Barrier dysfunction in the nasal allergy

Epithelial cells form the first physiological barrier against invasion by pathogens and the infiltration of allergens. Tight junctions (TJ), a cell–cell junctional complex located on the apical side of epithelial cells, have a critical role in the maintenance of epithelial barrier function. Impaired TJ structures are observed in patients with asthma, atopic dermatitis and nasal allergy; therefore, the dysfunction of epithelial barriers might be involved in the initiation or progression of allergic diseases. Protease-containing allergens and environmental pollutants enhance paracellular transport in epithelial cells through disruption of epithelial barrier function. This suggests that the disruption of TJ leads to the promotion of allergen delivery into the subepithelia, resulting in the progression of allergic diseases. Thus, protection of the epithelial barrier function might prevent or inhibit the development or exacerbation of allergic diseases. Recently, we reported that diesel exhaust particles (DEP), the main component of particulate patter 2.5, exacerbated allergic rhinitis (AR) in a mouse model through TJ disruption. In addition, we revealed that the oxidative stress-mediated pathway is involved in the effects caused by DEP and that nasal treatment with a reactive oxygen species (ROS) scavenger suppressed DEP-induced TJ disruption and exacerbation of AR. In this review, we focus on the relationship between TJ disruption and allergic disease. Furthermore, we discuss our recent findings regarding TJ disruption and the exacerbation of AR

胎生期の低用量抗菌薬摂取が、子の腸内細菌叢や体脂肪組成に及ぼす影響

Several environmental factors during the prenatal period transgenerationally affect the health of newborns in later life. Because low-dose antibiotics have been used for promoting the growth of crops and livestock in agriculture, humans may have ingested residual antibiotics for several decades. However, the effect of prenatal administration of low-dose antibiotics on newborns’ health in later life is unclear. In the present study, we found that prenatal treatment of murine mothers with low-dose antibiotics increased the abundance of bacteria of the phylum Firmicutes and the genera Clostridium IV and XIVa in feces from pups. In addition, the body fat percentage of mice in the antibiotic-treated group was higher than those in the control group at 12 weeks of age even though all pups were fed a standard diet. The body fat percentage of all mice was correlated with the abundance of fecal bacteria of Clostridium IV and XIVa. These results predict that low-dose antibiotic administration during the prenatal period affects the gut microbiota of newborns and possibly their health in later life

Effects of Consuming Xylitol on Gut Microbiota and Lipid Metabolism in Mice

The sugar alcohol xylitol inhibits the growth of some bacterial species including Streptococcus mutans. It is used as a food additive to prevent caries. We previously showed that 1.5–4.0 g/kg body weight/day xylitol as part of a high-fat diet (HFD) improved lipid metabolism in rats. However, the effects of lower daily doses of dietary xylitol on gut microbiota and lipid metabolism are unclear. We examined the effect of 40 and 200 mg/kg body weight/day xylitol intake on gut microbiota and lipid metabolism in mice. Bacterial compositions were characterized by denaturing gradient gel electrophoresis and targeted real-time PCR. Luminal metabolites were determined by capillary electrophoresis electrospray ionization time-of-flight mass spectrometry. Plasma lipid parameters and glucose tolerance were examined. Dietary supplementation with low- or medium-dose xylitol (40 or 194 mg/kg body weight/day, respectively) significantly altered the fecal microbiota composition in mice. Relative to mice not fed xylitol, the addition of medium-dose xylitol to a regular and HFD in experimental mice reduced the abundance of fecal Bacteroidetes phylum and the genus Barnesiella, whereas the abundance of Firmicutes phylum and the genus Prevotella was increased in mice fed an HFD with medium-dose dietary xylitol. Body composition, hepatic and serum lipid parameters, oral glucose tolerance, and luminal metabolites were unaffected by xylitol consumption. In mice, 40 and 194 mg/kg body weight/day xylitol in the diet induced gradual changes in gut microbiota but not in lipid metabolism

Glycolate is a Novel Marker of Vitamin B2 Deficiency Involved in Gut Microbe Metabolism in Mice

Microbes in the human gut play a role in the production of bioactive compounds, including some vitamins. Although several studies attempted to identify definitive markers for certain vitamin deficiencies, the role of gut microbiota in these deficiencies is unclear. To investigate the role of gut microbiota in deficiencies of four vitamins, B2, B6, folate, and B12, we conducted a comprehensive analysis of metabolites in mice treated and untreated with antibiotics. We identified glycolate (GA) as a novel marker of vitamin B2 (VB2) deficiency, and show that gut microbiota sense dietary VB2 deficiency and accumulate GA in response. The plasma GA concentration responded to reduced VB2 supply from both the gut microbiota and the diet. These results suggest that GA is a novel marker that can be used to assess whether or not the net supply of VB2 from dietary sources and gut microbiota is sufficient. We also found that gut microbiota can provide short-term compensation for host VB2 deficiency when dietary VB2 is withheld

Effects of Low-Dose Non-Caloric Sweetener Consumption on Gut Microbiota in Mice

Non-caloric artificial sweeteners (NASs) provide sweet tastes to food without adding calories or glucose. NASs can be used as alternative sweeteners for controlling blood glucose levels and weight gain. Although the consumption of NASs has increased over the past decade in Japan and other countries, whether these sweeteners affect the composition of the gut microbiome is unclear. In the present study, we examined the effects of sucralose or acesulfame-K ingestion (at most the maximum acceptable daily intake (ADI) levels, 15 mg/kg body weight) on the gut microbiome in mice. Consumption of sucralose, but not acesulfame-K, for 8 weeks reduced the relative amount of Clostridium cluster XIVa in feces. Meanwhile, sucralose and acesulfame-K did not increase food intake, body weight gain or liver weight, or fat in the epididymis or cecum. Only sucralose intake increased the concentration of hepatic cholesterol and cholic acid. Moreover, the relative concentration of butyrate and the ratio of secondary/primary bile acids in luminal metabolites increased with sucralose consumption in a dose-dependent manner. These results suggest that daily intake of maximum ADI levels of sucralose, but not acesulfame-K, affected the relative amount of the Clostridium cluster XIVa in fecal microbiome and cholesterol bile acid metabolism in mice

ras Mutations in Endocrine Tumors : Mutation Detection by Polymerase Chain Reaction‐Single Strand Conformation Polymorphism

To elucidate the molecular basis for endocrine tumorigenesis, ras mutations in human endocrine tumors were analyzed using polymerase chain reaction‐single strand conformation polymorphism (PCR‐SSCP) analysis. Mutations of the H‐, K‐, N‐ras genes were examined in genomic DNAs from 169 successfully amplified primary endocrine tumors out of 189 samples. Four out of 24 thyroid follicular adenomas analyzed contained mutated N‐ras codon 61, and one contained the mutated H‐ras codon 61. One of the 19 pheochromocytomas revealed mutation of the H‐ras codon 13. No mutations of the ras gene were detected in pituitary adenomas, parathyroid tumors, thyroid cancers, endocrine pancreatic tumors, and adrenocortical tumors. Based on these findings we conclude that activation of the ras gene may play a role in the tumorigenesis of a limited number of thyroid follicular adenomas and pheochromocytomas, and that mutation of the ras gene is not frequent in other human endocrine tumors

Interprofessional education in medical schools in Japan

Interprofessional education (IPE) for medical students is becoming increasingly important, as reflected in the increasing number of medical schools adopting IPE. However, the current status of and barriers to pre-registration IPE implementation in Japanese medical schools remain unknown. The purpose of this study was to clarify the status and barriers of IPE implementation in medical schools in Japan. We conducted a curriculum survey from September to December 2016 of all 81 medical schools in Japan. We mailed the questionnaire and asked the schools’ undergraduate education staff to respond. The survey items were the IPE implementation status and barriers to program implementation. Sixty-four of the 81 schools responded (response rate 79.0%), of which 46 (71.9%) had implemented IPE, 42 (89.1%) as compulsory programs. Half of IPE programs were implemented in the first 2 years, while less than 10% were implemented in the latter years of medical programs. As part of the IPE programs, medical students collaborated with a wide range of professional student groups. The most common learning strategy was lectures. However, one-third of IPE programs used didactic lectures without interaction between multi-professional students. The most common perceived major barrier to implementing IPE was adjustment of the academic calendar and schedule (82.8%), followed by insufficient staff numbers (73.4%). Our findings indicate that IPE is being promoted in undergraduate education at medical schools in Japan. IPE programs differed according to the circumstances of each school. Barriers to IPE may be resolved by improving learning methods, introducing group discussions between multi-professional students in lectures or introducing IPE programs using team-based learning. In summary, we demonstrated the current status and barriers of IPE implementation in Japanese medical schools. Our findings will likely lead to the promotion of IPE programs in Japan

Infection risk in hemodialysis patient

Chronic care patients undergoing hemodialysis for treatment of end-stage renal failure experience higher rates of bloodstream-associated infection due to the patients' compromised immune system and management of the bloodstream through catheters. Staphylococcus species are a common cause of hemodialysis catheter-related bloodstream infections. We investigated environmental bacterial contamination of dialysis wards and contamination of hemodialysis devices to determine the source of bacteria for these infections. All bacterial samples were collected by the swab method and the agarose stamp method. And which bacterium were identified by BBL CRYSTAL Kit or 16s rRNA sequences. In our data, bacterial cell number of hemodialysis device was lower than environment of patient surrounds. But Staphylococcus spp. were found predominantly on the hemodialysis device (46.8%), especially on areas frequently touched by healthcare-workers (such as Touch screen). Among Staphylococcus spp., Staphylococcus epidermidis was most frequently observed (42.1% of Staphylococcus spp.), and more surprising, 48.2% of the Staphylococcus spp. indicated high resistance for methicillin. Our finding suggests that hemodialysis device highly contaminated with bloodstream infection associated bacteria. This study can be used as a source to assess the risk of contamination-related infection and to develop the cleaning system for the better prevention for bloodstream infections in patients with hemodialysis