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T A Woltman

Publications and source records attributed to T A Woltman.

4 recordsLinked to original sources

Relative blood-brain barrier permeabilities of the cholecystokinin receptor antagonists devazepide and A-65186 in rats.

The blood-brain barrier permeabilities of the type-A cholecystokinin receptor antagonists devazepide and A-65186 (Nalpha-3-quinolinoyl-D-Glu-N,N-dipentylamide) have been compared with those of the reference compounds iodoantipyrine, which readily penetrates the blood-brain barrier, and mannitol, which does not. Anaesthetized rats received a bolus injection into the left carotid artery of [14C]iodoantipyrine (0.25 microCi) combined with [3H]mannitol, [3H]devazepide or [3H]A-65186 (1 microCi each). Rats were decapitated 12s after injection and the brains were removed. Four samples of left cerebrum (ca 100 mg each) were solubilized overnight and 14C and 3H activity were measured. The brain-uptake index for each test compound was determined as [(3H/l4C for sample)]/[(3H/14C for injectate)] x 100, with a value of 100 representing blood-brain barrier permeability equal to that for iodoantipyrine. The brain-uptake index (mean+/-s.e.m.) was 1.6+/-0.3 for [3H]mannitol (n=5), 90.6+/-4.1 for [3H]devazepide (n=7, P<0.001 compared with mannitol) and 3.5+/-0.7 for [3H]A-65186 (n=4, P > 0.05 compared with mannitol, P < 0.001 compared with devazepide). Thus, devazepide readily penetrated the blood-brain barrier whereas A-65186 did not. It is concluded that devazepide and A-65186 are likely to be useful pharmacological tools for determining whether cholecystokinin is acting peripherally or at brain sites beyond the blood-brain barrier to produce satiety or any other function mediated by the type A cholecystokinin receptor.

Anesthesia↗

Feeding patterns of rats chronically ingesting an ethanol-containing liquid diet.

We compared the feeding patterns of rats ingesting a 36% ethanol-containing liquid diet for 30 days with those of rats pair-fed an isocaloric liquid control diet or provided control diet or ground rat chow ad libitum. Ethanol-fed rats consumed fewer calories per day and gained less body weight than rats fed control diets ad libitum. Daily caloric intakes were approximately 50% lower during the first 10 days and 20% thereafter. Lower intakes in ethanol-fed rats occurred through a decrease in mean meal size rather than number of meals per day, although meals were more evenly distributed diurnally. Pair-fed rats ingested most of their food in one or two meals within a few hours of presentation. In a related experiment, a 4-hr duodenal infusion of ethanol at a rate comparable to that of ethanol ingestion resulted in plasma ethanol levels of 28 +/- 4 mM and suppressed 5-hr intake by approximately 40% by increasing the mean postmeal interval and satiety ratio. These results suggest that the suppressive effect of ethanol ingestion on food intake may be mediated in part by a post-gastric mechanism of ethanol action.

Alcoholism↗

Structural changes in rat bone subjected to long-term, in vivo mechanical loading.

Woven bone formation is commonly observed when grossly altered loading conditions are imposed upon living bone tissue. The fate of this woven bone with time has not been fully characterized. In this study, rats underwent daily bending of the right tibia for a period of 3 to 14 weeks. New bone was formed in the region of maximum bending stresses on the right tibiae of all rats that underwent daily loading. The new bone was at first poorly mineralized with disorganized collagen structure. With time, the new bone consolidated into a well mineralized primary bone structure similar in appearance to pre-existing nonlamellar bone within the tibial cortex. Using the data from this study and previous studies, we were able to outline the sequence of events that occur during bone adaptation in the rat tibia loading model. Explosive new woven bone formation began to occur five days after the initial four-point bending session, and the amount of woven bone reached a peak after about 15 days. After the third week the new bone began to consolidate. Rapid mineralization occurred during the third and fourth weeks, with less rapid mineralization occurring for several weeks thereafter. After the 14 weeks, the new bone was fully mineralized, and new bone formation had stopped.

Animals↗