Inhaled corticosteroid use is associated with increased circulating T regulatory cells in children with asthma

Background

T regulatory (Treg) cells are important in balancing immune responses and dysregulation of Treg cells has been implicated in the pathogenesis of multiple disease states including asthma. In this study, our primary aim was to determine Treg cell frequency in the peripheral blood of children with and without asthma. The secondary aim was to explore the association between Treg cell frequency with allergen sensitization, disease severity and medication use.

Methods

Peripheral blood mononuclear cells from healthy control subjects (N?=?93) and asthmatic children of varying disease severity (N?=?66) were characterized by multi-parameter flow cytometry.

Results

Our findings demonstrate that children with asthma had a significantly increased frequency of Treg cells compared to children without asthma. Using a multivariate model, increased Treg cell frequency in children with asthma was most directly associated with inhaled corticosteroid use, and not asthma severity, allergic sensitization, or atopic status of the asthma.

Conclusion

We conclude that low dose, local airway administration of corticosteroids is sufficient to impact the frequency of Treg cells in the peripheral blood. These data highlight the importance of considering medication exposure when studying Treg cells and suggest inhaled corticosteroid use in asthmatics may improve disease control through increased Treg cell frequency.     

Effects of expression of <Emphasis Type="Italic">lcb1/lcb2</Emphasis> and <Emphasis Type="Italic">lac1/lag1</Emphasis> genes on the biosynthesis of ceramides

Ceramides are important signal messenger molecules due to their role in regulating diverse responses such as cell cycle arrest, apoptosis, and senescence. Yeasts are more suitable for ceramides production than any other microorganisms since they grow fast and are non-pathogenic. However, regulations of the expression of genes involved in sphingolipid synthesis pathway are required to enhance ceramides production. In this study, we investigated the effects of co-expression of two pairs of genes that encode for serine palmitoyltransferase and ceramide synthase, respectively. Effect of other genes of the enzymes associated with the sphingolipid synthesis pathway, 3-ketosphinganine reductase and sphinganine C-4 hydroxylase were also studied and compared. The genes were cloned in to pESC-URA vector. Saccharomyces cerevisiae was cultivated aerobically in YPDG medium at 30°C. Ceramides were seperated from cell extracts by solvent extraction and quantified by HPLC with ELSD. The highest ceramides production (10.52 mg ceramides/g cell) was obtained when 3-ketosphinganine reductase, which is encoded by tsc10 gene, was overexpressed. Also, S. cerevisiae SCEL2,1 overexpressing serine palmitoyltransferase encoded by lcb2 and lcb1 genes, and S. cerevisiae SCEG1C1 overexpressing ceramide synthase encode by lag1 and lac1 genes, showed a high level of ceramides production (10.08 mg ceramides/g cell and 9.88 mg ceramides/g cell, respectively).     

In vivo binding of [11C]tetrabenazine to vesicular monoamine transporters in mouse brain.

The time course of regional mouse brain distribution of radioactivity after i.v. injection of a tracer dose of [11C]tetrabenazine ([11C]TBZ) has been determined. Radiotracer uptake into brain is rapid, with 3.2% injected dose in the brain at 2 min. Egress from the brain is also very rapid, with only 0.21% of the injected dose still present in brain at 60 min. Radiotracer washout is slowest from the striatum and hypothalamus, consistent with binding to the higher numbers of vesicular monamine transporters in those brain regions. The rank order of radioligand binding at 10 min after injection is striatum greater than hypothalamus greater than hippocampus greater than cortex = cerebellum, similar to that found using in vitro assays of the vesicular monoamine transporters. Maximum ratios of striatum/cerebellum and hypothalamus/cerebellum were 2.85 +/- 0.52 and 1.69 +/- 0.25, respectively, at 10 min after injection. Co-injection of unlabeled tetrabenazine (10 mg/kg) or pretreatment with reserpine (1 mg/kg i.p., 24 h prior) was used to demonstrate specific binding of radioligand in striatum, hypothalamus, cortex, hippocampus and cerebellum. Distribution of [11C]TBZ was unaffected by pretreatment with the neuronal dopamine uptake inhibitor GBR 12935 (20 mg/kg i.p., 30 min prior). [11C]Tetrabenazine is thus a promising new radioligand for the in vivo study of monoaminergic neurons using Positron Emission Tomography.     

Biotechnology: developing countries and globalization

Biotechnology in a globalizing economy involves the participation of all countries–industrialized, developing and least developed, in the interconnected web of trade liberalization in closed and open-market economies. The various geopolitical or geocultural regions show striking approaches to the application of biotechnologies for development and the safeguarding of intellectual property rights. The generally held view that developing countries are doomed to being marginalized in a globalizing economy is, seemingly, in need of revision.     

Aspergillus terreus and its toxic metabolites as a food contaminant in some Egyptian Bakery products and grains

A. terreus isolates isolated from some bakery products, corn and rice were found to be able to produce territrems. 90% of theA. terreus isolated from bakery products were able to produce territrem A, with a mean of 0.09 ppm, while 80% ofA. terreus isolates produce territrem B with a mean of 0.24 ppm. On the other hand 31.8% of the isolates ofA. terreus from corn were able to produce territrem A with a mean of 0.44 ppm. ConcerningA. terreus isolates from rice, 66.7% were found to produce territrem A, with a mean of 5.28 ppm, and 77.8% of the isolates produced territrem B with a mean of 1.79 ppm.     

Adaptive evolution of G-protein coupled receptor genes

The phylogeny and patterns of nucleotide substitutions in the visual pigment genes, adrenergic receptor genes, muscarinic receptor genes, and in the human mas oncogene were studied by comparing their DNA sequences. The evolutionary tree obtained shows that the visual pigment genes and mas oncogene form one cluster and that the receptor genes form another. In the evolution of rhodopsin genes, synonymous substitutions outnumber nonsynonymous substitutions. This is consistent with the neutral theory of molecular evolution. However, the early evolutionary stages of alpha- and beta-adrenergic and muscarinic receptors are notable for significantly more nonsynonymous substitutions than synonymous substitutions, suggesting the acquisition of novel functional adaptations. Variable rates of nonsynonymous changes in different domains of these proteins reveal DNA segments that might have been important in their functional adaptations.      

Estrogen receptor ligands. Part 13: Dihydrobenzoxathiin SERAMs with an optimized antagonist side chain

An optimized side chain for dihydrobenzoxathiin SERAMs was discovered and attached to four dihydrobenzoxathiin platforms. The novel SERAMs show exceptional estrogen antagonist activity in uterine tissue and an MCF-7 breast cancer cell assay.     

ER quality control can lead to retrograde transport from the ER lumen to the cytosol and the nucleoplasm in plants

Quality control in the secretory pathway is a fundamental step in preventing deleterious effects that may arise by the release of malfolded proteins into the cell or apoplast. Our aims were to visualise and analyse the disposal route followed by aberrant proteins within a plant cell in vivo using fluorescent protein technology. A green fluorescent protein (GFP) fusion was detected in the cytosol and the nucleoplasm in spite of the presence of an N-terminal secretory signal peptide. In contrast to secreted GFP, the fusion protein was retained in the cells where it was degraded slowly, albeit at a rate much higher than that of the endoplasmic reticulum (ER)-retained derivative GFP-HDEL. The fusion protein could not be stabilised by inhibitors of transport or the cytosolic proteasome. However, the protein is a strong lumenal binding protein (BiP) ligand. Complete signal peptide processing even after long-term expression in virus-infected leaves rules out the possibility that the documented accumulation in the cytosol and nucleoplasm is because of the bypassing of the translocation pores. The data are consistent with the hypothesis that the fusion protein is disposed off from the ER via a retrograde translocation back to the cytosol. Moreover, accumulation in the nucleoplasm was shown to be microtubule dependent unlike the well-documented diffusion of cytosolically expressed GFP into the nucleoplasm. The apparent active transport of the GFP fusion into the nucleoplasm may indicate an as yet undiscovered feature of the ER-associated degradation (ERAD) pathway and explain the insensitivity to degradation by proteasome inhibitors.