The efficacy of hydrotalcite compared with OTC famotidine in the on-demand treatment of gastroesophageal reflux disease: a non-inferiority trial.

BACKGROUND: Antacids and gastric acid inhibitors are effective in the self-treatment of gastroesophageal reflux disease (GERD). The aim was to investigate onset of action of the antacid hydrotalcite compared with the OTC H2-receptor antagonist famotidine in patients suffering from heartburn. MATERIAL/METHODS: A total of 53 patients with endoscopically diagnosed GERD grade 0-1 took part in this open, randomized, parallel-group comparison trial: 26 patients received a single dose of 1000 mg hydrotalcite and 27 patients a single dose of 10 mg famotidine on the occasion of a symptomatic reflux episode. Severity of heartburn and accompanying symptoms were documented on a four-point verbal rating scale (VRS) at baseline and up to four hours after intake. Onset and duration of action were defined by the number of patients experiencing improvement of heartburn from severe or moderate to mild or none compared with baseline. RESULTS: Hydrotalcite was significantly superior (p<0.001) to famotidine in increasing the proportion of responders within the first 45 minutes, starting 10 minutes after drug intake. Between 60 and 120 minutes, both compounds showed equal efficacy. Three hours after intake the response rate was 90.9% for hydrotalcite and 92.0% for famotidine. After four hours the response rates were 86.4% for hydrotalcite and 96.0% for famotidine. In both groups, no adverse events were observed. CONCLUSIONS: The results indicate that hydrotalcite relieves the symptoms of gastroesophageal reflux faster than OTC famotidine and is equally effective for up to two hours. It is a safe and effective self-medication for on-demand treatment of heartburn.

Reduced expression of Ca2+-regulating proteins in the upper gastrointestinal tract of patients with achalasia.

AIM: To compare expression of Ca(2+)-regulating proteins in upper gastrointestinal (GI) tract of achalasia patients and healthy volunteers and to elucidate their role in achalasia. METHODS: Sarcoplasmic reticulum Ca(2+) ATPase (SERCA) isoforms 2a and 2b, phospholamban (PLB), calsequestrin (CSQ), and calreticulin (CRT) were assessed by quantitative Western blotting in esophagus and heart of rats, rabbits, and humans. Furthermore, expression profiles of these proteins in biopsies of lower esophageal sphincter and esophagus from patients with achalasia and healthy volunteers were analyzed. RESULTS: SERCA 2a protein expression was much higher in human heart (cardiac ventricle) compared to esophagus. However, SERCA 2b was expressed predominantly in the esophagus. The highest CRT expression was noted in the human esophagus, while PLB, although highly expressed in the heart, was below our detection limit in upper GI tissue. Compared to healthy controls, CSQ and CRT expression in lower esophageal sphincter and distal esophageal body were significantly reduced in patients with achalasia (P < 0.05). CONCLUSION: PLB in the human esophagus might be of lesser importance for regulation of SERCA than in heart. Lower expression of Ca(2+) storage proteins (CSQ and CRT) might contribute to increased lower esophageal sphincter pressure in achalasia, possibly by increasing free intracellular Ca(2+).

Effect of vitamin C-releasing acetylsalicylic acid on gastric mucosal damage before and after Helicobacter pylori eradication therapy.

The interaction between Helicobacter pylori (H. pylori) and nonsteroidal anti-inflammatory drugs (NSAIDs) such as acetylsalicylic acid is still controversial. This study was designed to compare the effect of acetylsalicylic acid and vitamin C-releasing acetylsalicylic acid on the gastric mucosal damage and microbleeding before and after eradication of H. pylori in 10 young healthy volunteers. Acetylsalicylic acid induced significantly more gastric lesions and higher microbleeding than acetylsalicylic acid-vitamin C. After successful H. pylori eradication therapy, acetylsalicylic acid induced significantly higher mucosal lesions and microbleeding than before eradication. In contrast, after acetylsalicylic acid-vitamin C, gastric lesion index was significantly lower and eradication therapy failed to aggravate it. All H. pylori-positive subjects showed significant up-regulation of antioxidant enzyme (superoxide dismutase, catalase, glutathione peroxidase). Plain acetylsalicylic acid stronger than acetylsalicylic acid-vitamin C reduced gastric gene expression of these antioxidant enzymes. H. pylori eradication significantly decreased expression of these enzymes and this was further enhanced by plain acetylsalicylic acid, but not acetylsalicylic acid-vitamin C. Under plain acetylsalicylic acid therapy, the expression of proinflammatory cytokines was increased before and after eradication of H. pylori. We conclude that vitamin C combined with acetylsalicylic acid, unlike plain acetylsalicylic acid without vitamin C, protects gastric mucosa in man probably due the attenuation of oxidative stress and proinflammatory cytokines.

Expression and functional role of serine/threonine phosphatases in rat esophagus.

BACKGROUND: Smooth muscle contraction is due to phosphorylation, while relaxation results from dephosphorylation of regulatory proteins such as the light chains of myosin (MLC20). Dephosphorylation of MLC20 is catalyzed by protein phosphatases (PP) types 1 and 2A. While some data are available on the expression and functional importance of PP1 and PP2A in vascular smooth muscle preparations, little is known of the importance of PP for force regulation in the gastrointestinal tract. MATERIAL/METHODS: Here we address the expression and functional importance of PP1 and PP2A in the rat esophagus. We measured both the isometric force of contraction and PP activity and also performed Western and Northern blotting for PPs in the tunica muscularis mucosae (TMM) and the muscularis mucosae propria (MM). RESULTS: Cantharidin (0.01-100 microM) inhibited PP activity in homogenates from TMM (IC50=20 KM) in a concentration-dependent manner. The mRNAs of catalytic and regulatory subunits (PP1 alpha, PP1 beta, PP2A alpha and M110) were detectable at 1.8 kb, 3.2 kb, 2.0 kb and 5.7 kb in both TMM and MM. Western blot analysis revealed PP1 in TMM and MM. PP2A (protein) was more abundant in TMM than in TMM. Cantharidin increased muscular tone in isolated preparations of TMM (starting at 100 microM) to 164.6 (14.8 % of predrug force at 300 microM (the highest concentration studied). This increase in force of contraction was comparable to that of 10 microM carbachol. CONCLUSIONS: The results suggest that PP activity can play an important role in the regulation of esophageal tone.

Neuroendocrinology of the pancreas; role of brain-gut axis in pancreatic secretion.

Exocrine pancreatic secretion, attributed initially to neural reflexes (nervism), was then found to depend also on enterohormones, especially secretin and cholecystokinin (CCK), released by the intestinal mucosa and believed to act via an endocrine pathway. Recently, CCK and other enterohormones were found to stimulate the pancreas by excitation of sensory nerves and by trigger of long vagovagal or ("brain-gut axis") enteropancreatic reflexes. Numerous neurotransmitters, such as acetylcholine, and certain neuropeptides, such as gastrin-releasing peptide (GRP), generated by neurons of the enteric nervous system (ENS) of the gut, have been implicated in the regulation of exocrine pancreas. Recently, peptides affecting appetite behavior and originating from the gut, such as leptin and ghrelin, or from the pancreas, such as pancreatic polypeptide and neuropeptide Y, appear to modulate the exocrine pancreas via hypothalamic centers. The aim of this review is to highlight the interaction of nerves and enterohormones in the regulation of exocrine pancreatic secretion.

H. pylori infection, atrophic gastritis, cytokines, gastrin, COX-2, PPAR gamma and impaired apoptosis in gastric carcinogenesis.

BACKGROUND: Helicobacter pylori (Hp) infection represents a crucial factor in pathogenesis of gastric cancer (GC). Factors emanating from bacterium as well as from environmental contributions such as salt diet and inadequate supply of antioxidants, affect the risk for GC development. RESULTS: Atrophic gastritis is considered to be a precursor lesion of intestinal type GC that is accompanied by hypergastrinemia with subsequent induction of cyclooxygenase-2 (COX-2), whose products are responsible for slowing apoptosis and for angiogenesis in GC tumor. The involvement of proinflammatory cytokines (especially IL-1 and IL-8) and reactive oxygen species (ROS) due to NF kappa B activation, increased cell proliferation combined with inhibition of apoptosis as well as upregulation of peroxisome proliferation activated receptor gamma (PPAR gamma) and inducible nitric oxide synthase (iNOS) appear to be major molecular biology alterations in pathogenesis of GC. CONCLUSIONS: These results suggest the therapeutic usefulness of inhibitors of gastrin expression and release such as powerful somatostatin analogs (Sandostatin) or blockers of COX-2 (coxibs) in the control of GC development and progression as chemopreventive agents. Comparative genomic and proteomic is the key in identifying biomarkers in host and bacterium for the prediction of gastric cancer in Hp-infected patients.

Relationship of clinical features and laboratory parameters to thyroid echogenicity measured by standardized grey scale ultrasonography in patients with Hashimoto's thyroiditis.

BACKGROUND: Hashimoto's thyroiditis is associated with a diffuse reduction in thyroid echo levels. The purpose of this study was to determine the degree of hypoechogenicity in correlation to clinical features and laboratory parameters. MATERIAL/METHODS: 52 patients with Hashimoto's thyroiditis under substitutive therapy with levothyroxine (50-200 g daily) and 100 normal euthyroid volunteers (with no features of autoimmune disease who were not taking any thyroid medication) as controls were investigated. Determination of plasma free thyroxine (FT4) and TSH as well as peroxidase- (TPO), thyroglobulin- and TSH receptor (TSH-R) antibodies were performed. Thyroid volume was measured by conventional ultrasonography. Tissue echogenicity was characterized by standardized grey scale ultrasonography under defined operating conditions. Mean densities were given in a histogram range of grey scales between 0-63 GWE (= Grauwerteinheiten). RESULTS: Patients with Hashimoto's thyroiditis revealed significantly lower echo levels (19.6+/-2.6 GWE) than controls (25.6+/-2.0 GWE, p<0.001). High graded hypoechogenicity was associated with large goiters, persistently increased TSH levels (subclinical hypothyroidism) and highly elevated TPO-antibodies. CONCLUSIONS: Standardized grey scale ultrasonography allows for reproducable correlations between functional status and morphological characteristics of the thyroid gland in Hashimoto's thyroiditis. The results hint at a stronger inflammatory process in higher grades of hypoechogenicity.

Impact of Helicobacter pylori and nonsteroidal anti-inflammatory drugs on gastric ulcerogenesis in experimental animals and in humans.

Helicobacter pylori (H. pylori) and nonsteroidal anti-inflammatory drugs (NSAID) are the most common pathogens in the gastroduodenal mucosa in animals and humans, but their relationship in ulcerogenesis has been little studied. According to some authors, H. pylori infection in humans does not act synergistically with NSAID on ulcer healing, therefore, there is no need to eradicate the germ. This notion is supported by the finding that the eradication of H. pylori does not affect NSAID-induced gastropathy treated with omeprazole and that H. pylori infection induces a strong cyclooxygenase-2 expression resulting in excessive biosynthesis of gastroprotective prostaglandins, which should in turn counteract NSAID-induced gastropathy and heal the existing ulcer. Other investigators claim that H. pylori infection acts synergistically with NSAID on ulcer development, therefore, H. pylori should be eradicated, particularly at the start of long-term NSAID therapy. Maastricht 2-2000 consensus also recommends eradication prior to NSAID treatment, but this eradication does not appear to accelerate ulcer healing or to prevent the recurrent ulcers in NSAID users. Our studies in almost 6,000 dyspeptic patients undergoing upper endoscopy and [(13)C]-urea breath test (UBT) revealed that about 70% of these patients are H. pylori (+) and about 30.6% of these develop gastroduodenal ulcers. Of these ulcers, over 70% were H. pylori (+) positive, 12% NSAID (+), 8% were both H. pylori (+) and NSAID (+), while 22% ulcers were H. pylori (-) and NSAID (-) or "idiopathic" ulcers. Basically, our results support Hawkey's concept and this also agrees with our findings in the rat model showing that: (1) there is no synergistic interaction between H. pylori infection and NSAID on gastric ulcer development, (2) H. pylori and NSAID are independent risk factors for peptic ulceration, and (3) NSAID therapy in H. pylori positive patients attenuates the ulcer development possibly due to direct inhibitory action of these drugs on H. pylori.

Case presentation of gastrinoma combined with gastric carcinoid with the longest survival record -- Zollinger-Ellison syndrome: pathophysiology, diagnosis and therapy.

BACKGROUND: Zollinger-Ellison syndrome is a very rare disease caused by tumor with gastrin producing cells accompanied by hypergastrinemia leading to gastric hypersecretion and peptic ulcers and their complications. CASE STUDY: Female case of gastrinoma (Zollinger-Ellison syndrome; Z-E) with a record of 38 yrs of survival. Acute gastro-duodenal ulcers started at 28 yr of age and Z-E was diagnosed by using gastrin assays. Basal and maximal acid outputs and ratio of basal/maximal outputs were away over normal limits. Because of ulcer recurrence and complications, patient was subjected to several gastric surgeries but refused total gastrectomy. She was also treated with many H2-receptor (R) antagonists and proton-pump inhibitors (PPI), each new drug being initially highly effective but then showing declining efficacy except when PPI, lansoprazole was used. The gastrin level rose in the course of disease from initial high value of 2000 pg/mL to the extreme 4500 ng/mL at present. During the last 2 yrs, metastasis mainly to liver developed and they were successfully treated by synthetic octapeptide derivative of somatostatin and, as a result, metastatis partly reduced and plasma gastrin drasticly decreased. Biopsy taken from liver metastasis showed the presence of typical gastrinoma cells with gastrin and chromogranin, while that from oxyntic mucosa revealed the ECL-cell hyperplasia with carcinoid tumors and unexpected gastric atrophy. CONCLUSIONS: This phenomenal case described in this article might be the new proven evidence needed by gastroenterologists to overturn the traditional treatment using total gastrectomy as a treatment of choice to the partial gastrectomy combined with proton pump inhibitors.