Biomedical subjects
Publications and source records attributed to G B Glavin.
Rats were orally administered ascorbic acid at a dose of 30 g/liter during either total starvation, partial starvation, the activity-stress ulcer procedure, or the restraint-cold procedure. In four experiments, ascorbic acid failed to exert significant protective action against stomach ulcer formation and, in fact, may have potentiated the ulcerogenic process.
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The effects of solid non-nutritive diet on pylorus-ligation ulcers were tested. An experimental group of 16 rats received a bulky mixture of silica and methylcellulose during 48 hr prior to ligation. Control rats were food deprived for the same period of time. A multivariate analysis of variance was applied to nine measures of the study. It was found that rumenal ulceration and total acidity were lower in experimental animals than in controls. This finding confirms a previous observation indicating that the physical property of diet has antiulcerogenic effects.
The incidence of starvation-induced gastric lesions was observed in Sprague-Dawley rats obtained from four different vendors (ARS/Sprague-Dawley, Hilltop, Holtzman, and Charles River). Food was withheld for 5 days from rats weighing 150, 200, 260 or 330 g. Glandular lesions occurred in 150 g rats; rumenal lesions occurred in 200+ rats. ARS/Sprague-Dawley rats developed more glandular lesions, whereas Hilltop rats developed more rumenal lesions.
A stainless steel gastric cannula was surgically implanted in the rat forestomach to allow gastric secretion to be collected continuously without restraining the animal. When gastric collections were not being made, the cannula was closed with a plugging screw. Rats with these cannulas were easily maintained without special care or complications for 12 months.
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The interpretive benefits of employing multivariate analysis methods on experimental data with more than one dependent variable are described heuristically and illustrated on a set of data from a simply designed experiment in physiological psychology. Multivariate analysis of variance (MANOVA) is performed on the 9 dependent variables contained in the sample data and on the four composites derived from a principal components analysis (PCA) of the variability of the nine. A linear discriminant analysis (LDA) is conducted following both MANOVA results, and 5 methods of determining the "important" dependent variables in the experimental-control group difference are presented and discussed in terms of the data at hand.
Rats were given either seven or 14 days of experience with either restricted feeding (2 hr/day) or activity (24 hr/day of access to activity wheels with ad libitum feeding). Animals were then subjected to the activity-stress ulcer procedure involving 1 hr/day of feeding and continuous access to running wheels. Neither experience with restricted feeding nor with activity wheels attenuated gastric ulceration, indicating that adaptation did not occur. Rats with either restricted feeding experience or activity experience died faster and exhibited more frequent and more severe stomach damage relative to nonexperienced controls.
Pregnant primiparous rats were subjected to four days of light restraint stress on postconception days 7 through 10, inclusive, coincident with the development of the fetal gastrointestinal system. Twenty male and twenty female offspring from prenatally stressed and nonstressed rats were then subjected to two hours of supine cold-restraint as adults. Eighty percent of nonprenatally stressed offspring developed gastric lesions, while 47.5% of offspring of prenatally stressed mothers displayed lesions. A significant sex-stress interaction was detected, indicating that male offspring from prenatally stressed mothers display less severe gastric lesions in response to restraint stress as adults than do male offspring from nonprenatally stressed mothers. Female offspring from both prenatal stress conditions showed similar levels of stress-induced lesions.
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We have reviewed the neurobiology of stress ulcers from animal models to potential pharmacotherapeutic mechanisms. The evidence strongly supports the hypothesis that certain stress-related gastric lesions are 'brain-driven' events which may be more effectively managed through central manipulations than by altering local, gastric factors. Recent advances in the use of anxiolytic and antidepressant drugs in the management of stress-related gastric mucosal injury further supports the contention that a brain-gut axis, which may have nervous, peptidergic and classic monoaminergic components, modulates the intricate and complicated pattern of communication between the brain and the stomach. Delineation of the precise pathways which make up this communication as well as their manipulation by various pharmacological agents will be the focus of future research endeavour.
Virtually all peptides are biologically active following central administration as a consequence of both direct and indirect cellular actions. Direct effects are mainly interactions with specific membrane receptors but may include unions with other components of the receptor/effector complex. Significant indirect biological effects of exogenous peptides, including apparent secretagogue effects on endogenous peptides largely overlooked in practice, result from extensive competition with endogenous peptides for degradative enzymes (peptidases). A consequence of this competition is enhancement of tonic or intermittent activity of endogenous peptides. The pharmacological profile of any peptide reflects or includes, therefore, the spectrum of endogenous peptides that is protected from peptidase action. It is likely that certain pharmacologically active peptides, including a large number of di-, tri- and oligo-peptides, elicit responses mainly or exclusively by competing for peptidases. Therefore, reliable estimates of the relative contributions of direct and indirect actions of exogenous peptides may be difficult, if not impossible, to obtain.
Rats were screened in an alcohol-water free-choice paradigm and divided into low-ethanol preferring (1.5-2.5 g/kg/day), medium-ethanol-preferring (2.5-4.5 g/kg/day) and high-ethanol-preferring (4.5-6.0 g/kg/day) groups. In addition, a non-ethanol-exposed group was included. Each of these groups was again subdivided with half the animals in a group being food deprived for 16 hr, and the other half having ad lib access to food. All rats were then subjected to restraint in the supine position in a cold (4-6 degrees C) environment for 3 hr. Significant differences in ulcer incidence and severity (cumulative length of the ulcers expressed in millimeters) occurred, suggesting that higher intake of alcohol is associated with greater ulcer severity. This pattern occurred for both food-deprived and non-deprived animals.
Rats were given 6% ethanol (v/v) as their only source of liquid for 4 days. On the basis of ethanol consumption (g/kg/day), animals were divided into high, medium and low ethanol consuming groups. A non-ethanol exposed control group was also included. Following a 24 hr food deprivation period, animals were restrained for 3 hr. No differences in gastric ulcer frequency or severity were noted with the exception of a slight tendency toward a lower incidence among ethanol consuming rats relative to controls. An unusual observation was the high incidence of duodenal ulcer observed only among ethanol consuming rats. This ethanol-stress interaction is discussed in terms of an animal's history of ethanol exposure.