Lower respiratory tract infections and gastrointestinal infections among mature babies in Japan

Background: Epidemiologic evidence regarding the background factors of childhood infections in Japan is scarce. The aim of the present study was therefore to investigate the rates and associated factors of hospitalization for lower respiratory tract infections (LRTI) and gastrointestinal infections (GII) among children with birthweight ≥2500 g and ≥37 weeks of gestational age. Method: The data for the study were collected at 18‐month health checkups in one city in Japan. The community database included information on the main outcome (past hospitalization) and 16 host, environmental, and parenting factors. The Kaplan–Meier method and log–rank test were used to determine sex differences in hospital admission for infection, and the Cox regression model to analyze sex‐specific factors associated with the hospitalization. Results: The proportion of children who were admitted to hospital before their 18‐month checkup was 7.1% for LRTI and 2.2% for GII. Hospital admission for LRTI among boys was higher than girls. Multivariate analysis indicated the following LRTI‐associated factors: child‐care attendance (hazard ratio [HR]= 1.97) and three or more adults living together (HR = 2.63) for boys; and child‐care attendance (HR = 4.30) and two or more children living together (HR = 4.57) for girls. GII‐associated factors were maternal age <25 years (HR = 3.45) for boys, and hand washing by caregivers after lavatory use and diaper changing (HR = 6.93) for girls. Conclusions: One out of 11 children was hospitalized because of LRTI or GII during their first 18 months, which was associated with a biologic factor (sex), environmental factors (child‐care attendance and family size), and parenting practices (shorter duration of exclusive breast‐feeding and caregivers' unfavorable hygiene practices).     

Effects of small pulsed nanocurrents on cell viability in vitro and in vivo: Implications for biomedical electrodes

Using a custom-built, implantable pulse generator, we studied the effects of small pulsed currents on the viability on rat aortic-derived cells (RAOC) in vitro. The pulsed currents (0.37 A/m²) underwent apoptosis within 24 h as shown by the positive staining for cleaved caspase-3 and classically apoptotic morphology. Based on these findings, we examined the effects of nanocurrents in vivo. The pulse generator was implanted subcutaneously in the rat model. The electrode|tissue interface histology revealed no difference between the active platinum surface and the neighboring control surface, however we found a large difference between electrodes that were functional during the entire experiment and non-active electrodes. These non-active electrodes showed an increase in impedance at higher frequencies 21 days post-implantation, whereas working electrodes retained their impedance value for the entire experiment. These results indicate that applied currents can reduce the impedance of implanted electrodes.     

Serum levels of hydroxylated PCBs, PCBs and thyroid hormone measures of Japanese pregnant women

Objectives

The purpose of this study was to investigate the associations between serum concentrations of hydroxylated PCBs (OH-PCBs) and PCBs and measures of thyroid hormone status of Japanese pregnant women.

Methods

The concentrations of free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroxine binding globulin (TBG) as well as 16 OH-PCB isomers and 29 PCB isomers were analyzed in the serum of 129 women sampled in the first trimester of gestation. Dietary and lifestyle information of the subjects was obtained by self-administered questionnaire. Multiple regression analysis was performed using measures of thyroid hormones as the dependent variable and serum levels of OH-PCBs/PCBs, urinary iodine concentration, and other potential covariates (age, BMI, smoking, etc.) as independent variables.

Results

Geometric mean (GM) concentration of the sum of 16 isomers of OH-PCBs was 120 pg/g wet wt. and that of 29 isomers of PCBs was 68 ng/g lipid wt., respectively, in the serum of the subjects. Iodine nutrition was considered adequate to high from urinary iodine level (GM, 370 μg/g creatinine). The mean concentration of TSH, fT4 and TBG was 1.34 ± 1.37 μIU/mL, 1.22 ± 0.16 ng/dL and 33.0 ± 6.4 μg/mL, respectively, with a small number of subjects who were outside the reference range. Multiple regression analysis revealed that serum concentrations of OH-PCBs/PCBs were not significantly associated with any of the measures of thyroid hormone status.

Conclusions

Exposure/body burden of OH-PCBs and PCBs at environmental levels does not have a measurable effect on thyroid hormones.     

Transient receptor potential vanilloid 1 - a polymodal nociceptive receptor - plays a crucial role in formaldehyde-induced skin inflammation in mice

Formaldehyde (FA) is irritating to the skin and is the main cause of sick building syndrome. However, the cutaneous reaction induced by long-term FA exposure has not been fully investigated. In our previous study, we demonstrated that repeated painting of 2% - 10% FA on mouse ears caused marked ear swelling and increased mRNA expression of transient receptor potential vanilloid 1 (TRPV1) and neurotrophins in the ear. TRPV1 is reported to be involved in neurogenic inflammation; therefore, in the present study, we investigated the role of TRPV1 in FA-induced skin inflammation using TRPV1 gene-knockout mice. Mice were painted with 5% FA once a week for 5 weeks, and ear swelling and mRNA expression were investigated. Ear swelling and increased expression of neurotrophins mRNA by FA provocation in wild-type mice were attenuated by disruption of the TRPV1 gene. Furthermore, painting with a threshold dose of capsaicin, which does not induce ear swelling in intact mice, caused marked ear swelling after painting the ear 5 times with FA, indicating that inflamed tissues after FA application are hypersensitive to various ligands of TRPV1 in mice. These results demonstrated that neurogenic inflammation via TRPV1 and neurotrophins could be involved in FA-induced dermatitis.     

CBS9106 is a novel reversible oral CRM1 inhibitor with CRM1 degrading activity

CRM1 plays an important role in the nuclear export of cargo proteins bearing nuclear exporting signal sequences. Leptomycin B (LMB), a well-known CRM1 inhibitor, possesses strong antitumor properties. However, its toxicity prevents it from being clinically useful. In this study, we demonstrate that a novel compound, CBS9106, inhibits CRM1-dependent nuclear export, causing arrest of the cell cycle and inducing apoptosis in a time- and dose-dependent manner for a broad spectrum of cancer cells, including multiple myeloma cells. CBS9106 reduces CRM1 protein levels significantly without affecting CRM1 mRNA expression. This effect could be reversed by adding bortezomib or LMB. Moreover, CBS9106-biotin allows capture of CRM1 protein by streptavidin beads in a competitive manner with LMB and vice versa. Mass spectrometric analysis shows that CBS9106 reacts with a synthetic CRM1 peptide that contains Cys528 but not with a Cys528 mutant peptide. Oral administration of CBS9106 significantly suppresses tumor growth and prolongs survival in mice bearing tumor xenograft without a significant loss in body weight. A reduced level of CRM1 protein is also observed in tumor xenografts isolated from mice treated with CBS9106. Taken together, these results indicate that CBS9106 is a novel reversible CRM1 inhibitor and a promising clinical candidate.     

Branched-chain amino acids as pharmacological nutrients in chronic liver disease

Branched-chain amino acids (BCAAs) are a group of essential amino acids comprising valine, leucine, and isoleucine. A low ratio of plasma BCAAs to aromatic amino acids is a physiological hallmark of liver cirrhosis, and BCAA supplementation was originally devised with the intention of normalizing amino acid profiles and nutritional status. However, recent studies on BCAAs have revealed that, in addition to their role as protein constituents, they may have a role as pharmacological nutrients for patients with chronic liver disease. Large-scale, multicenter, randomized, double-blinded, controlled trials on BCAA supplementation have been performed in Italy and Japan, and results demonstrate that BCAA supplementation improves not only nutritional status, but also prognosis and quality of life in patients with liver cirrhosis. Moreover, accumulating experimental evidence suggests that the favorable effects of BCAA supplementation on prognosis may be supported by unforeseen pharmacological actions of BCAAs. This review summarizes the possible effects of BCAAs on albumin synthesis and insulin resistance from clinical and basic viewpoints. We also review the newly discovered clinical impact of BCAAs on hepatocellular carcinoma and the prognosis and quality of life of patients with liver cirrhosis.