gastrins and Body-Weight

Topics: Adult; Age Factors; Aged; Animals; Body Constitution; Body Weight; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Energy Metabolism; Fasting; Female; Gastrins; Humans; Male; Middle Aged; Nutrition Disorders; Obesity; Protein Deficiency; Somatotypes

Topics: Anemia, Hypochromic; Body Weight; Bone Diseases; Chronic Disease; Diarrhea; Dumping Syndrome; Duodenal Obstruction; Duodenal Ulcer; Female; Follow-Up Studies; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Insulin; Male; Methods; Pentagastrin; Peptic Ulcer; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; Postoperative Complications; Recurrence; Stomach Ulcer; Vomiting

Topics: Body Weight; Cholecystokinin; Digestion; Digestive System Physiological Phenomena; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Gastrointestinal Motility; Glucagon; Humans; Hydrogen-Ion Concentration; Insulin; Pancreas; Pepsin A; Peptides; Secretin

Topics: Amylases; Body Weight; Carbon Isotopes; Carboxypeptidases; Chymotrypsin; Enzyme Activation; Gastrins; Humans; Iodine Radioisotopes; Lipase; Microspheres; Organ Size; Pancreas; Radioisotopes; Secretin; Selenium; Trypsin

Topics: Achlorhydria; Age Factors; Body Weight; Diagnosis, Differential; Duodenal Ulcer; Ethnicity; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Histamine; Humans; Male; Methods; Pentagastrin; Sex Factors; Stomach Diseases; Stomach Ulcer; Time Factors; Zollinger-Ellison Syndrome

Topics: Acetazolamide; Anemia; Body Weight; Drug Synergism; Female; Gastric Juice; Gastrins; Histamine; Humans; Insulin; Male; Parathyroid Hormone; Sex Factors; Stimulation, Chemical; Thyroxine

To determine if a 4-week course of 14 mg weekly GLP-1 agonist LY2428757 combined with 3 mg or 2 mg daily gastrin analogue TT223 (LY+TT223) results in long-term glycaemic changes.. Patients with in adequately-controlled type 2 diabetes mellitus ±metformin (N=151) were randomized to a 4-week course of LY+TT223 (3 mg), LY+TT223 (2 mg), LY+TT223 placebo (LY-only) or LY placebo+TT223 placebo (placebo). The primary objective was change in HbA1c from baseline to 5 month safter completion of therapy (i.e. at 6 months) and safety and tolerability with LY+TT223 versus LY-only.. LY groups showed HbA1c reductions during the active treatment phase. These did not persist during follow-up phase. Combining TT223 with LY did not result in additional glycaemic effects during treatment or follow-up. At 6 months, LSM ± SE for change in HbA1c from baseline was: LY+TT223 (3 mg): -0.1 ± 0.2%; LY+TT223 (2 mg): 0.1 ± 0.2%; LY-only: -0.2 ± 0.2%; placebo: 0.04 ± 0.2%. Secondary analyses were consistent with primary results. LY+TT223 was not superior to LY for other time points or end points, including insulin secretory response to mixed meal tolerance tests. The most common adverse events (nausea and vomiting) were more frequent with LY+TT223 versus LY-only. The safety profile was consistent with previous findings.. GLP-1+gastrin combination therapy did not improve glycaemic control versus GLP-1 alone.

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Gastrins; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Middle Aged

Gut hormones play an important role in the adaptation of the immature neonatal gut, and their secretion may be modulated by prebiotics. Furthermore, prebiotics are well known for their hypolipidemic potentials. We tested the hypothesis that prebiotics could alter motilin and gastrin secretion and reduce lipids in healthy preterms.. A total of 167 newborns were randomized to either a prebiotics enriched formula containing dietary oligosaccharides (short-chain galacto-oligo-saccharides/long-chain fructo-oligo-saccharides [scGOS/lcFOS]), at a concentration of 0.8 g/100 ml, or a common preterm formula. Day 1 and 16 basal motilin, gastrin concentrations, and lipids were evaluated together with growth parameters, gastric residue, bowel habits, and feeding tolerance. Adverse events including necrotizing enterocolitis (NEC) and septicemia were also recorded.. Mean motilin increase and day 16 mean values were greater for the intervention, compared with the control group (P = .001, P = .005, respectively), while gastrin remained high in both groups. Mean cholesterol and low density lipoprotein (LDL) increase were significantly greater in the control, compared with the intervention (P = .037, and P = .001) group. Day 16 LDL levels were significantly higher in the control group. Mean weight was increased in the control group, while gastric residue was less and stool frequency was increased in the intervention group. NEC and septicemia were not statistically different between groups.. A prebiotics enriched formula resulted in significant surge of motilin relating to reduced gastric residue, compared with a common preterm formula. Mean cholesterol change was lower, while LDL was not increased in the prebiotics group, compared with the control group.

Topics: Adult; Body Weight; Cholesterol; Cholesterol, LDL; Defecation; Double-Blind Method; Enterocolitis, Necrotizing; Feces; Female; Gastric Emptying; Gastrins; Gastrointestinal Tract; Growth; Humans; Incidence; Infant Formula; Infant, Newborn; Infant, Premature; Motilin; Oligosaccharides; Prebiotics; Pregnancy; Sepsis; Young Adult

To observe and explore the effect of Fuling () in alleviating the spleen deficiency symptom pattern (SDSP).. We established an animal model of SDS in Sprague-Dawley () rats by treating them with deficiency-inducing factors, including irregular feeding and tail clamping. Mice were administered Fuling () and its extracts (raw/cooked powder, aqueous/alcohol extract) by gavage once a day for 21 d. The body weight, rectal temperature, and spleen and thymus organ coefficients were calculated. The levels of motilin (MTL), gastrin (GAS), aquaporin 2 (AQP2), interleukin 2 (IL-2), IL-4, and 5-hydroxytryptamine (5-HT) in the serum and the level of AQP2 in the kidneys were evaluated by enzyme-linked immunosorbent assay.. Fuling () and its extracts did not change the body weight, rectal temperature, and organ coefficients of the spleen and thymus. However, it reduced the levels of MTL and GAS and increased the levels of IL-2 and AQP2. In addition, the levels of IL-4 and 5-HT showed no significant alteration.. These results suggested the crucial function of () in SDSP, especially promoting digestive function and water metabolism.

Topics: Animals; Aquaporin 2; Body Weight; Gastrins; Interleukin-2; Interleukin-4; Mice; Rats; Rats, Sprague-Dawley; Serotonin; Spleen; Wolfiporia

The present study has examined the antidiabetic effects of 21 days co-administration of xenin-8-Gln with the dual-acting fusion peptide, exendin-4/gastrin, as well as persistence of beneficial metabolic benefits, in high fat fed (HFF) mice. Xenin-8-Gln, exendin-4 and gastrin represent compounds that activate receptors of the gut-derived hormones, xenin, glucagon-like peptide-1 (GLP-1) and gastrin, respectively. Twice-daily administration of exendin-4/gastrin, xenin-8-Gln or a combination of both peptides significantly reduced circulating glucose, HbA1c and cumulative energy intake. Combination therapy with xenin-8-Gln and exendin-4/gastrin increased circulating insulin. All HFF mice treated with exendin-4/gastrin presented with body weight similar to lean control mice on day 21. Each treatment improved glucose tolerance and the glucose-lowering actions of glucose dependent insulinotropic polypeptide (GIP), as well as augmenting glucose- and GIP-induced insulin secretion, with benefits being most prominent in the combination group. Administration of exendin-4/gastrin alone, and in combination with xenin-8-Gln, increased pancreatic insulin content and improved the insulin sensitivity index. Pancreatic beta-cell area was significantly increased, and alpha cell area decreased, by all treatments, with the combination group also displaying enhanced overall islet area. Notably, metabolic benefits were generally retained in all groups of HFF mice, and especially in the combination group, following discontinuation of the treatment regimens for 21 days. This was associated with maintenance of increased islet and beta-cell areas. Together, these data confirm the antidiabetic effects of co-activation of GLP-1, gastrin and xenin cell signalling pathways, and highlight the sustainable benefits this type of treatment paradigm can offer in T2DM.

Topics: Animals; Body Weight; Diet, High-Fat; Drug Interactions; Energy Metabolism; Exenatide; Gastrins; Glucagon; Glycated Hemoglobin; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Metabolism; Mice; Pancreas; Peptide Fragments; Time Factors

Functional outcomes were prospectively compared between two types of reconstruction [double tract (L-DT; n = 15) and jejunal interposition (L-JIP; n = 15)] following laparoscopic half-proximal gastrectomy (LPG), including laparoscopic total gastrectomy (L-TG; n = 30) as a control group, at 1 year after surgery.. Clinical investigations were performed in each patient, and functional evaluations, involving the swallowing of an alimentary liquid containing acetaminophen (AAP), followed by measurements of the concentrations of AAP and hormones in the sitting (n = 5) and in the supine positions (n = 5), were carried out in each group.. The post-/preoperative body weight ratios were significantly higher in the L-DT and L-JIP groups than in the L-TG group. The AAP levels were significantly lower in the LPG group than in the LTG group. The AAP, insulin, and gastrin levels in the L-JIP group were markedly increased in the sitting position compared with the supine position, while those in the L-DT and L-TG groups were stable in both positions.. L-JIP and L-DT are procedures that maintain gradual intestinal absorption and help improve the quality of life. Intestinal absorption and hormonal secretion were relatively unaffected by the posture of the meal intake after L-DT, so L-DT might be the procedure providing the most stable results.

Topics: Acetaminophen; Aged; Body Weight; Female; Gastrectomy; Gastrins; Humans; Insulin; Intestinal Absorption; Jejunum; Laparoscopy; Male; Middle Aged; Perioperative Period; Plastic Surgery Procedures; Posture; Prospective Studies; Quality of Life; Stomach; Stomach Neoplasms; Time Factors

Recent studies suggest the possibility of the stomach playing a role in diabetes remission after bariatric surgery. In this study, we investigated whether bypassing the stomach alleviates diabetes in diabetic rodent model. Eighteen moderately obese and diabetic Sprague-Dawley rats were randomly assigned to Esophagoduodenostomy with or without gastric preservation (EDG and EDNG/total gastrectomy, respectively), and SHAM groups. Bodyweight, food intake, fasting glucose level, oral glucose tolerance test result (OGTT), and hormone levels (insulin, glucagon-like peptide-1, ghrelin, gastrin and glucagon) were measured preoperative and postoperatively. Postoperatively, bodyweight and food intake did not differ significantly between the EDG and EDNG groups. Postoperative fasting blood glucose and OGTT results declined significantly in the EDG and EDNG group when compared with the respective preoperative levels. Postoperative glucose control improvements in EDNG group was significantly inferior when compared to EDG. Compared preoperatively, postoperative plasma ghrelin and gastrin levels declined significantly in EDNG group. Preoperative and postoperative plasma GLP-1 level did not differ significantly among all the groups. Postoperatively, EDG group had significantly higher insulin and lower glucagon levels when compared with SHAM. In conclusion, bypassing and preserving the stomach resulted in superior glucose control improvements than total gastrectomy.

Topics: Animals; Bariatric Surgery; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Duodenostomy; Eating; Esophagostomy; Gastric Bypass; Gastrins; Ghrelin; Glucose; Glucose Tolerance Test; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Streptozocin; Treatment Outcome

The pharmacological effects of glutinous rice (GR) and GR amylopectin (GRA) on the gastrointestine were investigated in rhubarb-induced spleen deficiency rats by determining the levels of gastrointestinal hormones such as the peptides serum gastrin, amylase motilin, and somatostatin. GR and GRA were given by gavage at various doses of GR (7.5, 15, and 30 g per kg body weight) and GRA (3.8, 7.6, and 15 g per kg body weight) every day for 4 weeks, respectively. The results indicated that the final body weight of rats in the highest-dose GR (GRH) group and all the GRA groups significantly (P < 0.05) increased (7.2-12.1%) compared with the model control (MC) group. All the GR and GRA treated groups had significantly (P < 0.05) higher gastrin contents (32.8-51.2%), motilin levels (13.8-39.2%), and amylase contents (22.5-39.4%) and the GRH and highest-dose GRA (GRAH) groups had significantly (P < 0.05) lower somatostatin contents compared with the MC group. Meanwhile, the somatostatin contents were negatively correlated with the motilin levels (r = -0.964, P < 0.01) and amylase contents (r = -0.981, P < 0.01). The GRAH treatment group had the highest final body weight, gastrin contents, motilin levels, and amylase contents and the lowest somatostatin contents, which demonstrated that GRA might play the most important role in the spleen-regulating activities of GR.

Topics: Amylopectin; Animals; Body Weight; Disease Models, Animal; Dose-Response Relationship, Drug; Gastrins; Male; Motilin; Oryza; Plant Extracts; Rats; Rheum; Somatostatin; Spleen

A controversy developed between the benefits of energy drinks (EDs) versus the possible health threats since its revolution. Lack of information was a call to assess the effect of chronic consumption of Power Horse (PH) as one of the EDs, on the structure of pancreas and fundic mucosa of stomach in rats, and possible protective role of Omega-3.. Thirty two adult male albino rats were divided equally into 4 groups; control received group which only received a standard diet, Omega-3 group, PH group which given PH and PH plus Omega-3 group received both PH plus Omega-3 for 4 weeks. Biochemical assessment of blood glucose, serum insulin, gastrin, tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthetase (iNOS) was performed. The antioxidant activity and histopathological examination of both pancreatic tissue and fundic mucosa of stomach were assessed.. Administration of PH significantly increased serum insulin and glucose levels while it significantly reduced serum gastrin level compared to control. PH also caused oxidants/antioxidants imbalance in both pancreas and fundic mucosa. The latter revealed degenerative changes and increased apoptosis which was evident by increased caspase-3 immunoexpression. Pancreas exhibited signs of β-cells overstimulation. Fundic mucosa showed reduced number of parietal cells, gastrin hormone expression compared to control group. Omega-3 administration could alleviate, to some extent, these changes. It significantly decreased TNF-α, iNOS and reduced glutathione (GSH) as well as significantly increasing superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities compared to the group which received PH alone.. Power Horse intake significantly injures islet cells, pancreatic acini as well as the glandular cells of the fundic mucosa. Omega-3 decreases these detrimental effects mostly through its antioxidant and anti-inflammatory action.

Topics: Animals; Antioxidants; Blood Glucose; Body Weight; Energy Drinks; Fatty Acids, Omega-3; Gastric Mucosa; Gastrins; Hydrogen-Ion Concentration; Insulin; Male; Nitric Oxide Synthase Type II; Pancreas; Rats; Stomach; Tumor Necrosis Factor-alpha

Green tea catechins (GTCs) have been implicated in various physiological effects, including anti-carcinogenic activities. In the present study, we evaluated the effects of GTCs specifically on the development of gastritis and pre-malignant lesions in insulin-gastrin mice. Nine-week-old male INS-GAS mice (n=38) were supplemented with GTCs for 4 and 28 weeks, and their body weights, serum gastrin levels, histopathology and pro-inflammatory cytokine levels in gastric tissue and mucosal cell proliferation were monitored. Body weights of the GTC-treated mice were significantly lower than those of the untreated controls (P≤0.05). Serum gastrin levels were suppressed at the age of 37-weeks (P≤0.05). The histopathological scores indicated that the extent of dysplasia was significantly diminished (P≤0.05), although GTC supplementation did not affect the inflammation scores. The messenger RNA levels of interferon (IFN)-γ were significantly reduced at the age of 13 weeks (P≤0.05), although the changes did not reach statistical significance at the age of 37 weeks (P=0.056). The labeling index of Ki-67 immunohistochemistry was significantly decreased (P≤0.05). These results demonstrated that GTCs may play a protective role in the development of gastritis and pre-malignant lesions via an IFN-γ, gastrin, and mucosal cell proliferation-dependent mechanism in this rodent model and potentially in humans.

Topics: Animals; Anticarcinogenic Agents; Body Weight; Camellia sinensis; Catechin; Cell Proliferation; Drug Evaluation, Preclinical; Epithelial Cells; Gastric Mucosa; Gastrins; Gastritis; Interferon-gamma; Male; Mice; Stomach Neoplasms

In the present study, the therapeutic effects of Lactobacillus casei Qian (LC-Qian), the key microorganism in Tibetan yak yoghurt, on activated carbon-induced constipation were determined in vivo. ICR mice were treated with LC-Qian for nine days by oral administration. The body weight, defecation status, gastrointestinal transit and defecation time of mice were assessed, and the serum levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) were further evaluated. Bisacodyl was used as the positive control. The time until the first black stool defecation following carbon intake of the normal, control, 100 mg/kg bisacodyl-treated, Lactobacillus bulgaricus (LB)-treated, LC-Qian (L)-and LC-Qian (H)-treated mice was 93, 231, 121, 194, 172 and 157 min, respectively. Following treatment with LC-Qian, the gastrointestinal transit was increased to 52.4% [LC-Qian (L)] and 65.8% [LC-Qian (H)], while that in the group treated with the common lactic acid bacteria of LB was 40.3%. The MTL, Gas, ET, AChE, SP and VIP serum levels were significantly increased and levels of SS were reduced in mice following LC-Qian treatment compared with those in the control mice (P<0.05). Reverse transcription quantitative polymerase chain reaction indicated that LC-Qian raised the c-Kit, GDNF as well as SCF mRNA expression levels and reduced the TRPV1 and NOS expression levels in tissue of the small intestine in mice. These results suggested that lactic acid bacteria prevent constipation in mice, among which LC-Qian was the most effective.

Topics: Acetylcholinesterase; Animals; Body Weight; Carbon; Constipation; Defecation; Endothelins; Female; Gastrins; Gastrointestinal Transit; Gene Expression; Glial Cell Line-Derived Neurotrophic Factor; GPI-Linked Proteins; Intestine, Small; Lacticaseibacillus casei; Mice; Mice, Inbred ICR; Motilin; Probiotics; Proto-Oncogene Proteins c-kit; Somatostatin; Substance P; TRPV Cation Channels; Vasoactive Intestinal Peptide

The aim of this study was to investigate the effects of Lactobacillus fermentum Zhao (LF-Zhao) on activated carbon-induced constipation in ICR mice. ICR mice were administered lactic acid bacteria by gavage for 9 d. Body weight, diet intake, drinking amount, stool status, gastrointestinal transit distance and stool time, in addition to motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) levels in serum were monitored to evaluate the preventive effects of LF-Zhao on constipation. Bisacodyl, a laxative drug, was used as a positive control. Times to the first black stool for normal (untreated), control (no lactic acid bacteria treatment but activated carbon treated), bisacodyl-treated and L. delbrueckii subsp. bulgaricus (LB), LF-Zhao (L) (low concentration of 1×10(8) CFU/mL)- and LF-Zhao (H) (high concentration of 1×10(9) CFU/mL)-treated mice induced by activated carbon were 90, 218, 117, 180, 169 and 156 min, respectively. Following the consumption of LB, LF-Zhao (L) and LF-Zhao (H) or the oral administration of bisacodyl, the gastrointestinal transit distances were reduced by 55.2%, 61.3%, 70.6% and 94.6%, respectively. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Zhao compared with those in the control mice (p<0.05). These results demonstrated that lactic acid bacteria demonstrate preventive effects on mouse constipation and that LF-Zhao alleviated constipation symptoms better than LB.

Topics: Acetylcholinesterase; Animals; Body Weight; Carbon; Constipation; Defecation; Endothelins; Feces; Female; Gastrins; Gastrointestinal Transit; Laxatives; Limosilactobacillus fermentum; Mice, Inbred ICR; Motilin; Somatostatin; Substance P; Vasoactive Intestinal Peptide

To investigate the influence and mechanism of combining exercise with diet control on a model of lipid metabolism rat induced by high fat diet.. Twenty-four male Wistar rats were randomly divided into 3 groups of 8: normal, model and intervention. The model group and intervention group were fed with high fat diet, while the normal group received basal feed. From day 1, the intervention group was randomly given interventions such as swimming exercise and dietary restriction. The interventions duration were 28 days. At the end of the experiment, the levels of rats' body weight and liver weight were detected, the serum levels of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and hepatic triglyceride content (TG) were detected by using biochemical assay, serum level of gastrin (GAS), motilin (MTL) were assayed by the enzyme linked immunosorbent assay (ELISA).. Compared with the level of body weight and liver weight in the normal rats, body weight and liver weight in the rat of the model group were significantly increase (P<0.05 or P<0.01). Plasma concentrations of TC, LDL-C and hepatic TG in the model group were significantly increased compared with those in the normal group (P<0.05 or P<0.01). The contents of GAS, MTL, HDL-C in the model rats'plasma were significantly reduced compared with those of the normal group (P<0.05 or P<0.01). Compared with those in the model group, rats' body weight, liver weight, serum TC, LDL-C, and TG content of liver in the intervention group decreased significantly (P<0.05 or P<0.01). Meanwhile, serum content of GAS, MTL, HDL-C were significantly improved in the intervention rats compared to the model group.. The action of combining exercise with diet control for lipid metabolism disorder might be related to regulation of GAS, MTL and other gastrointestinal hormones.

Topics: Animals; Body Weight; Caloric Restriction; Cholesterol, HDL; Cholesterol, LDL; Diet, High-Fat; Gastrins; Hyperlipidemias; Lipid Metabolism; Liver; Male; Motilin; Organ Size; Physical Conditioning, Animal; Rats; Rats, Wistar; Swimming; Triglycerides

To investigate the effects and mechanisms of Gong-tone music on the immunological function in rats with the Chinese medicine syndrome of Liver (Gan)-qi stagnation and Spleen (Pi)-qi deficiency (LSSD).. Twenty five male Wistar rats of SPF grade were randomly divided into 5 groups: normal group, model group, Xiaoyao Powder () group, Gong-tone group and combined group (the combination of Gong-tone and Xiaoyao Powder), with 5 rats in each group. The rat model for the Chinese medicine syndrome of LSSD was induced by chronic bandage and irregular diet. The course of treatment was 21 days. After the treatment, the levels of serum gastrin and IgG were detected by enzyme-linked immunoabsorbent assay (ELISA). Phagocytosis of macrophages was detected by the neutral red uptake assay and T cell proliferation was investigated by 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay.. The serum gastrin, macrophage phagocytosis, IgG level and proliferation ability of T cells in the model group were significantly decreased compared with those in the normal group (P <0.05). Compared with those in the model group, the serum levels of gastrin, macrophage phagocytosis, IgG level and proliferation ability of T cells in Gong-tone, Xiaoyao Powder, and combined groups were significantly increased (P <0.05). The combined group was superior to either Gong-tone group or Xiaoyao Powder group.. Gong-tone music may upregulate the immunological function and play a role in adjuvant therapy in the Chinese syndrome of LSSD.

Topics: Animals; Auditory Perception; Behavior, Animal; Body Weight; Cell Proliferation; Depression; Gastrins; Immunoglobulin G; Liver; Macrophages; Male; Music; Phagocytosis; Qi; Rats; Rats, Wistar; Spleen; Syndrome; T-Lymphocytes

In addition to its glucoregulatory actions, exendin-4, a stable glucagon-like peptide-1 receptor agonist, exhibits protective effects in the pancreas and anti-obesity effects. Suitable combination treatment with other anti-obesity or pancreas protective agents would be an effective approach to optimize these additional effects. In the present study, we investigated the effects of the addition of omeprazole, a proton pump inhibitor, to exendin-4 in db/db mice, an experimental model of obesity and type 2 diabetes.. The effects repeated dose treatment for 14 days with exendin-4 (8 μg/kg, s.c.) and omeprazole (30 mg/kg, s.c.) on glycemic control, food intake, and body weight were determined in obese and hyperglycemic db/db mice. The effects of these treatments on plasma gastrin, ghrelin, and leptin levels were determined, along with effects on nausea-like symptoms. The pancreatic effects of the repeated dose treatment were assessed by measuring %HbA1c in the circulation as well as pancreatic insulin and glucagon content and glucokinase activity.. Combination treatment resulted in significant decreases in plasma leptin and ghrelin levels after repeated dosing. Omeprazole improved the anorectic and body weight-lowering effects and reversed the inhibitory effect of exendin-4 on gastrin levels after repeated dose treatment. The 14-day combination treatment significantly reduced glucose excursion and improved insulin levels, with a concomitant decrease in %HbA1c levels. It also improved glucokinase activity and pancreatic insulin content, with a significant decrease in glucagon content.. Combined treatment with omeprazole with exendin-4 reduces food intake and body weight gain, most likely through changes in plasma ghrelin and leptin levels, and improves pancreatic insulin and glucagon content by improving glucokinase activity.

Topics: Animals; Anti-Obesity Agents; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Gastrins; Glucagon; Hypoglycemic Agents; Insulin Resistance; Leptin; Male; Mice; Mice, Inbred Strains; Mice, Obese; Obesity; Omeprazole; Peptides; Venoms

Lizhong Pill, composed of radix Ginseng (Panax ginseng C.A. Meyer), rhizoma Zingiberis (Zingiber officinale Roscoe), rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala Koidz.) and radix Glycytthizae (Glycyrrhiza uralensis Fisch.), is a classical herbal product for curing spleen deficiency in traditional Chinese medicine (TCM), and reserpine treated rats show similar signs to TCM spleen deficiency pattern. This paper is aimed to explore the regulatory effect on neuroendocrinoimmune network by Lizhong Pill in reserpine induced TCM spleen deficiency rats.. 100 healthy adult male SD rats, with a mean weight of 200 g, were randomly divided into five groups in average: control group, reserpine treated group, atropine treated group, treatment groups with Lizhong Pill at high dose and low dose (equal to the dosage of crude drugs for 4 g/kg/d and 8 g/kg/d). Rats in reserpine treated group were induced by intraperitoneal injection of reserpine at 0.5 mg/kgd for 4 weeks. The levels of IL-1, IL-6 and gastrin were measured with radioimmunoassay, TNF-α and IFN-γ in serum were measured with ELISA, the level of vasoactive intestinal peptide (VIP) and substance P (SP) in small intestine were determined with radioimmunoassay, and the TNF-α and TGF-β positive cells in small intestine were detected by immunohistological staining. Data were analyzed with SAS 9.1 software package.. The rats in reserpine treated group, body weight, concentrations of IFN-γ, IL-1 and TNF-α in serum, expression of TGF-β in small intestine, VIP in small intestine decreased (P<0.05), and the level of IL-6 in serum, expression of TNF-α, SP in small intestine and gastrin were increased (P<0.05). Administration of Lizhong Pill at high dose could increase the body weights at day 21, and the weights of rats in Lizhong Pill groups were much higher compared to reserpine treated group. At high dose of Lizhong Pill could increase the level of TNF-α in serum. Lizhong Pill at high dose and low dose could reverse the changes of IL-1, IL-6 and IFN-γ, gastrin, expression of TGF-β and TNF-α, VIP and SP in small intestine.. The rats treated with reserpine, with similar signs to TCM spleen deficiency, show neuroendocrinoimmune disorders, and the restoration of the neuroendocrinoimmune disorders might be the part of mechanism of Lizhong Pill for reinforcing TCM spleen deficiency.

Topics: Animals; Atractylodes; Body Weight; China; Drugs, Chinese Herbal; Ethnopharmacology; Gastrins; Glycyrrhiza uralensis; Interferon-gamma; Interleukin-1; Interleukin-6; Intestine, Small; Male; Medicine, Chinese Traditional; Neuroimmunomodulation; Panax; Rats; Rats, Sprague-Dawley; Reserpine; Spleen; Substance P; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Vasoactive Intestinal Peptide; Zingiber officinale

We investigated whether corpus atrophic gastritis worsens in Mongolian gerbils (MGs) after long-term administration of proton pump inhibitor (PPI). MGs are an excellent model for studying Helicobacter pylori-related gastritis and adenocarcinoma.. MGs were separated into four groups (n =15/group); H pylori (ATCC43504) was inoculated into the OPZ(omeprazole)+Hp (H pylori) and Hp groups, a PPI (OPZ) was administered to the OPZ+Hp and OPZ groups and the control group received no treatment. MGs had access to food containing omeprazole (100 mg/kg body weight/day) for 6 months, after which their stomachs were removed and cut into nine sections (six sections in the fundus and three sections in the antrum). Corpus atrophy was evaluated by the absence of parietal cells in the six sections in the fundus. First, we calculated a percentage of the area devoid of parietal cells in each haematoxylin and eosin-stained section, and then we scored the degree of atrophy by adding the percentages of the six sections. A full score was 600.. Neutrophilic and lymphoid infiltrates were greater in the OPZ+Hp group than in the other groups. The corpus atrophy score in the OPZ+Hp group was significantly higher than that in the Hp group (p < 0.0048, Student t test). Significantly more adenocarcinomas were found in the OPZ+Hp (60%) than in the Hp (7%) group animals.. Long-term PPI administration promotes development of adenocarcinoma, which is associated with the progression of atrophic corpus gastritis in MGs infected with H pylori.

Topics: Adenocarcinoma; Animals; Body Weight; Cocarcinogenesis; Disease Models, Animal; Disease Progression; Drug Administration Schedule; Gastrins; Gastritis, Atrophic; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Male; Metaplasia; Proton Pump Inhibitors; Stomach; Stomach Neoplasms

To investigate the effect of a high-protein diet on corpus atrophic gastritis in Helicobacter pylori-infected Mongolian gerbils, H. pylori was administered orally to 5-wk-old Mongolian gerbils; and the animals were then fed a control diet (Group C); a high-fat diet (Group F: 40% fat); a high-protein diet (Group P: 32% protein); or a high-fat, high-protein diet (Group FP: 40% fat, 32% protein) for 50 wk beginning at 7 wk of age. In uninfected animals, the mucosal thickness of the corpus was significantly greater in Group P and Group FP than in Group C (P < 0.05). In infected animals, the serum gastrin level was significantly decreased in Group FP and marginally significantly decreased in Group P (P = 0.057) in comparison to Group C. The mucosal thickness of the corpus was significantly greater in Group P and Group FP than in Group C (P < 0.05). Mean inflammation and atrophy scores in the corpus were significantly lower in the high-protein groups (Groups P and FP) than in the control groups (Groups C and F; both inflammation and atrophy: P < 0.05). In conclusion, long-term administration of a high-protein diet suppresses corpus atrophic gastritis in H. pylori-infected Mongolian gerbils.

Topics: Animals; Antibodies, Bacterial; Body Weight; Caseins; Dietary Fats; Dietary Proteins; Gastric Fundus; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Male; Metaplasia; Organ Size; Severity of Illness Index; Specific Pathogen-Free Organisms; Stomach; Stomach Neoplasms

Long-term use of proton pump inhibitors (PPIs) has been reported to worsen corpus atrophic gastritis in patients with Helicobacter pylori infection. On the other hand, PPIs have been associated with fundic gland-type gastric polyps and various histological changes. In the present study, we attempted to establish a protocol for omeprazole (OPZ) administration to rats over a longer period and examined the morphological changes in the gastric mucosa after administration of OPZ for 6 months. A total of 34 Wistar rats (8 weeks old) were used. In a preliminary experiment to determine the appropriate dose of OPZ, the rats had ad libitum access to food containing different doses of OPZ for 1 month. We found an approximate dose of 100 mg/kg body weight/day of OPZ to be most suitable from the point of view of intragastric pH, body weight, and serum gastrin level. In the experiment proper, rats were divided into two groups, either control or OPZ diets, and morphological changes in the gastric mucosa in each group were then examined by hematoxylin and eosin and immunohistochemical staining with alpha-amylase, trypsin, and chromogranin A. Multiple vacuolar degeneration of parietal cells and numerous small mucous cells were evident at 1 month after treatment with OPZ. At 6 months after treatment with OPZ, cystic degeneration and acinar-cell-like cells containing red granules positive for alpha-amylase and trypsin and negative for chromogranin A were detected in the OPZ rats. The serum gastrin level in the OPZ group was significantly higher than that in the control group. We have established a protocol for long-term administration of OPZ in rats that is a useful model for analyzing morphological changes after long-term PPI therapy. Long-term OPZ treatment causes hypergastrinemia and pancreatic acinar cell metaplasia in this animal model.

Topics: alpha-Amylases; Animals; Anti-Ulcer Agents; Body Weight; Chromogranin A; Dose-Response Relationship, Drug; Drug Administration Schedule; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Gastrins; H(+)-K(+)-Exchanging ATPase; Male; Metaplasia; Models, Animal; Omeprazole; Pancreas; Pancreatic Diseases; Parietal Cells, Gastric; Proton Pump Inhibitors; Rats; Rats, Wistar; Time Factors; Trypsin

Mucolipidosis type IV (MLIV) is an autosomal recessive lysosomal storage disorder caused by mutations in the MCOLN1 gene, which encodes the 65-kDa protein mucolipin-1. The most common clinical features of patients with MLIV include severe mental retardation, delayed motor milestones, ophthalmologic abnormalities, constitutive achlorhydria, and elevated plasma gastrin levels. Here, we describe the first murine model for MLIV, which accurately replicates the phenotype of patients with MLIV. The Mcoln1(-/-) mice present with numerous dense inclusion bodies in all cell types in brain and particularly in neurons, elevated plasma gastrin, vacuolization in parietal cells, and retinal degeneration. Neurobehavioral assessments, including analysis of gait and clasping, confirm the presence of a neurological defect. Gait deficits progress to complete hind-limb paralysis and death at age ~8 mo. The Mcoln1(-/-) mice are born in Mendelian ratios, and both male and female Mcoln1(-/-) mice are fertile and can breed to produce progeny. The creation of the first murine model for human MLIV provides an excellent system for elucidating disease pathogenesis. In addition, this model provides an invaluable resource for testing treatment strategies and potential therapies aimed at preventing or ameliorating the abnormal lysosomal storage in this devastating neurological disorder.

Topics: Animals; Body Weight; Disease Models, Animal; Eye Diseases; Gastric Mucosa; Gastrins; Gene Targeting; Hindlimb; Inclusion Bodies; Longevity; Mice; Mice, Knockout; Mucolipidoses; Nervous System Diseases; Paralysis; Pyramidal Cells; Retinal Degeneration; Stomach Diseases; Survival Analysis; Transient Receptor Potential Channels; TRPM Cation Channels

The authors recently reported that gastrin gene knockout (GAS-KO) mice had an increased risk for colon carcinogenesis in response to azoxymethane (AOM) compared with their wild type (WT) littermates. In the current report, the authors discuss the predisposition of GAS-KO mice to develop obesity and metabolic hormonal changes that may contribute to their increased risk of colon carcinogenesis.. The weight and deposition of fat was monitored in the mice over a 14 month period, using magnetic resonance imaging and nuclear magnetic resonance techniques. Changes in plasma concentrations of ghrelin, leptin, insulin, and glucose were assessed using radioimmunoassay analysis and enzyme-linked immunosorbent assays. Preneoplastic markers of colon carcinogenesis (aberrant crypt foci [ACFs]), in response to AOM, were measured in a subset of obese versus lean GAS-KO mice and were compared with the markers in WT mice.. Increases in visceral adiposity were evident by age 2 months in GAS-KO mice, resulting in macroscopic obesity by age 7 months. Hyperinsulinemia and insulin:glucose ratios were increased significantly in GAS-KO mice as young as 1 month and preceded alterations in nonfasting leptin and ghrelin levels. The number of ACFs per mouse colon were increased significantly in the following order: obese GAS-KO mice > lean GAS-KO mice > WT mice. Fasting plasma insulin levels were 0.88 +/- 0.1 ng/mL, 1.45 +/- 0.3, and 2.76 +/- 0.9 ng/mL in the WT, GAS-KO lean, and GAS-KO obese mice, respectively.. The current results suggest the novel possibility that loss of amidated gastrins may increase adipogenesis, hyperinsulinemia, and colon carcinogenesis in GAS-KO mice. The increase in colon carcinogenesis may be due in part to hyperinsulinemia, increased obesity, and other associated hormone changes that were measured in GAS-KO mice.

Topics: Animals; Azoxymethane; Body Weight; Carcinogens; Colonic Neoplasms; Gastrins; Gene Expression; Ghrelin; Glucose; Hyperinsulinism; Insulin; Insulin Resistance; Leptin; Magnetic Resonance Imaging; Male; Mice; Mice, Knockout; Obesity; Peptide Hormones; Precancerous Conditions; Radioimmunoassay; Thinness

Increasing beta-cell mass and/or function could restore glucose homeostasis in diabetes mellitus. Hitherto, trophic factors for beta-cell regeneration after toxic events have been difficult to identify. We evaluated the application of gastrin and epidermal growth factor after alloxan-induced pancreatic beta-cell damage.. After alloxan treatment (70 mg/kg), mice were implanted with Alzet osmotic minipumps releasing gastrin and epidermal growth factor for one week. We monitored glycaemia, did histological analyses of the pancreata and quantified pancreatic beta-cell mass and insulin content.. Alloxan treatment alone resulted in a persisting hyperglycaemic state. Combined gastrin and epidermal growth factor treatment restored normoglycaemia in 3 days, an effect which seemed permanent. Glucose tolerance tests showed normal glucose responsiveness. Gastrin on its own and epidermal growth factor on its own did not alleviate hyperglycaemia. Islet mass, islet density and pancreatic insulin content were higher in mice treated with gastrin and epidermal growth factor than in untreated mice with persisting hyperglycaemia. In normoglycaemic control mice treatment with gastrin and epidermal growth factor did not affect these parameters. We detected transitional cytokeratin-positive ductal to endocrine insulin-expressing cells and noted increased ductal but not beta-cell proliferation.. Our results show that combined treatment with gastrin and epidermal growth factor can induce sufficient regeneration of a functional islet mass to restore glucose homeostasis.

Topics: Alloxan; Animals; Blood Glucose; Body Weight; Cell Count; Cell Division; Diabetes Mellitus, Experimental; Epidermal Growth Factor; Gastrins; Glucose Tolerance Test; Immunohistochemistry; Infusion Pumps, Implantable; Insulin; Islets of Langerhans; Keratins; Male; Mice; Mice, Inbred C57BL; Organ Size; Pancreas; Pancreatic Ducts

Whereas severe duodenal ulcer is the hallmark of acid hypersecretion in Zollinger-Ellison syndrome (ZE) and similar states, the esophagus also is at high risk. We quantified the incidence of esophagitis and various risk factors that might contribute to it.. Sixty-eight acid hypersecretors (basal acid output >15 mmol/h), 50 patients with ZE, and 18 patients without ZE with normal gastrin levels were studied by gastric analysis, serum gastrin levels, and endoscopy. In 44 of 68 patients, esophageal manometry was performed after the esophagus had healed.. Erosive esophagitis, grade 2 or worse, was found in 65%; an additional 15% had heartburn only, for a total reflux disease incidence of 80%. ZE accounted for 95% of severe esophagitis. Patients with and without esophagitis had the same high overnight fasting gastric residual volume and acidity, as well as basal and peak acid and pepsin outputs. However, patients with esophagitis had a lower median lower esophageal sphincter pressure (LESP) of 15.5 vs. 23 mm Hg in those without symptoms; the critical discriminator threshold was 16 mm Hg. Multivariate analysis further identified frequent vomiting and obesity as positive predictors of esophagitis, whereas Helicobacter pylori was a strong negative predictor (odds ratio, 0.16), possibly related to an elevated LESP in patients infected with H. pylori.. Erosive esophagitis is very common in acid hypersecretors. Identified risk factors that could promote abnormal esophageal exposure to the high acid and pepsin levels in our population of hypersecretors were vomiting, LESP < 16 mm Hg, and obesity, whereas H. pylori appeared to protect the esophagus not by reduced acid, but through an elevated LESP.

Topics: Adult; Age Distribution; Analysis of Variance; Body Weight; Case-Control Studies; Esophagitis; Esophagoscopy; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Helicobacter pylori; Humans; Incidence; Male; Manometry; Middle Aged; Multivariate Analysis; Probability; Prognosis; Risk Factors; Sampling Studies; Severity of Illness Index; Sex Distribution; Zollinger-Ellison Syndrome

Rescue with tissue-engineered small intestine (TESI) after massive small bowel resection (MSBR).. Short bowel syndrome is a morbid product of massive small bowel resection. We report the first replacement of a vital organ by tissue engineering with TESI after MSBR.. Ten male Lewis rats underwent TESI implantation with green fluorescent protein (GFP)-marked cells (TESI+, n = 5) or sham laparotomy (TESI-, n = 5) followed by MSBR. Side-to-side anastomosis of TESI to proximal small intestine was performed or omitted. TESIO animals underwent implantation of engineered intestine with no further surgery. Weights were measured QOD until day 40. Transit times were measured. DNA assay was performed with computer morphometry. Northern blots of RNA were probed for intestinal alkaline phosphatase (IAP) and villin. Hematoxylin and eosin, S100, and smooth muscle actin immunohistochemistry were performed. Blood was collected at sacrifice.. All 10 rats initially lost then regained weight. The initial rate of weight loss was higher in TESI+ versus TESI-, but the nadir was reached a week earlier with more rapid weight gain subsequently to 98% preoperative weight on day 40 in animals with engineered intestine versus 76% (P < 0.03). Serum B12 was higher at 439 pg/mL versus 195.4 pg/mL. IAP mRNA appeared greater in TESI+ than TESIO, with constant villin levels. Histology revealed appropriate architecture including nerve. GFP labeling persisted.. Anastomosis of TESI significantly improved postoperative weight and B12 absorption after MSBR. IAP, a marker of differentiation in intestinal epithelium, is present in TESI, and GFP labeling was accomplished.

Topics: Actins; Alkaline Phosphatase; Animals; Body Weight; Gastrins; Gastrointestinal Transit; Immunohistochemistry; Intestine, Small; Male; Microfilament Proteins; Organoids; Rats; Rats, Inbred Lew; RNA; S100 Proteins; Tissue Engineering; Vitamin B 12

Disturbances of gastric motor, secretory and/or sensory functions are frequently associated with gastritis. The aim of this study was to characterize motor and secretory alterations associated to chemically-induced gastritis in mice. Mild gastritis was induced with 0.1% iodoacetamide administered intragastrically and added to the drinking water for a 6 days period. A significant loss of body weight and a reduction in food and water intake was observed in iodoacetamide-treated animals compared with those receiving vehicle. At the end of the treatment period, no macroscopic alterations were observed in the gastric mucosa of iodoacetamide-treated mice. However, histological sections revealed a mixed inflammatory infiltrate, with a predominance of mast cells in the submucosa; suggesting a mild gastritis. Gastric emptying rate of a nutrient solid meal was not modified in mice with gastritis compared with normal controls. In animals with gastritis, basal gastric acid secretion was increased compared with normal controls. Basal gastric acid secretion was not modified by either indomethacin or compound 48/80. Secretory response to secretagogues (pentagastrin and histamine) was enhanced during gastritis. Hypersecretory responses to both gastrin and histamine in iodoacetamide-treated mice were blocked by the mast cell stabilizer sodium cromoglycate, and enhanced by indomethacin, without affecting the secretory response in normal mice. These results suggest that mild gastritis alters gastric acid secretory responses through a mechanism related, at least partially, to mast cells activation. Moreover, prostaglandins also modulate secretory responses during mild inflammation. This animal model of gastritis might be useful to characterize pathophysiological changes and potential therapeutic targets in secretory-related gastric pathologies.

Topics: Animals; Anti-Inflammatory Agents; Body Weight; Cromolyn Sodium; Drinking; Eating; Gastric Acid; Gastric Emptying; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Agents; Histamine; Indomethacin; Iodoacetamide; Irritants; Male; Mice; Pentagastrin; Pharmaceutical Vehicles

Menetrier's disease is characterized by giant gastric folds with foveolar hyperplasia and cystic dilatation, hypoproteinemia, and enhanced mucus secretion. The etiology remains unresolved and an effective treatment has yet to be established. Here we show that histamine H(2)-receptor deficient mice developed gastric pathophysiological changes resembling Menetrier's disease for up to 17 months of observation. Mutant mice were found to have an increased stomach weight, enlarged gastric folds with cystic dilatation, hypergastrinemia, hypoalbuminemia, increased mucus secretion and overexpression of mucosal transforming growth factor (TGF) alpha. Both a cholecystokinin (CCK)(2)-receptor antagonist and an epidermal growth factor (EGF)-receptor tyrosine kinase inhibitor significantly reduced the increase in stomach weight. It appears that lack or downregulation of histamine H(2)-receptors might be involved in the pathogenesis of Menetrier's disease.

Topics: Animals; Body Weight; Gastric Mucosa; Gastrins; Hydrogen-Ion Concentration; Hyperplasia; Hypoproteinemia; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mucus; Organ Size; Phenotype; Receptors, Histamine H2; Serum Albumin; Stomach; Stomach Diseases; Syndrome

The effect of food restriction (FR) on spontaneous intestinal carcinogenesis in multiple intestinal neoplasia (Min) mice was examined. Thirty male Min mice were allotted to ad libitum feeding control and 20% FR groups from six weeks of age until the end of the 13-week experimental period. Although the total number of visible intestinal polyps in the FR group was not significantly different from the control group value, a significant decrease in large-sized polyps (>2 mm) and an increase in small-sized polyps (< or =2 mm) were observed in the distal small intestine. In this segment, the percentage of apoptotic cells counted in intestinal polyps in the FR group was significantly higher than in the control group, the percentage of proliferating cell nuclear antigen (PCNA)-positive cells not being significantly different. These results indicate that the FR may inhibit the growth of intestinal polyps in the Min mouse, and that apoptosis contributed in part to the inhibitory effect.

Topics: Animals; Apoptosis; Body Weight; Cell Division; Energy Intake; Food Deprivation; Gastrins; Genes, APC; Immunoenzyme Techniques; Intestinal Neoplasms; Intestinal Polyps; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Proliferating Cell Nuclear Antigen

Methyleugenol, a food flavor and fragrance agent, was tested for toxicity in male and female F344/N rats and B6C3F1 mice. Groups of 10 males and 10 females per sex per species were administered 0, 10, 30, 100, 300 or 1000 mg methyleugenol/kg body weight in 0.5% aqueous methylcellulose by gavage, 5 days per week for 14 weeks. Additional groups of rats and mice of each sex were dosed similarly and used for hematology and clinical chemistry studies. Groups of 10 male and 10 female rats and mice received the vehicle by gavage on the same dosing schedule and served as vehicle controls. For serum gastrin, gastric pH and cell proliferation studies groups of 10 female rats were given 0, 37, 75 or 150 mg/kg, once daily 5 days per week for 30 or 90 days or 300 or 1000 mg/kg for 30 days; male mice were given 0, 9, 18.5, 37, 75, 150 or 300 mg/kg for 30 or 90 days. For the gastrin, pH and cell proliferation studies, groups of 10 female rats and 10 male mice were given the vehicle for 30 or 90 days and served as controls. Methyleugenol administration to rats induced erythrocyte microcytosis and thrombocytosis in male and female rats. It also caused an increase in serum alanine aminotransferase and sorbitol dehydrogenase activities and bile acid concentration, suggesting hepatocellular injury, cholestasis or altered hepatic function. Additionally, methyleugenol induced hypoproteinemia and hypoalbuminemia, evidenced by decreased total protein and albumin concentrations in both male and female rats, suggesting in inefficiency of dietary protein utilization due to methyleugenol-induced toxic effects on the liver and glandular stomach of rats and mice. The increase in gastrin and gastric pH of rats and mice given methyleugenol suggests that gastrin feedback was impaired and resulted in conditions not conducive to protein digestion. In rats, methyleugenol caused an increase in the incidences of hepatocyte cytologic alteration, cytomegaly, Kupffer cell pigmentation, mixed foci of cellular alteration and bile duct hyperplasia of the liver and atrophy and chronic inflammation of the mucosa of the glandular stomach. In mice, it caused an increase in the incidence of cytologic alteration, necrosis, bile duct hyperplasia and subacute inflammation of the liver and atrophy, degeneration, necrosis, edema, mitotic alteration, and cystic glands of the fundic region of the glandular stomach. The increased incidences of adrenal gland cortical hypertrophy and/or cytoplasmic alteration in

Topics: Alanine Transaminase; Animals; Body Weight; Cell Division; Cytotoxicity Tests, Immunologic; Dose-Response Relationship, Drug; Erythrocytes; Eugenol; Female; Gastric Mucosa; Gastrins; Hydrogen-Ion Concentration; L-Iditol 2-Dehydrogenase; Liver; Male; Mice; Mutagens; Organ Size; Organ Specificity; Rats; Rats, Inbred F344; Thrombocytosis

Keratinocyte growth factor (KGF) is a potent mitogen and may be of value for the treatment of conditions such as short bowel syndrome and chemotherapy-induced mucositis. However the most efficacious route and method of administration is unclear.. Rats maintained by total parenteral nutrition (TPN) were given KGF (1 mg/kg/rat/day, i.v.) infused continuously or as a once-daily injection. The same dose was also given s.c. to chow-fed rats. Changes in gut growth were assessed by measurement of wet weight, proliferation (vincristine induced metaphase arrest) and crypt branching index. Changes in gut hormone profile were also determined to examine if any trophic effects were mediated via this mechanism.. KGF caused a 70-100% increase in wet weight of the stomach, small and large intestine of TPN-fed rats (P < 0.01) with no significant differences seen between the two methods of administration. The increase in metaphase counts was greatest in the stomach (about seven-fold P < 0.01), but was less pronounced in the distal small intestine and colon (about 50% increase). The trophic effect of KGF was much less prominent in orally-fed rats. Crypt branching index was significantly reduced by KGF in the proximal small intestine of TPN, but not orally-fed rats. Plasma gastrin, PYY, total glucagon, enteroglucagon and GLP-1 all increased by two-three-fold (all P < 0.01) in response to KGF whereas insulin levels fell by about 25% in the TPN group.. The mitogenic action of KGF occurred predominantly in the stomach and proximal small intestine. Its efficacy was less pronounced in orally-fed animals, suggesting KGF may be of greatest benefit in conditions associated with lowered intestinal proliferation. Clinical trials of KGF can probably use single daily i.v. injections without reduction in efficacy.

Topics: Animals; Body Weight; Fibroblast Growth Factor 10; Fibroblast Growth Factor 7; Fibroblast Growth Factors; Gastrins; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Growth Substances; Intestinal Mucosa; Male; Metaphase; Organ Size; Peptide Fragments; Peptide YY; Protein Precursors; Rats; Rats, Wistar

To investigate the effect of feeding forage legumes containing condensed tannins (CT) on internal parasitism, red deer calves were fed either lucerne (Medicago sativa; 0.1 per cent CT), birdsfoot trefoil (Lotus corniculatus; 1.9 per cent CT) or sulla (Hedysarum coronarium; 3.5 per cent CT) and trickle-infected with deer-origin gastrointestinal nematode and lungworm (Dictyocaulus sp.) larvae for 5 weeks, then slaughtered at 7 weeks. There was a significant negative linear relationship between dietary CT concentration and abomasal nematode burdens. No significant differences in faecal egg counts, lungworm burdens or voluntary feed intake were found. Deer fed sulla had higher liveweight gain, carcass weight and carcass dressing-out percentage, higher serum total protein and albumin concentration and lower serum gastrin concentration and faecal lungworm larval count, compared with lucerne-fed deer. Inclusion of sulla in diets for young red deer may reduce the impact of internal parasites and/or reduce the dependence on anthelmintic treatment.

Topics: Animal Feed; Animals; Blood Proteins; Body Weight; Deer; Dictyocaulus; Dictyocaulus Infections; Diet; Digestive System; Energy Intake; Fabaceae; Feces; Gastrins; Larva; Parasite Egg Count; Pepsinogen A; Plants, Medicinal; Tannins

Food intake and body weight are determined by a complex interaction of regulatory pathways. To elucidate the contribution of the endogenous peptide cholecystokinin, mice lacking functional cholecystokinin-A receptors were generated by targeted gene disruption. To explore the role of the cholecystokinin-A receptor in mediating satiety, food intake of cholecystokinin-A receptor-/- mice was compared with the corresponding intakes of wild-type animals and mice lacking the other known cholecystokinin receptor subtype, cholecystokinin-B/gastrin. Intraperitoneal administration of cholecystokinin failed to decrease food intake in mice lacking cholecystokinin-A receptors. In contrast, cholecystokinin diminished food intake by up to 90% in wild-type and cholecystokinin-B/gastrin receptor-/- mice. Together, these findings indicate that cholecystokinin-induced inhibition of food intake is mediated by the cholecystokinin-A receptor. To explore the long-term consequences of either cholecystokinin-A or cholecystokinin-B/gastrin receptor absence, body weight as a function of age was compared between freely fed wild-type and mutant animals. Both cholecystokinin-A and cholecystokinin-B/gastrin receptor-/- mice maintained normal body weight well into adult life. In addition, each of the two receptor-/- strains had normal pancreatic morphology and were normoglycemic. Our results suggest that although cholecystokinin plays a role in the short-term inhibition of food intake, this pathway is not essential for the long-term maintenance of body weight.

Topics: Animals; Body Weight; Cholecystokinin; Eating; Female; Gastrins; Male; Mice; Mice, Knockout; Receptor, Cholecystokinin A; Receptors, Cholecystokinin

Gastrectomy leads to osteopenia in the rat. The present study describes the effects of gastrectomy on bone morphology. Rats were subjected to gastrectomy or sham operation. Four weeks after the operation the rats were killed and both tibiae were removed. Bone morphology of the left tibia was analyzed with quantitative computer tomography, the right tibia with histomorphometry. Bone length, bone mineral content, as well as indices of bone resorption and formation were measured in the metaphysis and the diaphysis. Gastrectomy had no effect on longitudinal bone growth but it led to a low bone mineral content at both sites. Bone resorption was increased by gastrectomy, as shown by an increase in the medullary cavity area in the diaphysis. Gastrectomy also reduced bone formation, as shown by a decreased periosteal circumference and a decrease in the mean periosteal bone apposition in the diaphysis. In conclusion, gastrectomy-evoked osteopenia reflects impaired formation and increased resorption of bone.

Topics: Animals; Body Weight; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Bone Regeneration; Bone Resorption; Calcification, Physiologic; Calcitonin; Calcium; Diaphyses; Gastrectomy; Gastrins; Male; Osteogenesis; Parathyroid Hormone; Periosteum; Rats; Rats, Sprague-Dawley; Tibia; Weight Gain

In humans, gastric surgery results in in osteopenia via mechanisms that are insufficiently understood; surgery-induced changes in the hormonal axes involving the stomach, thyroid, and the parathyroids may play a role. To study this in more detail, we evaluated calcium (Ca), magnesium (Mg), and phosphorus (P) metabolism as well as physical, chemical, and histomorphometric bone parameters in rats rendered hypergastrinemic by fundectomy (FX). In independent experiments, the response to an oral Ca challenge was investigated in intact rats versus FX, and in thyroidectomized versus thyroid-intact FX rats. Sixteen weeks following FX, body weight was approximately 80% that of sham-operated controls. In urine, P excretion was elevated fivefold, the pH was significantly decreased, and cAMP excretion was elevated as compared with controls; serum parathyroid hormone (PTH), calcitonin, 25OHD, Ca, Mg, and P were normal; gastrin and 1,25(OH)2D were elevated. On the basis of bone ash mineral content, FX rats developed significant osteopenia, and histomorphometry indicated only slightly elevated bone turnover and mineralization. Following oral Ca, thyroid-intact FX rats developed hypercalcemia, serum gastrin decreased, and calcitonin increased significantly; in thyroidectomized FX rats, calcitonin remained at baseline levels although there was a similar degree of hypercalcemia; PTH decreased during the hypercalcemic period in both groups. Serum gastrin did not correlate with calcitonin or PTH, and in multivariate regression analysis the only predictor of serum 1, 25(OH)2D was urinary phosphorus. It was concluded that in the FX rat (1) osteopenia is not caused by intestinal Ca malabsorption, vitamin D, Ca deficiency, or secondary hyperparathyroidism; (2) osteopenia may be related to PTH-independent urinary hyperexcretion of P, followed by a rise of serum 1,25(OH)2D; (3) the existence of endocrine axes among gastrin, calcitonin, and PTH cannot be substantiated. FX osteopenia appears to be related to gastric acid abolition, and the reactive hypergastrinemia probably stabilizes the mass and turnover of bone.

Topics: Animals; Body Weight; Bone and Bones; Calcitonin; Calcium; Calcium, Dietary; Energy Intake; Gastrectomy; Gastric Fundus; Gastric Mucosa; Gastrins; Humans; Magnesium; Male; Minerals; Parathyroid Hormone; Phosphorus; Rats; Rats, Sprague-Dawley; Reference Values; Stomach; Thyroidectomy; Vitamin D

The present study was performed to examine the effect of ageing on pancreatic hyperplasia observed after proximal small bowel resection (PSBR). Young and old Wistar rats were randomly assigned to two groups, which underwent either an approximate 90% PSBR or a jejunal and ileal transection (TRC). One week after the operation, the pancreatic wet weight and the protein, DNA and RNA content of the pancreas were all significantly higher in young PSBR rats than in young TRC rats. However, no differences were seen in the old rat groups. Plasma enteroglucagon levels were elevated in both young and old PSBR rats, but the ratio of increase between the PSBR and TRC groups was significantly higher in young rats. Plasma cholecystokinin and gastrin levels did not increase after PSBR in either the young or old rats. These findings suggest that pancreatic hyperplasia observed after PSBR is attenuated by ageing, probably due to an insufficient increase in plasma enteroglucagon levels.

Topics: Aging; Amylases; Animals; Body Weight; Cholecystokinin; DNA; Eating; Gastrins; Glucagon-Like Peptides; Hyperplasia; Intestine, Small; Lipase; Male; Organ Size; Pancreas; Radioimmunoassay; Rats; Rats, Wistar; RNA; Trypsinogen

The effects of bilateral adrenalectomy on the serotonin-, somatostatin-, and gastrin-immunoreactive cells in the rat gastrointestinal tract were studied four weeks after surgery. Body weight was reduced and the small intestine shorter in adrenalectomized animals compared with controls, while no changes were found in the histology of the mucosa. In the adrenalectomized animals the number of serotonin-immunoreactive cells was increased in the cecum and large intestine, while the somatostatin-immunoreactive cells were decreased in number in the antrum and increased in the corpus, cecum, and large intestine. The gastrin-immunoreactive cells in the antrum were not affected in number, but their nuclear size was enlarged, possibly indicating increased cellular activity.

Topics: Adrenal Glands; Adrenalectomy; Animals; Body Weight; Digestive System; Gastric Mucosa; Gastrins; Intestinal Mucosa; Male; Rats; Rats, Sprague-Dawley; Serotonin; Somatostatin; Time Factors

Treatment with omeprazole, a long-acting proton pump inhibitor of acid secretion, induces hypergastrinemia. In chickens, omeprazole induces growth not only of the acid-producing mucosa (probably reflecting the trophic action of gastrin), but also of the parathyroid glands (hypertrophy + hyperplasia), while suppressing bone density and body weight gain without affecting blood calcium. The first part of the present study was concerned with the effect of omeprazole, ergocalciferol (vitamin D2), and restricted food intake on the gene expression of parathyroid hormone (PTH) in the parathyroid glands of the chicken. Chickens were treated with omeprazole (400 micromol/kg/day, I.M.), food restriction, omeprazole + food restriction, ergocalciferol (250 000 IU/kg/day, S.C.), or ergocalciferol + omeprazole for 5 weeks. The weight gain of the chickens was monitored, and the weights of the parathyroid glands and femurs were determined at sacrifice. PTH mRNA in the parathyroid glands was analyzed by Northern blot. The second part of the study examined the effect of 3 weeks of continuous gastrin infusion (chicken gastrin 20-36, 5 nmol/kg/hour, S.C.) on the expression of PTH mRNA in the parathyroid glands. Omeprazole reduced the body weight and femur density (ash weight per volume) while greatly increasing the weight of the parathyroid glands and the PTH gene expression. Food restriction alone and ergocalciferol alone (at a dose that raised blood Ca2+) were without effect, but food restriction greatly enhanced the omeprazole-evoked increase in parathyroid gland weight and PTH gene expression. Gastrin increased the weight of the parathyroid glands and reproduced the effect of omeprazole on PTH gene expression. Hence, it seems likely that the effect of omeprazole reflects the ensuing hypergastrinemia.

Topics: Animals; Body Weight; Calcium; Chickens; Ergocalciferols; Food Deprivation; Gastrins; Gene Expression Regulation; Omeprazole; Parathyroid Hormone; Phosphorus; Vitamin D

1 The so-called enterochromaffin-like (ECL) cells constitute 65-75% of the endocrine cells in the acid-producing part of the rat stomach. They produce and secrete histamine and pancreastatin, a chromogranin A (CGA)-derived peptide, in response to gastrin, Cholecystokinin (CCK)B/gastrin receptor blockade is known to suppress their activity. 2 We have examined the time course of the deactivation of the ECL cells following treatment with the selective CCKB receptor antagonists RP73870 and YM022. The drugs were given by continuous subcutaneous infusion for a time span of 1 h to 3 weeks and the serum gastrin concentration and various ECL cell parameters were measured (oxyntic mucosal histidine decarboxylase (HDC) activity, histamine and pancreastatin concentrations, HDC mRNA and CGA mRNA levels, and circulating pancreastatin concentration). 3 The two antagonists caused a prompt and dramatic decline in the oxyntic mucosal HDC activity and HDC mRNA level. The HDC activity started to decline after 1-2 h, was reduced by 60-70% after 6 h and was maximally suppressed (80-90%) after 24-48 h. The HDC mRNA level was reduced after 12 h and was at about 20% of the pretreatment level after 2-4 days of infusion. The ECL cell histamine concentration was lowered by about 50% after 7-10 days. 4 RP73870 and YM022 lowered the serum pancreastatin concentration and the oxyntic mucosal CGA mRNA level. The serum pancreastatin concentration was reduced by 40% after 6 h and the reduction was maximal after 2-3 days. A decline in the oxyntic mucosal CGA mRNA level was noted after 12 h with a maximal reduction after 2-4 days of infusion. The ECL cell pancreastatin concentration was reduced by 30-40% after 3 weeks. 5 The infusion of RP73870 and YM022 induced hypergastrinaemia. The serum gastrin concentration started to rise after 2-4 h, there was a 2 fold increase after 6 h and maximal increase (3-4 fold) after 2-3 days of treatment. 6 In conclusion, CCKB/gastrin receptor blockade promptly deactivates the ECL cells. Deactivation, manifested in a greatly reduced HDC activity, was apparent after 1-2 h of the infusion. The serum pancreastatin concentration and the oxyntic mucosal HDC mRNA and CGA mRNA levels were greatly reduced after 1-2 days. The ECL cell concentrations of histamine and pancreastatin declined quite slowly by comparison.

Topics: Animals; Anti-Ulcer Agents; Benzodiazepines; Body Weight; Chromogranin A; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Histamine; Hormone Antagonists; Male; Pancreatic Hormones; Phenylurea Compounds; Rats; Rats, Sprague-Dawley; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; RNA, Messenger; Stomach; Time Factors

The aim of this study was to test the antagonist of LH-RH (Cetrorelix), agonist [D-Trp6]LH-RH (triptorelin) and new bombesin antagonists RC-3940-II and RC-3950-II for their effect on the growth of an androgen-independent prostate cancer cell line, DU-145, xenografted into nude mice. Xenografts were grown in male nude mice, and after 4 weeks, the animals were treated either with saline (control) or with one of the analogues. One group of mice was given a combination of Cetrorelix and RC-3950-II. Treatment was given for 4 weeks. Tumour and body weights, and tumour volumes were measured. At sacrifice, tumours were dissected for histological examination and receptor studies. Serum was collected for measurement of hormone levels. The final tumour volume in control animals injected with saline was 577 +/- 155 mm3 and that of animals treated with Cetrorelix only 121.4 +/- 45 mm3 (P < 0.01). Bombesin antagonists RC-3940-II and RC-3950-II also significantly reduced DU-145 tumour volume in nude mice to 84.9 +/- 19.9 and 96.8 +/- 28 mm3, respectively. Agonist [D-Trp6]LH-RH did not significantly inhibit tumour growth. Serum levels of LH were decreased to 0.08 +/- 0.02 ng/ml (P < 0.05) in the Cetrorelix treated group as compared to 1.02 +/- 0.1 ng/ml for the controls, and testosterone levels were reduced to castration levels (0.01 +/- 0.01 ng/ml). Specific receptors for EGF and LH-RH in DU-145 tumours were significantly downregulated after treatment with Cetrorelix, RC-3940-II and RC-3950-II. Although LH-RH could be a local regulator of growth of prostate cancer, the fall in LH-RH receptors is not fully understood and the inhibitory effects of Cetrorelix and bombesin antagonists on DU-145 tumour growth might be attributed at least in part to a downregulation of EHF receptors. Since Cetrorelix and bombesin antagonists inhibit growth of androgen-independent DU-145 prostate cancers, these compounds could be considered for the therapy of advanced prostate cancer in men, especially after relapse.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Bombesin; ErbB Receptors; Gastrins; Genitalia, Male; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Mice; Mice, Nude; Peptide Fragments; Prostatic Neoplasms; Receptors, Bombesin; Receptors, LHRH; Testosterone; Transplantation, Heterologous; Tumor Cells, Cultured

In adult gastric epithelium, gastrin and somatostatin regulate parietal cell acid secretion; however, their expression and function in the fetus are largely unknown. We defined the developmental expression of gastrin and somatostatin in the fetal rabbit stomach and determined their effects on fetal acid secretion. To define peptide expression, fetuses from 12 time-mated New Zealand white rabbit does were analyzed at successive ages during the third trimester (term is 31 days). Peptides were extracted from fetal gastric tissue by boiling in water and then in acetic acid. Amidated gastrin and somatostatin levels were measured by radioimmunoassay using antisera 1296 for gastrin and 8402 for somatostatin. To determine the effects of gastrin and somatostatin, pentagastrin (64 microg/kg/hr) or octreotide (35 microg/kg/hr) were infused intravenously in conscious pregnant rabbits at 28 days of gestation for 3 hr. Fetuses (n = 45) were harvested and gastric acid was titrated with 0.02 N NaOH. Gastrin and somatostatin tissue content were 12 +/- 3 and 51 +/- 6 pmol/g at gestational day 20, respectively, and increased to 146 +/- 10 and 162 +/- 5 pmole/g by day 30 (P < 0.05). Between days 24 and 26, when gastric acid was first detectable, the molar ratio of somatostatin to gastrin decreased from 5.0 +/- 1.0 to 1.1 +/- 0.1 (P < 0.05). Fetal gastric acid content (micromole) was 28.5 +/- 1.7 in controls, 27.5 +/- 1.9 with pentagastrin treatment, and 15.8 +/- 1.4 micromole with octreotide (P < 0.05). In summary, 1) In fetal gastric tissue, gastrin increased 12-fold and somatostatin increased 3-fold between days 20 and 30 of gestation. 2) The decreased ratio of somatostatin to gastrin between days 24 and 26 of gestation coincides with the onset of fetal gastric acid secretion in the fetal rabbit. 3) Maternal administration of octreotide inhibited fetal gastric acid content; however, pentagastrin had no effect. We conclude that, in the fetal rabbit stomach, the relative expression of gastrin and somatostatin may regulate the onset of parietal cell acid secretion.

Topics: Analysis of Variance; Animals; Body Weight; Embryonic and Fetal Development; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gene Expression Regulation, Developmental; Gestational Age; Maternal-Fetal Exchange; Octreotide; Organ Size; Pentagastrin; Pregnancy; Rabbits; Somatostatin; Stomach

In this study, we determined in vivo morphologic effects of continuous intravenous infusion of recombinant human epidermal growth factor (EGF) in adult Wistar rats. The EGF used consisted of the amino acid residues 1-48 of the human 53-amino-acid EGF molecule, purified from transfected Escherichia coli. Doses of 25, 100, or 250 micrograms/kg body weight were administered using Harvard digital syringe infusion pumps for 4 weeks. At necropsy, the submandibular salivary glands, Harderian glands, liver, kidneys (females only), and ovaries were enlarged and urinary bladders were thickened in 100- and 250-micrograms/kg rats. Numerous tissues of the 100- and 250-micrograms/kg rats contained hyperplastic epithelial cells, and selected organs also had mesenchymal cell proliferation. Epithelial proliferation was most pronounced in the trachea, nasal cavity, nasolacrimal duct, tongue, stomach, small intestine, large intestine, urinary tract, salivary gland ducts, and Harderian gland. Periportal hepatocytes were hypertrophic, correlating with increased liver weight. In addition, mesenchymal cell proliferation was evident in the gastric mucosa lamina propria and in heart valves in 100- and 250-micrograms/kg rats. Increased ovarian weight correlated with increased number and size of corpora lutea and an increased incidence of luteal cysts. Continuous systemic exposure of adult Wistar rats to high doses of EGF resulted in generalized epithelial hyperplasia and tissue-selective mesenchymal proliferation.

Topics: Amino Acid Sequence; Animals; Body Weight; Cell Count; Digestive System; Epidermal Growth Factor; Female; Gastrins; Humans; Hyperplasia; Infusions, Intravenous; Male; Molecular Sequence Data; Organ Size; Rats; Rats, Wistar; Recombinant Proteins; Respiratory System; Urogenital System

The effects of peptide histidine isoleucine (PHI) on the incidence and histology of colon tumors induced by azoxymethane (AOM), and on the labeling index of colon mucosa were investigated in Wistar rats. Rats received weekly s.c. injections of 7.4 mg/kg body weight of AOM for 10 weeks, and of 1.0 or 4.0 nmol/kg body weight of PHI until the end of the experiment in week 35. Administration of PHI at the higher, but not the lower dosage, significantly increased the incidence of colon tumors. PHI had no influence on the histology of colon tumors or adenocarcinomas. It also caused significant increase in the labeling index of colon epithelial cells. These findings indicate that PHI enhances colon carcinogenesis, and that its effect may be related to increasing proliferation of colon epithelial cells.

Topics: Adenocarcinoma; Animals; Azoxymethane; Body Weight; Colon; Colonic Neoplasms; Drug Synergism; Gastrins; Intestinal Mucosa; Peptide PHI; Rats; Rats, Wistar

We examined the effect of a liquid diet or a combined diet of liquid plus cellulose on the healing of gastric ulcers induced in rats in comparison with that of solid chow. Ulcers were induced in the fundus of the stomach by luminal application of an acetic acid solution. The healing of ulcers could be divided into two phases based on the healing rate: early phase (days 1 to 10) and late phase (days 10 to 20). The liquid diet, but not the combined one, administered for 10 days significantly accelerated ulcer healing in both the early and late phases. The length of the ruptured muscularis mucosa decreased only in the liquid diet group in both phases. Regeneration of the ulcerated mucosa in the chow diet group was observed only in the late phase, it being markedly inhibited in the liquid diet group. The serum gastrin level significantly decreased in the liquid and combined diet groups in contrast to that in the chow group. The liquid and combined diets significantly reduced gastric mucosal DNA synthesis. We conclude that 1) the healing in this gastric ulcer model comprises two phases, and 2) tissue contraction is a major factor for the healing of gastric ulcers in the early phase, while both tissue contraction and regeneration of the ulcerated mucosa are involved in the healing in the late phase.

Topics: Acetates; Acetic Acid; Animal Feed; Animals; Body Weight; Cell Division; Cellulose; Food, Formulated; Gastric Emptying; Gastric Mucosa; Gastrins; Male; Muscle Contraction; Muscle, Smooth; Rats; Stomach Ulcer

We investigated the effects of our synthetic bombesin/gastrin-releasing peptide (GRP) antagonists and somatostatin analogue RC-160 on the growth of human small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (non-SCLC) lines in nude mice. Athymic nude mice bearing xenografts of the SCLC NCl-H69 line or non-SCLC NCl-H157 line were treated for 5 and 4 weeks, respectively, with somatostatin analogue RC-160 or various bombesin/GRP antagonists. RC-160, administered s.c. peritumorally at a dose of 100 micrograms per animal per day, inhibited the growth of H69 SCLC xenografts as shown by more than 70% reduction in tumour volumes and weights, as compared with the control group. Bombesin/GRP antagonists, RC-3440, RC-3095 and RC-3950-II, given s.c. peritumorally at a dose of 20 micrograms per animal per day, also inhibited the growth of H69 SCLC tumours. RC-3950-II had the greatest inhibitory effect and decreased tumour volume and weights by more than 80%. The growth of H-157 non-SCLC xenografts was significantly reduced by treatment with RC-160, but not with bombesin/GRP antagonist RC-3095. In mice bearing either tumour model, administration of RC-160 significantly decreased serum growth hormone and gastrin levels. Specific high-affinity receptors for bombesin and somatostatin were found on membranes of SCLC H69 tumours, but not on non-SCLC H157 tumours. Receptor analyses demonstrated high-affinity binding sites for epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) on the membranes of H69 and H157 tumours. EGF receptors were down-regulated on H69 tumours after treatment with RC-160 and bombesin/GRP antagonists. The concentration of binding sites for EGF and IGF-I on the H157 tumours was decreased after treatment with RC-160, but bombesin/GRP antagonist RC-3095 had no effect. These results demonstrate that bombesin/GRP antagonists inhibit the growth of H-69 SCLC, but not of H-157 non-SCLC xenografts in nude mice, whereas somatostatin analogue RC-160 is effective in both tumour models. This raises the possibility that these peptide analogues could be used selectively in the treatment of various subclasses of lung cancer.

Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Binding Sites; Body Weight; Bombesin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cell Division; Gastrin-Releasing Peptide; Gastrins; Gonadotropin-Releasing Hormone; Growth Hormone; Humans; Lung Neoplasms; Male; Mice; Mice, Nude; Molecular Sequence Data; Neoplasm Transplantation; Peptide Fragments; Peptides; Receptors, Somatotropin; Somatostatin; Substrate Specificity; Transplantation, Heterologous

The purpose of the study was to evaluate the trophic effects of endogenous hypergastrinemia and hypercholecystokininemia on intact and regenerating rat liver. We also examined the effects on the liver of portacaval shunting (PCS) alone or together with hypergastrinemia or hyperCCKemia. PCS is known to enhance the trophic effects of gastrin on the so-called enterochromaffin-like cells of the stomach and of CCK on the pancreas.. Hypergastrinemia was induced by treatment with omeprazole (400 mumol/kg/day) or extirpation of the acid-producing part of the stomach (fundectomy). HyperCCKemia was induced by pancreaticobiliary diversion (PBD). After 4 weeks half of the rats were killed; the rest underwent partial hepatectomy and were killed 60 h later. PCS rats were killed 4 weeks after start of omeprazole treatment or after PBD. The concentrations of circulating gastrin and CCK were measured by radioimmunoassay. The liver weight and DNA content were analyzed.. Endogenous hypergastrinemia and hyperCCKemia failed to stimulate growth of either intact or regenerating liver. There were no differences in liver weight and DNA content between rats subjected to PCS and to combinations of PCS and omeprazole treatment, on the one hand, and PCS and PBD, on the other.. Gastrin and CCK are unlikely to be physiologically important in the regulation of liver growth and regeneration in the rat.

Topics: Animals; Biliopancreatic Diversion; Body Weight; Cholecystokinin; DNA; Gastric Fundus; Gastrins; Liver; Liver Regeneration; Male; Omeprazole; Organ Size; Portacaval Shunt, Surgical; Rats; Rats, Sprague-Dawley

The role of cortisol in the development of gastric function was investigated in the fetal pig. Pregnant sows (term = 114 +/- 2 days, n = 10) were anaesthetized (pentobarbitone) and osmotic minipumps containing either saline or cortisol inserted subcutaneously into fetuses at 82-84 (n = 11) or 91-96 (n = 14) days gestation. Six days later the infused pigs were removed by Caesarean section and the stomach and its contents collected for analysis. Samples were also obtained from unoperated (control) fetal pigs (n = 51) removed under anaesthesia at intervals from 70 days gestation until term. The concentrations of acid in gastric fluid, gastrin in plasma and antral tissue (bioactive as well as precursor forms), and cobalamin(CBL)-binding proteins in fundic tissue were low in control pigs until 100 days gestation. During the last 2 weeks before term, large increases occurred in gastric fluid acidity (from pH 6-7 to pH 3 at birth), plasma amidated gastrin (from 10 to 90 pM) and CBL-binding protein concentration (from 10 to 80 pmol (g fundus)-1). These changes occurred in parallel with a surge in plasma cortisol (from 20 to 200 ng ml-1). Immature fetuses infused with cortisol had significantly higher gastric acidity, plasma amidated gastrin, and concentration of CBL-binding proteins than the corresponding control fetuses (P < 0.05). Across age and treatment groups, significant correlations were found between log10 plasma cortisol values and the above parameters (r = 0.59-0.76, P < 0.01). The results suggest that endogenous cortisol secretion stimulates the secretion of gastric acid, gastrin and CBL-binding proteins in the prenatal period of the pig.

Topics: Animals; Body Weight; Embryo, Mammalian; Embryonic and Fetal Development; Fetus; Gastric Acid; Gastrins; Gastrointestinal Contents; Hydrocortisone; Hydrogen-Ion Concentration; Pyloric Antrum; Stomach; Swine; Transcobalamins

The effects of combined administration of bombesin (40 micrograms/kg body weight) and the ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopropane (DAP), on the development of large and small intestinal tumors and the incidence of their metastasis to the peritoneum induced by azoxymethane (AOM, 7.4 mg/kg body weight), the ODC activity of the intestinal wall, and the labeling index of the intestinal mucosa and tumor were investigated in inbred Wistar rats. Rats received weekly s.c. injections of AOM for 10 weeks, s.c. injections of bombesin every other day, and drinking water containing DAP (2.5 g/l) until the end of the experiment at week 40. Administration of bombesin significantly increased the incidence of intestinal tumors at week 40. It had no influence on the location, size, histological features or depth of involvement of intestinal adenocarcinomas, but significantly increased the incidence of their metastasis to the peritoneum. It also resulted in a significant increase in the intestinal ODC activity and labeling index. Administration of DAP with bombesin significantly reduced the enhancement of intestinal carcinogenesis by bombesin. Although the combined use of DAP with bombesin had little or no influence on the location, size, histological features, or depth of involvement of intestinal cancers, the incidence of their metastasis was significantly reduced. DAP significantly attenuated bombesin enhancement of the intestinal ODC activity and labeling index. These findings indicate that ODC inhibition attenuated the enhancement of intestinal carcinogenesis and metastasis to the peritoneum.

Topics: Adenocarcinoma; Animals; Azoxymethane; Body Weight; Bombesin; Cell Division; Diamines; Drug Synergism; Gastrins; Intestinal Mucosa; Intestinal Neoplasms; Male; Neoplasm Metastasis; Ornithine Decarboxylase Inhibitors; Peritoneal Neoplasms; Rats; Rats, Wistar

Highly selective vagotomy (HSV) or sham operation was performed in male rats. Fifteen weeks later bone mineralization, fractional intestinal absorption and balance, urinary excretion, and serum levels of calcium, magnesium and phosphorus, together with serum gastrin, parathyroid hormone, calcitonin, vitamin D metabolites, osteocalcin, isoenzymes of alkaline phosphatase, and the urinary excretion of cyclic AMP and hydroxyproline were assessed. HSV induced chronic hypergastrinemia and enhanced the weight of the fundus, antrum, and pancreas. Body weight, food intake, intestinal absorption, mineral balance, and bone mineralization were unaffected by HSV, whereas serum parathyroid hormone levels and urinary hydroxyproline excretion were increased. It is concluded that in the rat 1) HSV has a trophic effect on gastric and extragastric tissues; 2) gastric acid production is not a major determinant of intestinal calcium absorption; and 3) normal bone mass in the presence of signs of hyperparathyroidism indicates an intrinsic capacity of HSV to interfere with calcium metabolism, probably via hypergastrinemia, gastrin being an element of the gastro-parathyroid axis. Our present findings underscore the fact that osteopenia after HSV in man may be a rare finding, but it cannot be ruled out that bone disease found after partial or total gastrectomy may be due in part to concomitant vagotomy.

Topics: Animals; Body Weight; Bone and Bones; Bone Diseases, Metabolic; Eating; Gastrins; Humans; Male; Minerals; Rats; Rats, Sprague-Dawley; Vagotomy, Proximal Gastric

Short-chain fatty acids (SCFAs) are trophic to small intestinal and colonic mucosa. This study determined whether SCFAs infused into the cecum out of continuity stimulated jejunal and colonic cellularity and whether these effects were mediated by the autonomic nervous system and/or enterotrophic hormones.. To eliminate direct trophic effects of SCFAs in contact with mucosa, 60 rats underwent cecal isolation with placement of an infusion catheter into the proximal cecum, formation of distal cecocutaneous stoma, and restoration of intestinal continuity with ileocolonic anastomosis. Rats underwent cecal denervation or remained normally innervated and received 1 of 3 infusions for 10 days: SCFAs, saline, or no infusion. Twenty-four additional rats were assigned to the same groups but underwent infusion into the proximal colon (in circuit).. Cecal infusion of SCFAs into innervated rats increased (P < 0.05) jejunal DNA, villous height, surface area, crypt depth, and gastrin without increasing colonic variables. In denervated rats, SCFAs did not significantly affect these variables. However, direct intracolonic infusions of SCFAs increased (P < 0.05) colonic mucosal DNA and crypt depth.. Jejunotrophic effects of cecally infused SCFAs are mediated afferently by the autonomic nervous system and are associated with increased jejunal gastrin. SCFAs have local trophic effects on the colon.

Topics: Animals; Body Weight; Cecum; Colon; Denervation; DNA; Fatty Acids, Volatile; Gastrins; Jejunum; Male; Peptide YY; Peptides; Proteins; Rats; Rats, Sprague-Dawley

The effect of somatostatin on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) was investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and s.c. injections of 200 micrograms/kg body wt of somatostatin every other day from the beginning of the experiment until the end of week 16. Pre-neoplastic and neoplastic lesions staining for gamma-glutamyl transpeptidase (GGT) or placental type glutathione-S-transferase (GST-P) were examined histochemically. Administration of somatostatin for 16 weeks resulted in significant reduction in the percentage volume of GGT-positive and GST-P-positive lesions. The incidence, number and size of hepatocellular carcinomas were significantly less in rats treated with somatostatin than in untreated rats. Administration of somatostatin significantly decreased the labeling indices of pre-neoplastic lesions and adjacent liver. These findings indicate that somatostatin inhibits hepatocarcinogenesis and that this effect may be related to its effect in decreasing cell proliferation in pre-neoplastic lesions.

Topics: Animals; Body Weight; Carcinogens; gamma-Glutamyltransferase; Gastrins; Glutathione Transferase; Liver; Liver Neoplasms, Experimental; Male; Nitrosamines; Organ Size; Precancerous Conditions; Rats; Rats, Sprague-Dawley; Somatostatin

Nude mice bearing xenografts of the androgen-independent human prostate cancer DU-145 were treated for 4-5 weeks with somatostatin analog RC-160 or the bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095. Tumor growth in animals treated with somatostatin analog RC-160 at a dose of 100 micrograms/day s.c. was significantly inhibited within 14 days of the start of the experiment. At necropsy, in mice given RC-160, tumor weight and volume were significantly decreased compared with control mice. Treatment with RC-3095 at a dose of 20 micrograms/day s.c. also suppressed tumor growth, the inhibition being significant after 2 weeks, but the reduction in tumor volume and weight was smaller than that produced by RC-160. Therapy with RC-160 significantly decreased serum growth hormone and gastrin levels. Specific binding sites for bombesin, somatostatin and epidermal growth factor (EGF) were found in the DU-145 tumor membranes. Receptors for EGF were significantly down-regulated after therapy with RC-3095 and RC-160. The finding that somatostatin analog RC-160 and bombesin/GRP antagonist RC-3095 inhibit the growth of androgen-independent prostate tumors in mice might be of practical importance for human prostate cancer therapy.

Topics: Amino Acid Sequence; Androgens; Animals; Binding Sites; Body Weight; Bombesin; Cell Line; Gastrin-Releasing Peptide; Gastrins; Growth Hormone; Humans; Male; Mice; Mice, Nude; Molecular Sequence Data; Peptide Fragments; Peptides; Prostatic Neoplasms; Somatostatin

Effects of strategic anthelmintic treatment on pathophysiologic and immunomologic changes induced by infection with Ostertagia ostertagi and Cooperia oncophora were studied in 2 groups, of 12 calves each: an infected group, inoculated with 200,000 mixed O ostertagi and C oncophora third-stage larvae (L3) on day 1; and an infected-treated group, similarly inoculated, but treated with ivermectin at 9 and 33 days. All calves were also inoculated at 12 weeks with Brucella abortus vaccine, at 13 weeks with bovine rhinotracheitis vaccine (bovine herpesvirus 1), and at 14 weeks with a soluble O ostertagi L3 extract, then were allowed to graze on a contaminated pasture. Four calves from each group were slaughtered at 7, 11, and 19 weeks of the study. Calves of the infected group had significantly (P < 0.05) lower weight gain than did those in the infected-treated group (60.90 kg vs 75.86 kg). They also had high plasma pepsinogen and serum gastrin values, and low serum albumin concentration from 2 or 4 weeks. Calves in the infected-treated group had steady weight gain and no significant changes in albumin and gastrin values. They also had less severe abomasal lesions and higher carcass yield. Compared with calves of the infected-treated group, those of the infected group had significantly (P < 0.05) lower blood lymphocyte reactivity to phytohemagglutinin at 14 and 16 weeks, to concanavalin A at 10 weeks, to pokeweed mitogen at 14 weeks, and to soluble O ostertagi L3 extract at 2, 4, and 14 weeks. (ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Anthelmintics; Body Weight; Brucella abortus; Brucella Vaccine; Cattle; Cattle Diseases; Gastrins; Gastrointestinal Diseases; Herpesvirus 1, Bovine; Lymphocyte Activation; Lymphocytes; Male; Nematoda; Nematode Infections; Orchiectomy; Ostertagiasis; Parasite Egg Count; Pepsinogens; Time Factors; Viral Vaccines; Weight Gain

Numerous clinical and experimental studies suggest that gastrin plays an important part in the development of colorectal cancer in humans. This study was done to assess the influence of omeprazole induced hypergastrinaemia on the development of colorectal tumours in an experimental animal model. Forty female Sprague-Dawley rats received either omeprazole (40 mumol/kg) or vehicle (0.25% methylcellulose) by once daily oral gavage throughout the experiment. All animals received 12 consecutive weekly subcutaneous injections of azoxymethane (10 mg/kg/week) beginning at week 6. Serum gastrin concentrations were measured during weeks 1 and 5 and at death (week 27). Chronic omeprazole treatment resulted in appreciable hypergastrinaemia during the study, mean gastrin concentrations in omeprazole treated rats being raised by up to nine to 10 fold, compared with vehicle treated control rats (p < 0.001). Despite this, tumour incidence in the omeprazole group was significantly lower at 63%, compared with 95% in the vehicle only group (p < 0.02). The median number of tumours in the omeprazole group (1) compared with the vehicle group (3) was also significantly lower (p = 0.02). Average tumour size, site distribution, and the comparative frequencies of adenomas and adenocarcinomas were similar in the two groups. This study shows that omeprazole protects against colorectal carcinogenesis in this model despite causing appreciable hypergastrinaemia. The mechanism by which this occurs is unclear and merits further investigation. Because of the compounding protective effects of omeprazole, this model is not a suitable one for studying the longterm trophic effects of gastrin on the colon.

Topics: Animals; Azoxymethane; Body Weight; Colonic Neoplasms; Eating; Female; Gastrins; Omeprazole; Rats; Rats, Sprague-Dawley; Rectal Neoplasms

The influence of different physiological stimuli on plasma concentrations of the acid-stimulating hormone gastrin and on the tissue concentrations of its precursor, progastrin, were examined in the conscious rat. Plasma concentrations were measured by radioimmunoassay using antibody specific for the C-terminus of biologically active (amidated) gastrins, and tissue concentrations of progastrin were measured after size exclusion chromatography by radioimmunoassay using antibody specific for the C-terminus of rat progastrin. Plasma and antral tissue were taken from control rats fed ad libitum, from rats fasted for 48 h, and from fasted or fed rats treated with the proton pump inhibitor omeprazole to reduce acid-induced inhibition of gastrin release. Plasma gastrin concentrations were depressed 4-fold by fasting and this was reversed by treatment with omeprazole; in rats fed ad libitum and treated with omeprazole plasma gastrin was elevated 8-fold. Fasting did not significantly change the plasma clearance of gastrin, indicating that changes in endogenous circulating levels are attributable to altered secretion rather than metabolism. Tissue progastrin concentrations were depressed 3-fold in fasted rats compared with rats fed ad libitum. Treatment of fasted rats with omeprazole produced a 2-fold increase in tissue progastrin; but in spite of the substantial elevation of plasma gastrin in fed rats treated with omeprazole, tissue progastrin was elevated by only about 50%. Sulphation at Tyr103 of progastrin was not changed by fasting or omeprazole. An estimate of the conversion of progastrin to amidated gastrin was determined as the tissue progastrin clearance, i.e. the weight of antral mucosa in which progastrin is converted to amidated gastrin and secreted per minute to maintain plasma concentrations. Conversion rates were increased 7-fold in fed omeprazole-treated rats compared with controls; in fasted rats treated with omeprazole the rate of conversion was depressed 50% compared with controls. It is concluded that changes in the lumen of the stomach are able to influence the processes by which progastrin is converted to its active amidated products.

Topics: Amino Acid Sequence; Animals; Body Weight; Chromatography; Dose-Response Relationship, Drug; Fasting; Gastric Mucosa; Gastrins; Male; Metabolic Clearance Rate; Molecular Sequence Data; Omeprazole; Protein Precursors; Pyloric Antrum; Radioimmunoassay; Rats; Rats, Wistar; Stomach; Time Factors

The effect of gastric fundectomy with hypergastrinaemia on the pancreas in rats was studied for 14 months. Rats with hypercholecystokininaemia that had had a pancreaticobiliary diversion (PBD) operation and sham operated rats served as controls. Fundectomised rats showed a significant increase in pancreatic weight and total DNA and protein content compared with sham operated rats. DNA flow cytometry showed a significantly higher ratio of tetraploid to diploid nuclei in pancreatic tissue after fundectomy than after sham operation. Mean values of all these variables were significantly lower after fundectomy than after PBD. Acidophilic atypical acinar cell foci of the pancreas were diagnosed in both fundectomised and PBD operated rats, but not in sham operated controls. The volume density and 3H-thymidine labelling index of the acidophilic atypical acinar cell foci were significantly lower after fundectomy than after PBD. Changes consistent with pancreatic adenoma were diagnosed in the PBD group only. In conclusion, fundectomy lasting about half of the life span in rats causes pancreatic hyperplasia and hypertrophy, as well as development of acidophilic atypical acinar cell foci. Although hypergastrinaemia is a prominent feature, it may not be the only factor responsible for this pancreaticotrophical effect of fundectomy.

Topics: Animals; Autoradiography; Body Weight; Cholecystokinin; DNA; Gastric Fundus; Gastrins; Hypertrophy; Male; Organ Size; Pancreas; Ploidies; Rats; Rats, Wistar; Time Factors

This study was designed to investigate abnormal gastric acid secretion in ventromedial hypothalamic (VMH)-lesioned rats. Basal secretion and secretion stimulated by pentagastrin (25 micrograms/kg, IP) or histamine (2 mg/kg/h, IV) were significantly higher in VMH-lesioned rats than in sham VMH-lesioned rats. Subdiaphragmatic vagotomy and methyl atropine treatment (5 mg/kg, IV) remarkably decreased both basal (about 36-44%) and stimulated secretion (about 36-67%) in VMH-lesioned rats, but did not completely reverse it to normal. Serum insulin and glucose levels were significantly higher in VMH-lesioned rats, but serum gastrin levels were not. VMH-lesioned rats showed significantly heavier gastric dry weight; however, no difference in the mucosal layer/total layer ratio of the gastric wall and the density of the parietal cells was observed between the two groups, indicating that the total number of parietal cells might have increased in VMH-lesioned rats because the increase of gastric dry weight can be presumed to be due to increase of the gastric mucosal layer as well as total layer. These results suggest that vagal activation is one of the main contributors to hypergastric acid secretion in VMH-lesioned rats, but that other factors such as increase of parietal oxyntic cell number may also contribute.

Topics: Animals; Blood Glucose; Body Weight; Brain Mapping; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Insulin; Neural Pathways; Parietal Cells, Gastric; Rats; Rats, Sprague-Dawley; Stomach; Vagus Nerve; Ventromedial Hypothalamic Nucleus

Female Syrian golden hamsters with N-nitroso-bis (2-oxopropyl) amine (BOP)-induced pancreatic cancers were treated for 2 months with bombesin/gastrin-releasing peptide (GRP) antagonist D-Tpi6,Leu13 psi(CH2NH)Leu14 bombesin(6-14) (RC-3095). Bombesin and GRP(14-27) were also administered alone and in combination with the antagonist RC-3095. RC-3095 exerted a dose-dependent inhibitory effect on growth of pancreatic cancers. The number of animals with pancreatic cancers was significantly lower in the group treated with 60 micrograms/day of RC-3095 and the weight of tumorous pancreata was reduced. Administration of bombesin or GRP alone did not stimulate the growth of pancreatic tumors and, in fact, had a slightly suppressive effect on cancers which was significant only in Experiment I. Bombesin and GRP (14-27) given together with RC-3095 did not nullify the inhibitory effect of the antagonist on pancreatic cancer growth. Actually, a greater inhibition of pancreatic tumors was observed after administration of RC-3095 together with bombesin or GRP, than with RC-3095 alone. The mechanism of action of bombesin, GRP, and bombesin antagonists on pancreatic cancers appears to be complex. The inhibitory effect of bombesin antagonists on pancreatic cancer growth was accompanied by a decrease in the binding capacity of EGF receptors in tumor membranes. Administration of bombesin also caused a down-regulation of EGF receptors and the greatest decrease in binding capacity of EGF receptors was observed after treatment with RC-3095 in combination with GRP. Inhibition of pancreatic cancer can thus be tentatively explained by some common pathways in the action of bombesin, GRP and their antagonists, that could be mediated by interference with EGF-receptor mechanisms.

Topics: Animals; Body Weight; Bombesin; Carcinoma; Cricetinae; Dose-Response Relationship, Drug; Down-Regulation; Epidermal Growth Factor; ErbB Receptors; Female; Gastrin-Releasing Peptide; Gastrins; Growth Hormone; Insulin-Like Growth Factor I; Mesocricetus; Nitrosamines; Pancreatic Neoplasms; Peptide Fragments; Peptides; Receptors, Bombesin; Receptors, Neurotransmitter

The effects of ursodeoxycholic acid (UDCA) and 1 alpha-hydroxyvitamin D3 on pathophysiological changes following massive resection of the distal small bowel (75%) were investigated by using adult beagle dogs. After surgery, body weight decreased, watery diarrhea occurred, and the transit time of the alimentary tract shortened. These undesirable consequences lessened markedly after oral administration of UDCA, though 1 alpha-hydroxyvitamin D3 was not effective. Plasma levels of both 25-hydroxyvitamin D3 and 24, 25-dihydroxyvitamin D3 decreased after surgery, while plasma 1 alpha, 25-dihydroxyvitamin D3 concentrations remained unchanged during the observation period of six months. Although fasting plasma concentrations of total bile acid were not reduced, the integrated response to a meal decreased significantly after surgery in spite of the administration of UDCA. The concentration of UDCA in the gallbladder bile increased markedly in dogs which received UDCA. Taurine-conjugated bile acids accounted for more than 90% of the gallbladder bile. Postprandial hypergastrinemia occurred following the massive small bowel resection in the control group and in the group which received 1 alpha-hydroxyvitamin D3 alone, while it did not occur in the group given UDCA together with 1 alpha-hydroxyvitamin D3. These results indicate that administration of UDCA after massive resection of the small intestine is effective in maintaining good nutritional state.

Topics: Administration, Oral; Animals; Bile; Bile Acids and Salts; Body Weight; Cholecalciferol; Dogs; Female; Food; Gastrins; Intestine, Small; Ursodeoxycholic Acid

1. Simultaneous 24 h intragastric acidity and plasma gastrin concentration profiles were determined in 35 healthy young women and 96 healthy young men. 2. The females had a consistently lower median hourly intragastric acidity, and a higher median hourly plasma gastrin concentration, throughout the 24 h. 3. The 24 h integrated intragastric acidity was significantly lower in the female group (females, 485 mmol.h.l-1; males, 842 mmol.h.l-1. P less than 0.001). The 24 h integrated plasma gastrin concentration was significantly higher in the female group (females, 407 pmol.h.l-1; males, 185 pmol.h.l-1; P less than 0.001).

Topics: Adult; Body Weight; Circadian Rhythm; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Male; Sex Factors

Thirty-four patients with H2-blocker-resistant reflux esophagitis subsequently healed by 40 mg omeprazole daily entered a maintenance study with 20 mg omeprazole. In 31 evaluable cases the observation period was at least 12 months (mean 24 months). Esophagitis remained in remission in two thirds of patients despite dose reduction. Relapses of esophagitis occurred in 10 cases within six months, which rapidly healed by increasing the omeprazole dose to 40 mg. No further recurrence with 20 mg omeprazole was found later than six months. Peptic strictures primarily requiring repeated dilatation in six patients during healing with omeprazole did not reappear while on omeprazole maintenance. Major side effects that could be attributed to omeprazole were not observed. Gastrin levels remained within or slightly above the normal range in the vast majority. It is concluded that omeprazole maintenance treatment in severe reflux esophagitis is an effective and safe therapy.

Topics: Adult; Aged; Body Weight; Drug Administration Schedule; Drug Resistance; Esophagitis, Peptic; Esophagoscopy; Female; Follow-Up Studies; Gastrins; Histamine H2 Antagonists; Humans; Lung Diseases; Male; Middle Aged; Omeprazole; Prospective Studies; Recurrence; Remission Induction

The structural and functional properties of the pancreas are known to be affected by a number of hormones, particularly those of the gastrin-CCK family, yet little is known about the responsiveness of the pancreas to gastrin-CCK peptides during the latter stages of life. The present investigation examined the changes in pancreatic growth, the activity, and the steady-state mRNA levels of some of the digestive enzymes during advancing age and after administration of gastrin. Groups of 3-, 6-, 12-, and 16-month-old male Fischer-344 rats were infused (osmotic minipump) with either gastrin G-17 (250 ng/kg/h) or saline (controls) for 14 days. In control pancreas, aging resulted in slight progressive reduction in pancreatic DNA, RNA, and protein concentrations. This decrease was markedly enhanced by gastrin treatment in 16-month-old rats. Pancreatic amylase and trypsin (TRP) activities in these animals were also slightly decreased with aging, whereas the steady-state mRNA levels of both enzymes were significantly higher in 16-month-old rats than in their 3-month-old counterparts. However, in 16-month-old rats, the steady-state mRNA levels of amylase and TRP were significantly reduced after gastrin administration, when compared with the corresponding controls. Chymotrypsin (CHY) activity in the pancreas remained essentially unchanged between 3- and 12-month-old rats, but in 16-month-old animals it was markedly decreased. CHY activity was further reduced by gastrin treatment only in the 16-month-old group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Amylases; Analysis of Variance; Animals; Body Weight; Chymotrypsin; DNA; Gastrins; Gene Expression Regulation, Enzymologic; Male; Organ Size; Pancreas; Pancreatin; Rats; Rats, Inbred F344; RNA; RNA, Messenger; Trypsin

Chickens treated with the H+/K+ ATPase inhibitor omeprazole, to inhibit gastric acid secretion, failed to gain weight and showed decreased food intake compared with controls. The gastrin antagonist PD134308 reversed the action of omeprazole on food intake. Since exogenous gastrin decreased food intake, and since omeprazole increased plasma gastrin concentrations, the results suggest that elevated plasma gastrin in chicken exerts a satiety effect.

Topics: Animals; Animals, Newborn; Body Weight; Chickens; Depression, Chemical; Eating; Gastrins; Indoles; Meglumine; Omeprazole; Radioimmunoassay; Receptors, Cholecystokinin; Satiety Response

We studied the effects of hormonal manipulation by orchiectomy, alone or in combination with the aromatase inhibitor aminoglutethimide (AGT), and by luteinizing hormone-releasing hormone agonist (LH-RH-A) (goserelin) treatment on the development of early putative (pre)neoplastic lesions induced in the pancreas of rats and hamsters by azaserine and N-nitrosobis(2-oxopropyl)amine respectively. Treatment of the animals started 1 week after the last injection with carcinogen and continued for 4 months. Orchiectomy caused a significant inhibition of growth of acidophilic atypical acinar cell nodules in the rat model, whereas surgical castration did not show an effect in the hamster model. In rats, but not in hamsters, orchiectomy resulted in a significant decrease in body weight and in absolute, but not relative pancreatic weight. Treatment of the animals with AGT or goserelin did not cause a significant effect on the development of either putative preneoplastic acinar lesions in rat pancreas or early ductular lesions in hamster pancreas. Hamsters showed clearly higher plasma epidermal growth factor (EGF) and insulin-like growth factor 1 (IGF-1) concentrations than rats, while plasma testosterone levels were significantly lower. Plasma EGF and IGF-1 levels decreased with increasing age in both control and treatment groups. Compared to controls there were no clear unequivocal effects of treatment on EGF, IGF-1 and gastrin levels. Plasma testosterone levels decreased by orchiectomy and LH-RH-A treatment. In rats hormone-induced effects on food intake and altered nutritional status might be important with respect to the development of carcinogen-induced preneoplastic pancreatic lesions.

Topics: Aminoglutethimide; Animals; Azaserine; Body Weight; Buserelin; Carcinogens; Cricetinae; Epidermal Growth Factor; Gastrins; Goserelin; Male; Mesocricetus; Nitrosamines; Orchiectomy; Organ Size; Pancreatic Neoplasms; Precancerous Conditions; Rats; Rats, Inbred Strains; Somatomedins; Testosterone

Studies in the rat have shown that partial gastric corpectomy, in which about 75% of the acid-producing oxyntic mucosa was removed, leads to markedly reduced acid secretion and a feedback increase in the plasma gastrin levels. Ten weeks after operation, the gastric enterochromaffin (ECL)-like cell density in the remaining part of the oxyntic mucosa had increased significantly. In the present study, the effects on the gastric ECL cells of lifelong persistent hypergastrinemia induced by partial (75%) corpectomy have been investigated. Seventy-five partially corpectomized rats and 40 control rats were investigated for plasma gastrin and oxyntic mucosal changes in a 124-week study. The partially corpectomized rats showed increased plasma gastrin levels after the operation; the mean increase compared with the controls was almost 10-fold during the entire study. The remaining oxyntic mucosa of the partially corpectomized rats differed from that of control rats in two respects, showing first general hypertrophy and second a marked hyperplasia of argyrophil ECL cells. The degree and incidence of these changes increased towards the end of the study, i.e., in the aging rats. An age-related increase in ECL-cell density occurred spontaneously also in the control rats but to a lesser extent than in the partially corpectomized group. ECL-cell carcinoids were found in the oxyntic mucosa of 26 of the 75 partially corpectomized rats. The first carcinoid was found 78 weeks after the beginning of the study. Six rats with carcinoids (23%) were found before week 104 (2 years) and the remainder, 20 (77%), were discovered later. No carcinoid tumor was found in the control rats. It is concluded that lifelong hypergastrinemia induced by partial corpectomy leads to the development of ECL-cell carcinoids in the oxyntic mucosa of some rats towards the end of their life span. This observation strongly supports the hypothesis that the gastric ECL-cell carcinoids found in rats treated with antisecretory drugs are caused by long-standing hypergastrinemia developing secondary to inhibition of gastric acid secretion.

Topics: Animals; Body Weight; Carcinoid Tumor; Enterochromaffin Cells; Feedback; Female; Gastric Mucosa; Gastrins; Hyperplasia; Hypertrophy; Parietal Cells, Gastric; Rats; Rats, Inbred Strains; Stomach; Stomach Neoplasms; Time Factors

This study was designed to measure plasma gastrin and somatostatin levels in infants and to simultaneously investigate the infants' metabolic status as reflected by the body weight as well as by the blood levels of FFA, D-beta-hydroxybutyrate and glucose. Healthy infants (n = 94) who were born at term were studied cross-sectionally during their first four days of life. We found that the gastrin concentration (mean +/- SD) on the first day of life was 118 +/- 37 pmol/l. Subsequently the concentration decreased and reached its lowest value on the third day; 94 +/- 27 pmol/l (P less than 0.05). On the fourth day the mean concentration increased to the same level as on the first day. There was a significant (P less than 0.01) increase in somatostatin concentrations from 18 +/- 6 pmol/l on the first day to 26 +/- 7 pmol/l on the fourth day and the concentrations were highly related (P less than 0.0001) to postnatal age. We conclude that the decrease in gastrin concentration is probably related to the low volume of breast milk ingested during the first days after delivery, and therefore to the low secretory activity of the gastrin-producing cells. The infants' catabolic condition during that time was evidenced by the reduction in body weight, the decrease in plasma glucose level and the increase in FFA and D-beta-hydroxybutyrate levels. The gastrin increase found on the fourth day reflects most likely, the change in breast milk availability which occurs with the establishment of lactation. The mechanisms controlling the release of somatostatin remains to be established.

Topics: 3-Hydroxybutyric Acid; Blood Glucose; Body Weight; Breast Feeding; Fatty Acids, Nonesterified; Female; Gastrins; Humans; Hydroxybutyrates; Infant, Newborn; Male; Radioimmunoassay; Somatostatin

Atrophy of the gastrointestinal mucosa that occurs in pair-fed control rats is not observed in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated rats (1). Our objective was to determine if the gastrointestinal trophic hormone, gastrin, is involved in the antiatrophy effect of TCDD on the gut mucosa. Adult male Sprague-Dawley rats treated with 100 micrograms/kg of TCDD were slightly hypergastrinemic 7 days after dosing and markedly hypergastrinemic 14 days after treatment whereas pair-fed control rats were normogastrinemic. After 14 days of feed restriction, atrophy of the oxyntic gland and ileum mucosa occurred in pair-fed control rats but only atrophy of the ileum mucosa developed in TCDD-treated animals. The oxyntic gland mucosa of TCDD-treated rats was protected from mucosa atrophy as well as from mucosa erosions. The protection against feed restriction-induced atrophy was demonstrated by measurements of oxyntic gland mucosal height and DNA and protein content. Since hypergastrinemia stimulates growth of oxyntic gland mucosa, but not ileum mucosa, the antiatrophy effect of TCDD on mucosa of the oxyntic gland might in part be due to hypergastrinemia. In support of this interpretation, TCDD treatment exerted an antiatrophy effect on the oxyntic gland mucosa only when TCDD-treated animals were hypergastrinemic. For example, hypergastrinemia does not develop within the first 48 hr after TCDD administration, and TCDD treatment affords no protection against fasting-induced atrophy of the oxyntic gland mucosa during this time. On the other hand, the ability of TCDD treatment to protect against feed restriction-induced erosions of the oxyntic gland mucosa might be mediated by hypergastrinemia since these events occur at a later time.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Anti-Ulcer Agents; Atrophy; Body Weight; Eating; Fasting; Gastric Mucosa; Gastrins; Male; Parietal Cells, Gastric; Polychlorinated Dibenzodioxins; Rats; Rats, Inbred Strains

The effect of tetragastrin on pancreatic tumors induced by azaserine was investigated in Wistar rats. Rats were given 25 weekly injections of 10 mg/kg body weight of azaserine and 1 mg/kg body weight of tetragastrin as a suspension in olive oil every other day. Carcinogen-induced pancreatic lesions were examined by histochemical techniques, and were classified as ATPase-positive or ATPase-negative. In week 62, quantitative histological analysis showed that prolonged administration of tetragastrin had little or no influence on the number and size of the carcinogen-induced pancreatic lesions, although it caused significantly increased cell proliferation, indicated by a greater labelling index of the pancreatic acinar cells.

Topics: Adenosine Triphosphatases; Animals; Azaserine; Body Weight; Cell Division; Gastrins; Male; Mitotic Index; Organ Size; Pancreatic Neoplasms; Rats; Rats, Inbred Strains; Tetragastrin

The effects of neurotensin on the incidence, number, size, and histology of colon tumours induced by azoxymethane (AOM) were investigated in Wistar rats. Rats were given 10 weekly injections of AOM (7.4 mg kg-1 body weight) and were also given 200 micrograms kg-1 of neurotensin in depot form every other day until the end of the experiment. In week 40, prolonged alternate-day administration of neurotensin resulted in significant increases in the number and size of colon tumours and the incidence of adenocarcinomas penetrating muscle layer and deeper. However, neurotensin did not influence the incidence of tumour-bearing rats and the histological appearance of colon tumours. Administration of neurotensin caused a significant increase in the labelling index of the colon cancers but not that of colon mucosa. These findings indicate that neurotensin enhanced the growth of colon tumours, possibly related to its effect in increasing proliferation of colon cancer cells.

Topics: Adenocarcinoma; Adenoma; Animals; Azoxymethane; Body Weight; Colonic Neoplasms; Drug Synergism; Gastrins; Male; Neurotensin; Rats; Rats, Inbred Strains

Vagotomy is known to reduce acid secretion and to increase serum gastrin concentrations. However, there is minimal information on the effect of vagotomy on parietal cell mass or gastrin cell mass. Basal and maximal acid secretions and fasting serum gastrin concentrations were measured in 22 gastric fistula dogs with pyloromyotomy before and up to 56 days following complete bilateral truncal vagotomy (n = 11) or sham vagotomy (n = 11). Dogs underwent total gastrectomy on postoperative days 9 (n = 5 per group) or day 56 (n = 6 per group). Parietal cells were stained with Luxol fast blue and parietal cell mass determined with computer-assisted histomorphometry. Parietal cell mass averaged 10.68 +/- 0.90 billion in control dogs and correlated significantly with maximal acid output (r = 0.76; P less than 0.01). Vagotomy reduced maximal acid output by 40%-50% (P less than 0.001) but had no significant effect on parietal cell mass (8.99 +/- 1.00 billion). Vagotomy increased serum gastrin concentrations significantly, but antral gastrin cell mass in vagotomized dogs (5.66 +/- 1.00 million) was not significantly different than that in control dogs (4.74 +/- 0.50 million). Thus, vagotomy did not lead to parietal cell hypoplasia or gastrin cell hyperplasia despite profound alterations in parietal cell and gastrin cell function.

Topics: Animals; Body Weight; Dogs; Fasting; Gastric Acid; Gastrins; Male; Osmolar Concentration; Parietal Cells, Gastric; Pyloric Antrum; Vagotomy, Truncal

It has been hypothesized that G-cell hyperplasia secondary to increased food consumption in the obese Zucker rat was responsible for the hypergastrinemia observed in vivo and from the isolated perfused stomach preparation. This possibility was investigated in pair-feeding experiments wherein the food intake of obese animals was restricted to match that of lean littermates from 5 to 8 weeks of age. Dietary restriction reduced the antral G-cell population of the obese rat to a similar level as that seen in lean animals, supporting the view that hyperphagia is the trigger for G-cell hyperplasia. However, basal gastrin levels measured in vivo and in vitro from the stomach preparation of the pair-fed obese animals were not significantly lower than those of obese animals fed ad libitum. Thus, abnormal feeding behavior in the obese phenotype cannot be directly related to gastrin hypersecretion and G-cell hyperplasia is not the primary cause of hypergastrinemia.

Topics: Animals; Body Weight; Diet; Eating; Gastrins; Models, Biological; Obesity; Pyloric Antrum; Rats; Rats, Zucker

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) produces a delayed onset hypergastrinemia in rats. The purpose of the present study was to determine if the increased serum gastrin concentrations were caused by decreased gastric acid secretion, decreased plasma clearance of gastrin, and/or decreased gastric emptying. It was found that TCDD treatment decreased gastric acid secretion as determined by decreases in gastric secretory volume, acidity, and total acid output in pylorus-ligated rats. Also, both dose-response and time-course curves for decreased gastric acid secretion in TCDD-treated rats were similar to those for hypergastrinemia. These findings, as well as a significant inverse correlation between serum gastrin concentrations and total gastric acid output in rats treated with graded doses of TCDD (5-100 micrograms/kg), suggest that TCDD-induced decreases in gastric acid production cause elevated serum gastrin concentrations. Neither hypergastrinemia nor decreased gastric acid secretion were observed in pair-fed control rats, demonstrating that neither effect was secondary to undernutrition. The TCDD-induced decrease in gastric acid secretion was not caused by a decrease in the number of acid-secreting parietal cells in the stomach, but rather was associated with a decrease in parietal cell responsiveness to gastrin-elicited acid secretion. This was evidenced by both elevated serum gastrin concentrations and a pharmacological dose of pentagastrin failing to stimulate gastric acid secretion in TCDD-treated rats. The disappearance of iv-administered gastrin-17 from the serum was not affected by TCDD treatment, suggesting that reduced serum gastrin clearance is not responsible for the TCDD-induced hypergastrinemia. Although a marked decrease in gastric emptying of a 51Cr-labeled liquid test meal was also observed in TCDD-treated rats, the lowest dose of TCDD required to produce this effect was greater than that needed to cause hypergastrinemia. This suggests that the hypergastrinemic effect of TCDD is not secondary to a decrease in gastric emptying. We conclude that the most probable cause of hypergastrinemia in TCDD-treated rats is decreased gastric acid secretion.

Topics: Animals; Body Weight; Gastric Acid; Gastric Emptying; Gastric Mucosa; Gastrins; Male; Polychlorinated Dibenzodioxins; Rats; Rats, Inbred Strains

Intestinal tissue mass was significantly reduced throughout the gastrointestinal tract (p less than 0.001) of intravenously fed (TPN) rats. Urogastrone-epidermal growth factor, (URO-EGF), reversed these changes. Although plasma enteroglucagon and gastrin levels showed a small increase with URO-EGF, this was far less than the gut tissue weight change, suggesting that it was unlikely that they were involved in modulating the proliferative response of the intestine to URO-EGF. Peptide tyrosine tyrosine (PYY) levels were however significantly increased by URO-EGF, indicating that PYY may possibly have a role in the modulation of intestinal cell proliferation.

Topics: Animals; Body Weight; Digestive System; Epidermal Growth Factor; Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptides; Male; Organ Size; Parenteral Nutrition, Total; Peptide YY; Peptides; Rats; Rats, Inbred Strains

This study was undertaken in male Sprague-Dawley rats to test the hypothesis that chronic ingestion of a low dose of nicotine suppresses body weight gain. The results from this study suggest that chronic nicotine ingestion induces weight loss in rats without the loss of their food intake. To determine whether the nicotine-induced body weight reductions are associated with endocrinological changes, the levels of gastrin and CCK in plasma were measured by specific radioimmunoassays and were found significantly elevated during chronic ingestion of nicotine. The data indicate that reduction of body weight mass by nicotine might be dependent on both hormonal and metabolic factors.

Topics: Animals; Body Weight; Cholecystokinin; Feeding Behavior; Gastrins; Male; Nicotine; Rats; Rats, Inbred Strains; Time Factors

In order to evaluate the effectiveness of a gastric implant in an animal model of dietary obesity, silicone implants (2.5 ml) were inserted into the stomachs of male rats maintained on a chow or "cafeteria" diet. At the time of implantation, the cafeteria fed rats weighed 14% more than chow fed controls. Overweight cafeteria fed animals lost weight in response to the gastric implant, whereas control chow fed animals did not. Both implant groups had significant increases in stomach weights in contrast to sham implant groups, but the increase was much less in the cafeteria diet group. The fasting plasma levels of the gastrointestinal hormones, gastrin and pancreatic polypeptide, and oxytocin (a marker of vagal afferent function) were measured by radioimmunoassay. Cafeteria fed sham or implanted animals had significantly higher fasting levels of plasma oxytocin and gastrin, and significantly lower plasma levels of pancreatic polypeptide than the chow fed groups. These studies demonstrate that the gastric implant has more effect on weight in overweight animals on a palatable mixed diet, perhaps related to both mechanical and neural factors.

Topics: Animals; Body Weight; Diet; Gastrins; Male; Obesity; Organ Size; Oxytocin; Pancreatic Polypeptide; Prostheses and Implants; Rats; Rats, Inbred Strains; Stomach

The nude mouse has been used to evaluate the effect of gastrin on xenografted tissues, but little is known about long-term actions of gastrin on native organs in this species. We investigated the impact of chronically administered synthetic pentagastrin on the nude mouse. Six groups of mice (eight animals each) received intraperitoneal injections twice daily for 14 days with saline or pentagastrin at 0.5, 5, 50, 500, or 5,000 micrograms/kg. Behavior, overall health, and body weight were unaffected by this treatment. Of the seven organs examined at necropsy, only the pancreas showed a weight gain in response to pentagastrin treatment, and this occurred only at the highest dose. Total DNA content of the pancreas decreased in a dose-related manner, indicating hypoplasia, whereas pancreatic RNA content increased, indicating hypertrophy. No effect on the stomach was observed. This work indicates that the nude mouse is less sensitive than other species to visceral growth regulation by pentagastrin, and that toxicity is low.

Topics: Animals; Body Weight; DNA; Dose-Response Relationship, Drug; Gastrins; Male; Mice; Mice, Nude; Organ Size; Pancreas; Pentagastrin; RNA

The midportions of rat small intestines were resected by 90 per cent, and the residual intestines studied for the effects of diet on mucosal morphology, nutrition and gastrointestinal hormones. Groups of rats were fed chow, an elemental diet (ED), or an ED + dietary fiber (EDF) for 1 or 3 weeks. Nonresected rats which were fed chow or ED for 3 weeks were used as controls. Nutritional parameters, such as concentrations of serum total protein, albumin and transferrin were favorable but gain in body weight was not. The parameters indicated that resected rats fed EDF fared better than resected rats fed ED. Mucosal villous height in the residual jejunum, similar in all the resected groups after 1 week, was significantly increased in the resected rats fed chow or EDF after 3 weeks, but did not differ between 1 and 3 weeks in the resected rats fed ED. Changes in the number of villous epithelial cells and villous width were also examined. The level of plasma enteroglucagon was high in the rats fed chow or EDF after both 1 and 3 weeks, and was positively correlated with the increases in villous height. Levels of serum gastrin were not affected by dietary change. Luminal nutrients were significantly associated with the adaptive changes in the mucosa of the residual intestine, and mucosal morphology was also considerably influenced by dietary change.

Topics: Adaptation, Physiological; Animal Feed; Animals; Body Weight; Diet; Dietary Fiber; Food, Formulated; Gastrins; Glucagon-Like Peptides; Intestinal Mucosa; Intestine, Small; Male; Nutritional Status; Rats; Rats, Inbred Strains

The postprandial secretion of insulin, gastrin and somatostatin was studied in 23 extremely obese subjects and nine normal-weight controls after a liquid test meal. Apart from a significantly higher insulin level in the obese group, no significant intergroup difference was found. The effect of weight loss on the same hormones was studied in 18 patients 6 months after gastric banding. The mean weight loss during this period was 33 +/- 2.1 (SEM) kg. There was significant decrease in postprandial insulin secretion after gastric banding, but neither gastrin nor somatostatin levels were altered.

Topics: Adult; Body Weight; Female; Food; Gastrins; Humans; Insulin; Male; Methods; Obesity, Morbid; Radioimmunoassay; Somatostatin; Stomach

We studied the early time-course of gastrin, somatostatin, and gut growth responses to 70% resection of mid-small intestine. Serum and antral gastrin increased by the 2nd day following resection and remained elevated for the 10-day period of study. Antral somatostatin remained unchanged, suggesting that the increase in gastrin was a selective antral response. Duodenum and ileum showed marked growth stimulation, which was progressive with time, and earlier and greater in duodenum. In contrast, gastric growth was unaffected. Thus, early responses to resection are characterized by specificity of gastrin, somatostatin, and growth effects.

Topics: Animals; Body Weight; Gastrins; Intestine, Small; Male; Rats; Rats, Inbred Strains; Somatostatin

To assess the effect of malnutrition on gastric acidity and gastric bacterial colonization, we studied 35 severely malnourished Bangladeshi children before (0 wk) and after (3 wk) they received nutritional rehabilitation for 3 wk. These results were compared with those obtained from a similarly examined group of 20 better-nourished Bangladeshi children. Gastric acid output, both basal and after betazole stimulation, was significantly lower in the malnourished group at 0 wk compared with the better-nourished children (p less than 0.01): basal 0.22 vs. 0.52 mEq HCl/h and stimulated 0.90 vs. 2.5 mEq HCl/h. Both the concentration of acid and the rate at which gastric juice was secreted were decreased in the malnourished group but serum gastrin levels were not significantly different. After 3 wk, the malnourished children had improved from 61% (+/- 9.0%; SD) to 81% (+/- 8.1%) of expected weight-for-height and were not significantly different than the better-nourished group (86% +/- 11%). Nevertheless, gastric acid concentration remained depressed in the 3-wk group, although the rate of gastric juice secretion equaled levels observed in the better-nourished group. None of the better-nourished children had detectable gram-negative bacterial colonization of their gastric juice. In contrast, 26 of 32 (81%) malnourished children at 0 wk were colonized--even after betazole stimulation, 11 of 33 (33%) gastric juice samples yielded viable organisms--suggesting that the decrease in gastric acid output greatly reduced the gastric acid barrier. Interestingly, only 9 of 20 (45%) better-nourished children had gastric juice with basal pH values below 4.0, suggesting that the gastric acid barrier may be an intermittent defense factor in Bangladeshi children.

Topics: Age Factors; Bacteria; Bangladesh; Body Weight; Child; Child, Preschool; Gastric Acid; Gastrins; Humans; Infant; Parenteral Nutrition, Total; Protein-Energy Malnutrition; Stomach

Growth of neomucosa has been investigated as a means to increase intestinal surface area in the short-bowel syndrome. Functional neomucosa grows over patched intestinal defects, but the effect of the patching procedure on absorption is unknown. The purpose of this study was to determine morphologic and nutritional responses to intestinal patching after resection. Fifteen dogs (13 to 19 kg) underwent either 75% resection of the small intestine (control group, n = 5), simultaneous resection and patching of the intestinal remnant with colon serosa (simultaneous group, n = 5), or resection with patching 12 weeks later (delayed group, n = 5). Caloric intake was standard in the three groups. Animals were killed 40 weeks after resection or patching. At that time, defects were 95% covered with neomucosa in both patched groups. Intestinal remnant length increased significantly in controls (139 +/- 20% initial length) compared to the simultaneous group (99 +/- 6%, p less than 0.05) but not to the delayed group (119 +/- 11%). Villous height of intestinal mucosa was greater in the control and delayed groups than in the simultaneous group (714 +/- 36 and 624 +/- 111 versus 535 +/- 54 micron, p less than 0.05). Fasting gastrin levels were significantly greater in patched animals than after resection alone (p less than 0.05). Intestinal transit by barium meal was significantly longer in patched animals (18 +/- 7 minutes versus 11 +/- 6, p less than 0.05). Body weight and serum albumin level were significantly lower in patched animals at death. Fecal weight, moisture, and fat excretion were significantly increased in the simultaneous group. Although intestinal patching results in the growth of neomucosa and prolonged transit time, it has a deleterious effect on absorption and nutritional status. In part, this may be related to inhibition of intestinal adaptation and gastric hypersecretion in patched animals.

Topics: Animals; Body Weight; Cholesterol; Colon; Dogs; Feces; Gastrins; Gastrointestinal Transit; Ileum; Intestinal Absorption; Intestinal Mucosa; Intestines; Nutritional Status; Serum Albumin

The results of our preliminary experience with the gastric balloon program for weight loss in morbidly obese patients are reported. In a pilot project, we measured gastric-acid secretion, gastrin and cholecystokinin (CCK) levels in ten patients before and during balloon therapy in a study of the impact of the balloon on gastric physiology. Gastric-acid secretion tended to decrease following balloon treatment, while gastrin and CCK levels were unchanged suggesting that weight loss is achieved by mechanisms, which are not mediated by gastrin or CCK. The balloon program was then expanded to a group of 29 patients who met the criteria. They were followed for a period of 4 months. Average weight loss for the group was 31 +/- 4 pounds for a monthly average of 8 pounds. The main complications were gastric ulcers in four patients and a small-bowel obstruction in one patient. Satisfactory weight loss was achieved in 80 per cent of patients, but this benefit must be balanced against a relatively high incidence (17%) of side effects, some of which were quite serious. Therefore, the gastric balloon program should still be considered experimental.

Topics: Adult; Body Weight; Cholecystokinin; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Obesity, Morbid; Prospective Studies; Prostheses and Implants

Since little is known about the pathophysiology of pyloric stenosis, we created a partial gastric outlet obstruction in 13 Wistar rats by placing a nonabsorbable ligature of defined size around the pylorus. Sham operations were performed in 10 rats. The animals from both groups were killed after four months. G-cell count and gastrin content were determined in 10 parallel strips, which were cut by razor blades mounted on a handle. Gastric size and weight as well as thickness of mucosal and muscular layers and serum gastrin concentration were also determined. Body weight of the animals with pyloric stenosis was lower and gastric weight higher than that of the controls. Furthermore, we found an enlarged G-cell area and G-cell hyperplasia, an increased surface area and thickness of the mucosal and muscular layers of the stomach, and in the majority of rats, elevated serum gastrin levels. Total G-cell count was 583,720 +/- 90,561 in the rats with pyloric stenosis and 385,775 +/- 15,820 (mean +/- SEM) in the control rats (P less than 0.04). We conclude that partial gastric outlet obstruction in rats leads to G-cell hyperplasia and that this experiment may serve as a model for pyloric stenosis in man.

Topics: Animals; Body Weight; Cell Count; Chromaffin System; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Hyperplasia; Hypertrophy; Male; Organ Size; Pyloric Stenosis; Rats; Rats, Inbred Strains; Stomach

We investigated whether the trophic actions of prostaglandins, omeprazole, and indomethacin on gastric mucosa lead to accelerated healing of gastric ulcers in the rat. Cryoulcers were produced in the corpus area and treated with 16,16-dimethyl prostaglandin E2 (5 or 100 micrograms/kg b.i.d., intragastrically), omeprazole (40 mumol/kg once daily, subcutaneously), indomethacin (2 mg/kg b.i.d., subcutaneously), or placebo. At the end of the treatment, plasma gastrin, cell labeling index (autoradiography with [3H]thymidine), and the size and depth of mucosal defects were measured. Compared with placebo, omeprazole accelerated ulcer healing as indicated by a smaller ulcer area [1.1 +/- 0.2 vs. 4.8 +/- 1.2 mm2 (mean +/- SEM)] and smaller ulcer depth (383 +/- 31 vs. 488 +/- 41 microns) after 10 days of treatment. Prostaglandins did not affect ulcer healing despite thickening of gastric corpus mucosa. Indomethacin delayed ulcer healing and reduced the labeling index. Omeprazole induced a marked hypergastrinemia (208 +/- 12 vs. 66 +/- 12 pmol/L on day 5, and 469 +/- 23 vs. 58 +/- 16 pmol/L on day 10). The results indicate that abolishment of acid secretion by omeprazole accelerates healing. Trophic actions and "cytoprotective" effects by prostaglandins are not relevant for ulcer healing in this model.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Autoradiography; Body Weight; Gastric Mucosa; Gastrins; Indomethacin; Male; Omeprazole; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Stomach Ulcer

Topics: Adolescent; Body Weight; Child; Female; Gastrins; Growth Disorders; Growth Hormone; Humans; Insulin; Male; Nutrition Disorders

Adaptive growth and precocious expression of sucrase activity occur in the small intestine of artificially reared (AR) rat pups fed a hormone-free diet. The physiological mechanisms underlying adaptive intestinal growth were studied. Day 12 rat pups that received jejunal isografts subcutaneously on day 0 were subjected to artificial feeding and were killed on day 16. Crypt cellularity and DNA labeling index in isografts from AR, but not from mother-fed, rats increased significantly to levels found in in situ host jejunum of AR rats, indicating that humoral regulatory mechanisms are responsible for intestinal cell proliferation in AR pups. Radioimmunoassays of serum corticosterone, thyroxine, insulin, and gastrin and of gastric gastrin contents revealed that only serum corticosterone concentrations were significantly elevated, suggesting that corticosterone plays a critical role for intestinal growth. To examine this possibility directly, day 12 rats were adrenalectomized (ADX) and AR by continuous infusion of diets containing 0, 10, or 50 micrograms/ml corticosterone. Serum corticosterone concentrations paralleled the infused doses of corticosterone. Jejunal DNA labeling index increased in all ADX AR rats at day 13 in a dose-dependent manner. Increased jejunal DNA labeling index was maintained on day 14 in intact AR rats and ADX AR rats fed 10 micrograms/ml corticosterone but not in ADX AR rats receiving 0 or 50 micrograms/ml. We conclude that endogenous corticosterone is one of the systemic factors responsible for the adaptive increase in intestinal growth of AR rats.

Topics: Adrenalectomy; Animal Feed; Animals; Body Weight; Cell Division; Corticosterone; DNA; Gastrins; Hormones; Insulin; Intestines; Rats; Stomach; Thyroxine

The effect of ileo-jejunal transposition (IJT) on the intestinal adaptation after total colectomy was investigated in 4 mongrel dogs. Hyperenteroglucagonemia was observed in the IJT with colectomy group, especially in postprandial state. Obvious hyperplastic changes were observed in all part of the small intestinal mucosa in the colectomy with IJT group. However, there were no significant differences in body weight changes between the colectomy with IJT group and the colectomy group. Postprandial plasma gastrin levels were lower in the colectomy with IJT group compared to the control. These results suggest that IJT causes hyperenteroglucagonemia and intestinal mucosal hypertrophy in colectomized dogs. Enteroglucagon may have an inhibitory effect on postprandial gastrin release.

Topics: Adaptation, Physiological; Animals; Body Weight; Colectomy; Dogs; Gastrins; Glucagon; Glucagon-Like Peptides; Hypertrophy; Ileum; Intestinal Mucosa; Intestines; Jejunum; Peptides

The influence of food deprivation on gastric G- and D-cells and on parietal cells was studied in the rat. In fed controls and groups of rats fasted for 12 and 96 h G-, D- and parietal cell densities, somatostatin and gastrin concentration in antral and fundic specimens and serum gastrin were compared. Gastrin in antral mucosa, serum gastrin, G-cell density as well as antral D-cell density decreased in long-term fasted rats by 52%, 90%, 58% and 42%, respectively. Fundic D-cell density remained unchanged. After 96 h starvation somatostatin concentration slightly increased in antral mucosa (+35%; P less than 0.05), but decreased in fundic mucosa (-40%; P less than 0.05). Parietal cell density was not influenced by prolonged fasting. These findings demonstrate that changes in D-cell morphology and mucosal somatostatin content are not parallel and that the rat gastric D-cell is less dependent on food in the gastric lumen than the G-cell. The unaltered fundic D-cell density reflects the functional activity of gastric D-cell which has also been shown to be independent of the presence or absence of food.

Topics: Animals; Body Weight; Gastric Fundus; Gastric Mucosa; Gastrins; Male; Organ Size; Pyloric Antrum; Rats; Rats, Inbred Strains; Somatostatin; Starvation

We recently reported trophic response of transplantable mouse colon cancer cells (MC-26) to pentagastrin, in vivo, and demonstrated gastrin receptors on MC-26 cells, in vitro. In the present study, growth of MC-26 cells in mice, in response to pentagastrin, was studied in relation to binding kinetics and capacity of gastrin receptor. Gastrin receptor levels on mouse fundic and colonic membranes and on MC-26 cellular membranes were determined before MC-26 cell inoculation and designated as Day 0 levels. Four groups of mice were next inoculated with MC-26 cells and given injections of either pentagastrin (treated) or normal saline (control) for 10 or 15 days. At the end of the treatment periods, body, tumor, fundic, and colon weights were noted and gastrin receptor measured. tumor and fundic weights increased significantly within 15 days of pentagastrin treatment, compared to control values. In control (non-pentagastrin treated) mice, the binding affinity of gastrin receptor on tumor membranes was significantly decreased and associated with the complete loss of high-affinity gastrin receptor (Kd = less than 0.5 nM) by Day 15 of tumor growth. On the other hand, both the binding affinity and gastrin receptor levels of tumor membranes were maintained at Day 0 values by pentagastrin treatment. Endogenous gastrin was therefore ineffective in maintaining high-affinity gastrin receptor on control tumors. A significant number of low-affinity gastrin-binding sites (Kd = less than 2 nM) appeared in control tumors by Day 15, which could reflect rapid dedifferentiation or conformational changes of gastrin receptor in the absence of high levels of normal regulatory hormones. These studies demonstrate that the trophic effects of gastrin on MC-26 cells are probably mediated by its regulation and maintenance of the binding affinity and capacity of gastrin receptor on the cancer cells, in vivo.

Topics: Animals; Body Weight; Colon; Colonic Neoplasms; Gastric Fundus; Gastrins; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Pentagastrin; Receptors, Cell Surface; Receptors, Cholecystokinin; Time Factors

The trophic effect of truncal vagotomy was studied in rats. Three months after vagotomy and pyloroplasty pancreatic weight was significantly increased by 40% (p less than 0.001). Gastric stasis and consecutive distension of the stomach was observed in the majority of vagotomized animals despite pyloroplasty; the trophic effect of vagotomy on the pancreas was most pronounced in animals with severe stomach distension. Basal gastrin levels were increased after truncal vagotomy but did not correlate to gastric stasis and to the hypertrophy and hyperplasia of the exocrine pancreas. Basal pancreatic polypeptide hexapeptide levels were not altered after vagotomy. Morphometric studies on the endocrine pancreatic tissue showed that the relative volume density decreased due to the increase in exocrine tissue. However, the total islet cell mass remained constant. It is concluded that chronic truncal vagotomy has a trophic effect on the exocrine but not on the endocrine pancreas; additional factors besides gastrin seem to be responsible for this.

Topics: Animals; Body Weight; Gastrins; Islets of Langerhans; Male; Pancreas; Pancreatic Polypeptide; Pylorus; Rats; Rats, Inbred Strains; Vagotomy

To determine if amniotic fluid or its constituent trophic factors influence fetal gastrointestinal tract development we developed models of fetal esophageal ligation to prevent swallowing of amniotic fluid and fetal esophageal cannulation with infusion of various substances to mimic fetal swallowing. A total of 43 fetuses was studied. Esophageal ligation resulted in a 32% reduction in gastric weight and a 40% reduction in serum gastrin level, compared to unoperated controls, whereas intestinal and liver weights were unchanged. Gastric acid concentration averaged 43.4 +/- 7.7 mumole/ml in control fetuses, but only 0.5 +/- 0.5 mumole/ml following esophageal ligation. Infusion of Ringer's lactate solution intragastrically did not prevent the changes in gut development seen after esophageal ligation. In contrast, infusion of bovine amniotic fluid resulted in relatively normal gut development, with a gastric acid concentration of 28.5 +/- 6.9 mumole/ml and liver and gastric weights and serum gastrin levels no different from control. Epidermal growth factor had a potent trophic effect on both somatic and gastrointestinal fetal growth and resulted in a mean gastric acid concentration of 35.2 +/- 6.6 mumole/ml. In contrast, pentagastrin, although restoring gastric weight to control values, had no effect on gastric acid secretion, with a mean of 0.1 +/- 0.1 mumole/ml. We conclude that fetal swallowing of amniotic fluid is essential in fetal gastrointestinal development, possibly via luminal trophic actions of peptides such as epidermal growth factor and gastrin.

Topics: Amniotic Fluid; Animals; Body Weight; Catheterization; Digestive System; Esophagus; Female; Gastric Acidity Determination; Gastrins; Gestational Age; Ligation; Organ Size; Pregnancy; Rabbits

In an attempt to elucidate histogenesis of stomach cancer, quantitative analysis and measurement of DNA contents of various atypical lesions were sequentially made in the process of gastric carcinogenesis of Wistar strain of rats. Along with this, the effect of vagotomy on the development of atypical or neoplastic lesions were studied. A variety of focal lesions in the glandular stomach were seen in the middle or 4 and 12 weeks after the oral administration of N-methyl-N'-nitrosoguanidine (MNNG, 83 mg/l in drinking water) for 25 weeks. Both upward and downward growth was found in the intramucosal atypical lesions as well as frank carcinoma; the former lesions were histologically classified into 3 (Type I--Type III). On the basis of DNA distribution pattern, Type III lesions were considered to be intramucosal carcinoma and Type II to include precancerous state in some instances. In a group of rats vagotomized 1 week prior to the start of MNNG administration, there were significantly more lesions than in a group of MNNG alone. In contrast to the latter group which developed lesions in an uniform distribution pattern along the lesser curvature in the pyloric region, lesions in the former were characterized by random distribution pattern.

Topics: Adenocarcinoma; Animals; Body Weight; DNA, Neoplasm; Gastric Mucosa; Gastrins; Male; Methylnitronitrosoguanidine; Rats; Rats, Inbred Strains; Stomach Neoplasms; Vagotomy

This report deals with the effect of feeding inhibitors of pancreatic and brush border enzymes on pancreatic growth and enzyme composition and secretion. Raw soybean flour containing trypsin inhibitors caused pronounced growth of the pancreas which was accompanied by increased enzyme content and increased CCK and gastrin concentration in the plasma. Feeding of an amylase inhibitor to a starch-rich diet induced a marked fall in amylase content and secretion without changing growth parameters of the pancreas, indicating that not starch but glucose is the trigger for the maintenance of amylase content and secretion of the pancreas. The addition of an alpha-glucosidase inhibitor (acarbose) to a sucrose- or maltose-rich semisynthetic diet did not cause significant alteration in pancreatic growth or enzyme composition or secretion. In man pancreatic function was also unaltered by 8 weeks' intake of 3 X 200 mg acarbose.

Topics: Acarbose; Adaptation, Physiological; alpha-Amylases; Amylases; Animals; Blood Proteins; Body Weight; Cholecystokinin; Diet; DNA; Enzyme Inhibitors; Gastrins; Glycine max; Glycoside Hydrolase Inhibitors; Humans; Male; Oligosaccharides; Organ Size; Pancreas; Rats; Rats, Inbred Strains; Trisaccharides; Trypsin Inhibitors

Variations of the pancreatic parenchyma, the gastric mucosa and the intestinal mucosa were studied in adult male Wistar rats on day 8 and 15 after hypophysectomy. All results were compared with those obtained in pair-fed control rats. Hypophysectomy affected small intestine as well as gastric mucosa. Hypotrophy was observed on day 8 as most of the morphological parameters reached the maximal decrease. By contrast, hypoplasy occurred on day 15, when the labeling index (LI) decreased significantly. In the intestine, however, a decrease of the LI was observed only for the upper proliferative cells of the crypts. In the gastric mucosa, the LI was reduced only in the proliferative zone containing progenitor cells (isthmic region). Consequently, the cell differentiation is not similarly affected on all levels of the digestive tract.

Topics: Animals; Body Weight; Cell Division; Gastric Mucosa; Gastrins; Hypophysectomy; Intestinal Mucosa; Male; Microscopy, Electron; Organ Size; Pancreas; Polysaccharides; Rats; RNA; Stomach

This work investigates the effect, on the rat pancreas, of a chronic administration of bombesin in function of the dose and duration of treatment and examines whether this effect may be mediated by the release of endogenous gastrin or cholecystokinin. Bombesin, administered three times daily for 5 or 15 days, induced a marked increase in pancreatic weight, its protein, RNA and enzyme contents with the dose of 10 micrograms/kg body weight; the ratios of pancreatic weight, protein and RNA contents to DNA contents increased significantly after a 5 day treatment, suggesting cellular hypertrophy. Pancreatic DNA content was markedly enhanced after a 15 day treatment, suggesting cellular hyperplasia. Antrectomy decreased plasma gastrin levels, but did not alter the pancreatico-trophic action of a 10 micrograms/kg bombesin treatment for 5 days. Proglumide, an inhibitor of cholecystokinin and gastrin in the pancreas, did not affect the growth of the pancreas induced by a 10 micrograms/kg bombesin treatment for 5 days. It is concluded that chronic bombesin induces, in the rat pancreas, cellular hypertrophy or hyperplasia depending on the duration of treatment. Pancreatic hypertrophy is not mediated by the release of endogenous gastrin or cholecystokinin.

Topics: Amylases; Animals; Body Weight; Bombesin; Cholecystokinin; Chymotrypsin; Gastrectomy; Gastrins; Lipase; Microscopy, Electron; Organ Size; Pancreas; Proglumide; Rats; Receptors, Cell Surface; Receptors, Cholecystokinin; RNA

Some tumors are responsive to hormone manipulation. Some gastric and colonic adenocarcinomas from both humans and animals have specific gastrin receptors. A transplantable mouse colon adenocarcinoma cell line (MC-26) contains gastrin receptors; growth of MC-26 colon cancer in vivo is stimulated by pentagastrin (PG). The purpose of this study was to determine whether a gastrin-receptor antagonist, proglumide (PGL), would inhibit growth of MC-26 colon cancer and prolong survival in tumor-bearing mice. Subcutaneous tumors were induced by injecting single-cell suspensions of MC-26 cells into 50 mice divided into 10/group. In Experiment 1, all mice received 1 X 10(5) tumor cells and treatment groups were divided as follows: Group A received intraperitoneal (IP) saline (0.2 ml tid beginning on day 1); B, IP, PGL (250 mg/kg tid) from day of tumor cell inoculation; and C, IP PGL (250 mg/kg tid) from day 7 after tumor implantation. In Experiment 2, mice were inoculated with half the number of tumor cells. Group I mice received saline and Group II received PGL in the same manner starting on day 1. Tumors were measured and all mice were sacrificed on day 23. In Experiment 1, mean tumor area in Group B (PGL-treated) was significantly smaller than Group A on days 11, 14, 17, and 21. Tumors of Group C were significantly smaller than controls on day 21. Survival of PGL-treated mice was significantly prolonged. In Experiment 2, mean tumor area, mean tumor weight, and tumor DNA and RNA content were significantly less in the PGL-treated group than control. It was concluded that growth of a gastrin-responsive colon cancer was inhibited and host survival was enhanced by treatment with a gastrin-receptor antagonist. Hormone manipulation may be a useful treatment for gastrointestinal cancers.

Topics: Adenocarcinoma; Animals; Body Weight; Cell Division; Cell Line; Colon; Colonic Neoplasms; Gastric Fundus; Gastrins; Glutamine; Mice; Organ Size; Pancreas; Proglumide; Receptors, Cell Surface

The effects of truncal vagotomy after administration of N-methyl-N'-nitro-N-nitrosoguanidine on the incidence and number of gastric carcinomas and gastric acid secretion, gastrin secretion, antral pH, and duodenal reflux were investigated in inbred Wistar rats. Rats were subjected to truncal vagotomy after N-methyl-N'-nitro-N-nitrosoguanidine treatment. Vagotomy significantly increased the incidence and number of adenocarcinomas of the glandular stomach. It also resulted in significantly more atypical glandular hyperplasias, which are precursors of gastric cancer. Furthermore, it caused a decrease in gastric secretion and an increase in mucosal pH in the antrum but did not increase duodenal reflux. These findings indicate that vagotomy has a promoting effect on the development of gastric cancers. The reduced gastric acid secretion, but not duodenal reflux, may be related to this increased incidence of gastric cancer.

Topics: Animals; Body Weight; Duodenogastric Reflux; Gastric Acid; Gastric Juice; Gastrins; Male; Methylnitronitrosoguanidine; Rats; Rats, Inbred Strains; Stomach Neoplasms; Time Factors; Vagotomy

Plasma concentrations of gastrointestinal hormones were measured by radioimmunoassay in fasted rats 9 days after infection with a range of doses of Nippostrongylus brasiliensis. Values for infected rats fed ad libitum were compared with those of weight matched, pair fed, uninfected rats to control for the possible effects of dose-dependent reductions in food intake associated with infection. The plasma concentrations of some of the gastrointestinal hormones in infected rats were very different from those of their pair fed partners. The magnitude and direction of the changes varied according to the hormone being examined. Plasma concentrations of gastrin and pancreatic polypeptide were similar in pair fed and infected rats at all doses used. For the other hormones assayed, infection was associated with dose-related changes. The plasma concentrations of cholecystokinin and insulin were slightly but significantly reduced in infected rats. In contrast, secretin, enteroglucagon, and pancreatic glucagon concentrations were markedly increased. At the highest dose given (52 larvae/g body wt), the plasma levels of secretin and enteroglucagon in infected rats were elevated 9 X and 15 X, respectively. A comparison of the changes seen in N. brasiliensis-infected rats with those reported for other helminth infections revealed striking differences. The possible etiology of alterations in plasma gastrointestinal hormone concentrations and their contribution to the pathological changes seen in animals infected with helminths are discussed.

Topics: Animals; Body Weight; Cholecystokinin; Energy Intake; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Male; Nematode Infections; Nippostrongylus; Pancreatic Polypeptide; Rats; Secretin

A clinical, endoscopic, and histological study of 206 cases of nodular hyperplasia of Brunner's glands was carried out. Firm nodules with a reddened surface due to hyperplastic Brunner's glands were limited mainly to the first part of the duodenum and affected almost exclusively male patients. Gastric acid secretion after pentagastrin stimulation was significantly increased compared to normal. In most cases, biopsies of the nodule center revealed spreading of Brunner's glands from within the lamina propria to the surface epithelium, whereas in biopsies performed between nodules, Brunner's glands were limited to the deeper part of the mucosa. Thirty-six nodules completely removed by diathermy were composed almost entirely of Brunner's glands. The frequent association with duodenal ulcer, chronic gastric erosions, and cobblestone pattern of the gastric body mucosa, as well as the significant hypersecretory state, suggest that hyperacidity plays a role in the pathogenesis of nodular hyperplasia of Brunner's glands.

Topics: Biopsy; Body Weight; Brunner Glands; Duodenitis; Duodenoscopy; Duodenum; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Hyperplasia; Male

Nutrients are believed to have a direct trophic effect on the cells of the gastrointestinal mucosa. However, no normal constituent of the diet has ever been shown to stimulate mucosal growth when administered orally. Sham-operated and antrectomized rats were fed 20 g of powdered commercial rat pellets daily or 20 g of food containing dimethylamine (100 mumol/g food). After 7 days rats were killed and growth of the mucosa of the oxyntic gland portion of the stomach and 2-cm segments of duodenum, jejunum, and proximal colon was determined. Antrectomy resulted in significant decreases in the weight and the DNA, RNA, and protein content of all four tissues and serum gastrin levels. Feeding amines abolished the differences in the oxyntic gland and duodenal mucosa. In general, the effect of amines decreased distally. Feeding amines did not significantly alter serum gastrin levels. These data indicate that dietary amines may directly stimulate the growth of gastrointestinal mucosa. These results may explain some of the proximal-to-distal gradients described for the growth of the mucosa.

Topics: Amines; Animals; Body Weight; Diet; DNA; Gastric Mucosa; Gastrins; Intestinal Mucosa; Male; Organ Size; Proteins; Rats; Rats, Inbred Strains; RNA

Sympathetic involvement in the lateral hypothalamic (LH) lesion syndrome was examined. Male rats were surgically or chemically sympathectomized and then given LH lesions. At 24 hr postlesion, lesion-induced hyperglycemia but not hyperthermia was attenuated by splanchnicectomy and celiac ganglionectomy. Hyperthermia but not hyperglycemia was attenuated by adrenal demedullation, adrenalectomy, and neonatal guanethidine treatment. Guanethidine-sympathectomized rats also displayed lower basal temperatures, more perilesion chromatolysis, and severer external symptoms than their controls. No form of sympathectomy affected lesion-induced gastric pathology, plasma gastrin concentrations, or body weight loss. Nor did any sympathectomy influence the recovery of ingestive behavior, daily food intake, the feeding response to 2-deoxy-D-glucose, or body weight maintenance in recovered LH-lesion subjects. These results suggest that sympathetic hyperactivity contributes to some aspects of the acute LH syndrome: Hyperglycemia results from sympathetic outflow to the abdomen, whereas hyperthermia is determined by circulating catecholamines and extraabdominal sympathetic innervation. The results fail to support the hypothesis that chronic increases in sympathetic tone are responsible for the reduced food intake and body weight of the LH-lesion rat.

Topics: Animals; Blood Glucose; Body Temperature; Body Weight; Gastrins; Hypothalamic Area, Lateral; Hypothalamic Diseases; Insulin; Male; Rats; Stomach; Sympathetic Nervous System; Syndrome

23 obese and 17 control subjects were studied after ingestion of a heavy breakfast, and 11 obese and 11 control subjects were studied after ingestion of a mixed liquid test meal. Five subjects from the latter group were also studied two and six weeks after a jejuno-ileal bypass operation and the remaining six subjects from this group were studied twelve weeks after a stapled gastric partitioning. No significant differences in fasting or postprandial serum gastrin levels were found between the obese and the lean subjects, neither when studied with the breakfast meal nor when studied with the mixed liquid test meal. After the jejuno-ileal bypass operation the serum gastrin levels were not significantly different from the preoperative ones, whereas both the fasting and the postprandial serum gastrin levels were significantly augmented after the stapled gastric partitioning procedure. The group operated on with the latter method was also studied with an insulin test before and after the operation. Similar to that seen after ingestion of the mixed liquid test meal, the serum gastrin levels after the insulin-induced hypoglycemia were significantly higher postoperatively.

Topics: Adult; Aged; Body Weight; Fasting; Female; Food; Gastrins; Humans; Ileum; Jejunum; Male; Middle Aged; Obesity; Somatotypes; Time Factors

Extensive small bowel resection produces pancreatic hyperplasia and increases plasma gastrin levels in the rat. Because gastrin is known as a trophic factor for the exocrine pancreas, we studied the effect of endogenous variations of gastrin induced by different gastric operations on the rat pancreas in both resected and transected animals. Vagotomy increased plasma gastrin level while antrectomy decreased it; pyloroplasty was without any effect. These gastric operations enhanced slightly but not significantly the pancreatic weight, its protein and DNA content. A 90% jejunoileal resection alone increased markedly these parameters while mitotic figures appeared in acinar cells. Pyloroplasty, vagotomy and antrectomy did not modify the changes induced by intestinal resection itself except the level of protein. These findings suggest that hypergastrinemia produced by intestinal resection is not responsible for pancreatic hyperplasia.

Topics: Animals; Body Weight; DNA; Gastrectomy; Gastrins; Hyperplasia; Intestine, Small; Malabsorption Syndromes; Male; Organ Size; Pancreas; Proteins; Pylorus; Rats; Rats, Inbred Strains; Short Bowel Syndrome; Vagotomy, Proximal Gastric

Intracisternal administration of the tetradecapeptide peptide bombesin suppresses gastric acid release. Other studies have shown that the ventromedial hypothalamus (VMH) may have an inhibitory role in gastric regulation. To determine if the inhibition of gastric acid secretion by intracisternally administered bombesin is mediated by the ventromedial hypothalamus, bombesin was injected intracisternally in rats with ventromedial hypothalamic lesions. Neither anterior nor posterior VMH lesions altered the effects of bombesin on gastric acid, concentration, volume, total output, or on serum gastrin. The bombesin-induced rise in gastric pH was very mildly attenuated by both lesions. The previous finding of enhanced gastric acid secretion after anterior VMH lesions was confirmed. The results suggest that the VMH is not crucial in the bombesin-induced inhibition of acid secretion.

Topics: Animals; Body Weight; Bombesin; Cisterna Magna; Gastric Acid; Gastrins; Hydrogen-Ion Concentration; Hypothalamus, Middle; Male; Peptides; Rats; Rats, Inbred Strains

The effect of vagotomy on the enterochromaffin (argentaffin) cells in the rat gastrointestinal tract was studied 6 weeks after the operation. No effect was found, as indicated by the following parameters--the frequency of the silver-positive cells in different parts of the digestive tract, the intensity of the argentaffin reaction in the individual cells, and the nuclear size of the enterochromaffin cells.

Topics: Animals; Body Weight; Cell Division; Cell Nucleus; Chromaffin System; Enterochromaffin Cells; Gastrins; Male; Rats; Rats, Inbred Strains; Vagotomy

Concentrations of somatostatin-like immunoreactivity (SRIF-LI) were measured in cerebral cortex, hippocampus, septum-POA, median eminence, gastric antrum, fundus and pancreas in adult female hamsters to determine whether changes in somatostatin could be related to increased growth hormone (GH) secretion and somatic growth that follow bilateral transections of hippocampus (n = 18; 17 controls). In addition, choline acetyltransferase (CAT) activity was measured in the four brain regions in hippocampectomized (n = 10) and control hamsters (n = 10) to gain insight into the relationship between these two neurotransmitters. Hippocampal transections induced: significant acceleration of somatic growth; increased serum GH concentrations; increased concentrations of SRIF-LI in septum-POA and gastric antrum; reduced concentrations of SRIF-LI in hippocampus and pancreas; and reduced CAT activity in the hippocampus. These results suggest that somatostatinergic and cholinergic projections to hippocampus via fornix suppress GH and somatic growth in adult hamsters and that reduced release of SRIF-LI in the gastric antrum may contribute to the acceleration of somatic growth through facilitated nutrient digestion and entry.

Topics: Acetylcholine; Animals; Body Weight; Brain; Choline O-Acetyltransferase; Cricetinae; Female; Gastrins; Growth Hormone; Hippocampus; Mesocricetus; Preoptic Area; Septum Pellucidum; Somatostatin; Stomach

Antrectomy reduced the levels of circulating gastrin but did not change jejunal morphology. In vitro and in vivo absorption as well as the activity of some brush border enzymes were increased. The observed alterations are discussed on the basis of antrectomy-induced alterations in the release of gastrointestinal hormones, gastric and pancreatic secretion and gastric emptying.

Topics: Animals; Body Weight; DNA; Female; Gastrins; Jejunum; Pancreas; Pyloric Antrum; Rats; Rats, Inbred Strains; RNA

It is generally agreed that the adaptive response in the residual bowel after major intestinal resection is dependent on luminal nutrition and pancreaticobiliary secretions. Recent evidence, however, suggests that humoral mechanisms, e.g., gastrin or enteroglucagon, may also play a part in this process. A 75% proximal small bowel exclusion was performed in 16 male Wistar rats and the excluded bowel was fashioned into a Thiry-Vella fistula. Half of the animals were allowed food ad libitum, while the rest were fed intravenously. The animals were killed at 12 days, and plasma, gastrin, and enteroglucagon were measured, while cell proliferation was determined by measuring the crypt cell production rate employing a stathmokinetic method using vincristine and crypt microdissection. In addition to these animals, 16 rats had a jejunal transection only, with half of these animals nourished intravenously, while the remainder were allowed food ad libitum. In the Thiry-Vella rats, plasma enteroglucagon was greater with oral feeding (566 +/- 59 pmol/L) than with intravenous feeding (120 +/- 452 pmol/L) (p less than 0.01), but gastrin levels did not differ in the two groups. In the ileum in continuity, crypt cell production rate per hour was greater in the orally fed animals (52 +/- 8) compared with the intravenously fed group (18 +/- 5) (p less than 0.001). In the excluded fistula, crypt cell production rate per hour was reduced by 23.8 +/- 2 in orally fed rats, but this was greater than in the intravenously fed group (16 +/- 1.5) (p less than 0.01). Both orally and intravenously fed transected rats had significantly lower plasma hormone levels, and reduced crypt cell production rate compared with the respective Thiry-Vella groups. This study suggests a distinct role for a humoral agent responsible for the proliferative changes seen after small bowel resection, and in this respect enteroglucagon appears more relevant than gastrin.

Topics: Adaptation, Physiological; Animals; Body Weight; Cell Division; Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptides; Ileum; Intestinal Fistula; Intestine, Small; Male; Parenteral Nutrition; Rats; Rats, Inbred Strains

During a 3-year period proximal gastric vagotomy without drainage and selective gastric vagotomy with drainage were performed in 61 patients with duodenal ulcer. Of these, 57 patients were followed for 3-6 years. 77% were symptom-free (Visick I); 8,3% were improved but still have periods of dyspepsia (Visick II) and 14% were failures because of recurrent ulcer (Visick III). There were seven duodenal recurrences in the bulb, and one prepyloric recurrence. There were no operative deaths or major complications. The side effects, like diarrhoea and dumping, after proximal gastric vagotomy and selective vagotomy were mild and rare. The majority of our patients gained their ideal body weight within the first six months from surgery. Blood chemistry did not show any deficiency in haemoglobin secondary to vagotomy, but plasma basal level of gastrin was constantly higher after surgery. It is concluded that 3-6 years after proximal gastric vagotomy and selective gastric vagotomy for duodenal ulcer there was a 14% recurrence rate, but the absence of mortality, severe complications or significant side effects seems to be at least as important as the high recurrence rate.

Topics: Adolescent; Adult; Aged; Body Weight; Diarrhea; Drainage; Duodenal Ulcer; Follow-Up Studies; Gastrins; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Recurrence; Retrospective Studies; Vagotomy; Vagotomy, Proximal Gastric

Two groups, each containing 16 male Wistar rats, had either 75 per cent small bowel resection or jejunal transection; 8 animals from each group; had previously been subjected to pancreatico-biliary diversion. All animals were killed 12 days after the operation, plasma enteroglucagon levels were measured and crypt cell production rate (CCPR) at different sites of the remaining small intestine was measured using a metaphase arrest technique with vincristine. In each of the resected groups there was a significant increase in the CCPR and enteroglucagon levels compared with the transected groups. Furthermore it was found that the CCPR and enteroglucagon levels were higher in the resected group without the pancreatico-biliary diversion compared with the resected group with the diversion. This study, although it confirms the importance of pancreatico-biliary secretions in intestinal adaptation, could also indicate that a humoral factor may be important in the control of intestinal cell proliferation. Our findings do not exclude the possibility that enteroglucagon could be a candidate for such a role.

Topics: Adaptation, Physiological; Animals; Bile; Body Weight; Cell Division; Energy Intake; Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptides; Intestine, Small; Jejunum; Male; Pancreas; Rats; Rats, Inbred Strains

The present study examined the effects of a 60% reduction in food intake on kinetic and morphometric parameters in the small intestine of adult male Lewis rats. We observed that, after 20 days, the wet weight of jejunum and ileum, thickness of muscularis externa of duodenum, crypt depth throughout the intestine, and DPM/mg and DPM/crypt in ileum were decreased in animals on reduced food intake when compared to their paired, normally fed controls. These results demonstrated that reduced food intake caused distinctive effects focused primarily in the ileum, thus opening to question the use of the technique of pair feeding as a control for studies of intestinal cell proliferation in which manipulations of the animals result in altered food intake or body weight.

Topics: Animals; Body Weight; Cell Division; Epithelium; Food Deprivation; Gastrins; Glucagon; Ileum; Intestine, Small; Kinetics; Male; Organ Size; Rats; Rats, Inbred Lew; Rats, Inbred Strains

A 60-year-old patient developed signs and symptoms of glucagonoma syndrome (dermatitis, weight loss, anemia and hypoaminoacidemia). However, diabetes mellitus was absent. Glucagonoma was suspected because of markedly elevated plasma glucagon levels and the tumor was subsequently removed by surgery. Acidethanol extraction of the tumor and immunohistochemistry provided evidence of the presence of all four islet hormones, particularly that of glucagon and pancreatic polypeptide and to a lesser extent of somatostatin and insulin. Immunohistochemistry of the tumor (but not plasma) also showed the presence of alpha-HCG. Plasma glucagon immunoreactivity consisted to a large extent (approx. 90%) of a high molecular form of glucagon, probably proglucagon. In spite of the presence of alpha-HCG - which is assumed to be a marker of malignancy - the patient has been free of recurrence for the 2 1/2 years since surgery. The increasing number of cases reported during the past few years demonstrates that the syndrome is more common than previously suspected. Glucagon secretion and its typical clinical picture may be a valuable marker of a multihormonal pancreatic tumor. In a case of suspected glucagonoma, diagnosis can be established simply by obtaining a plasma glucagon level measurement.

Topics: Adenoma, Islet Cell; Anemia; Body Weight; Dermatitis; Gastrins; Glucagon; Glucagonoma; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Pancreatic Neoplasms; Pancreatic Polypeptide; Secretin; Syndrome

Fasting serum cholesterol, triglycerides, thyroxine, triiodothyronine, uric acid, gastrin, and insulin were measured in a group of 24 Muslims at the beginning and end of Ramadan--the Muslim month of fasting. There was a significant increase in the levels of total serum cholesterol, thyroxine, and uric acid and a significant fall in body weight. There was no significant change in the levels of total serum triglycerides, triiodothyronine, gastrin, insulin (fasting), or in the rise in gastrin or insulin 1/2 h after food. These changes, although unlikely to affect normal people, may be significant in patients. Physicians working in Muslim countries should be aware that Ramadan may affect some laboratory findings.

Topics: Adult; Body Weight; Cholesterol; Fasting; Female; Gastrins; Humans; Insulin; Islam; Male; Thyroxine; Triglycerides; Triiodothyronine; Uric Acid

Levels of gastrin-cholecystokinin-like immunoreactivity were measured in three brain regions (cortex, diencephalon, brainstem) and the pituitary gland in groups of genetically obese Zucker rats and their non-obese littermates. The obese animals had significantly increased body weights and significantly lowered brain weights. However, levels of gastrin-cholecystokinin-like immunoreactivity were not different between the two groups in any of the regions measured. These results contrast with a recent report [11] in which ob/ob mice were found to have decreased levels of cholecystokinin in their brains.

Topics: Animals; Body Weight; Brain Chemistry; Brain Stem; Cerebral Cortex; Cholecystokinin; Diencephalon; Gastrins; Male; Obesity; Organ Size; Pituitary Gland; Radioimmunoassay; Rats; Rats, Inbred Strains; Species Specificity; Tissue Distribution

Twenty-four male albino rats were given daily intraperitoneal injections of vasoactive intestinal polypeptide (VIP), motilin, human gastrin I (1-17) or the diluent control vehicle at a dose of 100 micrograms/kg for four consecutive days and food intake, water intake, body weight, and running wheel activity were determined every 24 hours. Animals injected with motilin or human gastrin I (1-17) exhibited decreased food intake relative to those injected with VIP or diluent, which did not differ from each other, although food intake increased reliably over days. The mean water consumption followed the same pattern as that of food intake. As expected from the above results, VIP produced weight gains as compared with rats injected with motilin or gastrin but not reliably more than after diluent. A reliable effect of trials for weight gain was the greatest on day three. Running wheel activity was not affected by injections of human gastrin I (1-17), motilin, or diluent but was reliably decreased by VIP. No significant differences existed across days. Although the results indicate that GI peptides may affect behavior when injected systemically and that like other peptides they have multiple effects, caution is urged in the interpretation of behavioral results at this time.

Topics: Animals; Behavior, Animal; Body Weight; Drinking; Eating; Gastrins; Gastrointestinal Hormones; Male; Motilin; Motor Activity; Rats; Rats, Inbred Strains; Vasoactive Intestinal Peptide

Topics: Adult; Body Weight; Fasting; Female; Gastrins; Humans; Male; Middle Aged; Obesity

The proliferation of antral gastrin cells after fasting and refeeding of rats was studied by using a quantitative histologic method for determining the gastrin cell number and a radioautographic technique after injections of tritiated thymidine for recognizing and quantitating the newly formed gastrin cells. The total number of gastrin cells decreased 68% (P less than 0.01) after a 4-day fasting period, whereas refeeding of rats during 6 days after a 4-day fasting period resulted in a 79% (P less than 0.01) increase of the gastrin cell mass. The labeling index of gastrin cells after six daily injections of tritiated thymidine given during this period of refeeding was significantly (P less than 0.01) increased when compared with this value in control animals. The observed intensity of the proliferative response during refeeding was compatible with the increase in gastrin cell number observed during refeeding. These observations indicate that a new population of gastrin cells is formed in the antral glands when rats are refed after fasting.

Topics: Animals; Body Weight; Cell Count; Cell Division; Eating; Epithelial Cells; Fasting; Gastrins; Mucous Membrane; Pyloric Antrum; Rats

Blood serum immunoreactive gastrin level (IRG) was measured in infants with hypertrophic pyloric stenosis before and after corrective surgery and in a control group children of corresponding age. No significant difference in IRG level was found between the stenotic infants and the control group. In the stenotic infants IRG values were higher at the seventh day after than before the operation and significantly higher in those infants in whom gain of body weight was noted during that time as compared with the infants without gain of weight. These observations remain in agreement with the view that the main role of gastrin in infants is trophic action on the mucosa of the upper gastrointestinal tract.

Topics: Body Weight; Gastrins; Humans; Hypertrophy; Infant; Pyloric Stenosis; Radioimmunoassay

Cods were equipped with cannulae for drainage of the stomach and for separate perfusion of the stomach (pure sea-water) and intestine (diluted sea-water). Acidity and volume of gastric effluence were measured. Plasma immunoreactive gastrin and vasoactive intestinal polypeptide (VIP) were assayed in some experiments. The high rate of "basal" acid secretion was further elevated by i.m. administration of bombesin, but not by pentagastrin. Exogenous VIP inhibited acid secretion. Following 5 h of bombesin infusion, plasma gastrin-IR was unaffected while VIP-IR was depressed compared to saline-treated controls. The possibility that bombesin stimulates acid secretion by inhibiting VIP-release is discussed.

Topics: Animals; Body Weight; Bombesin; Female; Fishes; Gastric Juice; Gastrins; Gastrointestinal Hormones; Male; Pentagastrin; Peptides; Radioimmunoassay; Vasoactive Intestinal Peptide

Integrated postprandial serum gastrin levels were studied in a prospective series of 144 Chinese patients with duodenal ulcer in relation to sex, total body weight, age of onset and duration of ulcer symptoms, blood group status, and positivity for familial dyspepsia. Postprandial gastrin was unrelated to sex, total body weight, duration of symptoms, and blood group status. Patients whose onset age was in the first two decades (early onset group) had significantly higher postprandial gastrin than those with onset age in the 4th and 6th decades (P less than 0.01). This was found to be associated with the presence in the early onset group (n = 35) of a high proportion of patients with positive family history of ulcer dyspepsia (n = 24), in whom postprandial gastrin was significantly higher than those without such history (P less than 0.01). These results suggest that early onset patients who are positive for family history of ulcer dyspepsia segregate to form one subgroup of duodenal ulcer. They also offer a clue that familial hypergastrinaemia may be one marker for familial duodenal ulcer.

Topics: Adolescent; Adult; Age Factors; Blood Group Antigens; Body Weight; Child; Duodenal Ulcer; Dyspepsia; Female; Food; Gastrins; Humans; Male; Middle Aged; Prospective Studies; Sex Factors; Time Factors

The effects of endogenous hypergastrinemia and hypogastrinemia on the exocrine and endocrine pancreas were studied in the rat. Hypergastrinemia was induced by antral exclusion, and hypogastrinemia by antral resection. The studies were made 14 weeks after surgery. The total weight of the pancreas was increased both in hypergastrinemic and hypogastrinemic animals, due to hypertrophy of the exocrine cells. In contrast, the volume and total weight of the pancreatic islets were decreased. There was no numerical difference in the A-, D-, PP-cells between the hyper- and hypogastrinemic animals, respectively, and the controls. The number of insulin-producing (B-) cells was certainly reduced after the induction of hypogastrinemia. There was, however, signs of increased B-cell activity, which might contribute to an underestimation of the number of B-cells with the technique used. These findings do not support the hypothesis that antral gastrin has trophic influence on either exocrine or endocrine pancreas.

Topics: Animals; Body Weight; Gastrins; Hypertrophy; Islets of Langerhans; Male; Organ Size; Pancreas; Pyloric Antrum; Rats

The effect of prolonged metiamide administration on serum gastrin, gastrin content of the antrum and gastric corpus, and G-cell population was studied in the rat. A single subcutaneous injection of metiamide (200 mg/kg) at the onset of 16 days of continous treatment with three daily injections was followed by a fivefold increase in serum gastrin level at 4 hr in fasted and at 4 and 6 hr in fed rats. After 16 days of metiamide, the fed rats showed a peak in serum gastrin level of the same magnitude as on day 1, but only at 4 hr. Two hours later, the levels decreased rapidly to basal values. In the fasted animals, the response to metiamide was reduced to a threefold increase at 2 hr. There was no difference in gastrin content of the antrum and gastric corpus nor in volume density of the G-cells after the prolonged treatment compared with the controls. It is concluded that in spite of rises in serum gastrin, prolonged metiamide medication has no effect on the gastrin content of the antrum and gastric corpus nor on the G-cell population in the rat. Furthermore, after prolonged treatment, metiamide-induced gastrin release is diminished.

Topics: Animals; Body Weight; Cell Count; Fasting; Gastric Mucosa; Gastrins; Male; Metiamide; Organ Size; Pyloric Antrum; Rats; Stomach; Thiourea

Topics: Body Weight; Diet, Reducing; Epinephrine; Gastrins; Humans; Ileum; Jejunum; Obesity

The effects of truncal vagotomy and pyloroplasty and proximal gastric vagotomy on gastric acid hypersecretion, hypergastrinemia, and growth after massive bowel resection were studied in beagle puppies. In puppies with 80% enterectomy, neither type of vagotomy alters significantly the postprandial hypersecretion of acid from the Heidenhain pouch or the concentration of serum gastrin. Proximal gastric vagotomy tended to decrease the hypersecretion more than did truncal vagotomy. In beagle puppies undergoing 70% small bowel resection, growth was significantly decreased but survival was not impaired. Neither proximal gastric vagotomy nor truncal vagotomy and pyloroplasty reversed completely the impaired growth produced by massive resection. Proximal gastric vagotomy caused a small improvements in growth, while truncal vagotomy and pyloroplasty resulted in a slight decrease in growth. It remains possible that proximal gastric vagotomy could be of value in the management of growing infants with hypersecretion of acid due to short bowel syndrome.

Topics: Animals; Body Weight; Dogs; Female; Gastric Juice; Gastrins; Growth; Intestine, Small; Pylorus; Stomach; Vagotomy

Subcutaneous injections of a large dose of tetragastrin (2 mg/day) into a rat for 4 weeks caused hypertrophy of parietal cells of the stomach, intestinal glandular cells of the duodenum, and pancreatic acinar cells. Ths histometrical analysis revealed that these trophic effects of tetragastrin were produced in varying degrees in different sites.

Topics: Animals; Body Weight; Duodenum; Gastrins; Male; Pancreas; Rats; Stomach; Tetragastrin

Seven pairs of rats were simultaneously infused with a chemically formulated nutritionally complete amino acid-glucose diet which was delivered, at the same rate, into a central vein or into a feeding gastrostomy. The intragastrically infused rats showed greater weight gain than did the intravenously infused rats. This could not be explained by fluid retention since intake and output were similar in the two groups of animals. There was a greater increase in serum immunoreactive insulin (IRI) at day 8 in the intragastrically infused animals, but a smaller increment in serum immunoreactive pancreatic glucagon (IRG) at that point. Levels of enteroglucagon or glucagon-like immunoreactivity (GLI) were maintained in the intragastrically infused rats but declined markedly in the intravenously infused rats. It is possible that the greater release of IRI seen with the intragastric amino acid-glucose feeding contributes to better disposal of nutrients and greater weight gain. The presence of nutrients in the intestinal lumen may have stimulated the release of GLI, which in turn is insulinotropic.

Topics: Amino Acids; Animals; Body Weight; Enteral Nutrition; Gastrins; Gastrostomy; Glucose; Male; Metabolism; Parenteral Nutrition; Parenteral Nutrition, Total; Rats; Water-Electrolyte Balance

Topics: alpha-Glucosidases; Animals; Body Weight; DNA; Eating; Gastrins; Ileum; Intestinal Mucosa; Intestine, Small; Jejunum; Male; Organ Size; Parenteral Nutrition; Parenteral Nutrition, Total; Protein Biosynthesis; Rats; RNA

The propulsion and mixing of small bowel contents were studied in conscious rats 14 days after antral resection, antral exclusion and gastroentero-anastomosis in order to evaluate the influence of hypo-, hyper- and normogastrinemia, respectively, on the net result of small bowel muscular activities. The quantitative measures of propulsion and mixing did not differ significantly between the groups. There was, however, a significant correlation between high serum gastrin and increased intestinal mixing after antral exclusion and gastroentero-anastomosis. This finding supports earlier studies on gastrin effects on the small bowel obtained by exogenous gastrin infusion.

Topics: Animals; Body Weight; Gastrins; Gastrointestinal Motility; Intestine, Small; Male; Pyloric Antrum; Rats

Oral intake of an elemental diet maintains small intestinal mucosal mass compared to the atrophy seen after intravenous infusion of the same diet. The greatest difference in intestinal mass occurs in the proximal bowel and is thought to occur because of rapid absorption in the proximal small bowel. This study was designed to determine the effects of the individual components of the elemental diet and their site of administration within the small bowel on small intestinal mass. Rats were maintained on intravenous alimentation and the proximal gut (by intragastric infusion) or the ileum was continuously infused with equal volumes of 30% dextrose, 5% dextrose, 5% amino acids, saline, or 30% mannitol. After 1 week of combined intravenous alimentation and gut infusion, the rats were killed and parameters of small intestinal epithelial mass were determined sequentially for the entire bowel. Although saline- and mannitol-infused controls did not differ from uninfused intravenously fed rats, proximal infusion of 30% dextrose reproduced the effects of a complete elemental diet. Proximal infusion of amino acids but not 5% dextrose had a limited effect on the duodenum and jejunum. Ileal infusion of 30% dextrose led to local hyperplasia of the site of infusion and in addition produced hyperplasia of the proximal gut. Ileal amino acid infusion, but not 5% dextrose infusion, led to local ileal hyperplasia. We conclude that: (1) intraluminal dextrose and amino acids have direct effects in maintaining gut mass (2) the gut is more responsive to amino acids compared to 5% dextrose, and (3) ileal 30% dextrose infusion leads to remote effects in the proximal gut, perhaps mediated by hormonal or neurovascular factors.

Topics: Amino Acids; Animals; Body Weight; DNA; Epithelial Cells; Gastrins; Glucose; Ileum; Infusions, Parenteral; Intestinal Mucosa; Intestine, Small; Jejunum; Male; Nutritional Physiological Phenomena; Organ Size; Proteins; Rats; Stomach

The morphology of the parathyroids in rats with hypergastrinemia, induced by antral exclusion, was compared with that of glands from untreated rats and animals from which the main source of gastrin- 17 was excluded (antral resection). Fourteen weeks after induction of hypergastrinemia the volume of the parathyroids was significantly increased owing to hyperplasia of the parenchymal cells. Removal of the antral gastrin-producing capacity of the same duration was not accompanied by any significant changes in the parathyroids. These findings suggest that hypergastrinemia could be a stimulus for the development of hyperplasia of the parathyroids, and that it may be an etiological factor in the production of hyperparathyroidism.

Topics: Animals; Body Weight; Calcium; Cell Count; Gastrins; Hyperparathyroidism; Hyperplasia; Male; Organ Size; Parathyroid Glands; Pyloric Antrum; Rats

The clearance rates of synthetic human gastrin-17-I were measured in man, dog, and cat. Half-life of disappearance and acid secretory potency (D50) were also measured in man and dog. The clearance rates in dog and cat were, respectively, 3 and 8 times more than in man. Accordingly, the half-life of gastrin-17 in the dog (3.5 min) was 3 times shorter than in man (9.5 to 10.5 min). The D50 for acid secretion was proportional to the clearance rate and yielded approximately similar increments of serum gastrin, indicating an equal sensitivty to gastrin-17 at cellular level in the three species. An inverse allometric relation between clearance rate and body weight was consistent with the known greater efficiency of metabolic and eliminatory processes in species of small size. Recent studies of the disposal of other gastrointestinal hormones indicate that the concepts developed theoretically for secretory stimulants and confirmed experimentally for gastrin-17 may have wider applicability.

Topics: Animals; Body Weight; Cats; Dogs; Dose-Response Relationship, Drug; Gastric Juice; Gastric Mucosa; Gastrins; Half-Life; Humans; Infusions, Parenteral; Male; Metabolic Clearance Rate; Secretory Rate; Species Specificity

Serum and antral gastrin were measured in rats infected with either Trichinella spiralis or Hymenolepis diminuta as a step in testing the hypothesis that parasites change certain aspects of host physiology by altering gastrointestinal (GI) hormone levels or responses to GI hormones. Parasitism with T. spiralis was associated with inflammatory changes in the small bowel mucosa and with a significant increase in serum gastrin. Neither changes in hormone level nor inflammation were induced in tapeworm-infected rats. These results reveal the capacity of tissue penetrating parasites to alter the level of circulating gastrin. This finding coupled with considerable indirect evidence suggests that some of the pathologic changes induced in hosts by enteric parasites may be due to changes in functions that are regulated by GI hormones.

Topics: Animals; Body Weight; Gastrins; Hymenolepiasis; Intestinal Diseases, Parasitic; Male; Pyloric Antrum; Rats; Trichinellosis

The effects of hypophysectomy and subsequent replacement therapy with growth hormone on serum and antral gastrin levels was investigated in both fasted and nonfasted pair-fed rats. Hypophysectomy caused a 57% decrease in serum and 47% decrease in antral gastrin content in 18-hr fasted animals. In nonfasted animals, hypophysectomy resulted in a 42% fall in serum gastrin and a 76% fall in antral gastrin. Animals were given injections of growth hormone over a 10-day period, then fasted 16 to 18 hr before being killed. Doses of 100 to 200 mug per 100 g of body weight were ineffective, but a dose of 500 mug per 100 g was sufficient to restore completely serum gastrin levels to intact control values. In nofasted rats this same dose raised serum gastrin to intact levels and increased antral gastrin significantly over hypophysectomized levels, but did not increase it to control values. When given to pair-fed intact animals, growth hormone caused slight but not significant elevations in serum and antral gastrin. The effect of growth hormone on gastrin secretion and /or synthesis may be a significant physiological factor in the regulation of normal gastrointestinal function and growth.

Topics: Animals; Body Weight; Food; Gastrins; Growth Hormone; Hypophysectomy; Male; Pituitary Gland; Pyloric Antrum; Rats; Stimulation, Chemical

Topics: Atropine; Body Weight; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Injections, Intramuscular; Injections, Intravenous; Insulin; Male; Radioimmunoassay; Secretory Rate

In previous communications we have reported using the rat fed by total parenteral nutrition to examine the effects of the absence of food from the gut on functional and structural parameters of the gastrointestinal tract. In the current study three groups of animals were fed parenterally; one received a continuous infusion of pentagastrin equal to about one-half the D50 for acid secretion, another received a comparable infusion of histamine, and a third group was given only the liquid diet. These animals were compared to orally fed sham operated controls. The parenterally fed animals had significantly lower levels of antral and serum gastrin. When compared to whole body weight, the weights of the oxyntic gland area of the stomach, the pancreas, and the small intestine were significantly lower. In addition, the total and specific activities of the disaccharidase enzymes were significantly reduced. Pentagastrin prevented both the decreases in weights of the gastrointestinal tissues and the decreases in dissaccharidase activity. Histamine was without effect. We conclude that pentagastrin prevents the changes in gastrointestinal structure and function caused by the absence of food from the gut and that the trophic action of gastrin is necessary for the maintenance of the functional and structural integrity of the gastrointestinal tract.

Topics: Animals; Body Weight; Digestive System; Digestive System Physiological Phenomena; Gastrins; Glucosidases; Histamine; Intestine, Small; Kidney; Male; Organ Size; Pancreas; Parenteral Nutrition; Pentagastrin; Peroxidases; Pyloric Antrum; Rats; Stomach; Sucrase

This study examines the effect of prolonged absence of oral food intake on structural parameters of the gastrointestinal tract in rats maintained nutritionally by intravenous feeding for up to 3 weeks. During this time, their body weights increased by 22%. Controls fed a nearly isocaloric oral diet were sham operated and harnessed in the same manner as their parenterally fed counterparts. Parenteral feeding resulted in a significant decrease in the weights (per 100 g body weight) of the oxyntic gland area of the stomach, small intestine, and pancreas. The weights of the spleen, testes, kidneys, and antral region of the stomach were unaltered. In the small intestine there was a significant loss of DNA and a near doubling of the RNA:DNA ratio in the parenterally fed animals. In the absence of an oral diet antral gastrin levels decreased to one-thirtieth of the control level. The following conclusions are suggested by these results. First, the oral intake and/or physical presence of food within the gastrointestinal tract are necessary for structural maintenance of some tissues of that tract. Second, the disproportionate decrease in weight that occurs in certain tissues is apparently unrelated to the absence of nutrients which might normally be utilized directly from the lumen. Third, maintenance of normal tissue stores of the hormone, gastrin, is dependent on stimuli provided by oral ingestion and the presence of food in the gastrointestinal tract.

Topics: Animals; Body Weight; Digestive System; DNA; Food; Gastrins; Intestine, Small; Kidney; Male; Organ Size; Pancreas; Parenteral Nutrition; Physical Stimulation; Proteins; Pyloric Antrum; Rats; RNA; Spleen; Stimulation, Chemical; Stomach; Testis

One hundred and twelve consecutive patients selected for surgical treatment for duodenal ulcer disease were treated by a graded gastrectomy according to the Moynihan modification of the Billroth II partial gastrectomy. A large partial gastrectomy (R) (2/3-3/4 gastrectomy) was done in patients who after maximal stimulation with histamine showed a high acid output (MAO greater than 30 mEa/hr), and a small resection (r) (1/3-1/2 gastrectomy) in low secretors (MAO less than 30 mEq/hr). The material was prospectively controlled by admission to hospital at 3 months, 1 year and 5 years postoperatively. The preoperative values of MAO found in R and r were 42.8 and 21.5 mEq/hr (p less than 0.001), respectively. The postoperative MAO values at the 3-month control were 4.5 and 3.0 mEq/hr by R and r, respectively, which shows that the grading of resection had been successful. Atrophic gastritis increased in frequency from 4% at the time of operation to 72% at the 1-year control...

Topics: Adolescent; Adult; Aged; Anemia; Biopsy; Body Weight; Celiac Disease; Child; Duodenal Ulcer; Female; Folic Acid Deficiency; Follow-Up Studies; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Male; Middle Aged; Norway; Postgastrectomy Syndromes; Prospective Studies; Recurrence; Work Capacity Evaluation

Topics: Animals; Body Weight; Calcitonin; Female; Gastric Juice; Gastrins; Immobilization; Lactates; Male; Peptic Ulcer; Swine; Time Factors

Topics: Age Factors; Alkaline Phosphatase; Animals; Body Weight; DNA; Galactosidases; Gastrins; Glucosidases; Intestine, Small; Organ Size; Pentagastrin; Proteins; Pyloric Antrum; Radioimmunoassay; Rats; Rats, Inbred Strains; RNA; Weaning

Topics: Adult; Body Weight; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Female; Food; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Radioimmunoassay; Stimulation, Chemical; Time Factors

Topics: Animals; Body Surface Area; Body Weight; Cats; Dogs; Dose-Response Relationship, Drug; Gastrins; Half-Life; Histamine; Humans; Pentagastrin; Peptides; Species Specificity; Stimulation, Chemical; Swine

Topics: Animals; Body Weight; Cineradiography; Dogs; Female; Gastrins; Gastroenterostomy; Gastrointestinal Motility; Glucose; Jejunum; Sodium Chloride; Stomach; Time Factors; Vomiting

Topics: Body Weight; Gastric Acidity Determination; Gastric Juice; Gastrins; Half-Life; Humans; Infusions, Parenteral; Metabolic Clearance Rate; Radioimmunoassay; Regression Analysis; Time Factors

Topics: Animals; Biological Assay; Blood Glucose; Body Weight; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Liver; Male; Organ Size; Pyloric Antrum; Rabbits; Starvation

Topics: Adult; Aged; Black People; Body Weight; Duodenal Ulcer; Dyspepsia; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Injections, Intramuscular; Male; Middle Aged; Nigeria; Stimulation, Chemical

Topics: Aging; Animals; Body Weight; Gastric Juice; Gastrins; Organ Size; Rats; Stomach

Topics: Animals; Body Weight; Drug Synergism; Gastric Juice; Gastric Mucosa; Gastrins; Male; Nicotine; Pepsin A; Peptic Ulcer; Peptides; Rats; Stimulation, Chemical; Succinates

Topics: Body Surface Area; Body Weight; Gastric Juice; Gastrins; Humans

Topics: Animals; Body Weight; Fasting; Gastric Juice; Gastrins; Male; Peptides; Pyrazoles; Rats; Stimulation, Chemical; Time Factors; Water-Electrolyte Balance

Topics: Adult; Age Factors; Aged; Body Weight; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Male; Methods; Middle Aged; Peptic Ulcer; Secretory Rate; Sex Factors; Stomach Ulcer; Time Factors; Vagus Nerve

Topics: Acetazolamide; Animals; Body Weight; Cats; Cholecystokinin; Dogs; Exocrine Glands; Furosemide; Gastrins; Humans; Neostigmine; Pancreatic Juice; Rats; Scopolamine; Serotonin