Gastric and duodenal mucosal ornithine decarboxylase and damage after corticosterone

1990 ◽  
Vol 258 (6) ◽  
pp. G942-G950 ◽  
Author(s):  
J. Y. Wang ◽  
L. R. Johnson
Keyword(s):  
Gastric Mucosa ◽  
Ornithine Decarboxylase ◽  
Single Injection ◽  
Plasma Corticosterone ◽  
Duodenal Mucosa ◽  
Surface Epithelium ◽  
Xiphoid Process ◽  
Maximum Increase ◽  
Dna And Rna ◽  
Microscopic Damage

We recently found that stress increases gastric and duodenal ornithine decarboxylase (ODC) activity and damages both tissues. The current study investigated whether corticosterone induces ODC activity in gastric and duodenal mucosa in rats and compared plasma corticosterone levels after stress and treatment with corticosterone to determine whether this hormone mediated the effects of stress on the mucosa. Rats were fasted 22 h, placed in a restraint cage, and immersed in water to the xiphoid process for 6 h. Stress markedly increased plasma corticosterone levels; the increase was 10.5 times control and lasted the duration of stress. The maximum increase was observed 1 h after a single injection of corticosterone (5 mg/kg sc) and represented 11.1 times control values. By 6 h, plasma corticosterone had returned to normal levels. A single injection of corticosterone had no effect on the gastric mucosa, but duodenal ODC was increased significantly from 4 to 8 h after injection, peaking at 6 h. Histological examination revealed no damage in either tissue. Administration of corticosterone three times daily for 3 days dramatically elevated ODC activity and produced significant microscopic damage. The surface epithelium of the stomach was disrupted, with many surface cells shed, and most villi were absent from the duodenal mucosa. Corticosterone also markedly decreased DNA and RNA content of both tissues. Inhibition of ODC with DL-alpha-difluoromethylornithine additionally decreased DNA, RNA, and protein content, exacerbating the damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Induction of gastric and duodenal mucosal ornithine decarboxylase during stress

1989 ◽  
Vol 257 (2) ◽  
pp. G259-G265 ◽  
Author(s):  
J. Y. Wang ◽  
L. R. Johnson
Keyword(s):  
Enzyme Activity ◽  
Protein Content ◽  
Ornithine Decarboxylase ◽  
Duodenal Mucosa ◽  
Xiphoid Process ◽  
Dna And Rna ◽  
Microscopic Damage ◽  
Oxyntic Gland ◽  
Degree Of Damage ◽  
Microscopic Inspection

The purpose of this study was to determine whether gastric and duodenal mucosal ornithine decarboxylase (ODC) activity increased during a period of ulcer-producing stress and whether changes in enzyme activity altered the severity of damage. Rats were fasted for 22 h, placed in a restraint cage, and immersed in water to the xiphoid process for different times lasting from 2 to 8 h. After 6 h, stress slightly increased gastric mucosal ODC and caused a sevenfold increase in duodenal mucosal ODC activity. Macroscopic ulcers developed in the oxyntic gland mucosa but not duodenal mucosa. Interestingly, however, after 6 h microscopic inspection showed an absence of most villi from the duodenum. DNA, RNA, and protein content of both tissues decreased over the time rats were exposed to stress. DL-alpha-Difluoromethylornithine (DFMO, a specific ODC inhibitor) prevented the increase in ODC in both tissues and increased the loss of DNA and RNA from duodenal mucosa. The degree of damage was not altered by DFMO in either tissue in response to 6 h of stress. These results show that 1) stress causes microscopic damage to the duodenum, 2) stress increases ODC in both gastric and duodenal mucosa, and 3) the inhibition of ODC during 6 h of stress does not alter the severity of damage.

Expression of protooncogenes c-fos and c-myc in healing of gastric mucosal stress ulcers

1994 ◽  
Vol 266 (5) ◽  
pp. G878-G886 ◽  
Author(s):  
J. Y. Wang ◽  
L. R. Johnson
Keyword(s):  
Gastric Mucosa ◽  
Ornithine Decarboxylase ◽  
Thymidine Incorporation ◽  
Healing Process ◽  
Mucosal Healing ◽  
Xiphoid Process ◽  
Stress Ulcers ◽  
Polyamine Biosynthesis ◽  
Polyamine Synthesis ◽  
Oxyntic Gland

The current study determines the hypothesis that expression of protooncogenes c-fos and c-myc is involved in the mechanism of polyamine-stimulated healing in gastric mucosal stress ulcers. Rats were fasted 22 h, placed in restraint cages, and immersed in water to the xiphoid process for 2-6 h. Animals were killed either immediately after stress or at 2-h intervals up to 24 h after 6 h of stress. Stress caused both visible lesions and induction of ornithine decarboxylase (ODC) activity in the oxyntic gland mucosa after 2 h. Increased ODC activity was paralleled by increases in the mucosal polyamines putrescine, spermidine, and spermine. Exposure to stress led to appearance of c-fos mRNA and oncoprotein in the gastric oxyntic gland mucosa at 2 h and its disappearance by 4 h. Baseline expression of c-myc was enhanced significantly after 6 h of stress and remained elevated for 4 h. This change in the expression of c-fos and c-myc mRNA and oncoprotein preceded an increased rate of [3H]thymidine incorporation into mucosal DNA. Administration of alpha-difluoromethylornithine (DFMO, 500 mg/kg ip) totally prevented the marked increases in ODC activity and polyamine levels. DFMO also completely inhibited the expression of c-fos and significantly decreased c-myc mRNA and oncoprotein in the gastric mucosa of stressed rats. The healing process, which was significant by 12 h, was markedly inhibited by DFMO. These results show that 1) mucosa exposed to stress exhibits increased expression of c-fos and c-myc following increased polyamine synthesis and 2) inhibition of polyamine biosynthesis by DFMO decreases both protooncogene expression and mucosal healing.

Relationship between ornithine decarboxylase activity and gastric damage

1987 ◽  
Vol 253 (1) ◽  
pp. G1-G6
Author(s):  
C. H. Thirumalai ◽  
C. C. Tseng ◽  
K. Tabata ◽  
L. R. Fitzpatrick ◽  
L. R. Johnson
Keyword(s):  
Gastric Mucosa ◽  
Protein Content ◽  
Ornithine Decarboxylase ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
Intragastric Administration ◽  
Decarboxylase Activity ◽  
Nacl Concentration ◽  
Gross Lesions ◽  
Microscopic Damage

Hypertonic NaCl increases the activity of gastric mucosal ornithine decarboxylase (ODC). Intragastric administration of concentrated NaCl solution also induces ulcers in the glandular gastric mucosa. The relationship between ODC activity and gastric mucosal damage and the significance of ODC increases in hypertonic NaCl-treated rats are unknown. Rats were fasted 24 h before being given 1.0 ml of 3.4 M NaCl, 120 mM aspirin in 100 mM HCl or 50% ethanol intragastrically. The oxyntic gland mucosa was removed and assayed for ODC and in some experiments DNA, RNA, and protein content. DNA, RNA, and protein content were decreased by 3.4 M NaCl, and these decreases were much greater if ODC was inhibited by pretreatment with alpha-difluoromethylornithine (DFMO). Both aspirin and 3.4 M NaCl induced ODC activity 6 h later. However, DFMO increased the lesion index only in NaCl-treated rats. Although ethanol produced damage, it had no effect on ODC levels, and DFMO did not alter the severity of ethanol lesions. When different concentrations (0.4, 0.8, 1.6, 2.5, and 3.4 M) of NaCl were administered, ODC activities were increased 6 h later in rats receiving 1.6, 2.5, and 3.4 M NaCl but not lower concentrations. Gross lesions appeared in response to the 2.5 M dose and increased with increasing NaCl concentration. However, microscopic damage of the gastric mucosa occurred at all the concentrations tested. These data show that 1) ODC activation is not necessarily produced by damage, 2) in the case of NaCl, increasing damage increases ODC, and 3) ODC appears to have a role in the prevention of a recovery to damage caused by NaCl.

scholarly journals Duodenal Bulb Mucosa with Hypertrophic Gastric Oxyntic Heterotopia in Patients with Zollinger Ellison Syndrome

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Emil Kohan ◽  
David Oh ◽  
Hank Wang ◽  
Salar Hazany ◽  
Gordon Ohning ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Gastric Acid ◽  
Duodenal Bulb ◽  
Duodenal Mucosa ◽  
Heterotopic Gastric Mucosa ◽  
Blue Staining ◽  
Surface Epithelium ◽  
The Novel ◽  
Zollinger Ellison Syndrome ◽  
Gastric Type

Objectives. Zollinger-Ellison Syndrome (ZES) results in hypersecretion of gastric acid (via gastrinoma) leading to peptic ulcers, diarrhea, and abdominal pain. We describe the novel discovery of hypertrophic, heterotopic gastric mucosa in the proximal duodenal bulb in patients with ZES, which we hypothesize results in an increased incidence of postbulbar ulcers in patients with ZES (a mechanism previously unreported). We determined the incidence of the novel finding of duodenal gastric oxyntic hypertrophic heterotopia (GOH) in patients with ZES. Methods. Seven patients with ZES were enrolled. The diagnosis of ZES was established by hypergastrinemia, gastric acid hypersecretion, and a positive secretin test or based on biopsy specimens (evaluated via tissue staining). Basal acid output (BAO) and baseline gastrin secretion were determined by established methods. Endoscopic examinations with methylene blue staining and biopsy of the gastric and duodenal mucosa were conducted in all patients every 3–6 months for an average of 5 years. Results. The duodenal mucosa demonstrated hypertrophic GOH in 5 out of 7 patients with ZES and an intact stomach and duodenum. Biopsies from the bowel mucosa demonstrated patchy replacement of surface epithelium by gastric-type epithelium with hypertrophic oxyntic glands in the lamina propria in 5 patients. Two of the patients had no evidence of GOH in the duodenal bulb. Patients with GOH had an average serum gastrin level of 1245 pg/mL and BAO of 2.92 mEq/hr versus 724 pg/mL and 0.8 mEq/hr in patients without GOH. Conclusions. This study demonstrated the presence of duodenal mucosa with GOH in 5 out of 7 patients with ZES and an intact stomach and duodenum. The presence of hypertrophic and heterotopic gastric mucosa is proposed to result from increased gastrin levels and may contribute to the increased incidence of postbulbar ulcers in these patients.

Role of ornithine decarboxylase in repair of gastric mucosal stress ulcers

1990 ◽  
Vol 258 (1) ◽  
pp. G78-G85 ◽  
Author(s):  
J. Y. Wang ◽  
L. R. Johnson
Keyword(s):  
Enzyme Activity ◽  
Gastric Mucosa ◽  
Ornithine Decarboxylase ◽  
Specific Inhibitor ◽  
Xiphoid Process ◽  
Stress Ulcers ◽  
Gastric Mucosal Lesions ◽  
Mucosal Lesions ◽  
Extensive Damage

The purpose of this study was to determine whether ornithine decarboxylase (ODC) has a role in mucosal repair during the first 24 h after stress-induced damage. Rats were fasted 22 h, placed in a restraint cage, and immersed in water to the xiphoid process for 6 h. Animals were killed either immediately after the period of stress or at 2-h intervals up to 24 h thereafter. Gastric mucosal ODC increased significantly from 0 to 12 h and peaked 4 h after the 6-h stress period. By 24 h enzyme activity in the gastric mucosa was near normal. Macroscopic lesions were regularly produced after 6 h of stress. Histologically, stress caused extensive damage to the superficial epithelial cells, extending in some cases into the mucosa and beyond the basal lamina. However, after stress the mucosa recovered quickly, returning to near normal 24 h later. The decreases in mucosal content of DNA, RNA, and protein caused by stress also were restored and reached near-normal levels 24 h after stress. alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ODC, not only inhibited the ODC activity but significantly delayed the recovery from injury as well. DFMO also prevented the restoration of DNA, RNA, and protein content of the gastric mucosa. In conclusion, stress-induced gastric mucosal lesions are accompanied by significant increases in ODC activity. The increased ODC is necessary for the normal repair of the mucosa.

Polyamine synthesis in liver and kidney of flounder in response to methylmercury

1976 ◽  
Vol 231 (2) ◽  
pp. 560-564 ◽  
Author(s):  
CA Manen ◽  
B Schmidt-Nielsen ◽  
DH Russell
Keyword(s):  
Ornithine Decarboxylase ◽  
Single Injection ◽  
Recovery Phase ◽  
Winter Flounder ◽  
Decarboxylase Activity ◽  
Pseudopleuronectes Americanus ◽  
Toxic Dose ◽  
Polyamine Synthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Liver And Kidney

The effect of methylmercury administration on polyamine synthesis was studied in the liver and kidney of the winter flounder (Pseudopleuronectes americanus). A single injection of methylmercury resulted in five- and sevenfold elevations of ornithine decarboxylase activity in the liver and kidney within 15 and 45 h, respectively. There were elevations of both putrescine- and spermidine-stimulated S-adenosylmethionine decarboxylase activities (approximately 1.5-fold) in both tissues. Evaluation of the polyamine accumulation patterns in these tissues indicated that in the liver all three polyamines increased in concentration until 48 h and then decline. In the kidney, the concentration of putrescine increased steadily until it was 200% of control at 72 h and then declined. Spermidine concentration decreased throughout the time studied and was 17% of control at 1 wk. There was no significant change in the concentration of spermine throughout the period studied. The changes in the polyamine pools and in the activities of the polyamine biosynthetic enzymes after methylmercury administration are consistent with an involvement of the polyamines in the recovery phase to a toxic dose of methylmercury.

scholarly journals Expression of apoptotic and proliferation factors in gastric mucosa of patients with systemic sclerosis correlates with form of the disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Katarina Boric ◽  
Snjezana Mardesic ◽  
Dusanka Martinovic Kaliterna ◽  
Mislav Radic ◽  
Ivana Tadin Hadjina ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Gastric Mucosa ◽  
Caspase 3 ◽  
Smooth Muscle Actin ◽  
Surface Epithelium ◽  
Gastric Disease ◽  
Loss Of Function ◽  
Ki 67 ◽  
Deposition Surface ◽  
High Prevalence

AbstractDespite high prevalence of patients with gastric disease in systemic sclerosis (SSc), its pathogenesis is still poorly understood. We immunohistochemically analysed biopsies of gastric mucosa (GM) in 5 controls and 15 patients with different forms of SSc: limited cutaneous (lc), diffuse cutaneous moderate (sys1) and severe (sys2). The number of positive cells was analysed by a Kruskall-Wallis test, P < 0.05 was considered statistically significant. Percentage of proliferating (Ki-67 positive) cells was highest in sys1 (3% in superficial and 4,6% in deeper parts of GM), which dropped to 1% in sys2. Percentage of α-smooth muscle actin (α-SMA) positive cells was 5% in controls, 9% in superficial GM, while in deeper GM rose from 7% to 19% in sys1 and sys2, thus indicating increased myofibroblast population. Caspase-3 positive apoptotic cells characterized 1,5–2% of controls, 8% of superficial and 6% of deeper GM cells in sys1. In sys2, apoptosis affected 50% of surface epithelial and gland cells and 30% of deeper glands, and correlated with increased fibrosis and decreased syndecan-1 expression. Our data demonstrate that sys1 is the most „active” proliferating form of SSc. Sys2 characterize collagen deposition, surface epithelium defects, extensive apoptosis and low proliferation, GM atrophy and loss of function.

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