Helicobacter pylori affects the quality of experimental gastric ulcer healing in a new animal model.

Helicobacter pylori has been implicated in the genesis of human gastritis, dyspepsia, and peptic ulcers. However, its influence in the quality of experimental gastric ulcer healing has not been previously investigated. Standardized gastric fundic ulcers were produced in 50 male Sprague-Dawley rats (150-200 g) by a 4 mm in diameter focal, serosal application of 100% acetic acid. Thirty rats were administered 2 ml H. pylori suspension (urease producing, ATCC 43504) in normal saline (10(8) CFU/ml) 2x/day for 7 days. Twenty rats (controls) received 2 ml normal saline 2x/day for 7 days. Gastric ulcer surface area was measured under a dissecting microscope and mucosal specimens were obtained for qualitative and quantitative histology. No gross or microscopic duodenal abnormalities were identified at sacrifice. Ninety percent of control rats showed grossly and microscopically entirely healed ulcers. The remaining 10% showed partially reepithelialized ulcers (area, 0.78 to 1.77 mm2; mean, 1.27 +/- 0.7 mm2). The grossly "healed" mucosa demonstrated marked dilatation of gastric glands lined with mature surface epithelial cells. Parietal cells were scanty (5-10% of all cells). One hundred percent of the H. pylori-exposed rats showed persistence of chronic active ulcers (area, 1.76 to 19.63 mm2; mean, 8.95 +/- 6.15 mm2). The ulcer beds were infiltrated by acute and chronic inflammatory cells, abundant fibroblasts, and capillary networks. The raised ulcer borders were characterized by dilated glands lined by mature surface epithelial cells. Various special stains demonstrated the presence of H. pylori in the surface mucus and within the crypts.(ABSTRACT TRUNCATED AT 250 WORDS)     

大鼠实验性胃溃疡自愈期间胰岛PP细胞的免疫组织化学研究

目的 探讨胰多肽在大鼠胃溃疡自愈期间的可能作用及意义.方法 应用免疫组织化学PAP法、形态计量和图像分析法,研究大鼠胃溃疡自愈期间胰岛PP细胞的形态学、细胞的面数密度(NA)及平均灰度变化.结果 与正常组和盐水组比较,胃溃疡组大鼠胰岛PP细胞NA于溃疡第6d明显下降,平均灰度值升高(P＜0.05);溃疡第10～28d,PP细胞NA升高、平均灰度值下降(P＜0.05);尤以第10d最明显.胰岛PP细胞免疫组织化学的形态观察结果与同期图像分析结果基本一致.结论 胰岛PP细胞在实验性胃溃疡自愈期间,其细胞NA和平均灰度均发生改变.提示PP细胞参与了胃溃疡自愈的调节过程.     

Influence of nonsteroidal anti-inflammatory compounds on healing of chronic gastric ulcers in rats

Pre-treatment with NOSAC led to an increase of ulcer index in a dose-dependent manner indicating the aggravation of gastric lesions under the influence of NOSAC. The severity of mucosal lesions was diminished by lengthening the time between the last day of pre-treatment with NOSAC and the day on which ulcers were induced. When NOSAC were administered after the induction of gastric ulcers, the healing of the latter was significantly delayed.     

Clinicopathological features of duodenal bulb biopsies and their relationship with upper gastrointestinal diseases

AimTo assess the prevalence of the lesions in duodenal bulb mucosa and the relationship between duodenal lesions and upper gastrointestinal diseases, including helicobacter pylori infection.MethodsClinical, endoscopic and pathological data of the cases with duodenal bulb and gastric mucosal biopsy from January 2005 to May 2017 were analyzed retrospectively.ResultsA total of 3540 patients were enrolled. The biopsy from protuberant lesions with endoscopic morphology are mostly duodenal gastric heterotopia or adenoma. The biopsy from duodenal ulcers are often observed in inflammatory changes and gastric metaplasia.Patients with gastric heterotopia had a significantly lower prevalence of chronic atrophic gastritis, intestinal metaplasia, and gastric ulcer; and much higher prevalence of gastroesophageal reflux disease and gastric fundic polyps.Patients with gastric metaplasia had been positively associated with gastroesophageal reflux disease, and negatively associated with gastric fundic polyps.There were positive correlation between helicobacter pylori infection and duodenal active inflammation, Brunner gland hyperplasia, gastric metaplasia and duodenal ulcer. However, Patients with gastric heterotopia in bulb had been negatively associated with helicobacter pylori infection.ConclusionsThe mucosa lesions in duodenal bulb were associated with concurrent gastric fundic gland polyps, gastroesophageal reflux disease, duodenal ulcer, and helicobacter pylori infection.     

大鼠实验性胃溃疡自愈期间垂体远侧部ACTH细胞的免疫电镜研究

用成年雄性Ｗｉｓｔａｒ大鼠，分为溃疡组和对照组。用免疫电镜包埋后免疫金间接法村记ＡＣＴＨ细胞，研究胃溃疡自愈过程中垂体远侧部ＡＣＴＨ细胞的超微结构变化，结果显示，在实验性胃溃疡第４ｄ，一些ＡＣＴＨ细胞含少量很小的分泌颗粒，沿质膜分布，有较多的ＡＣＴＨ细胞胞质出现许多空泡。溃疡第６ｄ，ＡＣＴＨ细胞的高尔基复合体发达，其扁囊膨大部含中等电子密度的内容物，其内可见金颗粒标记。溃疡６－１０ｄ，较多的ＡＣＴ     

Repair processes in the rat stomach with indolent experimental ulcers

A gastric ulcer was induced in rats by burning with acetic acid by Okabe's method. Repair processes in the gastric mucosa in the zone of the ulcer defect and adjacent fundal glands and also at a distance from the ulcer were studied by quantitative methods (determination of the cell composition of the glands, counting the daily number of DNA-synthesizing cells and the number of mitoses). On the 15th day after formation of the ulcer the level of proliferation in this zone was found to be much higher than in the control, whereas at a distance from the ulcer it was unchanged. On the 40th day regeneration took place with an even higher rise in the level of DNA synthesis and cell division. By this time the number of regenerating glands and the total number of cells forming them had increased. Similar changes were found up to 180 days close to the suture in glands of the resected rat stomach.Laboratory of Growth and Development, Institute of Human Morphology, Academy of Medical Sciences of the USSR, Moscow. Laboratory of Gastroenterology, Research Institute of Balneology and Physiotherapy, Pyatigorsk. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 2, pp. 226–229, February, 1980.     

Intestinal metaplasia of the regenerative epithelia in 549 gastric ulcers

Histopathologic changes in the regenerative epithelia of 549 foci of gastric ulcer were studied. About 70 per cent of the regenerative epithelia revealed intestinal metaplasia of the so-called complete or incomplete type. Parietal cells and chief cells were occasionally observed in the regenerative epithelia of ulcers located in fundic gland areas or at fundopyloric gland borders. It is possible that the regenerative epithelium frequently reverts to intestinal epithelium during the regenerative process, later redifferentiating into normal gastric mucosa or remaining as intestinal metaplasia and that, thus, only a few foci of intestinal metaplasia are precancerous lesions.     

An immunocytochemical study of regeneration of gastric epithelia in rat experimental ulcers

We experimentally observed the process of regeneration of gastric mucosal cells in ulcers induced by surgical removal of the fundic mucosa of rats. The techniques utilized were immunocytochemistry, laser confocal microscopy, and transmission electron microscopy (TEM). Routine TEM and PAS reaction were used for parietal cells, chief cells, and mucous cells. As markers of parietal cells, H⁺-K⁺ ATPase, Na⁺-K⁺ ATPase, carbonic anhydrase, and aquaporin 4 (AQP4) were used, and for chief cells pepsinogen was used. Healing process of mucosal defect was as follows. On day 2 after the operation, the single-layered regenerating epithelium (RE) originating from the marginal epithelium of the ulcer extended over the granulation tissue of the ulcer base towards the center. Regenerating glands (RGs) appeared in the ulcer margin. The cells appearing first in the RE were undifferentiated cells that had a high nucleus: cytoplasm ratio and abundant free ribosomes. On day 5, the ulcer was almost filled with RGs. Most cells stained positive for PAS reaction. A few immature parietal cells stained weakly with H⁺-K⁺ ATPase, Na⁺-K⁺ ATPase, carbonic anhydrase, and aquaporin-4 antibodies, and a few immature chief cells stained weakly with pepsinogen antibody were also observed on day 5. On day 10, the ulcer was filled with RGs. The RGs in the periphery of the ulcer stained positive for markers of mature parietal cells and chief cells, whereas the center of the ulcer was composed of immature parietal cells and chief cells. By day 25, the mucosal defect was filled with normal gastric glands formed by maturation of the RGs. The undifferentiated cells that first appeared in the ulcer margin seem to differentiate to special functioning cells of the stomach 5–10 days after ulcer formation.     

Microcirculatory disturbances in gastric mucosa during ulcer disease and effects of serotonin on their dynamics

Experiments on rat model of stress-induced gastric ulcers revealed marked circulatory disturbances in ulcerated gastric mucosa associated with arteriolar spasm and venous congestion and leading to perivascular edema, diapedesis of erythrocytes, and microhemorrhages. These changes were most pronounced on day 1 after ulcer modeling and progressively decreased during healing (day 14–21). On day 3, arterial hyperemia developed against the background of venous congestion, which was probably related to progressive repair. Serotonin adipinate administered after ulcer modeling accelerated the development of arterial hyperemia (day 1) and reduced venous congestion and extravascular changes. Pretreatment with serotonin was even more effective in attenuating venous congestion and extravascular changes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 9, pp. 268–271, September 2000     

大鼠实验性胃溃疡自愈期间胰岛A细胞的结构和功能变化

目的　探讨胰岛Ａ细胞参与溃疡自愈调节的可能途径。　方法　应用形态计量、放射免疫测定及透射电镜方法，研究大鼠实验性胃溃疡自愈期间胰岛Ａ细胞的面数密度、超微结构及血清胰高血糖素的变化。　结果　与正常组及盐水组比较，Ａ细胞面数密度于溃疡后６ｄ、１０ｄ 明显增加（Ｐ＜ ０．０１）。溃疡后１４ｄ 开始呈减小趋势，２８ｄ 基本恢复正常。Ａ细胞超微结构变化在溃疡后第６～１４ｄ 较明显，主要表现为：（１）细胞核增大，异染色质减少，核周隙扩张；（２）部分Ａ 细胞粗面内质网增多，有的呈板层状排列，有的扩张成囊泡；（３）部分Ａ 细胞内分泌颗粒增多，大小不等，密度不一。血浆胰高血糖素水平从溃疡后１４ｄ 到２１ｄ 呈增高趋势（Ｐ＜ ０．０１），２８ｄ 时接近正常。　结论　胰岛Ａ细胞的形态和功能变化表明，它通过增加其细胞数目及增强其合成与分泌胰高血糖素的功能，积极参与了胃溃疡自愈的调节过程。     

Roles of inducible nitric oxide synthase in the development and healing of experimentally induced gastric ulcers

The roles of inducible nitric oxide synthase (iNOS) in the development and healing of gastric ulcers have not been fully characterized. We characterized iNOS expression in experimentally induced ulcers in rat and mouse stomachs and investigated the roles of iNOS using iNOS gene-deficient (iNOS-/-) mice and wildtype mice. Gastric ulcers were induced in rats and mice by the application of acetic acid and cryoinjury, respectively. iNOS expression was detected on days 1-7 and peaked 3 days after ulcer induction in the rat. iNOS-positive cells were distributed mainly among the infiltrating cells and fibroblasts in the ulcer bed. The almost similar courses of healing and iNOS expression were observed in the ulcers of mice. During the course of healing, the iNOS gene status did not affect cell proliferation in the healing zone or vessel formation in the ulcer bed. iNOS deficiency, however, caused larger ulcers and severer inflammation during ulcer healing; the clearance of inflammatory cells in the ulcer bed by apoptosis was also delayed when the ulcer was re-epithelialized in the iNOS-deficient mice. These results indicate that iNOS is expressed in the ulcer bed and that iNOS activity may play beneficial roles in the ulcer repair process, possibly by regulating inflammation.     

Potential stem cell—Conditioned medium and their derived exosomes versus omeprazole in treatment of experimental model of gastric ulcer

Gastric ulcer is a common frequent clinical problem affecting all age and gender. This work aims to compare between the therapeutic effects of stem cell derived exosomes, stem cells conditioned medium and omeprazole on the healing of gastric ulcer model.Fifty rats were, assigned into 5 groups; control, gastric ulcer, omeprazole-treated, conditioned medium- treated, and exosomes-treated groups. Gastric ulcer was induced by aspirin dissolved in 1% carboxymethyl cellulose at a daily dose of 200 mg/kg for 5 consecutive days. Stomach specimens were obtained for histological, biochemical, and immunohistochemical assessments.The gastric ulcer group revealed widening of the fundic glands lumen containing, exfoliated dead cells. There was a remarkable distortion of the normal histological structure of the gastric mucosa with surface lining epithelial cell sloughing, vascular congestion and inflammatory cell infiltration. Both exosomes and conditioned medium treatments ameliorated almost all of the histopathological changes. Interestingly, the healing effect of exosomes was greater because it restored the histological architecture of gastric mucosa to nearly normal.In conclusion, this work may pave the future for using stem cell derived exosomes as a more convenient and effective adjuvant therapy in gastric ulcer.     

大鼠颌下腺GnRH及其受体的免疫组织化学双标记和年龄变化

用免疫组织化学法，以邻片双标记技术研究了大鼠颌下腺内ＧｎＲＨ及ＧｎＲＨ受体的分布；并对不同的发育阶段大鼠颌下腺内ＧｎＲＨ及其受体进行了原位定量分析，结果表明，雄性成年大鼠颌下腺浆液性腺泡的腺上皮细胞及各级导管上皮细胞既呈ＧｎＲＨ又呈ＧｎＲＨ受体免疫反应性。     

Sequential morphological changes of ulceration in the glandular stomach of rats induced by iodoacetamide.

Two groups of 25 male Wistar rats were given 0.1% iodoacetamide (IAM) with or without 0.4% Tween 60 in their drinking water for 12 weeks. Two or three rats from each group were sacrificed at intervals for sequential morphological observations on ulceration of gastric mucosa. The ulcers invariably developed in the fundic region adjacent to the limiting ridge, and they penetrated the muscle coats and extended to the serosal lining on continuous treatment with IAM for 9 weeks. The ulcers appeared chronic, but when IAM was discontinued the healing process began rapidly and the mucosa regenerated almost completely within six weeks. Regenerating epithelium on areas of ulcer differentiated progressively, and the renewed mucosa showed pyloric metaplasia.     

Microcirculatory disturbances in gastric mucosa during ulcer disease and effects of serotonin on their dynamics

Experiments on rat model of stress-induced gastric ulcers revealed marked circulatory disturbances in ulcerated gastric mucosa associated with arteriolar spasm and venous congestion and leading to perivascular edema, diapedesis of erythrocytes, and microhemorrhages. These changes were most pronounced on day 1 after ulcer modeling and progressively decreased during healing (day 14-21). On day 3, arterial hyperemia developed against the background of venous congestion, which was probably related to progressive repair. Serotonin adipinate administered after ulcer modeling accelerated the development of arterial hyperemia (day 1) and reduced venous congestion and extravascular changes. Pretreatment with serotonin was even more effective in attenuating venous congestion and extravascular changes.     

SEQUENTIAL MORPHOLOGICAL CHANGES OF ULCERATION IN THE GLANDULAR STOMACH OF RATS INDUCED BY IODOACETAMIDE

Two groups of 25 male Wistar rats were given 0.1% iodoacetamide (IAM) with or without 0.4% Tween 60 in their drinking water for 12 weeks. Two or three rats from each group were sacrificed at intervals for sequential morphological observations on ulceration of gastric mucosa. The ulcers invariably developed in the fundic region adjacent to the limiting ridge, and they penetrated the muscle coats and extended to the serosal Mng on continuous treatment with IAM for 9 weeks. The ulcers appeared chronic, but when IAM was discontinued the healing process began rapidly and the mucosa regenerated almost completely within six weeks. Regenerating epithelium on areas of ulcer differentiated progressively, and the renewed mucosa showed pyloric metaplasia.     

Effects of glyprolines on development and healing of acetate ulcers in rats

We studied glyprolines influence on development and healing of acetate ulcers in rats. A maximal ulcer area has developed four days after application of acetic acid to gastric serous mucosa. Estimation of ulcer area in the control and experimental animals receiving a physiological solution or peptides was carried out on day 4 or 7 after ulcerogenesis. Single administration of PGP, PG or GP in an equimolar dose of 3.7 mcmol/kg (i/p) during 1-3 days after the application significantly reduced ulcers by 88%, 93% and 94%, respectively, compared to the controls. Administration of these peptides for 4-6 days after application led to a significant reduction of the lesions by 46,50 and 96%, respectively, vs controls. Thus, glyprolines inhibit development of acetic ulcers and enhance their healing.     

Biopsy from the base of gastric ulcer may find gastric cancer earlier

Gastric cancer is one of the most common malignancies in the world; however, its exact mechanism of development which may be relevant to many factors is still unclear, such as age, diet, Helicobacter pylori infection, smoking, polyps, chronic gastric ulcer and so on. Chronic gastric ulcer is considered as precancerous lesion of gastric cancer. The above-mentioned diseases are usually diagnosed by endoscopy and biopsy. In general, biopsy specimens are usually taken from the edges of lesions, seldom from the base. In patients with chronic gastric ulcer, especially healing or healed benign ulcer, we took the biopsy specimens from both the edges and the base of ulcers in the follow-up. Malignant lesions were found in several cases of chronic gastric ulcer, in which specimens were taken from the base of lesions. Therefore, we hypothesize that biopsy from the base of healing or healed chronic gastric ulcer in the second or third endoscopy may find gastric cancer earlier than traditional biopsy.     

大鼠实验性胃溃疡自愈期间胰岛素原mRNA原位杂交的形态与计量研究

为了探讨胰岛素水平与消化道溃疡的关系，将成年雄性Ｗｉｓｔａｒ大鼠制成胃溃疡动物模型，用地高辛标记的ｐｒｏ－ＩｎｓｃＲＮＡ探针原位杂交方法，观察大鼠实验性胃溃疡自愈期间胰岛Ｂ细胞内ｐｒｏ－ＩｎｓｍＲＮＡ的变化，并对其杂交信号进行定量分析。结果显示，在胃溃疡模型术后第６和第１０ｄ，胰岛Ｂ细胞内的杂交信号增强，表明在溃疡愈合早期ｐｒｏ－ＩｎｓｍＲＮＡ的表达量增加。结合本室以往的研究结果，初步讨论了胰岛素参与胃溃疡自愈的调节过程及其意义