Eleven phthalate esters and di(2-ethylhexyl) adipate in oneweek duplicate diet samples obtained from hospitals and their estimated daily intake

Plasticizers in duplicate diet samples obtained over 1 week were analysed in order to estimate daily intake. The phthalate esters were as follows: diethyl, dipropyl, dibutyl, dipentyl, dihexyl, butylbenzyl, dicyclohexyl, di(2-ethylhexyl), dioctyl, diisooctyl (mixture of isomers) and diisononyl (mixture). Di(2-ethylhexyl) adipate was also determined. Homogenized samples of composite meals were extracted with acetonitrile, lipids were removed by extraction into n-hexane and the acetonitrile layer was cleaned using FlorisilR and R Bondesil PSA dual layer column. Phthalates were determined by GC/MS (SIM). Phthalate recovery from the fortified food mixture by this method was 62.5-140.8%. Quality assurance as assessed by three laboratories indicated coefficient of variance in the levels of detected phthalates in same lot samples as below 10%. Detection limits were 0.1-23ng/g for each phthalate. One-week duplicate diet samples provided by three hospitals in three remote prefectures of Japan were analysed as individual meals. In all 63 samples, DEHP was present at the highest level among all phthalates in the range 10-4400ng/g. The intake of plasticizers estimated from all samples was 519 µ g DEHP/day, 86 µ g DEHA/day, 65 µ g DINP/day, and 4.7 µ g BBP/day. Calculated DEHP in 2-day samples out of 21 days exceeded EU TDI for a person of 50kg body weight (1850 µ g per day). Disposable PVC gloves used during the preparation of meals were suspected as the source of the high DEHP content. One-day intake of the other phthalates and DEHA was below 7% of TDI in all cases. High concentrations of DEHP (5990ng/g) was found in baby food used in quality assurance work. The source of contamination was the PVC-tube used during production and was effectively reduced by replacing the tube by one made of stainless steel.     

Design,Synthesis, and Biological Evaluation of Lysine Demethylase 5 C Degraders

Lysine demethylase 5 C (KDM5C) controls epigenetic gene expression and is attracting great interest in the field of chemical epigenetics. KDM5C has emerged as a therapeutic target for anti-prostate cancer agents, and recently we identified triazole 1 as an inhibitor of KDM5C. Compound 1 exhibited highly potent KDM5C-inhibitory activity in in vitro enzyme assays, but did not show strong anticancer effects. Therefore, a different approach is needed for the development of anticancer agents targeting KDM5C. Here, we attempted to identify KDM5C degraders by focusing on a protein-knockdown strategy. Compound 3 b , which was designed based on compound 1 , degraded KDM5C and inhibited the growth of prostate cancer PC-3 cells more strongly than compound 1 . These findings suggest that KDM5C degraders are more effective as anticancer agents than compounds that only inhibit the catalytic activity of KDM5C.     

Contribution of Invariant Natural Killer T Cells to the Clearance of Pseudomonas aeruginosa from Skin Wounds

Chronic infections are considered one of the most severe problems in skin wounds, and bacteria are present in over 90% of chronic wounds. Pseudomonas aeruginosa is frequently isolated from chronic wounds and is thought to be a cause of delayed wound healing. Invariant natural killer T (iNKT) cells, unique lymphocytes with a potent regulatory ability in various inflammatory responses, accelerate the wound healing process. In the present study, we investigated the contribution of iNKT cells in the host defense against P. aeruginosa inoculation at the wound sites. We analyzed the re-epithelialization, bacterial load, accumulation of leukocytes, and production of cytokines and antimicrobial peptides. In iNKT cell–deficient (Jα18KO) mice, re-epithelialization was significantly decreased, and the number of live colonies was significantly increased, when compared with those in wild-type (WT) mice on day 7. IL-17A, and IL-22 production was significantly lower in Jα18KO mice than in WT mice on day 5. Furthermore, the administration of α-galactosylceramide (α-GalCer), a specific activator of iNKT cells, led to enhanced host protection, as shown by reduced bacterial load, and to increased production of IL-22, IL-23, and S100A9 compared that of with WT mice. These results suggest that iNKT cells promote P. aeruginosa clearance during skin wound healing.     

A menu generator for audio visual networks

An audio visual system can enhance its controllability by an interactive and user-friendly menu through which a user issues commands to control audio visual devices. One of the serious problems encountered in such menu development is that end-user's requirement specifications vary in screen layouts, device configurations and commands contents, and often involves extensive manual programming. We have definedMacroMMenu formally as a tree structure menu system model restricting a menu transition graph, and designed and implemented an automated menu prototyping system which includes a menu generator calledInteractive Proto. UsingInteractive Proto through a visual programming language, end-users themselves, who are usually non-programmers, can easily define menu specification, input this source specification, and the targetMacro Menu is generated automatically.     

Genotoxicity of nano/microparticles in in vitro micronuclei, in vivo comet and mutation assay systems

Background

Recently, manufactured nano/microparticles such as fullerenes (C₆₀), carbon black (CB) and ceramic fiber are being widely used because of their desirable properties in industrial, medical and cosmetic fields. However, there are few data on these particles in mammalian mutagenesis and carcinogenesis. To examine genotoxic effects by C₆₀, CB and kaolin, an in vitro micronuclei (MN) test was conducted with human lung cancer cell line, A549 cells. In addition, DNA damage and mutations were analyzed by in vivo assay systems using male C57BL/6J or gpt delta transgenic mice which were intratracheally instilled with single or multiple doses of 0.2 mg per animal of particles.

Results

In in vitro genotoxic analysis, increased MN frequencies were observed in A549 cells treated with C₆₀, CB and kaolin in a dose-dependent manner. These three nano/microparticles also induced DNA damage in the lungs of C57BL/6J mice measured by comet assay. Moreover, single or multiple instillations of C₆₀ and kaolin, increased either or both of gpt and Spi^- mutant frequencies in the lungs of gpt delta transgenic mice. Mutation spectra analysis showed transversions were predominant, and more than 60% of the base substitutions occurred at G:C base pairs in the gpt genes. The G:C to C:G transversion was commonly increased by these particle instillations.

Conclusion

Manufactured nano/microparticles, CB, C₆₀ and kaolin, were shown to be genotoxic in in vitro and in vivo assay systems.     

Partner's Stress Status Influences Social Buffering Effects in Rats.

The relationship between a social partner's stress status and the social buffering effect was examined in adult male Wistar rats. Fear-conditioned rats were exposed to the same context along with either a shocked or nonshocked conspecific partner. Changes in body temperature and behavioral responses were monitored in order to compare the effects of social buffering, and the Fos protein in the paraventricular nucleus was immunostained. The presence of the partner rat attenuated stress-induced hyperthermia, as well as behavioral responses and Fos expression in response to the fearful context, and nonshocked partners were more effective than shocked partners. These findings suggest that the social buffering effect depends on the stress status of the accompanying conspecific animal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time-resolved diffuse optical tomographic imaging for the provision of both anatomical and functional information about biological tissue

We present in vivo images of near-infrared (NIR) diffuse optical tomography (DOT) of human lower legs and forearm to validate the dual functions of a time-resolved (TR) NIR DOT in clinical diagnosis, i.e., to provide anatomical and functional information simultaneously. The NIR DOT system is composed of time-correlated single-photon-counting channels, and the image reconstruction algorithm is based on the modified generalized pulsed spectral technique, which effectively incorporates the TR data with reasonable computation time. The reconstructed scattering images of both the lower legs and the forearm revealed their anatomies, in which the bones were clearly distinguished from the muscles. In the absorption images, some of the blood vessels were observable. In the functional imaging, a subject was requested to do handgripping exercise to stimulate physiological changes in the forearm tissue. The images of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentration changes in the forearm were obtained from the differential images of the absorption at three wavelengths between the exercise and the rest states, which were reconstructed with a differential imaging scheme. These images showed increases in both blood volume and oxyhemoglobin concentration in the arteries and simultaneously showed hypoxia in the corresponding muscles. All the results have demonstrated the capability of TR NIR DOT by reconstruction of the absolute images of the scattering and the absorption with a high spatial resolution that finally provided both the anatomical and functional information inside bulky biological tissues.     

Postnatal changes in activation of polyunsaturated fatty acid,acylation of lysophosphoglyceride,and phosphorylation of diacylglycerol in cortical gray matter of rat cerebrum

Activation of polyunsaturated fatty acid, acylation of lysophosphoglyceride, and phosphorylation of diacylglycerol in postnatal developing rat cerebrum were studiedin vitro, using cortical gray matter homogenates. The rate of n-3 and n-6 fatty acid activation was maximal at ten days after birth and minimal at adulthood. Acylation of lysophosphoglyceride was most active at the neonatal stage and gradually decreased with age. In addition, the amount of phosphatidic acid formed from 1, 2-dioleoyl-glycerol was also maximum at the neonatal stage, and then gradually decreased. These results suggest that the specific activity of glycerolipid synthesis in cortical gray matter declines during postnatal development.