"Wasanbon" sugar is handmade sugar which has been manufactured traditionally in Japan by a unique refining procedure, and is used in the making of Japanese traditional confectionary. No reports have been published on the substances responsible for the unique aroma of "Wasabon" sugar. In this paper, the contents and compositions of the aroma in "Wasabon" sugar and refinery final molasses are reported as studied by column chromatography, gas chromatography, mass spectrometry and sensory evaluation. The samples are the first press-off molasses ("Ara-mitsu" molasses) refinery final molasses, "Shiroshita" sugar (prerefined sugar) and "Wasabon" sugar. The summarized results are as follows: In the acidic fraction, the aroma of 3-phenylpropionic acid is similar to the stored aroma of "Wasabon" sugar, whereas the aroma of its methyl ester was not similar to that aroma. Although aroma contents of the weakly acidic fraction in "Wasabon" sugar and refinery final molasses are 8.5 to 8.7% of those of the acidic fraction, and their main components are cyclotene and maltol, which are formed by thermal degradation of sugar. These components show a higher preference than other weakly acidic fraction aromas, by a paired preference test. Cyclotene and maltol increased about 3.7 and 1.5 times, respectively, by the heating of "Shiroshita" sugar.
Background Vedolizumab safety and efficacy have been established in many populations all over the world, but have never been studied in Japan. We report results from a Phase 3, randomized, double-blind, placebo-controlled study of vedolizumab in Japanese patients with active ulcerative colitis (UC). Methods Patients with moderate-to-severe UC were enrolled into Cohort 1 (double-blinded) or Cohort 2 (open-label) in the induction phase. Cohort 1 was randomized 2:1 to receive 300 mg vedolizumab or placebo, while Cohort 2 received vedolizumab 300 mg only, at Weeks 0, 2, and 6. Patients from Cohorts 1 and 2 showing a clinical response to vedolizumab at Week 10 were randomized 1:1 to receive vedolizumab or placebo (double-blinded) at Week 14 and then every 8 weeks up to Week 54 as the maintenance phase. The primary endpoint was clinical response at Week 10, for the induction phase, and clinical remission at Week 60, for the maintenance phase. Results A total of 292 patients were enrolled into the induction phase (246 in Cohort 1, 46 in Cohort 2); 83 patients achieved response to vedolizumab and were subsequently enrolled into the maintenance phase. Clinical response rates at Week 10 were 39.6% (65/164) and 32.9% (27/82) in the vedolizumab and placebo groups in Cohort 1, respectively (adjusted odds ratio [AOR] = 1.37, 95% CI 0.779–2.399; p = 0.2722). In the maintenance phase, clinical remission rate at Week 60 was significantly higher in the vedolizumab group, at 56.1% (23/41), versus 31.0% (13/42) for placebo (AOR = 2.88, 95% CI 1.168–7.108; p = 0.0210). Most adverse events were mild to moderate in intensity, and no deaths occurred during the study period. Conclusions Vedolizumab showed numerically greater efficacy compared with placebo as induction therapy, but the difference was not statistically significant. Vedolizumab was significantly superior to placebo as maintenance therapy in Japanese patients with UC. Vedolizumab has favourable safety and tolerability in these patients. Trial registration ClinicalTrials.gov: NCT02039505.
The optimal dietary fat content to induce clinical remission in active Crohn's disease has been the subject of controversy. We therefore performed a prospective, randomized, controlled study to compare the effects of nutrient formulas differing in the amount of medium-chain triglycerides (MCT).Thirty-six patients with active Crohn's disease whose Crohn's disease activity index (CDAI) was > or =150 were included in the study. A formula with 3.4 g of fat per 2000-kcal dose was used as the nutrient formula with a low-fat content (ED group), and a formula with 55.6 g of fat per 2000-kcal dose was used as the nutrient formula with a high amount of MCT (TL group).The rate of short-term remission induction at 6 weeks was 67% in the ED group and 72% in the TL group (p = NS). Therapy markedly reduced the high CDAI and van Hees activity index in both groups, with no significant difference in the pattern of the time-course changes. C-reactive protein levels, erythrocyte sedimentation rate, and low serum albumin and plasma prealbumin levels normalized over the course of therapy, with no significant difference between the 2 groups. The assessment of fatty acid fractions revealed that the triene/tetraene ratio began to increase at 2 weeks in the ED group. The serum levels of linoleic acid, an omega-6 fatty acid, almost always varied within the normal range during the treatment period in the TL group, but in the ED group, levels began to decrease significantly at 2 weeks. The levels of linolenic acid, an omega-3 fatty acid, decreased in both groups.Both nutrient formulas induced clinical remission in about two-thirds of patients. The results of the present study suggest that it is not necessary to restrict the amount of MCT when given in liquid form to patients with active Crohn's disease.
Exfoliative cytologic findings of the oral mucosa in three cases of Acatalasemia (Takahara's disease) were investigated by means of Papanicolaou's method. Three cases were sisters of the same family, 19, 22, and 15 years of age. Oroantral fistula was noticed in the left molar area in Case 2 and Case 3 complained of loosening of anterior lower teeth with marginal gingivitis in the left lower molar ares. Smears were prepared by the following technics: 1) Scraping four different areas of the oral mucosa---hard palate, gingiva, radix linguae and buccal mucosa without causing bleeding. 2) Sediment taken from centrifuged mouth washings by physiologic saline solution. 3) Cells caught by membrane filter or both of them. All the smears were stained by Papanicolaou's technic and histologic examination of the gingiva was made in comparison with cytologic smears in Case 3. Thus keratinization of the epithelial cells were studied. 1) Keratinizing tendency was the same as those of normal mucosa in Cases 1 and 3. In the ulcerating area of Case 3 keratinized cells showed an increase as healing was going on, while they showed a marked decrease in Case 2, which might be due to the decrease of local resitance associated with ulcerative changes and the influence of partial denture. 2) Exfoliated cells of the whole oral mucosa in case of mouth washings Cases 1 and 3 showed the same findings as normal cases and Case 2 showed a marked decrease of keratinized cells. These findings were same as those of four different areas of the oral mucosa. 3) Gingiva of Case 3 showed little difference from normal mucosa in histopathologic findings.
Previously, we proposed a rare autosomal recessive inherited enteropathy characterized by persistent blood and protein loss from the small intestine as chronic nonspecific multiple ulcers of the small intestine (CNSU). By whole-exome sequencing in five Japanese patients with CNSU and one unaffected individual, we found four candidate mutations in the SLCO2A1 gene, encoding a prostaglandin transporter. The pathogenicity of the mutations was supported by segregation analysis and genotyping data in controls. By Sanger sequencing of the coding regions, 11 of 12 other CNSU patients and 2 of 603 patients with a diagnosis of Crohn's disease were found to have homozygous or compound heterozygous SLCO2A1 mutations. In total, we identified recessive SLCO2A1 mutations located at seven sites. Using RT-PCR, we demonstrated that the identified splice-site mutations altered the RNA splicing, and introduced a premature stop codon. Tracer prostaglandin E2 uptake analysis showed that the mutant SLCO2A1 protein for each mutation exhibited impaired prostaglandin transport. Immunohistochemistry and immunofluorescence analyses revealed that SLCO2A1 protein was expressed on the cellular membrane of vascular endothelial cells in the small intestinal mucosa in control subjects, but was not detected in affected individuals. These findings indicate that loss-of-function mutations in the SLCO2A1 gene encoding a prostaglandin transporter cause the hereditary enteropathy CNSU. We suggest a more appropriate nomenclature of "chronic enteropathy associated with SLCO2A1 gene" (CEAS).
