摘要:

Variants of hepatitis B virus (HBV), hepatitis C virus (HCV) and of the hepatitis Delta virus (HDV) have been identified in patients both with acute and chronic infections. In the HBV DNA genome, naturally occurring mutations have been found in all viral genes, most notably in the genes coding for the structural envelope and nucleocapsid proteins. In the HCV RNA genome, the regions coding for the structural envelope proteins 1 and 2 as well as the 3’-contiguous nonstructural region 1 were found to be hypervariable. Viral variants may be associated with a specific clinical course of the infection, e.g. acute-fulminant or chronic hepatitis. Specific mutations may reduce viral clearance by immune mechanisms (‘immune escape’) or response to antiviral therapy (‘therapy escape’). Furthermore, mutations of envelope epitopes can lead to viral variants which are not recognized or neutralized by antibodies to wild-type virus, resulting in ‘diagnosis escape’ or ‘vaccine escape’. The exact contribution, however, of specific mutations to the pathogenesis and natural course of HBV, HCV or HDV infection, including the development of hepatocellular carcinoma, remains

ISSN:0012-2823    

DOI:10.1159/000201226

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The antroduodenal motor effects of ranitidine, and H2-receptor antagonist with cholinergic activity, and neostigmine, a cholinomimetic drug, were compared in 16 patients with idiopathic gastroparesis characterized by dysmotility-like dyspepsia, delayed gastric emptying at scintigraphy and absence of gastroduodenal phase 3 of the migrating motor complex during a manometric recording of at least 300 min. After overnight fasting in 8 of these patients, neostigmine was administered intravenously at a dose of 0.5 mg, and in the remaining 8 patients ranitidine was given intravenously at a dose of 100 mg. Ranitidine induced a gastroduodenal phase 3 activity in a significantly (p < 0.02) higher percentage of patients (87.5%) in comparison with neostigmine (25%). In the majority of patients, neostigmine induced only an irregular increase in gastroduodenal motor activity sometimes characterized by propagated and nonpropagated clustered contractions. This property of ranitidine of inducing a phase 3 activity in these patients cannot be ascribed to its weak cholinergic activity, as neostigmine, which has a more intense cholinergic activity than ranitidine, is unable to produce the effect demonstrated by ranitidine. Another unknown mechanism able to trigger the neurohormonal program of migrating motor complex phase 3 or to abolish inhibitory influences should be taken into account to explain this effect of ranitidine.

ISSN:0012-2823    

DOI:10.1159/000201227

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The concept of an alkaline tide which compensates for gastric acid secretion suggests the possibility of indirect measurement of gastric acid secretion. This study was designed to determine whether postprandial changes in renal and respiratory function could be used to assess gastric secretion in healthy adults. Volunteers ate one of three standard (low, medium or high protein) breakfasts on separate days. A fall in urine acid output was observed during 2 h after the high protein meal, but not after the medium or low protein meal. Fasting subjects showed a similar fall in urine acid output over a 2-hour period. Pretreatment with ranitidine 150 mg b.i.d. had no effect on basal or postprandial urine acid output. We conclude that changes in urine acid output are not related to the gastric secretory response to food. In a separate study, treatment with omeprazole 20 mg daily had no effect on postprandial respiratory function (minute ventilation; mixed expired CO2; minute volume of CO2 respiratory exchange ratio; venous blood pH, pCO2 or bicarbonate; and end tidal CO2). Thus we were unable to detect a respiratory alkaline tide after a standard breakfast. These findings suggest that any respiratory or urinary compensation for gastric acid secretion is too small to be of physiological or clinical significance.

ISSN:0012-2823    

DOI:10.1159/000201228

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

One of the results of gastric cytoprotection is the generation of a juxtamucosal stable pH, maintained close to neutrality by several factors among which bicarbonate secretion and mucus layer. Since Helicobacter pylori (HP) induces structural and functional changes in the gastric mucus, this study was carried out to investigate the relationship between juxtamucosal pH and HP colonization. Thirty-one dyspeptic subjects who denied a past history of gastric or duodenal ulcer and free of endoscopic lesions were studied. Juxtamucosal pH of the gastric body, antrum and duodenum and gastric luminal fluid pH were measured during upper gastrointestinal endoscopy by a flexible glass electrode passed through the biopsy channel of a gastroscope. Multiple biopsies were subsequently taken for histological investigation, HP culture and a urea quick test. Twelve subjects (39%) were infected by HP (HP+). Juxtamucosal pH (mean ± SE) was significantly lower (p = 0.0014) in the gastric body (5.67 ± 0.16) in HP+ than in HP-negative (HP- 6.41 ± 0.13 subjects, but not in the antrum (6.50 ± 0.20 in HP+ vs. 6.52 ± 0.09 in HP-) and in the duodenum (6.80 ± 0.14 in HP+ vs. 6.94 ± 0.08 in HP- subjects). No difference was found in gastric luminal fluid pH (1.71 ± 0.23 in HP+ vs. 1.80 ± 0.22 in HP-subjects). In conclusion, this study shows that dyspeptic HP+ patients have a reduced juxtamucosal pH in the gastric body but a pH in the antrum and duodenum similar to HP-

ISSN:0012-2823    

DOI:10.1159/000201229

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We examined the role of endogenous endothelin in the pathogenesis of hemorrhagic shock-induced gastric mucosal injury in rats. Animals were bled to induce hypotension (20-30 mm Hg) for 20 min and the shed blood was retransfused. Rats were sacrificed at the end of hypotension, 20 min, and 60 min after retransfusion, respectively. Gastric erosions were induced with this experimental protocol. The total area of erosions was minimal only at the end of hypotension, and increased time-dependently after blood retransfusion. Plasma endothelin concentration significantly increased at the end of hypotension and persistently increased after retransfusion, whereas in gastric endothelin concentration a significant increase was observed at 60 min after retransfusion. The gastric mucosal hemodynamics as assessed by continuous measurement with reflectance spectrophotometry showed ischemia associated with congestion after retransfusion. Treatment with a monoclonal antibody against endothelin (0.2 mg/100 g BW/h) prevented these hemodynamic disturbances, rendering a significant decrease in the total area of erosions at 20 and 60 min after retransfusion. These results strongly suggest an important role of circulating endothelin in the pathogenesis of hemorrhagic shock-induced gastric mucosal injury through mucosal microcirculatory perturbation.

ISSN:0012-2823    

DOI:10.1159/000201230

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The nutrient-dependent glucagon-like peptide-1 (7-36) amide (GLP-1) release was studied in comparison to the glucose-dependent insulin-releasing polypeptide (GIP) response in 10 healthy volunteers each undergoing various protocols. Plasma samples were saved up to 120 min after challenges by oral, intravenous or intraduodenal administration of nutrients. Basal plasma-GLP-1 concentrations ranged between 0.4 and 1.4 pM, maximal postprandial GLP-1 levels peaked between 10 and 12 pM. 120 min) increase of GLP-1 plasma levels occurred. When a mixed liquid meal was given (6 g soybean oil, 5g casein, 13 g glucose) immunoreactive (IR)-GLP-l rapidly increased and peaked after 5 min with declining levels after 30 min. In response to an intraduodenal infusion of a small glucose load (5.34 g within 120 min) a rapid, short-lasting GLP-1 response occurred whereas plasma GIP and insulin levels remained unaltered. Luminal perfusion of an isolated vascularly perfused rat ileum with a polydiet induced a rapid rise of portally released IR-GLP-1 which was followed by a sustained release. Glucose evoked sodium-dependently a sharp increase of IR-GLP-1 levels followed by a plateau release. The intraluminal infusion of a mixture of amino acids or fat was without any effect on IR-GLP-1. We hypothesize that in contrast to GIP the GLP-1 release from L cells is triggered by nervous reflexes, by putative humoral factor(s) being released from the upper small intestine in addition to nutrient stimuli acting at the luminal surface of the gut.

ISSN:0012-2823    

DOI:10.1159/000201231

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The gastrointestinal hormone cholecystokinin and the muscarinic agonist carbamylcholine are involved in pancreatic enzyme secretion through phospholipase C activation and production of the second messengers inositol trisphosphate and diacylglycerol. However, cholecystokinin induces growth of the pancreas whereas carbamylcholine does not. This study investigated the possibility of a specific cellular signalling transduction system through which cholecystokinin may induce pancreatic growth. Rat pancreatic acini were preincubated with 3H choline or 3H myristic acid to label phosphatidylcholine. They were then stimulated by caerulein, phorbol myristate acetate, and carbamylcholine; choline and phosphocholine release as well as phosphatidic acid and phosphatidylethanol production were measured to establish phospholipase D (PLD) activation. Caerulein, phorbolester and carbamylcholine increased phosphocholine release. Choline release was induced early by caerulein and later by phorbolester but not by carbachol. PLD was activated by caerulein and phorbolester but not by carbamylcholine. Increased intracellular calcium by A23187 had no effect on PLD activation but its chelation by BAPTA prevented caerulein-induced PLD activation. In conclusion, PLD seems to be selectively activated by caerulein and phorbol ester by two different mechanisms which are insensitive to carbamylcholine. It is suggested that the PLD pathway might be the cellular signalling system leading to pancreatic growth.

ISSN:0012-2823    

DOI:10.1159/000201232

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Twelve healthy volunteers (6 females, 6 males) between 26 and 36 years of age were enroled in this double-blind, randomized, placebo-controlled, three-way cross-over study. The objective was to determine the influence of lansoprazole (Agopton®, Takeda Pharma GmbH, Aachen), a novel proton pump inhibitor, in doses of 30 and 60 mg, on the intragastric pH, on meal-stimulated gastric acid secretion and on the concentration of gastrointestinal hormones and enzymes in serum and gastric juice. Active drug or placebo had to be taken as single daily morning doses on an empty stomach for 7 days. Each wash-out period between drug application periods was 2 weeks long. Lansoprazole induced a dose-related increase in intragastric pH as well as a relevant reduction of basal acid output, meal-stimulated acid output and meal-stimulated secretion volume. 60 mg lansoprazole was significantly superior to 30 mg in increasing intragastric pH. The basal secretion volume in volunteers on 30 and 60 mg lansoprazole were lower than in volunteers on placebo. Serum gastrin and serum pepsinogen concentrations increased in a dose-dependent manner. Pepsin output and pepsin activity in gastric juice were slightly decreased in volunteers on 30 mg lansoprazole and markedly suppressed in volunteers on 60 mg lansoprazole 2 h after meal stimulation. Intrinsic factor concentration increased in volunteers on lansoprazole with a clear dose relationship. The evaluation of laboratory data and reported nonserious adverse events proved the relative safety of this new antiulcer agent

ISSN:0012-2823    

DOI:10.1159/000201233

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

This study examined the gastroprotective effect of (R)-α-methylhistamine (MHA), a selective agonist of histamine H3receptors. Gastric lesions were induced in the rat by administering absolute ethanol in a volume of 1 ml. Stomachs were removed 1 h later and lesions evaluated both macroscopically and histologically. MHA dose-dependently inhibited ethanol-induced lesions in the range 1-100 mg/kg both by the intragastric and intraperitoneal route. Histological findings indicated that the number of mucous granules in surface and neck cells was increased and the process of reepithelialization was rapidly promoted by MHA. Thioperamide, at 10 mg/kg, inhibited the protective effect of 10 but not of 100 mg/kg of MHA. Larger doses of thioperamide could not be tested because of an interaction with ethanol causing central nervous system effects. Famotidine and indomethacin pretreatment only partially counteracted the MHA effect. The results indicate that MHA is highly effective in preventing ethanol-induced lesions but the exact mechanism is still uncertain

ISSN:0012-2823    

DOI:10.1159/000201234

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The potency of cisapride to stimulate esophageal motility is still a matter of conjecture. This double-blind placebo-controlled study assessed the effect of repeated oral doses of cisapride at 10 and 20 mg on interdigestive esophageal motility in 10 healthy male volunteers. In each experiment, esophageal motility was recorded continuously for 60 min with a sleeve sensor straddling the lower esophageal sphincter and four series of 10 wet swallows being performed. Analysis of motor events was computer assisted. Plasma cisapride levels amounted to 72.3 ± 6.1 ng/ml with 10 mg cisapride and 142.5 ± 11.9 ng/ml with 20 mg cisapride (p < 0.001 vs. 10 mg). Lower esophageal sphincter pressure increased from 20.6 ± 2.3 mm Hg (placebo) to 28.9 ± 2.3 mm Hg with 10 mg cisapride (p < 0.0001 vs. placebo) and to 26.8 ± 1.8 mm Hg with 20 mg cisapride (p < 0.001 vs. placebo). Cisapride increased amplitude, duration, and area but not contractility and peristaltic velocity of esophageal contraction waves. Cisapride caused a maximum rise in amplitude of 22.4%, in area of 19.4%, and in duration of 9.6%. Its effects were greatest in the proximal and middle smooth muscle segments and more pronounced with 10 than with 20 mg. We conclude that cisapride clearly increases lower esophageal sphincter pressure and, to a lesser extent, raises amplitude and prolongs duration of esophageal contraction waves. Effects on contraction waves seem to correlate with the density of cholinergic innervation. Increasing the dose above 10 mg in the steady state does not further enhance the effect in healthy subj

ISSN:0012-2823    

DOI:10.1159/000201235

出版商:S. Karger AG    

年代:1995

数据来源: Karger