Community based medicine in Japan

The community has important roles in the community based medicine and home care systems along with the differentiation of the functions of medical institutions. Patients under home care receive care of their family, the friends, community home care services and medical care by healthcare professionals. Patients can live in the community under medical care in a different category from in-hospital care. Community based medicine is the manifestation of healthcare supporting people who live. Healthcare professionals involved in community based medicine are required to give medical education and cooperate with community welfare works apart from medical care in the community.     

Factors of positive appraisal of care among Japanese family caregivers of older adults

The purpose of this study was to examine factors of positive appraisal of care among Japanese family caregivers of older adults. The Positive Appraisal of Care (PAC) scale used in this study is a multidimensional Japanese measure and has four domains: relationship satisfaction, consequential gain, role confidence, and normative fulfillment. Three hundred and thirty-seven caregivers participated in this survey. Multiple regression analyses revealed that social support and caregiver belief in caregiving had a consistent impact on all domains of the PAC, whereas the impact of caregiver and care recipient characteristics varied among the domains. For example, caregiver age had a significant impact on role confidence and normative fulfillment but not on relationship satisfaction and consequential gain. The differential impact of caregiver and care recipient characteristics on the domains of the PAC underlines the usefulness of a multidimensional measurement.     

Abundance of polymers degrading microorganisms in a sea-based solid waste disposal site

In order to assess the degradability of plastics in solid waste disposal landfill sites, microbial populations capable of degrading five kinds of plastic-constituting polymers, poly epsilon-caprolactone (PCL), polylactic acid (PLA), polyethylene glycol (PEG), poly-beta-hydroxybutyrate (PHB) and cellulose acetate (CA), in a sea-based solid waste disposal site were investigated. Enumeration of aerobic and anaerobic polymers-degrading microorganisms (PDMs) was performed against to total 8 leachate samples, which were seasonally collected from the facultative pretreatment pond and the aerated lagoon. Both aerobic and anaerobic PDMs for natural polymers, PHB and CA, were found in all of the samples, while those for chemically-synthesized polymers, PCL, PLA and PEG, could not be always detected. In most cases, the ratios of the PHB- and CA-degraders to the heterotrophic bacterial population were more than 0.1%. On the other hand, the ratios of PCL-, PLA- and PEG-degraders were often much lower. These data indicate that the plastics degradation potential is commonly present in the studied disposal site, and that the degradation potential for plastics composed of chemically-synthesized polymers is inferior to that of natural polymers. Population sizes of the PDMs correlated to those of heterotrophic bacteria, and the counts of aerobic heterotrophic bacteria and PDMs in the aerated lagoon tended to be higher than those of anaerobic ones, indicating that the aeration of the leachate resulted in the activation of growth of whole aerobic microbial community including the PDMs.     

Divergent responsiveness of two isoforms of the estrogen receptor to mixtures of contaminants of emerging concern in four vertebrates

Contaminants of emerging concern (CECs) are ubiquitous in aquatic environments with well‐established endocrine‐disrupting effects. A data matrix of 559 water samples was queried to identify two commonly occurring CECs mixtures in Great Lakes tributaries. One mixture consisted of eight agricultural CECs (AG), while another contained 11 urban CECs (UB). The known estrogenic compounds bisphenol A, estrone and nonylphenol were present in both mixtures. According to the EPA Tox21 in ToxCast database, AG and UB mixture at an environmentally relevant concentration were estimated to account for 6.5% and 3.4% estrogenicity of the model endocrine disruptor estradiol‐17β, respectively. Two isoforms of the estrogen receptor (Esr1 and ‐2, former Erα and Erβ) cloned from fathead minnow, bluegill sunfish, American alligator and human, responded differently to AG and UB mixtures. Human and bluegill Esr1 were the most sensitive to AG and UB mixtures, respectively. Fathead minnow Esr1 and Esr2b were the least sensitive to 10× AG and UB in estrogen dose equivalents, respectively. Even at environmentally documented concentrations, UB significantly activated bluegill Esr1. Moreover, 100× concentrated UB hyperstimulated fathead minnow Esr1 beyond the maximum induction of estradiol‐17β. These results indicate that efficacious receptors and species differ in their response to CEC mixtures. Furthermore, estrogenicity may be present in some CECs not previously considered estrogenic, or, alternatively, estrogenicity of a mixture may be enhanced through chemical interactions. Our study highlights the need for further studies of CECs utilizing a variety of receptors cloned from diverse species.     

Potential of an Interorgan Network Mediated by Toxic Advanced Glycation End-Products in a Rat Model

Excessive intake of glucose and fructose in beverages and foods containing high-fructose corn syrup (HFCS) plays a significant role in the progression of lifestyle-related diseases (LSRD). Glyceraldehyde-derived advanced glycation end-products (AGEs), which have been designated as toxic AGEs (TAGE), are involved in LSRD progression. Understanding of the mechanisms underlying the effects of TAGE on gene expression in the kidneys remains limited. In this study, DNA microarray analysis and quantitative real-time polymerase chain reaction (PCR) were used to investigate whether HFCS-consuming Wister rats generated increased intracellular serum TAGE levels, as well as the potential role of TAGE in liver and kidney dysfunction. HFCS consumption resulted in significant accumulation of TAGE in the serum and liver of rats, and induced changes in gene expression in the kidneys without TAGE accumulation or upregulation of receptor for AGEs (RAGE) upregulation. Changes in specific gene expression profiles in the kidney were more correlated with TAGE levels in the liver tissue than in the serum. These findings suggest a direct or indirect interaction may be present between the liver and kidneys that does not involve serum TAGE or RAGE. The involvement of internal signal transduction factors such as exosomes or cytokines without IL-1β and TNF-α is suggested to contribute to the observed changes in kidney gene expression.     

Oxidation of 5-methoxy-N,N-diisopropyltryptamine in rat liver microsomes and recombinant cytochrome P450 enzymes

The oxidative metabolism of 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), a tryptamine-type designer drug, was studied using rat liver microsomal fractions and recombinant cytochrome P450 (CYP) enzymes. 5-MeO-DIPT was biotransformed mainly into a side-chain N-deisopropylated metabolite and partially into an aromatic ring O-demethylated metabolite in liver microsomal fractions from untreated rats of both sexes. This metabolic profile is different from our previous findings in human liver microsomal fractions, in which the aromatic ring O-demethylation was the major pathway whereas the side-chain N-deisopropylation was minor [Narimatsu S, Yonemoto R, Saito K, Takaya K, Kumamoto T, Ishikawa T, et al. Oxidative metabolism of 5-methoxy-N,N-diisopropyltryptamine (Foxy) by human liver microsomes and recombinant cytochrome P450 enzymes. Biochem Pharmacol 2006;71:1377-85]. Kinetic and inhibition studies indicated that the side-chain N-dealkylation is mediated by CYP2C11 and CYP3A2, whereas the aromatic ring O-demethylation is mediated by CYP2D2 and CYP2C6 in untreated male rats. Pretreatment of male rats with beta-naphthoflavone (BNF) produced an aromatic ring 6-hydroxylated metabolite. Recombinant rat and human CYP1A1 efficiently catalyzed 5-MeO-DIPT 6-hydroxylation under the conditions used. These results provide valuable information on the metabolic fate of 5-MeO-DIPT in rats that can be used in the toxicological study of this designer drug.     

Estrogen receptor subtypes selectively mediate female mouse reproductive abnormalities induced by neonatal exposure to estrogenic chemicals

Perinatal exposure to estrogens such as diethylstilbestrol (DES), and to estrogenic chemicals, induces persistent anovulation caused by alteration of hypothalamic-pituitary-gonadal (HPG) axis, polyovular follicles, uterine abnormalities and persistent vaginal changes in mice. Most activities of estrogenic chemicals are mediated through estrogen receptor alpha (ERalpha) and/or ERbeta. However, little was known about the relative contribution of the individual ER subtypes in induction of abnormalities. We tested the effects of neonatal exposure to ER selective ligands and DES on female mice. Transactivation assays using mouse ERalpha and ERbeta showed that 10(-10)M DES activated both ER subtypes and that the ERalpha agonist (propyl pyrazole triol, PPT) and the ERbeta agonist (diarylpropionitrile, DPN) selectively activated their respective ERs at 10(-9)M. Neonatal female mice were injected subcutaneously with DES, PPT or DPN and the animals were examined at 13 and 15 weeks of age, respectively. Persistent estrous smears and anovulation were induced in all mice by 0.025-2.5 microg DES and 2.5-25 microg PPT, but not by DPN, suggesting that the observed anovulation was primarily mediated through ERalpha. Disorganization of uterine musculature and ovary-independent vaginal epithelial cell proliferation accompanied by persistent expression of EGF-related genes and interleukin-1-related genes were also mediated through ERalpha. In contrast, polyovular follicles were induced by neonatal treatment with both ERalpha and ERbeta ligands, suggesting that ovarian abnormalities are mediated through both ER subtypes.     

Water fat separation using the single acquisition "sandwich" type 3-point Dixon method to optimize knee joint scans

In this paper, we tried to evaluate the effect of water-fat separation on and to optimize the scan condition of the newly developed "Sandwiched" 3-point Dixon method at 0.35 Tesla (T), for knee joint imaging. Using a 0.35T superconductive open magnet system with a solenoid type knee coil, one male and two female normal volunteers (27-37 y.o.) underwent knee joint imaging. Each sequence provided good water-fat separated images. At 0.35T, the gradient echo provided a better contrast than the spin echo. Optimal cartilage-marrow and cartilage-fluid contrast could be obtained at a frip angle (FA) of 90 degrees. There was no significant correlation between cartilage-marrow, cartilage-fluid contrast and repetition time (TR) values within the tested range. Cartilage-fluid and cartilage-marrow contrast were both best at an FA of 90 degrees with the gradient echo sequence. TR from 350 ms to 650 ms did not cause any significant contrast difference in the fat suppressed images. This method is useful and could be the only practical choice for obtaining fat suppressed T1 weighted images for joint magnetic resonance (MR) imaging at 0.35T.     

The effects of static magnetic fields and X-rays on instability of microsatellite repetitive sequences

To determine the genetic effect of static magnetic fields (SMF), which are not supposed to produce any significant DNA damage, we took advantage of DNA mismatch repair (MMR) deficient cells, in which all the errors produced during DNA replication are left uncorrected. We first established a simple and less labor-intensive method to analyze genetic changes in microsatellite repetitive sequences in the MMR-deficient cells. After exposure to a strong SMF (6.34T) for 24 h, both MMR deficient HCT116 cells and proficient HeLa S3 cells did not exhibit any significant effect on microsatellite changes. Moreover, when HCT116 cells were synchronized at the G1/S boundary by aphidicolin and exposed to SMF during the whole S-phase, no increase in microsatellite changes was either observed. In contrast, irradiation by a low dose X-ray (2Gy) significantly increased microsatellite changes in HCT116 cells. This suggested that exposure to strong SMF may not induce any significant level of genetic changes in microsatellite sequences.     

Wnt family genes and their modulation in the ovary-independent and persistent vaginal epithelial cell proliferation and keratinization induced by neonatal diethylstilbestrol exposure in mice

Proliferation and differentiation of cells in female reproductive organs, the oviduct, uterus and vagina, are regulated by endogenous estrogen. In utero exposure to a synthetic estrogen, diethylstilbestrol (DES), induces vaginal clear-cell adenocarcinoma in humans. In mice, perinatal exposure to DES results in abnormalities such as polyovular follicles, uterine circular muscle disorganization and persistent vaginal epithelial cell proliferation. We reported the persistent gene expression change such as interleukin-1 (IL-1) related genes, insulin-like growth factor-I (IGF-I) and its downstream signaling in the mouse vagina exposed neonatally to DES. In this study, we found persistent up-regulation of Wnt4 and persistent down-regulation of Wnt11 in the vagina of mice exposed neonatally to DES and estrogen receptor α specific ligand. Also Wnt4 expression in vagina is correlated to the stratification of epithelial cells with the superficial keratinization of vagina, but not epithelial cell stratification only.