Scandium Ion-Promoted Electron-Transfer Disproportionation of 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-Oxide (PTIO•) in Acetonitrile and Its Regeneration Induced by Water.

2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO•), a persistent nitronyl nitroxide radical, has been used for the detection and trapping of nitric oxide, as a redox mediator for batteries, for the activity estimation of antioxidants, and so on. However, there is no report on the reactivity of PTIO• in the presence of redox-inactive metal ions. In this study, it is demonstrated that the addition of scandium triflate, Sc(OTf)3 (OTf = OSO2CF3), to an acetonitrile (MeCN) solution of PTIO• resulted in an electron-transfer disproportionation to generate the corresponding cation (PTIO+) and anion (PTIO-), the latter of which is suggested to be stabilized by Sc3+ to form [(PTIO)Sc]2+. The decay of the absorption band at 361 nm due to PTIO•, monitored using a stopped-flow technique, obeyed second-order kinetics. The second-order rate constant for the disproportionation, thus determined, increased with increasing the Sc(OTf)3 concentration to reach a constant value. A drastic change in the cyclic voltammogram recorded for PTIO• in deaerated MeCN containing 0.10 M Bu4NClO4 was also observed upon addition of Sc(OTf)3, suggesting that the large positive shift of the one-electron reduction potential of PTIO• (equivalent to the one-electron oxidation potential of PTIO-) in the presence of Sc(OTf)3 may result in the disproportionation. When H2O was added to the PTIO•-Sc(OTf)3 system in deaerated MeCN, PTIO• was completely regenerated. It is suggested that the complex formation of Sc3+ with H2O may weaken the interaction between PTIO- and Sc3+, leading to electron-transfer comproportionation to regenerate PTIO•. The reversible disproportionation of PTIO• was also confirmed by electron paramagnetic resonance (EPR) spectroscopy.

DOSE ESTIMATION TO WILD MEDAKA AROUND FUKUSHIMA DAI-ICHI NUCLEAR POWER PLANT.

More than 10 y have passed since the Fukushima Dai-ichi Nuclear Power Plant (F1-NPP) accident, but there are still many areas with high levels of radioactive contamination, especially reservoirs and lakes, where the levels decrease slowly. The exposed dose to non-human biota is of great concern. In this work, the exposure dose to wild medaka (small aquarium fish) around F1-NPP was measured/estimated by two approaches: in situ measurement and with the ERICA assessment tool. S2 is a reservoir located 7.5 km from F1-NPP, and the ambient dose rate was 25.0 µSv per h in 2012, but decreased to 4.82 µSv per h in 2021. The external exposure dose rate to wild medaka living there was 0.8-11.8 µGy per h (2017-21) by in situ measurement, and the estimated dose rate with the ERICA assessment tool was 0.6-54.5 µGy per h (2012-21). The estimated and measured doses to wild medaka are not expected to cause any significant radiation effects.

Fluorescence in situ hybridization analysis of chromosomal aberrations in mouse splenocytes at one- and two-months after total body exposure to iron-56 (Fe) ion particles or X-rays.

High atomic number and energy (HZE) particles such as iron-56 (Fe) ions are a major contributor to health risks in long-term manned space exploration. The aim of this study is to understand radiation-induced differential genotoxic effects between HZE particles and low linear energy transfer (LET) photons. C57BL/6J Jms female mice of 8 weeks old were exposed to total body irradiation of accelerated Fe-particles with a dose ranging from 0.1 to 3.0 Gy or of X-rays with a dose ranging from 0.1 to 5.0 Gy. Chromosomal aberrations (CAs) in splenocytes were examined by fluorescence in situ hybridization at 1- and 2-months after exposure. Clonal expansions of cells with CAs were found to be induced only by X-rays but not by Fe-particles. Dose-dependent increase in the frequencies of stable-type CAs was observed at 1- as well as 2-months after exposure to both radiation types. The frequencies of stable-type CAs in average were much higher in mice exposed to X-rays than those to Fe-particles and did not change significantly between 1- and 2-months after exposure to both radiation types. On the other hand, the frequencies of unstable-type CAs induced by X-rays and Fe-particles were not much different, and they appeared to decrease with time from 1- to 2-months after exposure. These results suggested that larger fraction of stable-type CAs induced by Fe-particles might be non-transmissible than those by X-rays because of some associating lethal alterations on themselves or on other chromosomes in the same cells and that these cells might be removed by 1-month after Fe-TBI. We also demonstrated that exposure to Fe-particles induced insertions at relatively higher frequency to other stable-type CAs than X-rays. Our findings suggest that insertions can be used as indicators of past exposure to high-LET particle radiation.

Enhanced Effects of Chronic Restraint-Induced Psychological Stress on Total Body Fe-Irradiation-Induced Hematopoietic Toxicity in Trp53-Heterozygous Mice.

Humans are exposed to both psychological stress (PS) and radiation in some scenarios such as manned deep-space missions. It is of great concern to verify possible enhanced deleterious effects from such concurrent exposure. Pioneer studies showed that chronic restraint-induced PS (CRIPS) could attenuate Trp53 functions and increase gamma-ray-induced carcinogenesis in Trp53-heterozygous mice while CRIPS did not significantly modify the effects on X-ray-induced hematopoietic toxicity in Trp53 wild-type mice. As high-linear energy transfer (LET) radiation is the most important component of space radiation in causing biological effects, we further investigated the effects of CRIPS on high-LET iron-particle radiation (Fe)-induced hematopoietic toxicity in Trp53-heterozygous mice. The results showed that CRIPS alone could hardly induce significant alteration in hematological parameters (peripheral hemogram and micronucleated erythrocytes in bone marrow) while concurrent exposure caused elevated genotoxicity measured as micronucleus incidence in erythrocytes. Particularly, exposure to either CRISP or Fe-particle radiation at a low dose (0.1 Gy) did not induce a marked increase in the micronucleus incidence; however, concurrent exposure caused a significantly higher increase in the micronucleus incidence. These findings indicated that CRIPS could enhance the deleterious effects of high-LET radiation, particularly at a low dose, on the hematopoietic toxicity in Trp53-heterozygous mice.

Synergistic Effects of Chronic Restraint-Induced Stress and Low-Dose 56Fe-particle Irradiation on Induction of Chromosomal Aberrations in Trp53-Heterozygous Mice.

Astronauts can develop psychological stress (PS) during space flights due to the enclosed environment, microgravity, altered light-dark cycles, and risks of equipment failure or fatal mishaps. At the same time, they are exposed to cosmic rays including high atomic number and energy (HZE) particles such as iron-56 (Fe) ions. Psychological stress or radiation exposure can cause detrimental effects in humans. An earlier published pioneering study showed that chronic restraint-induced psychological stress (CRIPS) could attenuate Trp53 functions and increase carcinogenesis induced by low-linear energy transfer (LET) γ rays in Trp53-heterozygous (Trp53+/-) mice. To elucidate possible modification effects from CRIPS on high-LET HZE particle-induced health consequences, Trp53+/- mice were received both CRIPS and accelerated Fe ion irradiation. Six-week-old Trp53+/- C57BL/6N male mice were restrained 6 h per day for 28 consecutive days. On day 8, they received total-body Fe-particle irradiation (Fe-TBI, 0.1 or 2 Gy). Metaphase chromosome spreads prepared from splenocytes at the end of the 28-day restraint regimen were painted with the fluorescence in situ hybridization (FISH) probes for chromosomes 1 (green), 2 (red) and 3 (yellow). Induction of psychological stress in our experimental model was confirmed by increase in urinary corticosterone level on day 7 of restraint regimen. Regardless of Fe-TBI, CRIPS reduced splenocyte number per spleen at the end of the 28-day restraint regimen. At 2 Gy, Fe-TBI alone induced many aberrant chromosomes and no modifying effect was detected from CRIPS on induction of aberrant chromosomes. Notably, neither Fe-TBI at 0.1 Gy nor CRIPS alone induced any increase in the frequency of aberrant chromosomes, while simultaneous exposure resulted in a significant increase in the frequency of chromosomal exchanges. These findings clearly showed that CRIPS could enhance the frequency of chromosomal exchanges induced by Fe-TBI at a low dose of 0.1 Gy.

Reduced High-Dose Radiation-Induced Residual Genotoxic Damage by Induction of Radioadaptive Response and Prophylactic Mild Dietary Restriction in Mice.

Radioadaptive response (RAR) describes a phenomenon in a variety of in vitro and in vivo systems that a low-dose of priming ionizing radiation (IR) reduces detrimental effects of a subsequent challenge IR at higher doses. Among in vivo investigations, studies using the mouse RAR model (Yonezawa Effect) showed that RAR could significantly extenuate high-dose IR-induced detrimental effects such as decrease of hematopoietic stem cells and progenitor cells, acute radiation hematopoietic syndrome, genotoxicity and genomic instability. Meanwhile, it has been demonstrated that diet intervention has a great impact on health, and dietary restriction shows beneficial effects on numerous diseases in animal models. In this work, by using the mouse RAR model and mild dietary restriction (MDR), we confirmed that combination of RAR and MDR could more efficiently reduce radiogenotoxic damage without significant change of the RAR phenotype. These findings suggested that MDR may share some common pathways with RAR to activate mechanisms consequently resulting in suppression of genotoxicity. As MDR could also increase resistance to chemotherapy and radiotherapy in normal cells, we propose that combination of MDR, RAR, and other cancer treatments (i.e., chemotherapy and radiotherapy) represent a potential strategy to increase the treatment efficacy and prevent IR risk in humans.

Radiation effects on wild medaka around Fukushima Dai-ichi Nuclear Power Plant assessed by micronucleus assay.

Since the Fukushima Dai-ichi Nuclear Power Plant (F1-NPP) accident in 2011, radiation effects on wildlife in the contaminated areas have been a major concern. The outskirts of the F1-NPP are mainly rural areas, where many rice fields, streams and reservoirs are located. We searched for wild medaka (small aquarium fish) around the F1-NPP and found two wild medaka habitats (S1 and S2). S1 is a stream located 4 km from the F1-NPP, where the ambient dose equivalent rate was 0.4-0.9 µSv/h (2013-14), and S2 is a reservoir located 7.5 km from the F1-NPP, where the ambient dose equivalent rate was 9.8-22 µSv/h (2013-14 and 2017-18). Dosimeters were placed for one day at the locations where the medaka were captured, and the absorbed dose rates were estimated. Radiation effects on wild medaka were examined using micronucleus assay between 2013 and 2018. No significant difference in frequency of micronucleated gill cells was observed among the wild medaka from S1, S2 and our cultivated medaka that were used as a control.

Altered Response to Total Body Irradiation of C57BL/6-Tg (CAG-EGFP) Mice.

Application of green fluorescent protein (GFP) in a variety of biosystems as a unique bioindicator or biomarker has revolutionized biological research and made groundbreaking achievements, while increasing evidence has shown alterations in biological properties and physiological functions of the cells and animals overexpressing transgenic GFP. In this work, response to total body irradiation (TBI) was comparatively studied in GFP transgenic C57BL/6-Tg (CAG-EGFP) mice and C57BL/6 N wild type mice. It was demonstrated that GFP transgenic mice were more sensitive to radiation-induced bone marrow death, and no adaptive response could be induced. In the nucleated bone marrow cells of GFP transgenic mice exposed to a middle dose, there was a significant increase in both the percentage of cells expressing pro-apoptotic gene Bax and apoptotic cell death. While in wild type cells, lower expression of pro-apoptotic gene Bax and higher expression of anti-apoptotic gene Bcl-2, and significant lower induction of apoptosis were observed compared to GFP transgenic cells. Results suggest that presence of GFP could alter response to TBI at whole body, cellular and molecular levels in mice. These findings indicate that there could be a major influence on the interpretation of the results obtained in GFP transgenic mice.

Diallyl Disulfide Mitigates DNA Damage and Spleen Tissue Effects After Irradiation.

BACKGROUND Several factors found in foods are beneficial to human health and they may contribute to radiation protection. Taking food factors could be an easy way to reduce the effects of radiation after nuclear accidents, as well as secondary radiation risks after cancer radiotherapy or space missions. Here, diallyl disulfide (DADS), a component of garlic oil, was studied for its ability to mitigate radiation damage. MATERIAL AND METHODS We investigated the effects of DADS on micronucleus (MN) formation and apoptosis in HepG2 cells by use of 4-Gy X-ray irradiation. We also assessed the effects of DADS on radiation damage in vivo by evaluating MN formation in bone marrow cells in mice (BALB/c, 8-week-old females) after oral intake of DADS prior to irradiation with 4 Gy. Several tissue effects were also investigated. RESULTS The presence of DADS inhibited MN formation, whereas DADS had no influence on the radiation-induced inhibition of cell cycle progression in HepG2 cells. An increase in apoptosis in HepG2 cells was induced after irradiation, and this effect was stronger in the presence of DADS than in its absence. In mice, when DADS was administered daily for 3 days prior to irradiation, MN formation in irradiated mice was decreased. The decrease in MN formation in mice was greater with 0.5% DADS compared to 1% DADS. Moreover, an increase in spleen weight observed 3 weeks after irradiation was suppressed in mice administered DADS. CONCLUSIONS DADS is a potential radiation-protective agent that effectively mitigates DNA damage, and its effects in the spleen observed after irradiation may be related to inflammation and carcinogenesis.

A small fish model for quantitative analysis of radiation effects using visualized thymus responses in GFP transgenic medaka.

Purpose: The aim of this study was to establish a new method of real-time, in vivo detection of radiation damage and recovery. Methods: The thymus was observed under fluorescent light in a green fluorescent protein transgenic medaka. After irradiation, medaka thymus images were analyzed to quantify the effects of radiation by measuring changes in thymus size. A single acute irradiation of X-rays (0-30 Gy) or heavy Fe ions (0-10 Gy) was delivered to the medaka. Images were captured 0, 1, 2, 3, 5, 7, 11, and 21 d after irradiation. Dose-response assessment was conducted to provide a direct measurement of the effects of the radiation. Conclusion: A biomonitoring system to detect the effects of radiation in real time was established. Using this system, the threshold doses for the induction of thymic atrophy by acute X-rays and Fe ions were 2-5 Gy and 0.5-1 Gy, respectively. The Relative Biological Effectiveness (RBE) of Fe-ion to X-rays was estimated to be around 3. This system may be used to evaluate the risk from concurrent exposure to hazards, such as chemicals and radiation, and for aging research.

Increased Hematopoietic Stem Cells/Hematopoietic Progenitor Cells Measured as Endogenous Spleen Colonies in Radiation-Induced Adaptive Response in Mice (Yonezawa Effect).

The existence of radiation-induced adaptive response (AR) was reported in varied biosystems. In mice, the first in vivo AR model was established using X-rays as both the priming and the challenge doses and rescue of bone marrow death as the end point. The underlying mechanism was due to the priming radiation-induced resistance in the blood-forming tissues. In a series of investigations, we further demonstrated the existence of AR using different types of ionizing radiation (IR) including low linear energy transfer (LET) X-rays and high LET heavy ion. In this article, we validated hematopoietic stem cells/hematopoietic progenitor cells (HSCs/HPCs) measured as endogenous colony-forming units-spleen (CFU-S) under AR inducible and uninducible conditions using combination of different types of IR. We confirmed the consistency of increased CFU-S number change with the AR inducible condition. These findings suggest that AR in mice induced by different types of IR would share at least in part a common underlying mechanism, the priming IR-induced resistance in the blood-forming tissues, which would lead to a protective effect on the HSCs/HPCs and play an important role in rescuing the animals from bone marrow death. These findings provide a new insight into the mechanistic study on AR in vivo.

Ultrahigh-temperature tensile creep of TiC-reinforced Mo-Si-B-based alloy.

In this study, the ultrahigh-temperature tensile creep behaviour of a TiC-reinforced Mo-Si-B-based alloy was investigated in the temperature range of 1400-1600 °C at constant true stress. The tests were performed in a stress range of 100-300 MPa for 400 h under vacuum, and creep rupture data were rationalized with Larson-Miller and Monkman-Grant plots. Interestingly, the MoSiBTiC alloy displayed excellent creep strength with relatively reasonable creep parameters in the ultrahigh-temperature range: a rupture time of ~400 h at 1400 °C under 137 MPa with a stress exponent (n) of 3 and an apparent activation energy of creep (Qapp) of 550 kJ/mol. The increasing rupture strains with decreasing stresses (up to 70%) and moderate strain-rate oscillations in the creep curves suggest that two mechanisms contribute to the creep: phase boundary sliding between the hard T2 and (Ti,Mo)C phases and the Moss phase, and dynamic recovery and recrystallization in Moss, observed with orientation imaging scanning electron microscopy. The results presented here represent the first full analysis of creep for the MoSiBTiC alloy in an ultrahigh-temperature range. They indicate that the high-temperature mechanical properties of this material under vacuum are promising.

Bilateral Cytomegalovirus Retinitis in a Patient with Systemic Lupus Erythematosus.

PURPOSE: The purpose of this study was to report the case of a patient who underwent vitrectomy for bilateral rhegmatogenous retinal detachment caused by cytomegalovirus (CMV) retinitis while undergoing steroid and immunosuppressant therapy for systemic lupus erythematosus (SLE). CASE REPORT: We report on a 29-year-old female who was undergoing steroids and immunosuppressants treatment for SLE at Osaka Medical College Hospital, Takatsuki City, Japan. Examination of the patient due to prolonged and worsening diarrhea revealed positive test results for C7-HRP, and she was diagnosed with CMV colitis. She was subsequently admitted to the hospital and started on intravenous ganciclovir for treatment. Approximately 1.5 months later, her primary complaint was deterioration of the upper visual field in her left eye, and she was then referred to the Department of Ophthalmology. Numerous granular exudative spots were found around the lower retinal area of her left eye with retinal breaks that had developed in an area of retinal necrosis that resulted in retinal detachment. After time was allowed for the patient's general condition to improve, a vitrectomy was performed on that eye. The patient subsequently developed a similar retinal detachment in her right eye, for which she underwent a vitrectomy. Although the patient required multiple surgeries on both eyes, her retinas currently remain reattached and the inflammation has subsided. CONCLUSION: The findings of this study show that strict attention must be paid to SLE patients on immunosuppressive therapy due to the possible association of CMV retinitis.

Morphological defects in native Japanese fir trees around the Fukushima Daiichi Nuclear Power Plant.

After the accident at the Fukushima Daiichi Nuclear Power Plant (F1NPP) in March 2011, much attention has been paid to the biological consequences of the released radionuclides into the surrounding area. We investigated the morphological changes in Japanese fir, a Japanese endemic native conifer, at locations near the F1NPP. Japanese fir populations near the F1NPP showed a significantly increased number of morphological defects, involving deletions of leader shoots of the main axis, compared to a control population far from the F1NPP. The frequency of the defects corresponded to the radioactive contamination levels of the observation sites. A significant increase in deletions of the leader shoots became apparent in those that elongated after the spring of 2012, a year after the accident. These results suggest possibility that the contamination by radionuclides contributed to the morphological defects in Japanese fir trees in the area near the F1NPP.

Evolutionary pathway of pseudogenization of globin genes, α5 and ß5, in genus Oryzias.

Hemoglobin transports oxygen in many organisms and consists of α- and ß-globin chains. Previously, using molecular phylogenetic analysis, we proposed that both α- and ß-globins of teleost could be classified into four groups. We also showed that the Hd-rR strain of medaka (Oryzias latipes) inhabiting southern Japan had all four groups of globin genes but that the α- and ß-globin genes of group III were pseudogenized (α5(ψα), ß5(ψß)). Based on the small degree of nucleotide variations, the pseudogenization of ß5 was assumed to have occurred at a relatively late stage of evolution. Here, we compared the α5(ψα)-ß5(ψß) of two other strains of O. latipes and found that both α5(ψα) and ß5(ψß) of the northern Japanese and Korean strains were pseudogenized similar to those of Hd-rR. In a Philippine population (Oryzias luzonensis), α5(ψα) was also pseudogenized, but the structure was different from that of O. latipes, and ß5(ψß) was almost deleted. Interestingly, an Indonesian population (Oryzias celebensis) had α5 and ß5 genes that were deduced to be functional. Indeed, they were expressed from the young to adult development stages, and this expression pattern was consistent with the expression of α2 and ad.α1 in Hd-rR. Because α2 and ad.α1 in Hd-rR were assigned to groups I and II, respectively, we speculate that their expression patterns might be altered by pseudogenization of group III genes. These results provide a basis for further investigations of recruiting and changing expression patterns of one globin gene after pseudogenization of other globin genes during evolution.

The Parapineal Is Incorporated into the Habenula during Ontogenesis in the Medaka Fish.

The parapineal is present in many teleost families, while it is absent in several others. To find out why the parapineal is absent at adult stages in the latter families, the development of the epithalamus was examined in the medaka fish (Oryzias latipes). For this purpose, a green fluorescent protein-transgenic medaka line, in which the pineal complex (pineal and parapineal) is visible fluorescently, was used. We found that a distinct parapineal was present in the roof plate at early developmental stages. Subsequently, however, the parapineal and the associated roof plate began to be incorporated into the habenula between embryonic stages 28 and 29. Between embryonic stages 29 and 30, the entire parapineal was incorporated into the habenula. That is, the parapineal became a small caudomedial region (termed the 'parapineal domain') within the left habenula in the majority of embryos, resulting in the left-sided asymmetry of the epithalamus. Thereby the left habenula became larger and more complex than its right counterpart. In the minority of embryos, the parapineal was incorporated into the right habenula or into the habenulae on both sides. In the majority of embryos, the parapineal domain projected a fiber bundle to a subnucleus (termed the 'rostromedial subnucleus') in the left habenula. The rostromedial subnucleus sent axons, through the left fasciculus retroflexus, to the rostral region of the left half of the interpeduncular nucleus. We further found that the ratio of the left-sided phenotype was temperature dependent and decreased in embryos raised at a high temperature. The present study is the first demonstration that the supposed lack of a distinct parapineal in adult teleost fishes is due to ontogenetic incorporation into the habenula.

[A Simultaneous Determination Method with Acetonitrile-n-Hexane Partitioning and Solid-Phase Extraction for Pesticide Residues in Livestock and Marine Products by GC-MS].

A simultaneous determination method was examined for 312 pesticides (including isomers) in muscle of livestock and marine products by GC-MS. The pesticide residues extracted from samples with acetone and n-hexane were purified by acetonitrile-n-hexane partitioning, and C18 and SAX/PSA solid-phase extraction without using GPC. Matrix components such as cholesterol were effectively removed. In recovery tests performed by this method using pork, beef, chicken and shrimp, 237-257 pesticides showed recoveries within the range of 70-120% in each sample. Validity was confirmed for 214 of the target pesticides by means of a validation test using pork. In comparison with the Japanese official method using GPC, the treatment time of samples and the quantity of solvent were reduced substantially.

Proliferation following tetraploidization regulates the size and number of erythrocytes in the blood flow during medaka development, as revealed by the abnormal karyotype of erythrocytes in the medaka TFDP1 mutant.

BACKGROUND: For the delivery of oxygen, the correct size/number of erythrocytes is required for proper blood flow. RESULTS: By combined analyses of wild-type (WT) medaka and the kyoho (kyo) mutant, we found proliferation-mediated adaptation for size/number of erythrocytes in the blood flow during medaka development. Before the start of heart beating in the WT medaka, the karyotype of erythrocytes was 2N-4N. After the start of blood flow, the karyotype changed to 4N-8N with tetraploidization, and the cell size became larger. After the start of intersegmental and pharyngeal blood flow, the erythrocytes became smaller. The medaka mutant kyo showed erythrocytes of large size, and positional cloning of kyo demonstrated the candidate gene TFDP1, indicating higher polyploidization due to arrest in S-phase in erythrocytes of the kyo mutant. CONCLUSIONS: From our findings, we uncovered a previously unrecognized system for the regulation of the size/number in the blood flow:proliferation of erythrocytes following tetraploidization during embryonic development.

Low-dose total-body carbon-ion irradiations induce early transcriptional alteration without late Alzheimer's disease-like pathogenesis and memory impairment in mice.

The cause and risk factors of Alzheimer's disease (AD) are largely unknown. Studies on possible radiation-induced AD-like pathogenesis and behavioral consequences are important because humans are exposed to ionizing radiation (IR) from various sources. It was reported that total-body irradiations (TBI) at 10 cGy of low linear energy transfer (LET) X-rays to mice triggered acute transcriptional alterations in genes associated with cognitive dysfunctions. However, it was unknown whether low doses of IR could induce AD-like changes late after exposure. We reported previously that 10 cGy X-rays induced early transcriptional response of several AD-related genes in hippocampi without late AD-like pathogenesis and memory impairment in mice. Here, further studies on two low doses (5 or 10 cGy) of high LET carbonion irradiations are reported. On expression of 84 AD-related genes in hippocampi, at 4 hr after TBI, 5 cGy induced a significant upregulation of three genes (Abca1, Casp3, and Chat) and 10 cGy led to a marked upregulation of one gene (Chat) and a downregulation of three genes (Apoe, Ctsd, and Il1α), and, at 1 year after TBI, one gene (Il1α) was significantly downregulated in 10 cGy-irradiated animals. Changes in spatial learning ability and memory and induction of AD-like pathogenesis were not detected by in vivo brain imaging for amyloid-ß peptide accumulation and by immunohistochemical staining of amyloid precursor protein, amyloid-ß protein, tau, and phosphorylated tau protein. These findings indicate that low doses of carbon-ion irradiations did not cause behavioral impairment or AD-like pathological change in mice.

Effects of alendronate or alfacalcidol on bone metabolic indices and bone mineral density in patients with ophthalmologic disease treated with glucocorticoid.

OBJECTIVES: Glucocorticoid (GC) is usually used for the treatment of systemic inflammatory diseases. We performed the prospective study to clarify the effects of alendronate or alfacalcidol on bone metabolic indices and bone mineral density (BMD) in 90 patients treated with GC for ophthalmologic diseases without systemic disorders for 12 months. METHODS: BMD was measured with dual-energy X-ray absorptiometry. Serum bone-specific alkaline phosphatase (BAP) and urinary Type I collagen cross-linked N-telopeptide (NTx) were measured as bone metabolic indices. RESULTS: BMD values in the alendronate group were significantly higher than those in the alfacalcidol group during 12 months. Alendronate significantly reduced urinary NTX levels from the baseline during 12 months, although alfacalcidol did not affect them. Serum BAP levels in the alendronate group were significantly lower than those in the alfacalcidol group during 9 months. The effects of alendronate on BMD and NTx in male patients seemed to be somewhat potent compared with those in female patients. CONCLUSIONS: Alendronate is effective to prevent BMD loss and bone resorption induced by GC treatment in patients with ophthalmic diseases without systemic disorders. There might be sex differences in the potency of alendronate effects.