A review of spontaneous ulcer disease in domestic animals: chickens, cattle, horses, and swine.

The human species is perhaps unique for its high incidence of spontaneous, chronic ulcer of the glandular mucosa of the stomach and duodenum. Nevertheless, spontaneous ulcers, usually of the stomach, commonly occur in many domestic animals. Some of these lesions are chronic and they may occur in either the glandular or squamous-lined regions of the stomach. As with the human disease(s) the pathogenesis in domestic animals is multifactorial, poorly understood, and variable between and within species. Some parallelisms exist in aggressive and defensive factors, but parasitic factors, via gastrinemia, and a histaminic factor via diet may occur in some animal ulcers. Underlying environmental stresses, of debated importance with the human disease but of proven importance in several rat ulcer models, may play a key role in some spontaneous gastric ulcer situations in swine and cattle. This is manifest in crowding and transporting situations. Seasonal, age, and weaning factors also alter the incidence of ulcer in cattle. Psychologic/environmental stress-related factors, as well as drug and physiologic stress factors appear to upset the balance in the horse between resistance and aggressive mucosal factors. Dietary factors which are highly important in ulcer disease in swine and chickens, have not yet been incriminated in spontaneous, equine ulcer disease. More investigation of the pathogenesis of domestic animal ulcers will prove useful for both human and veterinary medicine in terms of a) elucidating pathogenetic mechanisms for all species, b) may provide new animal models for study, and c) may enhance prevention of such lesions in domestic animals for economic and humanitarian reasons.     

Gastroprotective,cytoprotective and antioxidant effects of Oleum cinnamomi on ethanol induced damage

Peptic ulcer disease is a gastrointestinal disorder defined by mucosal damage and free oxygen radicals associated with peptic ulcer and gastritis. Cinnamon is a traditional herb used for many diseases and it has also effects as an antioxidant, anti-inflammatory, antispasmodic and anti-ulcerative. Our research is based on oxidative stress and effects of Oleum cinnamomi on stomach, liver and kidney disorders induced by ethanol. In our experiment, 2–3 month old male Sprague–Dawley rats were used. One hour before the mucosal damage induced by 70 % ethanol, O. cinnamomi (2.5 ml/kg) was added into the groups. Gastric pH, analysis of gastric mucus and ulcer index were calculated from samples obtained from the stomach. Superoxide dismutase (SOD), malondialdehyde and catalase (CAT) levels were determined in stomach, liver and kidney homogenates and erythrocyte hemolysate. Histopathological examination of stomach, liver and kidney were determined with H&E staining. The non-treated ulcerative group showed higher scores than the control group which was treated with O. cinnamomi, when ulcer scores, gastric mucus and pH level of stomach are compared. Increased lipid peroxidation levels were observed in the liver, kidney and erythrocyte hemolysate. SOD activity was decreased in liver whereas increased in stomach of ethanol treated ulcerative groups. CAT levels were increased in stomach and liver of ethanol treated rats. Histopathological findings showed that ethanol treatment cause multiply organ damage such as stomach, liver and kidney injury. O. cinnamomi treatment protected these tissues from ethanol-induced damage. Consequently, the current investigation shows that O. cinnamomi has protective effects on ethanol-induced oxidative and mucosal damage.     

The results of Helicobacter pylori eradication on repeated bleeding in patients with stomach ulcer

The triple therapy of Helicobacter pylori eradication prevents repeated bleeding from stomach ulcer. The aim of this one-way blind prospective study was to evaluate the efficiency of the two-week triple therapy for Helicobacter pylori eradication in preventing renewed bleeding in patients with stomach ulcer within one year. This research included 60 hospitalized patients with bleeding stomach ulcer and positive Helicobacter pylori infection, 34 men and 26 women (average age 59.7 years). The patients were given therapeutic scheme of omeprazol--amoxicilin--metrodinazol (OAM) eradication for 14 days. Eradication of H. pylori infection was defined as lack of proof of the infection one month or several months after therapy suspension. By applying triple OAM therapy within two weeks the eradication was successful in 72%. In the group of 17 H. pylori positive patients there were 8 patients (47.6%) with repeated stomach ulcer and 3 patients (18%) with bleeding. Within the group of 43 H. pylori negative patients there were only 2 patients (4.65%) with repeated stomach ulcer and 1 patient (2%) with bleeding, during the observed period of 12 months. This research confirms the hypothesis about the necessity of eradication of Helicobacter pylori infection in patients with bleeding stomach ulcer as prevention of repeated bleeding.     

Protective and therapeutic effects of Argyreia speciosa against ethanol-induced gastric ulcer in rats

The protective and therapeutic effects of Argyreia speciosa Sweet (Convolvulaceae) against ethanol-induced gastric ulcer in rats were evaluated. Ethanolic and water extracts of the aerial plant parts (200 mg/kg body weight) were orally administered daily for seven days prior to or after ulceration with one oral dose of 1 mL absolute ethanol on 24-h empty stomachs. Rats were divided into eleven groups. Group 1 served as control. To groups 2 and 3 each extract was administered. Groups 4 to 6 received each extract or ranitidine (100 mg/kg body weight) prior to ulcer induction. Groups 7 to 9 received each extract or ranitidine post ulcer induction. Groups 10 and 11 were gastric ulcerative rats after one hour and one week of ethanol induction. The evaluation was done through measuring ulcer indices: stomach acidity and volume, lesion counts, mucus, and prostaglandin E2 contents. Oxidative stress marker, i. e. malondialdehyde, glutathione, and superoxide dismutase, were estimated. Certain marker enzymes for different cell organelles, i. e. succinate and lactate dehydrogenases, glucose-6-phosphatase, acid phosphatase, and 5'-nucleotidase, were evaluated. The work was extended to determine the collagen content and the histopathological assessment of the stomach. Gastric ulcer exhibited a significant elevation of the ulcer index, antioxidant levels, collagen content, and the marker enzymes. The water extract attenuated these increments and was more potent as a protective agent, while the ethanol extract exhibited stronger therapeutic potency. In conclusion, A. speciosa acted as antiulcer agent. More detailed studies are required to identify the compounds responsible for the pharmacological effect.     

大豆甙元磺酸钠对应激性胃粘膜损伤的影响及其机制探讨

目的：观察大豆甙元磺酸钠对力竭应激性渍疡的影响,探讨其可能的作用途径。方法：采用小鼠力竭性游泳,计数胃部溃疡点数建立应激溃疡模型,腹腔注射不同剂量的大豆甙元磺酸钠及一氧化氮合酶（NOS）抑制剂（L-NAME）并通过NADPH-黄递酶组织化学法检测胃壁NOS阳性神经元的变化。结果：大豆甙元磺酸钠具有保护胃粘膜的作用,且呈剂量效应;L-NAME可防止应激引起的胃粘膜损伤,L-NAME与有效剂量的大豆甙元磺酸钠联合使用后,大豆甙元磺酸钠对胃粘膜的保护作用明显增强;正常及应激小鼠胃壁NOS神经节数目基本不变,大豆甙元磺酸钠对正常小鼠胃壁NOS神经元影响不明显,而对应激小鼠胃壁单位面积及单个神经节内NOS阳性神经元数目均有显著降低作用。结论：应激时NO升高可导致溃疡,大豆甙元磺酸钠能够保护胃粘膜,其作用是通过抑制应激状态下NOS的升高,限制应激状态下NO过度升高,起到保护胃粘膜的作用。     

Immunohistochemical localization of basic fibroblast growth factor in the healing stage of mouse gastric ulcer

The aim of this study was to clarify the involvement of basic fibroblast growth factor (bFGF) in gastric ulcer healing. For this purpose, light and electron microscopic immunohistochemical studies for bFGF were performed using an experimental gastric ulcer model of mice. Ulceration was induced by the application of acetic anhydride to the serosal surface of the body of the stomach. Stomach tissues were investigated of mice at 5 days and 3 weeks respectively after treatment and also of untreated normal mice. Five days after treatment an ulcer was seen in the stomach of the experimental mice. Immunohistochemistry revealed that bFGF was localized in fibroblasts in the ulcer bed. The growth factor was distributed throughout the cytoplasm excluding organelles involved in the usual secretory system, such as rough endoplasmic reticulum, Golgi apparatus and secretory vacuoles. bFGF was also detected in the nucleus. Three weeks after treatment the surface of the ulcer lesion was completely covered by regenerated epithelium. The stomach tissues were immunohistochemically negative for bFGF both inside and outside the scar region; untreated normal stomach tissues were also negative for bFGF. These results suggest that the growth factor plays important roles in gastric ulcer healing.     

Interaction between prostacyclin and colchicine on the gastric mucosa of rat in different experimental ulcer models

The effect of prostacyclin and colchicine on the fundic gastric mucosa of adult female Wistar rats was investigated in stress (immobilization) and indomethacin induced ulcer models. Under prostacyclin treatment the ulcer index decreased significantly in both ulcer models. This effect was inhibited by colchicine. The nuclear volume of fundic epithelial cells increased significantly after application of either type of ulcerogenic stimulus. Prostacyclin did not influence the nuclear volume changes in stress ulcer, while it prevented this phenomenon in indomethacin-induced ulceration. Following colchicine treatment the nuclear volume decreased in both ulcer models. After combined prostacyclin and colchicine treatment the nuclear shrinkage remained unaltered in stress ulcer, while in indomethacin ulcer the nuclear volume decreasing effect of the separately administered drugs disappeared after combined treatment. The latter phenomenon was interpreted as an antagonistic interaction between prostacyclin and colchicine.     

The DOPA and dopamine content in the hypothalamus and brain stem of rats with an experimental stomach ulcer against a background of a course of acupuncture

In experiments on rats with experimental ulcer of the stomach (EUS) using spectrofluorometric method the increase of DOPA and dopamine (DA) in brain stem, has been revealed as well as DOPA in hypothalamus. Change of the level of DOPA takes place at an early stage of ulcer formation. Acupuncture (AP) inserts essential corrections into the distribution of catecholamines under study. So, the content of DOPA and DA in hypothalamus and particularly in the brain stem in rats with EUS against the background of AP sharply increases. It has been supposed that AP realizes its therapeutic influence during ulcer disease due to the alteration of catecholaminergic brain system.     

Seasonal variations of inflammation and ulcer incidence as assessed by upper digestive tract endoscopy

A retrospective analysis of 3650 endoscopies shows that frequency of inflammation and ulcer incidence both in the stomach and the duodenal bulb were similar in consecutive seasons of the year. The conclusion is drawn that there may be seasonal (circannual) factors which predispose aggression to mucosa both in the stomach and duodenum, which in turn leads to seasonal occurrence of inflammation as well as to ulcer incidence.     

胃溃疡对大鼠胃中HAP1表达的影响

建立冰乙酸性大鼠胃溃疡模型,采用ABC法进行免疫组织化学染色,观察并探讨胃溃疡对胃壁中HAP1(huntingtin as-soc iated protein 1,HAP1)表达的影响。结果溃疡组大鼠胃壁中HAP1阳性细胞数目及光密度与正常进食的大鼠相比显著增多。     

A method of inducing chronic gastric and duodenal ulcer by electrocoagulation in rats

The described method includes electrocoagulation of the serous membrane of the stomach or duodenum by means of surgical diathermy. Under Nembutal general anaesthesia laparotomy was done and a ball-tip electrode was applied to the exposed anterior wall of the stomach or duodenal bulb. At the site of its contact with the serosa coagulation developed visible as a white spot approximately the size of the electrode tip. The ulcerogenic process triggered in this way developed within three days after the procedure. A deep ulcer in the mucosa developing during that time assumed in the second week the shape of a crater. From that time on ulcer healing began and progressed as evidenced by gradual diminution of its size. Complete healing of an untreated ulcer occurred in most animals after about five weeks. The extent of the ulcer niche was determined under a stereoscopic microscope calculating its area in mm2. A comparison of ulcer area in the animals treated with drugs inducing ulcer healing with this area in control rats made possible quantitative evaluation of the therapeutic effect.     

Certain Mechanisms regulating cell renewal in the gastric mucosa in peptic ulcer

A study was made of the effect of an aqueous extract of human gastric mucosa on the mitotic activity of the surface epithelium of the mouse stomach. The extract was found to exert a statistically significant inhibitory action. An extract from the mucosa of the stomach resected for duodenal ulcer exerted a more pronounced inhibitory action as compared with an extract from the stomach resected for gastric ulcer. This fact may be accounted for by a greater content of mature differentiated cells in duodenal ulcer. Tissue-specific action of gastric chalone is indicated by the absence of mitotic inhibition in the small intestinal mucosa.     

Dynamics of DNA synthesis in the gastric mucosa in ulcer

Anomalous DNA synthesis was seen in the stomach mucosa of mice with experimental stomach ulcer during different phases of the ulcerous process, using histoautoradiography. At the early stage of ulcer formation a decrease in the label index (LI) is seen. Formation of the ulcer, morphologically similar to the shronic one, is accompanied by growth of the number of DNA-synthesizing cells in its margins. Over a period of ulcer healing proliferative activity of epithelium decreases approximately to an initial level. Histoautoradiographic studies of bioptates of the stomach mucosa obtained under spot gastroscopy in patients suffering from the ulcerous disease allowed to reveal intensifying proliferative activity of epithelium in the ulcer margins. Similar changes in LI were found in gastritis, followed by the gland affection, and in atrophic gastritis.     

Role of bone marrow derived-mesenchymal stem cells against gastric ulceration: Histological,immunohistochemical and ultrastructural study

The current study aimed to assess the antiulcerogenic impact of mesenchymal bone marrow stem cells (BMMSCs) against gastric ulcer induced by the use of piroxicam in rats and to compare this effect with the antiulcer drug “Pantoloc ®” proton pump inhibitors. The study included histological, histochemical, immunohistochemical and ultrastructural examination in stomach of rats in different study groups. In the ulcerated group, the glandular region of the stomach displayed clear mucosal lesions occurring as perforations along the stomach axis. In addition, stomach displayed degeneration of surface mucous cells accompanied by pyknosis, vacuolation among parietal cells in ishmus region, basal region with vacuolated chief cells and karyolitic nucleus of parietal cells. Moreover, Stomach sections of ulcer model rats showed intensive immunoreactivity to cytokeratin 20, Cox 2 and PCNA. Findings of the present study have shown that BMMSCs have an ameliorative effect against piroxicam-induced gastric ulcer in rats. Collectively, the proposed work has shown that BMMSCs have a curative capacity as an antiulcer due to their high antioxidant activity. Further studies are required in molecular levels to understand the mechanism of action during treatment.     

Increased frequency of activated T-cells in the Helicobacter pylori-infected antrum and duodenum

Helicobacter pylori colonize the human stomach and duodenum. The infection has been shown to induce a strong T-cell response in the stomach, whereas the response within the duodenum has been poorly characterized. Furthermore, it remains to be elucidated whether the T-cell response may contribute to ulcer formation in the host. In this study, the frequency of different T-cell subsets, their degree of activation and expression of co-stimulatory receptors in biopsies from the duodenum as well as the antrum were studied by immunohistochemistry and flow cytometry. It was also evaluated whether there are differences in the T-cell responses between duodenal ulcer patients and asymptomatic carriers that might explain why only 10-15% of the infected subjects develop duodenal ulcers. The frequencies of CD4+, CD8+ and CD45RO+, i.e. memory T-cells, were significantly increased in the antrum, and the number of CD25+ cells was considerably higher in both the antrum and duodenum of duodenal ulcer patients and asymptomatic carriers as compared to uninfected individuals. Interestingly, the levels of immunosuppressive CTLA-4+ cells were significantly higher in the duodenum of duodenal ulcer patients, as compared to the asymptomatic carriers. H. pylori cause activation of T-cells in the duodenum as well as in the stomach. Our observation of higher levels of CTLA-4+ cells in the duodenum of duodenal ulcer patients than in the asymptomatic carriers suggests that a suppressive T-cell response may be related to the development of duodenal ulcers.     

Somatostatin depletion of the gut and pancreas induced by cysteamine is not prevented by vagotomy or by dopamine agonists

The role of endogenous somatostatin in the pathogenesis of duodenal was investigated in the present study by using the cysteamine animal model of the disease. Our previous studies showed a rapid and multiorgan depletion of somatostatin immunoreactivity (SIR) in rats given a single dose of duodenal ulcerogen cysteamine. We now determined whether acetylcholinergic and dopaminergic modulation (both known to influence the development of duodenal ulcer) are accompanied by modification of cysteamine-induced SIR depletion in rat organs. Vagotomy performed either 1 or 18 h before cysteamine administration did not interfere with the chemically induced SIR decrease in pancreas, gastric and duodenal mucosa. Vagal denervation alone had no marked influence on SIR levels but if combined with cysteamine, the SIR depletion in the stomach was significantly more pronounced than after the duodenal ulcerogen alone. Pretreatment with the dopamine agonists bromocriptine or lergotrile (known to prevent the chemically induced duodenal ulcers) did not influence the SIR depletion by cysteamine. Thus cysteamine depletes endogenous somatostatin in peripheral organs (e.g., stomach, duodenum, pancreas) by mechanisms independent of both vagus nerve and dopamine agonists. A role of central somatostatin depletion leading to disinhibition of vagus is also considered in the pathogenesis of experimental duodenal ulcer.     

Comparative study of perturbations of peripheral markers in different stressors in rats

Stress has been implicated in the etiopathogenesis of several diseases. In the present study, the effects of acute (AS), chronic (CS), and chronic unpredictable stress (CUS) were studied on the ulcer index, adrenal gland mass, and biochemical and hormonal changes in rats. The stress was provided in the form of immobilization-immobilization for 150 min, once only, and for 10 consecutive days in CS and CUS. In CUS, animals received variable unpredictable stressors. Immediately after stress, animals were decapitated, blood was collected, and plasma was separated for the estimation of plasma glucose, triglyceride, cholesterol, creatine kinase (CK), corticosterone, and insulin. The adrenal gland and stomach were also dissected for mass and ulcer scoring, respectively. AS significantly increased the ulcer index, plasma glucose, CK, corticosterone, and insulin. CS and CUS significantly increased the ulcer index, adrenal gland mass, and corticosterone. In CS, a significant decrease in plasma triglyceride and cholesterol levels was found, but in CUS only cholesterol was decreased significantly. High CK activity and hyperglycemia maintain the energy demands of metabolism, and elevated corticosterone desensitizes the insulin receptor in AS. In CS and CUS, prolonged elevation of corticosterone shifts metabolism to utilization of lipids as a secondary substrate by gluconeogenesis. From our experiment, it is clear that AS causes maximum activation of energy metabolism, which becomes specific after habituation in prolonged CS. These biochemical manipulations in the body by using different types of stressors are good markers that can be of great use to understand, target, and manage stress-induced etiologies.     

Changes in the intensity of protein synthesis in the gastric mucosa following the laser irradiation of a duodenal ulcer]

The intensity of protein synthesis (incorporation/pool) is usually low in normal stomach mucosa and enhanced in exacerbation of peptic ulcer; following the effective laser therapy it decreases only in one third of cases. Therefore the scarring of ulcer not always coincides with the normalization of protein synthesis. The results characterize also the community of reactions in stomach and duodenal mucose membranes. The changes in protein synthesis intensity following the laser irradiation depended neither on the initial size of ulcer nor on the age of patient and the total duration of disease.     

Experimental bases of endoscopic correction of the secretory function of the stomach

The article gives experimental data proving the usage of the method of bloodless reduction of gastric secretion through endoscope in case of peptic ulcer. Pricking around the secretory zones of the stomach with hypertonic glucose solution conducted on 35 mongrel dogs led to a stable reduction of acid producing function of the stomach. Morphological changes of the stomach mucous membrane were mainly expressed in the atrophy of glands. The analysis of the test results gives opportunity to recommend the clinical introduction of the method in complex treatment of peptic ulcer.     

Plants of the American continent with antiulcer activity.

Peptic ulcer is a chronic and appalling disease. Today, it is dominant among the diseases that affect the world's population. The principal factors causing this disease are inadequate dietetic habits, prolonged use of non-steroidal anti-inflammatory drugs, stress and infection by Helicobacter pylori, in addition to other factors of genetic origin. The present work is a literature survey of plant extracts from the American continent that have been reported to show antiulcer activity. This review refers to 58 plants with their families, parts used, type of extract used, model bioassays and their activity. This work intends to aid the researchers in the study of natural products appropriate to the treatment of stomach and intestinal diseases, in general, and peptic ulcer in particular.