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Biomedical subjects

G R Greenberg

Publications and source records attributed to G R Greenberg.

At least 19 recordsLinked to original sources
PubMed1995

Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators.

BACKGROUND: Although corticosteroids are highly effective in improving symptoms of Crohn's disease, they may have substantial toxicity. In some patients, attempts to discontinue corticosteroids are unsuccessful. METHODS: We conducted a double-blind, placebo-controlled multicenter study of weekly injections of methotrexate in patients who had chronically active Crohn's disease despite a minimum of three months of prednisone therapy. Patients were randomly assigned to treatment with intramuscular methotrexate (25 mg once weekly) or placebo for 16 weeks. The patients also received prednisone (20 mg once a day), which was tapered over 10 weeks unless their condition worsened. The primary outcome measure was clinical remission at the end of the 16-week trial. Remission was defined by the discontinuation of prednisone and a score of < or = 150 points on the Crohn's Disease Activity Index. RESULTS: A total of 141 patients were randomly assigned in a 2:1 ratio to methotrexate (94 patients) or placebo (47 patients). After 16 weeks, 37 patients (39.4 percent) were in clinical remission in the methotrexate group, as compared with 9 patients (19.1 percent) in the placebo group (P = 0.025; relative risk, 1.95; 95 percent confidence interval, 1.09 to 3.48). The patients in the methotrexate group received less prednisone overall than those in the placebo group (P = 0.026). The mean (+/- SE) score on the Crohn's Disease Activity Index after 16 weeks of treatment was significantly lower in the methotrexate group (162 +/- 12) than in the placebo group (204 +/- 17, P = 0.002). The changes in quality-of-life scores and serum orosomucoid concentrations were similar. In the methotrexate group, 16 patients (17 percent) withdrew from treatment because of adverse events (including asymptomatic elevation of serum aminotransferase in 7 and nausea in 6), as compared with 1 patient (2 percent) in the placebo group. CONCLUSIONS: In a group of patients with chronically active Crohn's disease, methotrexate was more effective than placebo in improving symptoms and reducing requirements for prednisone.

Adult↗
PubMed1995

Effect of intervention in inflammatory bowel disease on health-related quality of life: a critical review.

UNLABELLED: Health-related quality of life (HRQOL) is a quantitative measurement of subjective perception of health state, including emotional and social aspects. It can be reliably measured with several valid instruments. Previous reviews of the literature suggested inadequate attention to HRQOL in studies of interventions in inflammatory bowel disease. PURPOSE: This study was undertaken to assess the current status of the quality of measurement of HRQOL in studies of inflammatory bowel disease and to review the clinical conclusions warranted by the literature. METHOD: Medicine was searched for articles relating to ulcerative colitis, Crohn's disease, or inflammatory bowel disease and quality of life since 1981. The articles found were reviewed for citations of further articles. The adequacy of HRQOL measure was assessed and graded, and the study design was categorized to assess the strength of the literature on the whole. RESULTS: A trend was found toward higher quality of HRQOL measurement in the period 1988 to 1994 compared with 1981 to 1987. Most of the improvement was because of increased use of standardized and multidomain but unvalidated and unpublished questionnaires for measurement. CONCLUSIONS: Confidence in the following clinical conclusions in studies of surgical interventions in inflammatory bowel disease is limited by study design: that pelvic pouch is not inferior to ileostomy, that specific domains of HRQOL are differentially affected by different surgical procedures, and (with less confidence) that surgery is helpful in Crohn's disease. Medical studies have demonstrated that high quality HRQOL measures can be integrated into randomized, prospective trials. Clinically equivalent treatments have shown differential effects or HRQOL: 9 mg daily of budesonide is superior to 15 mg, and hydrocortisone foam enemas are superior to prednisolone. Home parenteral nutrition has received modest support, limited again by study design. It is recommended that standard tests of HRQOL be used to increase comparability of studies and to increase the quality of this literature in general. In particular the Inflammatory Bowel Disease Questionnaire, Rating Form of Inflammatory Bowel Disease Concerns, and Direct Questioning of Objectives are recommended.

Clinical Trials as Topic↗
PubMed1995

Quality of life, nutritional status, and gastrointestinal hormone profile following the Whipple procedure.

BACKGROUND: To compare the quality of life, nutritional status, and gastrointestinal profiles of post-Whipple patients and postcholecystectomy patients. METHODS: A cross-sectional survey of post-Whipple procedure patients and age- and sex-matched postcholecystectomy patients was performed. Quality of life was assessed using six instruments: Time Trade-off Technique, Direct Questioning of Objectives, Gastrointestinal Quality of Life Index, Sickness Impact Profile, Physician Global Assessment, and Visick Scale. A gastrointestinal symptomatology questionnaire was completed. Nutritional status was assessed by weight, the Subjective Global Assessment instrument, and skin anthropometry. Fasting and postprandial serum gastrin, somatostatin, insulin, pancreatic glucagon, enteroglucagon, and pancreatic polypeptide were measured. RESULTS: The quality of life and gastrointestinal function of the Whipple patients was excellent and was not significantly different from that of the control subjects. There were no significant differences in gastrointestinal symptomatology although 5 Whipple patients complained of greasy bowel movements, and 1 patient reported difficulty maintaining weight. Despite this, nutritional status was within normal limits in all subjects. Six patients in the Whipple group followed a diabetic diet, 1 required insulin, and 3 required an oral hypoglycemic agent, whereas none of the control subjects were diabetic. There were no significant differences in the mean basal, peak, or integrated postprandial responses of the gut hormones with the exception of pancreatic polypeptide and gastrin (in patients having a standard Whipple procedure only). CONCLUSION: Quality of life and nutritional status are excellent in patients following a Whipple procedure.

Adult↗
PubMed1995

Vagal control of fasting somatostatin levels.

UNLABELLED: The relationship between fasting intestinal motility, plasma concentration of somatostatin and vagal integrity was examined in four conscious dogs. Small intestinal motility was recorded using subserosally implanted bipolar electrodes. The cervical vagosympathetic trunks, previously isolated in skin loops, were blocked by cooling. In the fasted state, peaks in somatostatin concentration were observed during phase III of the migrating myoelectric complex (MMC). During vagal blockade, small intestinal MMCs persisted but with phase II being absent or decreased in duration in the duodenum and upper jejunum. Somatostatin levels significantly decreased to below the basal levels observed prior to blockade. No cycling of somatostatin levels was evident during the period of vagal blockade. Upon termination of vagal cooling, normal motility returned and somatostatin levels returned to their pre-blockade levels. IN CONCLUSION: (1) plasma somatostatin levels cycle with phase III of the MMC in the upper small intestine; (2) the cycling of fasting somatostatin concentrations is primarily dependent upon intact vagal pathways; and (3) basal plasma somatostatin levels are in part vagally dependent.

Adaptation, Physiological↗
PubMed1994

Oral budesonide for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group.

BACKGROUND: Corticosteroids are the most efficacious drugs for inducing remission in active Crohn's disease, but their benefits are frequently offset by serious side effects. Budesonide is a corticosteroid with high topical antiinflammatory activity but low systemic activity because of extensive hepatic metabolism. We investigated the efficacy and safety of an oral controlled-ileal-release preparation of budesonide in patients with active Crohn's disease involving the ileum or ileum and proximal colon. METHODS: In a double-blind, multicenter trial, 258 patients were randomly assigned to receive placebo or one of three doses of budesonide--3, 9, or 15 mg daily. The primary outcome measure was clinical remission, as defined by a score of 150 or less on the Crohn's disease activity index. RESULTS: After eight weeks of treatment, remission occurred in 51 percent of the patients in the group receiving 9 mg of budesonide (95 percent confidence interval, 39 to 63 percent), 43 percent of those receiving 15 mg (95 percent confidence interval, 31 to 55 percent), and 33 percent of those receiving 3 mg (95 percent confidence interval, 21 to 44 percent), as compared with 20 percent of those receiving placebo (P < 0.001, P = 0.009, and P = 0.13, respectively). Improvements in the quality of life, as measured by the patients' responses to the inflammatory bowel disease questionnaire, paralleled these remission rates. Location of disease, prior surgical resection, and previous use of corticosteroids did not affect the outcome. A total of 119 patients (46 percent) were withdrawn from the study before the trial ended, 96 because of insufficient therapeutic effects, 13 because of adverse reactions, and 10 because of noncompliance. Budesonide caused a dose-related reduction in basal and corticotropin-stimulated plasma cortisol concentrations but was not associated with clinically important corticosteroid-related symptoms or other toxic effects. CONCLUSIONS: In an eight-week trial, an oral controlled-release preparation of budesonide at an optimal daily dose of 9 mg was well tolerated and effective against active Crohn's disease of the ileum and proximal colon.

Administration, Oral↗
PubMed1994

Critical assessment of body-composition measurements in malnourished subjects with Crohn's disease: the role of bioelectric impedance analysis.

Bioelectric impedance analysis (BIA) has been widely used for assessment of body composition in healthy subjects but has not been validated in malnourished patients. This study compared calculation of fat-free mass (FFM) by five methods to determine whether the currently used equations for total body water (TBW) as assessed by BIA were applicable to 19 malnourished patients with Crohn's disease. When compared with TBW assessed by H2(18)O dilution, BIA was higher by 5.9 +/- 1.1% (P < 0.005). A stepwise-multiple-regression equation was derived to validate BIA: TBW (kg) = 0.25 (ht2/resistance) + 0.29 (wt) + 3.63 (r = 0.97, SEE = 0.28). Comparison of the hydration of FFM (TBW by 18O dilution/FFM) between methods showed that total body potassium (TBK) gave a significantly higher value when compared with the reference method of body protein, mineral, and 18O analysis. Dual-energy x-ray absorptiometry (DXA) provided a value for TBW/FFM in close agreement with the reference method. We conclude that BIA overestimates TBW, and TBK underestimates FFM in malnourished patients. DXA provides an accurate measurement of body fat in malnutrition.

Absorptiometry, Photon↗
PubMed1994

Neural modulation of glucose-dependent insulinotropic peptide (GIP) and insulin secretion in conscious dogs.

Glucose-dependent insulinotropic peptide (GIP) is a potent incretin, but it remains unclear whether this effect is dependent upon intact vagal pathways. In four conscious dogs, plasma GIP, plasma insulin, and plasma glucose responses were measured after intraduodenal administration of a defined formula diet, after glucose was perfused intraduodenally, and after insulin-mediated hypoglycemia with and without bilateral cryogenic blockade of the cervical vagus nerves. Vagal blockade did not alter elevations of plasma GIP after the defined formula diet or after glucose. However, with the vagi blocked plasma insulin responses were suppressed after the enteral diet (-52 +/- 8%) and after intraduodenal glucose (-55 +/- 4%), without changes in plasma glucose. Intravenous atropine (50 micrograms/kg) did not modify the GIP responses to intraduodenal perfusions of the defined formula diet or to glucose, but did suppress plasma insulin responses to baseline values. Insulin hypoglycemia without or with vagal blockade had no effect on basal concentrations of plasma GIP. These results indicate that vagal muscarinic and nonvagal muscarinic pathways participate in the control of the intestinal phase of insulin secretion, but the regulation of GIP secretion is independent of vagal or muscarinic neural control mechanisms.

Animals↗
PubMed1994

Comparison of amino acid v peptide based enteral diets in active Crohn's disease: clinical and nutritional outcome.

Elemental diets are considered an effective primary treatment for active Crohn's disease. This study examined the hypothesis that improvement occurs because of the presence of amino acids or the low fat content, or both. A randomised, controlled trial was undertaken in 40 patients with active Crohn's disease to evaluate clinical and nutritional outcomes after an amino acid based diet containing 3% fat was given by a feeding tube compared with a peptide based diet containing 33% fat. After three weeks' treatment, clinical remission occurred in 84% of patients who were given the amino acid diet and 75% of patients who received the peptide diet (p = 0.38). Plasma linoleic acid concentration was reduced after the amino acid but not the peptide diet. An increase in total body nitrogen was associated with the magnitude of nutritional depletion before treatment and at six months' follow up, only patients who showed gains in total body nitrogen after enteral nutrition had a sustained clinical remission. This study shows that peptide based high fat diets are as effective as amino acid low fat diets for achieving clinical remission in active Crohn's disease. Improved total body protein stores but not essential fatty acid depletion may be an important indicator of a sustained remission.

Adult↗
PubMed1994

Mechanisms coordinating gastric and small intestinal MMC: role of extrinsic innervation rather than motilin.

We have investigated the role of vagal and efferent adrenergic innervation coordinating the gastric and small intestinal migrating motor complexes (MMCs) after removal of the pylorus, duodenum, and upper jejunum in three dogs. The cervical vagus nerves were previously isolated in bilateral skin loops to permit reversible cooling blockade of the vagi. Pharmacological alpha- and beta-receptor blockade was accomplished by bolus intravenous injection of phentolamine and propranolol followed by intravenous infusion of the combined drugs. Gastric and upper jejunal MMC-like activity was initially absent after bowel resection but reappeared after 1-4 mo with the gastric and jejunal MMC-like activities coordinated as if the jejunum were the duodenum. Motilin peaks were absent. All gastric contractions were abolished by vagal blockade. Pharmacological adrenergic blockade immediately induced an intense burst of contractile and electrical activity in the stomach, which propagated to the distal ileum. This phase III-like burst was followed by ongoing intermittent bursts of contractile and electrical activity in the stomach and small intestine, lasting throughout the blockade, without further MMC-like activity. Vagal cooling blockade in combination with adrenergic blockade did not restore gastric MMC-like activity but abolished or decreased the number of gastric contractions, with the reappearance of the small intestinal MMC. Atropine boluses abolished all control and adrenergic blockade-induced stomach and small intestinal contractile and electrical activity. In conclusion, after duodenectomy, the gastric MMC-like activity that is reestablished and is coordinated with the small intestinal MMC is vagally dependent and cholinergic, but its cyclical nature requires adrenergic efferent pathways. Under these circumstances, coordination of the gastric and jejunal MMCs appears to require extrinsic innervation.

Animals↗
PubMed1994

Cholecystokinin type A receptors mediate intestinal fat-induced inhibition of acid secretion through somatostatin-14 in dogs.

This study was designed to examine whether one or both principle molecular forms of somatostatin (SLI), somatostatin-28 (S-28) and somatostatin-14 (S-14), mediate inhibition of stimulated gastric acid by intestinal fat and to determine whether the mode of action includes activation of type A cholecystokinin (CCK) receptors in conscious dogs. SLI molecular forms were separated by gel filtration chromatography after extraction of acidified plasma on octadecyl silyl cartridges and quantified by RIA. Basal plasma levels of S-28 and S-14 were 4.1 +/- 0.6 and 3.6 +/- 0.3 fmol/ml, respectively. Intraduodenal perfusion with a 10% fat emulsion increased plasma S-28 by 6.3 +/- 1.2 fmol/ml (P < 0.01) and S-14 by 17.8 +/- 2.6 fmol/ml (P < 0.001), and suppressed by 76 +/- 3% (P < 0.001) gastrin (150 pmol/kg.h)-stimulated gastric acid. Blockade of type A CCK receptors with MK-329 (75 micrograms/kg, i.v.) abolished S-28 and S-14 responses (both P < 0.001) and completely reversed the inhibitory effect of gastric acid produced by intraduodenal fat. Intravenous infusions of S-14 dose-dependently inhibited gastrin-stimulated secretion with an estimated 50% inhibitory dose of 125 pmol/kg.h that achieved an incremental plasma S-14 rise of 40 +/- 2 fmol/ml; infusions of S-28 at 30 pmol/kg.h increased plasma S-28 by 47 +/- 3 fmol/ml without altering acid output. The SLI antagonist cyclo-[7-aminoheptanoly-Phe-D-Trp-Lys-Thr(BZL)] (CyCam) reversed by 89 +/- 4% (P < 0.001) exogenous S-14-induced inhibition of gastrin-stimulated acid secretion, but did not influence gastric acid output after the infusion of S-28. CyCam also reversed by 139 +/- 9% (P < 0.001) the early phase of fat-induced acid inhibition; in the late phase, CyCam treatment was associated with a further 2-fold elevation of plasma peptide-YY (PYY) to 102 +/- 6 fmol/ml (P < 0.001) and a 75 +/- 5% suppression of gastric acid. Simulation of this plasma PYY increment with infusions of PYY at 50 pmol/kg.h inhibited by 44 +/- 5% gastrin-stimulated acid secretion. These results indicate that in conscious dogs, endogenous CCK mediation of intraintestinal fat-induced inhibition of stimulated acid secretion occurs in part through CCK type A receptor activation of S-14 secretion. Modulation of gastric acid by S-14 includes both inhibition and attenuation of further suppression via counterregulation of PYY secretion.

Amino Acid Sequence↗
PubMed1994

Sulfasalazine and mesalazine for the maintenance therapy of Crohn's disease: a meta-analysis.

OBJECTIVE: The aim of this meta-analysis was to determine whether therapy with sulfasalazine or mesalazine is effective in the maintenance of clinical remission in patients with Crohn's disease. METHODS: Computerized searches of bibliographic databases were carried out to identify studies published up to October 1993 that were randomized controlled trials of sulfasalazine or mesalazine as single drug therapy in the prevention of symptomatic disease relapse in quiescent Crohn's disease. We extracted and statistically aggregated data from the trials, using a fixed effects model. RESULTS: A total of 10 eligible trials involving a total of 1022 patients were identified. Therapy with sulfasalazine or mesalazine reduces the risk of clinical relapse of Crohn's disease after 12 months [relative risk (RR) = 0.77, 95% confidence interval (CI) 0.64-0.92]. The benefit is less apparent at 3-6 months [RR = 0.86, 95% CI 0.67-1.09]. Subgroup analysis indicated that therapeutic benefit exists for mesalazine but not for sulfasalazine [RR for mesalazine = 0.63, 95% CI 0.50-0.79; RR for sulfasalazine = 1.08, 95% CI 0.81-1.44]. CONCLUSIONS: Maintenance therapy with mesalazine or sulfasalazine reduces the risk of clinical disease relapse in Crohn's disease after 1 yr. This benefit is seen primarily in the more recent studies that have used mesalazine as the therapeutic agent.

Aminosalicylic Acids↗
PubMed1993

Regulation of somatostatin-14 and -28 secretion by gastric acid in dogs: differential role of cholecystokinin.

BACKGROUND: Prosomatostatin-derived peptides include two principle bioactive molecular forms, somatostatin 28 (S-28) and somatostatin 14 (S-14). This study examined whether there is a functional relationship between gastric acid secretion and the release of S-28 and S-14 into the circulation. METHODS: In conscious dogs with gastric and duodenal cannulas, S-28 and S-14 responses, measured after extraction of acidified plasma and separation by gel chromatography, were evaluated by administration of nutrients and acid-inducing secretagogues without and with omeprazole. RESULTS: Ingestion of a solid meal caused equivalent plasma elevations of S-28 and S-14, whereas infusions of histamine and gastrin selectively increased plasma S-14. Omeprazole decreased meal-stimulated S-28 (-67% +/- 8%; P < 0.01) and S-14 (-56 +/- 9%; P < 0.01) and abolished S-14 increases to histamine and gastrin. Intraduodenal perfusions of a liquid protein meal increased S-28 above S-14, comprising approximately 71% of total somatostatin-like immunoreactivity released, and omeprazole suppressed S-28 (-87% +/- 5%; P < 0.01) without influencing S-14. Similar responses occurred after exogenous cholecystokinin. Moreover, pretreatment of the intraduodenal protein meal with the cholecystokinin-A receptor antagonist MK-329 abolished increases of S-28 and S-14 and caused a further twofold increase of gastric acid (P < 0.025). CONCLUSIONS: In the fed state, gastric acid causes direct release of S-14 from the stomach, but the acid-dependent component of S-28 secretion requires cholecystokinin as a cofactor. Negative feedback regulation between somatostatin and gastric acid secretory responses to nutrients may include S-28 modulated, in part, by cholecystokinin.

Animals↗
PubMed1993

Differential neural regulation of circulating somatostatin-14 and somatostatin-28 in conscious dogs.

Somatostatin-like immunoreactivity (SLI) released into the circulation after nutrients or secretagogues is heterogeneous. To determine whether similar neural pathways regulate secretion of SLI molecular forms, circulating somatostatin-28 (S-28) and somatostatin-14 (S-14) responses to ingestion of a solid meal, intraduodenal perfusion of a liquid defined formula meal, and intravenous infusion of cholecystokinin octapeptide (CCK-OP, 250 pmol.kg-1.h-1) were measured in four conscious dogs with and without cryogenic blockade of the cervical vagus nerves. SLI was separated by gel-filtration chromatography of extracted, acidified plasma and quantified by radioimmunoassay. Basal plasma concentrations of S-28 were 4.1 +/- 0.6 fmol/ml and of S-14 were 3.8 +/- 0.4 fmol/ml. Ingestion of the solid meal increased plasma SLI threefold, and elevations of S-28 and S-14 were equivalent. After the intraduodenal liquid meal or infusion of CCK-OP, plasma SLI rose twofold, but increments of S-28 exceeded S-14, comprising approximately 70% of SLI released. Vagal blockade by cooling reversibly inhibited both the S-28 and S-14 responses to the solid meal, intraduodenal liquid meal, and CCK-OP. In contrast, atropine (50 micrograms/kg iv), given after solid food, intraduodenal nutrients, and CCK-OP, suppressed S-28 but further increased S-14 responses. Atropine did not, however, alter the suppression of S-14 and S-28 by vagal cooling.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Calcitonin gene-related peptide-I preferentially stimulates secretion of somatostatin from intestinal cultures.

Calcitonin gene-related peptide (CGRP)-I has been reported to inhibit gastric acid secretion through stimulation of gastric somatostatin-14 (S-14) release. To establish whether some of the effects of CGRP-I on intestinal function might also be mediated through somatostatin, fetal rat intestinal cultures were treated with test agents for 2 h, and the secretion of somatostatin-like immunoreactive (SLI) peptides was determined by RIA. The intestinal cultures have been previously found to synthesize and secrete both major forms of intestinal somatostatin (S-28 and S-14). Rat (r) CGRP-I treatment of the intestinal cultures stimulated SLI secretion to 163 +/- 33% of the control level at 3.3 x 10(-7) M (P < 0.01) and 227 +/- 30% of the control level at 10(-6) M (P < 0.001). In contrast, the structurally related peptide, human CGRP-II, had no effect on total SLI release at any concentration up to 10(-6) M. Gel permeation chromatography revealed that rCGRP-I increased the secretion of S-14 by 22 +/- 6-fold (P < 0.01) compared to the control value, whereas that of S-28 increased nonsignificantly by only 2 +/- 1-fold. Thus, the ratio of S-28 to S-14 secreted into the medium decreased from 1.7 +/- 0.2 in control medium to 0.2 +/- 0.3 after rCGRP-I treatment (P < 0.01). As the ratio of S-28 to S-14 stored by the cells was not altered by rCGRP-I treatment, these findings suggest that intestinal S-28 and S-14 may be secreted by two distinct intestinal D-cells with different sensitivities to rCGRP-I or by a single D-cell type containing distinct pools of S-14 and S-28 that have different sensitivities to rCGRP-I. The results of these in vitro studies further indicate that in vivo, CGRP-I may modulate aspects of intestinal function through its stimulation of the secretion of S-14.

Animals↗
PubMed1992

Tandem cloning of bacteriophage T4 nrdA and nrdB genes and overproduction of ribonucleoside diphosphate reductase (alpha 2 beta 2) and a mutationally altered form (alpha 2 beta 2(93)).

To investigate the role of ribonucleoside diphosphate reductase in the deoxyribonucleoside triphosphate synthetase multienzyme complex induced by bacteriophage T4 infection and to study the expression of the T4 nrdA and nrdB genes, we have constructed separate plasmid expression strains overproducing their respective alpha 2 and beta 2 protein products. Because complementation of the two proteins to form an active alpha 2 beta 2 enzyme presented complications, nrdA and nrdB, each with its own tac promoter, were also cloned in tandem into a single expression vector. The resulting plasmid (pnrdAB) overproduces ribonucleoside diphosphate reductase. Phage T4 nrdB93, described by Wirak et al. (D. O. Wirak, K. S. Cook, and G. R. Greenberg, J. Biol. Chem. 263:6193-6201, 1988) contains a lesion in exon II of the gene. The mutation causes not only a temperature-sensitive inactivation of the catalytic structure of the beta 2(93) protein and of its ability to interact with alpha 2 protein to form the alpha 2 beta 2(93) enzyme but also a profound non-temperature-sensitive decrease in the formation of the beta 2(93) protein. An expression vector overproducing active alpha 2 beta 2(93) was constructed by site-directed mutagenesis of the nrdB gene.

Base Sequence↗
PubMed1992

Relationship of postprandial motilin, gastrin, and pancreatic polypeptide release to intestinal motility during vagal interruption.

Experiments were performed to determine how postprandial motilin, gastrin, and pancreatic polypeptide plasma concentrations measured during vagal blockade relate to coincident small intestinal motility patterns. Feeding produced a postprandial pattern of intestinal motility coincident with a sustained increase in gastrin and pancreatic polypeptide and a decline in motilin plasma concentrations. Vagal blockade replaced the fed pattern with one similar to migrating motor complex (MMC) activity. Highest motilin plasma concentrations were observed during phase III of this MMC-like activity, as occurs in the fasted state. Vagal blockade reduced but did not abolish the postprandial increase in plasma gastrin and pancreatic polypeptide concentrations. Termination of vagal cooling produced a decline in motilin and an elevation in gastrin and pancreatic polypeptide concentrations, coincident with the return of the fed pattern. In conclusion, during vagal blockade in the fed state (i) motilin, but not gastrin or pancreatic polypeptide plasma concentrations, fluctuate with the MMC-like activity, and any measurement of motilin concentration under these circumstances must be interpreted on the basis of gut motility patterns, and (ii) gastrin and pancreatic polypeptide concentrations are marginally elevated, but these changes are not enough to disrupt the MMC or have any motor effect. Lastly, the fed pattern and the postprandial changes in motilin, gastrin, and pancreatic polypeptide concentrations are in part dependent upon intact vagal pathways.

Animals↗
PubMed1992

Influence of gastric acid on circulating somatostatin-14 and -28 released after insulin-induced hypoglycemia in conscious dogs.

Insulin hypoglycemia is a potent mechanism for somatostatin secretion into the circulation. Whether the associated increase in gastric acid mediates the rise of one or both principle molecular forms of somatostatin, somatostatin-14 (S-14) and somatostatin-28 (S-28), was examined in four conscious dogs. Somatostatin molecular forms were separated by gel filtration chromatography after extraction of acidified plasma on octadecyl silyl cartridges and quantified by RIA. Basal plasma levels of S-14 and S-28 were 3.4 +/- 0.2 and 4.1 +/- 0.6 fmol/ml, respectively. After hypoglycemia induced by insulin, plasma S-14 increased by 29.5 +/- 3.9 fmol/ml (P less than 0.001), and plasma S-28 increased by 7.2 +/- 0.9 fmol/ml (P less than 0.01). Suppression of hypoglycemia-mediated gastric acid secretion after the administration of omeprazole or ranitidine inhibited elevations of S-14 by 82 +/- 6% (P less than 0.001) and 81 +/- 7% (P less than 0.001), respectively, but had no effect on the rise of S-28. Atropine (50 micrograms/kg, iv), which also suppresses gastric acid secretion after insulin hypoglycemia, decreased S-14 by 59 +/- 3% (P less than 0.01) without influencing S-28. Atropine given after omeprazole treatment, however, increased S-14 levels observed after atropine (P less than 0.001) or omeprazole (P less than 0.001) alone and was equivalent to control levels. S-28 remained unaltered after atropine and omeprazole treatment. These results in conscious dogs indicate that after vagal stimulation induced by insulin hypoglycemia 1) both S-14 and S-28 are released into the circulation, but S-14 predominates; 2) gastric acid contributes directly to the stimulation of S-14, but not S-28, secretion; 3) muscarinic inhibitory mechanisms participate in the regulation of S-14 secretion, and this mechanism is amplified when vagally stimulated gastric acid secretion is suppressed; and 4) nonmuscarinic mechanisms mediate in part S-28 secretion. This study suggests the presence of a reciprocal functional relationship between gastric acid secretion and circulating S-14 that is mediated by vagal muscarinic mechanisms.

Animals↗