Predictive capacity of different bioelectrical impedance analysis devices,with and without protocol,in the evaluation of adolescents

Objectivethis study was performed to determine the predictive capacity of four different bioelectrical impedance analysis (BIA) devices in the assessment of adolescents, with and without a protocol.Methodsa cross-sectional study was performed with 215 adolescents aged 10 to 14 years, of both genders, evaluated through anthropometry and body composition by dual energy X-ray absorptiometry (DXA) and by four different BIA devices, with and without a protocol. The following tests were used: Kolmogorov-Smirnov's, chi-squared, Student's t or Mann-Whitney's, Kruskal-Wallis's, Wilcoxon's, and kappa index. The ROC curves were constructed and the sensitivity, specificity, and positive and negative predictive values were calculated.Resultsof the 215 adolescents, 44.2% had excessive body fat. The tetrapolar BIA device equipped with eight tactile electrodes showed more sensitivity and results that were closer to those obtained by DXA (area under the ROC curve [AUC] = 0.964 with protocol and AUC = 0.973 without protocol, p < 0.001), as well as greater agreement (k = 0.67 with protocol and k = 0.63 without protocol, p < 0.001). The evaluation without protocol was similar to that by DXA in most investigated situations (p > 0.05).ConclusionBIA is capable of predicting alterations in adolescents’ body composition. When it is impossible to perform the assessment with a protocol, its results may be useful in population studies.     

A new nanoemulsion formulation improves antileishmanial activity and reduces toxicity of amphotericin B

This work aimed to optimise a new nanoemulsion (NE) formulation loaded with Amphotericin B (AmB) and to evaluate its in vivo antileishmanial activity and in vitro haemolytic toxicity. The influence of gradual increases in pressure, using a high-pressure homogeniser, was evaluated. The NE was characterised for droplet size, polydispersity index, zeta potential and encapsulation efficiency (EE). For antileishmanial activity studies, AmB-NE was administered intravenously in mice infected by Leishmania infantum chagasi, which causes Visceral Leishmaniasis (VL). When the NE was submitted to gradual increases in pressure, the PI values and droplet size decreased. The droplet size (～145?nm) was lower than that obtained in previous studies. The zeta potential was negative and the EE was almost 100%. The haemolytic toxicity, evaluated on human red blood cells, for AmB-loaded NE was lower than that observed for the conventional AmB (C-AmB). C-AmB at 2?mg/kg was very toxic. In contrast, administration of the AmB-loaded NE, at same dose, did not result in any sign of acute toxicity, promoting a significant reduction in parasite burden as compared to the C-AmB. These findings suggest that this new AmB-loaded NE constitutes an attractive alternative for the treatment of VL due to improved efficacy and lower toxicity.     

Influence of VKORC1 gene polymorphisms on the effect of oral vitamin K supplementation in over-anticoagulated patients

Significant inter-individual variability on the effect of vitamin K to reverse overanticoagulation has been identified. Genetic polymorphisms of the vitamin K epoxide reductase complex subunit 1 (VKORC1) gene might explain in part this variability. The objective of this study was to evaluate the influence of VKORC1 ?1639G>A and 3730G>A polymorphisms on the effect of oral vitamin K supplementation in overanticoagulated patients. We performed an interventional trial of oral vitamin K supplementation in over-anticoagulated outpatients (international normalized ratio [INR] ≥ 4). Subjects received vitamin K (2.5–5.0 mg) according to baseline INR and were genotyped by real time polymerase chain reaction (PCR). INR values were determined at 3, 6, 24 and 72 h after supplementation. We evaluated 33 outpatients, 61 % were males, with a mean age of 62 ± 12 years old. There was a significant decrease in INR values over time for both polymorphisms after oral vitamin K. At 3 h after supplementation, patients carrying the G allele for the ?1639G>A polymorphism had a greater decrease in INR values compared to AA patients (p < 0.05 for difference among groups; p < 0.001 for time variation; p = 0.001 for time × group interaction), with differences of ?1.01 for GG versus AA (p = 0.003) and ?0.84 for GA versus AA (p = 0.024). Mean INR value at 24 h was 1.9 ± 0.6 and at 72 h was 2.1 ± 0.7, with no differences among genotypes. No significant interaction was identified between the 3730G>A polymorphism and vitamin K supplementation. Our study indicated that the VKORC1 ?1639G>A polymorphism plays a role in the response to acute vitamin K supplementation in over-anticoagulated patients, with faster decrease of INR value in patients carrying the G allele.     

Economic assessment of different administration modes for total parenteral nutrition

AIM: Total parenteral nutrition can be administered with separate bottles or complete admixtures prepared by commercial firms, the hospital pharmacy, or hospital subcontractors. The aim of this study was to compare overall cost of total parenteral nutrition using different administration modes. METHODS: Overall production costs of hospital parenteral admixtures were calculated from five expenditures (raw materials, consumable items, annual depreciation, control costs, staff costs). Cost for the other administration modes were evaluated for an identical formula. Time spent by nurses and the cost of connecting material was estimated to determine the overall cost for one day of parenteral nutrition. RESULTS: Total cost was 46.04 euros/day with separate bottles, 50.61 euros/day for hospital preparations, 65.41 and 72.87 euros/day for industrial preparations and 82.02 euros/day for formulations prepared by subcontractors. CONCLUSION: Hospital preparations offer, for minimal outlay, an alternative for parenteral nutrition of much higher quality than the separate bottles method.     

CD95 engagement induces disseminated endothelial cell apoptosis in vivo: immunopathologic implications

Fas (CD95) is a death receptor involved in apoptosis induction on engagement by Fas ligand (CD95L). Although CD95L-mediated apoptosis has been proposed as a pathogenic mechanism in a wide range of diseases, including graft-versus-host disease, systemic CD95 engagement in mice by agonistic CD95-specific antibodies or by soluble multimeric CD95L (smCD95L), though lethal, has been reported to cause apoptosis only in a limited range of cell types, that is, hepatocytes, hepatic sinusoidal endothelial cells, and lymphocytes. Another member of the tumor necrosis factor (TNF)/CD95L family, TNF-alpha, induces disseminated vascular endothelial cell apoptosis, which precedes apoptosis of other cell types and lethal multiorgan failure. Here we show that systemic CD95 engagement in vivo by agonistic CD95-specific antibody or smCD95L causes rapid, extensive, and disseminated endothelial cell apoptosis throughout the body, by a mechanism that does not depend on TNF-alpha. Disseminated endothelial cell apoptosis was also the first detectable lesion in a murine model of acute tissue damage induced by systemic transfer of allogeneic lymphocytes and did not occur when allogeneic lymphocytes were from CD95L-defective mice. Both vascular and additional tissue lesions induced by agonistic CD95-specific antibody, smCD95L, or allogeneic lymphocytes were prevented by treatment with an inhibitor of caspase-8, the upstream caspase coupled to CD95 death signaling. Vascular lesions are likely to play an important role in the pathogenesis of allogeneic immune responses and of other diseases involving circulating CD95L-expressing cells or smCD95L, and the prevention of CD95-mediated death signaling in endothelial cells may have therapeutic implications in these diseases.     

Host defense and inflammatory gene polymorphisms are associated with outcomes after HLA-identical sibling bone marrow transplantation

We made the hypothesis that donor and recipient gene polymorphisms that drive the host response to microorganisms could be associated with infections after bone marrow transplantation (BMT). HLA-identical BMT was performed for patients with acute (n = 39) or chronic leukemia (n = 68). Genotyping was performed in 107 D/R DNA pairs for gene polymorphisms of cytokines (tumor necrosis factor-alpha [TNF-alpha] and TNF-beta, interleukin-1 receptor antagonist [IL-1Ra], IL-6, and IL-10), adhesion molecules (CD31 and CD54), Fcgammareceptors (FcgammaRIIa, IIIa, IIIb), mannose-binding lectin (MBL), and myeloperoxidase (MPO). First infection (overall) and first episodes of bacterial, viral, or invasive fungal infection were studied retrospectively for 180 days after BMT. Univariate and multivariate analyses, using death as a competing event, were performed to study risk factors. In multivariate analysis, first overall infections were increased in patients with the FcgammaRIIa R-131 genotype (hazard ratio [HR] = 1.92; P =.04), and severe bacterial infections were increased when the MPO donor genotype was AG or AA (HR = 2.16; P =.03). Viral and invasive fungal infections were not influenced by any genetic factor studied. Interestingly, we also found that (1) time to neutrophil recovery was shorter when donors were FcgammaRIIIb HNA-1a/HNA-1b (HR = 1.77; P =.002); (2) donor IL-1Ra (absence of IL-1RN*2) increased the risk for acute graft-versus-host disease (GVHD) (II-IV) (HR = 2.17; P =.017); and (3) recipient IL-10 (GG) and IL-1Ra genotypes increased the risk for chronic GVHD (P =.03 and P =.03, respectively). Finally, 180-day transplantation-related mortality rates were increased when donors were FcgammaRIIIb HNA-1a/HNA-1a or HNA-1b/HNA-1b (HR = 2.57; P =.05) and donor MPO genotype was AA (HR = 5.14; P =.004). In conclusion, donor and recipient gene polymorphisms are informative genetic risk factors for selecting donor/recipient pairs and could help in the understanding of mechanisms involved in host defenses of BM transplant recipients.