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Biomedical subjects

T E Adrian

Publications and source records attributed to T E Adrian.

At least 73 records · Page 4Linked to original sources
PubMed1997

Growth hormone and glutamine do not stimulate intestinal adaptation following massive small bowel resection in the rat.

BACKGROUND: Certain nutrients and other trophic factors are highly sensitive stimulants of intestinal adaptation following short bowel syndrome. Growth hormone and glutamine in a modified diet have been shown to enhance nutrient absorption in patients with severe short bowel syndrome. However, neither growth hormone nor glutamine is capable of enhancing adaptation in an animal model. This study was conducted to determine if the combination of glutamine and growth hormone could enhance gut adaptation following massive small bowel resection in the rat. METHODS: Thirty-four male rats received 70% jejunoileal resection. The first group received glycine and rat growth hormone, the second glutamine and rat growth hormone, and the third glycine but no growth hormone. RESULTS: There was no evidence that the combination of glutamine and growth hormone could enhance mucosal mass, mucosal protein, or mucosal DNA levels relative to the other two control groups of animals. Likewise, sucrase activities were not enhanced by glutamine and growth hormone. CONCLUSIONS: It is unlikely that the combination of glutamine and growth hormone will be of benefit in the treatment of patients with short bowel syndrome. The results in previous human studies can be alternatively explained by the long-term nonspecific effect of enteral nutrition on gut adaptation.

Adaptation, Physiological↗
PubMed1997

Islet hormone secretion in pancreatic cancer patients with diabetes.

The diabetes or impaired glucose tolerance that occurs in most patients with pancreatic cancer is characterized by profound insulin resistance. Recent evidence suggests that the diabetes may result from the presence of the tumor rather than being a predisposing factor to development of the malignancy. Some islet hormones have been shown to exhibit diabetogenic effects. To investigate the potential role of these hormones in the diabetic state associated with pancreatic cancer, we measured islet hormones during fasting in pancreatic cancer patients (n = 30), patients with other malignancies (n = 43), and healthy controls (n = 25). Preoperative pancreatic cancer patients were classified as normal glucose tolerance (NGTT), impaired glucose tolerance (IGTT), non-insulin-requiring diabetes (NIRD), and insulin-requiring diabetes (IRD). Nine pancreatic cancer patients were studied after tumor removal by subtotal pancreatectomy. Some preoperative pancreatic cancer patients (n = 19), postoperative patients (n = 9), and controls (n = 8) were also studied during hyperglycemia and following glucagon injection. Fasting plasma C-peptide was elevated in NIRD pancreatic cancer patients compared to controls. Fasting levels of islet amyloid polypeptide (IAPP), glucagon, and somatostatin were elevated in NIRD and IRD patients. IAPP and glucagon, but not somatostatin, normalized following subtotal pancreatectomy. During hyperglycemia, increases in C-peptide and IAPP were seen only in controls and in NGTT and postoperative pancreatic cancer patients. After glucagon infusion, IAPP levels increased in controls and nondiabetic cancer patients; C-peptide levels increased in controls, nondiabetic patients, and NIRD. Responses of C-peptide and IAPP to glucagon normalized after pancreatectomy. During hyperglycemia, glucagon levels fell in all groups except IGTT patients and a decrease in somatostatin concentrations was seen in controls.

Adenocarcinoma↗
PubMed1997

Trophic effects by epidermal growth factor on duodenal mucosa and exocrine pancreas in rats.

Epidermal growth factor (EGF) is a potent growth factor with possible implications on the regulation of pancreatic secretion and duodenal absorption but also on pancreatic tumor growth. In the present study the growth effect on duodenal mucosa and pancreas by a 14-day continuous infusion of three different doses of EGF (4, 30 and 60 micrograms EGF/kg/24 h) was studied in rats. The EGF content in duodenal mucosa and pancreatic tissue was significantly increased by 30 and 60 micrograms/kg/24 h of EGF while plasma levels were only marginally increased. Neither duodenal mucosal nor pancreatic weights were changed but DNA content in both tissues was increased with the higher EGF doses. Long-term EGF infusion has moderate trophic effect on duodenal mucosa and the pancreas. There is a high tissue uptake of EGF, specially in duodenal mucosa. The hyperplasia seems to be related to tissue levels of EGF but not to plasma levels.

Animals↗
PubMed1997

Chronic low dose islet amyloid polypeptide infusion reduces food intake, but does not influence glucose metabolism, in unrestrained conscious rats: studies using a novel aortic catheterization technique.

Islet amyloid polypeptide (IAPP) is a 37-amino acid polypeptide coproduced with insulin in the beta-cells of the pancreatic islets. The physiological effects of IAPP have not been established. Although effects on glucose metabolism are seen only at pharmacological doses both in vitro and in vivo, effects on food intake have been shown at near-physiological concentrations. The aim of the present study was to investigate the effects of similar elevations of circulating plasma IAPP levels on glucose metabolism in rats and to evaluate the function of a novel aortic catheterization technique. In a cross-over design, two sets of experiments in which conscious unrestrained rats received chronic IAPP infusions at 0 and 2 or 0 and 7 pmol/kg min were performed. Peripheral glucose disposal was determined by means of the hyperinsulinemic euglycemic clamp technique. Chronic elevations of circulating IAPP at concentrations that reduced food intake [43.5 +/- 6.2 g (control) vs. 35.7 +/- 8.2 g (IAPP; P < 0.01) and 34.0 +/- 2.2 g (control) vs. 28.8 +/- 1.4 g (IAPP; P = 0.07) for the 7 and 2 pmol/kg x min experiments, respectively] had no effect on the glucose metabolic rate [GMR; 18.5 +/- 0.6 mmol/kg x h (control) vs. 18.7 +/- 0.9 mmol/kg x h (IAPP) and 14.4 +/- 0.7 mmol/kg x h (control) vs. 15.6 +/- 0.7 mmol/kg x h (IAPP) for the 7 and 2 pmol/kg x min experiments, respectively]. Thus, effects on glucose metabolism are unlikely to explain the anorectic effect of IAPP.

Amyloid↗
PubMed1997

Gastrointestinal hormone in dumping syndrome and reflux esophagitis after gastric surgery.

Several problems are associated with gastric resection, including the dumping syndrome, reflux esophagitis, and malabsorption. A better understanding of the pathophysiological changes will shed light on new and improved therapy. Serum levels of seven circulating gastrointestinal hormones following a standardized solid meal and a brief score of symptoms were evaluated in 10 patients after partial distal gastrectomy and 12 patients after total gastrectomy, both groups reconstructed by Billroth II anastomosis, and 9 age-matched healthy controls. Patients underwent resection for gastric cancer and were studied 45 +/- 10 months after surgery. At the time of study, the patients had adapted well to surgery and no longer exhibited the severe symptoms of dumping seen immediately post-operatively. In contrast, the total gastrectomy patients exhibited the symptoms of reflux esophagitis. The gastrointestinal hormone changes could be divided into three patterns; obtunded responses (gastrin, PP), normal release (motilin, GIP) and increased secretion (CCK, neurotensin, PYY). In these, the early reaction of neurotensin correlated with the scores of late dumping syndrome and reflux esophagitis. In the literature, many gastrointestinal hormones have been shown to respond as an enhancement rather than adaptation. In other gastrointestinal hormones, secretin belonged to the obtunded type and enteroglucagon were classified in the increased type. However, pathophysiological significance of these hormonal changes remained uncertain. The late adaptive changes in gastrointestinal hormone secretion may help to compensate for loss of gastric motor function which accompanies gastric resection. On the other hand, these hormonal changes may exacerbate the esophageal reflux following gastrectomy.

Adaptation, Physiological↗
PubMed1996

Bombesin may stimulate proliferation of human pancreatic cancer cells through an autocrine pathway.

Bombesin is trophic to normal pancreas and acinar cell adenocarcinoma, but its effects on ductal cell tumors are undetermined. The autocrine growth effects of bombesin on well-differentiated (HPAF, CD11) and poorly differentiated (CD18, PANC-1) human ductal pancreatic cancer cell lines were investigated. Receptor binding of labeled bombesin was measured in a whole-cell microplate assay. Bombesin production was measured by radioimmunoassay. Proliferative responses were quantified using the MTT assay. Messenger RNA for bombesin and its receptor were identified by primer extension analysis. A single class of high-affinity binding sites was detected on HPAF and CD18 cells. Similar affinities and high receptor densities were found on the 2 cell lines. Bombesin was secreted by all 4 cell lines during 24-hr culture in serum-free media, and its recovery was enhanced in the presence of protease inhibitors. Primer extension analysis demonstrated the presence of mRNA for both bombesin and its receptor in HPAF, CD18, CD11 and PANC-1 cells, even though no functional receptor was found in the latter 2 lines. Bombesin significantly stimulated the proliferation of HPAF and CD18 cells. This trophic effect was inhibited by the specific bombesin antagonist RC-3095. Bombesin may act as an autocrine growth factor in some human pancreatic cancer cell lines. Furthermore, other cell lines transcribe mRNA for bombesin receptors but have no functional bombesin receptors, suggesting a genetic or post-translational change in the receptor for these cells. Bombesin may be involved as a growth factor in the development of pancreatic ductal adenocarcinoma in humans. This possible autocrine growth pathway may provide an avenue for therapeutic intervention in this malignant disease.

Bombesin↗
PubMed1996

Smooth muscle contractility after intestinal resection.

Intestinal resection is followed by structural and functional adaptation of the remnant, including motor adaptation. Since changes also occur in intestinal smooth muscle, our aim was to determine whether changes in motor function are related to changes in smooth muscle contractility. Eighteen dogs underwent transection alone (GPI, n=6), 50% distal resection (GP II, n = 6) and 50% distal resection with jejunocolostomy (GP III, n = 6). Histologic measurements and length-tension studies with response to carbachol were made at 12 weeks. Longitudinal muscle (LM) length tended to increase in the resected animals but not significantly (174 +/- 23 and 180 +/- 23 vs 156 +/- 16 cm, GP II, GP III, and GP I, respectively). Circular muscle (CM) length was similar in all three groups (8.2 +/- 0.9 and 7.9 +/- 0.6 vs 7.5 +/- 0.6 cm). Both CM and LM tended to be thicker in the resected groups (CM: 660 +/- 163 and 733 +/- 139 vs 569 +/- 199 micron; LM: 213 +/- 77 and 246 +/- 76 vs 220 +/- 104 micron, GP II, GP III, and GP I, respectively, NS). Length-tension relationships for both CM and LM were similar in all three groups. The length (Lo) at which maximal active tension (To) was achieved was 130-140% initially in both LM and CM. Passive tension at Lo and the response to cholinergic stimulation were similar in all three groups. There were no significant differences in absolute active and total tension generated or force/cm2. The carbachol dose responses were similar with the maximal active tension occurring at 10(-4) M carbachol. The ED50 was greater in CM than in LM (P < 0.05 for transection animals). The ED50 was lower after resection and bypass (P < 0.05 GP III vs Gp I). There were no significant differences in in vitro smooth muscle length tension relationships or the response to cholinergic stimuli of jejunum 12 weeks after resection with or without bypass of the ICJ. Thus, any changes in motor adaptation during this period are related to earlier transient effects or other factors.

Adaptation, Physiological↗
PubMed1996

Duodenogastric reflux causes growth stimulation of foregut mucosa potentiated by gastric acid blockade.

We investigated whether duodenogastric reflux (DGR) together with gastroesophageal reflux causes growth stimulation of the foregut mucosa and if additional gastric acid suppression enhances the effect of DGR. DGR was induced in rats using a split gastroenterostomy. A cardiomyotomy was performed across the gastroeophageal junction in order to enhance reflux into the esophagus. DGR rats were divided into six subgroups: DGR, DGR + truncal vagotomy, DGR + omeprazole, DGR + gastrin receptor blockade, DGR + omeprazole + gastrin receptor blockade, and DGR + gastrin. Two sham groups, one with and one without omeprazole treatment, served as controls. DGR significantly increased the weight and DNA content of the esophageal and gastric mucosa, which was further enhanced by vagotomy or omeprazole. Histology revealed foveolar hyperplasia in the stomach and esophageal mucosal hyperplasia in these groups. In addition, severe esophagitis was found in the DGR group receiving omeprazole. Omeprazole without DGR had no growth-stimulating effect on the foregut mucosa. DGR-induced growth stimulation was accompanied by hypergastrinemia. Increased growth in the stomach but not the esophagus was inhibited by gastrin receptor blockade. Gastrin administration did not result in enhancement of DGR-induced growth stimulation of the foregut mucosa. It is concluded that DGR, often present in severe reflux esophagitis, causes mucosal growth of the foregut of rats. This trophic response may explain why severe reflux esophagitis is associated with an increased risk of esophageal adenocarcinoma. DGR-induced growth stimulation of the foregut is potentiated by gastric acid suppression, suggesting that chronic antisecretory medication in gastroesophageal reflux may not always be advisable. Omeprazole + DGR caused severe esophageal damage, which may explain why antisecretory medication may fail to heal severe reflux esophagitis.

Animals↗
PubMed1996

Role of peptide YY and enteroglucagon after low anterior resection. Comparison between straight and colonic J-pouch anastomosis.

PURPOSE: It has been shown in several studies that a colonic J-pouch obviates much of the early dysfunction after a low anterior resection in terms of urgent and frequent bowel movements. In search for specific mediators of the postoperative functional adaptation, two gut peptides, peptide YY and enteroglucagon, were studied METHODS: Plasma and "neorectal" mucosal levels of both peptides were measured in 12 patients with a straight coloanal anastomosis and in 11 patients with a colonic J-pouch anastomosis. Patients were part of a randomized trial comparing straight and colonic pouch anastomosis. Fasting plasma samples of both peptides were collected intraoperatively, after one week, before loop ileostomy closure, and at 1, 3, and 12 months after loop ileostomy closure. RESULTS: There was no difference between the straight and the pouch groups in plasma concentrations of either peptide at any time period postoperatively. The only longitudinal hormonal changes were transient increases in mucosal peptide YY content at one-month follow-up and in mucosal enteroglucagon content before loop ileostomy closure. CONCLUSION: Peptide YY and enteroglucagon responses in these patients appear not to be major factors for improved outcome after formation of a colonic pouch in low anterior resection.

Adaptation, Physiological↗
PubMed1996

Time course of adaptive regulatory peptide changes following massive small bowel resection in the dog.

Basal and postprandial concentrations of gastrointestinal hormones were measured in 12 dogs before and at one and three months after a 75% small bowel resection. Five animals were studied again at six months. Concentrations of enteric hormones and neuropeptides, measured in the proximal jejunum and distal ileum adjacent to the anastomotic site at the time of euthanasia, were compared with concentrations in control tissues taken from each animal at the time of resection. Increased basal and postprandial levels of gastrin (P < 0.05), cholecystokinin (CCK, P < 0.05), glucose-dependent insulinotropic peptide (GIP, P < 0.01), peptide YY (PYY, P < 0.001), and enteroglucagon (P < 0.001), were seen at one month after small bowel resection. In contrast, no significant changes were seen in concentrations of secretin, motilin, neurotensin, somatostatin, PP, or glucagon. Concentrations of enteroglucagon, GIP, and PYY remained high throughout the six-month study period. In contrast, gastrin and CCK had normalized by three months. Thus, only enteroglucagon, PYY, and GIP showed sustained elevations following enterectomy; the gastrin and CCK changes were transient. Following enterectomy, concentrations of vasoactive intestinal polypeptide (VIP) were reduced by about 50% in mucosal (P < 0.001) and muscle (P < 0.05) layers of proximal and distal gut. In contrast, calcitonin gene-related peptide (CGRP) was increased by about twofold in jejunal and ileal mucosa (P < 0.05), and CGRP elevations were even more marked in the muscle layers (P < 0.001). Somatostatin and neuropeptide Y (NPY) concentrations were similar to controls in all areas except for a small decrease in NPY in ileal mucosa (P < 0.05). These findings suggest that the increased motilin and PP concentrations previously reported after bowel resection in man are more likely to reflect underlying inflammatory bowel disease rather than enterectomy. The normalization of hypergastrinemia explains why the increased acid secretion after small bowel resection is transient. These results provide evidence for independent secretory control of enteroglucagon and PYY, which are both products of intestinal L cells. In addition, these studies reveal marked changes in enteric neuropeptide concentrations following bowel resection. VIP, which is thought to be a major inhibitory transmitter in the gut, is markedly reduced, while CGRP, which is mainly localized in sensory afferent fibers, is increased. These major neuropeptide changes are likely to be of importance in the adaptive responses to massive small bowel resection.

Adaptation, Physiological↗
PubMed1996

Smooth muscle adaptation after intestinal transection and resection.

Changes in motor function occur in the intestinal remnant after intestinal resection. Smooth muscle adaptation also occurs, particularly after extensive resection. The time course of these changes and their interrelationship are unclear. Our aim was to evaluate changes in canine smooth muscle structure and function during intestinal adaptation after transection and resection. Twenty-five dogs underwent either transection (N = 10), 50% distal resection (N = 10), or 50% proximal resection (N = 5). Thickness and length of the circular (CM) and longitudinal (LM) muscle layers were measured four and 12 weeks after resection. In vitro length-tension properties and response to a cholinergic agonist were studied in mid-jejunum and mid-ileum. Transection alone caused increased CM length in the jejunum proximal to the transection but did not affect LM length or muscle thickness. A 50% resection resulted in increased length of CM throughout the intestine and thickening of CM and LM near the anastomosis. Active tension of jejunal CM increased transiently four weeks after resection. Active tension in jejunal LM was decreased 12 weeks after transection and resection. Sensitivity of CM to carbachol was similar after transection and resection. It is concluded that: (1) Structural adaptation of both circular and longitudinal muscle occurs after intestinal resection. (2) This process is influenced by the site of the intestinal remnant. (3) Only minor and transient changes occur in smooth muscle function after resection. (4) Factors other than muscle adaptation are likely involved in the changes in motor function seen following massive bowel resection.

Adaptation, Physiological↗
PubMed1996

Cholecystokinin mediation of colonic absorption via peptide YY: foregut-hindgut axis.

Peptide YY (PYY), a 36-amino-acid polypeptide, is found in abundance in the colon, a region where its physiologic roles are unknown. Previous studies have revealed a substantial increase in plasma PYY after cholecystokinin (CCK) administration. PYY is released from the hindgut in response to a meal and inhibits CCK release. In this study we evaluated the effects of CCK and PYY on intestinal absorption of water and electrolytes. Colonic, ileal, or jejunal Thiry-Vella fistulas (TVFs) were created in 12 dogs, and intestinal continuity was reestablished. The TVFs were perfused with an isotonic buffer solution containing [14C] PEG as a volume marker. Electrolyte and water transport were measured every 15 minutes, and plasma PYY and CCK levels were measured by radioimmunoassay. Group 1 dogs received an intravenous bolus of MK329, a specific CCK receptor antagonist, at 20 nmol/kg after a standard mixed meal; group 2 colonic TVF dogs received a meal and an intravenous bolus of PYY polyclonal antibody at 1 mg/kg. Postprandially, all three regions of the bowel became significantly proabsorptive for water, sodium, and chloride. In the colon postprandial absorption was abolished by MK329 starting 60 minutes after a meal, whereas specific CCK receptor blockade blunted ileal absorption. CCK receptor blockade did not affect postprandial absorption in the jejunum. Postprandial PYY levels did not rise in MK329-treated animals. PYY antibody reduced colonic absorption during the postprandial phase. Reduction of meal-induced colonic absorption and PYY release by MK329 in awake dogs suggests an important foregut-hindgut hormonal feedback loop. Foregut-derived CCK stimulates hindgut PYY release, which in turn stimulates colonic absorption while inhibiting further CCK release.

Animals↗
PubMed1996

Effects of ischaemia and reperfusion on vasoactive neuropeptide levels in the canine infrarenal aortic revascularization model.

Infrarenal aortic cross-clamping is associated with remote vascular events, including myocardial infarction and renal insufficiency. The purpose of this study was to determine whether hindlimb ischaemia and reperfusion associated with infrarenal aortic cross-clamping results in the production of vasoactive regulatory neuropeptides. A canine model of infrarenal aortic cross-clamping was used for the study. Serial blood samples were drawn, prior to, at the time of, and serially following placement of the clamp and subsequent release of the clamp and reperfusion. Ischaemia resulted in increased mean(s.e.m.) plasma levels of neuropeptide Y (NPY) (initial 10.0(1.8) pmol/l versus ischaemia 24.7(2.3) pmol/l, P < 0.001) and vasoactive intestinal polypeptide (VIP) (initial 2.53(0.5) pmol/l versus ischaemia, 7.3(1.3) pmol/l, P < 0.05). Reperfusion produced three-fold elevation of VIP (initial 2.5(0.5) pmol/l versus reperfusion 9.6(1.5) pmol/l, P < 0.001), two-fold elevation in the plasma levels of endothelin-1 (initial 1.3(0.1) pmol/l versus reperfusion maximum 2.5(0.3) pmol/l, P < 0.01) and NPY (initial 10.0(0.8) pmol/l versus reperfusion maximum 23.9(2.3) pmol/l, P < 0.001). Ischaemia and reperfusion did not alter calcitonin gene-related peptide (CGRP) (a potent vasodilator) levels. Endothelin-1 (ET-1) plasma levels were also increased following haemorrhagic shock (initial 1.3(0.1) pmol/l versus exsanguination 3.4(0.4) pmol/l, P < 0.001), but not during ischaemia (initial 1.3(0.1) pmol/l versus ischaemia maximum 1.7(0.2) pmol/l, P = 0.7). It was concluded that vasoactive regulatory peptides are released following ischaemia, reperfusion and shock in the canine infrarenal aortic revascularization model and, therefore could contribute to remote vascular events observed with infrarenal aortic cross-clamping.

Animals↗
PubMed1996

Effects of voluntary physical exercise on high-fat diet-promoted pancreatic carcinogenesis in the hamster model.

We examined the effect of voluntary physical exercise (running wheels) on pancreatic carcinogenicity of N-nitrosobis-(2-oxopropyl) amine (BOP) in groups of female Syrian hamsters fed a high-fat (HF) diet in which corn oil was 24.6% of the diet or a low-fat (LF) diet in which corn oil was 4.5% of the diet. Each group was divided into an exercising (EX) group (LF-EX and HF-EX) and a sedentary (S) group (LF-S and HF-S). All hamsters were treated with BOP (20 mg/kg body wt) weekly for two weeks beginning four weeks after the experimental diets, which were fed from weaning. A modified glucose tolerance test was performed before the BOP injections and then again at 20 and 40 weeks, and the levels of glucose, insulin-like growth factor I, and insulin were determined in the plasma samples. At the end of the experiment, serum levels of lipid metabolites were also examined in six hamsters from each group. The experiment was terminated 44 weeks after the BOP treatment. Pancreatic ductal/ductular adenocarcinoma incidence was significantly higher in hamsters fed the HF diet (HF-S and HF-EX) than in those fed the LF diet (LF-S and LF-EX). In all groups, glucose and insulin-like growth factor I levels remained within the normal range throughout the experiment, whereas insulin and lipid metabolite levels were significantly elevated in all hamsters fed the HF diet (HF-S and HF-EX). Exercise significantly reduced the insulin level in the group fed the HF diet but did not influence the cancer burden, possibly by the generation of reactive lipid metabolites. Overall, the results showed that voluntary physical exercise does not influence the promotional action of the HF diet on pancreatic carcinogenesis in hamsters. This action could be attributed to the ability of the HF diet to increase the secretion of insulin, which has a growth-promoting and mitogenic effect on pancreatic cells, and to the effect of an HF diet or physical exercise in producing excess free radicals.

Adenocarcinoma↗
PubMed1996

Gastric juice protects against the development of esophageal adenocarcinoma in the rat.

OBJECTIVE: The authors investigate the effects of gastric juice on tumorigenesis in a rat model of esophageal adenocarcinoma. SUMMARY BACKGROUND DATA: In rats treated with the carcinogen methyl-n-amyl nitrosamine, squamous cancer of the esophagus develops in a time- and dose-dependent manner. When methyl-n-amyl nitrosamine treatment is preceded by an operation to induce reflux of duodenal and gastric juice into the esophagus, there is an increased yield of esophageal tumors, many of which are adenocarcinomas. When only gastric juice refluxes into the esophagus, the tumor yield is less and adenocarcinomas are not found. METHODS: Two hundred seventy 8-week old Sprague-Dawley rats were studied. Twenty unoperated rats served as controls. The remaining rats underwent the following operations: esophagoduodenostomy with gastric and vagal preservation to induce duodenogastroesophageal reflux (n = 48); esophagoduodenostomy with antrectomy and Billroth 1 reconstruction to produce reflux of duodenogastric juice with the exclusion of the antrum (n = 53); esophagoduodenostomy with proximal gastrectomy to induce hypergastrinemia and reflux of duodenogastric juice with exclusion of the body and forestomach (n = 51); esophagoduodenostomy plus total gastrectomy to produce reflux of duodenal juice alone (n = 50); and esophagoduodenostomy with vagal and gastric preservation but with division of the duodenum just beyond the pylorus and reimplantation into the jejunum, 13 cm distal to the esophagoduodenostomy. This produced reflux of duodenal juice with gastric juice diverted downstream, (n = 48). At 10 weeks of age, all rats were given 4 weekly doses of carcinogen (methyl-n-amyl nitrosamine, 25 mg/kg intraperitoneally), and survivors were killed at 36 weeks of age. RESULTS: The prevalence rate of esophageal adenocarcinoma was 30% in rats with duodenogastroesophageal reflux and 87% in rats with reflux of duodenal juice alone. Fifty-six percent of rats with reflux of duodenogastric juice with exclusion of the antrum and 72% of rats with reflux of duodenogastric juice with the exclusion of the body and forestomach developed adenocarcinoma, showing a progression increase in the prevalence of adenocarcinoma as less gastric juice was permitted to reflux with duodenal juice into the esophagus. CONCLUSION: In this rat model, the presence of gastric juice in refluxed duodenal juice against the development of esophageal adenocarcinoma. The protective effect appears to be due to acid secretion from the stomach. Continuous profound acid suppression therapy may be detrimental by encouraging esophageal metaplasia and tumorigenesis in patients with duodenogastroesophageal reflux.

Adenocarcinoma↗
PubMed1996

Chronic infusion of islet amyloid polypeptide causes anorexia in rats.

Islet amyloid polypeptide (IAPP) is a hormonal peptide that at high doses has been shown to reduce food intake. In the present study, the dose-response effects of subcutaneous infusion of IAPP (0, 2, 7, and 25 pmol.kg-1.min-1) for 8 days on food intake and meal patterns in rats were investigated. At the end of the experiment, plasma was obtained and levels of IAPP were measured by radioimmunoassay. IAPP dose-dependently and transiently inhibited food intake. The minimal effective dose (2 pmol.kg-1.min-1) caused a small but significant (up to 14%, P < 0.01) inhibition of food intake that lasted 5 days. The highest dose administered (25 pmol.kg-1.min-1) had the greatest effect (up to 44%, P < 0.001), which lasted throughout the 8-day period. Reductions in feeding during light and dark phases occurred through a decrease in number of meals consumed rather than meal size or meal duration. IAPP also decreased body weight gain and water intake dose dependently. IAPP infusion of 2, 7, and 25 pmol.kg-1.min-1 increased plasma IAPP concentrations from a basal level of 10.3 +/- 0.7 pM to 35.1 +/- 5.4, 78.1 +/- 11.2, and 236.6 +/- 23.6 pM, respectively, values that are likely to be close to physiological and within the pathophysiological ranges. Thus IAPP may play an important physiological or pathophysiological role in control of food intake.

Amyloid↗