Immunoprotective effects of oral intake of heat-killed Lactobacillus pentosus strain b240 in elderly adults: a randomised, double-blind, placebo-controlled trial.

Oral intake of Lactobacillus pentosus strain b240 (b240) has been shown to enhance the secretion of salivary secretory IgA in elderly adults. However, its clinical benefits remain to be determined. We tested the hypothesis that b240 exerts a protective effect against the common cold in elderly adults. The design of the present study was a randomised, double-blind, placebo-controlled trial (RCT) with parallel three-group comparison. For this purpose, 300 eligible elderly adults were randomly allocated to one of three groups, namely a placebo, low-dose or high-dose b240 group. Participants in the low-dose and high-dose b240 groups were given tablets containing 2 × 10(9) or 2 × 10(10) cells, respectively, of heat-killed b240, while those in the placebo group were given tablets without b240. Each group consumed their respective tablets once daily for 20 weeks. The common cold was assessed on the basis of a diary. Change in quality of life was evaluated using the SF-36. Of the total participants, 280 completed the 20-week RCT. The accumulated incidence rate of the common cold was 47·3, 34·8 and 29·0 % for the placebo, low-dose b240 and high-dose b240 groups, respectively (P for trend = 0·012). Lower incidence rates were consistently observed throughout the experimental period in the b240 groups (log-rank test, P= 0·034). General health perception, as determined by the SF-36®, dose-dependently increased in the b240 groups ( P <0·025). In conclusion, oral intake of b240 significantly reduced the incidence rate of the common cold in elderly adults, indicating that b240 might be useful in improving resistance against infection through mucosal immunity.

Industry views of biosimilar development in Japan.

OBJECTIVE: To understand the issues around biosimilar development by pharmaceutical companies in Japan, which has emerged as an urgent issue in guaranteeing the availability of affordable biopharmaceuticals and a reduction in drug costs. METHODS: Various regulatory guidelines related to biosimilar development are carefully reviewed. We then interviewed representatives of 11 Japanese companies to explore issues related to the manufacturing, immunogenicity, development costs and regulation of biosimilars. RESULTS: Our investigations show that Japan is unlikely to produce more than a handful of biosimilars domestically in the near future. We also found that regulatory guidelines for biosimilars will be needed for Japanese developers to plan and initiate production, in order to provide affordable biopharmaceuticals to Japanese patients. CONCLUSION: These results represent that regulatory guidelines for biosimilars, encouraging competition with maintaining incentive for innovation, will be needed for Japanese developers to plan and initiate biosimilar development.

Overview of the clinical application of regenerative medicine products in Japan.

OBJECTIVE: To identify barriers to the clinical application of regenerative medicine products (RMPs) in Japan. METHODS: Current Japanese regulatory systems and guidelines were compared with those of the United States (US) and the European Union (EU). A questionnaire was administered to representatives from 23 Japanese companies and 10 research institutes, and an in-person semi-structured interview was conducted with representatives from 10 companies that develop RMP. RESULTS: We found that Japan, the US and the EU have similar pre-clinical safety guideline frameworks relating to RMP. However, differences exist between these countries with respect to their review and approval systems and the implementation of guidelines, and these represent major barriers to the clinical application of RMP in Japan. Most companies studied are facing regulatory hurdles such as stringent review processes and regulatory guidelines that do not provide detailed practical examples of the pre-clinical quality and safety data required. CONCLUSIONS: These results suggest that effective regulatory infrastructure including regulatory systems, guidelines, and communication channels between product developers and regulatory bodies are essential for the prompt clinical application of RMP in Japan.

[Use of complementary and alternative medicine and health problems].

OBJECTIVE: Remarkable growth in use of alternative and complementally medicine (CAM) has recently been noted from consume to trends, detail surveys are limited. In this study, to clarify the actual state of use of CAM and associated problem, we performed a cross sectional study in a town using a self-administrated questionnaire. METHODS: The questionnaire including demographic variables, subjective health status and health practices was addressed by people in Oguni town in Kumamoto. Use of kampo, supplements/healthy food, chiropractic, massage, yoga/meditation, acupuncture, kiko/thai-chi, aromatherapy/herbal medicine and hot springs was assessed in the questionnaire in terms of frequency, prescription or advice from physicians, purpose, and satisfaction. RESULTS: The response rate was 83.33%. Use increased with aging and female employed CAM more frequently than male subjects. Most frequently consumed were supplement/health foods in both females (47.0%) and males (35.3%). The most prescribed was Kampo in both sexes (24.8% and 11.4%) About 70% of the subjects had visited chiropractics therapies. CONCLUSION: From 57.0% of subjects had used at least one CAM in the past six months, a high value compared with results from other countries. The rates were particularly large in female and elderly subjects. It is thus possible that the impact of CAM on health promotion policy is not inconsequential.

Spectrophotometric assay of superoxide anion formed in Maillard reaction based on highly water-soluble tetrazolium salt.

A novel highly water-soluble tetrazolium salt, WST-1 (4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate sodium salt), can be reduced to water-soluble formazan with a superoxide anion. Here, the WST-1 assay was applied to detect the superoxide anion generated during the Maillard reaction. A sample solution containing carbonyl compounds such as glyceraldehyde and glycolaldehyde (5 mM) and Na-acetyl-L-lysine (10 mM) was incubated for 2 days at 37 degrees C. The detection of a superoxide anion generated in the sample was performed by the WST-1 assay, and the result was compared with the cytochrome c assay. The reduction of WST-1 was almost perfectly (86-96%) inhibited by the addition of the superoxide dismutase (SOD). On the contrary, the reduction of cytochrome c was slightly (20-25%) inhibited by the addition of SOD. A similar result was observed for the addition of 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron). These results mean that the specificity of WST-1 to the superoxide anion was superior to that of cytochrome c. It was also possible to continuously monitor superoxide anion generation during the Maillard reaction by the coexistence of WST-1 in the reaction solution.

Influence of antibiotic exposure in the early postnatal period on the development of intestinal microbiota.

The influence of antibiotic exposure in the early postnatal period on the development of intestinal microbiota was monitored in 26 infants including five antibiotic-treated (AT) subjects orally administered a broad-spectrum antibiotic for the first 4 days of life and three caesarean-delivered (CD) subjects whose mothers were intravenously injected by the similar type of antibiotics in the same period. The faecal bacterial composition was analysed daily for the first 5 days and monthly for the first 2 months. Terminal restriction fragment length polymorphisms in the AT subjects showed less diversity with the attenuation of the colonization of some bacterial groups, especially in Bifidobacterium and unusual colonization of Enterococcus in the first week than the control antibiotic-free infants (AF, n=18). Quantitative real-time PCR showed overgrowth of enterococci (day 3, P=0.01; day 5, P=0.003; month 1, P=0.01) and arrested growth of Bifidobacterium (day 3, P=0.03) in the AT group. Furthermore, after 1 month, the Enterobacteriaceae population was markedly higher in the AT group than in the AF group (month 1, P=0.02; month 2, P=0.02). CD infants sustained similar, although relatively weaker, alteration in the developing microbiota. These results indicate that antibiotic exposure at the beginning of life greatly influences the development of neonatal intestinal microbiota.

Critical issues for effective collaboration between academia and industry in the field of regenerative medicine in Japan.

AIM: To identify which factors are important barriers to effective collaboration between Japanese academia and industry in the field of regenerative medicine. METHODS: In November-December 2006, in-person semistructured interviews were conducted with representatives from nine Japanese companies that are engaged in developing regenerative medicine products in collaboration with academia and two academic scientists with the successful collaborative experiences with companies. RESULTS & CONCLUSIONS: The major barriers to collaboration relate to the inadequacy of particular systems in academic institutions (particularly technology licensing organizations and mobility between industry and academia), the knowledge deficit of academic personnel with respect to industry, the inadequacy of particular governmental support systems and the Japanese public's view of these collaborations, which has resulted in overly strict conflict of interest guidelines. We suggest some approaches to overcome these barriers.

Differences in developing intestinal microbiota between allergic and non-allergic infants: a pilot study in Japan.

The bacterial compositions of feces were monitored in the first 2 months for 15 infants born in Japan, including eight subjects who developed allergy by the age of 2 years. Primer sets targeting six predominant bacterial groups in the infant intestine, Bacteroidaceae, Enterobacteriaceae, bifidobacteria, enterococci, lactobacilli, and the Clostridium perfringens group, were used for real-time PCR to quantitate each population in the feces. The population of Bacteroidaceae was significantly higher in the allergic group at the ages of 1 month (P=0.03) and 2 months (P=0.05) than in the non-allergic group, while no statistically significant difference was observed for the other bacterial populations.