Eotaxin/CCL11 levels correlate with myocardial fibrosis and mast cell density in native and transplanted rat hearts

Myocardial fibrosis contributes to hemodynamic and cardiac functional alterations commonly observed posttransplantation. Cardiac mast cells (MC) have been linked to fibrosis in posttransplantation hearts. Eotaxin, which has been shown to be involved in fibrogenesis, has been demonstrated to be increased in production in cardiac macrophages. The aim of our study was to correlate myocardial fibrosis during heart transplant rejection in the rat with eotaxin/chemokine [c-c motif] ligand 11 (CCL11) expression, and with various subtypes of infiltrating cardiac MC, namely connective-type MC (CTMC) and mucosa-type MC (MMC).

Alveolar inflammation in cystic fibrosis

In infected lungs of the cystic fibrosis (CF) patients, opportunistic pathogens and mutated cystic fibrosis transmembrane conductance regulator protein (CFTR) contribute to chronic airway inflammation that is characterized by neutrophil/macrophage infiltration, cytokine release and ceramide accumulation. We sought to investigate CF lung inflammation in the alveoli.

Atorvastatin attenuates hepatic fibrosis in rats after bile duct ligation via decreased turnover of hepatic stellate cells

Activation of hepatic stellate cells (HSC) and transdifferentiation to myofibroblasts following liver injury is the main culprit for hepatic fibrosis. Myofibroblasts show increased proliferation, migration, contraction, and production of extracellular matrix (ECM). In vitro, HMG-CoA reductase inhibitors (statins) inhibit proliferation and induce apoptosis of myofibroblastic HSC. To investigate the antifibrotic effects of atorvastatin in vivo we used bile duct ligated rats (BDL).

Increased liver stiffness in alcoholic liver disease: differentiating fibrosis from steatohepatitis

To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).

Science to practice: Can diffusion-weighted MR imaging findings be used as biomarkers to monitor the progression of renal fibrosis?

In an experimental murine model of unilateral ureteral obstruction, Togao et al demonstrated that diffusion-weighted (DW) magnetic resonance (MR) imaging can depict and enable monitoring of abnormal changes in the progression of renal fibrosis; because these microstructural changes are complex and multifactorial, future studies focused on their specificity should be performed before they are applied in clinical trials.

Type of CFTR mutation determines risk of pancreatitis in patients with cystic fibrosis

Different mutations in the cystic fibrosis gene (CFTR) are associated with different functional status of the exocrine pancreas. We investigated whether CFTR genotypes determine the risk of pancreatitis in patients with cystic fibrosis (CF).

Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis: validation and reference data

In questionable cystic fibrosis (CF), mild or monosymptomatic phenotypes frequently cause diagnostic difficulties despite detailed algorithms. CF transmembrane conductance regulator (CFTR)-mediated ion transport can be studied ex vivo in rectal biopsies by intestinal current measurement (ICM).

A systematic review of medical interventions for oral submucous fibrosis and future research opportunities

Oral Diseases (2011) 17 (Suppl. 1), 42-57 Oral submucous fibrosis (OSF) is a chronic, insidious disease caused by areca nut use, and is associated with both significant morbidity (including pain and reduced oral opening) and an increased risk for malignancy. This systematic review explored and updated the current medical (i.e., non-surgical) interventions available for the management of OSF. Of the 27 published medical interventions, there were four randomized controlled trials. The overall quality of these randomized controlled studies was assessed using the GRADE approach and significant limitations that challenged the conclusions were found. However, this review was valuable in terms of identifying opportunities to provide recommendations for future research, in terms of the populations to research, the types of interventions needed, the types of outcomes to be measured, the study designs needed, and the infrastructure required to conduct studies. The next step is to initiate a pathway for a low-cost research plan leading to the development of a brief protocol for future clinical trials in this field, with an emphasis on conducting studies in regions of the world where OSF is prevalent.

A subset of metzincins and related genes constitutes a marker of human solid organ fibrosis

Metzincins and functionally related genes play important roles in extracellular matrix remodeling both in healthy and fibrotic conditions. We recently presented a transcriptomic classifier consisting of 19 metzincins and related genes (MARGS) discriminating biopsies from renal transplant patients with or without interstitial fibrosis/tubular atrophy (IF/TA) by virtue of gene expression measurement (Roedder et al., Am J Transplant 9:517-526, 2009). Here we demonstrate that the same algorithm has diagnostic value in non-transplant solid organ fibrosis. We used publically available microarray datasets of 325 human heart, liver, lung, kidney cortex, and pancreas microarray samples (265 with fibrosis, 60 healthy controls). Expression of nine commonly differentially expressed genes was confirmed by TaqMan low-density arrays (Applied Biosystems, USA) in 50 independent archival tissue specimens with matched histological diagnoses to microarray patients. In separate and in combined, integrated microarray data analyses of five datasets with 325 samples, the previously published MARGS classifier for renal post-transplant IF/TA had a mean AUC of 87% and 82%, respectively. These data demonstrate that the MARGS gene panel classifier not only discriminates IF/TA from normal renal transplant tissue, but also classifies solid organ fibrotic conditions of human pancreas, liver, heart, kidney, and lung tissue samples with high specificity and accuracy, suggesting that the MARGS classifier is a cross-platform, cross-organ classifier of fibrotic conditions of different etiologies when compared to normal tissue.