Evaluating the therapeutic potential of one-carbon donors in nonalcoholic fatty liver disease.

Defect in one-carbon metabolism is one of the multiple underlying pathological pathways contributing to NAFLD pathogenesis. Hence, our study was designed to examine whether different one-carbon donors; betaine, choline, and folic acid would possess beneficial effects in NAFLD treatment. Rats were fed with high fat diet and NAFLD rats were orally treated with different doses of betaine or choline or folic acid for 28 days. All used one-carbon donors had dose-dependent ameliorating effects on NAFLD as they succeeded to reduce body and relative liver weights, serum lipids and liver enzymes. These were accompanied by decreasing hepatic fat accumulation and amending hepatic histological structure. They also improved serum and hepatic redox systems (total glutathione (tGSH), reduced GSH, oxidized GSSG, and GSH/GSSG ratio), hepatic S-adenosylmethionine/S-adenosyl homocysteine (SAM/SAH) ratio and increased hepatic global DNA methylation. There were some discrepancies in the dose and the extent of their effect, where folic acid showed the most prominent effects that could be mediated through the significant surge in hepatic SAM/SAH ratio and better efficient correction of one-carbon metabolism than the other donors. Thus, one-carbon donors can be strongly considered in NAFLD management and might influence the whole therapeutic approaches of fatty liver diseases.

Impact of chronic nicotine administration on bone mineral content in young and adult rats: a comparative study.

The aim of this study was to evaluate the effects of chronic nicotine administration on bone mineral homeostasis in rapidly growing young rats in comparison to effects in adult male rats. Two doses of nicotine (3 and 4.5mg/kg/day, as nicotine hydrogen tartrate) were used and rat treatment was continued for 6 months. In this study, all nicotine-treated rats weighed less than control rats and the effect was dose-dependent. Also, rats treated with nicotine had lower femoral wet weight and showed a significant reduction in femoral mid-shaft cortical width and femoral and lumbar vertebral ash weights. These effects were associated with a significant reduction of ash calcium and phosphorus contents of the femora and lumbar vertebrae. The bone mineral-lowering effects of nicotine were more severe in the lumbar vertebral spongy bone than in the femoral compact bone and these changes were more marked in adult rats than in young rats. An additional interesting observation was that the femora of young rats treated with nicotine were significantly shorter than those of control young rats. Also, the values of the femoral ash weight per unit length were significantly decreased in nicotine-treated adult rats but not in nicotine-treated young rats. Thus, these results show that nicotine-induced changes in bone vary with age. The clinical relevance of this study is that it may provide justification to insist that all people in general and the risky young group in particular should be warned against the hazards of the negative effects of nicotine on bone.

Changes of serum growth factors (IGF-I & IGFBP-2) and prediction of response to chemotherapy in patients with acute myeloid leukemia.

Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) possess mitogenic properties promoting cellular proliferation and inhibiting cellular apoptosis. Thus, IGF-system may play a role in tumor proliferation. In the present study, we investigated IGF-I and IGFBP-2 in patients with acute myeloid leukemia (AML) for their predictive value to identify patients who could be responsive to conventional induction chemotherapy. Serum levels of IGF-I and IGFBP-2 were measured (using commercial ELISA kits) in 22 patients with AML. Following treatment, patients were followed up 14 days after the induction cycle to determine if they achieved hematological remission or not. Accordingly, patients were divided into two groups: Responders (10 patients) and Non-Responders (12 patients). No significant difference was observed in IGF-1 between Responders and Non-Responders, neither before (79.26 +/- 4.568 pg/ml vs 72.225 +/- 3.62 pg/ml, respectively) nor after induction cycle (74.87 +/- 3.669 pg/ml vs 69.783 +/- 4.329 pg/ml, respectively). However, IGFBP-2 was significantly lower in Responders than in Non-Responders both at diagnosis (4250 +/- 155.099 pg/ml vs 6866.67 +/- 352.122 pg/ml, respectively) as well as after induction cycle of chemotherapy (4130 +/- 324.225 pg/ml vs 7150.00 +/- 265.290 pg/ml, respectively). It is concluded that, serum IGFBP-2 is considered as an independent factor that adds additional information for the prediction of relapse or treatment failure and patients with concentration > or = 4900 pg/ml at diagnosis are suspected to be nonresponders to conventional induction chemotherapy.