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Background: Innate immune system participates actively into inflammatory processes, with immune cells and liver secreting a number of immune peptides. Among them, both soluble CD14 receptor (sCD14) and human neutrophil alpha-defensins (HNDs) may represent serum markers of necro-inflammation in obese patients with non-alcoholic fatty liver disease. Methods: To verify this hypothesis, we investigated changes in circulating levels of sCD14 and HNDs in 11 severely obese young women following surgery-induced weight loss (bilio-pancreatic diversion). Patients were evaluated before surgery and 2 years later, with NAS score evaluated on liver biopsies and whole body glucose uptake ( M value) by euglycemic hyperinsulinemic clamp. Results: NAS score improved in nine patients [median NAS score in the whole sample, 6 (5-6) vs. 3 (3-4), p = 0.016]. Serum concentrations of HNDs decreased significantly in all ( p = 0.016), whilst sCD14 increased only in the nine women who showed the amelioration of the NAS score [2.4 (1.7-2.6) vs. 2.6 (2.3-3.3) μg/ml, p = 0.001]. NAS score and HNDs correlated significantly both before ( r = 0.671, p = 0.02) and after weight loss ( r = 0.683, p = 0.029), NAS score and sCD14 only before surgery ( r = 0.605, p = 0.04). The M value increased in all patients [2.67 (1.99-3.01) vs. 6.89 (6.35-7.32) mg kg min; p = 0.01], but independently of NAS score changes. Conclusions: Changes in levels of HNDs and sCD14 accompany those in hepatic necro-inflammation due to surgical-induced weight loss. Further studies are needed to verify any causative role of these peptides in non-alcoholic steatohepatitis. [ABSTRACT FROM AUTHOR]

This article looks at pediatric Non Alcoholic Fatty Liver Disease (NAFLD) among co-morbidities. It reviews the concepts about pediatric NAFLD, its pathogenesis, diagnosis and treatment, with particular regard to lifestyle and food habits. It also indicates the possible causes of pediatric NAFLD. It highlights the association of NAFLD with abdominal obesity, insulin resistance and features of metabolic syndrome.

Permanent neonatal diabetes mellitus (PNDM) is a rare condition characterized by severe hyperglycemia constantly requiring insulin treatment from its onset. Complete deficiency of glucokinase ( GCK) can cause PNDM; however, the genetic etiology is unknown in most PNDM patients. Recently, heterozygous activating mutations of KCNJ11, encoding Kir6.2, the pore forming subunit of the ATP-dependent potassium (KATP) channel of the pancreatic β-cell, were found in patients with PNDM. Closure of the KATP channel exerts a pivotal role in insulin secretion by modifying the resting membrane potential that leads to insulin exocytosis. We screened the KCNJ11 gene in 12 Italian patients with PNDM (onset within 3 months from birth) and in six patients with non-autoimmune, insulin-requiring diabetes diagnosed during the first year of life. Five different heterozygous mutations were identified: c.149G>C (p.R50P), c.175G>A (p.V59M), c.509A>G (p.K170R), c.510G>C (p.K170N), and c.601C>T (p.R201C) in eight patients with diabetes diagnosed between day 3 and 182. Mutations at Arg50 and Lys170 residues are novel. Four patients also presented with motor and/or developmental delay as previously reported. We conclude that KCNJ11 mutations are a common cause of PNDM either in isolation or associated with developmental delay. Permanent diabetes of non autoimmune origin can present up to 6 months from birth in individuals with KCNJ11 and EIF2AK3 mutations. Therefore, we suggest that the acronym PNDM be replaced with the more comprehensive permanent diabetes mellitus of infancy (PDMI), linking it to the gene product (e.g., GCK-PDMI, KCNJ11-PDMI) to avoid confusion between patients with early-onset, autoimmune type 1 diabetes. Hum Mutat 25:22-27, 2005. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]