Long-term exposure to fine particulate matter and natural-cause and cause-specific mortality in Japan.

BACKGROUND: A number of studies have linked long-term exposure to particulate matter with aerodynamic diameter <2.5 µm (PM2.5) with mortality, but most of these studies were conducted in Europe and North America. Studies in Asian countries had been conducted at relatively high exposures. We evaluated the association of long-term exposure to PM2.5 and natural-cause and cause-specific mortality in Japan, where PM2.5 levels are relatively low compared with levels in other Asian countries. METHODS: A cohort of 75,531 participants underwent basic health checkups in Okayama City in 2006 or 2007. We followed the participants until the end of 2016. Average PM2.5 levels from 2006 to 2010 were obtained and assigned to the participants by geographical location. We used the Cox proportional hazard models to estimate hazard ratios for a 5-µg/m3 increase in PM2.5 levels for natural-cause or cause-specific mortality, adjusting for potential confounders. RESULTS: PM2.5 exposure was associated with increased risk of mortality; the hazard ratios were 1.29 (95% confidence interval = 1.18, 1.41) for mortality from natural causes, 1.16 (1.02, 1.32) for cardiorespiratory mortality, and 1.63 (1.13, 2.34) for lung cancer mortality. PM2.5 exposure was more strongly associated with cardiorespiratory mortality from hypertension, pneumonia and influenza, and chronic obstructive pulmonary disease than with ischemic heart disease or cerebrovascular disease. Elderly participants and smokers tended to have higher effect estimates. CONCLUSION: Long-term exposure to PM2.5 can increase the risk of natural-cause, cardiorespiratory, and lung cancer mortality in Japan.

Application of terahertz absorption spectroscopy to evaluation of aging variation of medicine.

The absorption spectra of three kinds of medicines both before and after the expiration date: Amlodin OD(®) (5 mg), Basen OD(®) (0.2 mg) and Gaster D(®) (10 mg) have been measured by terahertz time domain spectroscopy (THz-TDS). All the medicines show some differences in the THz absorption spectra between medicines before and after the expiration dates. X-Ray powder diffraction (XRD) studies of all medicines suggest that the polymorph of the main effective compound is not changed before and after the expiration date. Therefore, the differences in the THz spectra between medicines before and after the expiration dates arise from aging variation of diluting agents and/or from modifications of intermolecular interaction between the effective compounds and diluting agents.

Protective effect of montmorillonite on plasmid DNA in oral gene delivery into small intestine.

Montmorillonite, a bioinert clay mineral, was examined as a novel vector for an oral gene-delivery system. The complex of montmorillonite and plasmid DNA encoding the enhanced green fluorescent protein (EGFP) gene was prepared at various weight ratios, and then transfected into cultured intestinal epithelial cells (IEC-6) in vitro. The EGFP gene was clearly transcribed when the transfection was performed using the montmorillonite-plasmid complex at a weight ratio of 0.05:1. In contrast, no gene expression was detected by reverse transcription-polymerase chain reaction (RT-PCR) analysis when the transfection was performed with naked plasmid. Various plasmid preparations were given orally to mice, and the gene expression in the stomach and small intestine was examined by RT-PCR. Although no gene expression was detected in the mice receiving an oral administration of naked plasmid or polyethyleneimine-plasmid complex, the EGFP gene complexed with montmorillonite was expressed in the small intestine. These results indicate that montmorillonite protected the plasmid DNA from the acidic environment in the stomach and DNA-degrading enzymes in the intestine, and successfully delivered it into cells of the small intestine.

Effects of the counterion on dielectric spectroscopy of a montmorillonite suspension over the frequency range 10(5)-10(10) Hz.

Dielectric measurements were carried out on suspensions of montmorillonite clay exchanged with three different counterions: sodium, ammonium, and tetramethylammonium (TMA). Only two dielectric absorption peaks could be identified for the clay sample with the TMA counterion, whereas three peaks were found for the two inorganic counterions. The dielectric process observed at around 10 GHz is due to the orientation of bulk water molecules, judging from the relaxation time and relaxation strength. The relaxation strength of the process occurring at around 10 MHz was compared with the coefficient of adiabatic compressibility obtained from ultrasound velocity measurements. The increase in the relaxation strength with decreasing compressibility indicates that the process at around 10 MHz is caused by the orientation of bound water molecules on the clay samples. The relaxation strength of the process occurring at around 10 MHz for the TMA sample was remarkably small. Furthermore, the network structure of the bound water molecules can be characterized by a property peculiar to the TMA sample, taking into account the value of its Cole-Cole parameter. Results for the relaxation strength of the process occurring at around 100 kHz were compared with those for electrophoretic mobility. This comparison revealed that discrimination between bound ions and ions in the diffuse double layer is important, and both the relaxation and electrophoretic results could be satisfactorily explained by surface polarization of the clay.

Novel transdermal drug delivery system with polyhydroxyalkanoate and starburst polyamidoamine dendrimer.

In search of an efficient transdermal drug delivery system (TDDS), a polyhydroxyalkanoate (PHA)-based system with a polyamidoamine dendrimer was examined. Tamsulosin was used as the model drug. The dendrimer was found to act as the weak enhancer. By adding the dendrimer, the dendrimer-containing PHA matrix achieved the clinically required amount of tamsulosin permeating through the skin model. This is also the first report of the application of PHA and dendrimer to the TDDS.

Mechanism of enhancement effect of dendrimer on transdermal drug permeation through polyhydroxyalkanoate matrix.

The possible application of polyhydroxyalkanoate (PHA) in transdermal drug delivery systems (TDDSs) for tamsulosin was previously reported. PHAs containing the drugs, ketoprofen, clonidine and tamsulosin showed good adhesiveness to the skin model used, that is, shed snake skin, and dispersed well all model drugs tested. The model drugs hardly permeated through snake skin in solution form. However, these drugs permeated well through snake skin from the PHA matrix. It was previously reported that the addition of a dendrimer, a polymeric permeation enhancer, is effective for the TDDS for tamsulosin to establish an effective clinical TDDS. The effect of dendrimer addition was examined in TDDSs for ketoprofen and clonidine. The dendrimer added did not show an enhancement effect on the TDDSs for the two drugs. To investigate the mechanism of the enhancement effect of a dendrimer on the tamsulosin TDDS, X-ray analyses were performed. With dendrimer addition, drug crystallization in PHA was promoted. The crystal in PHA had highly ordered and changed its space group. These findings are very important for exploiting high-performance PHA-based TDDSs.