ABSTRACT
In this study, we present a novel product consisted of red grape cells (RGC) grown in culture and evaluated its effect on human LDL oxidation (in vitro) and inflammatory stress (in an in vivo rat model). We analyzed RGC for its polyphenols content and characterized RGC-derived resveratrol (RES) and its properties; and finally, we characterized the pharmacokinetic profile of RGC-RES in human plasma. RGC has demonstrated a strong inhibitory effect on LDL oxidation with IC50 as low as 8.0 µg/ml. RGC significantly reduced rats inflamed paw size induced by carrageenan injection. LC/MS analysis has shown that the main polyphenol in RGC was RES with one hexose moiety. The human pharmacokinetic analysis (clinicaltrials.gov NCT01747252) revealed relatively high bioavailability and two distinctly separated plasma concentration peaks at 1 and 5 h. The present study demonstrates antioxidant and anti-inflammatory traits of RGC that warrants further research in both pre-clinical and clinical settings.
Subject(s)
Lipoproteins, LDL/chemistry , Stilbenes/pharmacology , Vitis/classification , Vitis/cytology , Adult , Animals , Biological Availability , Carrageenan/toxicity , Cross-Over Studies , Edema/chemically induced , Edema/drug therapy , Humans , Indomethacin/pharmacology , Inflammation/chemically induced , Inflammation/drug therapy , Lipoproteins, LDL/metabolism , Male , Oxidation-Reduction , Rats , Rats, Sprague-Dawley , Resveratrol , Stilbenes/chemistry , Stilbenes/pharmacokineticsABSTRACT
BACKGROUND: Injectable dermal fillers have become important alternatives to traditional surgical procedures for the correction of facial wrinkles and restoration of facial volume. The physical properties of a dermal filler/volumizing agent, and the host tissue response to the agent, influence its clinical performance and patient outcomes. METHODS: In this study, several key physical properties of the new porcine collagen dermal filler Dermicol-P35 27G were measured and compared with those of commercially available hyaluronic acid-based dermal fillers. Furthermore, the in vivo properties of implanted Dermicol-P35 27G were evaluated by histologic and histopathologic methods. RESULTS: This study found that Dermicol-P35 27G provides a lower extrusion force profile and yield point compared with the hyaluronic acid-based dermal fillers tested. At 2 years, staining of punch biopsy specimens with hematoxylin and eosin and Herovici stains revealed no inflammatory cells and no evidence of other adverse events in any of the samples containing Dermicol-P35 27G. Within-implant colonization by fibroblasts depositing new collagen and the formation of elastin within the implanted collagen material (as shown by Luna staining) suggest that Dermicol-P35 27G is a bioactive implant. CONCLUSIONS: Compared with several hyaluronic acid-based dermal fillers, Dermicol-P35 exhibited lower extrusion force, higher viscosity under low shear rate, and a higher modulus of elasticity. Results of histologic evaluation indicated that Dermicol-P35 27G did not elicit an inflammatory response and was well integrated within the host tissue. Together, these results suggest that Dermicol-P35 27G offers several advantages that may result in improved clinical experiences for both patients and clinicians.
Subject(s)
Collagen/administration & dosage , Cosmetic Techniques , Dermis/drug effects , Skin Aging/drug effects , Adult , Aged , Animals , Biopsy , Collagen/adverse effects , Collagen/immunology , Dermis/immunology , Dermis/pathology , Elasticity , Female , Fibroblasts/drug effects , Fibroblasts/pathology , Humans , Hyaluronic Acid/adverse effects , Hyaluronic Acid/chemistry , Hyaluronic Acid/immunology , Male , Middle Aged , Shear Strength , Swine , Viscosity , Young AdultABSTRACT
In studies of the outstanding salt tolerance of the unicellular green alga Dunaliella salina, we isolated a cDNA for a salt-inducible mRNA encoding a protein homologous to plant beta-ketoacyl-coenzyme A (CoA) synthases (Kcs). These microsomal enzymes catalyze the condensation of malonyl-CoA with acyl-CoA, the first and rate-limiting step in fatty acid elongation. Kcs activity, localized to a D. salina microsomal fraction, increased in cells transferred from 0.5 to 3.5 M NaCl, as did the level of the kcs mRNA. The function of the kcs gene product was directly demonstrated by the condensing activity exhibited by Escherichia coli cells expressing the kcs cDNA. The effect of salinity on kcs expression in D. salina suggested the possibility that salt adaptation entailed modifications in the fatty acid composition of algal membranes. Lipid analyses indicated that microsomes, but not plasma membranes or thylakoids, from cells grown in 3.5 M NaCl contained a considerably higher ratio of C18 (mostly unsaturated) to C16 (mostly saturated) fatty acids compared with cells grown in 0.5 M salt. Thus, the salt-inducible Kcs, jointly with fatty acid desaturases, may play a role in adapting intracellular membrane compartments to function in the high internal glycerol concentrations balancing the external osmotic pressure.
Subject(s)
Acetyltransferases/genetics , Chlorophyta/genetics , Membrane Lipids/metabolism , Sodium Chloride/pharmacology , 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase/drug effects , 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase/genetics , 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase/metabolism , Acetyltransferases/drug effects , Acetyltransferases/metabolism , Amino Acid Sequence , Chlorophyta/drug effects , Chlorophyta/enzymology , Cloning, Molecular , DNA, Complementary/chemistry , DNA, Complementary/genetics , Escherichia coli/genetics , Fatty Acid Desaturases/metabolism , Fatty Acid Elongases , Fatty Acids/metabolism , Gene Expression Regulation, Enzymologic/drug effects , Microsomes/drug effects , Microsomes/metabolism , Molecular Sequence Data , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino AcidABSTRACT
To investigate the mechanism of formaldehyde tolerance in Gram-negative bacteria, two formaldehyde-tolerant strains, Escherichia coli VU3695 and Halomonas sp. MAC (DSM 7328), and formaldehyde-sensitive revertants obtained by ethidium bromide or novobiocin treatment were studied. The presence of high levels of formaldehyde dehydrogenase activity alone proved insufficient to confer tolerance to high formaldehyde concentrations, as shown by high activity displayed by formaldehyde-sensitive revertants of Halomonas MAC. Moreover, formaldehyde-tolerant strains also proved to be tolerant to high concentrations of acetaldehyde and glutaraldehyde, which are not oxidized by formaldehyde dehydrogenase. Treatment with sublethal concentrations of EDTA rendered the resistant strains highly sensitive to formaldehyde without affecting the activity of formaldehyde dehydrogenase. Comparison of the outer membrane proteins of formaldehyde-resistant strains with those of their sensitive revertants showed the presence of at least one additional high molecular mass protein in the tolerant strains. It is concluded that formaldehyde tolerance in the bacteria studied depends on the composition and structure of the outer membrane.
