Response of chronic denervated gastric pouches of rats to food and histamine

1962 ◽  
Vol 203 (4) ◽  
pp. 641-643 ◽  
Author(s):  
R. S. Alphin ◽  
T. M. Lin
Keyword(s):  
Hydrochloric Acid ◽  
Gastric Secretion ◽  
Acid Secretion ◽  
Dose Range ◽  
Gastric Pouch ◽  
Free Base ◽  
Conscious Rat ◽  
Volume Output ◽  
Dose Levels

The volume output and hydrochloric acid secretion from the denervated gastric pouch of the rat in response to food and histamine were studied. Food was given at three dose levels—1.25, 2.5, and 5.0 g—and histamine (as free base) was given subcutaneously at dose levels of 0.34, 0.7, 1.4, and 2.8 mg/kg. The results show that the chronic denervated gastric pouch of the rat responds in a graded manner to both food and histamine in a certain dose range. Although rats are not as sensitive to histamine as humans and dogs, the chronic gastric pouch of the conscious rat is far more sensitive to histamine than the stomach of the pyloric-ligated or anesthetized rat. The feasibility of using this preparation for testing the effect of agents inhibiting food- or histamine-stimulated gastric secretion is discussed.

Inhibition of cephalic and antral phases of gastric secretion by antral chalone

1962 ◽  
Vol 202 (4) ◽  
pp. 716-720 ◽  
Author(s):  
James C. Thompson ◽  
Harvey J. Lerner ◽  
Jorge A. Tramontana
Keyword(s):  
Hydrochloric Acid ◽  
Gastric Secretion ◽  
Portal Vein ◽  
Acid Secretion ◽  
Acid Output ◽  
Insulin Hypoglycemia ◽  
Heidenhain Pouch ◽  
Pavlov Pouch

The effect of antral acidification on the antral and cephalic phases of gastric secretion has been studied. Cross-transfusions were carried out between pairs of dogs in which blood from the portal vein of one dog was administered to another dog with a denervated fundic pouch. Transfusion of blood collected during acidification of the antrum resulted in a diminution of Heidenhain pouch acid secretion in response to food and to topical acetylcholine of 64% and 83%, respectively. The effect of antral acidification on gastric secretion stimulated by insulin hypoglycemia was studied in dogs prepared with Pavlov and isolated antral pouches (innervated and denervated). Irrigation of the antral pouch with .1 n hydrochloric acid resulted in a 92% decrease in Pavlov pouch acid output.

scholarly journals Inhibition of Gastric Secretion of Hydrochloric Acid in vivo by Carbonic Anhydrase Inhibition

Nature ◽  
1952 ◽  
Vol 170 (4325) ◽  
pp. 499-499 ◽  
Author(s):  
HENRY D. JANOWITZ ◽  
HENRY COLCHER ◽  
FRANKLIN HOLLANDER
Keyword(s):  
Hydrochloric Acid ◽  
Carbonic Anhydrase ◽  
Gastric Secretion ◽  
Carbonic Anhydrase Inhibition ◽  
Inhibition Of Gastric Secretion

Effects of bombesin on food intake and gastric acid secretion in cats

1989 ◽  
Vol 256 (1) ◽  
pp. R181-R186
Author(s):  
A. Bado ◽  
M. J. Lewin ◽  
M. Dubrasquet
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Gastric Secretion ◽  
Acid Secretion ◽  
Gastric Fistula ◽  
Single Class ◽  
Heidenhain Pouch ◽  
Daily Food Intake ◽  
Feeding Experiments ◽  
Daily Food

The brain and gut peptide bombesin has been reported both to stimulate gastric secretion and to induce satiety. To understand how the peripheral administration of bombesin affects food intake and whether gastric mechanisms are involved, a comparative study of the doses of bombesin active on gastric secretion, gastric emptying, and food intake was undertaken in cats provided with a gastric fistula and a denervated Heidenhain pouch. The smallest dose of intravenous bombesin that stimulated significantly basal acid secretion (20 pmol.kg-1.h-1) by the gastric fistula also enhanced meal-stimulated acid secretion by the Heidenhain pouch (+138%, P less than 0.01), delayed gastric emptying of a liquid protein meal (-30%, P less than 0.01), and suppressed food intake when the test meal was allowed to reach the stomach (-15%, P less than 0.01). Conversely, in sham-feeding experiments, the same dose of bombesin increased food intake (+35%, P less than 0.01). In full-day experiments conducted in nonfasted cats, bombesin decreased both the food intake in the 4-h period after the infusion and the daily food intake, whereas octapeptide cholecystokinin induced a transient satiety but did not decrease daily food intake. These results indicate that in cats the interaction of bombesin with "pregastric" mechanisms is not sufficient to induce satiety and that a relation could exist between the effects of bombesin on gastric secretion, emptying, and food intake. A single class of receptors might be involved in these peripheral effects of bombesin.

Note on the Digestion of Starch in the Stomach

1897 ◽  
Vol 21 ◽  
pp. 96-104
Author(s):  
W. G. Aitchison Robertson
Keyword(s):  
Hydrochloric Acid ◽  
Gastric Secretion ◽  
Caustic Potash ◽  
Gastric Fluid ◽  
Acid Solutions ◽  
Dilute Solution ◽  
Pure Acid ◽  
Starch Solution ◽  
Normal Human ◽  
Image Position

The following experiments were performed with normal human gastric secretion. After thoroughly washing out the stomach of a healthy man, several ounces of a dilute solution of Caffyn's liquor carnis were introduced into it. After the lapse of an hour the contents of the stomach were drawn off, filtered, and used instead of the pure acid solutions in former experiments. The acidity of the gastric fluid was due to inorganic acid and amounted to 0·15 per cent. hydrochloric acid.This experiment shows that, in the stomach, with an acidity of the contents less than that even normally present in the gastric secretion, the action of ptyalin is wholly restrained.Was the ferment merely inhibited from action by the acid, or was it destroyed ?To determine this, I took equal volumes of this gastric fluid, 1 per cent, starch solution, and saliva, and having mixed them, carefully neutralised the mixture with a solution of caustic potash, using very delicate test-papers to show the neutral point.On examining the mixture shortly after neutralisation, the whole of the starch was found to have undergone conversion. It reduced Fehling's solution strongly, and contained 0·22 per cent. of reducing substance. This demonstrates that, with an acidity equal to 0·05 per ′cent, hydrochloric acid, the action of ptyalin is restrained.I performed similar experiments with the gastric fluid from a case of chronic gastric catarrh, the acidity of which was equal to 0·067 per cent. hydrochloric acid.

Phase I study of spirogermanium given daily.

1983 ◽  
Vol 1 (5) ◽  
pp. 331-336 ◽  
Author(s):  
S S Legha ◽  
J A Ajani ◽  
G P Bodey
Keyword(s):  
Continuous Infusion ◽  
Tumor Regression ◽  
Dose Range ◽  
Maximum Tolerated Dose ◽  
Optimum Dose ◽  
Second Phase ◽  
Clinical Effects ◽  
Third Phase ◽  
Dose Levels ◽  
Dose Limiting Toxicity

Spirogermanium, an azaspirane compound, has recently had limited clinical trials using a schedule of intravenous injection one to three times every week. The observation of clinical antitumor activity and lack of myelosuppression prompted us to investigate further the clinical effects of spirogermanium administered on various schedules. A total of 52 patients with advanced metastatic tumors refractory to standard therapy were treated with spirogermanium. Three different schedules of drug administration were evaluated. Initially, a short daily IV infusion for 5 days every week was evaluated, starting with a dose of 30 mg/m2/day. A total of 22 patients received 69 courses with a dose range of 30-120 mg/m2/day for 5 days every week. The maximum tolerated dose was 100 mg/m2/day IV over 1 hr and 120 mg/m2 over 2-3 hr. In the second phase of the study, 12 patients received 41 courses of spirogermanium as a 24-hr continuous infusion for 5 days/wk at a dose of 150-375 mg/m2/day. The maximum tolerated dose was 200 mg/m2/day for 5 days. In the third phase of the study, 18 patients received spirogermanium as a continuous infusion daily for a median of 30 days (range 6-77 days) in a dose range of 100-200 mg/m2/day. The maximum tolerated dose was 150 mg/m2/day. Of the 44 assessable patients, 3 demonstrated a partial response and 3 had minor tumor regression; all responses occurred in lymphoma patients. The dose-limiting toxicity of spirogermanium was neurologic; other side effects consisted of mild anorexia, nausea and vomiting, and possible lung toxicity. There was no clear evidence of cumulative toxicity despite daily administration of spirogermanium. Our data suggest that spirogermanium can be administered daily by several different schedules, and the optimum dose depends on the infusion time and the duration of therapy. The delivery of drug by continuous infusion permitted administration of twofold higher dose levels compared to the standard IV schedules used in previous studies.

scholarly journals Tg.rasH2 Mice and not CByB6F1 Mice Should Be Used for 28-Day Dose Range Finding Studies Prior to 26-Week Tg.rasH2 Carcinogenicity Studies

2017 ◽  
Vol 36 (4) ◽  
pp. 287-292 ◽  
Author(s):  
Madhav G. Paranjpe ◽  
Jessica Belich ◽  
Tom J. Vidmar ◽  
Reem H. Elbekai ◽  
Marie McKeon ◽  
...  
Keyword(s):  
Selection Process ◽  
Dose Range ◽  
Maximum Tolerated Dose ◽  
High Dose ◽  
Dose Selection ◽  
Range Finding ◽  
Body Weights ◽  
Vehicle Test ◽  
High Doses ◽  
Dose Levels

Our recent retrospective analysis of data, collected from 29 Tg.rasH2 mouse carcinogenicity studies, determined how successful the strategy of choosing the high dose for the 26-week studies was based on the estimated maximum tolerated dose (EMTD) derived from earlier 28-day dose range finding (DRF) studies conducted in CByB6F1 mice. Our analysis demonstrated that the high doses applied at EMTD in the 26-week Tg.rasH2 studies failed to detect carcinogenic effects. To investigate why the dose selection process failed in the 26-week carcinogenicity studies, the initial body weights, terminal body weights, body weight gains, food consumption, and mortality from the first 4 weeks of 26-week studies with Tg.rasH2 mice were compared with 28-day DRF studies conducted with CByB6F1 mice. Both the 26-week and the earlier respective 28-day studies were conducted with the exact same vehicle, test article, and similar dose levels. The analysis of our results further emphasizes that the EMTD and subsequent lower doses, determined on the basis of the 28-day studies in CByB6F1 mice, may not be an accurate strategy for selecting appropriate dose levels for the 26-week carcinogenicity studies in Tg.rasH2 mice. Based on the analysis presented in this article, we propose that the Tg.rasH2 mice and not the CByB6F1 mice should be used in future DRF studies. The Tg.rasH2 mice demonstrate more toxicity than the CByB6F1 mice, possibly because of their smaller size compared to CByB6F1 mice. Also, the Tg.rasH2 males appear to be more sensitive than the female Tg.rasH2 mice.

THE ROLE OF HISTAMINE IN GASTRIC HYDROCHLORIC ACID SECRETION

1962 ◽  
Vol 99 (1 The Manegment) ◽  
pp. 30-44 ◽  
Author(s):  
T. M. Lin ◽  
R. S. Alphin ◽  
F. G. Henderson ◽  
D. N. Benslay ◽  
K. K. Chen
Keyword(s):  
Hydrochloric Acid ◽  
Acid Secretion
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