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In Japan, with the increasing prevalence of gastroesophageal reflux disease (GERD) and growing public interest, the Japanese Society of Gastroenterology issued Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009 and a revised 2nd edition in 2015. A number of studies on GERD were subsequently conducted in Japan and abroad, and vonoprazan, a potassium-competitive acid blocker (P-CAB), became available for the first time in Japan in February 2015. The revised 3rd edition (Japanese edition), which incorporates new findings and information, was published in April 2021. These guidelines are summarized herein, particularly sections related to the treatment of GERD. The important clinical issues addressed in the present revision are (i) the introduction of treatment algorithms that classify GERD into reflux esophagitis and non-erosive reflux disease, (ii) the clarification of treatment algorithms based on to the severity of reflux esophagitis, and (iii) the positioning of vonoprazan in the treatment for GERD. The present guidelines propose vonoprazan as the initial/maintenance treatment for severe reflux esophagitis. They also recommend vonoprazan or PPI as an initial treatment for mild reflux esophagitis and recommended PPI and proposed vonoprazan as maintenance treatment. These updated guidelines offer the best clinical strategies for GERD patients in Japan and hope that they will be of global use for the diagnosis and treatment for GERD.

Aflatoxin M1 (AFM1) is a mycotoxin that often contaminates milk. Like other mycotoxins, it is thermostable and potentially carcinogenic. The present work was carried out to evaluate the ability of microorganisms isolated from Indonesian kefir grains to reduce AFM1 in contaminated phosphate buffer saline (PBS). Fourteen isolates of lactic acid bacteria, both aerobic (LAE) and anaerobic (LAN), and nine isolates of yeast (YEA) were used. The significantly highest AFM1 reduction percentage was shown by the isolate LAE7 (29.3 ± 0.6%) after 4 h incubation. DNA sequencing of LAE7 and YEA2 isolates showed that these isolates had homology (level of similarity) with species of Lactobacillus kefiri strain A/K and Saccharomyces cerevisiae NRRL Y-12632, respectively. The present work proved that isolates from Indonesian kefir grains could reduce AFM1 and have the potential for practical use.

Background Supragastric belching (SGB) may play a role in the pathophysiology of proton pump inhibitors (PPIs)-refractoriness in gastroesophageal reflux disease (GERD). SGB may be present in up to 40% of reflux symptoms in PPI-refractory GERD. Most reports on SGB have come from Western countries, and little is known about the prevalence and relevance of SGB in Asian refractory GERD patients. This study aimed at comparing the role of SGB in GERD patients in Japan and the UK. Methods We re-analyzed impedance-pH monitoring tracings from patients who were referred to tertiary centers in Japan and the UK due to PPI-refractory reflux symptoms. The prevalence of excessive SGB and the impact of SGB on reflux symptoms were compared between the two countries. Results Impedance-pH tracings from124 Japanese and 83 British patients were re-analyzed. Japanese patients were significantly younger and had smaller body mass index than the British (P P = 0.006). Logistic regression analysis showed that the geographical/cultural difference was the only factor associated with the different prevalence of SGB (odds ratio; 2.91, 95% CI 1.09–7.73, P = 0.032). SGB were related to typical reflux symptoms very rarely in Japan [0% (0–4.9)] compared to the UK [35% (0–54.1)] (P = 0.071). Conclusions The prevalence of SGB and their impact on reflux symptoms is significantly lower in Japan compared to the UK. The difference is not related to reflux parameters but might come from ethnic/cultural factors to be further characterized.

Os potenciais riscos associados à exposição às microcistinas (MCs) requerem o desenvolvimento de pesquisas voltadas para métodos de análise visando ao monitoramento eficiente e rápido de águas. O trabalho avaliou a aplicação dos imunoensaios ELISA desenvolvido em laboratório (LABicELISA) e o comercial (kit ELISA) para detecção de MCs em águas (n=22). O LABicELISA demonstrou ser mais sensível que o kit ELISA, apresentando limite de quantificação de 0,05 e 0,12 µg.L-1, respectivamente. Os resultados demonstraram que ambos os imunoensaios foram eficientes para detecção e análise de MCs em diferentes tipos de água (sintéticas, de mananciais destinados ao abastecimento e de reservatórios), com coeficiente de correlação de 0,997 e forte correlação na exatidão e precisão. O emprego do LABicELISA proporcionou análise com custo aproximado e reduzido de 100 vezes em relação ao do kit ELISA, podendo assim, aplicar em larga escala de abrangência para monitoramento de mananciais superficiais no país.

OBJECTIVE: High-resolution manometry (HRM) is the current standard for characterization of esophageal body and esophagogastric junction (EGJ) function. We aimed to examine the prevalence of abnormal esophageal motor patterns in health, and to determine optimal thresholds for software metrics across HRM systems. DESIGN: Manometry studies from asymptomatic adults were solicited from motility centers worldwide, and were manually analyzed using integrated relaxation pressure (IRP), distal latency (DL), and distal contractile integral (DCI) in standardized fashion. Normative thresholds were assessed using fifth and/or 95th percentile values. Chicago Classification v3.0 criteria were applied to determine motor patterns across HRM systems, study positions (upright vs supine), ages, and genders. RESULTS: Of 469 unique HRM studies (median age 28.0, range 18-79 years). 74.6% had a normal HRM pattern; none had achalasia. Ineffective esophageal motility (IEM) was the most frequent motor pattern identified (15.1% overall), followed by EGJ outflow obstruction (5.3%). Proportions with IEM were lower using stringent criteria (10.0%), especially in supine studies (7.1%-8.5%). Other motor patterns were rare (0.2%-4.1% overall) and did not vary by age or gender. DL thresholds were close to current norms across HRM systems, while IRP thresholds varied by HRM system and study position. Both fifth and 95th percentile DCI values were lower than current thresholds, both in upright and supine positions. CONCLUSIONS: Motor abnormalities are infrequent in healthy individuals and consist mainly of IEM, proportions of which are lower when using stringent criteria in the supine position. Thresholds for HRM metrics vary by HRM system and study position.

Background Esophagogastric junction contractile integral (EGJ-CI) and EGJ morphology are high-resolution manometry (HRM) metrics that assess EGJ barrier function. Normative data standardized across world regions and HRM manufacturers are limited. Methods Our aim was to determine normative EGJ metrics in a large international cohort of healthy volunteers undergoing HRM (Medtronic, Laborie, and Diversatek software) acquired from 16 countries in four world regions. EGJ-CI was calculated by the same two investigators using a distal contractile integral-like measurement across the EGJ for three respiratory cycles and corrected for respiration (mm Hg cm), using manufacturer-specific software tools. EGJ morphology was designated according to Chicago Classification v3.0. Median EGJ-CI values were calculated across age, genders, HRM systems, and regions. Results Of 484 studies (28.0 years, 56.2% F, 60.7% Medtronic studies, 26.0% Laborie, and 13.2% Diversatek), EGJ morphology was type 1 in 97.1%. Median EGJ-CI was similar between Medtronic (37.0 mm Hg cm, IQR 23.6-53.7 mm Hg cm) and Diversatek (34.9 mm Hg cm, IQR 22.1-56.1 mm Hg cm, P = 0.87), but was significantly higher using Laborie equipment (56.5 mm Hg cm, IQR 35.0-75.3 mm Hg cm, P < 0.001). 5(th) percentile EGJ-CI values ranged from 6.9 to 12.1 mm Hg cm. EGJ-CI values were consistent across world regions, but different between manufacturers even within the same world region (P = 0.3) but higher in women (P < 0.001). Conclusions EGJ morphology is predominantly type 1 in healthy adults. EGJ-CI varies widely in health, with significant gender influence, but is consistent within each HRM system. Manufacturer-specific normative values should be utilized for clinical HRM interpretation.

Objective Limitations of existing impedance-pH thresholds include small sample size of normative studies, inclusion of artefactual pH drops and incorrect identification of impedance reflux events. We aimed to obtain new impedance-pH thresholds from expert consensus analysis of tracings from a large number of healthy subjects. Design Of 541 studies performed worldwide using two different systems (Diversatek, USA, and Laborie, Netherlands), 150 tracings with oesophageal diagnoses, behavioural disorders and study-related artefacts were excluded. The remainder studies were subject to two reviewer consensus analysis, in-person or through video conference, consisting of editing meals and pH drops, identification of impedance reflux and postreflux swallow-induced peristaltic wave (PSPW) using strict pre-established criteria and measurement of distal mean nocturnal baseline impedance (MNBI). Results Consensus analysis was performed in 391 tracings (age 32.7 years, range 18-71, 54.2% female). Normative thresholds were significantly different between Diversatek and Laborie (total acid exposure time: 2.8% and 5%; reflux episodes: 55 and 78; MNBI at 3 cm: 1400 and 1500 ohms, at 5 cm: 1400 and 1800 ohms). Males had higher acid exposure, more reflux episodes and lower MNBI. Significant regional differences were identified, including higher PSPW scores in Western countries, and higher MNBI in Asia using Diversatek, and higher acid exposure in the Netherlands, higher MNBI in Asia and South Africa, and lower MNBI in Turkey using Laborie. Conclusion Normal impedance-pH monitoring thresholds have regional and system-related differences. Clinical interpretation needs to use normal thresholds valid for the system used and world region, following careful editing of the tracings., Queen Mary University of London, UK [DDCH1A3R], The study was conducted with financial support from Research Grant DDCH1A3R, Queen Mary University of London, UK.

Purpose of the guidelines The primary objective of these guidelines is to provide general clinicians with information that would guide them to make informed choices of the available diagnosis/treatment strategies for esophageal cancer (intended for malignant esophageal tumors of epithelial origin, not for any other non-epithelial malignant tumors of the esophagus or metastatic esophageal malignant tumors). Furthermore, these guidelines are also intended as an aid for healthcare professionals other than the physicians, patients, and patients’ family members, to obtain an understanding of the fundamental principles of the diagnosis and treatment of esophageal cancer. These guidelines are intended to allow physicians to undertake diagnosis and treatment of esophageal cancer by sharing the information contained in the guidelines and promote mutual understanding among the healthcare professionals, patients, and their family members.

We previously reported that cascade stomach was associated with reflux symptoms and esophagitis. Delayed gastric emptying has been believed to initiate transient lower esophageal sphincter relaxation (TLESR). We hypothesized that cascade stomach may be associated with frequent TLESR with delayed gastric emptying. Eleven subjects with cascade stomach and 11 subjects without cascade stomach were enrolled. Postprandial gastroesophageal manometry and gastric emptying using a continuous 13C breath system were measured simultaneously after a liquid test meal. TLESR events were counted in early period (0–60 min), late period (60–120 min), and total monitoring period. Three parameters of gastric emptying were calculated: the half emptying time, lag time, and gastric emptying coefficient. The median frequency of TLESR events in the cascade stomach and non-cascade stomach groups was 6.0 (median), 4.6 (interquartile range) vs 5.0, 3.0 in the early period, 5.0, 3.2 vs 3.0, 1.8 in the late period, and 10.0, 6.2 vs 8.0, 5.0 in the total monitoring period. TLESR events were significantly more frequent in the cascade stomach group during the late and total monitoring periods. In contrast, gastric emptying parameters showed no significant differences between the two groups. We concluded that TLESR events were significantly more frequent in persons with cascade stomach without delayed gastric emptying.

Background Vonoprazan (V), a potassium-competitive acid blocker, has a more durable acid-inhibitory effect as compared with standard-dose proton pump inhibitors (PPIs) but has not been compared with 2-4 times higher daily PPI doses administered in two divided doses. Aims To evaluate the acid-inhibitory effect of V 10/20 mg once-daily (OD; V10/V20) vs rabeprazole (R) 10/20 mg twice-daily (BID; R20/R40) in healthy Japanese volunteers. Methods This multicentre, randomised, open-label, two-period, crossover study compared V10 or V20 vs R20, or V20 vs R40 using three cohorts of 10 healthy Japanese adults. Within each cohort, subjects were randomised to receive V or R for 7 days and, following a washout period ≥7 days, the other treatment for 7 days. On day 6 of each period, 24-hours multichannel gastric impedance-pH monitoring was performed. Percent times pH ≥ 3, ≥4 and ≥5 (pH 3, 4 and 5 holding time ratios [HTRs]) in 24 hours were evaluated as primary pharmacodynamic endpoints. Results Acid-inhibitory effect (24-hours pH 3 HTR) of V20 was greater than those of R20 (91.0% vs 65.3%; P = .0049) and R40 (98.5% vs 85.9%; P = .0073). Similar results were obtained for 24-hours pH 4 and 5 HTRs. V20 also achieved greater nocturnal pH 4 (91.5% vs 73.2%; P = .0319) and 5 HTRs (78.8% vs 62.2%; P = .0325) as compared with R40. One subject (20%) developed diarrhoea while receiving R40 which was considered treatment-related. Conclusions Compared with 2-4 times the standard daily dose of R, V20 exerts a more potent and durable acid-inhibitory effect. Trial identifier: UMIN000022198 (www.umin.ac.jp/ctr/index.htm).

We combined immunoaffinity column (IAC) and enzyme-linked immunosorbent assay (ELISA) methods to develop a rapid method to analyze total aflatoxin (AF) in foods, using a large number of samples. Using newly developed monoclonal antibodies, with high cross-reactivity and high organic solvent tolerance, we developed the IAC-ELISA method. Our IAC-ELISA method showed a good correlation with the high-performance liquid chromatography method for corn samples spiked with total AF. Certain food samples, such as chili powder, chocolate, green coffee beans, and roasted coffee beans, are difficult to measure owing to their matrices, which affect ELISA adversely. Our IAC-ELISA method clearly improved the recovery rates (79 to 109%) compared with the ELISA method (97 to 164%) for four food samples. Our method is simple and quick; thus, it may be ideal for routine inspections.

Background/Aims Twenty-four-hour esophageal impedance and pH monitoring allows detection of all types of reflux episodes and is considered the best technique for identifying gastroesophageal refluxes. However, normative data for the Japanese population are lacking. This multicenter study aimed to establish the normal range of 24-hour esophageal impedance and pH data both in the distal and the proximal esophagus in Japanese subjects. Methods Forty-two healthy volunteers (25 men and 17 women) with a mean ± standard deviation age of 33.3 ± 12.4 years (range: 22-72 years) underwent a combined 24-hour esophageal impedance and pH monitoring. According to the physical and pH properties, distal or proximal esophageal reflux events were categorized. Results Median 45 reflux events occurred in 24 hours, and the 95th percentile was 85 events. Unlike previous reports, liquid-containing reflux events are median 25/24 hours with the 95th percentile of 62/24 hours. Acidic reflux events were median 11/24 hours with the 95th percentile of 39/24 hours. Non-acidic gas reflux events were median 15/24 hours with the 95th percentile of 39/24 hours. Proximal reflux events accounted for 80% of the total reflux events and were mainly non-acidic gas refluxes. About 19% of liquid and mixed refluxes reached the proximal esophagus. Conclusions Unlike previous studies, liquid-containing and acidic reflux events may be less frequent in the Japanese population. Non-acidic gas reflux events may be frequent and a cause of frequent proximal reflux events. This study provides important normative data for 24-hour impedance and pH monitoring in both the distal and the proximal esophagus in the Japanese population.

As an increase in gastroesophageal reflux disease (GERD) has been reported in Japan, and public interest in GERD has been increasing, the Japanese Society of Gastroenterology published the Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009. Six years have passed since its publication, and there have been a large number of reports in Japan concerning the epidemiology, pathophysiology, treatment, and Barrett's esophagus during this period. By incorporating the contents of these reports, the guidelines were completely revised, and a new edition was published in October 2015. The revised edition consists of eight items: epidemiology, pathophysiology, diagnosis, internal treatment, surgical treatment, esophagitis after surgery of the upper gastrointestinal tract, extraesophageal symptoms, and Barrett's esophagus. This paper summarizes these guidelines, particularly the parts related to the treatment for GERD. In the present revision, aggressive proton pump inhibitor (PPI) maintenance therapy is recommended for severe erosive GERD, and on-demand therapy or continuous maintenance therapy is recommended for mild erosive GERD or PPI-responsive non-erosive GERD. Moreover, PPI-resistant GERD (insufficient symptomatic improvement and/or esophageal mucosal break persisting despite the administration of PPI at a standard dose for 8 weeks) is defined, and a standard-dose PPI twice a day, change in PPI, change in the PPI timing of dosing, addition of a prokinetic drug, addition of rikkunshito (traditional Japanese herbal medicine), and addition of histamine H2-receptor antagonist are recommended for its treatment. If no improvement is observed even after these treatments, pathophysiological evaluation with esophageal impedance-pH monitoring or esophageal manometry at an expert facility for diseases of the esophagus is recommended.

The occurrence of deoxynivalenol (DON) was evaluated in 113 wheat samples from the northern and central/southwestern regions of Parana State, Brazil during the 2008 and 2009 growing seasons, and this rate of occurrence was used to estimate the DON dietary exposure. The DON determination was carried out by an indirect competitive enzyme-linked immunosorbent assay. DON was detected in 66.4% samples at levels ranging from 206.3 to 4732.3 lg/kg (mean 1894.9 lg/kg). The estimated daily intake (EDI) of DON through bread and pasta was evaluated in the inhabitants of Londrina City in northern Parana State, Brazil. The average intake of these inhabitants was 0.79 lg/kg body weight (b.w.) for bread and 0.35 lg/ kg b.w. for pasta. The total EDI was 1.13 lg/kg, which is above the Provisional Tolerable Daily Maximum Intake (PTDMI) of 1 lg/kg b.w. To our knowledge, this is the first report on natural DON occurrence in wheat and DON dietary exposure estimation from Parana, Brazil.

Aflatoxin B1 (AFB1), a mycotoxin found in food and feed, exerts harmful effects on humans and animals. The liver is the earliest target of AFB1, and its effects have been evaluated in animal models exposed to acute or chronic doses. Considering the possibility of sporadic ingestion of AFB1-contaminated food, this study investigated the impact of a single oral dose of AFB1 on liver function/cytokines and the lymphoproliferative response in mice. C57BL/6 mice were treated with a single oral AFB1 dose (44, 442 or 663 μg AFB1/kg of body weight) on the first day. Liver function (ALT, γ-GT, and total protein), cytokines (IL-4, IFN-γ, and IL-17), histopathology, and the spleen lymphoproliferative response to mitogens were evaluated on the 5th day. Although AFB1 did not produce any significant changes in the biochemical parameters, 663 μg AFB1/kg-induced hepatic upregulation of IL-4 and IFN-γ, along with liver tissue injury and suppression of the lymphoproliferative response to ConA (p < 0.05). In conclusion, a single oral dose of AFB1 exposure can induce liver tissue lesions, liver cytokine modulation, and immune suppression in C57BL/6 mice.

Comparisons between the acid inhibitory effects of rabeprazole and esomeprazole after single oral administration with standard doses have not been previously presented. We examined intra-gastric pH after oral administrations of these two proton pump inhibitors using 24-h pH monitoring. Fifty-four normal volunteers not infected by Helicobacter pylori were investigated. Using a cross-over design, we administered 10 mg of rabeprazole or 20 mg of esomeprazole in 27 at 30 min after supper and in the remaining 27 subjects at 15 min before supper, and performed 24-h pH monitoring. Intra-gastric pH data were nearly identical when the proton pump inhibitors were taken after meals. Even if the data were compared in different CYP2C19 genotypes, rabeprazole and esomeprazole did not show the difference. In poor metabolizer, both of the drugs showed stronger acid inhibition. When taken before meals, intra-gastric pH after esomeprazole administration was slightly but not significantly higher than that observed after rabeprazole administration not only in daytime but also in nighttime period. In conclusion, rabeprazole and esomeprazole were similarly effective when administered after a meal.

Hepatitis B virus (HBV) reactivation has been increasingly recognized in patients receiving chemotherapy and immunosuppressive therapy; however, the prevalence of HBV infection and rate of HBV screening in patients with rheumatic diseases remains unclear. In this study, we aimed to assess the prevalence of HBV infection and fulminant HBV hepatitis in patients with rheumatic diseases. We also investigated the rate of HBV screening before immunosuppressive therapy in patients with rheumatic diseases. A retrospective questionnaire survey was conducted in the North-east area (Tohoku) of Japan. Questionnaires, comprising 6 questions, were sent to 318 rheumatologists in May 2010, and responses were gathered until June 2011. In total, 71 rheumatologists (22.3%) responded to the survey. We enrolled 7,650 patients with rheumatoid arthritis (RA) and 1,031 patients with systemic lupus erythematosus (SLE). When limited to institutes at which almost all (≥ 90%) patients were tested for HBV serology, 1.1% (40/3,580) patients with RA and 0.3% (3/1,128) patients with SLE were positive for hepatitis B surface antigen (HBsAg), and 25.2% (177/703) patients with RA and 13.7% (34/248) patients with SLE were positive for hepatitis B core antibody (HBcAb). About one-third of rheumatologists did not check HBsAg and more than half did not check hepatitis B surface antibody (HBsAb) or HBcAb at all before therapy. Fulminant HBV hepatitis was observed in 1 RA patient who was current HBV carrier. In conclusion, the prevalence of HBV infection is high in patients with RA and SLE. HBV screening before immunosuppressive therapy should be strictly performed.

Helicobacter pylori (H. pylori) induces gastroduodenal diseases and vigorous humural and cellular immune abnormalities. In order to clarify the immunological changes before and after eradication of H. pylori, the percentages and ratios of the following cells in the peripheral blood of 32 H. pylori-infected patients and 25 control subjects were analyzed: CD4+ T cells, CD8+ T cells, T helper 1 cells (Th1), T helper 2 cells (Th2), CD4+CD25+ T cells, Foxp3+ regulatory T cells (Treg), CD4/CD8 ratio, and Th1/Th2 ratio. CD4/CD8 ratio was significantly higher in H. pylori-infected patients before (mean ± SD, 2.9 ± 1.9) and after (mean ± SD, 2.8 ± 1.6) eradication of H. pylori than in control subjects (mean ± SD, 2.1 ± 0.9). The percentage of Th2 cells was significantly higher in H. pylori-infected patients (mean ± SD, 2.6 ± 1.1) than in control subjects (mean ± SD, 1.9 ± 1.1; p H. pylori (mean ± SD, 2.3 ± 1.4) was lower than that before eradication. There was no significant difference between control subjects (mean ± SD, 4.1% ± 1.5%) and patients before H. pylori eradication (mean ± SD, 4.5% ± 2.4%) in the percentage of Tregs, but the percentage was significantly higher in patients after H. pylori eradication (mean ± SD, 5.2% ±2.6%) than in control subjects. The function of peripheral induced Tregs was reported to suppress the excessive immune reaction in chronic inflammation. These data suggest that Tregs may proliferate and be activated to suppress the activation of humoral immunity in H. pylori-infected patients, and these changes continue after 3 months or later of successful eradication of H. pylori.

Background Only a few studies –none from Asia– have been reported on high-resolution manometry (HRM) assessment of esophageal motor function in eosinophilic esophagitis (EoE). This study aimed to evaluate esophageal motility in Japanese patients with esophageal eosinophil infiltration and to clarify the association between esophageal dysmotility and symptoms, endoscopic findings, severity of eosinophilic infiltration, blood eosinophil count, and response to treatment. Methods Ninety-two patients underwent both esophageal manometry and endoscopic biopsy to determine eosinophil infiltration in esophageal mucosa, looking for esophageal motility disorders, between 2009 and 2016. Of these 92 patients, 18 patients (9 males, mean age, 52.5 years) who had esophageal eosinophilia (≥ 15 eosinophils per high power field)w ere enrolled in this study. Characteristic endoscopic findings included circular rings, linear furrowing, and white exudates. HRM [ManoScan; Given Imaging] was performed and evaluated by Chicago classification ver. 3. Results HRM revealed that 15 patients (83%) had esophageal motility disorders (7 achalasia, 2 esophagogastric junction outflow obstruction (EGJOO), 2 jackhammer esophagus, 1 diffuse esophageal spasm (DES), 3 Ineffective esophageal motility (IEM). Dysphagia was observed in all the patients with achalasia or EGJOO. GERD symptoms like regurgitation or heartburn occurred in most of the patients with EGJOO or IEM. Endoscopic findings of EoE did not differ among types of dysmotility. Severity of esophageal eosinophilia did not correlate with hypercontractile motility disorders. Four patients had blood eosinophilia; none of the achalasia patients or those with normal motility had blood eosinophilia. All the patients, except those with achalasia, were treated with a proton pump inhibitor (PPI). None of the patients with jackhammer esophagus or DES responded to PPI, but one (1/2, 50%) with EGJOO, one (1/3, 33%) with IEM, and two patients (2/3, 66%) with normal motility had their symptom relieved after PPI therapy. Seven patients, including 2 with achalasia, needed steroid therapy either by prednisolone or topical steroid orally. The patients with achalasia showed good temporary response to steroid, though they underwent ordinal myotomy afterwards. One with jackhammer esophagus did not respond to steroid therapy and needed repeated myotomy. Conclusion Symptom was a possible factor to predict a type of esophageal dysmotility. Presence of esophageal dysmotility may affect treatment strategy. Disclosure All authors have declared no conflicts of interest.

The objectives of this study were to clarify the effect of chemical fertilizer and manure application on methane (CH4) and nitrous oxide (N2O) emissions from intensively managed grassland on Andosols in Japan and to determine the controlling factors of the CH4 and N2O emissions. The emission factors (EF) for both fertilizer- and manure-induced N2O emissions were calculated. Three experimental plots were set up in five grasslands across four climatic regions in Japan: one plot for treatment with chemical fertilizer (fertilizer plot); another plot for treatment with cattle manure and chemical fertilizer (manure plot), and the final plot was not treated with chemical fertilizer or manure (control plot). The type of chemical fertilizer was ammonium-based fertilizer or a combination fertilizer of ammonium and urea. CH4 and N2O emissions were measured at the study sites for six years. For the manure plot, a supplement of chemical fertilizer was added to equalize the supply rate of mineral nitrogen (N) relative ...

Aflatoxin M1 (AFM1) is an important biomarker that can be used to evaluate aflatoxin exposure in both humans and animals. The aim of this study was to evaluate the exposure degree of infants to AFM1 through consumption of breast milk and infant powdered milk in Brazil. For this purpose, the estimated daily intake (EDI) for infants was calculated based on the AFM1 levels analyzed in 94 breast milk (BM) samples collected in Southern Brazil, and 16 infant powdered milk (IPM) samples commonly commercialized in Brazil. AFM1 was detected in 5.3% (n = 5) and 43.8% (n = 7) of BM and IPM samples, with mean levels of 0.003 ng/g and 0.011 ng/g, respectively. All the IPM samples showed AFM1 levels lower than those established by the Brazilian guidelines (5 ng/g), and in most of the samples (81.25%) levels were below the maximum limit tolerated by the European Commission (0.025 ng/g). The EDI of AFM1 for infants aged zero to 12 months old showed values from 0.018 to 0.069 ng/kg body weight/day for BM, and 0.078 to 0.306 ng/kg body weight/day for IPM. Hazard index (HI) values for BM and IPM were less than one, except for IPM intended for infants up to one month. In conclusion, the exposure of infants to AFM1 was low, but continuous monitoring of mycotoxin levels is essential to minimize infant health risk.

An indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) based on an anti-aflatoxin B 1 monoclonal antibody was standardised and validated for aflatoxin screening in poultry feed samples and its performance was compared to high-performance liquid chromatography (HPLC). The ic-ELISA showed good linearity ( r 2 = 0.994) and detection limits of 1.25 ng g −1 for broiler feed and 1.41 ng g −1 for laying hen feed. Mean aflatoxin recovery rates by ic-ELISA were 102% (laying hen feed) and 98% (broiler feed). Aflatoxins were detected in 88.2% of the 34 broiler feed samples by ic-ELISA and HPLC at means of 10.48 ng g −1 and 8.41 ng g −1 , respectively, while 92% of laying hen feed samples ( n = 36) showed aflatoxin contamination at means of 20.83 and 19.75 ng g −1 . The standardised ic-ELISA showed reliability and a high correlation with HPLC of 0.97 (broiler feed) and 0.98 (laying hen feed) indicating its potential for aflatoxin screening in poultry feed samples.

Objective. To know the characteristics of endoscopic laryngeal and pharyngeal abnormalities in Japanese patients with laryngopharyngeal reflux symptoms (LPRS).Methods. A total of 146 endoscopic images of the larynx and pharynx (60 pairs for the rabeprazole group and 13 pairs for the control group) were presented to 15 otolaryngologists blinded to patient information and were scored according to several variables potentially associated with laryngopharyngeal reflux. The median value of the 15 scores for each item from each image was obtained. The mean pretreatment scores of each item and total score were assessed in both rabeprazole and control groups. In the rabeprazole group, the endoscopic findings before and after the 4-week treatment with rabeprazole were compared. Changes between corresponding duration in the control group were also evaluated.Results. The median and mean pretreatment total score was 3 and 3.02, respectively, from the 73 patients with LPRS. No significant differences were observed before and after treatment in either the rabeprazole or control groups for any item or total score. In 24 patients with a high pretreatment score (total score ≥ 4) from the rabeprazole group, significant decreases in scores for “thick endolaryngeal mucous” (0.54 to 0.17,P=0.017) and total (4.77 to 3.58,P=0.0003) were observed after the 4-week treatment.

Background. Helicobacter pylori chronically colonizes gastric/duodenal mucosa and induces gastroduodenal disease and vigorous humoral and cellular immune responses. Methods. In order to clarify the immunological changes induced by this infection, we determined the percentage and, as indicated, ratios of the following cells in peripheral blood of 45 H. pylori-infected patients and 21 control subjects: CD4+ T cell, CD8+ T cells, T helper 1 cells (Th1), T helper 2 cells (Th2), CD4+CD25+ T cells, Foxp3+ regulatory T cells (Tregs), CD4/CD8 ratio, and Th1/Th2 ratio. Results. The percentage of CD8+ T cells was significantly lower in H. pylori-infected patients (mean ± S D ; 1 8 . 0 ± 7 . 1 %) compared to control subjects (mean ± S D ; 2 3 . 2 ± 7 . 8 %) ( 𝑃 < 0 . 0 5 ). The CD4/CD8 ratio was significantly higher in H. pylori-infected patients (mean ± S D ; 3 . 1 ± 2 . 4 ) compared to control subjects (mean ± S D ; 2 . 1 ± 1 . 0 ) ( 𝑃 < 0 . 0 5 ). The Th1/Th2 ratio was significantly lower in H. pylori-infected patients (mean ± S D ; 1 0 . 0 ± 8 . 5 ) compared to control subjects (mean ± S D ; 1 4 . 5 ± 9 . 0 ) ( 𝑃 < 0 . 0 5 ). The percentage of CD4+CD25+ T cells in H. pylori-infected patients (mean ± S D ; 1 3 . 2 ± 6 . 2 %) was significantly higher than that in control subjects (mean ± S D ; 9 . 8 ± 3 . 4 %) ( 𝑃 < 0 . 0 5 ). However, there was no significant difference in Tregs. Conclusion. Tregs did not decrease, but the activation of humoral immunity and Th2 polarization were observed in the peripheral blood of H. pylori-infected patients. In some cases, these changes may induce systemic autoimmune diseases.

An experiment was conducted to investigate the effects of calcium (Ca) fertilization on oxalate content in napiergrass (Pennisetum purpureum) and on some blood parameters of sheep. Re-growth napiergrass was grown with or without Ca fertilizer and offered to sheep. Eight sheep, divided into two groups of 4 animals each were used. Calcium-fertilized napiergrass was offered daily to the animals as experimental treatment, whereas without Ca-fertilized napiergrass was given to the animals as control. Results showed that there was a trend to lower soluble and total oxalate concentrations in Ca-fertilized grass than control. The Ca-fertilized grass contained (p0.05) on Ca and Na concentrations in plants. Feeding of Ca-fertilized grass had no affect on the feed consumption, blood Mg level and daily gain of sheep. However, sheep fed control grass had lower (p

Wheat comprises one of the main ingredients in human diet, accounting for approximately 20 % of daily calories. Concerning the predominant frequency of deoxynivalenol (DON) producing Fusarium graminearum in wheat, DON occurrence in the State of Paraná (21 samples) and Rio Grande do Sul (15 samples), as well as the risk assessment of daily intake of DON in Londrina-PR, Brazil were evaluated. DON was detected in 72.2 % samples by high performance liquid chromatography (HPLC), which ranged from non-detectable to 1,592.21 ?g/kg, with average of 321.59 ?g/kg (limit of quantification= 87.75 ?g/kg). In order to calculate the estimated daily intake (EDI) of DON, a Food Frequency Questionnaire was applied to 260 persons (64.8 % female and 35.2 % male, from 8 to 76 years-old). The main food ingested were pasta (151 g/week) and bread (267 g/week), and based in these items, the average estimated daily intake (EDI) of DON was 0.308 ?g/kg body weight/day. This EDI was lower than Provisional Tolerable Daily Maximum Intake (PTDMI) settled in 1 ?g/kg b.w./day, although two persons showed estimated DON ingestion above PTDMI. The data ratify the importance of continuous monitoring and risk assessment targeted on DON exposure.O trigo é um dos alimentos mais consumidos na dieta humana, contribuindo com cerca de 20 % das calorias diárias. Considerando a predominância de Fusarium graminearum neste grão, a contaminação por desoxinivalenol (DON) foi avaliada em trigo dos Estados do Paraná (21 amostras) e do Rio Grande do Sul (15 amostras), assim como se estimou o risco da sua ingestão diária no município de Londrina-PR, Brasil. Utilizando Cromatografia Líquida de Alta Eficiência (CLAE), DON foi detectado em 72,2 % das amostras, variando de não detectável a 1592,21 ?g/kg, nível médio 321,59 ?g/kg (limite de quantificação= 87,75 ?g/kg). Para calcular a Ingestão Diária Estimada (IDE) de DON foi aplicado Questionário de Freqüência de Consumo de Alimentos a 260 indivíduos (8-76 anos, 64,8 % do gênero feminino e 35,2 % do masculino). Os derivados mais consumidos foram massas alimentícias (151 g/semana) e pão francês (267 g/semana). Baseado nesses alimentos, a IDE média de DON foi de 0,308 ?g/kg peso corporal/dia, sendo que dois indivíduos (0,8 %) apresentaram IDE superior a Ingestão Diária Máxima Tolerável Provisória (IDMTP) recomendada de 1 ?g/kg p.c./dia. A importância de contínuo monitoramento perante perigo de exposição a DON é evidente, sendo que os níveis máximos em trigo no Brasil foram recentemente publicados pela ANVISA.

In order to determine whether oxalate from grasses affects feed intake, blood calcium (Ca) and other blood parameters of adult sheep, two feeding trials were conducted. In Trial 1, one group of sheep received guineagrass (0.47% soluble oxalate) and another group received setaria (1.34% soluble oxalate) for 28 d. In Trial 2, one group of sheep received guineagrass while another group received the same grass treated with an oxalic acid solution (at a rate of 30 g oxalic acid/kg dry matter of hay) for 72 d. All sheep received concentrate mixtures (0.5% of body weight) throughout the experiment. In both trials, it was observed that plasma Ca concentration (11.0-11.7 mg/dl) was significantly (p 0.05) were observed in concentrations of magnesium, phosphorus and parathyroid hormone in plasma between the feeding of low and high oxalate-containing grasses. In addition, no differences (p>0.05)

Aflatoxin B1 (AFB1) is a mycotoxin classified as group 1 (human carcinogen) by International Agency for Research on Cancer - IARC, causing hazardous contamination in a wide variety of food and feed, where the monitoring depends on precision and accuracy of analytical method. The culture of AFB1 specific monoclonal antibody (mAb) secreting hybridoma was performed for further development of immunochemical methods. The growth of hybridoma AF2 was carried out in RPMI medium + 15 % fetal bovine serum (FBS), as well as the same medium gradually amended with H-SFM medium (25, 50, 75 and 100 % H-SFM). The protein concentration in the culture supernatant ranged from 1.80 to 10.88 mg/mL. The culture amended with FBS-free synthetic H-SFM medium reached production of reagent with higher degree of purity and lower risk, in addition to lower protein content (2.29 mg/mL reached with 100 % H-SFM), which approaches the real content of pure mAb. The indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and SDS-polyacrylamide gel electrophoresis (SDS-PAGE) showed anti-AFB1 activity and IgG corresponding bands, respectively, indicating feasible application of mAb produced in 100, 75 and 50 % H-SFM for further use in the development of AFB1 detecting biotools. This mAb production can be an initial step that can supply the self-sufficient immune-reagent in the rapid diagnosis at national condition, which is essential in the food quality and safety.Aflatoxina B1 (AFB1) é uma micotoxina classificada pela International Agency for Research on Cancer - IARC no Grupo 1 (carcinógeno ao humano), responsável pelo perigo de contaminação em ampla variedade de alimento e ração, cujo monitoramento depende de metodologia analítica precisa e exata. O trabalho visou cultivo do hibridoma secretor de anticorpo monoclonal (AcM) específico para AFB1 visando desenvolvimento de métodos imunoquímicos. Hibridoma AF2 foi cultivado em meio RPMI + 15 % de soro fetal bovino (SFB), assim como o mesmo meio com adição gradual de meio H-SFM (25, 50, 75 e 100 % H-SFM). A concentração proteica obtida no sobrenadante de cultura variou de 1,80 a 10,88 mg/mL. A introdução de meio sintético H-SFM isento de SFB permitiu obtenção de reagente com maior pureza e menor perigo, já que cultivos com maior proporção de H-SFM apresentou menor teor proteico (2,29 mg/mL em 100 % de H-SFM), sendo este provavelmente próximo ao teor real de AcM puro. O ensaio imunoenzimático competitivo indireto (ic-ELISA) e eletroforese em gel de poliacrilamida com SDS (SDS-PAGE) demonstraram atividade antiAFB1 e bandas correspondentes ao IgG, respectivamente, indicando viabilidade da aplicação de AcM produzido em 100, 75 e 50 % H-SFM para o desenvolvimento de bioferramentas para detecção de AFB1. Esta produção de AcM abre perspectiva perante autossuficiência de reagentes essenciais no diagnóstico rápido em condição nacional, contribuindo na qualidade e segurança de alimentos.

Oxalate occurs naturally in forage species, but excess levels of soluble oxalate adversely affect their nutritional quality as animal feed. Although induction of oxalate in plants has been associated with nitrate application, relatively little is known about oxalate in forage grasses. In the present study, we investigated oxalate accumulation and mineral uptake by napiergrass (Pennisetum purpureum, cv. dwarf-late) cultured in complete nutrient solution containing either solely nitrate or mainly ammonium as the main form of nitrogen. Total (shoot and root) yield of plants did not differ significantly between the nitrate and ammonium treatments. By contrast, the nitrogen form significantly affected oxalate accumulation and mineral uptake by plants. Nitrate application resulted in higher concentrations of soluble and insoluble oxalates in the shoot and soluble oxalate in the root than ammonium application. Nitrate application also resulted in higher concentrations of sodium and calcium in the shoot, and higher concentrations of sodium, calcium and magnesium in the root than ammonium application. The results suggest that the application of nitrate fertilizer as the sole source of nitrogen should be avoided in the cultivation of oxalate-rich forages, though further studies are needed under field conditions.