Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 297
Filtrar
1.
Sci Rep ; 10(1): 5989, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32249832

RESUMO

Drug absorption via the intestinal tissue is modulated by membrane permeability and metabolism in intestinal epithelial cells (IECs). In drug discovery research, using human IECs to evaluate membrane permeability and metabolic stability can offer very useful information when exploring for drug candidate compounds that have good bioavailability and when trying to predict the fraction absorbed and intestinal availability in humans. Here, we evaluated the pharmacokinetic functions of human IECs differentiated from human induced pluripotent stem cells (hiPSCs) in 3D cultures. As human IECs differentiated in 3D cultures form intestinal organoids and spheroids (herein termed organoids), their morphology makes it difficult to evaluate their pharmacokinetic functions. Therefore, we dissociated intestinal organoids into single cells and attempted to purify human IECs. We found that hiPSC-derived IECs (hiPSC-IECs) expressed the epithelial cell adhesion molecule (EpCAM) and could be highly purified by sorting EpCAM+ cells. The hiPSC-IEC monolayer showed a high TEER value (approximately 350 Ω × cm2). In addition, hiPSC-IECs oxidatively metabolized terfenadine (CYP3A and CYP2J2 substrate) and midazolam (CYP3A substrate). These results indicated that hiPSC-IECs form tight-junction and have cytochrome P450 enzymatic activities. In conclusion, we developed a novel application of hiPSC-derived intestinal organoids for drug testing.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32184185

RESUMO

BACKGROUND AND AIMS: Treatment options for irritable bowel syndrome with constipation (IBS-C) are limited-new prokinetic drugs are needed. We evaluated the efficacy and safety of minesapride (DSP-6952), a partial agonist with high affinity for 5-HT4 receptors, in patients with IBS-C in Japan. METHODS: We performed a double-blind phase 2 study of 171 patients with Rome III-defined IBS-C at 33 centers in Japan, from December 2012 through August 2013. Patients were randomly assigned to groups given minesapride (1, 4, 12, or 40 mg) or placebo once daily for 4 weeks. The primary outcome was efficacy, defined as improvement in the weekly frequency of complete spontaneous bowel movements (CSBMs), abdominal symptoms, and IBS-C symptoms (according to the Japanese version of the IBS severity index score). For evaluation of safety, adverse events (AEs) were recorded. RESULTS: The least squares mean change from baseline in the weekly frequency of CSBMs was greater in all minesapride groups than in the placebo group at week 4 (40 mg vs placebo, P=.040). The abdominal symptoms score improved in minesapride 40 mg group. The overall IBS severity index score decreased from baseline to week 4 in all treatment groups-especially in the 12 mg and 40 mg groups (P=.048 and <.001 vs placebo, respectively). The proportions of patients with treatment-emergent AEs in the pooled minesapride and placebo groups were 55.0% and 60.0%, respectively. The most common treatment-emergent AE was diarrhea (in 42.9% and 37.1% of patients in the pooled minesapride and placebo groups, respectively). CONCLUSIONS: In a phase 2 trial of patients with IBS-C in Japan, minesapride increased stool frequency (measured by CSBMs), reduced abdominal and overall IBS-C symptoms, and was well tolerated. Japan Pharmaceutical Information Center trial no: JapicCTI-122041.

3.
J Gastroenterol ; 55(4): 475-480, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32002672

RESUMO

In the original publication of the article, Table 1 and Figs. 2a, 2b, 3a were published with errors.

5.
Pharmacology ; 105(1-2): 102-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31536982

RESUMO

INTRODUCTION: Lubiprostone, a chloride channel activator, is said to reduce epithelial permeability. However, whether lubiprostone has a direct effect on the epithelial barrier function and how it modulates the intestinal barrier function remain unknown. Therefore, the effects of lubiprostone on intestinal barrier function were evaluated in vitro. METHODS: Caco-2 cells were used to assess the intestinal barrier function. To examine the expression of claudins, immunoblotting was performed with specific antibodies. The effects of lubiprostone on cytokines (IFNγ, IL-6, and IL-1ß) and aspirin-induced epithelial barrier disruption were assessed by transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) labeled-dextran permeability. RESULTS: IFNγ, IL-6, IL-1ß, and aspirin significantly decreased TEER and increased epithelial permeability. Lubiprostone significantly improved the IFNγ-induced decrease in TEER in a dose-dependent manner. Lubiprostone significantly reduced the IFNγ-induced increase in FITC labeled-dextran permeability. The changes induced by IL-6, IL-1ß, and aspirin were not affected by lubiprostone. The expression of claudin-1, but not claudin-3, claudin-4, occludin, and ZO-1 was significantly increased by lubiprostone. CONCLUSION: Lubiprostone significantly improved the IFNγ-induced decrease in TEER and increase in FITC labeled-dextran permeability. Lubiprostone increased the expression of claudin-1, and this increase may be related to the effect of lubiprostone on the epithelial barrier function.

6.
Mediators Inflamm ; 2019: 7859460, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31780871

RESUMO

Reg (regenerating gene) family proteins are known to be overexpressed in gastrointestinal (GI) tissues under conditions of inflammation. However, the pathophysiological significance of Reg family protein overexpression and its regulation is still unclear. In the present study, we investigated the profile of Reg family gene expression in a colitis model and focused on the regulation of Reg IIIß and IIIγ, which are overexpressed in inflamed colonic mucosa. C57BL/6 mice were administered 2% dextran sulfate sodium (DSS) in drinking water for five days, and their colonic tissues were investigated histopathologically at interval for up to 12 weeks. Gene expression of the Reg family and cytokines (IL-6, IL-17, and IL-22) was evaluated by real-time RT-PCR, and Reg IIIß/γ expression was examined by immunohistochemistry. The effects of cytokines on STAT3 phosphorylation and HIP/PAP (type III REG) expression in Caco2 and HCT116 cells were examined by Western blot analysis. Among Reg family genes, Reg IIIß and IIIγ were alternatively overexpressed in the colonic tissues of mice with DSS-induced colitis. The expression of STAT3-associated cytokines (IL-6, IL-17, and IL-22) was also significantly increased in those tissues, being significantly correlated with that of Reg IIIß/γ. STAT3 phosphorylation and HIP/PAP expression were significantly enhanced in Caco2 cells upon stimulation with IL-6, IL-17, and IL-22. In HCT116 cells, those enhancements were also observed by IL-6 and IL-22 stimulations but not IL-17. The link between type III Reg and STAT3-associated cytokines appears to play a pivotal role in the pathophysiology of DSS-induced colitis.

7.
J Neurogastroenterol Motil ; 25(4): 563-575, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31587548

RESUMO

Background/Aims: Magnesium oxide (MgO) has been frequently used as a treatment for chronic constipation (CC) since the 1980s in Japan. The aim of this study is to evaluate its therapeutic effects of MgO in Japanese CC patients. Methods: We conducted a randomized, double-blind placebo-controlled study. Thirty-four female patients with mild to moderate constipation were randomly assigned to either placebo (n = 17) or MgO group (n = 17) 0.5 g × 3/day for 28 days. Primary endpoint was overall improvement over the 4-week study period. Secondary endpoints were changes from baseline in spontaneous bowel movement (SBM), response rates of complete spontaneous bowel movement (CSBM), stool form, colonic transit time (CTT), abdominal symptom, and quality of life. Results: One patient failed to complete the medication regimen and was omitted from analysis: data from 16 placebo and 17 MgO patients were analyzed. The primary endpoint was met by 25.0% of placebo vs 70.6% of MgO group (P = 0.015). MgO significantly improved SBM changes compared to placebo ( P = 0.002). However, MgO did not significantly improved response rates of CSBM compared to placebo (P = 0.76). In addition, MgO significantly improved Bristol stool form scale changes (P < 0.001) and significantly improved CTT compared to the placebo group (P < 0.001). MgO significantly improved the Japanese version of the patient assessment of constipation quality of life (P = 0.003). Conclusion: Our placebo-controlled study demonstrated that MgO was effective treatment for improving defecation status and shortened CTT in Japanese CC patients with mild to moderate symptoms.

8.
Gut Liver ; 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31547640

RESUMO

Whether Helicobacter pylori eradication actually reduces the risk of metachronous gastric cancer (MGC) development remains a controversial question. In this review, we addressed this topic by reviewing the results of clinical investigations and molecular pathological analyses of the roles of H. pylori eradication and aspirin administration in the prevention of MGC. In regard to the clinical studies, the results of meta-analyses and randomized control trials differ from those of retrospective studies: the former trials show that H. pylori eradication has a preventive effect on MGC, while the latter studies do not. This discrepancy may be at least partly attributable to differences in the follow-up periods: H. pylori eradication is more likely to prevent MGC over a long-term follow-up period (≥5 years) than over a short-term follow-up period. In addition, many studies have shown that aspirin may have an additive effect on MGC-risk reduction after H. pylori eradication has been achieved. Both H. pylori eradication and aspirin use induce molecular alterations in the atrophic gastritis mucosa but not in the intestinal metaplasia. Unfortunately, the molecular pathological analyses of these interventions have been limited by short follow-up periods. Therefore, a long-term prospective cohort is needed to clarify the changes in molecular events caused by these interventions.

9.
Digestion ; : 1-10, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533100

RESUMO

INTRODUCTION: Impaired intestinal epithelial barrier function is a hallmark of a variety of pathological conditions such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). IBD patients with IBS-like symptoms show higher interleukin-13 (IL-13) serum levels and poor psychological well-being. Supplementary glutamine reduced the daily bowel movement frequency, improved the stool form, and normalized intestinal hyperpermeability. This study was aimed at assessing the effects of IL-13 and supplementary glutamine on human intestinal epithelial function in vitro. METHODS: Caco-2 cells were grown on TranswellTM inserts. -IL-13 was added to the basolateral compartment, and transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) labeled-dextran permeability measured. Effects of glutamine or the phosphatidylinositol-3-kinase inhibitor LY294002 were assessed. Involvement of tight junction proteins was assessed using Western blotting and immunofluorescence staining. RESULTS: IL-13 significantly decreased TEER and increased FITC labeled-dextran epithelial permeability. IL-13 stimulation decreased the claudin-1 expression and increased the claudin-2 expression. Glutamine alleviated IL-13-induced decrease of TEER and increase of FITC labeled-dextran permeability. Further, the phosphatidylinositol-3-kinase inhibitor showed this alleviating effect while the signal transducer and activator of transcription 6 inhibitor did not. CONCLUSIONS: IL-13 induced barrier integrity impairment by decreasing claudin-1 and increasing claudin-2. Glutamine alleviated IL-13-induced barrier dysfunction by increasing claudin-1 expression, via disruption of the phosphatidylinositol-3-kinase/Akt signaling pathway.

10.
Anticancer Res ; 39(9): 4687-4698, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519568

RESUMO

BACKGROUND/AIM: Propagermanium (PG) inhibits the CCL2/CCR2 axis, and has been shown to function as an immune modulator. This study investigated its anti-tumor mechanism in patients with refractory cancers. MATERIALS AND METHODS: Five healthy volunteers and 23 patients with refractory oral (n=8) or gastric (n=15) cancer received PG (30 mg/day). We performed flow cytometry (FCM) of peripheral blood mononuclear cells and in vitro killing assays. RESULTS: FCM revealed that CD16+/CD56Dim NK cells (i.e., mature, cytolytic subset) increased, and the apoptosis induction rate of cancer cells increased after PG administration. Among gastric cancer patients, median OS was 172.0 days. Two patients showed complete remission of lung or liver metastasis. Survival of patients with oral cancer also tended to be prolonged. CONCLUSION: PG induces NK cell maturation, and may potentiate anti-tumor activity.


Assuntos
Antineoplásicos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Neoplasias/imunologia , Neoplasias/mortalidade , Compostos Organometálicos/farmacologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Humanos , Estimativa de Kaplan-Meier , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Tomografia Computadorizada por Raios X
11.
Gut ; 68(11): 1928-1941, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31375601

RESUMO

OBJECTIVE: Antireflux surgery can be proposed in patients with GORD, especially when proton pump inhibitor (PPI) use leads to incomplete symptom improvement. However, to date, international consensus guidelines on the clinical criteria and additional technical examinations used in patient selection for antireflux surgery are lacking. We aimed at generating key recommendations in the selection of patients for antireflux surgery. DESIGN: We included 35 international experts (gastroenterologists, surgeons and physiologists) in a Delphi process and developed 37 statements that were revised by the Consensus Group, to start the Delphi process. Three voting rounds followed where each statement was presented with the evidence summary. The panel indicated the degree of agreement for the statement. When 80% of the Consensus Group agreed (A+/A) with a statement, this was defined as consensus. All votes were mutually anonymous. RESULTS: Patients with heartburn with a satisfactory response to PPIs, patients with a hiatal hernia (HH), patients with oesophagitis Los Angeles (LA) grade B or higher and patients with Barrett's oesophagus are good candidates for antireflux surgery. An endoscopy prior to antireflux surgery is mandatory and a barium swallow should be performed in patients with suspicion of a HH or short oesophagus. Oesophageal manometry is mandatory to rule out major motility disorders. Finally, oesophageal pH (±impedance) monitoring of PPI is mandatory to select patients for antireflux surgery, if endoscopy is negative for unequivocal reflux oesophagitis. CONCLUSION: With the ICARUS guidelines, we generated key recommendations for selection of patients for antireflux surgery.


Assuntos
Refluxo Gastroesofágico/cirurgia , Seleção de Pacientes , Adulto , Atitude do Pessoal de Saúde , Consenso , Técnica Delfos , Endoscopia , Monitoramento do pH Esofágico , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/patologia , Humanos , Manometria , Guias de Prática Clínica como Assunto , Padrões de Prática Médica
12.
Sci Rep ; 9(1): 12559, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467363

RESUMO

The risk of gastric cancer (GC) declines after Helicobacter pylori (H. pylori) eradication and long-term aspirin use. We evaluated the effects of H. pylori eradication (Cohort 1) and aspirin use (Cohort 2) on the methylation of microRNAs (miRNAs), such as miR-34c, miR-124a-3, miR-129-2, and miR-137, in the gastric mucosa with and without GC, i.e., in atrophic mucosal glands without intestinal metaplasia (non-IM) and intestinal metaplastic glands (IM). DNA was isolated from non-IM and IM separately using laser caption microdissection. In Cohort 1, H. pylori eradication was associated with a significant reduction of miR-124a-3 methylation only in non-IM, but not in IM. miR-129-2 methylation in non-IM may be a surrogate marker of GC in H. pylori-infected patients. In Cohort 2, aspirin did not reverse miRNA methylation in either non-IM or IM, irrespective of H. pylori infection. miR-129-2 methylation in non-IM was an independent predictive marker of GC in H. pylori-infected but not -eradicated patients. These results indicate that H. pylori eradication and aspirin use were less effective for improving methylation in IM than in non-IM; thus, these interventions are recommended at an early stage prior to the development of IM to prevent GC development. In addition, the effects of the interventions were not uniform for each miRNA gene.

13.
J Neurogastroenterol Motil ; 25(3): 343-362, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31327218

RESUMO

Background/Aims: There has been major progress in our understanding of the irritable bowel syndrome (IBS), and novel treatment classes have emerged. The Rome IV guidelines were published in 2016 and together with the growing body of Asian data on IBS, we felt it is timely to update the Asian IBS Consensus. Methods: Key opinion leaders from Asian countries were organized into 4 teams to review 4 themes: symptoms and epidemiology, pathophysiology, diagnosis and investigations, and lifestyle modifications and treatments. The consensus development process was carried out by using a modified Delphi method. Results: Thirty-seven statements were developed. Asian data substantiate the current global viewpoint that IBS is a disorder of gut-brain interaction. Socio-cultural and environmental factors in Asia appear to influence the greater overlap between IBS and upper gastrointestinal symptoms. New classes of treatments comprising low fermentable oligo-, di-, monosacharides, and polyols diet, probiotics, non-absorbable antibiotics, and secretagogues have good evidence base for their efficacy. Conclusions: Our consensus is that all patients with functional gastrointestinal disorders should be evaluated comprehensively with a view to holistic management. Physicians should be encouraged to take a positive attitude to the treatment outcomes for IBS patients.

14.
Sci Rep ; 9(1): 10526, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324814

RESUMO

Non-ampullary duodenal adenocarcinoma (NADC) is extremely rare. Little is known about its clinicopathological and molecular features or its management. Herein we retrospectively analyzed the cases of 32 NADC patients, focusing on microsatellite instability (MSI), genetic mutations, CpG island methylator phenotype (CIMP), and immunostaining including mucin phenotype and PD-L1 expression. The incidence of MSI, KRAS/BRAF/GNAS mutations and CIMP was 51.6%, 34.4%/3.1%/6.5% and 28.1%, respectively. PD-L1 expression was seen in 34.4% of patients. No significant associations between clinicopathological features and KRAS/BRAF/GNAS genetic mutations or CIMP were found. Histologically non-well-differentiated-type NADCs and those in the 1st portion of the duodenum were significantly associated with later stages (stages III-IV) (P = 0.006 and P = 0.003, respectively). Gastric-phenotype NADCs were frequently observed in the 1st portion and in late-stage patients; their cancer cells more frequently expressed PD-L1. Histologically, the non-well-differentiated type was an independent predictor of PD-L1 expression in cancer cells (OR 25.05, P = 0.04) and immune cells (OR 44.14, P = 0.02). Only late-stage disease (HR 12.23, P = 0.01) was a prognostic factor for worse overall survival in a Cox proportional hazards regression model. Our observation of high proportions of MSI and PD-L1 expression may prompt the consideration of immune checkpoint inhibitors as a new treatment option for NADCs.

15.
JCI Insight ; 4(9)2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31045572

RESUMO

The physiological process of defecation is directly controlled by colorectal motility. The transient receptor potential ankyrin 1 (TRPA1) channel is expressed in small intestine enterochromaffin cells and is involved in gastrointestinal motility via serotonin release. In the colorectum, however, enterochromaffin cell localization is largely distinct from that in the small intestine. Here, we investigated the role of lower gastrointestinal tract TRPA1 in modulating colorectal motility. We found that in colonic tissue, TRPA1 is predominantly expressed in mesenchymal cells of the lamina propria, which are clearly distinct from those in the small intestine. These cells coexpressed COX1 and microsomal prostaglandin E synthase-1. Intracolonic administration of TRPA1 agonists induced colonic contraction, which was suppressed by a prostaglandin E2 (PGE2) receptor 1 antagonist. TRPA1 activation induced calcium influx and PGE2 release from cultured human fibroblastic cells. In dextran sulfate sodium-treated animals, both TRPA1 and its endogenous agonist were dramatically increased in the colonic lamina propria, accompanied by abnormal colorectal contractions. Abnormal colorectal contractions were significantly prevented by pharmacological and genetic inhibition of TRPA1. In conclusion, in the lower gastrointestinal tract, mesenchymal TRPA1 activation results in PGE2 release and consequently promotes colorectal contraction, representing what we believe is a novel physiological and inflammatory bowel disease-associated mechanism of gastrointestinal motility.

16.
J Infect Chemother ; 25(10): 769-773, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31023569

RESUMO

BACKGROUND: Serum Helicobacter pylori (H. pylori) antibody kits (LZ and LIA) using the latex agglutination immunoassay method are commercially available, but few studies have been performed to determine their diagnostic accuracy or to compare their results with those of enzyme-linked immunosorbent assay (ELISA) kits (EP and EIA). METHODS: Sera were obtained from 213 hospital outpatients with dyspeptic symptoms. The serological results were compared with the result of the 13C-urea breath test (UBT) which seems to be reliable. RESULTS: Of the 213 subjects, 154 were diagnosed as positive for H. pylori infection according to the UBT. The sensitivities and specificities of these tests were 97.4% and 76.3%, 98.1% and 78.0%, 99.4% and 74.6%, and 98.1% and 71.2% for the EP, LZ, EIA and LIA tests, respectively. When the 13 subjects whose seropositive results of the four kits were completely opposite to the negative results of the UBT were excluded, the specificities of evaluated kits were all higher than 90%. The concordance rate between the EP and EIA tests was 98.1% (Spearman's rank correlation coefficient = 0.83) and that between the LZ and LIA tests was 97.1% (correlation coefficient = 0.91). The LZ gave higher antibody titer value than EP (p < 0.0001, Z = 9.82; Wilcoxon signed-rank test), and EIA gave higher value than LIA (p < 0.0001, Z = 6.43; Wilcoxon signed-rank test). CONCLUSIONS: The latex immunoassay method provided the same reliability to ELISA in terms of the diagnostic accuracy for current H. pylori infection, although we should take into account the titer value differences by each test method in practical use.


Assuntos
Anticorpos Antibacterianos/isolamento & purificação , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Testes de Fixação do Látex/instrumentação , Ureia/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Testes Respiratórios/instrumentação , Isótopos de Carbono/análise , Comércio , Ensaio de Imunoadsorção Enzimática/economia , Ensaio de Imunoadsorção Enzimática/instrumentação , Ensaio de Imunoadsorção Enzimática/estatística & dados numéricos , Feminino , Infecções por Helicobacter/sangue , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Humanos , Testes de Fixação do Látex/economia , Testes de Fixação do Látex/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ureia/química , Adulto Jovem
17.
J Gastroenterol ; 54(8): 718-729, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30919071

RESUMO

BACKGROUND: Long-term maintenance treatment of gastroesophageal reflux disease (GERD) is important to prevent relapse. Proton-pump inhibitors (PPIs) are used for both treatment and maintenance therapy of GERD. Recently, a potassium-competitive acid blocker vonoprazan was launched in Japan. We evaluated the comparative efficacy of vonoprazan and other PPIs for GERD maintenance. METHODS: A systematic literature search was performed using MEDLINE and Cochrane Central Register of Controlled Trials. Double-blind randomized controlled trials (RCTs) of PPIs, vonoprazan, and placebo for GERD maintenance published in English or Japanese were selected. Among them, studies conducted at the recommended dose and for the recommended use, and containing information on maintenance rate based on endoscopic assessment, were included. The comparative efficacies of treatments were estimated by performing a Bayesian network meta-analysis, which assessed the consistency assumption. Outcomes were number or rate of patients who maintained remission. RESULTS: Of 4001 articles identified, 22 RCTs were eligible for analysis. One study published as an abstract was hand-searched and added. The consistency hypothesis was not rejected for the analysis. The odds ratio of vonoprazan 10 mg to each PPI was 13.92 (95% credible interval [CI] 1.70-114.21) to esomeprazole 10 mg; 5.75 (95% CI 0.59-51.57) to rabeprazole 10 mg; 3.74 (95% CI 0.70-19.99) to lansoprazole 15 mg; and 9.23 (95% CI 1.17-68.72) to omeprazole 10 mg. CONCLUSIONS: The efficacy of vonoprazan in GERD maintenance treatment may be higher than that of some PPIs. However, a direct comparison of vonoprazan and PPIs is required to confirm these effects.

18.
Sci Rep ; 9(1): 4381, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30867532

RESUMO

Gut microbiota plays a pivotal role in various aspects of host physiology, including metabolism, gastrointestinal (GI) motility and hormonal secretion. In the present study, we investigated the effect of antibiotic-associated dysbiosis on metabolism and GI motility in relation to colonic expression of glucagon-like peptide-1 (GLP-1) and G protein coupled receptor (GPR)43. Specific pathogen-free (SPF) mice (ICR, 6 weeks old, female) were orally administered vancomycin (0.2 mg/ml) in drinking water for 7 days. In another experiment, germ-free (GF) mice (ICR, 6 weeks old, female) were subjected to oral fecal transplantation (FT) using a fecal bacterial suspension prepared from SPF mice that had received vancomycin treatment (FT-V) or one from untreated control SPF mice (FT-C). The gastrointestinal transit time (GITT) was measured by administration of carmine red (6% w/v) solution. The expression of GLP-1 and GPR43 was examined by immunohistochemistry and realtime RT-PCR, and the plasma GLP-1 level was measured by ELISA. In vancomycin-treated SPF mice, the diversity of the gut microbiota was significantly reduced and the abundance of Lactobacillus was markedly increased. Significant increases in body weight, cecum weight, plasma GLP-1 level and colonic GLP-1/GPR43 expression were also noted relative to the controls. These alterations were reproducible in GF mice with FT-V. Moreover, FT-V GF mice showed a significantly increased food intake and a significantly prolonged GITT in comparison with FT-C GF mice. Vancomycin-induced dysbiosis promotes body weight gain and prolongs GITT, accompanied by an increase of colonic GLP-1/GPR43 expression.

19.
Digestion ; 100(4): 286-294, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30844798

RESUMO

BACKGROUND/AIMS: Bile acids have recently been associated with the pathogenesis of irritable bowel syndrome (IBS). We therefore evaluated the expression of bile acid receptors in the intestinal mucosa of IBS patients as well as the effects of bile acids on small intestinal epithelial cells. METHODS: Intestinal biopsy specimens were obtained from 15 IBS patients and 15 healthy controls. The effects of bile acid stimulation on trans-epithelial electrical resistance (TEER) and permeability in differentiated Caco-2 cells were measured. Proinflammatory cytokines were measured by enzyme-linked immunosorbent assay. mRNA levels of bile acid receptors, including farnesoid X receptor (FXR), and cytokines were determined by real-time reverse transcription-PCR. Caco-2 cells were pre-incubated with the FXR antagonist guggulsterone. RESULTS: FXR mRNA expression at the terminal ileum was increased in IBS patients. Chenodeoxycholic acid (CDCA) significantly decreased TEER, increased permeability, and increased interleukin-8 (IL-8) release from Caco-2 cells. Pre-incubation with guggulsterone blocked CDCA-mediated IL-8 release; however, the decrease in TEER was not reversed. CDCA-induced IL-6 and IL-8 mRNA levels were blocked by guggulsterone. CDCA increased IL-6, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor release, whereas guggulsterone significantly blocked IL-6 and TNF-α release. CONCLUSIONS: FXR expression was elevated at the terminal ileum in IBS patients. CDCA increased proinflammatory cytokines, while guggulsterone blocked these increases.

20.
J Gastroenterol ; 54(4): 305-311, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30767076

RESUMO

Over almost 30 years since functional dyspepsia (FD) was defined, researchers have endeavored to elucidate the pathophysiology of functional gastrointestinal disorders. Now a consensus is emerging that the gastric symptoms of FD are caused mainly by gastric motility abnormalities and gastric hypersensitivity. The involvement of other causative factors including acid, Helicobacter pylori, psychological factors, and diet has been debated, but how they are involved in the manifestation of dyspeptic symptoms remains unclear. We believe that most of those factors cause FD symptoms by inducing gastric motility abnormalities and gastric hypersensitivity via the duodenum. Here, we discuss 2 possible reasons why patients with FD experience chronic upper abdominal symptoms: (1) the possibility that the contents of the duodenum of patients with FD differ from those of healthy persons and the different contents stimulate the duodenum, and (2) the possibility that the duodenum of patients with FD is more sensitive to noxious stimuli because of low-grade inflammation and increased mucosal permeability.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA