Deletion of SOCS2 Reduces Post-Colitis Fibrosis via Alteration of the TGFß Pathway.

Inflammatory bowel disease (IBD) is an immunologically mediated chronic intestinal disorder. Growth hormone (GH) administration enhances mucosal repair and decreases intestinal fibrosis in patients with IBD. In the present study, we investigated the effect of cellular sensitivity to GH via suppressor of cytokine signaling 2 (SOCS2) deletion on colitis and recovery. To induce colitis, wild type and SOCS2 knockout (SOCS2-/-) mice were treated with 3% dextran sodium sulphate (DSS), followed by a recovery period. SOCS2-/- mice showed higher disease activity during colitis with increased mRNA expression of the pro-inflammatory cytokines nitric oxide synthase 2 (NOS2) and interleukin 1 ß (IL1-ß). At recovery time point, SOCS2-/- showed better recovery with less fibrosis measured by levels of α-SMA and collagen deposition. Protein and mRNA expressions of transforming growth factor beta ß1 (TGF-ß1) receptors were significantly lower in SOCS2-/- mice compared to wild-type littermates. Using an in vivo bromodeoxyuridine (BrdU) proliferation assay, SOCS2-/- mice showed higher intestinal epithelial proliferation compared to wild-type mice. Our results demonstrated that deletion of the SOCS2 protein results in higher growth hormone sensitivity associated with higher pro-inflammatory signaling; however, it resulted in less tissue damage with less fibrotic lesions and higher epithelial proliferation, which are markers of GH-protective effects in IBD. This suggests a pleiotropic effect of SOCS2 and multiple cellular targets. Further study is required to study role of SOCS2 in regulation of TGFß-mothers against the decapentaplegic homolog (Smad) pathway.

Detection of Inborn Errors of Metabolism using Tandem Mass Spectrometry among High-risk Omani Patients.

OBJECTIVE: This is a report on the types and patterns of inborn errors of metabolism (IEMs) of amino acids, organic acids and fatty acids oxidation detected by Tandem Mass Spectrometry for a period of 10 years (1998-2008) at Sultan Qaboos University Hospital (SQUH), the major centre for diagnosis and management of IEM in Oman. METHODS: Tandem mass spectrometry (MS/MS) was used in the initial screening and diagnosis of IEMs in high risk neonatal and pediatric populations. RESULTS: Out of 1100 patients investigated, 119 were detected positive for IEM by MS/MS spectrometry. Twenty six different metabolic diseases were detected. Patients were categorized into three major groups: a) 54 with amino acids and urea cycle disorders, b) 35 with organic acid disorders, and c) 30 with fatty acid oxidation disorders. The commonest conditions encountered were maple syrup urine disease (MSUD), phenylketonuria (PKU), propionic and isovaleric acidurias, as well as HMG-CoA lyase deficiency and glutaric aciduria type II (GA-II). Most of these IEMs were over-represented in babies born to consanguineous parents, which is consistent with the recessive autosomal inheritance. CONCLUSION: This study shows that various types of IEMs, reported elsewhere, were also prevalent in Oman, but the pattern of prevalence and distribution is different. The situation, therefore, warrants the development of a nationwide screening and prevention program.