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This study examined the effects of ergothioneine (EGT) supplementation as an antioxidant on the quality of boar spermatozoa when using liquid and frozen preservation methods. In the first experiment, boar semen was preserved in an extender supplemented with 0, 50, 100 and 200 µM EGT, at 15 °C, part of the samples for one and another part for three weeks. In comparison with the control (without EGT), EGT supplementation at 100 µM significantly increased the percentage of total motility of spermatozoa that were preserved as a liquid both for one and three weeks (P < 0.05). EGT supplementation did not affect the quality of preserved spermatozoa, irrespective of the EGT concentration. In the second experiment, semen was frozen and thawed in the freezing extender supplemented with 0, 50, 100 and 200 µM EGT. In comparison with the control, the 100 µM EGT supplementation significantly increased the percentages of total and progressive motility of frozen-thawed spermatozoa (P < 0.05). EGT (100 µM) supplementation did not affect the viability, the plasma membrane integrity, or the acrosomal integrity of frozen-thawed spermatozoa. These findings indicate that supplementing extenders with 100 µM EGT may improve the motility of boar sperm in both liquid and freezing preservation methods. [ABSTRACT FROM AUTHOR]

Background: Metastatic castration‐resistant prostate cancer (mCRPC) is a genetically heterogeneous disease with a poor prognosis. The prevalence of mutations in homologous recombination repair (HRR) pathway genes, including BRCA1/2, as well as treatment patterns and clinical outcomes, are not well characterized among Japanese men with mCRPC. Methods: This multicenter, noninterventional cohort study enrolled Japanese men with mCRPC from 24 institutions between 2014 and 2018. Mutations in the 15 HRR‐related genes were assessed using archival primary or metastatic tumor samples. Patterns of sequential therapies for mCRPC were investigated. Patients were followed up for survival evaluation including prostate‐specific antigen progression‐free survival (PSA‐PFS) and overall survival (OS). Results: Of the 143 patients analyzed, HRR‐related mutations were detected in 51 patients (35.7%). The most frequently mutated genes were CDK12 (N = 19, 13.3%), followed by BRCA2 (N = 18, 12.6%), ATM (N = 8, 5.6%), and CHEK2 (N = 3, 2.1%). The most common type of first‐line therapy for mCRPC was next‐generation hormonal agents (NHA, 44.4%), followed by first‐generation antiandrogens (FGA, 30.3%), and taxanes (22.5%). Commonly prescribed first−/second‐line sequential regimens included FGA/NHA (17.6%), NHA/NHA (15.5%), and NHA/taxanes (14.1%). The median PSA‐PFS and OS for the entire cohort were 5.6 and 26.1 months, respectively. Patients carrying BRCA1/2 mutations had numerically shorter PSA‐PFS (median 3.3 vs. 5.9 months) and OS (median 20.7 vs. 27.3 months) than those without mutations. Conclusions: In conclusion, approximately one‐third of Japanese patients with mCRPC carried mutations in HRR‐related genes in this study. The real‐world outcomes of mCRPC are poor with conventional therapy, warranting an expansion of treatment options based on genetic abnormalities of the disease. [ABSTRACT FROM AUTHOR]

Abstract Background For patients with reflux esophagitis (RE), endoscopic findings alone (without the frequency and severity of symptoms) may not fully reflect the associated impact on health-related quality of life (QOL). There is not enough data about symptoms and QOL of Japanese patients with RE. The present study therefore investigated the epidemiological characteristics of such patients, and evaluated the efficacy and safety of omeprazole (and other gastrointestinal drugs, except proton pump inhibitors [PPIs]) in terms of improving patients' symptoms and QOL. Methods In a large-scale, specific clinical experience investigation of Japanese patients with RE, epidemiological characteristics, QOL and symptoms of the disease in relation to treatment with omeprazole and other gastrointestinal drugs, except PPIs, and safety data of omeprazole were collected. The Quality Of Life in Reflux and Dyspepsia questionnaire (QOLRAD) was used for QOL assessment. Results 9967 patients were included in the analysis (omeprazole: 7888). At baseline, 75.2% of patients had three or more upper gastrointestinal symptoms, and 31.5% of patients had six or more upper gastrointestinal symptoms. The overall mean QOLRAD score at baseline was 5.14 (the best score is 7). In the omeprazole group, the rate of satisfactory improvement in subjective symptoms was 61.7% and 81.8% at Weeks 4 and 8, respectively, and these were both significantly higher than those of patients treated with other drugs. In both the omeprazole group and the other drugs group, the QOLRAD score at Week 4 improved significantly from baseline, and the degree of improvement was significantly greater in the omeprazole group than in the other drugs group. The favourable tolerability profile of omeprazole was confirmed. Conclusion In a large-scale survey, omeprazole improved symptoms and QOL more effectively in Japanese patients with RE than other investigated drugs, and had a good tolerability profile. Trial Registration ClinicalTrials.gov identifier: NCT00859287.

Abstract Background The number of vertebrae in pigs varies and is associated with body size. Wild boars have 19 vertebrae, but European commercial breeds for pork production have 20 to 23 vertebrae. We previously identified two quantitative trait loci (QTLs) for number of vertebrae on Sus scrofa chromosomes (SSC) 1 and 7, and reported that an orphan nuclear receptor, NR6A1, was located at the QTL on SSC1. At the NR6A1 locus, wild boars and Asian local breed pigs had the wild-type allele and European commercial-breed pigs had an allele associated with increased numbers of vertebrae (number-increase allele). Results Here, we performed a map-based study to define the other QTL, on SSC7, for which we detected genetic diversity in European commercial breeds. Haplotype analysis with microsatellite markers revealed a 41-kb conserved region within all the number-increase alleles in the present study. We also developed single nucleotide polymorphisms (SNPs) in the 450-kb region around the QTL and used them for a linkage disequilibrium analysis and an association study in 199 independent animals. Three haplotype blocks were detected, and SNPs in the 41-kb region presented the highest associations with the number of vertebrae. This region encodes an uncharacterized hypothetical protein that is not a member of any other known gene family. Orthologs appear to exist not only in mammals but also birds and fish. This gene, which we have named vertnin (VRTN) is a candidate for the gene associated with variation in vertebral number. In pigs, the number-increase allele was expressed more abundantly than the wild-type allele in embryos. Among candidate polymorphisms, there is an insertion of a SINE element (PRE1) into the intron of the Q allele as well as the SNPs in the promoter region. Conclusions Genetic diversity of VRTN is the suspected cause of the heterogeneity of the number of vertebrae in commercial-breed pigs, so the polymorphism information should be directly useful for assessing the genetic ability of individual animals. The number-increase allele of swine VRTN was suggested to add an additional thoracic segment to the animal. Functional analysis of VRTN may provide novel findings in the areas of developmental biology.

What is known and objective: Esomeprazole, the S‐isomer of omeprazole, is a proton pump inhibitor which has been approved by over 125 countries, also known as NEXIUM®. Esomeprazole was developed to provide further improvement on efficacy for acid‐related diseases with higher systemic bioavailability due to the less first‐pass metabolism and lower plasma clearance. Esomeprazole is primarily metabolized by CYP2C19. Approximately <1% of Caucasians and 5%‐10% of Asians have absent CYP2C19 enzyme activity. Although the influence of various CYP2C19 phenotypes on esomeprazole pharmacokinetics has been studied, this is the first report in the Japanese population where 27 low CYP2C19 metabolizers were included. Methods: In this study, a population PK model describing the PK of esomeprazole was developed to understand the difference of CYP2C19 phenotypes on clearance in the Japanese population. The model quantitatively assessed the influence of CYP2C19 phenotype on esomeprazole PK in healthy Japanese male subjects after receiving repeated oral dosing. The inhibition mechanism of esomeprazole on CYP2C19 activity was also included in the model. Results and discussion: CYP2C19 phenotype and dose were found as statistically significant covariates on esomeprazole clearance. The apparent clearance at 10‐mg dose was 17.32, 9.77 and 7.37 (L/h) for homozygous extensive metabolizer, heterozygous extensive metabolizer and poor metabolizer subjects, respectively. And the apparent clearance decreased as dose increased. What is new and conclusion: The established population PK model well described the esomeprazole PK and model‐predicted esomeprazole PK was in good agreement with external clinical data, suggesting the robustness and applicability of the current model for predicting esomeprazole PK. [ABSTRACT FROM AUTHOR]

Background: Proton pump inhibitors (PPI) are widely used for the treatment of gastric acid‐related disease, but they are not approved for use in children in Japan. To assess the safety, pharmacokinetics, pharmacodynamics, and efficacy (gastrointestinal symptom improvement) of PPI in Japanese pediatric patients with gastric acid‐related disease, we conducted an 8 week, open‐label, parallel‐group, multicenter, phase I/III study of once‐daily oral esomeprazole use. Methods: Japanese children, aged 1–14 years with gastric acid‐related disease, were stratified by weight and age into five groups (10 patients/group) to receive esomeprazole as granules for suspension (10 mg) or capsules (10 mg or 20 mg) once daily. Results: Esomeprazole was absorbed and eliminated rapidly in all groups, with a median time to reach maximum plasma concentration of 1.47–1.75 h, an arithmetic mean terminal elimination half‐life of 0.80–1.37 h, and a weight‐correlated apparent total body clearance of 0.216–0.343 L/h/kg. Area under the plasma concentration–time curve during a dosage interval and maximum plasma drug concentration were generally higher in groups given a higher dose (20 mg) or with a lower age/weight, but also in patients identified as poor metabolizers on cytochrome P450 2C19 genotype. Most patients who had any upper gastrointestinal symptoms at baseline were asymptomatic at the end of the study. Thirty‐three patients (66%) reported ≥1 adverse events, including three patients who reported serious adverse events not judged to be causally related to esomeprazole. Conclusions: Oral esomeprazole, at 10 mg or 20 mg once daily, had a similar safety, efficacy, and pharmacokinetic profile in Japanese pediatric patients to that previously seen in adults and Caucasian children. [ABSTRACT FROM AUTHOR]

Fatty acid composition is an economically important trait in meat-producing livestock. To gain insight into the molecular genetics of fatty acid desaturase ( FADS) genes in pigs, we investigated the genomic structure of the porcine FADS gene family on chromosome 2. We also examined the tissue distribution of FADS gene expression. The genomic structure of FADS family in mammals consists of three isoforms FADS1, FADS2 and FADS3. However, porcine FADS cluster in the latest pig genome assembly (Sscrofa 10.2) containing some gaps is distinct from that in other mammals. We therefore sought to determine the genomic structure, including the FADS cluster in a 200-kbp range by sequencing gap regions. The structure we obtained was similar to that in other mammals. We then investigated the porcine FADS1 transcription start site and identified a novel isoform named FADS1b. Phylogenetic analysis revealed that the three members of the FADS cluster were orthologous among mammals, whereas the various FADS1 isoforms identified in pigs, mice and cattle might be attributable to species-specific transcriptional regulation with alternative promoters. Porcine FADS1b and FADS3 isoforms were predominantly expressed in the inner layer of the subcutaneous adipose tissue. Additional analyses will reveal the effects of these functionally unknown isoforms on fatty acid composition in pig fat tissues. [ABSTRACT FROM AUTHOR]