向精神薬服用患者の突然死症例におけるカリウムイオンチャネルに関する分子生物学的解析：QT延長症候群関連遺伝子の多型が危険因子となり得るか？

Psychotropic drugs can pose the risk of acquired long QT syndrome (LQTS). Unexpected autopsy-negative sudden death in patients taking psychotropic drugs may be associated with prolonged QT intervals and life-threatening arrhythmias. We analyzed genes that encode for cardiac ion channels and potentially associated with LQTS, examining specifically the potassium channel genes KCNQ1 and KCNH2 in 10 cases of sudden death involving patients administered psychotropic medication in which autopsy findings identified no clear cause of death. We amplified and sequenced all exons of KCNQ1 and KCNH2, identifying G643S, missense polymorphism in KCNQ1, in 6 of the 10 cases. A study analysis indicated that only 11% of 381 healthy Japanese individuals carry this polymorphism. Reports of previous functional analyses indicate that the G643S polymorphism in the KCNQ1 potassium channel protein causes mild IKs channel dysfunction. Our present study suggests that administering psychotropic drug therapy to individuals carrying the G643S polymorphism may heighten the risk of prolonged QT intervals and life-threatening arrhythmias. Thus, screening for the G643S polymorphism before prescribing psychotropic drugs may help reduce the risk of unexpected sudden death2013博士（歯学）松本歯科大

Oral administration of Lactobacillus gasseri SBT2055 is effective for preventing influenza in mice

The Lactobacillus gasseri SBT2055 (LG2055) is a probiotic lactic acid bacterium with properties such as bile tolerance and ability to improve the intestinal environment. In this study, we established that the oral administration of LG2055 exhibits efficacy to protect mice infected with the influenza virus A/PR8. The body weight losses were lower with the LG2055 administration after the PR8 virus infection. At 5 days after the infection, the virus titer was significantly decreased as was the amount of produced IL-6 in the lung tissue, the number of total cells in the bronchoalveolar lavage fluid was reduced by the LG2055 administration. The expression of the Mx1 and Oas1a genes, critical for the viral clearance in the lung tissues was increased by the pre-treatment with LG2055. These findings suggest that the LG2055 administration is effective for the protection against influenza A virus infection by the down-regulation of viral replication through the induction of antiviral genes expression

The physiological effects of EOS789

Background: Inorganic phosphate (Pi) binders are the only pharmacologic treatment approved for hyperphosphatemia. However, Pi binders induce the expression of intestinal Pi transporters and have limited effects on the inhibition of Pi transport. EOS789, a novel pan-Pi transporter inhibitor, reportedly has potent efficacy in treating hyperphosphatemia. We investigated the properties of EOS789 with comparison to a conventional Pi binder. Methods: Protein and mRNA expression levels of Pi transporters were measured in intestinal and kidney tissues from male Wistar rats fed diets supplemented with EOS789 or lanthanum carbonate (LC). 32Pi permeability was measured in intestinal tissues from normal rats using a chamber. Results: Increased protein levels of NaPi-2b, an intestinal Pi transporter, and luminal Pi removal were observed in rats treated with LC but not in rats treated with EOS789. EOS789 but not LC suppressed intestinal protein levels of the Pi transporter Pit-1 and sodium / hydrogen exchanger isoform 3. 32Pi flux experiments using small intestine tissues from rats demonstrated that EOS789 may affect transcellular Pi transport in addition to paracellular Pi transport. Conclusion: EOS789 has differing regulatory effects on Pi metabolism compared to LC. The properties of EOS789 may compensate for the limitations of LC therapy. The combined or selective use of EOS789 and conventional Pi binders may allow tighter control of hyperphosphatemia

Intestinal Microbiota is Different in Women with Preterm Birth: Results from Terminal Restriction Fragment Length Polymorphism Analysis - Figure 1

<p>A. Principal component analysis of fecal microbiota. Principal component analysis scores are plotted based on the relative abundance of OTUs of vaginal microbiota. The percentage of variation explained by the principal coordinates is indicated on the axis. Open circles (○) represent the non-PTL group, open triangles (△) the PTL group, and closed triangles (▴) the PTB group. A dotted line, on the left in Figure 1A, shows ‘cluster 1′, which contains all 10 cases of the PTB group, as well as 2/20 of the non-PTL group and 7/11 of the PTL group. A solid circle, on the right in Figure 1A, shows 90% of the non-PTL group (18/20) and 36.4% of the PTL group (4/11). The PTL group occupied an intermediate position between the non-PTL group and the PTB group. B. Principal component analysis of vaginal microbiota. Principal component analysis scores are plotted based on the relative abundance of OTUs of vaginal microbiota. The percentage of variation explained by the principal coordinates is indicated on the axis. Open circles (○) represent the non-PTL group, open triangles (△) the PTL group, and closed triangles (▴) the PTB group.</p

Impact of a history of cardiovascular disease and physical activity habits on the incidence of functional disability

Abstract We examined the impact of a history of coronary artery disease (CAD) or cerebrovascular disease (CVD) and physical activity habits on functional disability among community-dwelling Japanese adults. This population-based retrospective cohort study included 10,661 people aged 39–98 years in Japan (5054, men). Median follow-up was 3.7 years. During the study period, 209 functional disabilities occurred in the overall study population. In multivariable analysis, a history of CVD (hazard ratio [HR] 1.57 [95% CI: 1.00–2.45]) and no physical activity habit (HR 1.74 [1.27–2.39]) presented increased risks for functional disability. HRs for functional disability among patients with a CVD history with and without a physical activity habit were 1.68 (0.75–3.74) and 2.65 (1.49–4.71), respectively, compared with individuals without a history of CVD with a physical activity habit. Similar results were observed for CAD. We found no significant difference in the incidence of functional disability between the group with a history of CAD or CVD and physical activity habits and the group with no history of CAD or CVD and without physical activity habits. Physical activity habits had a favorable influence on avoiding functional disability regardless of a history of CAD or CVD. Future prospective studies are needed to clarify these associations