Re-invigorating Japan's commitment to global health: challenges and opportunities.

Over the past 50 years, Japan has successfully developed and maintained an increasingly equitable system of universal health coverage in addition to achieving the world's highest life expectancy and one of the lowest infant mortality rates. Against this backdrop, Japan is potentially in a position to become a leading advocate for and supporter of global health. Nevertheless, Japan's engagement with global health has not been outstanding relative to its substantial potential, in part because of government fragmentation, a weak civil society, and lack of transparency and assessment. Japan's development assistance for health, from both governmental and non-governmental sectors, has remained low and Japanese global health leadership has been weak. New challenges arising from changes in governance and global and domestic health needs, including the recent Great East Japan Earthquake, now provide Japan with an opportunity to review past approaches to health policy and develop a new strategy for addressing global and national health. The fragmented functioning of the government with regards to global health policy needs to be reconfigured and should be accompanied by further financial commitment to global health priorities, innovative non-governmental sector initiatives, increased research capacity, and investments in good leadership development as witnessed at the G8 Hokkaido Toyako Summit. Should this strategy development and commitment be achieved, Japan has the potential to make substantial contributions to the health of the world as many countries move toward universal coverage and as Japan itself faces the challenge of maintaining its own health system.

Estimating the Carcinogenic Potency of Second-Hand Smoke and Aerosol from Cigarettes and Heated Tobacco Products.

The revised Promotion Act, enforced in April 2020, allows the establishment of dedicated smoking rooms for heated tobacco products (HTPs). Since carcinogenicity assessment is unable to determine the safe level of secondhand smoke, we estimated excess lifetime cancer risk using previously reported risk factors. Assuming that nicotine inhalation is proportional to cancer potency, the lifetime cancer risk for HTP IQOS is expected to be below 10-5 (1/100,000), which is three orders of magnitude lower than that for cigarettes.

Exposure Assessment of Environmental Tobacco Aerosol from Heated Tobacco Products: Nicotine and PM Exposures under Two Limited Conditions.

It is too early to provide a clear answer on the impact of exposure to the second-hand aerosol of heated tobacco products (HTPs) in the planning of policy for smoke-free indoors legislation. Here, we conducted a preliminary study to evaluate indoor air quality with the use of HTPs. We first measured the concentration of nicotine and particulate matter (PM2.5) in the air following 50 puffs in the use of HTPs or cigarettes in a small shower cubicle. We then measured these concentrations in comparison with the use equivalent of smoking 5.4 cigarettes per hour in a 25 m3 room, as a typical indoor environment test condition. In the shower cubicle test, nicotine concentrations in indoor air using three types of HTP, namely IQOS, glo, and ploomTECH, were 25.9-257 µg/m3. These values all exceed the upper bound of the range of tolerable concentration without health concerns, namely 3 µg/m3. In particular, the indoor PM2.5 concentration of about 300 to 500 µg/m3 using IQOS or glo in the shower cubicle is hazardous. In the 25 m3 room test, in contrast, nicotine concentrations in indoor air with the three types of HTP did not exceed 3 µg/m3. PM2.5 concentrations were below the standard value of 15 µg/m3 per year for IQOS and ploomTECH, but were slightly high for glo, with some measurements exceeding 100 µg/m3. These results do not negate the inclusion of HTPs within a regulatory framework for indoor tolerable use from exposure to HTP aerosol, unlike cigarette smoke.

Developing a uniformed assessment tool to evaluate care service needs for disabled persons in Japan.

Until recently, the care services for disabled persons have been under rigid control by public sectors in terms of provision and funding in Japan. A reform was introduced in 2003 that brought a rapid increase of utilization of services and serious shortage of financial resources. Under these circumstances, the "Services and Supports for Persons with Disabilities Act" was enacted in 2005, requiring that the care service provision process should be transparent, fair and standardized. The purpose of this study is to develop an objective tool for assessing the need for disability care. In the present study we evaluate 1423 cases of patients receiving care services in 60 municipalities, including all three categories of disabilities (physical, intellectual and mental). Using the data of the total 106 items, we conducted factor analysis and regression analysis to develop an assessment tool for people with disabilities. The data revealed that instrumental activities of daily living (IADL) played an essential role in assessing disability levels. We have developed the uniformed assessment tool that has been utilized to guide the types and quantity of care services throughout Japan.

Search for the target genes involved in the suppression of antibody production by TCDD in C57BL/6 mice.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses antibody production through activation of a transcription factor, the aryl hydrocarbon receptor (AhR). To explore the genes that are involved in the suppression of antibody production by TCDD, we investigated TCDD-induced changes in gene expression in the CD4 T cells and B cells of C57BL/6 mice immunized with ovalbumin (OVA) plus alum as an adjuvant. Changes in gene expression were analyzed with Affymetrix oligonucleotide microarrays. The results showed that OVA-immunization alone up-regulated expression levels of many genes in the CD4 T cells as early as 3 h after immunization, with 55 up-regulated and 5 down-regulated. At 24 h, 42 genes were found to be up-regulated and 30 down-regulated. Fewer genes were affected in the B cells than in the CD4 T cells. In contrast to the up-regulation of genes induced by immunization in the CD4 T cells, administration of TCDD to mice 3 h prior to the immunization mainly caused down-regulation of genes in the CD4 T cells when compared with immunization alone, with 1 being up-regulated and 4 down-regulated at 3 h after immunization and 3 up-regulated and 34 down-regulated at 24 h. In particular, at 3 and 24 h, TCDD suppressed expression of three and seven genes, respectively, that were up-regulated by immunization. Another characteristic of the TCDD-induced changes in gene expression was the suppression of many genes encoding proteins that are involved in GTP-binding protein-linked signaling in CD4 T cells. These results suggest that the inhibition of immunization-induced gene expression and modulation of G-protein-linked signaling in CD4 T cells are responsible for the TCDD-induced suppression of antibody production.

T cell-derived IL-5 production is a sensitive target of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

The immune system is one of the organs most vulnerable to the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Among the various immunotoxic effects of TCDD, the thymus involution and suppression of IgM antibody production are well known sensitive reactions of the thymocytes and B cells affected by TCDD. Recently, we reported that TCDD greatly inhibits the production of type-2 helper T (Th2) cell-derived cytokines, especially IL-5, by the splenocytes in mice immunized with ovalbumin (OVA). In the present study, we investigated the dose-dependency of these TCDD immunotoxic effects in OVA-immunized mice to identify the most sensitive target. Mice of two age groups, 6 weeks old and 3 weeks old, were dosed with 0.3, 1.0, or 3.0 microg TCDD/kg and immunized with OVA using alum as an adjuvant. Seven days later, the thymus weight, thymocyte population, antigen-specific IgM in the plasma, and IL-5 production by the splenocytes were examined. Among them, IL-5 production was significantly suppressed by all three doses of TCDD and reduced to about 30% by even a small dose of 0.3 microg TCDD/kg in both age groups. The thymus weight was significantly reduced by 1.0 microg or 3.0 microg TCDD/kg, but IgM production was not affected by up to 3.0 microg/kg of TCDD in both age groups. Taken together, the Th2 cell-derived IL-5 production was the most sensitive endpoint detecting TCDD toxicity among those examined. Our results also suggest that effector T cells are targets more vulnerable to TCDD toxicity than thymocytes or antibody-producing B cells in the OVA-immunized mice.

Estimation of Japanese international financial assistance for HIV/AIDS control for 2003-2007: difficulties and limitations of data collection.

The purpose of this paper is to: (1) collect relevant data and estimate Japanese international financial assistance for HIV/AIDS control; (2) discuss the difficulties in collecting relevant data and the limitations of the collected data; and (3) conduct a comparative analysis on the estimated data with OECD and Kaiser Family Foundation aggregate data. The point is that we have comprehensively collected and estimated the data on Japanese international expenditures for HIV/AIDS control while there is no reliable data that is totally managed and published. In addition, we discuss the difficulties and limitations of data collection: unpublished data; insufficient data; inseparable data; problems of exchange rates; gaps between disbursement and commitment; and difference in year period among calendar, fiscal and organization-specific years. Furthermore, we show the risk of underestimating the Japanese international contribution to HIV/AIDS control on the basis of OECD and Kaiser data. In this respect, it is significant to comprehensively collect and estimate the data on Japanese international assistance for HIV/AIDS control. Finally, we derive the implication that it is crucial for a relevant international organization and/or individual countries to comprehensively collect and administer data for international cooperation in the development of health policies for HIV/AIDS.

Progress in global blood safety for HIV.

OBJECTIVE: To assess progress toward ensuring a globally safe blood supply. DESIGN AND METHODS: We examined 2 global databases for blood safety: (1) that of the United Nations General Assembly Special Session on HIV/AIDS (UNGASS) blood safety indicator; and (2) that of the Global Database on Blood Safety (GDBS), a database developed by the World Health Organization. The UNGASS data were collected through the Ministry of Health based on the GDBS data, followed by a reconciliation and cross-checking of the data by World Health Organization and United Nations Programme on AIDS (UNAIDS). RESULTS: The proportion of United Nations member countries reporting UNGASS data for blood safety is among the highest of all UNGASS indicators: 147 of 192 United Nations Member States participated in UNGASS reporting in 2008 and 125 of them (85%) submitted data on blood safety. Ninety-one of the 125 countries (73%) reported that 100% of collected blood units were screened in a quality assured manner, but 34 countries did not screen all collected blood units in accordance with minimum quality standards. GDBS data showed that 80.7 million blood units were collected globally in 167 countries during 2004-2005, of which 77.3 million were tested for HIV and at least 0.6 million of the remaining 3.4 million donations went untested. CONCLUSIONS: Progress has been made toward eliminating blood transfusion as a significant cause of HIV infection globally. Screening all donated blood for HIV in accordance with minimum quality standards remains vital, however, as health care systems should, at a minimum, do no harm. This goal is achievable and would assist in reaching Millennium Development Goals by 2015.

Maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and the body burden in offspring of long-evans rats.

OBJECTIVES: In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in a wide variety of developmental effects in pups at doses much lower than those causing overt toxicity in adult animals. We investigated the relationship between tissue concentrations of TCDD in dams and fetuses and developmental effects on pups. MATERIALS AND METHODS: Pregnant Long-Evans rats were given TCDD at a single oral dose of 12.5, 50, 200, or 800 ng of TCDD or [(3)H]-TCDD/kg bw on gestation day (GD) 15. Dams were sacrificed on GD16 and GD21, and the tissue concentrations of TCDD were measured in dams and fetuses. Pups were sacrificed on postnatal day (PND) 49 and PND63 for males and PND70 for females, and the reproductive effects and tissue concentrations of TCDD were determined. RESULTS: The sex ratio (male/female) on GD21 was significantly reduced at 50 ng TCDD/kg and at 12.5 and 50 ng TCDD/kg at birth, but not at other doses. Delayed puberty was observed in males at 200 ng TCDD/kg and in males and females at 800 ng TCDD/kg. Anogenital distance, testis weight, epididymal sperm count, sperm motility, and ejaculated sperm count were not affected. Estrous cyclicity was not different from that of the control in any treatment group. A dose-dependent decrease in weight of seminal vesicle and prostate on PND49 was observed. Prostate weight was significantly decreased at 800 ng TCDD/kg. At this dose, maternal body burden and TCDD concentration in fetuses were 290 pg TCDD/g and 52 pg TCDD/g on GD16, respectively. Reduced prostate weight is a sensitive and commonly observed endpoint so that the body burdens of dams and fetuses at the LOAEL of this endpoint could be served as the basis for establishing TDI for dioxins.