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K Gerhardt

Publications and source records attributed to K Gerhardt.

9 recordsLinked to original sources

Lectin-mediated drug delivery: influence of mucin on cytoadhesion of plant lectins in vitro.

As the mucous layer represents the first barrier to peroral lectin-mediated drug delivery, the influence of mucin on the cytoadhesive properties of lectins was studied in vitro by establishing a rapid and simple microplate format assay using pig gastric mucin (PGM) for coating the wells. The lectin-binding capacity of mucin followed the order WGA>>UEA-I>>LCA=STL>PNA>DBA. The PGM-binding of wheat germ agglutinin (WGA) was strongly dependent on pH being highest at pH 5.0. In comparison, PGM-binding of WGA was about 15% at gastric pH and 60-70% at intestinal pH. This points to unimpeded gastric transit of WGA-grafted formulations and favorable conditions within the intestine for binding to mucus coated enterocytes. Moreover the WGA-PGM interaction was concentration-dependent, specific and fully reversible. According to a competitive assay in the presence of Caco-2 monolayers, the PGM-binding of WGA was saturated and influenced by the lectin-concentration yielding 28% Caco-2 bound WGA (125 ng WGA/0.29 cm(2) monolayer) and 68% Caco-2 bound WGA (4 microg WGA/0.29 cm(2) monolayer), respectively. Following on from these results, lectins are expected to suffer at least partially from premature inactivation by shed off mucus like bioadhesives of the first generation, however initial but reversible mucus-binding of lectins offers partititioning to the cell membrane followed by uptake into the enterocyte.

Adhesives↗

Temporal bisection with trial referents.

In temporal bisection, the subject is required to compare the similarity of a probe duration with two referent durations. Two bisection experiments with human subjects are reported in which performance under three referent conditions was compared. In two of the conditions, no-referent and fixed-referent, the referent pair was constant throughout the session and was varied between sessions. In the no-referent condition, samples of the referents were presented at the beginning of a block of trials, but not on the probe trials. In contrast, in the fixed-referent condition, the referent pair was presented on each probe trial. In the third referent condition, roving-referent, the referent pair was also presented on each probe trial, but the values of the pair varied during a session rather than between sessions. The pseudologistic Model (PLM; Killeen, Fetterman, & Bizo, 1997) provided an excellent account of the data from all referent conditions and indicated that (1) the scalar variability was located in the perception of the probe and was independent of the structure of the bisection task, (2) the role of the referents was to set the criterion, (3) the probe was compared with the criterion rather than with the referents, and (4) the comparison of the probe with the criterion occurred even when trial referents were available.

Adult↗

Human spinal cord retains substantial structural mass in chronic stages after injury.

In chronic stages of human spinal cord injury, atrophy of the cord has been reported in regions both at and distant to the injury site. Local cord atrophy results from the direct effects of bony impact and ischemia, whereas distant atrophy results from anterograde (Wallerian) and retrograde axonal degeneration. However, the actual extent of degenerative changes in the chronically injured human spinal cord both at and remote from the injury site has rarely been reported, and has not been rigorously quantified to date. In the present study, we quantified the extent of spinal cord atrophy in 12 humans with chronic injury (2-34 years posttrauma) utilizing quantitative stereological assessment of spinal cord magnetic resonance images, and compared the results to uninjured human spinal cords. Focal cystic atrophy of the cord, characterized by signal attenuation on T1-weighted images, was regularly present at the actual site of impact injury and replaced a mean longitudinal area equaling less than one spinal cord segment in length (2.01 +/- 0.60 cm2, or a loss of 89.3 +/- 17.4% of the longitudinal area of one spinal cord segment). Spinal cord segments immediately rostral to the zone of cystic degeneration showed atrophy of only 19.4 +/- 7.5% of normal cord longitudinal area, and spinal cord segments immediately caudal to the zone of cystic degeneration showed atrophy of 16.5 +/- 4.1% of normal cord longitudinal area. Extensive spinal cord atrophy extending beyond the region of injury occurred in two of twelve cases (16.7%), and both were caused by late syrinx formation. Thus, spinal cord atrophy after trauma remains primarily restricted to the original site of injury. Experimental neural repair strategies should take into account the importance of "bridging" relatively short zones of cystic atrophy, then promoting axonal regeneration through potentially long segments of remaining cord parenchyma.

Adult↗

Fetal hearing.

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Autoradiography↗

Identification of oestrogen metabolites in human urine by capillary gas chromatography and mass spectrometry.

Oestrogen metabolites from the urine of males and pregnant and non-pregnant females were enriched by a procedure involving column chromatography on adsorber resins, gels and ion exchangers, enzymatic solvolysis and extraction, thereby separating the oestrogens from most of the interfering material. After derivatization of the oestrogens as their trimethylsilyl ethers profiles were measured with a fused silica column and a flame ionization detector by gas chromatography. Using a combination of capillary gas chromatography and mass spectrometry approximately 50 oestrogen metabolites were detected in the human urine of males and females, of which 19 were unknown urine compounds. Not all could be identified definitely owing to the lack of reference material. Mass spectra of trimethylsilylated oestrogens with functional groups at position 11 (11-dehydroestradiol, 11-dehydroestrone and 11 beta-hydroxyestrone) were discussed in their common and discernible fragmentations.

Chromatography, Gas↗