(S,R,S)-AHPC-PEG3-propionic acid

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 polyunsaturated fatty acids (PUFAs) consumed in low abundance in the Western diet. Increased consumption of n-3 PUFAs may have beneficial effects for a wide range of physiological outcomes including chronic inflammation. However, considerable mechanistic gaps in knowledge exist about EPA versus DHA, which are often studied as a mixture. We suggest the novel hypothesis that EPA and DHA may compete against each other through overlapping mechanisms. First, EPA and DHA may compete for residency in membrane phospholipids and thereby differentially displace n-6 PUFAs, which are highly prevalent in the Western diet. This would influence biosynthesis of downstream metabolites of inflammation initiation and resolution. Second, EPA and DHA exert different effects on plasma membrane biophysical structure, creating an additional layer of competition between the fatty acids in controlling signaling. Third, DHA regulates membrane EPA levels by lowering its rate of conversion to EPA's elongation product n-3 docosapentaenoic acid. Collectively, we propose the critical need to investigate molecular competition between EPA and DHA in health and disease, which would ultimately impact dietary recommendations and precision nutrition trials.

Purpose:The purpose of this study was to evaluate the implication of an ex vivo model for carrier-mediated retinal drug delivery using an Ussing chamber system. Methods:Dutch Belted Pigmented rabbits weighing 2-2.5 kg were used in these studies. Excised posterior segment tissues (RPE-choroid-sclera and sclera), mounted on the Ussing chamber, were used as an ex vivo model. Transport studies were carried out across sclera and RPE-choroid-sclera (RCS) tissue preparations in the sclera to retina (S --> R) and retina to sclera (R --> S) directions for 3 hr at 37 degrees C. The model was validated by permeability studies with paracellular and transcellular markers ([(3)H]mannitol and [(14)C]diazepam, respectively), tissue viability studies (bioelectrical and biochemical assays), and tissue histology and electron microscopy studies. Functional presence of a carrier-mediated transport system for folic acid (folate receptor alpha) was investigated on the basolateral side of the rabbit retina. Results:Results from bioelectrical, biochemical, and histological evaluation of tissue provide evidence that the RCS tissue preparation remains viable during the period of transport study. Permeability values of [(3)H]mannitol across sclera were 4.18 +/- 1.09 x 10(- 5) cm/s (R --> S) and 4.11 +/- 1.09 x 10(- 5) cm/s (S --> R) and across RCS were 1.77 +/- 0.31 x 10(- 5) cm/s (S --> R) and 1.60 +/- 0.19 x 10(- 5) cm/s (R --> S). Permeability values of [(14)C]diazepam across sclera were 2.37 +/- 0.38 x 10(- 5) cm/s (R --> S) and 2.70 +/- 0.70 x 10(- 5) cm/s (S --> R) and across RCS were 3.12 +/- 0.12 x 10(- 5) cm/s (R --> S) and 2.77 +/- 0.25 x 10(- 5)cm/s (S --> R). The rate of [(3)H]folic acid transport across RCS was found to be significantly higher in the S -->R direction (16.34 +/- 0.94 fmoles min(-1) cm(-2)) as compared with R --> S direction (9.38 +/- 1.44 fmoles min(-1) cm(-2)) and nearly 10-fold higher across sclera as compared with RCS in both directions. Transport of [(3)H]folic acid was found to be pH and temperature dependent and was inhibited by 44.5%, 35.1%, and 50.3% in the presence of unlabeled folic acid, 5-methyltetrahydrofolate (MTF), and Methotrexate (MTX).Conclusions:The RCS tissue preparation mounted on the Ussing chamber system, an ex vivo model, can be a useful tool for identification and characterization of carrier-mediated systems present on RPE (a major barrier for retinal drug delivery) and to study carrier-mediated retinal drug delivery via prodrug derivatization.

This paper presents experimental results from the use of biosurfactants in the remediation of a soil from a smelter in Poland. In the soil, concentrations of Cu (1659.1 mg/kg) and Pb (290.8 mg/kg) exceeded the limit values. Triple batch washing was tested as a soil treatment. Three main variants were used, each starting with a different plant-derived (saponin, S; tannic acid, T) or microbial (rhamnolipids, R) biosurfactant solution in the first washing, followed by 9 different sequences using combinations of the tested biosurfactants (27 in total). The efficiency of the washing was determined based on the concentration of metal removed after each washing (CR), the cumulative removal efficiency (Ecumulative) and metal stability (calculated as the reduced partition index, Ir, based on the metal fractions from BCR sequential extraction). The type of biosurfactant sequence influenced the CR values. The variants that began with S and R had the highest average Ecumulative for Cu and Pb, respectively. The Ecumulative value correlated very strongly (r > 0.8) with the stability of the residual metals in the soil. The average Ecumulative and stability of Cu were the highest, 87.4% and 0.40, respectively, with the S-S-S, S-S-T, S-S-R and S-R-T sequences. Lead removal and stability were the highest, 64-73% and 0.36-0.41, respectively, with the R-R-R, R-R-S, R-S-R and R-S-S sequences. Although the loss of biosurfactants was below 10% after each washing, sequential washing with biosurfactants enriched the soil with external organic carbon by an average of 27-fold (S-first variant), 24-fold (R first) or 19-fold (T first). With regard to environmental limit values, metal stability and organic carbon resources, sequential washing with different biosurfactants is a beneficial strategy for the remediation of smelter-contaminated soil with given properties.