Analysis of the Antioxidative Function of the Radioprotective Japanese Traditional (Kampo) Medicine, Hangeshashinto, in an Aqueous Phase

Oral mucositis (OM) is a common and painful complication of radiotherapy for head and neck cancer. Hangeshashinto (HST), a Japanese traditional medicine, is known to alleviate radiotherapy and/or chemotherapy-induced OM; however, the detailed mechanism has not yet been clarified. The aim of the present study is to clarify the details of the antioxidative functions of HST against reactive oxygen species (ROS) produced by radiation. The hydroxyl radical (•OH) scavenging ability and reduction ability was simultaneously measured using a modified electron paramagnetic resonance (EPR) spin trapping method. The superoxide (O2•−) scavenging ability was estimated by an EPR redox probing method. Water suspension of powdered HST and its seven constitutive crude drugs were tested. In addition, some of the main water soluble ingredients of the crude drugs were also tested. HST was found to scavenge both •OH and O2•−. Furthermore, HST was observed to reduce relatively stable nitroxyl radicals. Glycyrrhizae Radix (kanzo), Ginseng Radix (ninjin), Zizyphi Fructus (taiso), and glycyrrhizin (an ingredient of kanzo) were all found to be relatively good •OH scavengers. Scutellariae Radix (ogon) and Coptidis Rhizoma (oren) demonstrated reducing ability. In addition, acteoside and berberine chloride, which are water soluble ingredients of ogon and oren, respectively, also demonstrated reducing ability. Oren exhibited oxidative ability at higher concentrations, which may have a function to maintain catalytic redox action. The antioxidative function of HST probably worked in a balance of scavenging ROS, reducing stable free radicals and some minor oxidative effects

EPR based Estimation of Radiation-Induced Reactive Oxygen Species

Generation of reactive oxygen species (ROS) is considered as essential trigger of biological effects of ionizing radiations, and may be deeply linked with the radiation quality.Amounts of total oxidation reactions (i.e. oxidative free radical species, •OH and HO2•), H2O2 generations, Oxygen consumptions, and •OH generations induced by X-ray, 20 keV/μm carbon beam, and 80 keV/μm carbon beam were estimated using EPR based techniques.Total oxidation reactions were estimated as 3, 1.3, and 0.66 μmol/L/Gy, amount of H2O2 generations were 0.2, 0.57, and 0.35 μmol/L/Gy, oxygen consumptions were 0.4, 0.39, and 0.15 μmol/L/Gy for X-ray, 20 keV/μm carbon beam, and 80 keV/μm carbon beam, respectively. The ratio of H2O2 generation per oxygen consumption were increased with LET, and were 0.5, 1.46, 2.33 for X-ray, 20 keV/μm carbon beam, and 80 keV/μm carbon beam, respectively. The •OH generations expected to be localized on the track/range of the radiation beam/ray, and both sparse (≈ 3.3 mM) and very dense (> 1.7 M) •OH generations were suggested. Percentage of sparse •OH generation decreased with LET becoming higher.The SFRBM\u27s 23rd Annual Meeting, a joint meeting with the Society for Free Radical Research International (SFRBM/SFRRI 2016

Potential Activity of Amrubicin as a Salvage Therapy for Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin with an aggressive clinical course. Although anthracycline- and platinum-based regimens are empirically used as first-line treatments for metastatic or unresectable cases, no salvage therapy has been established. A 73-year-old man with platinum-refractory recurrent MCC was treated with amrubicin. The symptoms improved soon, and a partial response was achieved. A total of nine cycles of amrubicin were administered in nine months with manageable adverse events until disease progression was finally observed. The present findings suggest the potential of amrubicin monotherapy as a second-line therapy for patients with advanced/recurrent MCC

Intestinal Bacteria as Powerful Trapping Lifeforms for the Elimination of Radioactive Cesium

In March 2011, an accident at the Fukushima Daiichi Nuclear Power Plant led to major problems, including the release of radionuclides such as Cesium (Cs)-137 into the environment. Ever since this accident, Cs-137 in foods has become a serious problem. In this study, we determined the concentration of Cs-137 in the feces, urine, and ruminal contents of cattle and demonstrated the possibility of its elimination from the body by intestinal bacteria. The results revealed a high Cs-137 concentration in the feces; in fact, this concentration was higher than that in skeletal muscles and other samples from several animals. Furthermore, intestinal bacteria were able to trap Cs-137, showing an uptake ratio within the range of 38–81% in vitro. This uptake appeared to be mediated through the sodium–potassium (Na+-K+) ion pump in the bacterial cell membrane. This inference was drawn based on the fact that the uptake ratio of Cs-137 was decreased in media with high potassium concentration. In addition, it was demonstrated that intestinal bacteria hindered the trapping of Cs-137 by the animal. Cattle feces showed high concentration of Cs-137 and intestinal bacteria trapped Cs-137. This study is the first report showing that intestinal bacteria contribute to the elimination of Cs-137 from the body

第一次間主観性の発達過程における個人差の研究

Innate infant intersubjectivity (IS) has been observed to emerge clearly around the second month after birth. The first IS is called Primary Intersubjectivity (PIS) which is defined by synchronized body movement and proto-conversation between the infant and his/her parent. Although researchers have agreed the fact that IS is an important faculty for infants to consolidate relationship with their affectionate parents, we do not know its emerging process and individual differences in the process yet. In this study, 50 new mothers were asked to make a video-diary by recording their natural interactions with the baby at two, four, eight and thirteen week of infant age. To explore the PI emerging process and its individual differences, three-minute video-clips which included the scenes the infant was attentive to the mother more than 5s or showed active responses to her were extracted from each of video-diaries and infant\u27s PI behaviors were encoded. Results showed that although most infants evidenced PI behaviors until eight week of age, interestingly IP behaviors were not discernible in about 20% of infants even thirteenth week. Therefore, since three month of age, infants may develop through either the pathway of active intersubjective one or rather unsociable one

4か月児の社会的随伴性の弁別に及ぼす親の遊戯性の効果

Double Video paradigm(DVP) studies have found contradictory evidence regarding the young infants\u27 ability to discriminate their mother\u27s \u27Replay\u27 image from \u27Live\u27. This study examined the hypothesis that 4-month-old infants with high-levels-of-playful-behavior mothers are more likely to discriminate social contingency in the DVP. We also examined the relationships between the infants\u27 DVP behaviors and mothers\u27 free-play behaviors with their infant at home at home at 3 months of infant\u27s age. The results supported our hypothesis. Further, when the mothers\u27 behaviors were reduced as Playful Companion(PC) and Sensitive Support(SS), the level of PC more related to the infants\u27 detection of social contingency than SS. The different functions of mothers\u27 \u27playfulness\u27 and \u27sensitivity\u27 in communication with their infants are discussed

Comparative studies on DNA double strand breaks induced by sulforaphane and X-rays

Sulforaphane (l-isothiocyanate-4methylsulfinylbutane: SFN), an isothiocyanate, isolated from broccoli and other cruciferous vegetables is wellkown for cancer preventive agent. It was reported that SFN suppressed proliferation of cancer cells by cell cycle arrest and/or by inducing apoptosis by activating the caspase apoptosis pathway. After an accidental discovery of SFN inducing DNA strand breaks in our laboratory, we started to systematically study DNA double-strand breaks (DSBs) induced by this product, and the result was compared to that with X-rays. DSB is thought to be the most critical lesions for radiation induced damage and cells have severe biological consequences if this damage is not repaired or mis-repaired. HeLa cells were exposed to various concentrations of SFN and the cell growth was measured. The induction of DNA DSB was examined using constant field gel electrophoresis (CFGE) and gamma-H2AX assay. Our data revealed that cell growth was impaired in a SFN dose dependent manner. DNA DSBs were also induced in SFN dose and time dependent manners. The amount of DSBs induced by 20μM SFN for 48h, for example, correspond to that induced by 10 Gy X-rays. Moreover, our immuno-staining experiments indicated the appearance of Rad51 (homologous recombination repair (HRR) related protein) foci observed in a dose and time dependent manner along with the DNA DSB production. In contrast, there was no phosphorylation of DNA-PKcs (a critical non-homologous end joining (NHEJ) protein) observed in SFN exposed cells.In summary our data clearly demonstrate the induction of DNA DSBs by SFN, and these breaks seem to be predominantly repaired by the HRR pathway. These results give a possibility that SFN could be used as an effective anticancer agent.International Workshop on Radiation Damage to DN