Biomedical subjects

H T Debas

Publications and source records attributed to H T Debas.

At least 91 records · Page 5Linked to original sources

PubMed1985

Increased antral G-cell number and gastrin content in dogs after massive small bowel resection.

The effects of massive small-bowel resection on antral gastrin tissue concentration and G-cell number have been investigated in the dog. Tissue gastrin concentrations increased significantly after resection from 16.8 +/- 2.6 ng/mg wet weight to 30.3 +/- 3.2 ng. Immunoreactive gastrin cell number also increased from 29.8 +/- 2.5 cell/mm2 to 43.1 +/- 3.0 cells/mm2. Immunocytochemistry demonstrated that the hyperplastic gastrin cells were found in small groups, with the majority of the immunoreactivity located at the luminal pole of the cells. This finding, linked to hypogastrinemia in the dogs after massive small bowel resection, suggests that some of the hyperplastic G cells may have an exocrine rather than endocrine function.

Animals↗

PubMed1985

Peptide YY: metabolism and effect on pancreatic secretion in dogs.

Peptide YY is an ileocolonic peptide that inhibits meal-stimulated pancreatic secretion when infused in a dose of 400 pmol/kg X h. In this study pancreatic secretion was monitored in response to increasing doses of secretin or cholecystokinin-octapeptide (62.5, 125, 250, and 500 ng/kg X h) during the simultaneous infusion of either saline or peptide YY (400 pmol/kg X h). Peptide YY significantly (p less than 0.05) inhibited the secretory response to the three lowest doses of each pancreatic secretogogue, reducing the bicarbonate response to the 62.5-ng/kg X h dose of secretin by 86% +/- 6% and the protein response to the same dose of cholecystokinin by 57% +/- 16%. In the second limb of the study, the half-life of peptide YY (11.7 +/- 21 min) and the metabolic clearance rate (13.8 +/- 1.6 ml/kg X min) were found to be similar to those of other gastrointestinal hormones. We conclude that inhibition of meal-stimulated pancreatic secretion by peptide YY can be explained by its ability to decrease the responsiveness of the pancreas to endogenous secretogogues.

Animals↗

PubMed1985

Hypergastrinemia develops within 24 hours of truncal vagotomy in dogs.

Postvagotomy hypergastrinemia may result from withdrawal of tonic vagal inhibitory mechanism(s) or from G-cell hyperplasia secondary to diminished acid secretion. Early development of hypergastrinemia, after vagotomy, would favor the first mechanism, whereas delayed development would favor the second. We sought to distinguish between these two mechanisms and to determine whether alterations in somatostatin release might mediate postvagotomy hypergastrinemia. We measured plasma concentrations of gastrin and somatostatinlike immunoreactivity basally and in response to meal (pH controlled at 5.5) and to insulin hypoglycemia before and after truncal vagotomy in 11 dogs. Basal and postprandial hypergastrinemia were established within 24 and 48 h after vagotomy, respectively. Basal and meal-stimulated plasma somatostatinlike immunoreactivity concentrations were unaltered by vagotomy, although insulin hypoglycemia-induced rises in plasma somatostatinlike immunoreactivity were abolished by vagotomy. Our data suggest that neither G-cell hyperplasia nor alterations in somatostatin release explain postvagotomy hypergastrinemia in the dog. The observations support the hypothesis that postvagotomy hypergastrinemia results from the withdrawal of a tonic vagal inhibitory mechanism of gastrin release that is independent of somatostatin. Whether the tonic vagal inhibition of gastrin is direct or indirect is unknown.

Animals↗

PubMed1985

The role of amniotic fluid in fetal nutrition.

The contribution of amniotic fluid to fetal growth and gastrointestinal tract development was studied in a rabbit model. In the fetal rabbit, at 23 days gestation, 3 conditions were surgically produced: (1) prevention of swallowing of amniotic fluid by esophageal ligation (n = 8); (2) esophageal ligation but insertion of an esophageal cannula distally to allow continuous infusion into the stomach of bovine amniotic fluid to mimic fetal swallowing (n = 7); and (3) sham operation (n = 7). Fetuses were delivered by Caesarean section at 28 days gestation. Esophageal ligation resulted in significant reductions of birth weight and crown-rump length and a trend to decreased liver weight when compared to sham operated controls. Additionally, marked reductions in gastric and intestinal tissue weight and gastric acidity were found following esophageal ligation. These reductions in both somatic and gastrointestinal tract growth and gastric function were reversed by infusion of amniotic fluid intragastrically. We conclude that amniotic fluid provides 10% to 14% of the nutritional requirements of the normal fetus, and that amniotic fluid contains a potent and as yet undefined gastrointestinal tract trophic factor.

Amniotic Fluid↗

PubMed1985

Canine bombesin-like gastrin releasing peptides stimulate gastrin release and acid secretion in the dog.

The synthetic mammalian bombesin-like peptides, canine gastrin releasing peptide 27, 23 and 10, and porcine gastrin releasing peptide 27 were compared with amphibian bombesin 14 and 10 during intravenous infusions into six conscious dogs with chronic gastric cannulae. Gastrin and gastrin releasing peptide were measured in peripherally sampled venous blood by radioimmunoassay and gastric acid secretions were collected. All forms of gastrin releasing peptide stimulated gastrin release and gastric acid secretion in a dose-dependent manner. The larger canine and porcine peptides were more potent than the decapeptide. Bombesin 14 was more potent than bombesin 10. A rise in the venous concentration of immunoreactive gastrin releasing peptide of only 20 fmol ml-1 stimulated gastrin release to about 50% of maximal. Gastrin releasing peptide 10 was cleared from the circulation three times faster than the larger forms and this may account for the apparent differences in potency.

Animals↗

PubMed1985

Peptide YY inhibits meal-stimulated pancreatic and gastric secretion.

Peptide YY was recently isolated from porcine intestine and shown to exhibit marked structural homology with pancreatic polypeptide, a potent inhibitor of pancreatic exocrine secretion. We have examined the effects of infused peptide YY on gastric and pancreatic secretion in four mongrel dogs with gastric and pancreatic fistulas. A 15% liver extract meal was instilled intragastrically, and normal saline or one of three doses of peptide YY (200, 400, and 800 pmol X kg-1 X h-1) was infused into a peripheral vein. All three doses of peptide YY significantly inhibited meal-stimulated pancreatic fluid and bicarbonate secretion, with the lowest dose inhibiting secretion by 44.5 +/- 3.5 and 53.6 +/- 8.5%, respectively. Pancreatic protein secretion and gastric acid secretion were significantly inhibited by the two highest doses. The 200, 400, and 800 pmol X kg-1 X h-1 doses of peptide YY were associated with increments in peripheral blood of 201 +/- 24, 357 +/- 50, and 971 +/- 139 pM, respectively. These values compared with mean increments of 86.3 +/- 8.5 pM after a meat meal and 403 +/- 63 pM after intestinally perfused oleic acid. The present studies demonstrate that peptide YY inhibits gastric and pancreatic secretion and suggest that peptide YY may be the gastric and pancreatic inhibitor in ileocolonic mucosa that is released by perfusion of the intestine with oleic acid.

Amino Acid Sequence↗

PubMed1985

Cholecystokinin is not a peripheral satiety signal in the dog.

The doses of cholecystokinin (CCK) that have been shown to cause satiety after peripheral administration are pharmacological and whether "physiological" doses of exogenous CCK or endogenously released CCK have a satiety effect is not known. The purpose of the present study is threefold: to compare the potency of endogenous and exogenous CCK for their satiety, cholecystokinetic, and pancreozyminic actions; to determine whether small doses of CCK in the presence of gastric distension cause satiety; and to test the satiety effect of CCK administered centrally into the lateral cerebral ventricle. Dogs were prepared with cerebroventricular guides and esophageal and duodenal fistulas (n = 4), with chronic bile fistulas (n = 8), and chronic pancreatic fistulas (n = 7). Satiety effect was quantified in the esophageal fistula dog by the amount of blenderized food sham fed within 7.5 min. Duodenal perfusion of fat, used as a releaser of endogenous CCK, stimulated pancreatic protein, and gallbladder contraction with D50 values of 1.5 and 0.3 mmol/h, respectively, but had no effect on the volume sham fed (316 +/- 82 ml/min without and 371 +/- 41 ml/min with the maximal dose of sodium oleate infused). The D50 values of CCK-8 (pmol X kg-1 X h-1) for satiety and for stimulation of pancreatic enzyme secretion and gallbladder contraction were 440, 120, and 22, respectively. Injection of CCK-8 into the lateral cerebral ventricle inhibited sham feeding in a dose-dependent manner. We conclude that duodenal fat in doses producing maximal gallbladder and pancreatic stimulation has no satiety effect in the dog.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Opposing central and peripheral actions of brain-gut peptides: a basis for regulation of gastric function.

The existence of an increasing number of peptides in both the gut and the brain provides the basis for the concept of a brain-gut axis. However, to date, no unifying hypothesis has been put forward to explain the physiologic significance of this remarkable phenomenon. The present study examines the central and peripheral actions on gastric function of cholecystokinin octapeptide (CCK-8), somatostatin, and bombesin, all of which exist in both the gut and brain. Intravenous infusion of CCK-8, in doses of 50, 100, and 200 pmol X kg-1 X hr-1, caused 28%, 38%, and 52% inhibition, respectively, of the rate of gastric emptying of a liquid meal in dogs. By contrast, the injection of 32, 64, and 128 pmol X kg-1 into the lateral cerebral ventricle of these dogs accelerated gastric emptying by 6%, 26%, and 32%, respectively. Bombesin, which stimulated gastric acid secretion in a dose-dependent manner but which had no effect on the submaximal acid response to pentagastrin when administered peripherally, inhibited in a dose-dependent manner the submaximal response to pentagastrin when given centrally, with a maximal inhibition of 66% +/- 5%, at a dose of bombesin of 180 pmol X kg-1. Similarly, somatostatin-14 caused graded inhibition of pentagastrin-stimulated acid secretion when it was administered peripherally but caused dose-dependent augmentation of the acid response when it was given centrally. Maximal inhibition of 51% of the pentagastrin response occurred with a peripheral dose of somatostatin of 800 pmol X kg-1 X hr-1. By contrast, maximal augmentation of the pentagastrin response of 78% occurred when a dose of 400 pmol X kg-1 of the peptide was injected into the lateral ventricle. We conclude that CCK-8, bombesin, and somatostatin have opposing actions on gastric function when administered centrally and peripherally. We propose that this phenomenon may be common to all neuropeptides of the brain-gut axis and may provide a basis for central regulation of gut function.

Animals↗

PubMed1984

A new intraoperative test for completeness of vagotomy: the PCP-GABA (beta-parachlorophenol-gamma-aminobutyric acid) test.

PCP-GABA, an analogue of the neurotransmitter amino acid, GABA, is as effective a stimulant of vagal centers and acid secretion as sham feeding. Insulin hypoglycemia, a test hitherto widely used for the cephalic phase, is unsafe and nonspecific because it also stimulates catecholamine release which affects gastrin secretion. PCP-GABA, unlike insulin, causes no tachycardia or hypoglycemia; however, the major advantage of PCP-GABA is that it can be used safely intraoperatively to assess completeness of vagotomy. Its muscle relaxant action is an additional advantage in this regard. As an intraoperative test, PCP-GABA is given intravenously shortly after induction of anesthesia to stimulate acid secretion and to reduce gastric mucosal pH, which is measured by an intraluminal combination electrode. The electrode can be moved around through the intact gastric wall to take measurements from multiple sites. When vagotomy is complete, gastric mucosal pH increases to over 6. This test works well in the dog. We hope to assess its clinical use in the near future.

Animals↗

PubMed1984

Intravenous mixed amino acids and fats do not stimulate exocrine pancreatic secretion.

We compared the responses of the canine exocrine pancreas to intraduodenal versus intravenous administration of mixed amino acids, fat emulsion, and glucose. Graded doses of amino acid mixture and of fat emulsion gave graded responses in volume, protein, and bicarbonate when administered intraduodenally. In contrast, the same doses of the amino acid mixture and fat emulsion administered by central intravenous infusion caused no significant pancreatic secretion of volume, protein, or bicarbonate. Graded doses of glucose caused no statistically significant pancreatic secretion whether they were given intraduodenally or intravenously. We conclude, contrary to a previously published observation, that amino acids and fats given parenterally do not stimulate pancreatic secretion. As a corollary, it is reasonable to assume that the pancreas is not stimulated during total parenteral nutrition with acute pancreatitis or a pancreatic fistula.

Amino Acids↗

PubMed1984

Bethanechol prevents inhibition of gastric acid secretion by gastric inhibitory polypeptide.

Earlier studies of gastric inhibitory polypeptide (GIP) have shown that it is a powerful inhibitor of acid secretion in denervated gastric pouches. Other studies, however, have shown that it is a weak inhibitor in innervated stomach preparations. In this study we evaluated the inhibitory action of GIP in four dogs, each provided with both a vagally denervated (Heidenhain) pouch and a gastric fistula of the innervated stomach. The effect of intravenous infusion of pure porcine GIP (1 microgram X kg-1 X h-1) on pentagastrin dose response was studied with and without background infusion of bethanechol (25 micrograms X kg-1 X h-1). GIP powerfully inhibited pentagastrin-stimulated acid secretion from the Heidenhain pouch but not from the gastric fistula. The maximal inhibition was 76% for the Heidenhain pouch and 29% for the gastric fistula. Despite the attainment of high levels of circulating immunoreactive GIP (greater than 3,000 pg/ml) early after the onset of infusion of the peptide, inhibition occurred relatively late, suggesting that this action of GIP might be mediated by the release of some other substance(s). Background infusion of bethanechol totally abolished the inhibitory action of GIP in both the Heidenhain pouch and gastric fistula.

Animals↗

PubMed1984

Vagal control of gastrin release in the dog: pathways for stimulation and inhibition.

The vagus has a dual effect on gastrin: it both stimulates and inhibits its release. To determine the gastric vagal pathways for these opposing effects, plasma gastrin and acid responses to meal (intragastric titration of 15% liver extract, pH 5.5) and to insulin (0.5 U regular insulin intravenously) were studied in seven dogs in three consecutive stages: a control stage, after antral vagotomy (AV), and after subsequent proximal gastric vagotomy (PGV). AV abolished the plasma gastrin response to insulin but had no effect on either basal or meal-stimulated gastrin release. Subsequent PGV caused significant elevation in basal plasma gastrin concentration, no further change in the gastrin response to insulin, but a significant increase in meal-stimulated gastrin release. AV decreased acid response to insulin nonsignificantly and had no effect on meal-stimulated acid secretion. Subsequent PGV reduced by 90% the acid response to insulin, had negligible effect on the gastric fistula acid response to meal, but increased Heidenhain pouch response sixfold. These studies show that vagal stimulation of gastrin release is mediated along direct antral vagal pathways, while vagal inhibition requires intact vagal fibers to the proximal stomach. The mechanism by which the fundic vagal pathways exert an inhibitory influence on the G cell in the antrum is yet to be elucidated.

Animals↗

PubMed1984

Gastric function before and after gastric sympathectomy and subsequent truncal vagotomy.

A surgical technique for selective gastric sympathectomy (SGS) has been developed by total devascularization of the dog stomach with immediate revascularization via the divided and reanastomosed splenic artery and vein. Splenectomy is also performed to divert the entire splenic blood-flow to the stomach. Several months later biopsy of vessels from the gastric wall shows that all catecholamine staining is lost. Blood-flow studies using the aminopyrine clearance method show that a significant decrease in blood-flow occurs, particularly during maximal acid secretion. The effects of SGS on the gastric acid responses of 5 dogs were: (1) increased responsiveness to histamine with a left shift of the dose-response curve (D50 = 35 +/- 5 before, and 17 +/- 4 micrograms kg-1 hr-1 after; p less than 0.05); (2) increased response to insulin hypoglycemia (peak 15 min output = 3.5 +/- 0.9 before, and 5.5 +/- 0.9 mMol after; p less than 0.05); but (3) a reduction of acid response to meal (peak 15 min output = 7.1 +/- 0.9 before, 3.7 +/- 1 after; p less than 0.05). Propranolol, on the other hand, had no effect on the response to meal before SGS but enhanced it after SGS restoring the response to pre-SGS levels. Subsequent vagotomy abolished acid response to insulin but did not alter the post-SGS response to a meal. We conclude that the sympathetics exert a beta-adrenergic inhibitory influence on gastric acid response to insulin and histamine but not to food. Following SGS, the enhancing effect of propranolol probably implies supersensitivity of the stomach to circulating catecholamines.

Animals↗

PubMed1983

Reduced mortality from bleeding pseudocysts and pseudoaneurysms caused by pancreatitis.

Exigent hemorrhage from pseudocysts and pseudoaneurysms is the most rapidly lethal complication of pancreatitis. Of eight patients with this unusual entity seen by us, all had acute gastrointestinal hemorrhage; two patients had intraperitoneal bleeding as well. Preoperative visceral arteriograms accurately defined the bleeding lesion and greatly aided in planning operative strategy in six patients. Emergency celiotomy and arterial ligation were accomplished in seven patient, and one patient underwent successful transcatheter arterial embolization. Pancreatic resection was not required in any patient for control of hemorrhage, although gastrectomy was necessary in three cases. One elderly patient died of sepsis five weeks after operation. Our mortality of 12.5% compares favorably with the 37% overall mortality from 123 cases reported in the literature.

Alcoholism↗

PubMed1983

GABA-mimetic effect on gastric acid secretion. Possible significance in central mechanisms.

Parenteral administration of beta-(p-chlorophenyl)-gamma-aminobutyric acid (PCP-GABA), a lipophilic GABA mimetic, has been shown to aggravate stress-induced ulcerations in the rat. Since acid hypersecretion may be a possible mechanism for this, we studied the effect of graded doses of PCP-GABA on rat gastric acid secretion. The stimulatory effect of PCP-GABA was found to be dose-dependent, long-acting, and massive, exceeding the maximal effects of histamine and bethanechol. The acid stimulant effect of PCP-GABA was completely abolished not only by atropine but also by truncal vagotomy. Vagotomized, PCP-GABA-treated animals responded to bethanechol, suggesting that a peripheral (cellular) mechanism is not involved. We conclude that PCP-GABA acts centrally to activate vagal centers and to cause acid hypersecretion. Although hypersecretion of acid caused by PCP-GABA may be involved in the observed aggravation of stress-induced ulceration in the rat stomach, evidence for this has yet to be provided.

Animals↗

PubMed1983

Use of secretin in the roentgenologic and biochemical diagnosis of duodenal gastrinoma.

The use of secretin in the biochemical and roentgenologic diagnoses of a duodenal gastrinoma has been described. Preoperatively, the secretin test indicated that a gastrinoma and not a retained antrum was the cause of hypergastrinemia in a patient who had previously undergone Billroth II gastrectomy. Intravenous infusion of secretin during selective angiography resulted in greatly enhanced visualization of the tumor which allowed it to be localized to the duodenal stump. Several months postoperatively, the secretin test result had become negative, which presumably suggested that the tumor had been excised completely. Our experience has revealed that intravenous secretin might improve the diagnostic usefulness of selective angiography.

Aged↗

PubMed1983

Proximal gastric vagotomy interferes with a fundic inhibitory mechanism. A hypothesis for the high recurrence rate of peptic ulceration.

The mucosa of the proximal stomach contains a powerful inhibitor of acid secretion and gastrin release. The release of this inhibitor is dependent on intact vagal innervation of the proximal stomach. Thus, proximal gastric vagotomy interferes with the release of the inhibitor. After proximal gastric vagotomy for peptic ulcer, recurrence rates increase over time. In addition, there is some recovery of acid secretion. Although nerve regeneration or sprouting has been suggested as the possible explanation for these events, we propose that interference with the inhibitory mechanism of the proximal stomach may be another possible explanation for the increasing ulcer recurrence rates after proximal gastric vagotomy. At present, this is only a hypothesis and is suggested only by indirect evidence. Direct testing of the hypothesis will require complete purification of the inhibitor and the development of a specific radioimmunoassay.

Animals↗

PubMed1983

Preparation of the orthotopic autotransplanted pancreas for long-term exocrine studies.

The operative technique for the construction of an orthotopically autotransplanted pancreas with a permanent pancreatic fistula has been described. The operation is performed in two stages, with preparation of the transplant based on the gastroduodenal artery and superior pancreaticoduodenal vein in the first stage and construction of a Herrera-type permanent pancreatic fistula in the second stage. Elimination of warm ischemic time by dividing and reanastomosing the vessels on which the transplant will be based during the first stage while the pancreas continues to be perfused by its other vessels resulted in a uniformly successful outcome. The pancreatic transplant functioned well. The dogs were neither diabetic nor exocrine pancreatic deficient. Their responses to stimulation with exogenous secretin and the cholecystokinin analogue, cerulein, were only slightly less than those of dogs without a pancreatic transplant. This preparation should enable studies to be carried out that will better define the interactions of nerves and hormones in the control of pancreatic secretion.

Fistula↗