Antibody response against gastrointestinal antigens in demyelinating diseases of the central nervous system.

BACKGROUND: Antibodies against gastrointestinal antigens may indicate altered microbiota and immune responses in the gut. Recent experimental data suggest a connection between gastrointestinal immune responses and CNS autoimmunity. METHODS: Antibodies against gliadin, tissue transglutaminase (tTG), intrinsic factor (IF), parietal cells (PC) and Saccharomyces cerevisiae (ASCA) were screened in the sera of 45 patients with AQP4-seropositive neuromyelitis optica (NMO) and NMO spectrum diseases (NMO/NMO-SD), 17 patients with AQP4-seronegative NMO, 85 patients with clinically definite multiple sclerosis (MS), and 48 healthy controls (HC). RESULTS: Thirty-seven percentages of patients with AQP4-seropositive NMO/NMO-SD and 28% of patients with MS had at least one particular antibody in contrast to 8% of HC (P < 0.01, respectively). Antibodies were most common (46%) in AQP4-seropositive myelitis (P = 0.01 versus HS, P = 0.05 versus MS). Anti-gliadin and ASCA were more frequent in the AQP4-seropositive NMO-spectrum compared to controls (P = 0.01 and P < 0.05, respectively). CONCLUSION: Antibody responses against gastrointestinal antigens are common in MS and AQP4-seropositive NMO/NMO-SD, especially in longitudinally extensive myelitis.

Survey of Raynaud's phenomenon and systemic sclerosis based on a representative study of 10,000 south-Transdanubian Hungarian inhabitants.

OBJECTIVES: To assess the prevalence of Raynaud's phenomenon (RP) and of RP associated systemic sclerosis (SSc) in a large regional representative study. METHODS: Ten thousand individuals aged between 14-65 years participated in face-to-face interviews. The stratified sample of the South-West Hungarian population was representative for age, sex and urban or rural residence. Individuals reporting complaints suggesting the presence of "clinically significant" RP were asked to undergo a clinical investigation. Patients showing complaints provoked by taking something out of the freezer (-20 degrees C) compartment of the refrigerator and/or whether they had experienced digital ulcers were sorted into this category. RESULTS: The overall prevalence of RP was at least 578.9/10,000, and the prevalence of "clinically significant" RP could be calculated as at least 87.7/10,000 inhabitants. In this latter group 17.2% of the cases had either established SSc or anticentromere antibody or scleroderma capillary pattern on nailfold capillaroscopy. SSc with "clinically significant" RP and/or ulcers was identified in a prevalence of 9.1/10.000 individuals, whilst there was a prevalence of 14.7/10,000 of RP with either anticentromere antibody or scleroderma capillary pattern. CONCLUSIONS: "Clinically significant" RP affects almost 1% of the population. We identified cases with early stages of scleroderma spectrum disorder showing either anticentromere autoantibody or scleroderma capillary pattern. The prevalence of SSc was found to be higher than expected. It is reasonable to screen "clinically significant" RP cases for scleroderma-related symptoms because this approach makes it possible to identify patients with both SSc and early scleroderma related symptoms.

A biochemical and pharmacological approach to the genesis of ulcer disease II. A model study of stress-induced injury to gastric mucosa in rats.

Biochemical and molecular pharmacological studies were carried out in the gastric fundic mucosa during the development of stress ulcer in rats. The aims of this study were: (1) to evaluate the changes in membrane-bound ATP-dependent energy systems during the development of stress ulcer; (2) to prove (or to exclude) the presence of tissue hypoxia in the rat gastric mucosa during the development of stress ulcer; (3) to obtain further evidence of the existence of a feedback mechanism between ATP-ADP, ATP-cAMP, and cAMP-AMP transformations during the development of stress ulcer; (4) to analyze the different biochemical changes in the gastric mucosa before and after the macroscopic appearance of stress-induced gastric mucosal lesions (ulcers). The observations were carried out on both sexes of CFY-strain rats of 180 to 210 g body weight. The animals were deprived of food for 24 hours before the experiments. The animals were forced to swim in water (at 24 degrees C) for five hours. They were sacrificed at 0, 1, 2, 3, 4, and 5 hours after the introduction of stress. The tissue levels of ATP, ADP, AMP/ADP, and lactate were enzymatically measured; the cAMP was measured by radioimmunoassay. The adenylate pool (ATP + ADP + AMP), ratio of ATP/ADP, and "energy charge" [(ATP + 0.5 ADP)/(ATP + ADP + AMP)] were calculated. The membrane (Mg2(+)-Na(+)-K(+)-dependent) ATPase was prepared from the rat gastric fundic mucosa. Dose-response curves for epinephrine, cAMP, and AMP were determined on Na(+)-K(+)-dependent ATPase; also, the affinity, intrinsic activity curves, pD2, pA2 and alpha were calculated for all components. It was found that: (1) gastric mucosal lesions appeared and increased gradually from three hours after introduction of stress; (2) the extent of ATP-cAMP and cAMP-AMP transformations was increased considerably during the development of stress ulcer; (3) the extent of ATP-ADP transformation was completely inhibited; (4) the activity of Na(+)-K(+)-dependent ATPase from rat gastric fundic mucosa could be inhibited by epinephrine, cAMP, and AMP; (5) the ratio of ATP/ADP was unchanged in the first time period (from 0 to 3 hours), after which its value increased; (6) the value of "energy charge" (e.g., the extent of phosphorylation and/or dephosphorylation) of cells was decreased at two and three hours, after which its value returned to a normal level; (7) there was no increase in the tissue level of lactate; (8) several biochemical changes (decrease of ATP, ADP, "energy charge," increase of cAMP, AMP) preceded the macroscopic appearance of stress ulcer.(ABSTRACT TRUNCATED AT 400 WORDS)

Influence of [4Cl-D-Phe6,Leu17]VIP on VIP- and central TRH-induced gastric hyperemia.

The specific VIP receptor antagonist, [4Cl-D-Phe6,Leu17]VIP, infused i.v. blocked close-intra-arterial infusion of VIP-induced increase in gastric mucosal blood flow (GMBF, measured by the hydrogen gas clearance), and decrease in mean arterial blood pressure while not influencing basal levels in urethane-anesthetized rats. The thyrotropin-releasing hormone (TRH) stable analog, RX 77368, injected intracisternally (IC, 30 ng) increased GMBF and blood pressure. The VIP antagonist did not significantly reduce the GMBF response to IC RX 77368 while enhancing the rise in blood pressure. These findings indicate that [4Cl-D-Phe6,Leu17]VIP is an antagonist for exogenous VIP-induced gastric hyperemia and hypotension and that VIP modulates the systemic blood pressure response to IC RX 77368 at 30 ng while not playing a primary role in the increase of GMBF.

Changes of gastric mucosal biochemistry in ethanol-treated rats with and without acute surgical vagotomy.

The biochemical background of ethanol-(ETOH) induced gastric mucosal damage was studied in rats with intact vagus and after acute surgical vagotomy. Observations were carried out on Sprague-Dawley (CFY) strain rats of both sexes. Gastric mucosal lesions were produced by intragastric administration of 1 ml 96% ethanol. Bilateral truncal surgical vagotomy was carried out 30 min before ETOH administration. The number and severity of gastric mucosal lesions was noted 1 h after ETOH administration. Biochemical measurements (gastric mucosal level of ATP, ADP, AMP, cAMP and lactate) were carried out from the total homogenized gastric mucosa. The adenylate pool (ATP + ADP + AMP), energy charge ((ATP + 0.5 ADP)/(ATP + ADP + AMP)) and ratio of ATP/ADP were calculated. It was found that: 1) ATP transformation into ADP increased, while ATP transformation in cAMP decreased in ethanol-treated animals with intact vagus nerve, while these transformations were quite the opposite in vagotomized animals: 2) no significant changes were found in the tissue level of lactate: and 3) the extent of biochemical changes was significantly less after surgical vagotomy. It is concluded that an intact vagus is basically necessary for the metabolic adaptation of gastric mucosa.

Otilonium bromide enhances sensory thresholds of volume and pressure in patients with irritable bowel syndrome.

UNLABELLED: Visceral hyperalgesia has been suggested to play a role in the development of symptoms presented by irritable bowel syndrome patients. Otilonium bromide was developed to block smooth muscle Ca release to control cramping pain of these patients. AIMS: to determine whether otilonium bromide can influence sensory thresholds of patients suffering from irritable bowel syndrome. METHODS: 15 patients with Rome-II positive IBS were tested by Synectics Visceral Stimulator Barostat using rapid phasic distension (870 ml/min). The sensory threshold for first sensation, stool, pain and maximum tolerable volume and pressure were measured. All of the parameters were tested before and 1 week after the initiation of otilonium bromide (Spasmomen, Berlin Chemie, 3x40 mg) therapy. RESULTS: The perceptual thresholds for first sensation, stool, pain and maximum tolerable distention were, 8.8+/-1.7 Hgmm, 19.2+/-2.1 Hgmm, 26.3+/-2.8 Hgmm, 28.7+/-2.8 Hgmm for pressure, 90+/-21 ml, 145+/-28 ml, 208+/-25 ml, 213+/-28 ml for volume, before treatment, respectively. Otilonium bromide treatment did not influence the thresholds for first sensation and stool, 7.4+/-1.4 Hgmm, 20.7+/-4.6 Hgmm and 83+/-21 ml, 178+/-35.8 ml, respectively. The pressure threshold of pain was significantly higher 1 week after treatment (26.3+/-2.8 Hgmm vs. 29.1+/-5.5 Hgmm, P<0.05), but the volume threshold of this sensation remained unchanged (208+/-25 ml vs. 234+/-39 ml, not significant). The pressure (28.7+/-2.8 Hgmm vs. 38.1+/-3.4 Hgmm, P<0.05) and volume (213+/-28 ml vs. 278+/-27 ml, P<0.05) thresholds for maximum tolerable volume were increased by 7 days otilonium bromide treatment. CONCLUSION: These data suggest that otilonium bromide enhances sensory thresholds to recto-sigmoideal distention.

Vagus-mediated activation of mucosal mast cells in the stomach: effect of ketotifen on gastric mucosal lesion formation and acid secretion induced by a high dose of intracisternal TRH analogue.

TRH analogue, RX 77368, injected intracisternally (i.c.) at high dose (3 microg/rat) produces gastric mucosal lesion formation through vagal-dependent pathway. The gastric mucosal hyperemia induced by i.c. RX 77368 was shown to be mediated by muscarinic vagal efferent fibres and mast cells. Furthermore, electrical vagal stimulation was observed to induce gastric mucosal mast cell degranulation. The aim of the study was to assess the influence of ketotifen, a mast cell stabilizer, on RX 77368-induced gastric lesion formation and gastric acid secretion. RX 77368 (3 microg, i.c.) or vehicle (10 microL, i.c.) was delivered 240 min prior to the sacrifice of the animals. Ketotifen or vehicle (0.9% NaCl, 0.5 mL) was injected intraperitoneally (i.p.) at a dose of 10 mg x kg(-1) 30 min before RX 77368 injection. The extent of mucosal damage was planimetrically measured by a video image analyzer (ASK Ltd., Budapest) device. In the gastric acid secretion studies, the rats were pretreated with ketotifen (10 mg x kg(-1), i.p.) or vehicle (0.9% NaCl, 0.5 mL, i.p.), 30 min later pylorus-ligation was performed and RX 77368 (3 microg, i.c.) or vehicle (0.9% NaCl, 10 microL, i.c.) was injected. The rats were killed 240 min after i.c. injection, and the gastric acid secretion was measured through the titration of gastric contents with 0.1 N NaOH to pH 7.0. RX 77368 (3 microg, i.c.) resulted in a gastric mucosal lesion formation involving 8.2% of the corpus mucosa (n = 7). Ketotifen elicited an 85% inhibition on the development of mucosal lesions (n = 7, P < 0.001) whereas ketotifen alone had no effect on the lesion formation in the mucosa (n = 7). The RX 77368 induced increase of gastric acid secretion was not influenced by ketotifen pretreatment in 4-h pylorus-ligated animals. Central vagal activation induced mucosal lesion formation is mediated by the activation of mucosal mast cells in the stomach. Mast cell inhibition by ketotifen does not influence gastric acid secretion induced by i.c. TRH analogue in 4-h pylorus-ligated rats.

Failure of capsaicin-containing red pepper sauce suspension to induce esophageal motility response in patients with Barrett's esophagus.

UNLABELLED: The physiologic importance of afferent sensory pathways in the esophageal motor functions has been recently recognised. Capsaicin-sensitive sensory afferents were shown to play a role in the maintenance of mucosal integrity of the GI tract, and regulation of human esophageal motility. The aim of this study was to investigate the effect of topical application of capsaicin-containing red pepper sauce (Tabasco, 25%v/v, pH:7.0) suspension on the phasic activity of the human esophagus of healthy volunteers and patients with Barrett's esophagus. METHODS: The diagnosis of Barrett's esophagus was based on the findings of esophagoscopy and histology taken from the squamocolumnar junction of the esophagus. Esophageal motility was measured by perfusion manometry before and after application of red pepper sauce. RESULTS: Capsaicin containing red pepper sauce increases the motility response (LES tone, contraction amplitude, propagation velocity) of the human esophagus in healthy volunteers. This response failed in patients with Barrett's esophagus. CONCLUSION: Impaired esophageal sensory motor function may serve as one etiologic role in the development of Barrett's esophagus.

Vagal nerve and the gastric mucosal defense.

An essential role for an intact vagal nerve has been proven in the development of gastric mucosal cyto- and general protection. On the other hand, chemically-induced (ethanol, HCl, indomethacin) gastric mucosal damage is enhanced after acute surgical vagotomy. The aims of this paper were to study the possible mechanisms of the vagal nerve in the development of gastric mucosal defense. The following questions were addressed: 1) effect of surgical vagotomy on the development of ethanol- (ETOH), HCl-, and indomethacin (IND)-induced gastric mucosal damage: 2) changes in the gastric mucosal defense by scavengers, prostacyclin and other compounds (small doses of atropine and cimetidine; 3) changes in the gastric mucosal vascular permeability due to chemicals; 4) effect of indomethacin in the ETOH and HCl models with and without surgical vagotomy; 5) changes in the gastric mucosal content of prostacyclin and PGE2 in the ETOH and HCl models after surgical vagotomy; and 6) changes in the role of SH-groups in gastric mucosal defense after surgical vagotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

13C-Urea breath test is superior in sensitivity to detect Helicobacter pylori infection than either antral histology or rapid urease test.

There is no single technique which fulfils the criterion for a reference method to detect Helicobacter pylori (Hp) infection. The aim was to compare the results of antral histology (H), rapid urease test (U) and urea breath test (UBT) from antral biopsy samples in patients having gastric or duodenal lesions during upper GI endoscopy. We used the following methods: 1) biopsy specimens for histology (Warthin-Starry staining); 2) rapid urease test; and 3) 13C-urea breath test with infrared spectrometry. The total number of patients was 166 examined by H, U, and UBT. H, U and UBT were negative (-) in 64 patients and positive (+) in 51. The true positivity and false negativity (%, number of patients in parentheses) of each method based upon the positivity of the other two tests were: H+, U+ (54): UBT+, 94.4% (51) and UBT-, 5.6% (3); H+, UBT+ (57): U+, 89.5% (51) and U-, 10.5% (6); U+, UBT+ (65): H+, 78.5% (51) and H-, 21.5% (14). If Hp infection is considered to be positive when at least two tests detect the presence of Hp, UBT shows the highest sensitivity in comparison to histology of biopsy specimens and urease test. UBT is highly recommended as a screening test for Hp infection in patients presenting upper GI endoscopic alterations.

One year follow-up of patients after successful helicobacter pylori eradication therapy.

UNLABELLED: The aim of this study was to investigate the Helicobacter pylori (Hp) status of patients who underwent successful eradication therapy 1 year prior to the study and to evaluate their current symptoms. METHODS: all of the patients were initially evaluated by oesophago-gastro-bulboscopy and the Hp status was determined by at least two different methods [rapid urease test, histology or urea breath test (UBT)]. The Hp infection was treated with a 1-week triple therapy protocol, and the UBT was repeated 4-6 weeks later. We invited back 110 patients who had negative post-eradication UBT results 12+/-3 months prior to the study period. UBT was repeated and a questionnaire was completed about the previous and present complaints and medication. RESULTS: 80 of the 110 patients (73%) came back for the follow-up. Twenty five patients had peptic ulcer disease, 36 patients had gastritis or duodenitis without erosive lesions, and 19 patients had erosive form of gastritis or duodenitis initially. All of the patients except one in the erosive gastritis group had negative control UBT 1 year after the eradication, which means 1.25% recurrence rate within 1 year. The eradication therapy completely revealed the symptoms of 16 patients in the ulcer group (64%), 13 patients in the gastroduodenitis group (36%, P=0.03 vs. ulcer patients), 10 patients with erosive gastroduodenitis (52%), but this was only temporary. One year after the eradication therapy seven of the ulcer patients (28%), 11 patients with gastroduodenitis (31%) and seven patients with erosive gastroduodenitis (37%) were symptom-free. Most of the patients had epigastric pain (44%), heartburn (43%) and/or abdominal distension (33%). Nine ulcer patients (36%), 10 patients with gastroduodenitis (28%) and five patients with erosive gastroduodenitis (26%) were taking H(2)-blockers regularly. CONCLUSION: the 1-month post-eradication UBT was probable true negative in all of the evaluated cases, since 79 patients (98.75%) were also negative after 1 year. The Hp recurrence rate is very low (1.25%) in a 1-year period. The symptoms were relieved shortly after eradication therapy in the majority of patients with ulcer disease or erosive lesions. However, significantly smaller portion of the patients with gastroduodenitis became symptom-free. Only about one third of the treated patients remained symptom-free 1 year after the eradication.

The key-role of vagal nerve and adrenals in the cytoprotection and general gastric mucosal integrity.

BACKGROUND: Our laboratory group observed earlier that the gastric mucosal cytoprotective effect of prostacyclin (PGI(2)) disappeared after surgical vagotomy in rats. Similarly to this, the beta-carotene induced gastric cytoprotection disappeared in adrenalectomized rats too. AIMS: In these studies we aimed to investigate the possible role of vagal nerve and adrenals in the development of gastric mucosal lesions induced by exogenously administered chemicals (ethanol, HCl, NaOH, NaCl and indomethacin), and on the effects of cytoprotective and antisecretory drugs (atropine, cimetidine), and scavengers (vitamin A and beta-carotene). METHODS: The observations were carried out in fasted CFY strain rats. The gastric mucosal lesions were produced by intragastric (i.g.) administration of narcotising agents (96% ethanol; 0.6 M HCl; 0.2 M NaOH; 25% NaCl) or subcutaneously (s.c.) administered indomethacin (20 mg/kg) in intact, surgically bilaterally vagatomized, and adrenalectomized rats without or with glucocorticoid supplementation (Oradexon, 0.6 mg/kg given i.m. for 1 week). The gastric mucosal protective effect of antisecretory doses of atropine (0.1-0.5-1.0 mg/kg i.g.) and cimetidine (10-25-50 mg/kg i.g.), and vitamin A and beta-carotene (0.01-0.1-1.0-10 mg/kg i.g.) was studied. The number and severity of mucosal gastric lesions was numerically or semiquantitatively measured. In other series of observations the gastric acid secretion and mucosal damage were studied in 24 h pylorus-ligated rats without and with acute bilateral surgical vagotomy. RESULTS: It was found that: (1) the chemical-induced gastric mucosal damage was enhanced in vagotomized and adrenalectomized rats, meanwhile the endogenous secretion of gastric acid, and the development of mucosal damage can be prevented by surgical vagotomy; (2) the gastric cyto- and general protection produced by the drugs and scavengers disappeared in vagotomized and adrenalectomized rats; (3) the gastric mucosal protective effects of drugs and of scavengers returned after sufficient glucocorticoid supplementation of the rats. CONCLUSION: It has been concluded that the intact vagal nerve and adrenals have a key role in the gastric mucosal integrity, and in drugs- and scavengers-induced gastric cyto- and general mucosal protection.

Prevalence of the factor V Leiden mutation in human inflammatory bowel disease with different activity.

BACKGROUND: the developmental mechanism of inflammatory bowel disease (IBD) in patients is unknown, but it may be influenced by different environmental and genetical factors. AIMS of this study were: (1) to classify the IBD patients according the disease activity; and (2) to determine the presence of factor V Leiden mutation in IBD patients. PATIENTS AND METHODS: the observation was carried out in 49 patients with Crohn's disease (CD) and 29 patients with ulcerative colitis (UC). None of them had a history of thrombotic episodes. IBD was diagnosed by conventional clinical, endoscopic, radiological and histological criteria. The factor V Leiden mutation was detected by the polymerase chain reaction (PCR) method. Crohn's disease activity index (CDAI) was evaluated using the method of the National Cooperative Crohn's Disease Study. We determined the UC disease activity according to Truelove-Witts classification. RESULTS: The prevalence of factor V Leiden mutation was increased in both populations of the patients to compare it with healthy persons (14.28 and 27.58% vs. 5.26%, n=7/49 and 8/29 vs. 3/57). The statistical analysis did not show a significant relationship between the CDAI or the Truelove-Witts grade in UC and the presence of Leiden mutation. CONCLUSION: the presence of factor V Leiden mutation probably has a role in the development of IBD. Our results suggest a higher prevalence of this mutation in Central European patients than in Southern, Northern Europe or America, may be due to the genetical differences of these populations.

Role of nitric oxide in the gastric cytoprotection induced by central vagal stimulation.

The role of nitric oxide (NO) in the vagal cholinergic-mediated cytoprotective effect of intracisternal (i.c.) injection of the stable thyrotropin-releasing hormone (TRH) analog, RX 77368, was investigated in conscious rats. RX 77368 (1.5 ng i.c.) reduced by 88% gastric hemorrhagic lesions induced by oral administration of ethanol (60%). L-NG-Nitro-arginine methyl ester (L-NAME, 3 mg/kg i.v.), an inhibitor of NO synthase, abolished the cytoprotection provided by i.c. RX 77368. The effect of L-NAME was reversed by L- but not D-arginine. These results suggest that the L-arginine-nitric oxide pathway is involved in the cytoprotective effect of i.c. TRH analog, probably through the modulation of gastric mucosal blood flow.

Delayed gastric emptying induced by inhibitors of nitric oxide synthase in rats.

The effect of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester, on gastric emptying of a non-nutrient solution was investigated in conscious rats. NG-Monomethyl-L-arginine (10 mg/kg i.v.) and NG-nitro-L-arginine methyl ester (3 or 10 mg/kg i.v.) inhibited the 20-min rate of gastric emptying of liquids by 34%, 69% and 84% respectively, whereas the 0.3 mg/kg of NG-nitro-L-arginine methyl ester or 3 mg/kg of NG-monomethyl-L-arginine had no effect. The inhibitory effect of NG-nitro-L-arginine methyl ester (3 mg/kg) was prevented by L-arginine (300 mg/kg i.v.), but not by D-arginine (300 mg/kg i.v.). NG-Nitro-L-arginine methyl ester (0.3-10 mg/kg) induced a dose-related increase in mean blood pressure up to 161 +/- 10 mm Hg. Spontaneous hypertensive rats with a mean blood pressure of 180 +/- 5 mm Hg had a gastric emptying rate of 51.9 +/- 6.1%. These data indicate that NO synthase inhibitors given i.v. at doses that inhibit NO synthase, delay gastric emptying through mechanisms which are unrelated to changes in arterial blood pressure.

Ketotifen prevents gastric hyperemia induced by intracisternal thyrotropin-releasing hormone at a low dose.

The thyrotropin-releasing hormone (TRH) analog, RX 77368, (p-Glu-His-(3,3'-dimethyl)-Pro-NH2) injected intracisternally (i.c.) at low doses increases gastric mucosal blood flow through vagal cholinergic and calcitonin gene-related peptide dependent pathways. The influence of the mast cell stabilizer, ketotifen, on i.c. injection of RX 77368 (1.5 ng)-induced changes in gastric mucosal blood flow (hydrogen gas-clearance technique), gastric acid secretion and mean arterial pressure was studied in urethane-anesthetized rats. RX 77368 increased gastric blood flow by 131% and systemic arterial pressure by 11 mm Hg and decreased gastric mucosal vascular resistance by 54% whereas acid secretion was not altered within the 30 min period post injection. Ketotifen had no effect on these basal parameters but abolished i.c. RX 77368-induced increased gastric mucosal blood flow and decreased gastric vascular resistance. These data suggest that mast cells may be part of the peripheral mechanisms involved in vagal gastric hyperemia induced by TRH analog injected i.c. at a low dose.

Failure of prostacyclin, beta-carotene, atropine and cimetidine to produce gastric cyto- and general mucosal protection in surgically vagotomized rats.

Different chemicals (such as ethanol, HCl, drugs) produce gastric mucosal injury. A special type of gastric mucosal defense, which differed from the inhibition of gastric acid secretion, was discovered in response to small doses of prostaglandins. This phenomenon was termed "gastric cytoprotection". Later, the existence of gastric cytoprotection was proved using different compounds, such as vitamin A and other carotenoids, prostacyclin, small doses of anticholinergic and H2-blocking agents. These compounds produce cyto-protection by different mechanisms. In this study we tested the role of vagus nerve on the development of these different types of gastric cytoprotection. These compounds prevent ethanol-induced gastric mucosal injury in rats with intact vagus nerve, but their cyto- and mucosal protective effects disappear in surgically vagotomized rats. These results indicate that the intact vagus nerve is basically necessary for the overproduction of HCl and pepsin secretion, and for the development of gastric cytoprotection, produced by different compounds (e.g. prostacyclin, beta-carotene, small doses of atropine and cimetidine) acting without the presence of inhibition of gastric acid secretion.

Mechanisms of action of retinoids in gastrointestinal mucosal protection in animals, human healthy subjects and patients.

UNLABELLED: Retinoids prevent chemically induced gastric mucosal damage without inhibiting gastric acid secretion ("nutritional gastric cytoprotection"). The gastroprotective effects of retinoids do not depend on 1) vitamin A activity; 2) number of unsaturated double bonds; 3) the presence of a characteristic chemical structure of their terminal components; however, they depend on 1) intact vagal nerve and 2) adrenals in experimental animals. The gastric cytoprotective effect of retinoids produces a dose-dependent inhibition of ATP-transformation into ADP. It also increases the transformation of ATP into cAMP. Other features of these gastric cytoprotective effects of retinoids include: 1) The retinoid-induced gastric mucosal protection differs from that of PGs; 2) The cAMP is an intracellular signal in the development of gastric mucosal damage produced by chemicals (e.g., ethanol, HCl, indomethacin) and in the protection of gastric mucosa induced by retinoids (but not by PGs); 3) The gastric mucosal protection induced by retinoids and gastric mucosal permeability can be separated in time. The existence of gastric mucosal protection can be demonstrated in healthy persons (against indomethacin treatment), in patients with gastric ulcer (GU) and duodenal ulcer (DU) without any inhibition of gastric acid secretion. The serum levels of vitamin A and zeaxanthin were significantly decreased in patients with chronic gastrointestinal (GI) inflammatory diseases (e.g., terminal ileitis, ulcerative colitis), colorectal polyposis, and different (e.g., esophageal, gastric, pancreatic, hepatocellular and colorectal) malignant diseases. The serum levels of vitamin A provitamins were unchanged and their GI mucosal protective effects do not depend on vitamin A activity. CONCLUSIONS: 1) Abundant experimental and human observations clearly proved the defensive role of retinoids in the GI tract; 2) There is a correlation between the a) scavenger properties of retinoids vs. intact vagal nerve; b) scavenging properties vs. intact adrenals. 3) The GI mucosal protective effect of retinoids is correlated with biochemical changes in the GI mucosa.

Cellular energy status of the gastric mucosa and gastric mucosal prevention by vitamin A in indomethacin-treated rats.

To evaluate the cellular energy status of gastric mucosa during the development of gastric mucosal damage and its prevention by application of a cytoprotective scavenger (vitamin A) in rats treated with indomethacin, the tissue levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and lactate were measured enzymatically, while the concentration of cyclic adenosine monophosphate (cAMP) was measured by radioimmunoassay, 4 h after the treatment with indomethacin and vitamin A simultaneously. It was found that a) the tissue levels of ATP, cAMP, AMP and the ratio of ATP/ADP were increased dose-dependently in the gastric mucosa in connection with the development of gastric mucosal prevention produced by vitamin A, b) the tissue level of ADP was decreased dose-dependently by vitamin A in indomethacin-treated rats, and c) the value of "energy charge" and the ratio of the ATP-ADP was unchanged during the vitamin A treatment in indomethacin-treated rats. The presence of tissue hypoxia could not be proved either in the development of indomethacin-induced gastric mucosal damage nor in the prevention of gastric mucosal damage by vitamin A.