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Biomedical subjects

J Elashoff

Publications and source records attributed to J Elashoff.

At least 37 records · Page 2Linked to original sources
PubMed1984

Bioactivity of cholecystokinin analogues: CCK-8 is not more potent than CCK-33.

We determined the relative molar potencies of structural analogues of porcine cholecystokinin (CCK-39, CCK-33, CCK-8, and caerulein). Peptide concentrations delivered in infusates or present in bathing medium were measured by radioimmunoassay. The presence of albumin prevented loss of CCK-39 and CCK-33 from solution to a greater degree than loss of CCK-8 and caerulein from solution. As much as 10-fold differences in CCK-33 and CCK-39 concentrations were seen in albumin-containing versus nonalbumin-containing infusates. The potency estimates calculated from radioimmunoassay-corrected concentrations with CCK-8 as standard (potency 1.00) were canine pancreatic secretion in vivo: CCK-39 4.1, CCK-33 2.2, and caerulein 2.1; rat pancreatic secretion in vivo: CCK-39 2.1, CCK-33 5.4, and caerulein 5.4; rat pancreatic secretion in vitro: CCK-33 1.7, and caerulein 1.2; guinea pig gallbladder contraction in vivo: CCK-33 1.3, and caerulein 0.9; and guinea pig gallbladder contraction in vitro: CCK-33 1.8, and caerulein 5.8. Our data indicate that CCK-8 is not more potent than longer analogues and suggest that larger forms of CCK may be important mediators of the biological actions of CCK.

Albumins↗
PubMed1984

Autonomic regulation of somatostatin release: studies with primary cultures of canine fundic mucosal cells.

Using a newly developed system for culturing canine fundic mucosal cells, we examined regulation of the secretion of somatostatinlike immunoreactivity (SLI) by cholinergic and adrenergic transmitters. Enzyme-dispersed canine fundic mucosa cells were enriched in SLI content by counterflow elutriation and cultured on collagen for 42 h. Epinephrine alone, and in combination with gastrin, stimulated SLI secretion in a dose-dependent fashion. Propranolol did not alter the response to dibutyryl cAMP or gastrin but produced a parallel, rightward shift of the epinephrine dose-response curve with the dissociation constant (Ki) determined to be 14 nM by nonlinear curve fitting. Phentolamine, an alpha-adrenergic antagonist, enhanced SLI secretion in response to epinephrine, an effect reversed by the alpha 1-agonist methoxamine but not by the alpha 2-agonist clonidine. However, neither methoxamine nor clonidine alone inhibited the response to the beta-selective adrenergic agonist isoproterenol; thus, the existence of an adrenergic alpha 1-inhibitory receptor remained uncertain. Carbachol noncompetitively inhibited SLI secretion stimulated by gastrin, epinephrine, and dibutyryl cAMP. Atropine produced a parallel rightward shift of the carbachol dose-response curve (Ki = 0.4 nM). Pirenzepine also inhibited the effects of carbachol (Ki = 35 nM). Our studies suggest that SLI-containing cells in the canine fundic mucosa possess stimulatory beta-adrenergic receptors and inhibitory muscarinic receptors.

Adrenergic alpha-Agonists↗
PubMed1984

Gastric emptying and sieving of solid food and pancreatic and biliary secretions after solid meals in patients with nonresective ulcer surgery.

This study was undertaken to compare with previously published findings in normal subjects and subjects after truncal vagotomy and antrectomy the effects of nonresective ulcer surgery on (a) gastric emptying, grinding, and sieving of solid food and on (b) pancreatic and biliary secretions. Six subjects with proximal gastric vagotomy and 7 subjects with truncal vagotomy with pyloroplasty were studied using a previously validated indicator perfusion system with its aspiration port placed in the proximal jejunum. All subjects were given a meal of 30 g of 99mTc-liver, 60 g of beefsteak, and 100 ml of H2O. In conjunction with a gamma-camera to measure total gastric emptying of 99mTc-liver, this method allowed us to estimate the fraction of 99mTc-liver emptied from the stomach as particles of less than 1-mm diameter; in addition, we were able to measure jejunal concentrations and outputs of bile salts and pancreatic enzymes. In subjects with proximal gastric vagotomy, all parameters studied were indistinguishable from normal. Subjects with truncal vagotomy and pyloroplasty behaved similarly to subjects with vagotomy and antrectomy, showing (a) early precipitous emptying of food, (b) heterogeneous distribution of half-emptying times, (c) near normal concentration of biliary and pancreatic secretions, (d) markedly reduced jejunal flow rates, and (e) a reduction in postcibal trypsin secretion. In contrast to subjects after truncal vagotomy and antrectomy, however, the majority of subjects with vagotomy and pyloroplasty did not show a persistent defect in grinding and sieving of solid food.

Bile↗
PubMed1983

Recurrent ulcer after successful treatment with cimetidine or antacid.

This study was designed to compare the rates of duodenal ulcer healing and recurrence after treatment with cimetidine or antacid. Patients with endoscopically documented duodenal ulcer received cimetidine, 1200 mg daily, or Mylanta II, 7 oz daily, in a randomized, double-blind trial. For the 69 patients in each group who completed the healing phase of the trial, endoscopic ulcer healing was almost identical. At 2, 4, and 6 wk, the cumulative percent healed on antacid was 33%, 64%, and 80%, and on cimetidine it was 25%, 62%, and 86%. The 114 patients with healed ulcer were observed on no therapy and underwent additional endoscopy to detect recurrences when symptomatic or at 3, 6, and 12 mo. There was no difference in the frequency of recurrences between treatments. At 3 and 6 mo, the cumulative percentages of patients with recurrence were 29% and 56% after antacid therapy and 36% and 55% after cimetidine therapy. Some patient variables were associated with delayed ulcer healing or ulcer recurrence. These included sex, pain frequency, smoking, disease duration, and acid secretion.

Aluminum Hydroxide↗
PubMed1983

Effects of prostaglandin and indomethacin on diet-induced acute pancreatitis in mice.

This study was performed to determine the effects of exogenous prostaglandin and a prostaglandin synthetase inhibitor on experimental pancreatitis in mice. An ethionine-supplemented choline-deficient diet was used to induce pancreatitis in 4-6-wk-old Swiss Webster mice. Mice were injected subcutaneously with 16,16-dimethyl prostaglandin E2 (0.1, 1.0, 10 micrograms X kg-1 X day-1), indomethacin (0.05, 0.5, 5 mg X kg-1 X day-1), or saline for 7 days. The ethionine-supplemented choline-deficient diet was introduced 24 h after the first injection, and animals ate the test diet for 48 h. A 55% mortality was observed in control animals (n = 100) treated with carrier alone. Treatment with 10 micrograms X kg-1 X day-1 of 16,16-dimethyl prostaglandin E2 significantly decreased (p less than 0.01) mortality to 12% (n = 100). Improved survival was accompanied by a significant (p less than 0.05) decrease in the pancreatic content of free chymotrypsin and a decrease in histologic damage. Treatment with 5 mg X kg-1 X day-1 of indomethacin (n = 30) significantly (p less than 0.01) increased mortality in diet-treated rats from a control rate of 55% to 100%. These studies demonstrate a protective effect of prostaglandin on the pancreas and suggest a role for endogenous prostaglandins in the pathophysiology of pancreatitis.

16,16-Dimethylprostaglandin E2↗
PubMed1982

Characterization of bombesin effects on canine gastric muscle.

Synthetic bombesin increased the frequency and amplitude of spontaneously occurring contractions of muscle strips from antrum and corpus of the canine stomach in vitro. The effect of bombesin on frequency of contractions in this system was myogenic; was unrelated to receptors for acetylcholine, norepinephrine, substance P, or cholecystokinin; and was independent of extracellular calcium. The effect of bombesin on the amplitude in the circular muscle was unaffected by tetrodotoxin and atropine but locked by verapamil, whereas in the longitudinal muscle it was blocked by tetrodotoxin and atropine. In the circular antral muscle bombesin was approximately 100,000 times more potent than acetylcholine at threshold concentrations and was equipotent to cholecystokinin. The high potency of bombesin and its known presence in gastric nerve fibers make it a candidate for a neurotransmitter function in regulation of gastric mobility.

Acetylcholine↗
PubMed1982

Does basal cholinergic activity potentiate exogenous secretin for stimulation of pancreatic bicarbonate output in dogs?

In conscious dogs with gastric and pancreatic Thomas fistulas, we studied the effect of atropine sulfate (20 micrograms kg-1 h-1 intravenously) on bicarbonate output basally and in response to intravenous infusion of synthetic secretin (62.5, 125, 250, 500, 1,000 and 2,000 ng kg-1 h-1). We analyzed the data in an attempt to determine whether basal cholinergic activity potentiates the pancreatic bicarbonate response to secretin. Assuming that atropine suppresses all basal cholinergic activity, C (= bicarbonate response to basal cholinergic activity alone) was calculated by subtracting basal pancreatic bicarbonate output with atropine from that without atropine, S (= response to secretin alone) was calculated by subtracting basal pancreatic bicarbonate output with atropine from that in response to secretin with atropine. SwC was defined as the response to secretin acting simultaneously with (w) basal cholinergic activity and was calculated by subtracting basal pancreatic bicarbonate output with atropine from the response to secretin without atropine. If SwC was significantly greater than S + C (= sum of effects of stimulus alone and basal cholinergic activity alone) potentiation between basal cholinergic activity and secretin was assumed to exist. C was 30 +/- 9 mumol 15 min-1 for bicarbonate output. SwC of bicarbonate output was significantly (p less than 0.05) greater than S + C in response to the four lowest doses (62.5-500 ng kg-1 h-1) of secretin. We conclude that potentiation exists between basal cholinergic activity and low doses of exogenous secretin. Thus, basal cholinergic activity is an important modulator of pancreatic bicarbonate response to secretin.

Animals↗
PubMed1982

Reassessment of gastric acid inhibition by cholecystokinin and gastric inhibitory polypeptide in dogs.

The inhibition of gastrin 17-stimulated acid secretion by a partially purified cholecystokinin preparation (PcB) containing 1.2% cholecystokinin and 0.7% gastric inhibitory polypeptide immunoreactivity was compared with the inhibition produced by immunopurified cholecystokinin, cholecystokinin-depleted PcB, and gastric inhibitory polypeptide in 6 dogs with gastric fistulas. The dose-response curves for PcB and "pure" cholecystokinin were parallel and relative inhibitory potency of the pure peptide was 1.2. Dose-response curves of gastric inhibitory polypeptide and cholecystokinin-depleted PcB were similar, nonparallel to cholecystokinin dose response, and demonstrated potency significantly lower than that of PcB. When prepared without human albumin there were significantly higher losses of cholecystokinin-immunoreactivity by nonspecific adsorption from pure cholecystokinin solutions compared with PcB solutions. We conclude that inhibition of gastrin-stimulated acid secretion by partially pure cholecystokinin preparations can be explained by their cholecystokinin content and that previously reported differences in inhibitory potencies may be explained by nonspecific adsorption to glass from protein-free solutions.

Animals↗
PubMed1981

Search for resistances controlling canine gastric emptying of liquid meals.

Previous work has indicated that a chemoselective resistance controls gastric emptying. By use of meals of glucose or oleate, which were shown to empty spontaneously from dogs' stomachs half as fast as saline, we sought to locate this resistance by studying flow under controlled pressures in various regions of the gastrointestinal tract. In intact dogs, gastric outflow of glucose or oleate rose one-third as fast as outflow of saline as gastric pressure was raised, and this increased resistance to outflow of nutrients was unaffected by truncal vagotomy and pyloroplasty. In fistula dogs, gastroduodenal outflow rose linearly with gastroduodenal pressure gradients; outflow was markedly inhibited in a dose-related manner by intestinal oleate but not glucose. Inhibition by oleate was abolished by pyloroplasty. Glucose or oleate flowed into the small bowel from a barostat only slightly slower than saline. However, there was a strong inhibition of intestinal inflow of all three meals by gastric distension, an effect unaltered by truncal vagotomy. The findings suggest that gastric emptying is controlled by complex interactions among pressures and resistances, both within and beyond the stomach.

Animals↗
PubMed1981

Simultaneous gastric emptying of two solid foods.

A variety of radionuclide-labeled, solid foods have been used to measure gastric emptying. Implicit is the idea that the nuclide label identifies the rate of emptying of meal contents. The present studies tested whether different foods empty from the human stomach at different rates. Eight volunteers were fed meals of 200 ml of water + 213 g of beef stew + 52 g of chicken liver, with half the liver as 0.25-mm particles and half as 10-mm chunks, labeled with 99mTc and 113mIn, respectively, or the reverse. Another 8 subjects ingested 200 ml of water + 75 g of noodles, labeled with 123I, + 30 g of liver, labeled with 113mIn. Gastric emptying of each radionuclide was determined for 3 h by measuring the decline of counts in the gastric region of interest, using an Ohio Nuclear S410 gamma camera interfaced to a DEC computer. In each case, appropriate corrections were made for nuclear decay, down-scatter from 113mIn, and septal penetration. Seven of 8 subjects emptied 0.25-mm liver particles more quickly than 10-mm chunks of liver, while 1 subject emptied the two sizes of liver at the same rate. The t 1/2 for the 0.25-mm liver was 70 +/- 10 min; and for the 10-mm liver, 117 +/- 19 min (p less than 0.05). Six of 8 subjects emptied noodles much faster than liver, while 2 emptied the two foods at similar rates. The t 1/2 for the noodles was 52 +/- 8 min; and for the liver, 82 +/- 5 min (p less than 0.02). Since different foods in the same meal were found to empty at different rates, we conclude the gastric emptying of every food in a meal is not accurately represented by the emptying of a single, nuclide-labeled food. The different t 1/2s for the emptying of 10-mm liver in the two meals (p less than 0.05) probably reflected the influence of other meal components on gastric motility.

Food↗
PubMed1980

How gastric emptying of carbohydrate affects glucose tolerance and symptoms after truncal vagotomy with pyloroplasty.

It is commonly assumed that both abnormal glucose tolerance and postcibal symptoms after truncal vagotomy with pyloroplasty (V&P) are the result of rapid gastric emptying of carbohydrate; yet such correlations have not been established. These studies measured gastric emptying in symptomatic patients with V&P and normal subjects and sought correlations between rates of emptying and the time-courses of serum glucose and insulin as well as between emptying and symptoms. Gastric emptying in the V&P varied widely with different isocaloric meals of hypertonic glucose, taken in the erect vs. supine position, or of hypotonic starch taken in the erect posture as a solution or as solid balls of paste. Glucose and starch solutions were emptied abnormally rapidly in the erect posture, while glucose taken supine, and the starch balls were emptied more slowly. By contrast, all four meals emptied at about the same rates in the normal subjects. In both the V&Ps and the normals, there were weak correlations evident between the amount of carbohydrate emptied in the first 30 postcibal minutes and the rises in serum glucose or insulin. However, the presence or absence, the timing, and the qualitative nature of postcibal symptoms observed in the V&Ps did not correlate well with either the speed of emptying or the osmolarity of the carbohydrate meals.

Blood Glucose↗
PubMed1980

YAG laser treatment of experimental bleeding canine gastric ulcers.

The neodymium-YAG laser was used to treat bleeding experimental canine gastric ulcers in four separate studies: (a) Extensive investigation by using the 1.06 micron YAG laser wavelength was performed to determine optimal YAG laser treatment parameters to maximize hemostatic efficacy while minimizing associated tissue injury. Eight out of 43 combinations of power, pulse duration, and spot size, with and without coaxial CO2 were found to be best. The range of settings tested were 30-90 W for power; 0.2-1 sec pulse duration; and 2.0- and 3.4-mm spot sizes, with and without coaxial CO2. (b) Five of these treatment combinations were studied in more detail to assess the respective effect of spot size, pulse duration, and presence or absence of coaxial CO2 on tissue injury. In spite of optimizing treatment parameters and conditions, each combination caused significant damage to the gastric wall. No acute perforations occurred. (c) Endoscopic YAG laser treatments were applied successfully. Efficacy and total energy requirements were compared with similar treatments previously done at laparotomy. (d) In an attempt to reduce tissue damage, the YAG laser was modified to produce a 1.3-microm wavelength. YAG laser treatment using this alternative wavelength caused more immediate damage than the 1.06 micron wavelength. From these studies we conclude: (a) YAG laser photocoagulation effectively stopped experimental gastric ulcer bleeding when applied both at laparotomy and endoscopy; (b) compared to untreated ulcers, YAG laser treatment caused significant tissue damage despite control of several important variables (power output, spot size, pulse duration, and coaxial CO2); (c) increased total energy, larger spot size, and longer pulse duration appeared related to increased tissue injury with YAG laser treatment; total energy was the single most important factor. (d) Successful hemostasis with endoscopic application of the YAG laser required more total energy than treatment of laparotomy. (e) Modification of the YAG laser wavelength to 1.3 microns did not reduce tissue injury.

Acute Disease↗