85 research outputs found
Clinical trial design in adult reflux disease: a methodological workshop
No full textBackground: The development of well-tolerated acid suppressant drugs has stimulated substantial growth in the number of trials assessing therapy options for gastro-oesophageal reflux disease (GERD). Aim: To develop consensus statements to inform clinical trial design in adult patients with GERD. Methods: Draft statements were developed employing a systematic literature review. A modified Delphi process including three rounds of voting was used to reach consensus. Between voting, statements were revised based on feedback from the Working Group and additional literature reviews. The final vote was at a face-to-face meeting that included discussion time. Voting was conducted using a six-point scale. Results: At the last vote, 93% of the final 102 statements achieved consensus (defined a priori as being supported by ‡75% of the votes). The Working Group strongly supported the development of validated patientreported outcome instruments. Symptom assessments carried out by the investigator were considered unacceptable. There was agreement that exclusion from clinical trials should be minimized to improve generalizability, that prospective evaluation ideally requires electronic timed ⁄ dated methods and that endoscopists should be blinded to patient symptom status. Conclusions: Implementation of the consensus statements will improve the quality and comparability of trials, and make them compatible with regulatory requirements.J . Dent, P. J . Kahrilas, N. Vakil, S. Veldhuyzen Van Zanten, P. Bytzer, B. Delaney, K. Haruma, J. Hatlebakk, E. McColl, P. Moayyedi, V. Stanghellini, J . Tack and M. Vaezihttp://www3.interscience.wiley.com/journal/120088380/issu
Effect of histamine on rat gastric H(+)-K(+)-ATPase alpha-subunit expression
No full text The H(+)-K(+)-adenosinetriphosphatase (ATPase) is expressed in the parietal cell and is responsible for acid secretion by the stomach. Histamine binds to an H2 receptor and activates adenylate cyclase and intracellular calcium concentration ([Ca2+]i) elevation, stimulating acid secretion. It has been shown that omeprazole administered to rats increases serum gastrin and transiently increases the level of mRNA for the alpha-subunit of the pump, but this increase is blocked by the presence of the H2-receptor antagonist, famotidine [A. Tari, G. Yamamoto, K. Sumii, M. Sumii, Y. Takehara, K. Haruma, G. Kajiyama, V. Wu, G. Sachs, and J. H. Walsh. Am. J. Physiol. 265 (Gastrointest. Liver Physiol. 28): G752-G758, 1993]. These observations suggest that the release of histamine induced by gastrin is essential for the increase of the expression of mRNA induced by omeprazole. Infusion of histamine at 15 mumol.kg-1.h-1 i.v. for 1 h increased the alpha-subunit mRNA level by 144 +/- 2.4% and induced a stimulated morphological appearance of the parietal cell. These changes were inhibited completely by the competitive H2-receptor antagonist famotidine, which elevated gastric pH and serum gastrin. Famotidine also reduced the level of H(+)-K(+)-ATPase mRNA compared with control animals. No change in the expression of beta-actin mRNA was observed in any group of animals. These data provide direct evidence for histamine stimulation of H(+)-K(+)-ATPase alpha-subunit gene expression by activation of the H2 receptor. </jats:p
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No full textKajiyama, Tisoro Kaminsky, Walter Kawaguchi, Haruma Kimura, Yoshiharu Kirshenbaum, Gerald S. Kitayama, Tatsuki Klemm, Elisabeth Klemm, Dieter Koetz, Joachim Kohjiya, Shinzo Koide, Naohuki Korshak, Yuri Kratky, Christoph Kricheldorf, Hans R. Kubisa, Przemisla
Rationale and design of the VISION study: a randomized, open-label study to evaluate the long-term safety of vonoprazan as maintenance treatment in patients with erosive esophagitis
No full textNaomi Uemura,1 Yoshikazu Kinoshita,2 Ken Haruma,3 Takashi Yao,4 Ryoji Kushima,5 Tatsuhiro Kanoo6 1Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Kohnodai Hospital, Chiba, Japan; 2Department of Gastroenterology and Hepatology, Faculty of Medicine, Shimane University, Shimane, Japan; 3Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan; 4Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo, Japan; 5Department of Clinical Laboratory Medicine, Shiga University of Medical Science Hospital, Shiga, Japan; 6Takeda Pharmaceutical Co., Ltd, Osaka, Japan Abstract: Erosive esophagitis (EE) occurs when the epithelial mucosa is damaged due to gastric acid reflux, and the incidence of this disease is increasing in Japan due to changes in diet and lifestyle. The condition can be treated using proton pump inhibitors (PPIs) that act by irreversibly blocking the H+,K+-ATPase responsible for acid secretion. Vonoprazan is a K+ competitive channel inhibitor, which reversibly and potently inhibits gastric acid secretion. However, long-term data on vonoprazan use are limited. The aim of the VISION trial is to investigate the long-term efficacy and safety of vonoprazan in comparison with the PPI lansoprazole. This randomized, multicenter, 5-year, open-label study has a planned recruitment of 195 participants (2:1 allocation vonoprazan:lansoprazole) from 33 sites in Japan. The study comprises an 8-week “healing” phase (vonoprazan 20 mg or lansoprazole 30 mg p.o.) and a 260-week “maintenance” phase (vonoprazan 10 mg or lansoprazole 15 mg). Safety populations in both phases are defined as participants who receive at least one dose of the study or control drug in the healing and maintenance phases, respectively. The full analysis set in both phases is defined as participants who are randomized and receive at least one dose of the study or control drug in the healing and maintenance phases, respectively. The primary endpoint of the study is the histopathological evaluation of gastric mucosa for the presence of neoplastic alteration of gastric mucosal epithelial cells. Secondary efficacy endpoints include endoscopic EE recurrence rate and EE healing rate, and secondary safety endpoints include incidence of adverse events (coded using MedDRA terminology) and endoscopic evaluation of malignant changes in the gastric mucosa. Patient recruitment started in March 2016 and is now complete. The estimated study completion date is February 2022. Keywords: erosive esophagitis, gastric mucosa, lansoprazole, long-term safety, vonoprazan, K+ competitive channel inhibitor, neoplasi
Clinicoprognostical features of endometrial cancer patients with somatic mtDNA mutations
No full textSomatic mitochondrial DNA (mtDNA) mutations
have been found in a subset of endometrial cancers (EC) from
different populations. We have investigated the relationship
between mtDNA changes and clinical and pathological
variables of women affected by EC. mtDNA mutations were
detected both in early (3/32; 9%) and in advanced (1/8;
12%) stages of uterine tumors. However, patients carrying
the mtDNA mutations or the normal mtDNA sequence had
indistinguishable clinicopathological data, including age,
clinical stage, histological grade and type or depth of myometrial
invasion. It is noteworthy that mtDNA mutations
were not detected in hyperplastic endometrial tissues or in
ECs coexisting with hyperplasia, nor in a single case of
endometrial stromal sarcoma. LOH at the tumor suppressor
genes RB1 and TP53 as well as p16INK4A alterations (LOH,
gene deletion) were found in tumors carrying mtDNA
mutations. These results suggest that somatic mtDNA
mutations are detected in a subset of ECs, although they are
unrelated to clinicopathological variables of cancer
Review article: clinical significance of mucosal-protective agents: acid, inflammation, carcinogenesis and rebamipide
No full textGastroparesis
No full textGastroparesis is a disorder characterized by delayed gastric emptying of solid food in the absence of a mechanical obstruction of the stomach, resulting in the cardinal symptoms of early satiety, postprandial fullness, nausea, vomiting, belching and bloating. Gastroparesis is now recognized as part of a broader spectrum of gastric neuromuscular dysfunction that includes impaired gastric accommodation. The overlap between upper gastrointestinal symptoms makes the distinction between gastroparesis and other disorders, such as functional dyspepsia, challenging. Thus, a confirmed diagnosis of gastroparesis requires measurement of delayed gastric emptying via an appropriate test, such as gastric scintigraphy or breath testing. Gastroparesis can have idiopathic, diabetic, iatrogenic, post-surgical or post-viral aetiologies. The management of gastroparesis involves: correcting fluid, electrolyte and nutritional deficiencies; identifying and treating the cause of delayed gastric emptying (for example, diabetes mellitus); and suppressing or eliminating symptoms with pharmacological agents as first-line therapies. Several novel pharmacologic agents and interventions are currently in the pipeline and show promise to help tailor individualized therapy for patients with gastroparesis
Role of histamine2 receptor in increased expression of rat gastric H(+)-K(+)-ATPase alpha-subunit induced by omeprazole
No full text Omeprazole is a specific inhibitor in vivo of the functioning gastric acid pump, the H(+)-K(+)-adenosinetriphosphatase (ATPase), in the secretory canaliculus of the parietal cell. It has been shown previously that omeprazole in rats led to an increase in the mRNA for the alpha-subunit of the H(+)-K(+)-ATPase. Omeprazole causes a marked increase in circulating gastrin in this species, which in turn stimulates release of histamine from the enterochromaffin-like cell. The possible role of this pathway was investigated by the in vivo administration of famotidine, a potent H2 receptor antagonist. A single intraperitoneal dose of famotidine, 200 mg/kg, produced a transient hypergastrinemia peaking at 3 h and normalizing at 12 h, inhibition of secretion that lasted for 12 h, but no change in the level of the alpha-subunit mRNA or of beta-actin mRNA. In contrast, a single dose of omeprazole,xs 100 mg/kg, inhibited acid secretion and produced hypergastrinemia, peaking at 12 h, both effects lasting for the 24-h observation period. Omeprazole elevated the alpha-subunit mRNA transiently by more than threefold at 3 h, with normal levels being restored at 24 h. The administration of famotidine 1 h after omeprazole did not change the effects of omeprazole on acid secretion but elevated the gastrin levels further. There was now no elevation of the alpha-subunit mRNA for the first 6 h, but a small increase at 12 h and a further increase to approximately 2.5-fold at 24 h.(ABSTRACT TRUNCATED AT 250 WORDS) </jats:p
The Serum Levels of Endothelium Nitric Oxide Synthase in Positive Cases for Helicobacter pylori Stool Antigen
No full textBackground & Objectives: Endothelium nitric oxide synthase (eNOS) is a type of enzyme
which produces an endogenous factor called nitric oxide (NO). NO plays important role in
progress of euplastic diseases. In chronic gastritis, the increased level of NO causes damages
to DNA. The aim of present study is to evaluate eNOS concentration in sera of healthy people
and those infected by Helicobacter pylori.
Methods: The sera and stool specimens from 84 voluntaries (Female: 58.3%, Males 41.6%)
were collected. Helicobacter pylori antigen in the stool specimens and eNOS levels in sera
were determined using ELISA. Obtained data were analyzed using Excell software.
Results: The age range was from 1 to 78 years old (Mean: 30 years old). In terms of special
diseases, 70.2% did not have any special diseases, but 29.76% showed at least one special
disease, mainly thyroid disease and hypertension. The results for H. pylori stool antigen
detection showed that 16.6%, 29.76% and 53.57% of collected specimens were equivocal,
Helicobacter pylori negative and positive respectively. Comparison of sera concentrations of
eNOS showed that there is no significant change among these three groups.
Conclusion: As mentioned in results, the eNOS sera concentrations showed no significant
change in Helicobacter pylori positive and negative groups. Albeit the other studies showed
the significant increase in serum concentration of Helicobacter pylori positive patient, this
controversy may arise from race and variations in Helicobacter pylori pathogenic islands such
as those containing VacA and CagA. We propose to conduct a similar study in Ardabil to
focus on the pathogenic islands of H. pylori strains in this province
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