Inhibition of leukocyte migration after concanavalin A and phytohemagglutinin in patients with ulcers]

An attempt of the assessment of T-cells function in patients with gastric or duodenal ulcer has been undertaken. The studies involved 60 patients with gastric or duodenal ulcers and 47 individuals of the control group. Lymphocyte reactivity to different concentrations of concanavalin A and phytohemagglutinin has been assessed with leukocyte migration inhibition test. Lymphocyte T function has been examined also in patients with gastric or duodenal ulcers in reference to the theophylline-dependent and theophylline-sensitive subpopulation of T-cells. Leukocyte migration index values after phytohemagglutinin and concanavalin A did not differ significantly in patients with gastric or duodenal ulcers and theophylline-sensitive T-cells. Differences have been noted in the migration inhibition deficits. This phenomenon has been least frequent in case of phytohemagglutinin in the control group (5.8%) and most frequent in patients with gastric ulcer (62%). Percentage of patients responding to higher concanavalin A concentration (40 micrograms/ml) with leukocyte migration inhibition has been the highest in patients with duodenal ulcer. This index value has been significantly lower (p < 0.05) only in patients with duodenal ulcer and increased number of theophylline-dependent lymphocytes T. Increased reactivity of T-cells to higher concanavalin A concentration in patients with duodenal ulcer with theophylline-dependent T-cells in peripheral blood probably indicates increased the suppressor lymphocytes activity.     

Antiulcerogenic activity of Satavari mandur--an Ayurvedic herbo-mineral preparation

Satavari mandur (SM) is a herbo-mineral preparation containing Asparagus racemosus, which finds mention in ancient Indian texts for treatment of gastric ulcers. The ulcer protective effect of SM, 125-500 mg/kg given orally, twice daily for three, five and seven days, was studied on cold restraint stress-induced gastric ulcer in rats. The effective regimen was found to be 250 mg/kg given for five days and hence was used for further experiments. SM showed significant protection against acute gastric ulcers induced by pyloric ligation but was ineffective against aspirin- and ethanol-induced ulcers. Further, gastric juice studies showed that, SM significantly increased the mucosal defensive factors like mucus secretion, but had little or no effect on offensive factors like acid and pepsin secretion.     

中医药治疗胃溃疡的特色

胃溃疡是临床常见但十分棘手的消化系统疾病,主要临床表现为长期性、周期性、节律性上腹部疼痛。现代治疗多采用西医治疗,效果显著,但复发率高、不良反应较大。大量研究表明,祖国医学对治疗胃溃疡具有独特的优势,且在临床上取得了良好的疗效,尤其是大大降低了胃溃疡的复发率。关于中医药治疗胃溃疡的方式非常成熟且规范全面,主要包括辨证论治、专方加减、专药治疗、其他中医治法等,说明中医药治疗胃溃疡具有一定的特色及广阔的前景,同时也面临一些问题,需要医务人员共同思考并解决。现将中医药治疗胃溃疡的现状概述如下。     

IL-3 specifically inhibits GM-CSF binding to the higher affinity receptor

The inhibition of binding between human granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor by human interleukin-3 (IL-3) was observed in myelogenous leukemia cell line KG-1 which bore the receptors both for GM-CSF and IL-3. In contrast, this phenomenon was not observed in histiocytic lymphoma cell line U-937 or in gastric carcinoma cell line KATO III, both of which have apparent GM-CSF receptor but an undetectable IL-3 receptor. In KG-1 cells, the cross-inhibition was preferentially observed when the binding of GM-CSF was performed under the high-affinity binding condition; i.e., a low concentration of ¹²⁵I-GM-CSF was incubated. Scatchard analysis of ¹²⁵I-GM-CSF binding to KG-1 cells in the absence and in the presence of unlabeled IL-3 demonstrated that IL-3 inhibited GM-CSF binding to the higher-affinity component of GM-CSF receptor on KG-1 cells. Moreover, a chemical cross-linking study has revealed that the cross-inhibition of the GM-CSF binding observed in KG-1 cells is specific for the β-chain, M_r 135,000 binding protein which has been identified as a component forming the high-affinity GM-CSF receptor existng specifically on hemopoietic cells.     

Effect of polysaccharides from Angelica sinensis on gastric ulcer healing

Our previous study showed that a crude extract from Angelica sinensis (ASCE), which mainly consisted of polysaccharides, significantly promoted migration and proliferation of normal gastric epithelial cells. These results strongly suggest that ASCE has a direct wound healing effect on gastric mucosa. However, there is no report concerning the effect of ASCE on gastric ulcer healing in animal models. In this study, we found that ASCE promoted ulcer healing. The area of the ulcer was reduced. This was accompanied with a significant increase in mucus synthesis when compared with the control. Angiogenesis was inhibited by the treatment of ASCE. Cell proliferation, ODC and EGFR protein expression was not affected in this process. Thus, the mechanism of how ASCE accelerates ulcer healing in addition to its effect on mucus synthesis remains to be investigated.     

Role of Moringa oleifera on enterochromaffin cell count and serotonin content of experimental ulcer model

The present study has been undertaken to observe the effect of aqueous extract of M. oleifera (MO) leaf (300mg/kg body weight) on mean ulcer index, enterochromaffin (EC) cells and serotonin (5-hydroxytryptamine; 5-HT) content of ulcerated gastric tissue. Ulceration was induced by using aspirin (500 mg/kg, po), cerebellar nodular lesion and applying cold stress. In all cases increased mean ulcer index in gastric tissue along with decreased EC cell count was observed with concomitant decrease of 5-HT content. Pretreatment with MO for 14 days decreased mean ulcer index, increased both EC cell count and 5-HT content in all ulcerated group, but treatment with ondansetron, a 5-HT3 receptor antagonist, along with MO pretreatment increased mean ulcer index, decreased 5-HT content without any alteration in EC cell count. The results suggest that the protective effect of MO on ulceration is mediated by increased EC cell count and 5-HT levels which may act via 5-HT3 receptors on gastric tissue.     

Prevention of stress-induced gastric ulcers by dopamine agonists in the rat

Dopamine (DA) and DA agonists have been shown to exert a protective role against the formation of duodenal ulcers. The effect of stimulation of DA receptors on the development of stress-induced gastric ulcers is currently unknown. Accordingly, we evaluated the effect of several DA agonists on the development of gastric ulcers induced by 3 h of cold + restraint stress (CRS) in rats. Apomorphine, d-amphetamine, methylphenidate, and threo-dl-p-hydroxymethylphenidate (an hydroxylated analog of methylphenidate), significantly reduced both the incidence and severity of CRS-induced gastric ulcers. The gastric cytoprotection afforded by these agents was dose-related, and completely antagonized by pretreatment with the peripheally acting DA antagonist domperidone. Because domperidone blocks peripheral, but not central, DA receptors, and since the entry of threo-dl-p-hydroxymethylphenidate across the blood-brain barrier into the brain is restricted to a great extent, we conclude that stimulation of peripheral DA receptors is primarily involved in the gastric cytoprotection induced by dopamimetics.The pathogenesis of stress-induced gastric ulcers remains largely unknown, and significant efforts have been made over the last decade to functionally characterize some of the factors involved in the etiology of this disease. Considerable attention has been focused on gastric acid secretion, but its primary role in stress-induced gastric ulcer disease remains uncertain. In fact, agents which effectively inhibit or neutralize gastric acid secretion such as cimetidine or antacids do not necessarily exert protection against stress-induced gastric ulcers (1,2). Moreover, in our original studies with neurotensin, a brain and gastrointestinal peptide, we have found that central administration of this neuropeptide, which completely prevents the development of cold + restraint stress (CRS)-induced gastric ulcers, does not appreciably alter gastric acid secretion (2). These findings support the contention that gastric acid secretion may not be an important factor in the development of this type of gastric ulcer.There is, however, considerable evidence that the automatic nervous system plays an intermediary role in the development of these ulcers (3,4). In this regard, surgical or pharmacological blockade of the vagal (cholinergic) division of the autonomic nervous system prevents the appearance of stress-associated gastric ulcers (5,6). Direct stimulation of catecholamine receptors, or indirect activation via increased sympathetic outflow to the periphery (7,4,8–11) appears to produce a salutary effect of stress-induced gastric ulcers.Szabo and his associates (12, 13, 14) have extensively studied the anti ulcer effects of dopamine (DA) in duodenal ulcer formation. Whether DA also modifies the development of stress-induced gastric ulcers is currently unknown.We have therefore evaluated the effect of selected DA receptor agonists and antagonists on CRS-induced gastric ulcer formation in rats.     

尖顶羊肚菌菌丝体水提液对实验型胃溃疡的作用

研究尖顶羊肚菌菌丝体水提液对4种实验型胃溃疡模型的治疗作用。以大鼠幽门结扎致胃溃疡为模型,测定各组胃粘膜损伤指数、胃液分泌量和胃酸浓度;以大鼠乙酸烧灼、小鼠乙醇致胃粘膜损伤和小鼠水浸应激胃溃疡为模型,分别测定溃疡面积。结果表明尖顶羊肚菌菌丝体水提液可以不同程度抑制胃酸的分泌,减少胃液量,减少溃疡面积,促进溃疡面积的愈合,因此尖顶羊肚菌菌丝体水提液具有抗实验型胃溃疡的作用。     

Gastric antisecretory and antiulcer activity of oxytocin in rats and guinea pigs.

The effect of oxytocin (1 mg/kg s.c) on gastric acid secretion and on different experimentally induced gastric and duodenal ulcers was studied. The acute gastric ulcer models used were pylorus ligation, indomethacin, ethanol and histamine induced acute gastric ulcers. Chronic gastric ulcers were induced using acetic acid and duodenal ulcers by cysteamine hydrochloride. Oxytocin showed significant antisecretory and antiulcer activity in pylorus ligated rats. Similarly oxytocin reduced the ulcer index in histamine induced gastric ulcers in guinea pigs and cysteamine induced duodenal ulcers in rats. The antiulcer and antisecretory effect was comparable to that of ranitidine (50mg/kg, i.p) though less in intensity. However, it did not show any gastric cytoprotective effect in ethanol and indomethacin induced ulcer models but ranitidine showed protection (p<0.05) in later model. Oxytocin enhanced gastric ulcer healing in acetic acid induced chronic gastric ulcer model. The reversal of oxytocin effect by atosiban, an oxytocin receptor antagonist indicates a role for oxytocin receptors. The antiulcer activity of oxytocin can be attributed to its antisecretory effect.     

The effect of prostacyclin on gastric mucosal protein, DNA and RNA content, with special reference to different ulcer models

The effect of prostacyclin on gastric mucosal protein, DNA and RNA content has been investigated, either administered alone or in the course of indomethacin and stress-induced experimental ulcer models. It seems that: The oral administration of 100 micrograms/kg prostacyclin caused a prevailing DNA increase (decrease of the RNA/DNA ratio) in the rat gastric mucosa. Indomethacin and stress (restraint) ulcer formation were also followed by a predominant mucosal DNA increase which was maintained even during PGI2 treatment. The observed changes in RNA/DNA ratios were interpreted as a sign of accelerated cell renewal.     

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。     

川木香对实验性胃溃疡形成的抑制作用研究

目的:研究川木香对实验性胃溃疡形成的抑制作用.方法:采用利血平型小鼠胃溃疡模型、醋酸型大鼠胃溃疡模型,以雷尼替丁为对照药物,观察动物溃疡指数和溃疡抑制率.结果:川木香单体提取物(去氢木香内酯)、醋酸乙酯提取物、乙醇提取物,抑制利血平型溃疡存在统计学差异(与模型对照组比较,P＜0.01);醋酸乙酯提取物,抑制醋酸型溃疡存在统计学差异(与模型对照组比较,P＜0.05),其中高剂量组作用存在统计学差异(与模型对照组比较,P＜0.01).结论:川木香具有抑制实验性胃溃疡的形成作用,醋酸乙酯提取物可以作为川木香抑制胃溃疡形成的有效部位.     

脂类对盐酸,乙醇致大鼠胃粘膜损伤的保护作用

本实验用Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ大鼠胃内给予二山酰卵磷脂与三棕榈酰甘油酯１：４（ｗ／ｗ）混合物（每只鼠１ｍｌ,含５ｍｇ混合物）保护０．６ｍｏｌ／Ｌ盐酸致胃粘膜损伤,使溃疡指数及溃疡面积与胃总面积比分别降低了７６．２７％及８０．２４％（Ｐ＜０．０１）,胃粘膜表面疏水性及跨膜电位值显著增加（Ｐ＜０．０５）。该混合物对无水乙醇所致胃粘膜损伤无明显保护作用。提示脂类对盐酸致胃粘膜损伤的保护作用与其维持表面疏水性有关,但这种疏水表面对不同致损伤因子的作用是有差异的。     

Helicobacter pylori. One bacterium and a broad spectrum of human disease! An overview.

Since the historical rediscovery of gastric spiral Helicobacter pylori in the gastric mucosa of patients with chronic gastritis by Warren and Marshall in 1983, peptic ulcer disease has been largely viewed as being of infectious aetiology. Indeed, there is a strong association between the presence of H. pylori and chronic active gastritis in histology. The bacterium can be isolated in not less than 70% of gastric and in over 90% of duodenal ulcer patients. Eradication of the organism has been associated with histologic improvement of gastritis, lower relapse rate and less risk of bleeding from duodenal ulcer. The bacterium possesses several virulence factors enabling it to survive the strong acid milieu inside the stomach and possibly damaging host tissues. The sequence of events by which the bacterium might cause gastric or duodenal ulcer is still not fully elucidated and Koch's postulates have never been fulfilled. In the majority of individuals, H. pylori infection is largely or entirely asymptomatic and there is no convincing data to suggest an increase in the prevalence of peptic ulcer disease among these subjects. An increasingly growing body of literature suggests an association between colonization by H. pylori in the stomach and a risk for developing gastric mucosa-associated lymphoid tissue (MALT), MALT lymphoma, gastric adenocarcinoma and even pancreatic adenocarcinoma. The bacterium has been implicated also in a number of extra-gastrointestinal disorders such as ischaemic heart disease, ischaemic cerebrovascular disease, atherosclerosis, and skin diseases such as rosacea, but a causal role for the bacterium is missing. Eradication of H. pylori thus seems to be a beneficial impact on human health. Various drug regimens are in use to eradicate H. pylori involving the administration of three or four drugs including bismuth compounds, metronidazole, clarithromycin, tetracyclines, amoxycillin, ranitidine, omeprazole for 1-2 weeks. The financial burden, side effects and emergence of drug resistant strains due to an increase in the use in antibiotics for H. pylori eradication therapy need further reconsideration.     

Capsaicin and the stomach. A review of experimental and clinical data

Capsaicin, the pungent principle of hot pepper, because of its ability to excite and later defunctionalize a subset of primary afferent neurons, has been extensively used as a probe to elucidate the function of these sensory neurons in a number of physiological processes. In the rat stomach, experimental data provided clear evidence that capsaicin-sensitive (CS) sensory nerves are involved in a local defense mechanism against gastric ulcer. Stimulation of CS sensory nerves with low intragastric concentrations of capsaicin protected the rat gastric mucosa against injury produced by different ulcerogenic agents. High local desensitizing concentrations of capsaicin or systemic neurotoxic doses of the agent markedly enhanced the susceptibility of the rat gastric mucosa to later noxious challenge. Resiniferatoxin, a potent analogue of capsaicin possesses an acute gastroprotective effect similar to that of capsaicin in the stomach. The gastroprotective effect of capsaicin-type agents involves an enhancement of the microcirculation effected through the release of mediator peptides from the sensory nerve terminals with calcitonin gene-related peptide being the most likely candidate implicated. They do not depend on vagal efferent or sympathetic neurons or involve prostanoids. The gastric mucosal protective effect of prostacyclin is retained after systemic or topical capsaicin desensitization. Capsaicin-sensitive fibers are involved in the repair mechanisms of the gastric mucosa. A protective role for CS sensory nerves has also been demonstrated in the colon. In most studies, capsaicin given into the stomach of rats or cats inhibited gastric acid secretion. In humans, although recent studies provide evidence in favor of a beneficial effect of capsaicin on the gastric mucosa, an exact concentration-related assessment of the effect of the agent is still lacking.     

Bacterial colonization and healing of gastric ulcers: the effects of epidermal growth factor

Experimental gastric ulcers are rapidly colonized by various bacteria, resulting in significantly impaired healing. Epidermal growth factor (EGF) is capable of preventing bacterial colonization of the healthy intestinal mucosa. In this study, we examined the possibility that EGF accelerates gastric ulcer healing by reducing bacterial colonization of the ulcer. Gastric ulcers were induced by serosal application of acetic acid. The effect of daily administration of EGF on ulcer healing and bacterial colonization was assessed and compared with the effect of daily treatment with broad-spectrum antibiotics. EGF administration reduced colonization levels and accelerated ulcer healing as effectively as the antibiotic treatment. EGF was without effect on acid secretion or neutrophil infiltration into the ulcer. Bacterial growth was not inhibited in the presence of EGF in vitro. These results demonstrate that EGF reduces bacterial colonization during an established infection of a compromised mucosal surface. This effect may contribute to the ability of EGF to accelerate gastric ulcer healing. This effect is acid independent and not due to an anti-inflammatory effect or to direct bactericidal actions.     

Annexin-1 modulates repair of gastric mucosal injury

Annexin-1 is a glucocorticoid-inducible protein that plays an important effector role in the resolution of inflammation and has recently been shown to contribute to the resistance of the stomach to injury. Using an integrated genetic and pharmacological approach, we have tested the hypothesis that annexin-1 contributes to the healing of mucosal injury, given that such injury is accompanied by an inflammatory response, which is often associated with an overexpression of annexin-1 expression. Gastric ulcers were induced in mice through serosal application of acetic acid. Annexin-1 expression during the healing of the ulcers was examined. The effects on gastric ulcer healing of treatment with an annexin-1 mimetic (Ac2-26), an antagonist of the annexin-1 receptor (Boc2), or a glucocorticoid (dexamethasone) were examined. Finally, susceptibility to and healing of indomethacin-induced gastric lesions were compared in wild-type and annexin-1-deficient mice. Expression of annexin-1 was significantly increased in the gastric ulcer margin throughout the healing process. Treatment with an annexin-1 mimetic (Ac2-26) significantly enhanced gastric ulcer healing. In contrast, both dexamethasone and an formyl peptide receptor-like-1 (FPRL-1) antagonist impaired the early phase of ulcer healing. Annexin-1-deficient mice exhibited the same susceptibility as wild-type mice to indomethacin-induced gastric damage, but the healing of that damage was impaired in the former. These data support the hypothesis that annexin-1 contributes significantly to the process of healing of gastric mucosal damage.     

Effect of local injection with basic fibroblast growth factor (BFGF) and neutralizing antibody to BFGF on gastric ulcer healing, gastric secretion, angiogenesis and gastric blood flow.

Exogenous administration of bFGF was shown to accelerate tissue repair predominantly due to an increase in the formation of new microvessels (angiogenesis) suggesting that bFGF plays an important role in healing of gastric ulcer. This study was designed: 1) to examine the effect of local application of bFGF with or without neutralizing antibody (NA) to bFGF and 2) to determine the role of gastric secretion, gastric blood flow (GBF) at the ulcer margin and angiogenesis during gastric ulcer healing with or without local application of NA, bFGF or the combination of NA and bFGF. Chronic gastric ulcers were induced in Wistar rats by subserosal application of acetic acid (ulcer area 28 mm2) and gastric secretion during ulcer healing was assessed using animals additionally equipped with chronic gastric fistulas. The bFGF without or with NA to bFGF (10 ng/100 microl]), irrelevant antibodies (rabbit IgG; 10 microg/100 microl) or vehicle (saline) were locally injected into the subserosa immediately upon ulcer induction (day 0) and at day 2. Rats with acetic acid ulcers without subserosal injections served as controls. At day 11, all animals were anaesthetized and GBF was determined at the ulcer base, ulcer margin as well as in intact mucosa using the H2-gas clearance technique and the area of gastric ulcers was measured by planimetry. Gastric mucosa with ulcer was excised and the percentage of area covered with blood vessels, the number of fibroblasts and the percentage of connective tissue at the ulcer edge was assessed by histology. The gastric ulcers were healed spontaneously in control vehicle-treated rats at day 11 and this was accompanied by the significant increase in the GBF and number of microvessels in the ulcer area. The gastric secretion was suppressed immediately after ulcer induction and increased significantly at day 2 and day 11 but failed to return to that recorded in intact animals. In contrast, local application of bFGF inhibited gastric acid and pepsin outputs at each study time intervals tested and this effect was reversed by addition of NA to bFGF. Locally applied bFGF accelerated significantly ulcer healing and this was accompanied by the greater rise in the GBF of ulcer margin and more marked increase in number of microvessels as compared to those in vehicle-treated rats. Subserosal application of NA to bFGF prolonged significantly the ulcer healing and this effect was accompanied by a significant fall in the GBF at the ulcer margin and a decrease in number of capillaries in ulcer bed without significant alteration in gastric acid and pepsin outputs. The ulcer healing effect of bFGF and accompanying increase in the GBF at ulcer margin and in thenumber of microvessels as well as inhibition of gastric acid secretion evoked by bFGF were significantly attenuated by the addition of NA to bFGF. The number of fibroblasts and the distribution of connective tissue did not differ between groups studied. We conclude that; 1) depletion of endogenous bFGF at the ulcer area by specific NA to bFGF delays healing of gastric ulcers, reduces angiogenesis of ulcer bed and impairs the microcirculatory effect of this growth factor at the ulcer margin indicating that the availability of bFGF in the ulcer area plays a crucial role in the ulcer healing through induction of angiogenesis; 2) this prominent antiulcer effect of locally applied bFGF depends, at least in part, upon the inhibition of acid secretion by this peptide.     

Survivin、Dnmt 和CD44 在胃溃疡及胃癌中表达的差异

胃溃疡(Gastric Ulcer GU)和胃癌(Gastrio Cancer Gc)均是我国乃至全世界人群中的常见病、多发病。近年来,虽然胃溃疡的发病率开始呈下降趋势,但仍属消化系统疾病中最常见的疾病之一,目前已被认为是癌前病变之一。据统计,5%左右的胃溃疡可发生癌变,甚至有统计最高达29.4%的胃癌来自胃溃疡[1]。在世界范围内恶性肿瘤中,胃癌位居第4,病死率位居第2,在我国则居第1位。胃癌发生的分子机制研究表明多基因变异是细胞发生癌变的内因[2]。各种癌基因、抑癌基因和错配修复基因、细胞信号传导通路的异常、细胞周期调控改变及相关产物均对胃癌的发生发展产生影响。如Survivin、DNA甲基化和CD44等均是近年来在胃癌组织中发现的并成为研究热点的基因。通过对Survivin、Dnmt和CD44三种基因在胃溃疡及胃癌中表达的差异的了解,有助于加深对胃癌发生、发展及转移机制的认识,更好的为临床应用中胃溃疡及胃癌的治疗提供理论依据和找到更好的治疗方法。