PubMed · 11389306
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E Hughes, J H Lee. 2001. Otitis externa.. https://doi.org/10.1542/pir.22-6-191
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To evaluate whether vaccine administration via intragastric gavage is indicative for the outcome of edible vaccines, mice were orally immunised with ovalbumin (OVA) mixed with or without Vibrio cholerae toxin (CT) in various compositions via various routes: (1) OVA dissolved in saline and intragastrically (IG) administered ('IG'); (2) OVA mixed with food extract and administered IG ('food IG'); (3) food chow absorbed with OVA dissolved in saline and fed to the animals ('food'); and (4) OVA dissolved in saline and administered via drinking bottles ('drinking'). When given to naive mice, 'IG' and 'food IG' but not 'food' or 'drinking' induced anti-OVA IgG1 responses in serum, but oral boost immunisations were necessary. Serum IgA was not induced. Oral boosting of subcutaneously (SC) primed mice enhanced the IgG1 and IgA response in serum regardless of the route of immunisation or the vaccine composition. CT did not dramatically enhance the immune response. All immunisation routes except 'drinking' induced antigen-specific IgA antibody secreting cells (ASC) in the lamina propria of naive mice. But antigen-specific antibody responses in faeces were not observed. We concluded that oral (i.e. IG) administration is distinct from oral intake. The composition of the vaccine (food or saline) did not influence oral administration. We thus suggested that the route of administration greatly influenced the outcome of oral immunisation. Although oral administration is a well-accepted route to test the potentials of oral vaccines, our study demonstrated that it is merely indicative for the effectiveness of edible vaccines. Studies on the feasibility of edible vaccines should thus be performed by eating the vaccine.
The synthesis and biological evaluation of a series of functionalized pyrrolidine- and piperidine-containing analogues of our lead LTA(4) hydrolase inhibitor, SC-57461A, is described. A number of compounds showed excellent potency in our in vitro screens and several demonstrated good oral activity in a mouse ex vivo assay. These efforts led to the identification of SC-56938 (14) as a potent, orally active inhibitor of LTA(4) hydrolase.
The relative reinforcing effects of different doses of benzodiazepines were determined by giving rhesus monkeys concurrent access to different diazepam and midazolam concentrations. For each monkey a dose response function was obtained using three drug concentrations: low (L), intermediate (I), and high (H). The benzodiazepine and the water vehicle were concurrently available under independent fixed-ratio (FR) schedules. After establishing that each concentration was a reinforcer in comparison to vehicle, relative preference for the different concentrations was examined by making pairs of concentrations concurrently available under independent FR schedules. Three pairs were studied (H vs. L, H vs. I, and I vs. L). With both drugs, higher concentrations maintained greater response rates than lower concentrations. Thus, relative reinforcing effects increased with dose. These findings are similar to those obtained with other reinforcing drugs and provide further evidence that benzodiazepines share significant characteristics with other drug reinforcers. Importantly, absolute response rates (responses per session) obtained when only one drug dose was present were not reliably predictive of subsequent preferences for the dose. Both benzodiazepines served as effective reinforcers in that consistent levels of responding were maintained across doses and above vehicle levels under concurrent FR 32 schedules. As with other reinforcing drugs, the reinforcing effects of benzodiazepines increase with increases in dose over a broad range of values.