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Human Plasma Proteins (human + plasma_protein)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Domains of group A streptococcal M protein that confer resistance to phagocytosis, opsonization and protection: implications for vaccine development

MOLECULAR MICROBIOLOGY, Issue 1 2006
Jason D. McArthur
Summary Streptococcus pyogenes (group A streptococcus) colonizes skin and throat tissues resulting in a range of benign and serious human diseases. Opsonization and phagocytosis are important defence mechanisms employed by the host to destroy group A streptococci. Antisera against the cell-surface M protein, of which over 150 different types have been identified, are opsonic and contribute to disease protection. In this issue of Molecular Microbiology, Sandin and colleagues have comprehensively analysed the regions of M5 protein that contribute to phagocytosis resistance and opsonization. Human plasma proteins bound to M5 protein B- and C-repeats were shown to block opsonization, an observation that needs to be carefully considered for the development of M protein-derived vaccines. While safe and efficacious human group A streptococcal vaccines are not commercially available, candidate M protein-derived vaccines have shown promise in murine vaccine models and a recent phase 1 human clinical trial. [source]

Stereoselective renal tubular secretion of levocetirizine and dextrocetirizine, the two enantiomers of the H1 -antihistamine cetirizine

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2008
M. Strolin Benedetti
Abstract Competition for uptake and/or efflux transporters can be responsible for drug interactions. Cetirizine is mainly eliminated unchanged in urine through both glomerular filtration and tubular secretion. The aim of this study was to investigate whether the eutomer, levocetirizine, and the distomer, dextrocetirizine, have a similar tubular secretion. The renal clearance associated with tubular secretion was calculated from the renal clearance of levocetirizine and dextrocetirizine obtained in a study in healthy volunteers. The values of the unbound fraction in plasma were obtained in an in vitro study of the binding of 14C-cetirizine and 14C-levocetirizine to human plasma proteins using equilibrium dialysis and chiral high-performance liquid chromatography (HPLC) with on-line liquid scintillation counting. The unbound fraction was 0.074 for levocetirizine and 0.141 for dextrocetirizine. The tubular secretion of dextrocetirizine (44.5 mL/min) is higher than that of levocetirizine (23.1 mL/min), which may have consequences for drug interactions at the renal level. The higher tubular secretion for dextrocetirizine may be due to the higher free fraction available for secretion or to a higher affinity for (a) renal transporter(s) mediating the secretion pathway. [source]

Microseparation techniques for the study of the enantioselectivity of drug,plasma protein binding

BIOMEDICAL CHROMATOGRAPHY, Issue 3 2009
Laura Escuder-Gilabert
Abstract Stereoselectivity in protein binding can have a significant effect on the pharmacokinetic and pharmacodynamic properties of chiral drugs. The investigation of enantioselectivity of drugs in their binding with human plasma proteins and the identification of the molecular mechanisms involved in the stereodiscrimination by the proteins represent a great challenge for clinical pharmacology. In this review, the separation techniques used for enantioselective protein binding experiments are described and compared. An overview of studies on enantiomer,protein interactions, enantiomer,enantiomer interactions as well as chiral drug,drug interactions, including allosteric effects, is presented. The contribution of individual plasma proteins to the overall enantioselective binding and the animal species variability in drug,plasma protein binding stereoselectivity are reviewed. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Adsorption of human plasma proteins to modified titanium surfaces

CLINICAL ORAL IMPLANTS RESEARCH, Issue 5 2007
Michael N. Sela
Abstract Objectives: The aim of this study was to examine the effect of modified titanium (Ti) surfaces on the initial events of plasma proteins adsorption. Materials and methods: ,Ti disks' with three types of surface modifications were compared: machined, acid-etched and acid-etched and blasted. Physical and chemical characterizations of the surfaces were performed via scanning electron microscopy (SEM), atomic force microscopy (AFM) used for analysis of surface topography, characterization of the titanium oxide (TiO2) layer was carried out by X-ray photoelectron spectroscopy (XPS) and characterization of surface energy by the determination of contact angles. Evaluation of plasma proteins' adsorption to the treated Ti surfaces was performed by mass spectrometry, confocal laser scanning microscopy and XPS. Quantitative proteins' assessment was carried out by enzyme-linked immunosorbent assay. Results: SEM images revealed major differences in the topography of the examined surfaces. Acid-etched and blasted Ti surfaces were found to have higher roughness values and a thicker TiO2 layer as compared with acid-etched and machined surfaces. Moreover, acid-etched and blasted surfaces showed high surface area differentiation, pointing to a high increase in the three-dimensional (3D) surface area over the 2D surface area compared with the other surfaces. Adsorption of plasma proteins to the acid-etched and blasted Ti surfaces was both qualitatively and quantitatively more intense compared with the machined and acid-etched surfaces. This was shown for each examined protein, total proteins and by the removal degree of the protein coat. Conclusions: The preferential adsorption of plasma proteins to the acid-etched and blasted Ti surfaces may be explained by its topographical characteristics and by the increase of the 3D surface area of this modified surface. [source]