Treatment response in relation to inflammatory and axonal surrogate marker in multiple sclerosis

BACKGROUND: This study aimed to investigate if treatment response could retrospectively be related to inflammatory or axonal pathology as measured by plasma surrogate markers. METHODS: In this 1-year observational study 30 multiple sclerosis (MS) patients with relapsing-remitting disease were treated with intramuscular IFNbeta-1a or subcutaneous IFNbeta-1b. Responders and nonresponders were defined according to clinical and magnetic resonance imaging criteria. The control group consisted of 14 healthy subjects. Plasma levels of surrogate markers for inflammation (nitric oxide metabolites (NOx)), astrocytic activation (S100B) and axonal damage (NfH(SM135)) were measured using standard assays. RESULTS: There were 11 nonresponders and 19 responders to IFNbeta treatment. Median S100B levels were elevated in a higher proportion of treatment responders (63%, 42.9 pg/mL) compared to nonresponders (18%, 11.7 pg/mL, P < 0.05, Fisher's exact test) and controls (0%, 2 pg/mL, P < 0.001). Levels of NOx were found to be more frequently elevated in nonresponders (72%, 39 microM) compared to healthy controls (0%, 37 microM, P < 0.05). Levels of NfH(SM135) were more frequently elevated in responders (58%, 300 pg/mL, P < 0.001) and nonresponders (72%, 500 pg/mL, P < 0.001) compared to controls (0%, 4.5 pg/mL). CONCLUSION: Patients with relapsing-remitting MS who had surrogate marker supported evidence for astrocytic activation responded more frequently to treatment with IFNbeta

Microbiome diversity and metabolic capacity determines the trophic ecology of the holobiont in Caribbean sponges

Sponges are increasingly recognized as an ecologically important taxon on coral reefs, representing significant biomass and biodiversity where sponges have replaced scleractinian corals. Most sponge species can be divided into two symbiotic states based on symbiont community structure and abundance (i.e., the microbiome), and are characterized as high microbial abundance (HMA) or low microbial abundance (LMA) sponges. Across the Caribbean, sponge species of the HMA or LMA symbiotic states differ in metabolic capacity, as well as their trophic ecology. A metagenetic analysis of symbiont 16 S rRNA and metagenomes showed that HMA sponge microbiomes are more functionally diverse than LMA microbiomes, offer greater metabolic functional capacity and redundancy, and encode for the biosynthesis of secondary metabolites. Stable isotope analyses showed that HMA and LMA sponges primarily consume dissolved organic matter (DOM) derived from external autotrophic sources, or live particulate organic matter (POM) in the form of bacterioplankton, respectively, resulting in a low degree of resource competition between these symbiont states. As many coral reefs have undergone phase shifts from coral- to macroalgal-dominated reefs, the role of DOM, and the potential for future declines in POM due to decreased picoplankton productivity, may result in an increased abundance of chemically defended HMA sponges on tropical coral reefs

Using salt counterions to modify β2-agonist behaviour in vivo

This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. © 2016 American Chemical Society.There is a paucity of data describing the impact of salt counterions on the biological performance of inhaled medicines in vivo. The aim of this study was to determine if the coadministration of salt counterions influenced the tissue permeability and airway smooth muscle relaxation potential of salbutamol, formoterol, and salmeterol. The results demonstrated that only salbutamol, when formulated with an excess of the 1-hydroxy-2-naphthoate (1H2NA) counterion, exhibited a superior bronchodilator effect (p < 0.05) compared to salbutamol base. The counterions aspartate, maleate, fumarate, and 1H2NA had no effect on the ability of formoterol or salmeterol to reduce airway resistance in vivo. Studies using guinea pig tracheal sections showed that the salbutamol:1H2NA combination resulted in a significantly faster (p < 0.05) rate of tissue transport compared to salbutamol base. Furthermore, when the relaxant activity of salbutamol was assessed in vitro using electrically stimulated, superfused preparations of guinea pig trachea, the inhibition of contraction by salbutamol in the presence of 1H2NA was greater than with salbutamol base (a total inhibition of 94.13%, p < 0.05). The reason for the modification of salbutamol’s behavior upon administration with 1H2NA was assigned to ion-pair formation, which was identified using infrared spectroscopy. Ion-pair formation is known to modify a drug’s physicochemical properties, and the data from this study suggested that the choice of counterion in inhaled pharmaceutical salts should be considered carefully as it has the potential to alter drug action in vivo.Peer reviewe

Spinodal decomposition of off-critical quenches with a viscous phase using dissipative particle dynamics in two and three spatial dimensions

We investigate the domain growth and phase separation of hydrodynamically-correct binary immiscible fluids of differing viscosity as a function of minority phase concentration in both two and three spatial dimensions using dissipative particle dynamics. We also examine the behavior of equal-viscosity fluids and compare our results to similar lattice-gas simulations in two dimensions.Comment: 34 pages (11 figures); accepted for publication in Phys. Rev.