Gastrin Concentrations Research Articles

Acute Hemobilia and Hemocholecyst in 2 Dogs with Gallbladder Carcinoid

Acute Hemobilia and Hemocholecyst in 2 Dogs with Gallbladder Carcinoid

Gastrin increases mcl-1 expression in type I gastric carcinoid tumors and a gastric epithelial cell line that expresses the CCK-2 receptor

Elevated serum concentrations of the hormone gastrin are associated with the development of gastric carcinoid tumors, but the mechanisms of tumor development are not fully understood. We hypothesized that the antiapoptotic effects of gastrin may be implicated and have therefore investigated the role of antiapoptotic members of the bcl-2 family of proteins. AGS-GR human gastric carcinoma cells stably transfected with the CCK-2 receptor were used to assess changes in the expression of bcl-2 family members following gastrin treatment and the function of mcl-1 during apoptosis was investigated by use of small-interfering RNA (siRNA). Treatment of AGS-GR cells with 10 nM gastrin for 6 h caused maximally increased mcl-1 protein abundance. Gastrin-induced mcl-1 expression was inhibited by the transcription inhibitor actinomycin D and by the protein synthesis inhibitor cycloheximide. Downstream signaling of mcl-1 expression occurred via the CCK-2 receptor, protein kinase C, and MAP kinase pathways, but not via PI 3-kinase. Transfection with mcl-1 siRNA significantly suppressed mcl-1 protein expression and abolished the antiapoptotic effects of gastrin on serum starvation-induced apoptosis. Mcl-1 protein expression was also specifically increased in the type I enterochromaffin-like cell carcinoid tumors of 10 patients with autoimmune atrophic gastritis and hypergastrinemia. Gastrin therefore signals via the CCK-2 receptor, protein kinase C, and MAP kinase to induce expression of antiapoptotic mcl-1 in AGS-GR cells, and mcl-1 expression is also increased in human hypergastrinemia-associated type I gastric carcinoid tumors. Gastrin-induced mcl-1 expression may therefore be an important mechanism contributing toward type I gastric carcinoid development.

The Effects of Capsaicin on Gastrin Secretion in Isolated Human Antral Glands: Before and After Ingestion of Red Chilli

Capsaicin is known to have regulatory effects on gastrointestinal functions via the vanilloid receptor (VR1). We reported previously that endocrine-like cells in the human antrum express VR1. To identify VR1-expressing endocrine-like cells in human antral glands and to examine whether stimulation with capsaicin causes release of gastrin, somatostatin, and serotonin. Further, to investigate the effects of a chilli-rich diet. Gastroscopic biopsies were received from 11 volunteers. Seven of the 11 subjects agreed to donor gastric biopsies a second time after a 3-week chilli-rich diet containing 1.4-4.2 mg capsaicin/day. VR1-immunoreactive cells were identified by double-staining immunohistochemistry against gastrin, somatostatin, and serotonin. For the stimulation studies, we used an in vitro method where antral glands in suspension were stimulated with 0.01 mM capsaicin and physiological buffer was added to the control vials. The concentrations of secreted hormones were detected and calculated with radioimmunoassay (RIA). Results The light microscopic examination revealed that VR1 was localized in gastrin cells. The secretory studies showed an increase in release of gastrin and somatostatin compared to the control vials (P = 0.003; P = 0.013). Capsaicin-stimulation caused a consistent raise of the gastrin concentrations in the gland preparations from all subjects. A chilli-rich diet had an inhibitory effect on gastrin release upon stimulation compared to the results that were obtained before the start of the diet. This study shows that capsaicin stimulates gastrin secretion from isolated human antral glands, and that a chilli-rich diet decreases this secretion.

Gastrin, secretin, GIP and VIP alter levels of IL-2 and IFN-gamma in human peripheral blood mononuclear cells under various culture conditions.

Gastrointestinal hormones have traditionally been viewed as mere regulators of gut movement and secretions, but, it is becoming increasingly apparent that other body systems may be affected by these hormones. Secretion of gut hormones is influenced by the type of food we take. Therefore, the more we know about the effects of gut hormones on the various body tissues, the more we know about the different mechanisms by which our diets affect our health. This in vitro study aimed to explore the effects of physiologically-relevant concentrations of four gut hormones on the production of IL-2 and IFN- gamma by human peripheral blood mononuclear cells and how culture conditions may modify those effects. Peripheral blood mononuclear cells were separated by density gradient centrifugation from the blood of 15 adults. Cells were cultured with/without PHA and treated with four concentrations of gastrin, secretin, GIP and VIP. IL-2 and IFN- gamma in culture supernatants were assayed by ELISA. Gastrin, secretin, GIP and VIP increased IL-2 and IFN- gamma levels under some culture conditions and depressed IL-2 under other conditions. An increase was often observed under culture conditions in which the cytokine production was not initially high. Repeated administration of the hormone was also more likely to result in a stimulatory effect. Physiologically-relevant concentrations of gastrin, secretin, GIP and VIP are potential immunomodulators as they have shown their ability to alter the production of IL-2 and/or IFN- gamma under various culture conditions.

The Effect of Subchronic Administration of 7-(4-Fluorobenzyloxy)-2,3-dimethyl-1-{[(1S,2S)-2-methylcyclopropyl]methyl}-1H-pyrrolo[2,3-d]pyridazine (CS-526), a Novel Acid Pump Antagonist, on Gastric Acid Secretion and Gastrin Levels in Rats

In the present report, we evaluated the effect of the novel acid pump antagonist 7-(4-fluorobenzyloxy)-2,3-dimethyl-1-{[(1S,2S)-2-methylcyclopropyl]methyl}-1H-pyrrolo[2,3-d]pyridazine (CS-526) and 2-[3-methyl-4-(2,2,2-trifluoro-ethoxy)-pyridin-2-ylmethanesulfinyl]-1H-benzimidazole (lansoprazole) on rebound gastric acid secretion, using an intragastric dialysis membrane perfusion model and on the serum and antral gastrin level after a 14-day treatment in rats. The effect of CS-526 on gastric acid secretion was almost constant during the 14 days of treatment. After the 14-day treatment, gastric acid secretion had returned to pretreatment levels. However, CS-526 slightly increased and lansoprazole potently increased gastric acid secretion thereafter. In the posttreatment period, the influence on rebound gastric acid secretion by lansoprazole treatment was significant, but that by CS-526 was not. The serum gastrin concentration after the 14-day treatment with CS-526 did not increase significantly, even at 100 mg/kg/day. On the other hand, lansoprazole at 100 mg/kg/day significantly elevated the serum gastrin concentration. After the 14-day treatment with CS-526 at 100 mg/kg/day, the antral gastrin content significantly increased. Lansoprazole at the doses of 30 and 100 mg/kg/day also significantly increased the antral gastrin content after the 14-day treatment. The elevation of the serum gastrin level after the lansoprazole treatment was suppressed by the concomitant administration of CS-526. In conclusion, CS-526 has a potent antisecretory effect on gastric acid secretion without rebound gastric hypersecretion. Moreover, CS-526 had minimal effects on the serum and antral gastrin elevation. It is suggested that these effects on gastric acid secretion and serum gastrin after subchronic treatment with CS-526 would be beneficial in clinical use.

Serum gastrin levels and clinical conditions in response to early minimal feeding in premature infants

To study serum gastrin levels in response to early minimal feeding in premature infants and evaluate the clinical effect of early minimal feeding. Premature infants with critical score < or = 90 were randomly assigned into two groups: early minimal feeding group (n = 48), non-early minimal feeding group (n = 47). Other premature infants (n = 30) without any complications (critical score > 90) were assigned as normal control group. The premature infants in normal control group were fed with water at 6 h after birth, 1 - 2 ml/kg every time, after once or twice, they were fed with formula, increasing in the amount of formula gradually, until adequate. The premature infants in early minimal feeding group were fed with formula within 72 h after birth, 0.5 - 1 ml/kg, once every 3 h, the amount of formula was increased gradually, until adequate. The premature infants without early minimal feeding were not fed with formula until the illness was stable, the amount of formula was increased gradually until adequate. Situation of gastrointestinal feeding tolerance, growth and development, and clinical symptoms were observed and recorded for the three groups. Serum gastrin levels were monitored at 1, 3, 7 day after birth by radioimmunoassay. Serum gastrin concentrations in the three groups elevated from 1 to 7 days. In early minimal feeding group [(82.4 +/- 24.5) ng/L] and non-early minimal feeding group [(87.0 +/- 40.2) ng/L], the concentrations were significantly higher than those in normal control group [(66.4 +/- 19.7) ng/L] at day 1 (F = 3.36, P < 0.05). At day 3 and 7, the concentrations in early minimal feeding group [(96.3 +/- 14.6) ng/L, (113.0 +/- 16.5) ng/L] were significantly higher than those in non-early minimal feeding group [(73.9 +/- 13.5) ng/L, (92.4 +/- 12.2) ng/L] (P < 0.05). There were significant differences among the three groups in infants with feeding intolerance (2/30, 5/48, 14/47), the period reached full enteral feeding [(20.6 +/- 5.7) d, (27.8 +/- 6.1) d, (39.5 +/- 4.7) d], and in number of hospital day [(29.0 +/- 4.6) d, (39.0 +/- 4.8) d, (48.0 +/- 5.6) d] (P < 0.05). There were significant differences between early minimal feeding group and non-early minimal feeding group in the weight gain three and four weeks after birth [(19.1 +/- 2.4) g/d, (11.9 +/- 3.3) g/d], the period reached birthweight [(19.8 +/- 4.2) d, (25.2 +/- 5.1) d] (P < 0.05). There were no significant difference among the three groups in the weight gain in one and two weeks after birth [(5.9 +/- 2.9) g/d vs. (5.0 +/- 2.1) g/d], the numbers of premature infants with infection, anemia, apnea, or hypoglycemia. Early minimal feeding in premature infants leads to secretion of gastrin, promotes the development of gastrointestine and may not be associated with occurrence of complications.

알코올로 유도한 만성위궤양 흰쥐 모델에서 비타민 E 보충이 위궤양 치유에 미치는 영향

This study was carried out to examine the effects of vitamin E on chronic gastric ulcer induced by alcohol treatment in rats. Chronic gastric ulcer model was established by oral administration of 70% ethanol at one time and supply of 15% ethanol for additional 7 days. Male Sprague-Dawley rats, approximately 200 g, were fasted for 24 hours and orally gavaged with 1 mL of 70% ethanol for the induction of acute ulcer. A supply of 15% ethanol dissolved in distilled water for 7 days were followed to maintain chronic gastric ulcer. Acute ulcer group was sacrificed at 3 hours after oral administration of 1 mL of 70% ethanol. Chronic groups were divided into three groups according to vitamin E levels; low-vitamin E (LVE, 0 mg/mL oil/day), normalvitamin E (NVE, 1 mg/mL oil/day) and high-vitamin E (HVE, 10 mg/mL oil/day). These groups were fed vitamin E free diets which were made of vitamin E free vitamin mix followed AIN-93M pattern for 7 days. Histological findings of congestion, hemorrhage and necrosis in gastric tissue were shown severely in acute ulcer group and LVE group of chronic ulcer groups. The concentration of gastrin in serum was significantly higher in LVE group. The content of histamine in stomach was lower in acute ulcer group but there was no significant difference among the chronic groups regardless of vitamin E levels. Content of malondialdehyde (MDA) in gastric tissue was higher in HVE group and activities of antioxidant enzyme, glutathione peroxidase (GPx) and catalase, were lower in HVE group. Myeloperoxidase (MPO) activities as a marker of neutrophils infiltration was significantly higher in LVE group. These results suggested that vitamin E supplementation has positive effects on healing of alcohol-induced chronic gastric ulcer through alleviation of gastric tissue injuries and reduction of the MPO activity in gastric tissue and gastrin in serum.

Analyze the prevalence of gastroesophageal reflux disease in the end stage renal disease patients

Objective To investigate the prevalence of gastroeaophageat reflux disease(GERD)in the end stage renal disease patients(ESRD)with maintenance hemodialysis and the pathogenetic factors of GERD.Methods 60 cases who had heart burn and acid regurgitation symptoms were enrolled,31 cases of them were ESRD patients with maintenance hemodialysis,29 patients who were renal diseases free as control group.GERD was diagnosed by three methods:endoscopy,24h esophageal pH monitoring,endoscopic esophageal biopsy.GERD was established if any of these tests was positive.HP infection and serum gastrin were assessed too.Results (1)The prevalences of GERD in two groups were 83.9%,79.3% respectively and had no significant difference(P＞0.05).(2)The prevalence of HP infection in the ESRD group was significantly lower than control group(19 4% vs 51.7%,P＜0.05).(3)The concentration of serum gastrin in the ESRD group and control group was(102.61±30.80)ng/ml and (83.41±20.61)ng/ml,two group had significant difference(P＜0.05).Conclusion The prevalence of GERD inthe ESRD patients was higher than expected,and was correlated with absence of HP infection and hypergastinemia. Key words: Kidney failure,chronic; Gastroesophageal reflux; Prevalence

Feeding Behavior in Rats Subjected to Gastrectomy or Gastric Bypass Surgery

Background/Aim: Gastric bypass (GB) is usually designed to restrict food intake and to induce malabsorption. Gastric hormones have been thought to play a role in the regulation of food intake and body weight. The aim of the present study was to analyze feeding behavior after total gastrectomy (Gx) or GB in rats. Methods: Animals were subjected to Gx, GB, or sham operations. Eating and drinking behaviors after surgeries were assessed by a comprehensive laboratory animal monitoring system. Gastric hormones were measured by radioimmunoassay and energy density in feces by adiabatic bomb calorimeter. Results: Compared with sham operation, both Gx and GB reduced the body weight as measured during 3–8 weeks postoperatively, which was associated with increased energy expenditure per 100 g body weight. Daily accumulated food intake and meal size (during nighttime) were reduced following Gx, but not GB. The water intake (during daytime) was increased after Gx and GB. The energy density in feces was unchanged. Serum concentrations of ghrelin, obestatin, leptin, gastrin, and pancreastatin were greatly reduced after Gx. Conclusions: Control of food intake and meal size was independent of the food reservoir function of the stomach. Surgical depletion of gastric hormones is associated with reduced meal size, but increased water intake.

G cells and gastrin in chronic alcohol-treated rats

Numerous reports have described gastric mucosal injury in rats treated with high ethanol concentrations. However, to the best of our knowledge, ultrastructural characteristics of G cells and antral gastrin levels have not been previously reported, either in rats that chronically consumed alcohol or in human alcoholics. The goal of this study was to examine the effect of ethanol consumption (8.5 g/kg) over a 4-month period, under controlled nutritional conditions, on antral and plasma levels of gastrin, ultrastructure of G cells, morphometric characteristics of G cells by stereological methods, and analysis of endocrine cells in the gastric mucosa by immunohistochemistry. The chronic alcohol consumption resulted in a nonsignificant decrease in gastrin plasma levels and unchanged antral gastrin concentrations. A slightly damaged glandular portion of the gastric mucosa and dilatation of small blood vessels detected by histological analysis, suggests that ethanol has a toxic effect on the mucosal surface. Chronic alcohol treatment significantly decreased the number of antral G cells per unit area, and increased their cellular, nuclear, and cytoplasmatic profile areas. In addition, the volume density and diameter of G-cell granules, predominantly the pale and lucent types, were increased, indicating inhibition of gastrin release. Ethanol treatment also decreased the number of gastric somatostatin-, serotonin-, and histamine-immunoreactive cells, except the somatostatin cells in the pyloric mucosa, as well as both G: D: enterochromaffin cells (EC) cell ratios in the antrum and D: ECL cell ratios in the fundus. These results indicate that the change of morphometric parameters in G cells may be related to cellular dysfunction. Our findings also suggest that regulation of G-cell secretion was not mediated by locally produced somatostatin in ethanol-consuming rats, but may involve gastric luminal content and/or neurotransmitters of gastric nerve fibers.

Esomeprazole reduces gastroesophageal reflux after beer consumption in healthy volunteers

Objective. Patients with gastroesophageal reflux disease (GERD) are advised to avoid alcoholic beverages since alcohol consumption induces gastroesophageal reflux in healthy volunteers and increases it in patients with GERD. Proton-pump inhibitors (PPIs) are frequently administered for reflux symptoms but their effect on gastroesophageal reflux after alcohol consumption has not yet been fully studied. The aim of the present study was therefore to investigate the effect of esomeprazole, an S-enantiomer of omeprazole, on gastroesophageal reflux after beer consumption. Material and methods. In this placebo-controlled, double-blind, crossover study, 16 healthy male volunteers received 20 mg esomeprazole daily for one week. On day 7, in an acute experiment, the subjects then consumed 500 ml beer within 5 min. Subsequently, gastroesophageal reflux was monitored by pH-metry over a period of 3 h. In addition, gastric emptying was measured by ultrasonography and blood concentrations of ethanol, cholecystokinin and gastrin were determined. Results. Gastroesophageal reflux was significantly (p=0.001) reduced by 93% after treatment with esomeprazole (0.2%, median percentage of time pH<4) as compared to placebo (2.6%), but gastric emptying, blood ethanol and cholecystokinin concentrations were not significantly different after esomeprazole treatment. Plasma gastrin levels were significantly (p=0.0003) higher after esomeprazole (98.6±19.7 pg/ml) than after placebo (22.7±3.8 pg/ml) before beer consumption. However, there was no difference in the increase in plasma gastrin after beer consumption between the esomeprazole treatment and placebo. Conclusions. Esomeprazole significantly reduces gastroesophageal reflux after beer consumption in healthy volunteers. Gastric emptying of beer is not prolonged after treatment with esomeprazole, although compared with placebo, this PPI induced significantly higher plasma gastrin concentrations. Moderate alcohol consumption does not worsen gastroesophageal reflux when a PPI is administered.

The art of measuring gastrin in plasma: A dwindling diagnostic discipline?

The gastrointestinal hormone gastrin is measured in plasma in physiological, pathophysiological and diagnostic investigations. In the diagnosis of hypergastrinaemic diseases such as gastrinomas and gastric achlorhydria, measurement of gastrin concentrations in circulation is crucial. Gastrin circulates, however, not as a single peptide but as a mixture of peptides of different lengths and amino acid derivatizations. Moreover, in hypergastrinaemia the peptide pattern changes. Consequently, diagnostic gastrin measurements require immunoassays that recognize the pathological plasma patterns, which are characterized by a predominance of the large peptides (gastrin‐34 and gastrin‐71) and less, if any, of the shorter main form of gastrin in normal tissue, gastrin‐17. Alternatively, and in specific cases, “processing‐independent assays” (PIA) for progastrin may be considered, since hypersecreting gastrin cells also release substantial amounts of biosynthetic precursors and processing intermediates. Recently, gastrin kits that do not take the pathological plasma patterns into account have been marketed and may miss the diagnosis. Therefore, proper diagnosis of gastrinomas and other hypergastrinaemic diseases requires insight into cellular gastrin synthesis and peripheral metabolism, and also into the design of useful immunoassays. This review discusses the art of measuring gastrin in plasma with adequate diagnostic specificity.

GASTRIN IS NOT REQUIRED FOR LIVER REGENERATION

Although several growth factors are known to be essential for liver regeneration, the role of gastrin remains controversial. Liver regeneration was examined in wild-type (WT) and gastrin-deficient (gastrin KO) mice at days 2 and 10 after partial (40%) hepatectomy by measurement of liver weight. Hepatocyte proliferation and circulating gastrin concentrations were measured at the same time points by immunohistochemistry and radioimmunoassay, respectively. There was no significant difference in the rate of liver regeneration between gastrin KO and WT mice. Hepatocyte proliferation in both groups was increased at day 2 but had returned to baseline values by day 10. At day 2, hepatocyte proliferation in the gastrin KO mice was significantly higher than in WT animals, whereas at day 10, proliferation was significantly greater in the WT mice. The circulating gastrin concentration in the WT mice was significantly lower at day 10 than in unoperated WT animals. This study suggests that gastrin is not essential for liver regeneration after partial hepatectomy.

悪性貧血例における同一胃生検組織を用いた粘膜内 somatostatin, gastrin 含量に関する研究

悪性貧血例における同一胃生検組織を用いた粘膜内 somatostatin, gastrin 含量に関する研究

Reference range of serum calcitonin levels in humans: influence of calcitonin assays, sex, age, and cigarette smoking

The objective of this study was to re-evaluate the adult C(T) reference values determined by five different immunoassays and by introducing criteria for selecting control subjects. A prospective multicenter study. Three hundred and seventy-five clinically euthyroid subjects. We used five different C(T) immunoassays. Sera were assayed for the concentration of TSH, gastrin, procalcitonin, urea, calcium, and anti-thyroperoxidase antibodies. Screening for the various potential causes of hypercalcitoninemia led to the exclusion of 23% of the sera. Our reference value analysis dealt with 287 subjects (142 men and 145 women). The proportion of samples in which no C(T) was detected varied from 56% (for assay D) to 88% (for assay C). We observed significant correlations (whose magnitude depended on the assay used) between C(T) levels and age or body mass index (BMI) (primarily in men). The distribution of C(T) levels showed that 4.7, 9.8, 2.5, 6.5, and 8.0% of the values were over 10 pg/ml respectively. These values corresponded essentially to samples from 11 male subjects (median age: 55 years), most of whom were smokers. The highest C(T) values were around twice as high in men than women, and were higher in smokers than non-smokers. Conclusion In clinical practice (and after having excluded the usual causes of raised C(T) levels), the interpretation of C(T) assay results must take into account i) the method used; ii) the patient's gender, age, and weight; and iii) the potential influence of cigarette smoking.

Control of Gastric Acid Secretion in Somatostatin Receptor 2 Deficient Mice: Shift from Endocrine/Paracrine to Neurocrine Pathways

The gastrin-enterochromaffin-like (ECL) cell-parietal cell axis is known to play an important role in the regulation of gastric acid secretion. Somatostatin, acting on somatostatin receptor type 2 (SSTR(2)), interferes with this axis by suppressing the activity of the gastrin cells, ECL cells, and parietal cells. Surprisingly, however, freely fed SSTR(2) knockout mice seem to display normal circulating gastrin concentration and unchanged acid output. In the present study, we compared the control of acid secretion in these mutant mice with that in wild-type mice. In SSTR(2) knockout mice, the number of gastrin cells was unchanged; whereas the numbers of somatostatin cells were reduced in the antrum (-55%) and increased in the oxyntic mucosa (35%). The ECL cells displayed a reduced expression of histidine decarboxylase and vesicle monoamine transport type 2 (determined by immunohistochemistry), and an impaired transformation of the granules to secretory vesicles (determined by electron microscopic analysis), suggesting low activity of the ECL cells. These changes were accompanied by an increased expression of galanin receptor type 1 in the oxyntic mucosa. The parietal cells were found to respond to pentagastrin or to vagal stimulation (evoked by pylorus ligation) with increased acid production. In conclusion, the inhibitory galanin-galanin receptor type 1 pathway is up-regulated in the ECL cells, and the direct stimulatory action of gastrin and vagal excitation is enhanced on the parietal cells in SSTR(2) knockout mice. We suggest that there is a remodeling of the neuroendocrine mechanisms that regulate acid secretion in these mutant mice.

Hypergastrinemia increases gastric epithelial susceptibility to apoptosis

Plasma concentrations of the hormone gastrin are elevated by Helicobacter pylori infection and by gastric atrophy. It has previously been proposed that gastrin acts as a cofactor during gastric carcinogenesis and hypergastrinemic transgenic INS-GAS mice are prone to developing gastric adenocarcinoma, particularly following H. pylori infection. We hypothesised that the increased risk of carcinogenesis in these animals may partly result from altered susceptibility of gastric epithelial cells to undergo apoptosis. Gastric corpus apoptosis was significantly increased 48 h after 12Gy γ-radiation in mice rendered hypergastrinemic by transgenic (INS-GAS) or pharmacological (omeprazole treatment of FVB/N mice) methods and in both cases the effects were inhibited by the CCK-2 receptor antagonist YM022. However, no alteration in susceptibility to γ-radiation-induced gastric epithelial apoptosis was observed in mice overexpressing progastrin or glycine-extended gastrin. Apoptosis was also significantly increased in gastric corpus biopsies obtained from H. pylori-infected humans with moderate degrees of hypergastrinemia. We conclude that hypergastrinemia specifically renders cells within the gastric corpus epithelium more susceptible to induction of apoptosis by radiation or H. pylori. Altered susceptibility to apoptosis may therefore be one factor predisposing to gastric carcinogenesis in INS-GAS mice and similar mechanisms may also be involved in humans.

Chronic Mesenteric Ischemia Presenting as Helicobacter pylori-Negative Duodenal and Gastric Ulcers. Case Report and Literature Review

Purpose: Vascular insufficiency syndromes involving arterial supply can rarely present with peptic ulceration that is unrelated to H. Pylori infection or NSAID use. Gastric ischemia is extremely rare, given the rich arterial supply to the stomach. We are reporting an 80-year-old female who presented to our hospital with approximately 10 week history of postprandial nausea, abdominal discomfort and occasional vomiting. She described the pain as dull band-like discomfort in the periumbilical region. She denied any diarrhea, constipation, melena orhematochezia. Esophagogastroduodenoscopy three weeks prior to admission revealed multiple gastric and duodenal ulcers. H. Pylori wor up was negative. Colonoscopy revealed right-sided diverticulosis. Her pain was progressively getting worse without improvement with the use of a proton-pump inhibitor. She lost 15 pounds over 3 months and had multiple visits to the emergency department. The patient had history of hypertension, hyperlipidemia and pelvic vein thrombosis. She had a history of tobacco smoking and did not consume alcohol or illicit drugs. Her medications included rabeprazole, Lipitor, Coumadin and metoprolol. She was recently taken off her Alendronate. She denied any use of corticosteroids or NSAIDs. No icterus was present. The abdomen was soft, nondistended and had normal bowel sounds. There was tenderness in the periumbilical and epigastric region to palpation without palpable masses or rebound tenderness. The patient had guaiac-negative stool. Laboratory studies revealed normal lipase, amylase and liver function tests. Gastrin concentration was 376 pg per milliliter (normal range 0–110). Abdominal CT was unremarkable. Abdominal Doppler, Abdominal MRA and later traditional angiography demonstrated occlusion of the proximal aspects of the celiac artery and superior mesenteric arteries. The patient underwent repair of her celiac and superior mesenteric axis by anterograde bypass. She tolerated the surgery well and was discharged in a stable condition. Ischemic peptic ulcer disease is seldom diagnosed. Certainly, the reconstitution of the patient's well-being after revascularization suggest that this very unusual combination was responsible for her clinical picture and the endoscopic findings. Conclusion: This case suggests that ischemia as an etiology for peptic ulcer disease should be considered in H. Pylori negative ulcers even in gastric ulcers.

Morphometric and immunohistochemical study of the abomasum of red deer during prenatal development

The red deer is well suited to scientific study, given its economic importance as an animal to be hunted, and because it has a rich genetic heritage. However, there has been little research into the prenatal development of the stomach of ruminants in general, and none for the red deer. For this reason, we undertook histological evaluation of the ontogenesis of the abomasum in red deer. Histomorphometric and immunohistochemical analyses were carried out on 50 embryos and fetuses from the initial stages of prenatal life until birth. The animals were divided for test purposes into five experimental groups: group I [1.4-3.6 cm crown-rump length (CRL); 30-60 days, 1-25% of gestation]; group II (4.5-7.2 cm CRL; 67-90 days, 25-35% of gestation); group III (8-19 cm CRL; 97-135 days, 35-50% of gestation); group IV (21-33 cm CRL; 142-191 days, 50-70% of gestation) group V (36-40 cm CRL; 205-235 days, 75-100% of gestation). In the organogenesis of the primitive gastric tube of red deer, differentiation of the abomasum took place at 67 days, forming a three-layered structure: the epithelial layer (pseudostratified), pluripotential blastemic tissue and serosa. The abomasal wall displayed the primitive folds of the abomasum and by 97 days abomasal peak areas were observed on the fold surface. At 135 days the abomasal surface showed a single mucous cylindrical epithelium, and gastric pits were observed in the spaces between abomasal areas. At the bottom of these pits the first outlines of glands could be observed. The histodifferentiation of the lamina propria-submucosa, tunica muscularis and serosa showed patterns similar to those described for the forestomach of red deer. The abomasum of red deer during prenatal life, especially from 67 days of gestation, was shown to be an active structure with full secretory capacity. Its histological development, its secretory capacity (as revealed by the presence of neutral mucopolysaccharides) and its neuroendocrine nature (as revealed by the presence of positive non-neuronal enolase cells and the neuropeptides vasoactive intestinal peptide and neuropeptide Y) were in line with the development of the rumen, reticulum and omasum. Gastrin-immunoreactive cells first appeared in the abomasum at 142 days, and the number of positive cells increased during development. As for the number of gastrin cells, plasma gastrin concentrations increased throughout prenatal life. However, its prenatal development was later than that of the abomasum in sheep, goat and cow.

Carcinogenic Hypergastrinemia: Signet-Ring Cell Carcinoma in a Patient with Multiple Endocrine Neoplasia Type 1 with Zollinger-Ellison’s Syndrome

Gastric neuroendocrine tumors are rare neoplasms that originate from gastric enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin and its derivates have been reported to regulate epithelial cell proliferation, migration, and differentiation. Mutations in the epithelial cadherin (E-cadherin) gene have been shown to be associated with the occurrence of diffuse gastric carcinomas in affected families. In this study we investigated the histopathological and molecular findings in the gastrointestinal wall of a patient with multiple endocrine neoplasia type 1 with malignant duodenal gastrinoma and multiple gastric ECL cell tumors, who additionally developed a signet-ring cell carcinoma of the stomach. Biopsies from the gastrointestinal tract of a patient with multiple endocrine neoplasia type 1 were immunostained for vesicular monoamine transporter-2 and E-cadherin. Nonamidated gastrin products were measured in the serum of the patient using antibodies that react with progastrin, Gly-extended, and amidated gastrins. Genetic analyses were performed to exclude germ-line mutations within the E-cadherin gene. Immunohistochemical studies of gastric ECL cell tumors showed a largely diminished E-cadherin expression in comparison to gastric surface mucosa cells and a loss of E-cadherin expression in the cells of the signet-ring carcinoma. Detailed biochemical measurements revealed progastrin concentrations that were approximately 20%, and Gly-gastrin concentrations that were approximately 10% the amidated gastrin concentrations in plasma. Molecular analyses revealed no E-cadherin germ-line mutation. Our immunohistochemical studies might suggest that the gastrinoma-associated excessive progastrin tissue concentrations led to diminished expression of E-cadherin within the gastric mucosa and promoted tumor development of a signet-ring cell carcinoma.