Normal serum alanine aminotransferase activity in uncomplicated obesity

AIM: To evaluate serum alanine aminotransferase (ALT) activity in a well-characterized group of uncomplicated obese subjects and its correlation with insulin resistance, plasma adiponectin, and leptin concentrations. METHODS: One hundred and five uncomplicated obese subjects (87 women, 18 men, age 34.3±9.6 years, BMI 39.9±8.3 kg/m2)were studied. Serum ALT activity was evaluated. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp (M index) and fasting insulin. Plasma leptin and adiponectin levels were also measured. RESULTS: Serum ALT concentration in the whole group of uncomplicated obese subjects was 17.73±6.33 U/L with none of the subjects presenting ALT levels greater than 43 U/L and only 9 (11%) women and 3 (19%) men showed ALT levels >19 and >30 U/L for women and men, respectively. No significant difference was detected in serum ALT levels between severe obese subjects (BMI >40 kg/m2) and those with BMI <40 kg/m2 (18.63±6.25 vs 17.26±6.02 U/L). ALT was significantly correlated with fasting insulin (r=0.485, P= 0.02) and triglycerides (r= 0.358, P=0.03). CONCLUSION: Serum ALT activity is practically normal in uncomplicated obese subjects, independently of their obesity degree. These findings suggest the role of obesityrelated comorbidities and not of BMI as main risk factors for elevated ALT levels in obese subjects.     

Signaling pathways of D3-phosphoinositide-binding kinases in T cells and their regulation by PTEN

Phosphoinositide 3-kinases (PI3Ks) phosphorylate the D3 position of the myo -inositol ring of inositol phospholipids, producing, amongst others, phosphatidylinositol-(3,4,5)-trisphosphate. This activity is opposed by the lipid phosphatase PTEN, which catalyzes the removal of this phosphate. Stimulation of PI3Ks is elicited by engagement of receptors for antigen, cytokines and chemokines, and by co-stimulatory molecules. Kinases and other enzymes containing pleckstrin homology domains are activated by binding to these phospholipids, affecting a variety of cellular processes that control lymphocyte function, including cell survival, proliferation, chemotaxis and cytoskeletal reorganization. This review highlights the signaling pathways of these kinases and other enzymes in T cells, their biological effects, and their regulation by PTEN.     

Lipid body mobilization in the ExoU-induced release of inflammatory mediators by airway epithelial cells

This report addressed the question whether ExoU stimulation of airway epithelial cells may contribute to the inflammatory response detected in the course of Pseudomonas aeruginosa respiratory infections. Infection with PA103 P. aeruginosa elicited a potent release of IL-6 and IL-8, as well as of arachidonic acid (AA) and PGE(2) that was reduced by the bacterial treatment with MAFP, a cPLA(2) inhibitor. Airway cells from the BEAS-2B line and in primary culture were shown to be enriched in lipid bodies (LBs), that are cytoplasmic domains implicated in AA transformation into eicosanoids. However, cells infected with PA103 and with a mutant deficient in exoU but complemented with a functional gene exhibited reduced contents of LBs, and this reduction was inhibited by MAFP. FACS analysis showed that the decrease in the LB content correlated with the presence of intracellular PGE(2). Also, in PA103-infected cells, PGE(2) was immunolocalized in LBs, suggesting that the reduction in the cell content of the organelles was due to consumption of their glycerolipids, resulting in local synthesis of the prostanoid. In conclusion, we showed the ExoU ability to induce airway epithelial cells to overproduce PGE(2) and we speculate that LB may represent intracellular loci involved in ExoU-induced eicosanoid synthesis.     

Surface Roughness Analysis and Prediction with an Artificial Neural Network Model for Dry Milling of Co–Cr Biomedical Alloys

The aim of this paper is to conduct an experimental study in order to obtain a roughness (Ra) prediction model for dry end-milling (with an AlTiCrSiN PVD-coated tool) of the Co–28Cr–6Mo and Co–20Cr–15W–10Ni biomedical alloys, a model that can contribute to more quickly obtaining the desired surface quality and shortening the manufacturing process time. An experimental plan based on the central composite design method was adopted to determine the influence of the axial depth of cut, feed per tooth and cutting speed process parameters (input variables) on the Ra surface roughness (response variable) which was recorded after machining for both alloys. To develop the prediction models, statistical techniques were used first and three prediction equations were obtained for each alloy, the best results being achieved using response surface methodology. However, for obtaining a higher accuracy of prediction, ANN models were developed with the help of an application made in LabView for roughness (Ra) prediction. The primary results of this research consist of the Co–28Cr–6Mo and Co–20Cr–15W–10Ni prediction models and the developed application. The modeling results show that the ANN model can predict the surface roughness with high accuracy for the considered Co–Cr alloys.     

Recombinant IFN-γ abrogates allograft tolerance induced by donor-specific blood transfusion by restoring alloantibody production

Donor-specific tolerance to heart allograft was induced in adult Lewis rats by pregraft donor-specific blood transfusion (DST). We previously showed that this tolerant state is characterized by a dramatic inhibition of T cell and macrophage activation. In addition, tolerant animals could not mount an efficient anti-donor humoral response whereas transfer of sera from rejecting animals triggered rejection in tolerant animals. This tolerance can be abrogated by daily post-graft administration of recombinant IFN-γ (rIFN-γ). To elucidate the mechanisms of action of rIFN-γ, T cell, macrophage and B cell functions were assessed in allograft recipients. IFN-γ did not restore the expression of Th1-related cytokine mRNA or the activated macrophage product inducible nitric oxide synthase in allografts. Importantly, rIFN-γ treatment promptly restored the anti-donor humoral response in DST-treated recipients. We conclude that rIFN-γ treatment in DST-treated allograft recipients cannot reverse the unresponsive state of Th1 cells and macrophages infiltrating the graft, but can provide B cell help for IgG alloantibody production which is lacking in these animals.     

Relationship between plasma phospholipid polyunsaturated fatty acid composition and bone disease in renal transplantation

To investigate the relationship between polyunsaturated fatty acid (PUFA) and bone metabolism in renal transplant patients, plasma phospholipid (PP) PUFA levels, biochemical markers of bone turnover and bone mineral density (BMD) were determined in 22 recipients of a first renal allograft at baseline and after a mean 24.4 month follow-up. A significant increase in PP n-3 PUFA content, in the [n-3 PUFA/ arachidonic acid] ratio and in BMD values was observed, as well as a close correlation between the increase in PP n-3 PUFA content and femoral neck BMD. Multivariate regression analysis showed that BMD improvement was positively related to PP n-3 PUFA variation and baseline PP eicosapentaenoic acid levels, and negatively to PP arachidonic acid modification. Tacrolimus- versus cyclosporine-treated patients demonstrated a significant increase in femoral neck BMD and PP n-3 PUFA content. This is the first longitudinal study showing a link between PP-PUFA composition and bone disease in renal transplantation.