Assessing the Influence of Different Comorbidities Indexes on the Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in a Developing Country

Although the application of Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) has enabled better prediction of transplant-related mortality (TRM) in allogeneic hematopoietic stem cell transplants (AHSCT), data from developing countries are scarce. This study prospectively evaluated the HCT-CI and the Adult Comorbidity Evaluation (ACE-27), in its original and in a modified version, as predictors of post-transplant complications in adults undergoing a first related or unrelated AHSCT in Brazil. Both bone marrow (BM) and peripheral blood stem cells (PBSC) as graft sources were included. We analyzed the cumulative incidence of granulocyte and platelet recovery, sinusoidal obstructive syndrome, acute and chronic graft-versus-host disease, relapse and transplant-related mortality, and rates of event-free survival and overall survival. Ninety-nine patients were assessed. Median age was 38 years (18–65 years); HCT-CI ≥ 3 accounted for only 8% of cases; hematologic malignancies comprised 75.8% of the indications for AHSCT. There was no association between the HCT-CI or the original or modified ACE-27 with TRM or any other studied outcomes after AHSCT. These results show that, in the population studied, none of the comorbidity indexes seem to be associated with AHSCT outcomes. A significantly low frequency of high-risk (HCT-CI ≥ 3) in this Brazilian population might justify these results.     

Endurance Training Inhibits Insulin Clearance and IDE Expression in Swiss Mice

Introduction

Endurance training improves peripheral insulin sensitivity in the liver and the skeletal muscle, but the mechanism for this effect is poorly understood. Recently, it was proposed that insulin clearance plays a major role in both glucose homeostasis and insulin sensitivity. Therefore, our goal was to determine the mechanism by which endurance training improves insulin sensitivity and how it regulates insulin clearance in mice.

Methods

Mice were treadmill-trained for 4 weeks at 70–80% of maximal oxygen consumption (VO₂ max) for 60 min, 5 days a week. The glucose tolerance and the insulin resistance were determined using an IPGTT and an IPITT, respectively, and the insulin decay rate was calculated from the insulin clearance. Protein expression and phosphorylation in the liver and the skeletal muscle were ascertained by Western blot.

Results

Trained mice exhibited an increased VO₂ max, time to exhaustion, glucose tolerance and insulin sensitivity. They had smaller fat pads and lower plasma concentrations of insulin and glucose. Endurance training inhibited insulin clearance and reduced expression of IDE in the liver, while also inhibiting insulin secretion by pancreatic islets. There was increased phosphorylation of both the canonical (IR-AKT) and the non-canonical (CaMKII-AMPK-ACC) insulin pathways in the liver of trained mice, whereas only the CaMKII-AMPK pathway was increased in the skeletal muscle.

Conclusion

Endurance training improved glucose homeostasis not only by increasing peripheral insulin sensitivity but also by decreasing insulin clearance and reducing IDE expression in the liver.     

Zebrafish yolk lipid processing: a tractable tool for the study of vertebrate lipid transport and metabolism

Dyslipidemias are a major cause of morbidity and mortality in the world, particularly in developed nations. Investigating lipid and lipoprotein metabolism in experimentally tractable animal models is a crucial step towards understanding and treating human dyslipidemias. The zebrafish, a well-established embryological model, is emerging as a notable system for studies of lipid metabolism. Here, we describe the value of the lecithotrophic, or yolk-metabolizing, stages of the zebrafish as a model for studying lipid metabolism and lipoprotein transport. We demonstrate methods to assay yolk lipid metabolism in embryonic and larval zebrafish. Injection of labeled fatty acids into the zebrafish yolk promotes efficient uptake into the circulation and rapid metabolism. Using a genetic model for abetalipoproteinemia, we show that the uptake of labeled fatty acids into the circulation is dependent on lipoprotein production. Furthermore, we examine the metabolic fate of exogenously delivered fatty acids by assaying their incorporation into complex lipids. Moreover, we demonstrate that this technique is amenable to genetic and pharmacologic studies.KEY WORDS: Dyslipidemia, Lipoprotein, Yolk syncytial layer, Yolk sac, Placenta, Lecithotrophic     

Biotransformation of Phenylacetonitrile to 2-Hydroxyphenylacetic Acid by Marine Fungi

Marine fungi belonging to the genera Aspergillus, Penicillium, Cladosporium, and Bionectria catalyzed the biotransformation of phenylacetonitrile to 2-hydroxyphenylacetic acid. Eight marine fungi, selected and cultured with phenylacetonitrile in liquid mineral medium, catalyzed it quantitative biotransformation to 2-hydroxyphenylacetic acid. In this study, the nitrile group was firstly hydrolysed, and then, the aromatic ring was hydroxylated, producing 2-hydroxyphenylacetic acid with 51 % yield isolated. In addition, the 4-fluorophenylacetonitrile was exclusively biotransformed to 4-fluorophenylacetic acid by Aspergillus sydowii Ce19 (yield?=?51 %). The enzymatic biotransformation of nitriles is not trivial, and here, we describe an efficient method for production of phenylacetic acids in mild conditions.     

Synergic Effect of Photodynamic Therapy with Methylene Blue and Surfactants in the Inhibition of Candida albicans

Photodynamic therapy (PDT) has been originally developed for the treatment of cancer, but it has been successfully employed in the treatment of infectious diseases, including fungal infections. Surfactants are amphiphilic compounds that also have antifungal properties. The present work demonstrates the synergic effect of PDT with methylene blue (MB) and LED combined with four different surfactants in the killing of Candida albicans. Subinhibitory concentrations of CTAC, HPS, SDS and Triton X-100 were tested with MB PDT. The combined therapies proved to be more efficient than PDT or surfactants separately. The best results were obtained with CTAC and HPS and PDT with MB at the concentration of 32 μg/mL. In conclusion, the combination of surfactants and PDT is an alternative antifungal treatment that can achieve more effective performance with minimal discomfort to the patient.     

Temporal Progress of Yellow Sigatoka and Aerobiology of Mycosphaerella musicola Spores

An understanding of the progression of a disease is important in the adoption of control strategies as well as the evaluation of their efficacies. Temporal analysis is especially useful because it integrates the evolution of the interaction between the components of the pathosystem, as expressed by the accumulated data on the incidence and severity of disease and depicted by the disease progression curve. Within a given patho‐system, the dispersed airborne spores are important components in the progress of plant disease epidemics. Our aims were to evaluate the temporal dynamics of yellow Sigatoka in a banana plantation located in Coronel Pacheco, MG, Brazil, and to assess the aerobiology of Mycosphaerella musicola spores throughout the year. During the rainy season, we observed intense disease progression concomitant with high rates of leaf emission, which caused rapid reversal of the severity peaks after the maximum rates were reached. The yellow Sigatoka progress curve showed two peaks of extreme severity. The first, which occurred during the rainy season, was predominantly caused by a high concentration of conidia. The second, which occurred during the dry season, was predominantly caused by a high concentration of ascospores in the air. The ascospore concentrations were correlated with the severity of the disease 29 days later, indicating the average latency period of the disease in that region. The patterns of the severity curves for both peaks fit the monomolecular model, and the progression rates were higher during the rainy season than the dry season. The spore concentrations were the same at the two evaluated heights. In all evaluations, it was observed a higher concentration of ascospores than of conidia, with the greatest ascospore concentrations occurring during the early hours of the day and the greatest conidia concentrations occurring later, after the dew has dropped from the leaves.