The recognition of 111In-labeled galactosylated superoxide dismutase (Gal-SOD) and galactosylated bovine serum albumin (Gal-BSA) by the liver was investigated in mice after intravenous injection. 111In-labeled galactosylated proteins were recovered in the liver by amounts that were highly dependent on the degree of galactose modification and the administered dose. The distribution patterns were analyzed based on a physiological pharmacokinetic model including an uptake process with Michaelis-Menten kinetics in the liver and hepatic plasma flow. The Michaelis constant of hepatic uptake of 111In-Gal-SOD was observed to inversely correlate with the number of galactose residues, without a significant change in maximum rate of uptake or extrahepatic clearance. This relation could be applied to 111In-Gal-BSA and other galactosylated proteins by using the surface density of galactose residues as a degree of modification, suggesting galactose density controls ligand recognition by the asialoglycoprotein receptor. The analysis also indicated that increasing galactose density higher than 1.0 x 10(-3) molecules/A2 did not affect the distribution of galactosylated proteins due to limitation by the hepatic plasma flow rate. In conclusion, efficient delivery of proteins modified with galactose to the liver will be achieved by controlling both the galactose density on the protein surface and the administered dose.
Ocular infection is caused by both endogenous (resident) and exogenous (environmental) microbes. As the ocular surface interacts with both outer environment and its own resident microbiota, clinical ocular samples are predicted to contain a diverse set of microorganisms. Microscopy of sample smears is an important step in the diagnostic process of infectious diseases to interpret the culture results. Traditional culture techniques have several limitations in the detection and/or identification of uncharacterized bacteria of environmental origin. Molecular biological techniques, such as polymerase chain reaction of pathogen-specific virulence genes, 16S rRNA gene clone library analysis, and next-generation sequencing of 16S rDNA amplicons, compensate for diagnostic culture techniques in diagnosing infectious diseases. These techniques are expected to provide novel insights into the ocular microbiota and pathology of ocular infections. In this article, we describe various ocular infections, including contact lens-related keratitis, silicone buckle infection, and dacryocystitis, which were analyzed using molecular biological techniques. The advantages and disadvantages of these highly sensitive and inclusive microbiological detection systems for ocular infections are discussed.
Our study showed a high success rate for dacryoendoscopy-guided probing in CNLDO patients. The use of a dacryoendoscope allows direct visualization of the lacrimal passage and is likely to become necessary for managing CNLDO.
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