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1.
Gastrointest Endosc ; 51(4 Pt 1): 438-42, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10744816

ABSTRACT

BACKGROUND: Controversy exists concerning the safety and efficacy of colonic tattooing for the intraoperative identification of polypectomy sites. The purpose of this study was to determine (1) the concentrations of India ink and indocyanine green that resulted in high-visibility tattoos without significant tissue inflammation and (2) the India ink injection volume that produces best visibility at colonoscopy, laparoscopy, and laparotomy. METHODS: Twenty-two New Zealand white rabbits (2 kg) were anesthetized and injected with India ink (undiluted 1:10, 1:50, 1:100, 1:1000, 1:10,000) and indocyanine green as an undiluted, concentrated formulation (25 mL/2 mL solvent) or in a diluted form (25 mg/5 mL solvent) at various concentrations (1:10, 1:50, 1:100). Tuberculin syringes were used to create a 0.1 mL serosal bleb at two injection sites 2 cm apart. Laparotomy was repeated at days 1, 3, and 7 after injection. Additionally, 16 rabbits were injected with India ink at laparotomy and re-explored at 1 and 5 months. Twelve mongrel dogs (20 kg) were injected with 1.0 mL volumes. Re-exploration by colonoscopy, laparoscopy, and laparotomy was done at 7 days and 1 month. Tattoo visibility at re-exploration in both animal models was graded on a scale (0 = agent not seen, 1 = seen with difficulty, 2 = easily seen). Histology in the rabbit was judged by degrees of inflammation (0 = no inflammation, 2 = mild inflammation, 4 = moderate inflammation, 6 = severe inflammation). RESULTS: The concentrated indocyanine green solution was easily visible only on day 1 in the rabbit. Injections of both concentrated and diluted indocyanine green caused mucosal ulceration and moderate to severe inflammation. India ink studied at 7 days, 1 month, and 5 months after injection in the rabbit model was visible at all concentrations. The undiluted and 1:10 concentrations were easily seen and showed evidence of mucosal ulceration. Tattoos produced with all other India ink concentrations were visible without gross inflammation. India ink was also studied at 7 days and 1 month in dogs. The tattoo with the 1:100 concentration at 0.5 mL was seen consistently at colonoscopy, laparoscopy, and laparotomy with only a mild submucosal reaction at 7 days. The tattoos produced with the 1:100 and 1:1000 concentrations at 0.5 mL and 1.0 mL injection volumes were easily seen by all methods of intraabdominal visualization at 1 month with similar histology. CONCLUSION: Indocyanine green was an ineffective colonic tattooing agent. India ink was an effective colonic tattooing agent. Dilute concentrations that caused little to no inflammation could be visualized at 7 days and 1 month in rabbits and dogs and at 5 months in rabbits. India ink, at appropriated concentrations, appears to be a safe short- and long-term colonic tattooing agent.


Subject(s)
Carbon , Colonic Polyps/diagnosis , Coloring Agents , Indocyanine Green , Tattooing/methods , Animals , Colonic Polyps/surgery , Colonoscopy , Coloring Agents/adverse effects , Consumer Product Safety , Disease Models, Animal , Dogs , Dose-Response Relationship, Drug , Indocyanine Green/adverse effects , Laparoscopy , Laparotomy , Rabbits , Sensitivity and Specificity , Tattooing/adverse effects
2.
Dig Dis Sci ; 44(1): 20-4, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9952218

ABSTRACT

Irritable bowel syndrome (IBS) represents one of the most common gastrointestinal-related diagnoses. Although the precise etiologic basis of IBS is not known, a common presenting symptom is abdominal pain or discomfort that is thought to develop, at least in part, from a heightened awareness of visceral nociceptive input. Agents capable of reducing this heightened visceral nociception would, therefore, have utility in the treatment of IBS. In this study we evaluated the effects of intravenous and intracerebroventricular administration of a 5-HT3 receptor antagonist, alosetron, on blood pressure changes associated with rectal distension in anesthetized and awake dogs. This vasoactive reflex serves as a model for visceral nociception. For intracerebroventricular studies, the cerebroventricular guides were placed over the lateral ventricle. In anesthetized studies, blood pressure was measured by femoral artery cannulation. In awake studies, blood pressure was monitored by noninvasive measurement. A rectal balloon was placed in the rectum of each dog and maintained throughout the experiments. Each dose of alosetron was given to the dogs as an intravenous or intracerebroventricular bolus, and every 30 min the rectal balloon was inflated and blood pressure responses observed. In both anesthetized and awake dogs alosetron produced a significant inhibition of the vasoactive reflex. In particular, alosetron showed high potency when administered intracerebroventricularly. Alosetron, administered either centrally or peripherally, appears to modulate the visceral nociceptive effect of rectal distension in dogs.


Subject(s)
Blood Pressure/drug effects , Carbolines/pharmacology , Nociceptors/drug effects , Rectum/drug effects , Serotonin Antagonists/pharmacology , Animals , Blood Pressure/physiology , Carbolines/administration & dosage , Dogs , Injections, Intravenous , Injections, Intraventricular , Rectum/physiology , Serotonin Antagonists/administration & dosage
3.
Am J Physiol ; 273(2 Pt 1): G399-403, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9277419

ABSTRACT

A monoclonal antibody to gastrin was used to study the role of circulating gastrin in mediating acid secretion stimulated by sham feeding in dogs. On separate days, four conscious, fasted, adult mongrel dogs with esophageal and gastric fistulae were pretreated intravenously with either 7 mg of gastrin monoclonal antibody (MAb 28.2), 7 mg of keyhole limpet hemocyanin monoclonal antibody as control, or 12.5 micrograms/kg atropine sulfate. Thirty minutes later, acid secretion was stimulated first by sham feeding for 5 min, then, 60 min later, by an intravenous infusion of a maximum stimulatory dose of histamine (40 micrograms/kg) for 60 min, and after returning to basal, by intravenous infusion of a submaximal stimulatory dose of gastrin (200 pmol.kg-1.h-1) for 60 min. Acid output from secretions collected every 15 min by gravity drainage was determined by titration to pH 7.0 with 0.2 N NaOH. Sham feeding-stimulated acid output (17.7 +/- 5.5 mmol/h) was significantly inhibited by administration of either MAb 28.2 (0 mmol/h) or atropine (1.7 +/- 1.1 mmol/h). Histamine-stimulated acid output (19.6 +/- 3.4 mmol/h) was not reduced by either pretreatment. Gastrin-stimulated acid output (3.9 +/- 0.6 mmol/h) was significantly reduced only by pretreatment with MAb 28.2 (0.1 +/- 0.1 mmol/h) and not by atropine (2.2 +/- 1.4 mmol/h). A background intravenous infusion of pentagastrin (0.5 microgram.kg-1.h-1) restored sham feeding-stimulated acid output blocked by administration of MAb 28.2, although the intrinsic acid response to sham feeding could not be seen with the background pentagastrin infusion. Furthermore, the plasma gastrin response to sham feeding was not blocked by atropine pretreatment. Because immunoneutralization of both gastrin and cholinergic blockade significantly inhibited acid output during sham feeding, circulating gastrin and cholinergic pathways are involved in mediating the cephalic phase of gastric acid secretion in dogs.


Subject(s)
Eating/physiology , Gastric Acid/metabolism , Gastrins/physiology , Animals , Antibodies, Monoclonal , Dogs , Gastrins/blood , Histamine/pharmacology , Immunologic Techniques , Osmolar Concentration , Pentagastrin/pharmacology
4.
Br Vet J ; 150(6): 547-53, 1994.
Article in English | MEDLINE | ID: mdl-7850444

ABSTRACT

Copper oxide powder administered in the form of two experimentally produced sustained-release rumen boluses significantly increased blood and liver copper concentrations in growing sheep. It was estimated that 7% of the copper released was stored in the liver. In two farm observation trials administration of two standard production boluses significantly increased blood copper concentrations in out-wintered suckler cows during late pregnancy and early lactation, and in growing cattle at grass in the summer over periods of at least 170 and 123 days, respectively.


Subject(s)
Cattle/metabolism , Copper/metabolism , Copper/pharmacokinetics , Trace Elements/administration & dosage , Vitamins/administration & dosage , Animals , Copper/blood , Delayed-Action Preparations , Female , Liver/metabolism , Powders , Pregnancy , Rumen , Sheep/physiology , Trace Elements/metabolism , Vitamins/metabolism
5.
Regul Pept ; 52(3): 227-34, 1994 Aug 04.
Article in English | MEDLINE | ID: mdl-7800854

ABSTRACT

Neuropeptide Y (NPY) has been established as a potent orexigenic peptide, and recent studies suggest that NPY stimulates cephalic phase secretion as well. However, it is not known whether NPY's effects are pharmacologic or physiologic. In order to determine the physiologic significance of NPY, we examined the effects of two putative NPY receptor antagonists, PYX-1 and PYX-2, on sham feeding and gastric acid secretion in dogs. Our results demonstrate that intracerebroventricular (i.c.v.) injection of PYX-1 and PYX-2 at 1000 pmol/kg doses significantly suppresses the gastric acid response to sham feeding in dogs. The volumes sham fed were not significantly altered with i.c.v. administration of the antagonists. Peripheral administration did not affect acid secretion nor sham feeding volumes. Our data suggest that central administration of the novel NPY antagonists, PYX-1 and PYX-2, results in significant suppression of acid secretion in dogs. This supports our hypothesis that NPY functions as a physiologic modulator of cephalic phase acid secretion.


Subject(s)
Eating/drug effects , Gastric Acid/metabolism , Neuropeptide Y/analogs & derivatives , Neuropeptide Y/physiology , Peptide Fragments/pharmacology , Receptors, Neuropeptide Y/antagonists & inhibitors , Animals , Dogs , Neuropeptide Y/pharmacology
6.
Dig Dis Sci ; 39(7): 1405-8, 1994 Jul.
Article in English | MEDLINE | ID: mdl-7913011

ABSTRACT

The recently synthesized calcitonin gene-related peptide (CGRP) antagonist, human alpha-CGRP 8-37, was used to study its effects on gastric acid secretion. Four dogs with gastric fistula were used to measure the antagonist's physiologic effects in the stomach. All dogs received a bactopeptone dextrose meal (intragastric titration to pH 5.5) with either continuous CGRP 8-37 (1000 pmol/kg/hr) or saline (control). Additionally, intravenous bombesin (75-600 ng/kg/hr) and bethanechol (12.5-100 micrograms/kg/hr) was tested in the presence of the antagonist. Plasma gastrin levels also were measured via radioimmunoassay (RIA) in control and CGRP 8-37-stimulated animals. Gastric acid secretion increased by 100% with infusion of 1000 pmol/kg/hr CGRP 8-37 when compared to the control. Acid output increased 98% with both intravenous antagonist and 600 ng/kg/hr bombesin when compared to bombesin alone. However, no augmentation of acid secretion by CGRP 8-37 was shown with 25 micrograms/kg/hr bethanechol. RIA of plasma gastrin demonstrated no effect with the antagonist when given alone and did not increase bombesin-stimulated gastrin release. We conclude that CGRP 8-37 blocks native CGRP inhibitory effects on gastric acid secretion. Our findings of potentiation of acid secretion by bombesin as well as no change in gastrin levels in the presence of the antagonist is likely due to a blockage in a noncholinergic neuron to the somatostatin cell. Furthermore, CGRP 8-37 did not increase bethanechol-stimulated acid secretion, most likely due to bethanechol's (acetylcholine) nearly ubiquitous positive effects on acid secretion.


Subject(s)
Calcitonin Gene-Related Peptide/pharmacology , Calcitonin/antagonists & inhibitors , Gastric Acid/metabolism , Peptide Fragments/pharmacology , Animals , Bethanechol , Bethanechol Compounds/pharmacology , Bombesin/pharmacology , Dogs
7.
Brain Res ; 635(1-2): 118-24, 1994 Jan 28.
Article in English | MEDLINE | ID: mdl-8173946

ABSTRACT

Neuropeptide Y (NPY) has been shown to increase basal gastric acid secretion in dogs. We examined the hypothesis that NPY might increase gastric acid secretion by interaction with central catecholaminergic control of acid secretion in dogs. Studies were performed in awake canines with gastric fistulas and cerebroventricular guides which allowed injection into the lateral cerebral ventricle. Intracerebroventricular (i.c.v.) injection of yohimbine (5 micrograms/kg) increased acid secretion compared to control (yohimbine: 9.1 +/- 3.3 mmol/h; control: 1.8 +/- 1.0 mmol/2 h P < 0.05), whereas prazosin and propranolol (both 5 micrograms/kg i.c.v.) had no effect, suggesting that there is tonic central alpha 2-adrenergic inhibition of acid secretion. NPY13-36 significantly increased acid secretion compared to control (NPY13-36 1000 pmol/kg i.c.v.: 5.6 +/- 1.9 mmol/2 h; control: 1.3 +/- 0.8 mmol/2 h, P < 0.05), whereas [Leu31,Pro34]-NPY had no effect, suggesting that the central effect of NPY is mediated at a Y2, probably pre-synaptic receptor. Finally, i.c.v. desmethylimipramine (DMI) inhibited the acid response to i.c.v. NPY when injected before but not after NPY (i.c.v. DMI then i.c.v. NPY: control, 15.2 +/- 6.6 mmol/2 h; DMI, 3.5 +/- 1.2 mmol/2 h, P < 0.05; i.c.v. NPY followed by i.c.v. DMI: control, 8.9 +/- 4.0 mmol/2 h; DMI, 9.9 +/- 2.9 mmol/2 h, P > 0.05). This suggests that NPY acts by decreasing noradrenaline release. These findings are compatible with the hypothesis that i.c.v. NPY increases acid secretion by decreasing tonic central adrenergic inhibition of acid by decreasing release of noradrenaline at a pre-synaptic level.


Subject(s)
Adrenergic Antagonists , Gastric Acid/metabolism , Neuropeptide Y/administration & dosage , Animals , Basal Metabolism , Desipramine/administration & dosage , Dogs , Female , Injections, Intraventricular , Male , Neuropeptide Y/analogs & derivatives , Peptide Fragments/administration & dosage , Receptors, Neuropeptide Y/analysis
8.
Gastroenterology ; 105(4): 1069-77, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8405851

ABSTRACT

BACKGROUND: Neuropeptide Y (NPY), a centrally located neurotransmitter, is known to increase appetite in fasted and satiated animals. In addition to evaluating NPY's effect on eating behavior, this study was intended to determine whether intracerebroventricular (ICV) NPY would have an effect on canine gastric and pancreatic secretion. METHODS: Four dogs were prepared with cerebroventricular guides and gastric and pancreatic fistulas. ICV and intravenous NPY was administered during intragastric titration of a glucose and peptone meal. During this study, gastric and pancreatic secretion was measured, as well as insulin levels and pancreatic polypeptide (PP). An additional set of four dogs were prepared with esophageal fistulas and cerebroventricular guides, and the effect of ICV NPY on sham feeding was studied. RESULTS: ICV NPY significantly increased sham feeding, meal-stimulated gastric and pancreatic secretion, basal gastric acid, pancreatic bicarbonate, insulin levels, and PP. Vagotomy blocked the effect of ICV NPY on gastric acid secretion in a urethane-anesthetized rat model with acute gastric fistula. CONCLUSIONS: ICV NPY increased sham feeding, gastric and pancreatic secretion, insulin levels, and PP in the dogs. NPY's effect on gastric secretion was blocked by vagotomy in a rat model. NPY should be considered a candidate mediator of cephalic phase secretion.


Subject(s)
Eating/drug effects , Gastric Mucosa/metabolism , Neuropeptide Y/administration & dosage , Neuropeptide Y/pharmacology , Pancreas/metabolism , Analysis of Variance , Animals , Bicarbonates/metabolism , Disease Models, Animal , Dogs , Eating/physiology , Female , Gastric Acid/metabolism , Gastric Acidity Determination , Gastric Fistula/metabolism , Glucose/administration & dosage , Injections, Intravenous , Injections, Intraventricular , Insulin/metabolism , Insulin Secretion , Male , Pancreatic Polypeptide/metabolism , Peptones/administration & dosage , Rats , Rats, Sprague-Dawley , Vagus Nerve/physiology
9.
Am J Physiol ; 265(2 Pt 1): G219-23, 1993 Aug.
Article in English | MEDLINE | ID: mdl-8368307

ABSTRACT

The role of cholecystokinin (CCK) as a central and peripheral satiety factor was studied using the CCK-B (L-365,260) and CCK-A (MK-329) receptor antagonists in esophageal-fistula dogs. Suppression of feeding was induced by either balloon gastric distension or small bowel nutrient infusion and was measured as the volume sham fed. Intracerebroventricular L-365,260 abolished satiety behavior from gastric distension (volume sham fed 2,667 +/- 211 ml vs. vehicle alone 1,217 +/- 446 ml, P < 0.05) but not small bowel infusion. Intravenous MK-329 abolished satiety behavior from small bowel infusion (volume sham fed 1,900 +/- 521 ml vs. vehicle alone 210 +/- 198 ml, P < 0.05) but not from gastric distension. The volume sham fed after intracerebroventricular MK-329 with balloon gastric distension or small bowel infusion did not differ from control. These results suggest that, in the brain, CCK is a physiological mediator of satiety behavior from gastric distension but not small bowel nutrients and, in the periphery, CCK is a physiological mediator of satiety behavior from small bowel nutrients but not gastric distension.


Subject(s)
Benzodiazepinones/pharmacology , Brain/physiology , Phenylurea Compounds , Receptors, Cholecystokinin/antagonists & inhibitors , Satiety Response/drug effects , Animals , Catheterization , Devazepide , Dogs , Enteral Nutrition , Injections, Intravenous , Injections, Intraventricular , Stomach/physiology
10.
Physiol Behav ; 53(6): 1231-4, 1993 Jun.
Article in English | MEDLINE | ID: mdl-8346312

ABSTRACT

Six mongrel dogs (18-20 kg) were prepared with gastric and esophageal fistulas. All dogs were studied under four experimental conditions. In conditions 1 and 3 the dogs were allowed to sham feed either a high-palatable or low-palatable meal on days 1-5 followed by a sham feed of a high-palatable or low-palatable meal on day 6. In conditions 2 and 4 the dogs were not sham fed (oral sensory deprived) on days 1-5 but were allowed to sham feed either a high-palatable or low-palatable meal on day 6. Total caloric requirement during each 6-day study was given by infusion of a liquid diet (Isocal) through the gastric fistula following the experiment. In condition 4, dogs deprived of oral sensation on days 1-5, significantly overconsumed their low-palatable meal on day 6. In condition 2, dogs deprived of oral sensation on days 1-5 also overconsumed their high-palatable meal on day 6, although this did not reach statistical significance. Dogs that received oral stimulation days 1-5 (conditions 1 and 3) did not overconsume their high- and low-palatable meals on day 6, suggesting that binge eating following short-term oral deprivation may be avoided if the diet provides adequate oral sensory stimulation. Body weights were well maintained throughout each study period and no changes were observed.


Subject(s)
Eating/physiology , Satiety Response/physiology , Sensory Deprivation/physiology , Taste/physiology , Animals , Dogs , Energy Intake/physiology , Enteral Nutrition , Gastric Acid/metabolism , Pancreatic Polypeptide/blood
12.
Physiol Behav ; 47(6): 1295-7, 1990 Jun.
Article in English | MEDLINE | ID: mdl-2395936

ABSTRACT

Six mongrel dogs with gastric and esophageal fistulas (n = 4) or with gastric and pancreatic fistulas (n = 2) were studied to determine the role of taste on gastric and pancreatic secretion. Stimulation of the back of the throat with a range of tastants produced gastric acid, bicarbonate, protein, and pancreatic polypeptide levels that were statistically equivalent to those produced with stimulation of the entire tongue. This suggests that the vagus nerve is the primary mediator of the cephalic phase response to tastants. There were marked individual differences among dogs in the responses to the ten tastants that were tested. On average, monosodium glutamate and seltzer, which mongrel dogs do not normally encounter in their diets, produced lower gastric acid secretion and pancreatic polypeptide release than sweet, sour, salty, bitter, and meaty tastes. The gastric acid secreted by the dogs with esophageal fistulas in response to tastes was only one-half as large as levels previously reported for sight/smell of food and only one sixth as large as those obtained with sham feeding.


Subject(s)
Bicarbonates/metabolism , Gastric Acid/metabolism , Gastric Mucosa/physiology , Pancreas/physiology , Pancreatic Polypeptide/metabolism , Taste/physiology , Animals , Arousal/physiology , Cranial Nerves/physiology , Dogs
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