人三叶因子2治疗大鼠胃溃疡的效果评价

目的探讨人三叶因子2（hTFF2）治疗大鼠胃溃疡的疗效。方法将48只雄性Wistar大鼠随机分为Ⅰ、Ⅱ、Ⅲ组，冰乙酸法制作慢性胃溃疡模型。造模时Ⅰ、Ⅱ、Ⅲ组于胃黏膜下分别注射pcDNA3．1-hTFF2（人三叶因子2插入pcDNA3．1载体；pcDNA3．1为真核表达载体，有进入胃黏膜下细胞的特性）西米替丁及pcDNA3．1。造模后7、14d各组分别处死8只大鼠，测定溃疡面积、胃液总酸度及黏液糖蛋白水平。结果Ⅰ、Ⅱ组较Ⅲ组溃疡面积明显缩小，Ⅱ组较Ⅰ、Ⅲ组胃总酸度明显降低，Ⅰ组较Ⅱ、Ⅲ组黏液糖蛋白量明显增加，P均〈0．001。结论pcDNA3．1-hTFF2单次局部注射可通过增加黏液糖蛋白的分泌促进大鼠胃溃疡愈合。     

Effect of Cimetidine on Gastric Mucosal Cell Proliferation in Man

Seven duodenal ulcer patients were treated for 3 months with cimetidine. Before and after treatment endoscopic biopsy specimens were taken for autoradiographic estimation of cell proliferation in the gastric mucosa in the antral and fundic part of the stomach and from the duodenum. In all three areas the estimated labeling index was increased during medication with cimetidine. The increase in epithelial cell renewal may participate in the ulcer healing effect of cimetidine.     

胃溃疡发生和愈合中细胞免疫功能的变化

目的:探讨细胞免疫功能在胃溃疡(GU)发生和愈合中的变化。方法:胃镜及病理证实的GU患者26例。在西咪替丁(1g/d〕治疗5—8周前后测定外周血T细胞亚群(APAAP桥联酶标法)及NK细胞活性(LDH释放法〕。20例健康人作为对照。结果:活动期GU患者CD_3~ ,CD_4~ ,CD_4~ /CD_8~ 比值及NK细胞活性分别为(55.1％±6.4％,41.4％±5.2％,1.69±0.24和29.7％±6.0％)明显低于正常人(P<0.05)。随着西咪替丁治疗使溃疡愈合,上述指标较用药前明显升高(分别为58.8%±6.8%,43.2％±5.0％,1.79±0.33和34.2％±5.9％,P<0.05),与正常人相似(P>0.05)。CD_8~ 治疗后(25.0％±7.1%)较治疗前(25.5％±6.8％)无明显变化(P>0.05)。结论:细胞免疫功能在GU的发生和愈合中有一定变化。除抑制胃酸外,西味替丁还能影响机体的免疫功能而治疗GU。     

Reducing meal-stimulated acid secretion versus reducing nocturnal acid secretion for healing of duodenal ulcer

Both meal-stimulated and nocturnal acid secretions have been shown to be abnormally increased in patients with duodenal ulcer. The relative efficacy of an acid-reducing regimen aimed specifically at controlling postprandial acid secretion compared with one that controls nocturnal acid secretion is, however, not known. The endoscopic healing rates at weeks 2, 4, 6, 8, 10, and 12 of three cimetidine regimens with identical total daily dose—bedtime (1200 mg), mealtime (400 mg three times a day with meals), and reference (200 mg three times a day with meals and 600 mg at bedtime)—were compared in a randomized study on 141 patients with endoscopically proven duodenal ulcer. Evaluating endoscopists were blinded to patients' form and duration of treatment and their clinical progress; patients were unaware of the comparative design of the study. Life-table analysis for the 12 weeks of observation revealed that the mealtime regimen resulted in significantly (P<0.05) better healing rates than either the bedtime or the reference regimen. The differences were accounted for largely by the significantly (P<0.04) better healing rate at two weeks with the mealtime regimen (68%) than with either the bedtime (47%) or the reference (45%) regimen. These findings indicate that a regimen that aims at controlling meal-stimulated acid secretion achieves a faster healing rate than one that aims at controlling nocturnal acid secretion in the treatment of duodenal ulcer, and they suggest that postprandial acid secretion plays a greater role than nocturnal acid secretion in the pathophysiology of this condition.This study was supported by the Peptic Ulcer Research Fund (311/041/0372), and by grants (311/030/8009/31, 311/030/8010/12, 335/041/0006, 311/030/8010/69) of the University of Hong Kong.     

Pneumonia versus aspiration pneumonitis in nursing home residents: diagnosis and management

OBJECTIVES: To determine the frequency of aspiration pneumonitis in nursing home residents with an initial diagnosis of pneumonia and to compare the clinical characteristics, management, and outcome of aspiration pneumonitis with those of pneumonia. DESIGN: Retrospective chart review. SETTING: Hospital geriatric unit for nursing home residents. PARTICIPANTS: Nursing home residents admitted to the inpatient geriatric unit with suspected pneumonia between May 1999 and April 2001 (n = 195 episodes). MEASUREMENTS: Aspiration events were defined as definite (witnessed or unwitnessed) or suspected. Aspiration pneumonitis was defined as symptoms/signs of lower respiratory tract infection plus a history of an aspiration event plus a lower lobe infiltrate on chest radiograph. Pneumonia was defined as symptoms/signs of lower respiratory tract infection plus an infiltrate on chest radiograph plus no history of an aspiration event. RESULTS: The 195 episodes were stratified into three clinical groups: aspiration pneumonitis (n = 86; aspiration history/infiltrate), pneumonia (n = 43; no aspiration history/infiltrate), and an aspiration event (n = 66; aspiration history/no infiltrate). In general, symptoms, signs, and laboratory tests were not useful in distinguishing between the three groups. Survivors with aspiration pneumonitis (13/75 (17%)) or with an aspiration event (20/60 (33%)) were significantly more likely not to be treated with an antibiotic or to be treated for 1 day or less than those with pneumonia (0/41; P <.001). Excluding those not treated, significantly more patients with pneumonia (33/40 (83%)) were discharged on antibiotic treatment than those with aspiration pneumonitis (35/70 (50%)) or an aspiration event (21/51 (41%); P <.001). There was no significant difference in hospital mortality between the three clinical groups. CONCLUSIONS: The findings of this study have implications for the diagnosis and management of suspected pneumonia in nursing home residents but require prospective validation.     

The role of the vagus nerve in the protective action of acid inhibitors on ethanol-induced gastric mucosal damage in rats

The role of vagus in the actions of different acid inhibitors on ethanol-induced gastric damage and mucosal blood flow (GMBF) changes was studied in anaesthetized rats, using an ex vivo stomach chamber preparation. Subdiaphragmatic bilateral vagotomy decreased the basal gastric acid secretion and GMBF; it also intensified ethanol-evoked lesions in the glandular mucosa. Misoprostol, omeprazole and cimetidine produced a similar degree of reduction in acid output. Misoprostol given subcutaneously (s.c.) (50 micrograms/kg), or added to the incubation solution (12.5 micrograms) for 15 min, markedly prevented ethanol-induced lesion formation and reduction in GMBF. The reversing effect of s.c. injection of misoprostol on either lesion formation or on GMBF reduction was attenuated by vagotomy. Omeprazole protected against lesion formation only when present in the incubation solution (12.5 mg) of ex vivo chamber preparations of both vagus-intact and vagotomized animals, but the effect was significantly less in the latter group. The drug also prevented the depressive action of ethanol in vagus-intact animals. Cimetidine pretreatment (50 mg s.c. or 12.5 mg in incubation solution), however, did not modify the effects of ethanol on lesion formation and the GMBF. The findings indicate that the three different types of acid inhibitors exert different actions on ethanol-induced gastric mucosal damage, although they produced similar inhibition of acid output. Vagotomy lowers the GMBF and attenuates the antiulcer action of misoprostol and omeprazole, especially when the drugs are given by the parenteral route.     

Wound healing of acetic acid-induced gastric ulcer in rats and the effects of cimetidine and calcitonin,with special reference to prolylhydroxylase and collagenase enzyme activity

The healing of acetic acid-induced gastric ulcer in rats and the effects of cimetidine and calcitonin were investigated with reference to the enzyme activity of both prolylhydroxylase and collagenase as related to histological findings. The rats were observed by endoscopy on the 3rd day after the subserosal injection of acetic acid; rats with ulcers were divided into three groups: non-treated, and cimetidine- and calcitonin-treated. The latter two groups were treated for 7 days. Prolylhydroxylase activity in active ulcers in the non-treated group was slightly higher on the 3rd day and significantly higher on the 10th day than the activity in control rats that had received subserosal injections of physiological saline solution on the respective days. In non-treated rats, the healed ulcer on the 10th day showed lower prolylhydroxylase activity than that in the active ulcer on the same day. Cimetidine did not affect prolylhydroxylase activity, but, with calcitonin, there was higher prolylhydroxylase activity in the healed than in the active ulcer, although the difference was not significant. Interstitial collagenase showed the highest activity on the 3rd day and decreased on the 10th day in non-treated rats. Collagenase activity was higher in the cimetidine-treated group, than that in the non-treated group, and numerous peroxidase-positive granulocytes were seen in the mucosa and submucosa. Calcitonin did not affect collagenase activity. The participation of both enzymes is indispensable in the healing process and the effects of anti-ulcer agents on these enzymes must be considered. A portion of this work was presented at the 16th Annual Meeting of the Experimental Ulcer Association of Japan, of which proceedings appear in Scand J Gastroenterol 1989; vol 24 (162).     

兰索拉唑对离体壁细胞酸分泌的影响

目的应用兔离体壁细胞为模型,研究兰索拉唑体外抑酸效果.方法应用细胞淘洗与连续密度梯度离心相结合的方法分离兔胃黏膜壁细胞,以14C氨基比林摄取为酸分泌指标,观察西咪替丁及兰索拉唑对离体壁细胞组胺诱导的酸分泌的影响.结果壁细胞纯度达80%以上进行实验,兰索拉唑能明显抑制离体壁细胞组胺诱导的酸分泌,对组胺刺激酸分泌的50%抑制量(IC50)为9.59×10-8mol/L,明显高于H2受体拮抗剂(3.70×10-5mol/L).结论兰索拉唑对兔离体壁细胞组胺诱导的酸分泌具明显的抑制作用,效果优于西咪替丁;本研究为国内开展新的抑酸剂基础与临床研究提供了新方法.     

Cimetidine and ranitidine protect against cold restraint-induced ulceration in rat by suppressing gastric acid secretion

The effect of the H₂-receptor antogonists cimetidine and ranitidine on pentagastrinstimulated gastric acid secretion in anesthetized rats, and gastric mucosal lesion formation and gastric motility in unanesthetized cold-restrained rats was studied. Both cimetidine and ranitidine suppressed pentagastrin-stimulated gastric secretion in a dose-dependent fashion. Cold restraint-induced lesion formation was not prevented with doses of both agents that inhibited acid secretion by 75%. Doses which suppressed pentagastrin-stimulated acid secretion more than 90% significantly prevented the development of gastric mucosal lesions produced by cold restraint. Doses of both H₂ blockers which demonstrated significant suppression of lesion formation had no effect on cold restraint-stimulated gastric contractility. We conclude that cimetidine and ranitidine suppress cold restraint-induced lesion formation by suppressing acid secretion and not by suppressing gastric contractility.This Research supported by the Veterans Administration and a grant from Smith Kline & Erench Laboratories.     

Effect of lansoprazole on histamine‐induced acid secretion in isolated rabbit parietal cells

OBJECTIVE: Lansoprazole (Takepron; Takeda) is extensively used in the treatment of acid‐related diseases. There are no prior studies of the effects of antisecretion drugs on parietal cells, but we recently developed a rabbit parietal cell model. This allowed us to compare the antisecretory effects of lansoprazole and cimetidine in vitro in the present study. METHODS: Parietal cells were isolated using cell elutriation and continuous density gradient centrifugation. The effect of cimetidine and lansoprazole on histamine‐induced acid secretion in rabbit parietal cells was investigated by measuring the accumulation of ¹⁴C‐aminopurine. RESULTS: The purity and viability of isolated parietal cells was >80 and 95%, respectively. Lansoprazole and cimetidine both significantly inhibited histamine‐stimulated acid secretion (10^?4 mol/L), but the 50% inhibition concentration (IC₅₀) of the two treatments was quite different. The IC₅₀ of cimetidine was 3.70 × 10^?5 mol/L, and that of lansoprazole was 9.59 × 10^?8 mol/L. CONCLUSIONS: Lansoprazole is much more effective than cimetidine in the in vitro inhibition of histamine‐stimulated acid secretion in rabbit parietal cells. This study developed a model for the study of acid inhibition drugs.     

Combination therapy of ecabet sodium and cimetidine compared with cimetidine alone for gastric ulcer: prospective randomized multicenter study

BACKGROUND AND AIM: Little is known about the clinical efficacy of co-therapy of ecabet sodium, a mucoprotective agent, and a histamine H2-receptor antagonist. The aim of the present study was to assess its additive benefit in combination with cimetidine for gastric ulcer. METHODS: In this prospective randomized study, after gastric ulcer was confirmed by endoscopy, 200 patients in 47 hospitals received either ecabet sodium 1 g b.i.d and cimetidine 400 mg b.i.d. (EC), or cimetidine 400 mg b.i.d. alone (C) for 8 weeks. Healing was examined by endoscopy at 4 and 8 weeks. RESULTS: Of the intention-to-treat (ITT) population (EC, 103; C, 97), 181 patients comprised the per protocol (PP) analysis (EC, 93; C, 88). At 4 weeks, healing rates were significantly higher in the EC group (60%) than in the C group (36%) ( p < 0.01). At 8 weeks, those by the ITT and PP analyses were 82% (EC) versus 58% (C), and 90% (EC) versus 64% (C), respectively ( p < 0.01 and p < 0.001). Symptom relief rates (EC vs C) at 2, 4 and 8 weeks were 73%versus 47% ( p < 0.01), 89%versus 66% ( p < 0.001), and 97%versus 73% ( p < 0.001), respectively. Significant additive effects of ecabet sodium were observed in patients aged 60 years or older, with solitary and medium to large ulcer, and without smoking or drinking habits. No adverse effects were critical. CONCLUSION: Ecabet sodium significantly augmented gastric ulcer healing and symptom relief by cimetidine, especially in the elderly.     

Effect of smoking on gastric acid secretion in patients with duodenal ulcer

The effect of smoking on gastric secretion was studied in 15 consecutive patients with duodenal ulcer--six normosecretors (basal acid output less than or equal to 3 mEq/h), and nine hypersecretors (basal acid output greater than 3 mEq/h). The volume, acid output, acid concentration, and pH of the gastric juice measured before, during and after 1 h of smoking did not show any significant difference in these patients taken as a single group, or when the normosecretors and hypersecretors were analysed as separate groups (P greater than 0.05 for each parameter in each group). The higher acid output before and during smoking in hypersecretors than in normosecretors was due to the higher acid concentration in the gastric juice (P less than 0.01). Study of the pH curves of the gastric juice after acute smoking showed that hypersecretors had a lower pH for a longer duration compared with normosecretors. This could make the hypersecretors with a history of chronic smoking more prone to developing duodenal ulcer.     

雷贝拉唑抑制大鼠胃壁细胞泌酸功能的机制研究

目的 探讨质子泵抑制剂雷贝拉唑对大鼠胃壁细胞泌酸功能的抑制作用.方法 将72只SD大鼠分成对照组(0.9%氯化钠溶液)、雷贝拉唑低剂量组(10 mg/kg)和雷贝拉唑高剂量组(20 mg/kg),每组24只.分别在1、2、4、6、12和24 h每组各处理4只大鼠.用氢氧化钠滴定法测定大鼠胃内pH值,比色法测定胃壁细胞内H+-K+-ATP酶活性,电镜下观察胃壁细胞超微结构的改变.结果 与对照组(1.97±0.30)相比,雷贝拉唑低剂量组(3.37±0.97)和高剂量组(5.96±0.26)在给药后1 h内胃液pH值显著升高(P<0.01),壁细胞H+-K+-ATP酶活性明显抑制(3.28±0.41比1.47±0.27和0.92±0.07,P<0.05).而且在给药12 h的差异仍有统计学意义(P<0.01).电镜下胃壁细胞超微形态改变与胃液pH值和壁细胞H+-K+-ATP酶活性变化相符.雷贝拉唑低剂量组与高剂量组在抑酸作用和起效时间方面差异有统计学意义(P<0.01).结论 壁细胞超微结构的变化和H+-K+-ATP酶活性能准确反映壁细胞的泌酸情况,雷贝拉唑能迅速强效抑制大鼠壁细胞的泌酸功能,且与剂量有关.     

Histological maturity of healed duodenal ulcer and ulcer recurrence after treatment with omeprazole or cimetidine

Abstract We investigated the relationship between histological maturity of healed duodenal ulcer and ulcer recurrence after treatment with omeprazole or cimetidine for 4 weeks. The healing rates, 92.5 and 72.4% in omeprazole-treated and cimetidine-treated groups, respectively, showed no significant difference between groups ( P > 0.05). Histologically, the regenerating mucosa of healed ulcer was divided into three categories: good, fair and poor patterns. Of the healed cases, 22 (59.5%) of 37 omeprazole-treated and 12 (28.6%) of 42 cimetidine-treated ulcers achieved a good pattern, showing significant difference between groups ( P = 0.01). The recurrence rate at 3 months showed statistically significant difference ( P < 0.05) between two groups: 5.4% in omeprazole-treated and 23.8% in cimetidine-treated patients. During the period between 3 and 6 months after healing, the difference in recurrence rate between omeprazole-treated and cimetidine-treated groups was statistically not significant (12.5% and 25%, respectively, P > 0.05), though the cumulative recurrence rate at 6 months showed a significant difference between groups (17.6% vs 44.7%, P = 0.027). All the recurrent cases of both groups had a fair or poor pattern of regenerating mucosa. The difference in recurrence rate was statistically significant between the healed ulcers with a good pattern and that with a fair or poor patterns both at 3 months and between 3 and 6 months after healing ( P > 0.001 in each). We concluded that better histological maturity of regenerating mucosa may contribute to the lower early recurrence in omeprazole-treated cases than in cimetidine-treated cases.     

Mechanism by which histamine increases gastric mucosal blood flow in the rat

The mechanism by which histamine increases gastric mucosal blood flow (GMBF) was investigated in the anesthetized rat. The experiment was performed in the presence of tripelennamine, an H₁ antagonist, to focus on the relationship between acid secretion (H₂-receptor-mediated response) and GMBF. The stomach was mounted on a Lucite chamber, perfused with saline, and GMBF was measured by laser Doppler flowmetry simultaneously with acid secretion. Under these conditions, histamine at the submaximal dose significantly increased GMBF as well as acid secretion, and this increase of GMBF was completely blocked when acid secretion was inhibited by cimetidine or omeprazole. The elevation of GMBF caused by histamine was also significantly attenuated when luminal H⁺ was removed by intraluminal perfusion with NaHCO₃ or glycine. Glycine by itself did not affect the increase of acid secretion induced by histamine and the increase of GMBF caused by isoproterenol, yet significantly inhibited the GMBF response induced by pentagastrin. Intraluminal perfusion with HCl also produced an increase of GMBF in a concentration-related manner, even in the presence of omeprazole during histamine infusion. Pretreatment of the animals with indomethacin significantly blocked the GMBF responses induced by either histamine or luminal HCl. These results suggest that the increase of GMBF during acid secretion induced by histamine may be caused by luminal H⁺ and involve endogenous prostaglandins in its mechanism.     

胃溃疡大鼠胃粘膜血流量与泌酸变化的研究

用手术将十二指肠内容物持续胃内反流制成大鼠胃溃疡及经转流后的溃疡愈合模型进行研究。结果表明,溃疡组于胃窦小弯侧可见8.84±3.08(m~2)~(-3)的慢性溃疡形成,并显示胃粘膜血流量降低,G细胞密度、壁细胞数增加。溃疡愈合组经转流后大部分溃疡已愈合,G细胞密度、壁细胞数降低,粘膜血流量增加。本实验提示,泌酸细胞增多,泌酸量增加和胃粘膜缺血可能是溃疡形成的重要因素,增加胃粘膜的血液供应,降低胃酸分泌可促进溃疡愈合。     

Elevated gastric acid secretion in patients with Barrett's metaplastic epithelium

Gastric acid secretion in response to a protein meal and to exogenously administered synthetic human gastrin 17-I was measured in patients with Barrett's esophagus, patients with uncomplicated gastroesophageal reflux, and normal age- and sex-matched controls. Acid secretion, both basally and in response to gastrin 17-I, was significantly greater in patients with Barrett's esophagus compared to normal individuals without reflux. Basal gastrin levels and meal-stimulated levels of the hormone were similar among all three groups. Sensitivity to gastrin, expressed as the concentration causing half-maximal acid secretion, was also similar among the study groups. It is speculated that elevated basal acid production in Barrett's esophagus may contribute to the pathogenesis of the disorder.Study supported by Smith, Kline, and French, Inc.