine and growth factor interactions, but may be a reversible phenomenon.

Daily labile plasma iron as an indicator of chelator activity in Thalassaemia major patients.

Labile plasma iron (LPI), a non-transferrin-bound component of plasma iron detected in iron overload disorders is a potential source of cellular iron accumulation and ensuing oxidative damage. Periodic monitoring of LPI over a 24 h time-span was used to compare the ability of chelation to control daily LPI levels in 40 Thalassaemia major patients (9-11/group) who had been receiving one of three different chelation protocols for more than a year: Group I. deferrioxamine overnight, Group II.

Targeted disruption of Smad3 confers resistance to the development of dimethylnitrosamine-induced hepatic fibrosis in mice.

Background: Hepatic fibrosis is characterized by a progressive accumulation of fibrillar extracellular matrix (ECM) proteins including collagen, which occurs in most types of chronic liver diseases. Transforming growth factor-beta (TGF-beta)/Smad3 signalling plays a central role in tissue fibrogenesis, acting as a potent stimulus of ECM accumulation.

Aim: To evaluate the potential protective role of Smad3 deficiency in the pathogenesis of liver fibrosis induced by dimethylnitrosamine (DMN) in Smad3 null mice.

Anemia in beta-thalassemia patients targets hepatic hepcidin transcript levels independently of iron metabolism genes controlling hepcidin expression.

Thalassemia associates anemia and iron overload, two opposite stimuli regulating hepcidin gene expression. We characterized hepatic hepcidin expression in 10 thalassemia major and 13 thalassemia intermedia patients. Hepcidin mRNA levels were decreased in the thalassemia intermedia group which presented both lower hemoglobin and higher plasma soluble transferrin receptor levels.

Smad3 knock-out mice as a useful model to study intestinal fibrogenesis.

Aim: To evaluate the possible differences in morphology and immunohistochemical expression of CD3, transforming growth factor beta1 (TGF-beta1), Smad7, alpha-smooth muscle actin (alpha-Sma), and collagen types I-VII of small and large intestine in Smad3 null and wild-type mice.

Methods: Ten null and ten wild-type adult mice were sacrificed at 4 mo of age and the organs (esophagus, small and large bowel, ureters) were collected for histology (hematoxylin and eosin, Masson thrichrome, silver staining), morphometry and immunohistochemistry analysis. TGF-beta1 levels of intestinal tissue homogenates were assessed by ELISA.

Prevention of fibrosis in experimental colitis by captopril: the role of tgf-beta1.

Background & Aims: There is a body of evidence to suggest that the local activation of angiotensin II (ANG II) plays a pivotal role in fibrogenic response involving the kidney, heart, lung, pancreas and liver. In such conditions, fibrosis is mediated, at least partially, through ANG II induction of the cytokine transforming growth factor-beta1 (TGF-beta1). Both ANG II and TGF-beta1 also seem to be involved in intestinal fibrosis and stenosis, particularly in Crohn's disease.

The labile iron pool of hepatocytes in chronic and acute iron overload and chelator-induced iron deprivation.

Background: The cytosolic labile iron pool (LIP) is a transitory, catalytically active compartment that has been implicated in cell iron homeostasis and in metal-induced cytotoxicity.

Aims: We attempted to define LIP levels in living hepatocytes derived from chronic overloaded rats and from normal hepatocytes either acutely loaded with iron or depleted by chelation.

Methods: LIP levels were measured in living rat hepatocytes derived from normal and iron-fed rats.