Understanding metabolism related differences in ocular efficacy of MGV354.

MGV354 was being developed as a novel ocular therapy for lowering of intraocular pressure, a key modifiable risk factor for glaucoma. MGV354 is an activator of soluble guanylate cyclase, an enzyme known to be involved in the regulation of IOP. MGV354 has been shown to robustly lower IOP over 24 h after a single topical ocular drop in rabbit and monkey pharmacology models. However, MGV354 failed to produce similar results in patients with ocular hypertension or open-angle glaucoma. With an objective of explaining the lack of efficacy in the clinic, we attempted to study whether human metabolism was significantly different from animal metabolism. The present study documents the investigation of metabolism of MGV354 in an effort to understand potential differences in biotransformation pathways of MGV354 in rabbits, monkeys, and humans. Overall twenty-six metabolites, formed via oxidative and conjugative pathways, were identified in vitro and in vivo. In vitro hepatic metabolism was qualitatively similar across species, with minor but distinct differences. There were no observable interspecies differences in the hepatic and ocular metabolism of MGV354. Although ocular metabolism was not as extensive as hepatic, the results do not explain the lack of efficacy of MGV354 in clinical studies.

A qualitative study of emergency department patients who survived an opioid overdose: Perspectives on treatment and unmet needs.

OBJECTIVE: Emergency medicine clinicians are uniquely positioned to deliver interventions to enhance linkage to evidence-based treatment for opioid use disorder (OUD) in the acute overdose period, yet little is known about patient perspectives to effectively engage patients immediately following opioid overdose. Our objective was to explore patients' perspectives on substance use treatment, perceived needs, and contextual factors that shape the choice of patients seen in the emergency department (ED) to engage with treatment and other patient support services in the acute post-opioid overdose period. METHODS: We administered a brief quantitative survey and conducted semistructured interviews with 24 adult ED patients receiving care after an acute opioid overdose between June 2016 and August 2017 in an urban, academic ED. We used constant comparison method and thematic analysis to identify themes across four levels of a modified social ecologic model (individual, interpersonal, organizational, and structural). RESULTS: The mean (±SD) age of the sample was 33.5 (±9.33) years; 83% were White and 12% were Black; 67% were male; and 83% were diagnosed with OUD, with a mean (±SD) of 3.25 (±2.64) self-reported lifetime opioid overdoses. Eight themes were identified as influencing participants' consideration of OUD treatment and other services: (1) perceptions about control of drug use, (2) personal experience with substance use treatment, (3) role of interpersonal relationships, (4) provider communication skills, (5) stigma, (6) availability of ED resources, (7) impact of treatment policies, and (8) support for unmet basic needs. CONCLUSIONS: Patients receiving ED care following overdose in our ED are willing to discuss their opioid use and its treatment in the ED and report a variety of unmet needs. This work supports a role for ED-based research evaluating a patient-oriented approach to engage patients after opioid overdose.

Synergistic and competitive aspects of the adsorption of poly(ethylene glycol) and poly(vinyl alcohol) onto Na-bentonite.

The competitive adsorption of poly(ethylene glycol) (PEG) and poly(vinyl alcohol) (PVOH) onto Na-bentonite has been assessed quantitatively. Particular emphasis was focused on the amount of organic located within the bentonite interlayer and any subsequent effects on the extent of layer expansion. The individual isotherms showed strong adsorption for both PVOH and PEG at amounts lower than the quantities required to produce a fully loaded bilayer (0.33 g of PVOH/g of clay) and single layered structures (0.10 g of PEG/g of clay), respectively. Above these concentrations, the incremental amounts adsorbed were smaller, and the concentration of adsorbates in solution gradually increased. Na-bentonite adsorbed more PVOH than PEG at any given concentration. In the competitive study, the amount of PVOH adsorbed was enhanced in the presence of PEG (0.10 and 0.30 g/g of clay), but less PEG was adsorbed. At low loadings of PVOH (0.02-0.10 g/g of clay), the amount of adsorbed PEG was increased but at higher PVOH levels PEG adsorption was reduced. The XRD data showed stepped changes in the d-spacing as the adsorbed amounts of both PEG and PVOH increased. The PEG-bentonite samples did not expand beyond a bilayer structure (18 Å), but the XRD data for PVOH-treated samples indicated the formation of multilayer structures (d ≥ 44 Å).

A new nano-TiO2 immobilized biodegradable polymer with self-cleaning properties.

This study concentrated on the direct immobilization of anatase nano titanium dioxide particles (TiO(2), 10nm particle size) into or onto a biodegradable polymer, polycaprolactone, by solvent-cast processes. The self-cleaning, namely photocatalytic properties of the produced materials were tested by photocatalytic removal of methylene blue as model compound and antimicrobial properties were investigated using Candida albicans as model microorganism. Produced TiO(2) immobilized polymer successfully removed methylene blue (MB, 1 × 10(-5)M) from aqueous solution without additional pH arrangement employing a UV-A light (365 nm) source. Almost 83.2% of dye was removed or decomposed by 5 wt% TiO(2) immobilized into PCL (0.08 g) and removal percentage reached to 94.2% with 5 wt% TiO(2) immobilized onto PCL after a 150 min exposure period. Although removal percentage decrease with increased ionic strength and usage of a visible light source, produced materials were still effective. TiO(2) immobilized onto PCL (5 wt%) was quite effective killing almost 54% of C. albicans (2 × 10(6)CFU/mL) after only 60 min exposure with a near visible light source. Control experiments employing PCL alone in the presence and absence of light were ineffective under the same condition.