Inappropriate CA 72-4 elevation in a Helicobacter pylori infected patient.

Carcinoma antigen 72-4 is a cell surface glycoprotein produced by gastric carcinoma cells. In the case presented, Helicobacter pylori infection induced an inappropriate elevation of this tumour antigen in a 66-year-old female patient, reaching values seen with gastric carcinomas. Extragastric sources of CA 72-4 elevation were ruled out. The elevation slowly returned to normal levels after two courses of triple and sequential eradication therapy, causing considerable anxiety for the patient and several costly examinations.

Six regimens for the eradication of Helicobacter pylori (Hp) in duodenal ulcer patients: three consecutive trials (1995-1999).

AIM: to present our experience in eradicating Hp in three consecutive trials performed between 1995 and 1999. METHODS: 320 duodenal ulcer outpatients have been enrolled in three open, prospective controlled trials. Hp infection was confirmed by Giemsa stain and Rut. In Trial I, 52 cases received 20 mg omeprazole + 2 x 250 mg clarithromycin + 2 x 500 mg tinidazole (OCT), 48 patients were given 20 mg omeprazole, 2 x 1000 mg amoxicillin + 2 x 500 mg metronidazole (OAM) for 7 days; in Trial II, 48 cases received 40 mg pantoprazole + 2 x 1000 mg amoxicillin + 2 x 500 mg clarithromycin (PAC) for 7 days and 5l cases 2 x 400 mg ranitidin bismuth citrate + 2 x 500 mg clarithromycin for 14 days (RBC-C); in Trial III, 60 cases were treated with 2 x 30 mg lansoprazole + 2 x 250 mg clarithromycin + 2 x 500 mg metronidazole and 6l patients received 2 x 400 mg ranitidin bismuth citrate+2 x 250 mg clarithromycin + 2 x 500 mg metronidazole (RBC-CM). The patients were controlled within 4-6 weeks by endoscopy in trials I-II and 13C-urea breath test in trial III. RESULTS: Eradication rates on ITT/PP basis were: OCT: 72.3/80.2% vs OAM 51.2/63.5% (P = 0.02/P = 0.03); PAC: 80.8/88.3% vs RBC-C 80.3/85.4% (P = 0.65/0.67) and LCM 78.3/92.1% vs RBC-CM 78.7/90.5% (P = 0.86/P = 0.93). Side effects occurred in 5.2, 8.6, 9.5, 14.5, 13.5 and 18.3% of the cases. CONCLUSION: Regimens using 2 x l PPI or RBC + 2 antibiotics for l week proved to be the most effective for Hp eradication in duodenal ulcer patients.

Colonic sensitivity in irritable bowel syndrome and normal subjects according to their hemispheric preference and cognitive style.

According to our earlier results, non-painful, weak afferent visceral signals may exert a steady influence on brain processes, including cognitive functions. In the present series colonic impulses of irritable bowel syndrome (IBS) subjects served as a model of chronic impact from the gut. Hemispheric preference, as well as cognitive style of information processing served as indicators of covert changes in brain functions. In twenty-one IBS patients and in ten control subjects of both sexes, the thresholds of minimal colonic distension sensitivity has been measured following the determination of hemispheric preference and of advantage in verbal or spatial information processing of the subjects. In IBS patients distension thresholds proved to be higher in verbals than in spatials, whereas in healthy controls the relationship of colonic thresholds and verbal versus spatial advantage was reversed. Among the normal controls with left hemisphere preference a significantly higher distension threshold has been observed than in those with right hemisphere preference, whereas in the IBS group such threshold-differences were not observable.

[Eradication of Helicobacter pylori in peptic ulcer patients]. / A Helicobacter pylori eradikációja peptikus fekélybetegekben.

The aim of this study was to compare in an open trial the efficacy of 2 x 500 mg clarithromycin + 2 x 1000 mg amoxicillin + 40 mg pantoprazole/day given for 7 days (I. group, 48 cases), with that of 2 x 500 mg clarithromycin + 2 x 400 mg ranitidine bismuth citrate/day given for 14 days (II. group, 51 cases). The diagnosis of peptic ulcer was established endoscopically. HP infection was confirmed the modified Giemsa stain and rapid urease test. After eradication all patients were given 2 x 150 mg ranitidine for one month. Controls were performed 4-6 weeks after eradication. Peptic ulcer healing was proven in the group I in 93.0% and in the group II in 91.6% (p > 0.05). On intention-to-treat basis, HP was eradicated in 80.3% (confidence interval, CI: 73-92.7%) in the I. and 80.3% (confidence interval: 76-95%) in the II. group (p > 0.05). Per protocol analysis revealed eradication rates of 88.3% (CI: 81-97.6%) and 85.4% (CI: 80-97%) (p > 0.05). Side effects were recorded in 9.5% and 14.5% of the cases. Both regimens were equally effective in the eradication of HP and healing of peptic ulcers.

[Prevalence of Helicobacter pylori, correlations between alcohol consumption and gastroduodenal damage]. / A Helicobacter pylori prevalenciája, az alkoholfogyasztás és a gastroduodenum károsodása közötti összefüggések.

We studied the prevalence of Helicobacter pylori (HP) infection, and that of upper gastro-intestinal tract lesions in chronic alcoholics. 73 chronic alcoholic, 74 duodenal ulcer and 40 non-ulcer dyspepsia patients were included. The prevalence and severity of HP infection and gastritis, profile of endoscopic lesions and the correlation between severity of alcohol consumption and that of HP infection were determined. HP was found in 31.5% of alcoholics, 83.78% of duodenal ulcer (p < 0.05) an 47.50% of non-ulcer dyspepsia cases (p > 0.18). The Genta score was in the same groups 0.47 +/- 0.09, 1.91 +/- 0.22 (p < 0.05), and 0.65 +/- 0.14 (p > 0.98). Endoscopy revealed oesophagitis in 23.6%, nonerosive gastritis in 24.5%, erosive gastritis in 13.6%, gastric ulcer in 17.5% and duodenal ulcer in 28.6% of alcoholics. Multiple findings were present in 51.8% and no lesion was found in 6.4% of the cases. Severity of gastritis was also lower in alcoholics as compared to duodenal ulcer patients. There was no correlation between severity of drinking and that of HP infection. Thus, heavy alcohol intake is associated with lower prevalence and severity of HP infection. However, alcoholics have significant, often multiple endoscopic lesions suggesting the role of other aetologic factors in addition to HP infection.

Prevention of indomethacin-induced acute gastric mucosal injury by spermine in the rat.

The effect of spermine tetrahydrochloride was investigated on the indomethacin-induced acute mucosal injury and mucosal lipid peroxidation in rats. Spermine was given orally at doses of 25, 75 and 150 mg/kg and, intraperitoneally at 10, 25 and 50 mg/kg 1 hour before 25 mg/kg indomethacin administration. Macroscopic injury was measured by the use of a stereomicroscope. Mucosal malondialdehyde (MDA) levels were determined by an HPLC method. Oral spermine reduced dose-dependently the extent of macroscopic injury from 22.87 +/- 2.88 mm to 11.8 +/- 2.48 mm (p < 0.01, 25 mg/kg), 6.53 +/- 4.19 mm (p < 0.0007, 75 mg/kg) and 0.25 +/- 0.25 mm (p < 0.0001,150 mg/kg). Intraperitoneally administered spermine prevented dose-dependently the indomethacin produced lesions from 19.25 +/- 4.31 mm to 12.63 +/- 3.18 mm (p < 0.01, 25 mg/kg) and to 0.33 +/- 0.33 mm (p < 0.001, 50 mg/kg). Doses necessary for intraperitoneal protection were lower than those achieving similar effect, orally suggesting different mechanisms of action. Neither oral or intraperitoneal spermine influenced the mucosal MDA levels.

[Growth factors in experimental ulcer]. / Növekedési faktorok kísérletes fekélyben.

Important role is attributed to the growth factors in the development, growth, and restitution after injury of the gastrointestinal tract. The common feature of growth factors is their ability to stimulate the growth and mitosis of quiescent cells in a nutritionally complete medium which in itself is not sufficient to initiate cell division. Epidermal growth factor prevents efficiently the experimentally induced acute gastric mucosal lesions induced by aspirin, absolute ethanol, HCl, NaCl, immobilization, and immersion and it accelerates the healing of acetic acid-induced chronic gastric and cysteamine-induced chronic duodenal ulcers. It proved to be also useful in the treatment of human gastric ulcers. Fibroblast growth factor possesses similar gastroprotective and chronic ulcer-healing properties. Its effects is much more potent than that of epidermal growth factor and that of H2-receptor blockers. The "trefoil"-peptides constitute the latest family of growth factors which are supposed to be involved in the regeneration of the normal and the ulcerated gastrointestinal mucosa. Polyamines are non-peptide growth promoting compounds present in all eukaryotic cells; their gastroprotective and ulcer-healing properties have also been published. The use of some growth factors as regenerative and angiogenic therapy could open a new, alternative way in the future management of peptic ulcer disease.

Carbonic anhydrase inhibitors: antisecretory and cytoprotective properties.

Experimental studies located carbonic anhydrase (CA) in the parietal cells close to secretory canaliculi, in superficial epithelial cells and gastric microvasculature. The role of CA is CO2 hydration resulting H+ for acid secretion and conversion of OH into HCO3-. Our studies showed that the physiological secretagogue histamine, acetylcholine and gastrin are all CA activators, achieving potentiating interactions. Catecholamines are also strong enzymatic activators. Beside sulfonamides, other CA inhibitors are anticholinergics, PGE and PGI2, some calcium channel blockers, alpha 2- and beta 1-adrenoceptor blockers and Zn2+. Cytoprotective properties of CA inhibitors gained experimental evidence in the past years. These effects could be based on increase of gastric mucosal blood flow, proved experimentally, which might be mediated by increase of endogenous prostaglandin synthesis and sulfhydryls and, respectively, motility changes. The unique combination of strong antisecretory effect with the cytoprotective action explain the outstanding clinical efficacy of CA inhibitors in the healing of gastric and duodenal ulcers.

Effects of the synthetic PGE1 derivative misoprostol on basal, stimulated and nocturnal acid secretion in duodenal ulcer cases. Mechanism of action.

We studied the antisecretory effect of the synthetic PGE1 derivative misoprostol. Basal, histamine-stimulated and nocturnal acid secretion were determined on separate days in 3 groups of endoscopically confirmed duodenal ulcer patients. Misoprostol or placebo were given in random order in doses of 200, 400 and 800 mcg. H+ concentration, acid output and pH of gastric content were determined. Additionally, the effect of misoprostol on purified and gastric mucosa carbonic anhydrase was determined according to Maren's micromethod. Misoprostol reduced dose-dependently basal acid secretion (by 54% after 200 mcg, by 82% after 400 mcg and, respectively, by 94% after 800 mcg) as well as stimulated secretion which was reduced after the same doses by 22% (p less than 0.05), 48% and 64% (p less than 0.001), respectively. Nocturnal secretion was significantly reduced for a period of 4 h, with a consecutive rise of gastric pH. In vitro, misoprostol inhibited dose-dependently purified and gastric mucosa carbonic anhydrase basal activity. In conclusion, misoprostol inhibits basal, nocturnal and histamine-stimulated secretion in duodenal ulcer patients, an effect which could be mediated by inhibition of carbonic anhydrase.

Prevention of non-steroidal anti-inflammatory agents induced acute gastric mucosal lesions by carbonic anhydrase inhibitors. An endoscopic study.

The present paper studies the effect of acetazolamide, an inhibitor of carbonic anhydrase, on acute gastric mucosal damage induced by non-steroidal anti-inflammatory drugs. The study was performed on healthy male subjects. The drugs tested were aspirin (1.5 g/day), indomethacin (75 mg/day), phenylbutazone (600 mg/day) and ibuprofen (600 mg/day) given for 7 days in 3 divided doses. Each drug was given to 5 cases in two separate periods, during which they were given acetazolamide 20 mg/kg/day or placebo in random order. Dyspeptic symptoms were evaluated. Endoscopy was performed before, and 3 and 7 days after NOSAC administration. Gastric mucosal lesions were evaluated according to the scale proposed by Lanza (J. Clin. Pharmacol., 24: 1984, 89) and the severity of the lesions was calculated. All drugs tested produced dyspeptic symptoms and acute mucosal damage of the gastric mucosa. Inhibition of gastric mucosa carbonic anhydrase by acetazolamide cessated promptly dyspeptic symptoms and reduced significantly the number and severity of drug-associated mucosal lesions.

Treatment of duodenal ulcers with ethoxzolamide, an inhibitor of gastric mucosa carbonic anhydrase.

Duodenal ulcer healing was followed by endoscopy in 186 ethoxzolamide-treated patients. Ethoxzolamide was given in doses of 5-10 mg/kg body weight/day in association with Na and K salts to avoid electrolytic losses. A control group of 161 duodenal ulcer patients received the usual doses of antacids and anticholinergics. The clinical course of pain, inhibition of gastric acid secretion and endoscopic healing of ulcers after 15 and 21 days of treatment were followed, together with the incidence of relapses over a 2-year period. Pain disappeared after 4-6 days of treatment in 91% of the ethoxzolamide-treated group and in 13% of the controls. After 10 days of treatment, ethoxzolamide reduced basal HCl output by 98%, in the control no significant secretory changes were recorded. Endoscopy showed healing in 92% of the cases after 15 days of treatment with ethoxzolamide and in 98% after 21 days; in controls, the corresponding figures were 36% and 46% respectively. Relapse rate after 6 months was 5% in the ethoxzolamide-treated patients and 38% in controls; after one year, relapses were endoscopically confirmed in 7% of the cases in the first group and in 51% respectively in controls; the same rate was 11% and 79% respectively after 2 years. Ethoxzolamide is superior to antacids and anticholinergics in healing duodenal ulcers.

"Ulcosilvanil"--an inhibitor of carbonic anhydrase--associated with adrenergic beta-blockers in the treatment of duodenal ulcers.

Knowing the in vivo inhibitory effect of the beta-adrenoreceptor antagonists on gastric mucosa carbonic anhydrase and the high clinical efficacy of "Ulcosilvanil" in the healing of gastric and duodenal ulcers, the authors combined propranolol with smaller doses of "Ulcosilvanil" in 925 active duodenal ulcer patients, divided into four groups. The first 236 patients were treated with small doses of "Ulcosilvanil" (20 mg/kg b.w./day active substance), the second group (of 258 cases) with high doses (35 mg/kg b.w./day) of "Ulcosilvanil", the third one (182 subjects) with propranolol only (60 mg/day) and the fourth group (349 patients) with small doses of "Ulcosilvanil" associated with 60 mg/day propranolol. Pain disappeared in all the cases of groups 1,2 and 4 after 3-6 days of treatment and in 40% of the third group. Basal acid output decreased, after 10 days of treatment, from 6.15 +/- 1.57 to 1.94 +/- 0.66 mEq/h in the first group (p less than 0.001), from 7.98 +/- 2.34 to 0.01 +/- 0.01 mEq/h in the second group (p less than 0.001), from 6.43 +/- 2.45 to 2.09 +/- 0.50 mEq/h in the third group (p less than 0.02) and from 6.76 +/- 2.80 to 0.011 +/- 0.01 mEq/h in the fourth group (p less than 0.001). Endoscopic healing was achieved, after 14 days of treatment, respectively in 78.5%, 92.4%, 51.6% and 88.41%; this percentages increased to 82.3%, 96.8%, 68.1% and 93.5% after 21 day of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of ZnSO4 upon gastric acid secretion and carbonic anhydrase.

Starting from the multiple role zinc holds in the enzymatic processes of the body and from some positive data concerning treatment with zinc sulphate in gastric ulcer, we have studied the effect of ZnSO4 on gastric acid secretion in duodenal ulcer patients, as well as that on purified and gastric mucosa carbonic anhydrase. Gastric secretory testing showed that zinc sulphate administered in doses of 60 ml/day (1% solution) for 10 days reduced basal acid secretion in duodenal ulcer patients by 57.7%. In vitro, concentrations of ZnSO4 ranging between 10(-6) and 10(-2)M, inhibit purified carbonic anhydrase activity in a dose-dependent manner, reaching maximum effect at 10(-2)M, when carbonic anhydrase activity dropped from 2060 +/- 65 IU to 660 +/- 85 IU. A similar dose-dependent inhibition was found with gastric mucosa carbonic anhydrase activity, where ZnSO4 at 10(-2)M reduces enzyme activity from its basal value of 1.58 +/- 0.36 EU/mg to 0.88 +/- 0.21 EU/mg. Besides this effect, zinc sulphate antagonized in vitro the activation of both purified and gastric mucosa carbonic anhydrase by histamine. In conclusion, the mechanism of antisecretory effect of ZnSO4 might well be the inhibition of the carbonic anhydrase in the gastric mucosa.

Effect of verapamil on purified bovine carbonic anhydrase. An in vitro study.

Relying on previous data which prove the activation of purified and gastric mucosa carbonic anhydrase by interaction of histamine with calcium ions, the present paper investigates the effect of verapamil, a specific antagonist of calcium transport, on purified bovine red cell carbonic anhydrase. In vitro determination of enzymatic activity according to Maren's micromethod showed that verapamil, in concentrations ranging from 10(-8)-10(-3) mol/l inhibits carbonic anhydrase basal activity in a dose-dependent manner. Thus, at 10(-3) mol/l verapamil concentration - representing its maximal effect - carbonic anhydrase basal activity drops from 2114 +/- 244 IU to 1100 +/- 86 IU (p less than 0.01). At this concentration, the drug antagonizes the activating effect of histamine: while maximum concentration (10(-2) mol/l) of histamine activates the enzyme from 2116 +/- 182 IU to 3979 +/- 411 IU the enzyme activity in the presence of verapamil changes in a non-significant way to 2162 +/- 148 IU (p less than 0.10). As calcium was omitted from the in vitro system, the mechanism described here is probably independent of ion transport inhibition. The physiologic importance of this effect for gastric secretion is to be further clarified.

Inhibition of carbonic anhydrase by pirenzepine.

Previous work of the authors established a parallelism between gastric mucosa carbonic anhydrase (CA) activity and the values of acid secretion. It was shown that histamine (Ht) is a physiological activator of CA, and that there could be histaminic H2 receptors located on the molecule of CA. Pirenzepine (GZ) is a drug recently introduced in the therapy of gastroduodenal ulcer (GDU). Although its effect of decreasing acid secretion is clinically known, its mechanism of action remains uncertain. Original investigations are presented proving by in vitro and in vivo experiments on pure CA and on CA from human red blood cells and gastric mucosa that GZ is a strong inhibitor of CA. In this concept, GZ may be considered both an enzymatic inhibitor and an antagonist of histaminic H2 receptors.

Inhibition of gastric mucosa carbonic anhydrase by pirenzepine in patients with gastroduodenal ulcers.

Pirenzepine (Gastrozepin) is a drug recently introduced in the therapy of gastroduodenal ulcer (GDU). Although its effect of decreasing acid secretion is clinically known, its mechanism of action remains uncertain. The authors present investigations proving by in vitro experiments carried out on pure carbonic anhydrase (CA) and on CA from human gastric mucosa that GZ is a strong inhibitor of CA. In this acceptation, GZ may be considered both an enzymatic inhibitor and an antagonist of histamine H2 receptors.