Biomedical subjects

A Shulkes

Publications and source records attributed to A Shulkes.

At least 109 records · Page 6Linked to original sources

PubMed1986

Profile of gastric stress ulceration following acute cervical cord injury: an animal model.

A reproducible model of acute gastric stress ulceration has been described in the tetraplegic rat. The characteristics of the development of acute gastric ulceration and the concentrations of plasma gastrin have been examined. There was a significant increase in gastric stress ulceration within 4 h of producing the tetraplegia. The ulceration was confined to the glandular portion of the stomach and occurred equally on crests and rugal troughs. Plasma gastrin concentrations were not changed by spinal cord section. This characterized model can serve as a basis for further investigation of the aetiology and prophylaxis of acute gastric ulceration in quadriplegia.

Animals↗

PubMed1985

Watery diarrhea-hypokalemia-achlorhydria syndrome and carcinoma of the esophagus.

The watery diarrhea-hypokalemia-achlorhydria syndrome associated with ectopic secretion of vasoactive intestinal peptide has only been conclusively documented with tumors originating in the pancreas or sympathetic chain. We report here the case of a 50-yr-old woman who developed this syndrome 3 wk after an apparently effective course of radiotherapy for an obstructing, mixed-cell carcinoma of the esophagus. High concentrations of vasoactive intestinal peptide were found in plasma (100-200 pmol/L; normal less than 20 pmol/L) and in the metastatic skin nodules (750 pmol/g) that later developed and that contained one of the two cell types from the original tumor. Stool volumes reached a plateau of 15-20 L/day, and potassium requirements were greater than 1000 mmol/day. Symptoms failed to respond to any of the regimens previously described as effective in this syndrome. After 14 wk of massive fecal fluid and electrolyte losses, symptoms resolved dramatically with the first dose of 5-fluorouracil. Plasma vasoactive intestinal peptide concentration returned to normal, where it remained despite subsequent evidence of renewed tumor spread. This case illustrates the unpredictability of the response of this syndrome to medical treatment, and suggests that vasoactive intestinal peptide secretion may occur in a wider range of tumors than has so far been described.

Achlorhydria↗

PubMed1985

The effect of neurotensin and secretin on gastric acid secretion and mucosal blood flow in man.

Neurotensin stimulates pancreatic secretion directly and by potentiating the effect of secretin. Neurotensin also inhibits gastric secretion. Secretin inhibits gastric secretion as well, but whether it also interacts with neurotensin is not known. Secretin is known to inhibit gastric mucosal blood flow (GMBF). The effect of neurotensin on GMBF is not known. Acid secretion (triple lumen perfused orogastric tube) and GMBF ([14C]aminopyrine clearance) were therefore measured in 6 subjects during neurotensin, secretin and neurotensin plus secretin infusions. Neurotensin plus secretin reduced acid secretion by a median 130 (range 34-394) mumol/min which was significantly greater than either neurotensin at 36 (7-67) mumol/min or secretin 54 (20-347) mumol/min alone (P less than 0.05). This effect appeared independent of GMBF. Neurotensin plus secretin reduced GMBF by 14 (12-27) ml/min but not significantly more than neurotensin at 11 (3-20) ml/min or secretin 18 (2-27) ml/min alone. Further, there was no correlation between changes in acid output and GMBF during infusion of the peptides. We conclude that the inhibitory effects of neurotensin and secretin on gastric secretion are at least additive and together they may function as an 'enterogastrone'.

Adult↗

PubMed1985

Gastric and intestinal release of vasoactive intestinal polypeptide in the milk-fed lamb.

Vasoactive intestinal polypeptide (VIP) has been proposed as the neurotransmitter of the atropine-resistant relaxation of gastric structures in the lamb. To examine this proposal VIP concentrations in plasma from arterial, gastric venous and intestinal venous blood were measured in healthy conscious lambs before, during and after teasing with, and sucking of milk. Basal arterial plasma VIP concentrations were undetectable (less than 3 pmol/l) and remained so during and after feeding. Before feeding VIP was detected in only 2 of 12 gastric venous plasma samples (5 and 13 pmol/l). During teasing with food there were increments in VIP of 19 +/- 4 pmol/l and during feeding of 27 +/- 5 pmol/l. VIP concentration in gastric venous plasma rapidly returned to fasting levels after cessation of sucking. In contrast VIP in the intestinal venous plasma did not rise during teasing or upon commencement of sucking but a peak increment of 34 +/- 6 pmol/l occurred at 5 min after cessation of feeding. The results are consistent with the hypotheses that VIP is released in anticipation of and during sucking from inhibitory neurones involved in relaxation of gastric structures and that intestinal release of VIP is a consequence of entry of digesta into the small intestine.

Animals↗

PubMed1985

The effect of cigarette smoking on gastric acid secretion and gastric mucosal blood flow in man.

Smoking leads to a higher incidence of peptic ulcer and delays healing of those ulcers. Possible mechanisms include increased gastric acid secretion, reduced gastric mucosal blood flow, and reduced duodenal bicarbonate production. In six subjects we determined the effect of one hour of cigarette smoking on gastric mucosal blood flow (14C-aminopyrine clearance), acid secretion (triple lumen perfused oro-gastric tube), and plasma levels of gastrin and pancreatic polypeptide. Smoking reduced acid secretion from a median of 433 (range 160-707) mumol/min to 166 (47-340) mumol/min (p less than 0.05) and blood flow from 66 (40-70) ml/min to 36 (22-58) ml/min (p less than 0.05). There was no change in plasma gastrin and the small rise in pancreatic polypeptide would be insufficient to affect duodenal bicarbonate production. We conclude that cigarette smoking decreased gastric acid secretion and gastric mucosal blood flow. The increased incidence of gastric ulcers seen in smokers may be related to this reduction in gastric mucosal blood flow.

Adult↗

PubMed1985

Ontogeny of gastric acidity in the ovine fetus.

Hypoacidity and hypergastrinaemia have been reported in the newborn human. However, little is known about in utero gastric acid secretion, and the relationship to fetal plasma gastrin levels. The longitudinal pattern of development of basal and stimulated gastric acid secretion in the non-anaesthetized fetal sheep has been studied during the last 45 days of gestation. Fetuses had cannulae inserted into the jugular vein, carotid artery and stomach. Gastric juice and blood was sampled daily from 101 days gestation until birth (145 days). Intermittent basal acid secretion began between 120 and 133 days of gestation. These fluctuations in gastric juice pH continued until birth. Overall there was a decline in gastric pH from 7.5 +/- 0.2 (SEM), for fetuses 101-105 days to 4.3 +/- 0.5 by 131-135 days. Mean fetal plasma gastrin was higher than maternal levels after 111-115 days but no correlation between fetal plasma gastrin levels and gastric pH could be demonstrated. Pentagastrin and histamine infusion did not stimulate acid secretion in fetuses younger than 115 days. After this age the fetuses became responsive to both pentagastrin and histamine. In contrast, cholinergic stimulation, using bethanechol, did not stimulate acid production until 10 to 15 days later, suggesting a hierarchy in the development of the control of acid secretion in the fetus. The lack of response to endogenous gastrin and the hierarchy in the control of acid secretion suggest either a lack of receptors on the parietal cell or the presence of an inhibitor of acid secretion. These studies are relevant to human physiology since the present findings show that the sheep and human have a similar gastrin/acid profile at birth.

Animals↗

PubMed1984

Characterization of a pancreatic tumor containing vasoactive intestinal peptide, neurotensin, and pancreatic polypeptide.

The biochemical characteristics of a pancreatic tumor from a patient with watery diarrhea, hypokalemia, hypochlorhydria, and steatorrhea is described Plasma concentrations of vasoactive intestinal peptide (VIP) were elevated 6-fold, those of neurotensin (NT) were elevated 10-fold, and those of pancreatic polypeptide (PP) were elevated 200-fold above the normal range. The pancreatic tumor removed was found to contain high concentrations of these peptides in a similar ratio to plasma. The tumor content of NT was 6 times higher than any previously reported, but no specific symptoms could be ascribed to NT. After removal of the tumor, plasma levels of VIP, NT, and PP returned to normal, and the diarrhea disappeared. Gel chromatography of plasma and tumor extracts indicated that all of the immunoreactive PP co-eluted with standard human PP. When the tumor extract was subjected to gel chromatography and high pressure liquid chromatography, two forms of VIP were detected, the major one resembling porcine VIP and a smaller more hydrophobic form detected by C- but not N-terminally directed VIP antisera. This smaller form was not present in normal ileum. Immunoreactive NT in plasma was predominantly an N-terminal fragment. High pressure liquid chromatography of the tumor extract revealed that approximately 75% of the NT immunoreactivity consisted of N-terminal fragments. In contrast, normal ileum contained only authentic NT-(1-13). Since N-terminal fragments of NT are thought to be biologically inactive, the nature of the immunoreactive NT should be determined before attempting to assign specific clinical symptoms to NT-secreting tumors.

Adenoma, Islet Cell↗

PubMed1984

Metabolism of neurotensin and pancreatic polypeptide in man: role of the kidney and plasma factors.

Neurotensin (NT) is a 13 amino acid peptide found predominantly in the ileum and it is released into the circulation by a meal. Much of the circulating NT consists of N terminal fragments which have no known biological activity. However, the sites and rates of NT metabolism are not known. In the present study the MCR and half-disappearance time of NT were estimated by infusing NT(1-13) into 10 normal subjects. The role of the kidney was assessed by studies in patients with chronic renal failure (CRF). The nature of the metabolites was characterized using region specific antisera and high pressure liquid chromatography (HPLC). The plasma pancreatic polypeptide response to the NT infusion was also measured. The NT MCR in normal subjects was 88 +/- 25 (SEM) ml/min X kg measured with the C terminal antiserum but only 9.9 +/- 0.8 ml/min X kg measured with the N terminal antiserum, a result consistent with the presence of long lasting N terminal fragments. HPLC of the plasma at equilibrium established that only 20% of the immunoreactivity was present as NT(1-13), with the majority as NT(1-8). No C terminal fragment were detected. Similarly, incubation of NT(1-13), 1-8, and 8-13 in plasma in vitro showed that N terminal fragments were stable in plasma, whereas C terminal fragments were completely metabolized. In patients with CRF, basal plasma NT (measured with the C terminal antisera) was significantly elevated and C terminal MCR was reduced by 82% and N terminal MCR by 32%. Thus the major effect of CRF was on the initial degradation of NT(1-13) to N terminal fragments. HPLC showed that over 60% of the NT was present as NT(1-13). In vitro degradation of NT was also slowed in CRF plasma. The increased proportion of intact biologically active NT in the circulation of the CRF patients could also explain the greater increase in pancreatic polypeptide levels during the NT(1-13) infusion. These studies have established that the metabolism of NT is influenced by the kidney and that the presence of predominantly N terminal fragments of NT in the peripheral circulation of normal subjects can be explained by a combination of renal and extrarenal factors.

Chromatography, High Pressure Liquid↗

PubMed1984

Secretion of neurotensin and its effects on the jejunum in the dog.

The triple-lumen perfusion technique was used to assess the effect of neurotensin on the canine jejunum; net water and electrolyte fluxes were measured during intravenous infusion of neurotensin and during preceding and succeeding control infusions of sodium chloride. A pharmacologic dose of neurotensin (70 pmol X kg-1 X min-1) converted basal net jejunal water and electrolyte absorption to net secretion (p less than 0.02); 3.2 pmol X kg-1 X min-1 of the peptide significantly inhibited net water and electrolyte absorption (p less than 0.05), and induced a transient but consistent increase in jejunal transmural potential difference; however, 1.3 pmol X kg-1 X min-1 had no significant effect on net jejunal water and electrolyte fluxes. Neurotensin (1.3 pmol X kg-1 X min-1) induced a rise in plasma neurotensinlike immunoreactivity which was greater than the increment occurring after a normal meal, but which could be reproduced in the same animals by infusion of oleic acid into the ileum. This latter stimulus, however, had no effect on jejunal potential difference, or net water and electrolyte fluxes. These observations do not support a hormonal role for neurotensin in the postprandial regulation of intestinal function in the dog, although they do not rule out the possibility of physiologic paracrine activity.

Action Potentials↗

PubMed1983

Cholinergic inhibition of meal stimulated plasma neurotensin like immunoreactivity in man.

Meal stimulated plasma neurotensin like immunoreactivity (NTLI) was compared during saline or atropine infusion in six volunteers over six hours. Plasma gastrin and pancreatic polypeptide were also measured to compare the timing of their release to that of NTLI. Like plasma gastrin and PP, plasma NTLI rose rapidly following the meal, rising from 27 +/- 7 pmol/l to a peak of 45 +/- 8 pmol/l at 20 minutes (p less than 0.05). Also, like that of pancreatic polypeptide, the release of NTLI was biphasic. Sixty minutes after the meal, plasma NTLI had returned to basal values, followed by a rise to a prolonged peak of 64 +/- 10 pmol/l between 90-180 minutes (p less than 0.05) returning once more to basal values by 240 minutes. Following atropine, basal plasma NTLI fell from 22 +/- 4 pmol/l to 11 +/- 2 pmol/l (p less than 0.05), but rose to basal levels 30-60 minutes after the meal, where it remained unaltered for the remainder of the study. We conclude that both basal and meal stimulated plasma NTLI are inhibited by cholinergic blockade. Further, the similar temporal relationship between plasma NTLI and pancreatic polypeptide in the late phase of the meal response, suggests that a component of NTLI may mediate part of the intestinal phase of pancreatic polypeptide release.

Adolescent↗

PubMed1983

Elevation of plasma gastrin and pancreatic polypeptide by electrical vagal stimulation in sheep: effects of sequential stimulation.

Gastrin and pancreatic polypeptide (PP) are released into the circulation by vagal stimulation. The individual effects of the anterior and posterior vagal trunks on the release of these peptides are unknown. Four sheep were anaesthetized and studied acutely: both vagi were dissected at the hiatus and the trunks divided. In two sheep, the distal ends of the anterior trunks were stimulated for 5 min with an 8 V, 1 ms impulse at 10 Hz. After 1 h the posterior trunks were stimulated similarly. In the other two sheep, the posterior trunk was stimulated and after 1 h the anterior vagal trunk was stimulated. The anterior and posterior trunk equally stimulated the release of both gastrin and PP in four animals. The second stimulation in these four animals resulted in an 18-fold greater integrated response of gastrin and 20-fold greater response of PP. This potentiation to the second stimulus was observed in further experiments even when the same trunk, posterior or anterior, was stimulated twice. The similarity of influence of the anterior and posterior trunks for the release of PP suggests the existence of mechanisms for vagally stimulated PP release other than branches direct from the vagal trunks.

Animals↗

PubMed1983

The effect of atropine on bombesin and gastrin releasing peptide stimulated gastrin, pancreatic polypeptide and neurotensin release in man.

The effects of 1-h infusions of bombesin and gastrin releasing peptide (GRP) at 50 pmol/kg per h and neurotensin at 100 pmol/kg per h on gastrin, pancreatic polypeptide (PP) and neurotensin release in man were determined following either saline or atropine infusion (20 micrograms/kg). Bombesin produced a rise in plasma neurotensin from 32 +/- 6 to 61 +/- 19 pmol/l and of PP from 26 +/- 8 to 36 +/- 7 pmol/l. There was a further rise of plasma PP to 50 +/- 13 pmol/l after cessation of the infusion. GRP had no significant effect on plasma neurotensin, but compared to bombesin, produced a significantly greater rise in plasma PP from 34 +/- 6 to 66 +/- 19 pmol/l during infusion. There was no post-infusional increase. At this dose, GRP was as effective as bombesin in releasing gastrin, although unlike bombesin its effect was enhanced by atropine. Neurotensin produced a rise in plasma PP from 17 +/- 4 to 38 +/- 8 pmol/l. Atropine blocked the release of PP during GRP and neurotensin infusion. Atropine had no effect on neurotensin or PP release during bombesin infusion, but did block the rise in plasma PP following bombesin infusion. We conclude that, in contrast to meal-stimulated neurotensin release, bombesin-stimulated neurotensin release is cholinergic independent. Despite structural homology, bombesin and GRP at the dose used are dissimilar in man in their actions and sensitivity to cholinergic blockade.

Adolescent↗

PubMed1983

Distribution of vasoactive intestinal peptide, bombesin, and gastrin-cholecystokinin like peptides in the avian intestinal tract and brain.

The distribution of vasoactive intestinal peptide (VIP), bombesin and gastrin-cholecystokinin in the chicken was studied by radioimmunoassay of tissue extracts. VIP was present in high concentrations in colon (186 +/- 29 pmol/g), cloaca (116 +/- 27 pmol/g), jejunum (97 +/- 14 pmol/g) and pancreas (15 +/- 3 pmol/g) but not detected in lung, liver or thymus. The highest concentration of bombesin was in the proventriculus (92 +/- 13 pmol/g), negligible in remaining gut but found in brain. Gel chromatography indicated two forms of bombesin: one form eluting with bombesin-14 and the other with gastrin releasing peptide. Gastrin-like immunoreactivity was found in low levels in the gut and brain. The concentrations were higher with an antiserum which cross reacted with the carboxy terminus common to gastrin-17 and CCK compared to a gastrin specific antisera (P less than 0.01). This suggests that the carboxy terminal region has been conserved during evolution. Each distribution pattern of bombesin, VIP and gastrin CCK is different, and distinct from that found in mammals, suggesting specific roles for these peptides in birds.

Animals↗

PubMed1983

Starvation in the rat: effect on peptides of the gut and brain.

The effects of starvation on the tissue concentrations of some peptides common to the gastrointestinal tract and the central nervous system have been examined. Groups of 6 rats were either fed ad libitum or starved for up to 4 days and killed by decapitation. Antrum, fundus, duodenum, jejunum, ileum, colon, pancreas and brain were dissected, weighed and then frozen on dry ice. The tissues were extracted sequentially in boiling water and 3% acetic acid, centrifuged and the supernatants radioimmunoassayed for gastrin, cholecystokinin (CCK), vasoactive intestinal peptide (VIP), gastric inhibitory peptide (GIP) and somatostatin. Each peptide was not assayed in each tissue. Starvation had no effect on the concentrations of peptides measured in the fundus (somatostatin and VIP), ileum (somatostatin, GIP, VIP) and colon (somatostatin, GIP, VIP). VIP concentration was increased in the jejunum and GIP was increased in both the duodenum and jejunum. Antral gastrin was the only peptide in the gastrointestinal tract to be decreased by food deprivation. Somatostatin concentration was approximately doubled in the antrum, duodenum, jejunum and pancreas. Brain VIP was unchanged. Brain somatostatin and CCK were significantly reduced by starvation. We conclude that starvation results in organ-specific and hormone-specific alterations in tissue concentrations of peptides of the gastrointestinal tract and the central nervous system.

Animals↗

PubMed1983

Meal stimulated neurotensin release following gastric partitioning for morbid obesity.

The meal stimulated neurotensin release was studied in morbidly obese patients in whom gastric partitioning was performed as treatment for the obesity. Basal neurotensin and the early postprandial response were not altered by the operation. However, the late phase response between 60 and 150 min was depressed, the integrated response being 1.27 (s.e.m. = 0.22) nmol/l. min postoperatively, to 1.66 (s.e.m. = 0.32) nmol/l. min preoperatively (P less than 0.05). As neurotensin is a peptide which inhibits gastric acid secretion and stimulates pancreatic bicarbonate release, long term ulcerogenic effects of gastric partitioning operations should be considered.

Adult↗

PubMed1983

Organ and plasma metabolism of neurotensin in sheep.

The metabolism of neurotensin (NT) across specific vascular beds of conscious sheep and the stability of NT in plasma have been quantitated. The nature of the metabolites has been characterized with region-specific antiserums and chromatography. NT-(1-13) was infused at 200 pmol X kg-1 X h-1 for 60 min into nine ewes, and blood samples were taken via cannulas in the aorta, pulmonary artery, portal vein, hepatic vein, renal vein, and jugular vein. Two antiserums, one directed towards the N-terminal end of NT (7852) and the other directed to the C-terminal end (C28) were used for radioimmunoassay. Pancreatic polypeptide (PP) was measured also. Using the steady-state concentrations in the aorta, the metabolic clearance rate of NT measured with C28 was 25.8 +/- 3.2 ml X kg-1 X min-1, twice that with 7852. The kidney, brain, and gut were the major organs clearing NT with a greater disappearance of C-terminal than N-terminal immunoreactivity. Gel chromatography of plasma at steady state showed that the NT immunoreactivity consisted of intact NT and N-terminal fragments; no C-terminal fragments were detected. Similarly, incubation of NT in plasma in vitro resulted in the generation of stable N-terminal fragments. The kidney was also the major organ involved in the clearance of PP both in the basal state and after stimulation by NT. Because the C-terminal end of NT is biologically active, these studies suggest that either N-terminal fragments have some unknown biological role or that NT is acting as a local hormone.

Animals↗

PubMed1983

Effect of somatostatin on liver blood flow in the rat.

The effect of portal and systemic intravenous boluses of somatostatin on total liver blood flow in rats was studied using the xenon-133 clearance technique. No change in liver blood flow was found when somatostatin was delivered into the portal circulation, but there was a significant reduction in liver blood flow when somatostatin was delivered into the systemic venous circulation. The results suggest that somatostatin exerts its effect on liver blood flow through the pre-hepatic splanchnic circulation rather than directly on the portal vein.

Animals↗

PubMed1982

A radioimmunoassay for neurotensin in human plasma.

A specific radioimmunoassay for neurotensin in plasma has been developed with a sensitivity of 2 pmol/l of plasma. The antiserum was directed towards the amino terminal region of neurotensin and did not cross-react with other gastrointestinal peptides. Non-specific interference was eliminated and the sensitivity increased by extracting the plasma samples with ethanol prior to assay. Within- and between-assay coefficients of variation were 7.8% and .12% respectively. The mean plasma concentration of neurotensin in 30 fasting subjects was 29 +/- 4 pmol/l. A mixed meal increased plasma neurotensin from 16 +/- 2 to 53 +/- 6 pmol/l at 2 h.

Antibody Formation↗