Inhibition Of Gastric Secretion Research Articles

Gastroesophageal Reflux Disease: Pathophysiology and New Treatment Trends.

Gastroesophageal reflux disease (GERD) is caused by the reflux of gastric contents into the esophagus due to a decline in esophageal clearance and anti-reflux barrier mechanisms. Mucosal injury is caused by a combination of gastric juice directly damaging the esophageal mucosa and the immune and inflammatory mechanism in which inflammatory cytokines released from the esophageal mucosal epithelium cause neutrophil migration, triggering inflammation. Gastric secretion inhibitors are the first-line treatment for GERD, but they can be combined with prokinetic agents and Chinese herbal remedies. However, pharmacotherapy cannot improve anatomical problems or prevent physical causes of GERD, such as reflux of non-acidic contents. Therefore, surgery can be warranted, depending on the pathology. Intraluminal endoscopic therapy, which is both less invasive and more effective than surgery, was recently developed and applied in Europe and the United States. In Japan, intraluminal endoscopic therapies, such as anti-reflux mucosectomy, anti-reflux mucosal ablation, and endoscopic submucosal dissection, for GERD have been independently developed.

Protective effect of Amauroderma rugosum ethanol extract and its primary bioactive compound, ergosterol, against acute gastric ulcers based on LXR-mediated gastric mucus secretions

BackgroundAmauroderma rugosum (Blume & T. Nees) Torrend (Ganodermataceae) is an edible mushroom with a wide range of medicinal values. Our previous publication demonstrated the therapeutic effects of the water extract of A. rugosum (WEA) against gastric ulcers. However, the protective effects of the ethanol extract of A. rugosum (EEA) on gastric mucosa and its major active constituents have not yet been elucidated. PurposeThis study aims to evaluate the gastroprotective effects and underlying mechanisms of EEA and its fat-soluble constituent, ergosterol, in acute gastric ulcers. Study design and methodSD rats were pre-treated with EEA (50, 100, and 200 mg/kg) or ergosterol (5, 10, and 20 mg/kg), and acute gastric ulcer models were constructed using ethanol, gastric mucus secretion inhibitor (indomethacin) or pyloric-ligation. The gastric ulcer area, histological structure alterations (H&E staining), and mucus secretion (AB-PAS staining) were recorded. Additionally, Q-PCR, western blotting, immunohistochemistry, ELISA, molecular docking, molecular dynamics simulations, MM-GBSA analysis, and surface plasmon resonance assay (SPR) were used to investigate the underlying mechanisms of the gastroprotective effect. ResultCompared with WEA, which primarily exerts its anti-ulcer effects by inhibiting inflammation, EEA containing fat-soluble molecules showed more potent gastroprotective effect through the promotion of gastric mucus secretion, as the anti-ulcer activity was partly blocked by indomethacin. Meanwhile, EEA exhibited anti-inflammatory effects by suppressing the production of IL-6, IL-1β, TNF-α, and NO, thereby inhibiting the MAPK pathway. Significantly, ergosterol (20 mg/kg), the bioactive water-insoluble compound in EEA, exhibited a gastroprotective effect comparable to that of lansoprazole (30 mg/kg). The promotion of gastric mucus secretion contributed to the effects of ergosterol, as indomethacin can completely block it. The upregulations of COX1-PGE2 and C-fos, an activator protein 1 (AP-1) transcription factor, were observed after the ergosterol treatment. Ergosterol acted as an LXRβ agonist via van der Waals binding and stabilizing the LXRβ protein without compromising its flexibility, thereby inducing the upregulation of AP-1 and COX-1. ConclusionEEA and its primary bioactive compound, ergosterol, exert anti-ulcer effects by promoting gastric mucus secretion through the LXRβ/C-fos/COX-1/PGE2 pathway.

Sonchus oleraceus L. Promotes Gastroprotection in Rodents via Antioxidant, Anti-Inflammatory, and Antisecretory Activities.

Sonchus oleraceus L. is an edible and medicinal plant used to treat stomachache and gastric ailments around the world. Thus, this study aimed to determine the gastroprotective mode of action of hydroalcoholic extract of S. oleraceus (HES). Mice were treated with HES before induction of gastric ulceration by ethanol/HCl. The area and histological appearance of ulcers were quantified, and mucus was measured histochemically. The effects of HES on inflammatory and oxidative markers were assessed in the ulcerated tissue. In addition, we investigated the gastric acid antisecretory activity of HES in pylorus-ligated rats. Chemical analyses of HES and its antioxidant activity were also performed in vitro. The HES (30 or 300 mg/kg) reduced the ulceration by 71.5 and 76.2%, respectively, compared with vehicle (p < 0.001), and the histological analysis confirmed the macroscopic results with elevation in mucin levels by 361.4 and 477.5%, respectively, compared with vehicle (p < 0.001). Moreover, the gastroprotection was accompanied by increases in GSH levels and in SOD, CAT, and GST activities; in parallel to a reduction in MPO activity and TNF levels. Furthermore, HES reduced the total acidity, and pepsin activity of the gastric juice of rats by 61 and 63%, respectively, compared to the vehicle. Phytochemical analysis indicated that luteolin-7-O-β-D-glucoside is the main active compound annotated in HES. Was also found that HES scavenged the DPPH radical with an IC50 of 15.41 μg/mL. In conclusion, the gastroprotective effects of HES involve reductions in oxidative stress and inflammatory injury, in conjunction with an increase in mucus layer and inhibition of gastric secretion. This study advances in elucidating the modes of the antiulcer potential of S. oleraceus and contributes to the prospection of new gastroprotective molecules.

Analysis of Patients with Focal Epilepsy and Drug-Resistant Epilepsy in Italy: Evaluation of Their Characteristics, Therapeutic Pathway and the Consumption of Healthcare Resources.

PurposeA retrospective analysis was conducted to estimate the number of patients with focal epilepsy and drug-resistant epilepsy (DRE) and their characteristics, the therapeutic patterns, the consumption of health resources in a real-world Italian setting.Patients and MethodsA retrospective study was carried out on the administrative databases of a sample of Italian Health Departments, covering approximately 8.7 million health-assisted individuals. All adult patients with at least one hospitalization for focal epilepsy and an electroencephalogram (between 01/2010 and 12/2019), and at least one prescription of antiseizure medication (ASM) (between 01/2011 and 12/2018) were included in the study. Patients with at least two treatment failures and treated with a subsequent ASM were considered DRE.ResultsOverall, 1897 patients with focal epilepsy (mean age 56 years, 47% male) were identified, of which 485 (25.6%) with DRE (mean age 53 years, 43% male). Among patients with focal epilepsy and DRE, respectively, 48% and 54% had essential hypertension, 23.4% and 26.6% had cardiovascular disease, and 46.3% and 62.1% had peptic ulcer/prescription of gastric secretion inhibitors. During follow-up, patients with focal epilepsy maintained first-line treatment for 53.9 months; among these, 52% passed to the second-line, and 485 (25.6% of the total) began third-line treatment. In patients with focal epilepsy, the mean cost was € 4448 (of which € 1410 were epilepsy-related), and in DRE patients total expenditures averages € 5825 (of which € 2165 were epilepsy-related). In both patients with focal epilepsy and DRE, hospitalizations represented the most impacting item of expenditure.ConclusionThe present analysis conducted in a setting of Italian clinical practice has shown that 25% of patients with focal epilepsy were resistant to antiepileptic treatments. Furthermore, these results showed that health-care costs for the management of epileptic patients were mainly accountable for the costs related to the disease-management and to hospitalizations.

MO525: Iron absorption and phosphate-lowering effects of ferric citrate hydrate are not influenced by gastric secretion inhibitors in patients with chronic kidney disease

Abstract BACKGROUND AND AIMS Ferric citrate hydrate (FC, Riona®), an oral iron-based phosphate binder in chronic kidney disease (CKD) patients, is also approved as an iron preparation for iron-deficiency anemia (IDA) in Japan. In the USA, ferric citrate (Auryxia®) is approved as a phosphate binder for dialysis-dependent CKD and an iron replacement product for the treatment of IDA in patients with CKD not on dialysis. Ingested iron is dissolved at a low pH of the secreted gastric acid in the stomach, which is an important process for its effective absorption [1]. Patients taking gastric acid secretion inhibitors (GASI), such as proton pump inhibitors and histamine-2 receptor antagonists, showed decreased iron absorption and increased risk of iron deficiency, which were dose- and treatment-duration-dependent [2]. The increase in the intragastric pH by concomitantly use of GASI might be affected on FC's iron absorption effect. METHOD We have conducted a retrospective study using data from two previous clinical studies to investigate FC in CKD patients with hyperphosphatemia. A 12-week, phase 3, multicenter, randomized, double-blind, placebo-controlled study in non–dialysis-dependent (ND) CKD patients (FC, n = 60, ; placebo, n = 30) (CTI-111 435) [3], and a 52-week, phase 3, multicenter, open-label, dose-titration study in CKD patients undergoing hemodialysis (HD) (FC, n = 180) (CTI-111 437) [4] were divided into with or without GASI, and levels of iron and phosphate related parameters were analyzed. RESULTS In ND patients, approximately 25% in FC (n = 14) and 50% (n = 14) in placebo used GASI. Mean [standard deviation (SD)] changes from baseline to end of treatment (EOT) in serum ferritin (ng/mL) were 109.83 (104.46) in FC with GASI, 142.68 (94.28) in FC without GASI, −22.49 (74.85) in placebo with GASI, and −3.43 (43.58) in placebo without GASI (Fig. 1a). Those in transferrin saturation (TSAT, %) were 16.64 (30.13) in FC with GASI, 17.07 (17.56) in FC without GASI, 2.86 (14.68) in placebo with GASI, and 1.31 (9.75) in placebo without GASI (Figure 1b). The mean (SD) dose of FC with or without GASI were 3240 mg/day (approximately 778 mg ferric iron) with GASI (n = 14) and 3445 mg/day (approximately 827 mg ferric iron) without GASI (n = 46), respectively. In HD patients, approximately 50% (n = 95) used GASI. Mean changes (SD) from baseline to EOT in serum ferritin (ng/mL) were 166.32 (153.70) with GASI and 155.16 (139.47) without GASI, and in TSAT (%) were 16.60 (19.44) with GASI and 16.02 (18.81) without GASI, respectively. The mean (SD) dose of FC with or without GASI were 2619 mg/day (approximately 629 mg of ferric iron) with GASI (n = 95) and 2854 mg/day (approximately 685 mg or ferric iron) without GASI (n = 85), respectively. In both studies, there were no differences in the changes from baseline to EOT in serum phosphate between with or without GASI. CONCLUSION GASI did not interfere with iron absorption and phosphate-lowering effects of FC in CKD patients with hyperphosphatemia.

Chronic Diarrhea and Weight Loss in an 18-month-old Boy.

Chronic Diarrhea and Weight Loss in an 18-month-old Boy.

DIAGNOSTIC UTILITY OF THE RAPID UREASE TEST FOR HELICOBACTER PYLORI IN GASTRIC JUICE SAMPLES

Objective: The purpose of this study is to compare the diagnostic performance of the rapid urease test for H. pylori in endoscopic samples of gastric juice compared with the same test in gastric mucosa. Materials and methods: Cross-sectional, comparative and prospective study with study of concordance of diagnostic tests, carried out with patients referred to a medical center in Bogotá DC, Colombia for the performance of an esophagogastroduodenoscopy. We included 130 patients older than 18 years, without antibiotic treatment or inhibitors of gastric secretion, or with any type of immunodeficiency, or cancer. Were processed in the sensibacterpyroli test device a sample of gastric antrum for Rapid Ureasa Test RUT in mucosa and for the sample of juice 5 mL was taken with suctionator 7A-23B pulmomed (USA) R, to compare results. Results: In this study the infection by Helicobacter pylori was detected by biopsy sample in 40.8% of the patients that corresponded to 53 patients, among (59.2%) 77 patients with negative values. The prevalence of H. pylori infection in this study was 40.8%. It was calculated of VPP and NPV: 95% and NPV: 89.3%. Conclusions: rapid urease test in gastric juice is a fast and economic test, with very good sensitivity and specificity, is also very useful to detect H. pylori infection.

Chronic pancreatitis is an acid dependent disease. Which mark to put at the end of the sentence: interrogative, exclamation, dot or ellipsis?

Chronic pancreatitis (CP) is one of the most widespread gastroenterological diseases, the pathogenic mechanisms of which are still under investigation. The authors gave a short overview of the main stages in the research of the relationships between gastric and pancreatic secretion, and the results of physiological studies, performed by I. P. Pavlov and his students. Being а strict follower of «nervousness» theory, the great physiologist and his associates made the incorrect conclusions about the presence of local nerve connections (peripheral reflex arc) between the duodenum and pancreas, not suggesting the presence of humoral interactions. The modern data have been presented that give the evidence that duodenal acidification results in the secondary deficiency of endogenous pancreatic enzymes, increased stimulation of pancreatic secretion, exacerbated symptoms of exocrine pancreatic insufficiency, increased secretory tension in pancreatic tissue, duct and tissue pressure, and increased risk of CP attack.However, a dot at the end of a statement «CP is an acid-dependent disease» is tentative. The proton pump inhibitors (PPIs) are used throughout for the treatment of acid-dependent diseases. However, neither European, nor Russian recommendations do include PPIs as a basic treatment for CP. The results of a prospective randomized controlled trial, which proved the effectiveness of CP treatment with the use of combination of analgesics and PPIs have been considered. However, the results of the only study are not enough to recommend the inclusion of PPI in the basic CP therapy. The analysis has been performed for the provisions of the European Guidelines for the Diagnosis and Treatment of Pancreatitis. These guidelines describe situations when PPIs should be included in the complex CP treatment. The data of evidence-based medicine have been presented, illustrating that suppression of gastric secretion can increase the effectiveness of enzyme preparations in comparison with the administration of pancreatin monotherapy. The advantages of pantoprazole among other of the PPIs’ representatives have been analyzed. A clinical case of CP treatment with a reasonable pantoprazole (Nolpaza) administration have been considered.

Cochlospermum regium (Mart. ex Schrank) Pilg.: Evaluation of chemical profile, gastroprotective activity and mechanism of action of hydroethanolic extract of its xylopodium in acute and chronic experimental models

Ethnopharmacological relevanceCochlospermum regium (Bixaceae) is a native shrub of Brazil and its xylopodium (infusion/decoction) is being used for the treatment of gastritis, ulcers, arthritis, intestinal infections, gynaecological infections, skin diseases, among others. The aim of the present study was to evaluate the gastroprotective/antiulcer activity and the mechanism of action of hydroethanolic extract of C. regium xylopodium (HECr), using in vitro and in vivo models. Additionally, phytochemical constituents were identified by high-performance liquid chromatography (HPLC). Materials and methodsC. regium xylopodium was macerated with ethanol/water to obtain the HECr. The phytochemical characterisation was carried out by HPLC. The antiulcer efficacy of HECr (25, 100 and 400 mg/kg, p.o.) was evaluated using acute acidified ethanol (HCl/EtOH), piroxicam and water immersion-induced experimental ulcer models. Chronic gastric ulcer healing activity of HECr was evaluated through acetic acid (99.8%) – induced model. Histological analysis and myeloperoxidase (MPO), glutathione (GSH), catalase (CAT) activities were also evaluated in chronic ulcer induced gastric tissues. The plausible mode of action of the HECr was assessed by estimation of gastric wall mucus production and the role of gastric secretion in pylorus ligature. The animals were also pre-treated with various inhibitors which includes indomethacin (10 mg/kg, p.o.) a selective inhibitor of cyclooxygenase, L-NAME (10 mg/kg, i.p.), an inhibitor of nitric oxide synthase, glibenclamide, a ATP-sensitive potassium channels (K+ATP) blocker (5 mg/kg, p.o.) or yohimbine (2 mg/kg, i.p.), an α2-adrenergic receptor antagonist. In vitro, Helicobacter pylori action was done by broth microdilution method. ResultsThe HPLC analysis data revealed the presence of gallic acid, rutin, myricetin, morin and kaempferol. HECr promoted protective effect against acute ulcers induced by HCl/EtOH with inhibitions of 47.52% (p < 0.01) and 62.69% (p < 0.001) at 100 and 400 mg/kg, and in piroxicam by 34.11% (p < 0.05), 49.14% (p < 0.01) and 61.34% (p < 0.001), at 25, 100 or 400 mg/kg, respectively, and in water restraint stress by 78.26% inhibition, p < 0.001, at the dose of 400 mg/kg when compared to the vehicle control group respectively. In the chronic gastric ulcer model, HECr (25, 100 and 400 mg/kg p.o.) significantly (p < 0.001) decreased the injured area by 58.80%, 77.87% and 71.10% respectively. Histological examination indicated that oral treatment of HECr promoted healing of gastric lesions by regenerating gastric mucosa layer with less inflammatory cells. HECr augmented the GSH, CAT activities and reduced MPO level. The pre-treatment with HECr increased the gastric wall mucus production. It also significantly altered the gastric secretion parameters by causing the reduction in the gastric juice volume, elevated the pH level and reduced the total acidity at all doses tested when compared with the vehicle group. HECr at the most active dose (100 mg/kg) reversed completely the reduction of PGs, NO production, closure of K+ATP- channels and α2-adrenoreceptor blockage – induced damages. In microdilution assay, the HECr showed good anti-Helicobacter pylori effect with MIC = 100 µg/mL. ConclusionThe HECr presented preventive and curative effects in the experimental gastric ulcer models, besides good anti-Helicobacter pylori activity, which supports the traditional medicinal use of the xylopodium of this plant for gastrointestinal diseases. The underlying mechanisms of this antiulcerogenic/antiulcer action involve, at least, augmentation of mucus production, inhibition of gastric secretion, stimulation of PGs and NO synthesis. And that it involves activation of K+ATP channels and α-2-adrenergic receptors, in addition to an antioxidant activity, probably due to the presence of gallic acid and flavonoids in HECr.

Corelations Between the Use of Medical Substances and the Incidence Infections Produced by Clostridium Difficile Species

Antibiotherapy is the main determinant of Clostridium difficile infection due to the imbalance determined in the intestinal flora. Clostridium difficile infection can be considered a current public health problem, given the increased incidence, both as a nosocomial infection as well as at community level, by excessive, uncontrolled and unjustified use of antibiotics, high contagiousness, negative influence on health systems in the increased number of days of hospitalization and implicitly increased costs, and last but not least, the substantial deterioration of the quality of the patient�s life. The retrospective study over a 12-month period over a group of 106 patients revealed the following profile of the patient affected by Clostridium difficile infection: females, aged 66.75 � 15.66, from the urban area, hospitalized in the medical section, who had diarrhea more than 2 days after admission, but up to 28 days after this event, due to prolonged antibiotic therapy with ceftriaxone, associated with a gastric secretion inhibitor, on a background of multiple associated pathologies. It is very important for all health systems to control this phenomenon and this is only possible by applying effective measures to prevent the onset of CDI, of relapses and contamination, thus identifying the judicious use of antibiotics.

Protective effect of struthanthus marginatus on ethanol-induced gastric damage in mice

Background: Our research group previously characterized the antioxidant and gastroprotective effects of Struthanthus marginatus (Loranthaceae), a medicinal herb used in Brazil as a healing agent. Objective: The aim of this study is to evaluate the chemical composition of aqueous extract of S. marginatus (AESm), as well as the mechanisms underlying its gastroprotective and ulcer healing properties using different protocols in mice. Materials and Methods: Gas chromatography-mass spectrometry and liquid chromatography/electrospray ionization-mass spectrometry-mass spectrometry/diode array detection analyses to evaluate the chemical composition of AESm were conducted. The antisecretory activity (basal or stimulated) was determined using the pyloric ligature method. The gastroprotective action of nitric oxide and sulfydryl groups (–SH groups) were evaluated using ethanol-induced gastric ulcer model. The healing ability was evaluated using an acetic acid-induced chronic ulcer. Results: Chromatographic analyses of AESm permitted to identify several compounds, including 3-trans-caffeoylquinic acid (3-trans-CGA), quercetin, and kaempferol as the major constituents. Oral treatment of animals with AESm (500 mg/kg/day) reduced the severity of ethanol-induced gastric damage similar to omeprazole and in a more pronounced manner than 3-trans-CGA. Such effect was significantly reduced in animals pretreated with Nω-nitro-L-arginine methyl ester. In addition, AESm inhibited gastric acid secretion in pylorus-ligated mice stimulated with histamine or pilocarpine similar to atropine or cimetidine, respectively. A decrease in acetic acid-induced gastric ulcers similar to that promoted by cimetidine was also observed. Conclusion: The results show that S. marginatus is rich in flavonoids and that these compounds contribute directly to the gastroprotective and ulcer healing effects of this herb. The inhibition of gastric secretion is the possible gastroprotective mechanism. Abbreviations Used: AESm: Aqueous Extract of S. marginatus; 3-trans-CGA= 3-trans-caffeoylquinic acid.

Antiulcer mechanisms of Vernonia condensata Baker: A medicinal plant used in the treatment of gastritis and gastric ulcer

Ethnopharmacological relevanceThe leaves from Vernonia condensata Baker are broadly used in folk medicine for the treatment of gastric ulcers and dyspepsia. The Brazilian Public Health System (SUS) describes this species as having the potential to serve as a new herbal product with therapeutic benefits. Aim of the studyThe purpose of the study was to evaluate the gastroprotective activity and gastric healing properties of a crude ethanolic extract from leaves of V. condensata (CEEV) in different animal models. Materials and methodsIn order to assess the gastroprotective potential of CEEV, ulcer models were established using ethanol and indomethacin. The gastric healing effect was then evaluated in the acetic acid-induced ulcer model, where the tissue was used to assess oxidative levels (reduced glutathione and lipid hydroperoxide levels, as well as superoxide dismutase and catalase activity), inflammatory [myeloperoxidase (MPO)] parameters, and mucin content. Furthermore, the ligature pylorus model, with and without secretagogue stimuli, was employed to investigate the mechanism of action of CEEV. In addition, H+K+-ATPase activity, MPO activity, and antioxidant activity through the DPPH assay were examined through in vitro trials. Phytochemical analyses were also performed. The ethanol/HCl-induced gastric ulcer method was employed to verify the gastroprotective effect of the main compound in CEEV. ResultsCEEV (30 and 300mg/kg, p.o) exhibited gastroprotective activity and prevented both gastric lesions induced by ethanol or indomethacin in rats. The gastric healing effect of CEEV (300mg/kg, p.o. taken twice a day for a duration of seven days) was confirmed by examining the macroscopic and microscopic appearance of chronic gastric ulcers induced by acetic acid in rats. The restorative effect of CEEV was accompanied by a significant increase in mucin content (PAS staining) and by a reduction in oxidative stress and inflammatory parameters at the site of the ulcer. Moreover, CEEV (300mg/kg), administered via an intraduodenal route, significantly reduced the volume, pH, total acidity and pepsin activity of gastric content in the pylorus ligature model in rats. The gastric acid antisecretory effect of CEEV was maintained even in the presence of cholinergic and gastrinergic, but not histaminergic, stimuli. In vitro, CEEV (1–10µg/ml) was able to scavenge free radical DPPH, but did not promote inhibitory effects on MPO or H+,K+-ATPAse activity. Phytochemical analysis of CEEV indicated that luteolin is the main compound present in the extract. However, luteolin (1, 3 and 10mg/kg, p.o or 1mg/kg, i.p.) did not promote gastroprotection against ethanol/HCl in mice. It is also important to mention that oral administration of CEEV did not produce any sign of acute toxicity in animals. ConclusionsV. condensata extract demonstrates gastroprotective effects through the inhibition of gastric secretion via cholinergic and gastrinergic pathways. Furthermore, it exhibits cytoprotective effects, involving antioxidant activity, an increase in mucin content and inhibition of neutrophil migration. Thus, this medicinal plant may be a suitable natural source for the prevention and treatment of gastric lesions.

胃酸分泌抑制薬内服下にて胃もたれ, 食欲不振を認めた血液透析患者に六君子湯が著効した2症例

胃酸分泌抑制薬内服下にて胃もたれ, 食欲不振を認めた血液透析患者に六君子湯が著効した2症例

Backflow prevention mechanism of laparoscopic Toupet fundoplication using high-resolution manometry.

The use of multichannel intraluminal impedance pH (MII-pH) and high-resolution manometry (HRM), which are new devices used to examine the esophageal function, has recently become common in Europe and the USA, thus garnering much attention. There have not been enough studies as of yet, however, on the esophageal motor function and the benefits of treatment after these devices have been used in laparoscopic fundoplication. To use MII-pH and HRM to study the treatment effectiveness of laparoscopic fundoplication and consider a backflow prevention mechanism for laparoscopic Toupet fundoplication. The study looked at 27 of a total of 60 patients undergoing laparoscopic fundoplication due to reasons of either gastroesophageal reflux disease or esophageal hiatal hernia between October 2012 and February 2014, who underwent a postsurgical HRM examination. Of these, 25 patients whose symptoms disappeared following surgery and who were not orally administered gastric secretion inhibitor (of whom nine were male, average age 55.9±14.9years, and of whom 76% underwent MII-pH) were taken as the subjects of the study. The postsurgical evaluation was conducted 3months after the operation. Using HRM, although no change was noted in the lower esophageal sphincter pressure (LESP) (p=0.943), an increase in lower esophageal sphincter pressure integral (p=0.024) and extensions in both overall length and abdominal length were noted (both p<0.001), while a significant improvement was noted in the lower esophageal sphincter (LES). Furthermore, the cases subjected to MII-pH demonstrated a reduced gastroesophageal reflux time, total number of liquid reflux episodes, and total number of reflux episodes (p<0.001, p=0.008, p=0.009). Backflow prevention mechanism of laparoscopic Toupet fundoplication is thus considered to improve the overall LES function without elevating LESP.

Proton pump inhibitors decrease melanogenesis in melanocytes.

Proton pump inhibitors (PPIs) are widely used as inhibitors of gastric juice secretion for treatment of gastroesophageal reflux disease. However, there are no previous studies of the effects on melanogenesis resulting from PPI treatments. Therefore, the aim of the present study was to investigate the effects of PPIs on melanogenesis in melan-a cells derived from immortalized mouse melanocytes. Tyrosinase activity and copper-chelating activity were measured spectrophotometrically. In addition, the melanin content and viability of melan-a cells treated with PPIs were assessed and the mRNA levels of melanogenesis-associated genes were measured by reverse transcription-polymerase chain reaction. Treatment with rabeprazole, but not the other PPIs tested, resulted in strong, dose-dependent inhibition of mushroom tyrosinase (TYR). By contrast, each of the PPIs tested exhibited copper-chelating activity. Treatment of melan-a cells with 100 µM concentrations of the PPIs resulted in significantly reduced melanin synthesis and reduced expression of several melanogenesis-associated genes, including TYR, TYR-related protein-1 (TRP-1) and TRP-2, and microphthalmia-associated transcription factor, but did not result in cytotoxic effects. These results suggest that PPIs inhibit melanin biosynthesis in melan-a cells via the downregulation of melanogenesis-associated genes. Furthermore, the findings indicate that PPIs in general could be utilized as skin-whitening agents and/or as biomaterial for treating hyperpigmentation disorders.

Pharmacists’ recommendations on the drug-drug interaction between precipitated calcium carbonate and gastric secretion inhibitors

Pharmacists’ recommendations on the drug-drug interaction between precipitated calcium carbonate and gastric secretion inhibitors

Occurrence of polymorphism in famotidine raw materials

Polymorphs are compounds with the same chemical composition, however the molecules are arranged in at least two different ways in the solid state. Famotidine is a histamine H2-receptor antagonist inhibitor of gastric secretion and widely used in gastric and duodenal ulcer disease. Two polymorphs are described for famotidine, A and B. The polymorph A is the most thermodynamically stable form and polymorph B is the kinetically favored form being marketed because it presents greater pharmacological activity. The aim of this study was to evaluate the occurrence of famotidine polymorphs in five raw materials acquired from different suppliers. The reference standard (USP) was also analyzed. All samples were characterized by powder X-ray diffraction (PXRD), infrared spectrophotometry (IR-ATR) and differential scanning calorimetry (DSC). PXRD analysis enables us to identify form B in five raw material samples and in the reference standard (USP). However, one of the raw materials additionally shows the presence of polymorphic form A. The DSC and IR-ATR techniques were essential to identify the polymorphic forms of famotidine confirming the results obtained by PXRD. Since the presence of polymorphs can compromise the effectiveness and safety of medicines and there is no official methodology of analysis and control of polymorphism in famotidine raw materials, the polymorphic contamination found in this study are being further analyzed and their physicochemical properties are being evaluated.

Reduction in gastrointestinal toxicity by gastric secretion inhibitors during S-1 monotherapy for patients with gastric cancer.

The purpose of this study was to retrospectively examine the effect of concomitant administration of gastric secretion inhibitors or gastrectomy on the frequency of gastrointestinal toxicity caused by 5-fluorouracil (5-FU) in gastric cancer patients receiving chemotherapy with S-1. In 62 gastric cancer patients treated with S-1 alone, data relating to the occurrence of gastrointestinal toxicity (diarrhea, vomiting, and nausea) and possible contributing factors were retrospectively collected, and logistic regression analysis was performed. Time-to-event data relating to the occurrence of gastrointestinal toxicity were also collected, and the effect of gastric secretion inhibitors on the time-to-event profiles was examined using a log-rank test. Logistic regression analysis suggested that the frequency of gastrointestinal toxicity was significantly reduced by the administration of gastric secretion inhibitors (p=0.01; odds ratio, 0.197; 95% confidence interval (CI), 0.056-0.694) and that gastrointestinal toxicity correlated with the estimated glomerular filtration rate (p=0.04; odds ratio, 0.956; 95% CI, 0.916-0.997). The median time-to-event of gastrointestinal toxicity was 85 d for patients that received gastric secretion inhibitors, which was significantly different from the 42 d for patients that did not receive the inhibitors (p=0.02, log-rank test). No clear effect of gastrectomy was found in the present study. The prophylactic use of gastric secretion inhibitors in gastric cancer patients treated with S-1 may decrease and delay the occurrence of gastrointestinal toxicity.

Proton pump inhibitors are associated with hypersensitivity reactions to drugs in hospitalized patients: a nested case‐control in a retrospective cohort study

Previous research has shown that gastric acid suppression by antacid drugs can promote allergic reactions to acid-labile food proteins. No data are available about whether antacid drugs can promote drug hypersensitivity reactions. The most potent and longer lasting inhibition of gastric secretion is provided by proton pump inhibitors (PPIs). We hypothesized that gastric acid suppression by proton pump inhibitors could be causative of drug hypersensitivity reactions during hospitalization. To estimate the risk of developing drug hypersensitivity reactions during the hospitalization of patients treated with proton pump inhibitors, and other associated factors. A nested case-control in a retrospective cohort study of hospitalized patients from September 2008 to December 2010 (70 771 admissions) was conducted using the registry of cases of interconsultations to the Allergy Department (161 confirmed cases of drug hypersensitivity reactions). A total of 318 controls were matched by first drug suspected in the hypersensitivity reaction, time of admission, age, gender and hospitalization wards. The relative risk of drug hypersensitivity reaction occurrence during hospitalization of patients treated with PPIs compared with those not treated in the period of study was significant (RR: 3.97; 95% CI: 1.97-8.29). After controlling for confounders in the nested case-control cohort, the use of PPIs persists as a predisposing factor (OR: 4.35; 95% CI: 2-9.45). Personal history of drug allergy and a long hospitalization time were other predisposing factors of drug hypersensitivity reactions (DHRs). The hazard that a DHR has occurred during PPI treatment was 3.7% per day. The hazard for immediate or accelerated reactions was 1.706 (P = 0.003) times that of delayed reactions. In hospitalized patients, the use of proton pump inhibitors was associated with a significant increase risk of drug hypersensitivity reactions along with a personal history of drug allergies and long hospitalization time.

PHP30 Using Nationwide Administrative Data to Evaluate Generic Drug Pricing and Physician Prescription

Promotion of generic drug utilization to reduce patient's out-of-pocket costs and improve insurance finance is a cross-national policy. The share of generics in Japan, 8.6% on a value basis, is lower than in other OECD countries. Although safety concerns, inventory management, drug charge margins and patient/physician brand preferences are cited as restraints to adoption of generic drugs prescriptions, their price-setting remains to be studied empirically. The purpose of this study is to verify the effects of price markups/levels of generic drugs on their prescription in hospitals under Diagnosis-Procedure-Combination (DPC) based payment system considered unaffected by drug charge margins and wherein prescription of the lowest-priced generic drugs is economically rational. A retrospective cohort study of inpatients with drug prescriptions for which generic drug is already marketed. 732 drugs of 20 categories from among calcium channel blockers, gastric secretion inhibitors, antibacterial drugs, hEPOs, cancer drugs and radiocontrast agents were included. Data were collected from 980 acute care hospitals in Japan during April 1, 2010 to March 31, 2011. A total of 2,768,456 (54.9%) among the study population of 5,041,157 cases were analyzed. An average of six price ranges existed for each dosage form of each drug, and price variability, such as 89 price ranges in total for calcium channel blockers, was found. Even after adjusting for other covariates, the share of prescriptions of the highest-priced generic drugs was the greatest among the price ranges of generic drug. Physician prescription was nearly uninfluenced by markups. Out results suggest that positive financial effects on medical insurance may result from lowering prices of generic drug in the highest price range rather than by aggregating those in the lowest range.