Changes of liver fat content and transaminases in obese children after 12-mo nutritional intervention

AIM: To assess a relationship between longitudinal changes in liver fat content and biochemical parameters in obese children after 1-year nutritional intervention.METHODS: Forty-six obese children, 21 males and 25 females, aged 6-14 years, underwent metabolic measurements, liver ultrasonography (US) and chemical-shift magnetic resonance imaging (MRI) examinations at baseline and after 1-year nutritional intervention. A child was defined obese if her/his body mass index (BMI) was above the age- and sex-adjusted BMI Cole’s curve passing through the cut-off of 30 kg/m² at 18 years. BMI Z scores were calculated and adjusted for age and gender by using the Cole’s LMS-method and Italian reference data. Biochemistry included serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Abdominal US and chemical-shift MRI were performed according to a randomized sequence. The same radiologist performed US by a GE Logiq 9 (General Electric Healthcare Medical Systems, Milwaukee, WI, United States) using a 3.5-MHz convex array transducer. Liver echogenicity was evaluated independently on videotape by 3 radiologists unaware of the child and MRI outcomes, and a consensus was established. Another experienced radiologist, unaware of the child and US data, performed the abdominal chemical-shift MRI with a 1-t system NT-Intera (Philips Medical Systems, Best, The Netherlands) and a phased-array coil. Liver fat fraction (FF) on MRI was judged elevated when greater than 9%. A FF > 18% was considered expressing more severe cases of fatty liver according to Fishbein. A nutritional-behavioral intervention was recommended to promote a normocaloric balanced diet and active lifestyle based on the Italian guidelines for treatment of childhood obesity.RESULTS: Compared to baseline, at the end of intervention children showed lower intakes of energy (mean ± SD: 2549 ± 1238 Kcal vs 1770 ± 622 Kcal, P < 0.0001), total fat (90 ± 47 g vs 52 ± 23 g, P < 0.0001), carbohydrates (356 ± 174 g vs 241 ± 111 g, P = 0.001), and protein (99 ± 48 g vs 75 ± 23 g, P = 0.006) intakes. Prevalence of FF ≥ 9% declined from 34.8% to 8.7% (P < 0.01), with a mean reduction of 7.8% (95%CI: 5.0-10.6). At baseline, FF was associated with liver biochemical parameters (maximum P < 0.001). At the end of the intervention association was found with AST (P = 0.017). Change of FF was associated with change in AST (P = 0.027) and ALT (P = 0.024). Rate of increased liver echogenicity declined from 45.6% to 21.7% (P < 0.0001). Liver echogenicity was associated with ALT at baseline only (P < 0.001). An age- and sex- adjusted multiple regression analysis showed that FF change was independently associated with change in serum AST (adjusted regression coefficient 0.348, P = 0.048).CONCLUSION: The results suggest that in obese children longitudinal changes in liver fat content based on MRI may be associated with change in serum transaminases suggesting novelty in monitoring nonalcoholic fatty liver disease.     

Efficacy of combined antiviral therapy with lamivudine and tenofovir in a liver transplanted girl with de novo hepatitis B virus infection

The management of de novo hepatitis B (HBV) infection in children after liver transplantation is not well defined. Because this infection may induce severe liver disease in the graft liver, an efficient antiviral therapy is desirable. Here, we describe the favorable viral outcome observed in a liver transplanted girl with de novo HBV infection following combination therapy with lamivudine and tenofovir.     

Effects of intracerebroventricular injection of dynorphin, leumorphin and alpha neo-endorphin on operant feeding in pigs

Young pigs, which are useful experimental animals for biomedical research, were prepared with lateral intracerebroventricular (ICV) cannulae and housed individually in cages fitted with operant panels, with food and water ad lib. ICV injection of 200 micrograms of dynorphin A 1-17 or 1-13 resulted in a significant meal commencing within 2-5 min. Shorter fragments of dynorphin (1-10, 1-9, 1-8) were ineffective at inducing feeding as was dynorphin B (rimorphin). In the same situation, leumorphin and alpha neo-endorphin (200 micrograms) elicited significant feeding but beta neo-endorphin did not. Dynorphin 1-17 or 1-13, administered 5 min before feeding started, increased meal size when pigs were fed after 4-h deprivation. Naloxone ICV (0.4 mg) significantly reduced food intake in pigs feeding after 4-h deprivation and its main effect was in the second half of the meal. Naloxone also abolished the effect of ICV dynorphin. It is concluded that dynorphin and related endogenous opioids are involved in the regulation of food intake in pigs.     

High-performance liquid chromatographic assay for the determination of the novel taxane derivative IDN5109 in mouse plasma

An HPLC assay was developed to determine the paclitaxel analogue 13-(N-tert.-butoxycarbonyl-beta-isobutylisoserinyl)-14-hydroxyb accatin-1,14-carbonate (IDN5109) and its epimer in mouse plasma. The method involves solid-phase extraction on cyano cartridges (recovery >75%), HPLC separation on symmetry shield column, a mobile phase of NaH2PO4 (10 mM) pH 5.2, acetonitrile (47:53) and detection at 227 nm. Retention times of IDN5109, its epiform and internal standard were 15, 24 and 25.5 min, respectively. The assay was linear from 0.10 to 10 microg/ml (r2 = 0.999), with a C.V. <5% and accuracy in the range of 95-107%. LOQ was 50 ng/ml for both compounds. Using this method IDN5109 pharmacokinetic was determined in mice.     

Dopaminergic D2 receptor activation modulates FGF-2 gene expression in rat prefrontal cortex and hippocampus

We have investigated the role of dopaminergic receptors in modulation of basic fibroblast growth factor (FGF-2) expression in rat prefrontal cortex and hippocampus, two brain regions important for cognition. We found that FGF-2 expression is upregulated by quinpirole, a D2 agonist, in prefrontal cortex and to a lesser extent in hippocampus. This modulation was specific for dopamine D2 receptors because no effect was observed when the dopamine D1 and D3 agonists, SKF38393 and 7-OH-DPAT, respectively, were administered. Our findings show that activation of dopaminergic D2 receptors modulates FGF-2 expression in rat prefrontal cortex and hippocampus. Our data highlight the complex modulation of FGF-2 expression in limbic areas pointing to this trophic molecule as a putative target of drugs used against acute and chronic neurodegenerative diseases such as Parkinson's disease.     

Association between serum values of C-reactive protein and cytokine production in whole blood of patients with type 2 diabetes

Diabetes mellitus accelerates atherosclerotic processes, and it is known that inflammation plays a key role in atherosclerosis. The aim of the present study was to evaluate in patients with Type 2 diabetes whether serum levels of CRP (C-reactive protein) are associated with cytokine production in whole blood. A total of 89 outpatients with Type 2 diabetes were enrolled, and blood pressure, body mass index, fasting blood glucose, glycated haemoglobin, cholesterol, triacylglycerols (triglycerides) and hs-CRP (high-sensitivity CRP) were measured. IL-6 (interleukin-6), IL-1beta (interleukin-1beta) and TNF-alpha (tumour necrosis factor-alpha) were measured before and after 24 h of incubation of whole blood with LPS (lipopolysaccharide) or saline. The basal values of IL-1beta, IL-6 and TNF-alpha were low and were not significantly related to hs-CRP levels. A univariate analysis showed that the level of IL-1beta and IL-6, obtained after 24 h of incubation of whole blood with LPS, increased significantly with increasing levels of hs-CRP and, after adjusting for potential confounders, IL-1beta still remained statistically significant. In our sample of patients with Type 2 diabetes, there was no association between serum hs-CRP levels and basal levels of IL-6, IL-1beta and TNF-alpha. Conversely, a significant association was observed between serum hs-CRP levels and IL-1beta and IL-6 production after 24 h of incubation of whole blood with LPS. In conclusion, our data suggest that patients with Type 2 diabetes and high hs-CRP levels may have an enhanced reactivity in response to specific stimuli that produce different interleukins, with possible implications in inflammatory atherosclerotic processes.     

Sleep pressure correlates of cognitive and behavioral morbidity in snoring children

STUDY OBJECTIVES: Sleep architecture is not preserved in children with sleep-disordered breathing but, rather, undergoes dynamic changes that exhibit significant correlation with severity of sleep-disordered breathing. A sleep pressure score (SPS) with a cutoff value of 0.25 was derived from analysis of a large cohort of snoring and control children. Neurocognitive batteries were applied to examine the potential effect of SPS. DESIGN: Prospective study. PARTICIPANTS: 199 children who underwent a battery of neurobehavioral tests following an overnight sleep study were assigned to SPSHigh (> or = 0.25) or SPSLow (< 0.25) groups, and their neurocognitive performances were compared. RESULTS: Children in the SPSHigh group were significantly more likely to have deficits in memory, language abilities, verbal abilities, and some visuospatial functions than were children in the SPSLow group. These effects remained highly significant after adjusting for confounding variables and exhibited small to moderate effect sizes. CONCLUSIONS: We conclude that a sleep-pressure numerical factor derived from the overnight polysomnogram in snoring children is associated with deficits in neurobehavioral daytime functions that is independent of respiratory disturbance and hypoxemia and suggests a significant role for disturbed sleep homeostasis in pediatric sleep-disordered breathing.