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1.
Radiat Res ; 201(2): 115-125, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38211765

ABSTRACT

The effects of long-term low-dose X-ray irradiation on the outer root sheath (ORS) cells of C3H/He mice were investigated. Mice were irradiated with a regime of 100 mGy/day, 5 days/week, for 12 weeks (Group X) and the results obtained were compared to those in a non-irradiated control (Group C). Potential protection against ORS cells damage induced by this exposure was investigated by adding the stable nitroxide radical 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) at 1 mM to the drinking water of mice (Group X + TEMPOL). The results obtained were compared with Group C and a non-irradiated group treated with TEMPOL (Group C + TEMPOL). After fractionated X-ray irradiation, skin was removed and ORS cells were examined by hematoxylin and eosin staining and electron microscopy for an abnormal nuclear morphology and nuclear condensation changes. Fractionated X-irradiated mice had an increased number of ORS cells with an abnormal nuclear morphology as well as nuclear condensation changes. Sections were also immunohistochemically examined for the presence of TdT-mediated dUTP nick-end labeling (TUNEL), 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), vascular endothelial growth factor (VEGF), nitrotyrosine, heme oxygenase 1 (HO-1), and protein gene product 9.5 (PGP 9.5). Significant increases were observed in TUNEL, 8-OHdG, and 4-HNE levels in ORS cells from mice in Group X. Electron microscopy also showed irregular shrunken ORS cells in Group X. These changes were prevented by the presence of TEMPOL in the drinking water of the irradiated mice. TEMPOL alone had no significant effects. These results suggest that fractionated doses of radiation induced oxidative damage in ORS cells; however, TEMPOL provided protection against this damage, possibly as a result of the rapid reaction of this nitroxide radical with the reactive oxidants generated by fractionated X-ray irradiation.


Subject(s)
Drinking Water , Nitrogen Oxides , Spin Labels , Animals , Mice , X-Rays , Hair Follicle , Vascular Endothelial Growth Factor A , Mice, Inbred C3H , Cyclic N-Oxides/pharmacology , Cyclic N-Oxides/therapeutic use
2.
Pharmaceutics ; 15(11)2023 Oct 26.
Article in English | MEDLINE | ID: mdl-38004516

ABSTRACT

Radiotherapy, in which X-rays are commonly used, is one of the most effective procedures for treating cancer. However, some cancer cells become resistant to radiation therapy, leading to poor prognosis. Therefore, a new therapeutic method is required to prevent cancer cells from acquiring radiation resistance. Photodynamic therapy (PDT) is a cancer treatment that uses photosensitizers, such as porphyrin compounds, and low-powered laser irradiation. We previously reported that reactive oxygen species (ROS) derived from mitochondria induce the expression of a porphyrin transporter (HCP1) and that laser irradiation enhances the cytotoxic effect. In addition, X-ray irradiation induces the production of mitochondrial ROS. Therefore, radioresistant cancer cells established with continuous X-ray irradiation would also overexpress ROS, and photodynamic therapy could be an effective therapeutic method. In this study, we established radioresistant cancer cells and examined the therapeutic effects and mechanisms with photodynamic therapy. We confirmed that X-ray-resistant cells showed overgeneration of mitochondrial ROS and elevated expression of HCP1, which led to the active accumulation of porphyrin and an increase in cytotoxicity with laser irradiation. Thus, photodynamic therapy is a promising treatment for X-ray-resistant cancers.

3.
J Clin Biochem Nutr ; 72(2): 107-116, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36936873

ABSTRACT

The impact of radiation-induced hydrogen peroxide (H2O2) on the biological effects of X-rays and carbon-ion beams was investigated using a selenium-deficient (SeD) mouse model. Selenium is the active center of glutathione peroxidase (GSH-Px), and SeD mice lack the ability to degrade H2O2. Male and female SeD mice were prepared by feeding a torula yeast-based SeD diet and ultrapure water. Thirty-day survival rates after whole-body irradiation, radiation-induced leg contracture, and MRI-based redox imaging of the brain were assessed and compared between SeD and normal mice. Thirty-day lethality after whole-body 5.6 Gy irradiation with X-rays or carbon-ion beams was higher in the SeD mice than in the normal mice, while SeD did not give the notable difference between X-rays and carbon-ion beams. SeD also did not affect the maximum leg contracture level after irradiation with carbon-ion beams, but delayed the leg contraction rate. In addition, no marked effects of SeD were observed on variations in the redox status of the brain after irradiation. Collectively, the present results indicate that SeD slightly altered the biological effects of X-rays and/or carbon-ion beams. GSH-Px processes endogenous H2O2 generated through mitochondrial respiration, but does not have the capacity to degrade H2O2 produced by irradiation.

4.
J Clin Biochem Nutr ; 72(2): 117-125, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36936881

ABSTRACT

High efficacy and minimal toxicity radioprotectors are desirable options for the hazards posed by nuclear medical and energy technologies and the dangers presented by nuclear weapons in an unstable global situation. Although cysteamine is an effective radioprotector, it has considerable toxicity. In this study, the protective effects of the less toxic organosulfur compounds 2-aminoethylthiosulfate (AETS), thiotaurine (TTAU), and hypotaurine (HTAU) against X-ray damage in mice were compared with that of cysteamine. Intraperitoneal injection of either AETS or cysteamine (2.2 mmol/kg body weight) 30 min before X-ray irradiation (7.0 Gy) provided 100% survival for 30 days, limited the decrease in erythrocytes and neutrophils over 9 days, and reduced damage to bone marrow and spleen over 9 days. Neither TTAU nor HTAU provided any protection. In mice, 30 min after AETS administration, non-protein thiol content increased in the spleen, indicating cysteamine generation by AETS hydrolysis, the active protective species of AETS. All examined compounds scavenged •OH under diffusion control in aqueous solution, which is inconsistent with the difference in the protective effects among the compounds. The results indicate that AETS protects animals from ionizing radiation by several mechanisms, including scavenging •OH as cysteamine.

5.
Cancers (Basel) ; 14(15)2022 Jul 27.
Article in English | MEDLINE | ID: mdl-35892902

ABSTRACT

The impact of the site of the Fenton reaction, i.e., hydroxyl radical (•OH) generation, on cytotoxicity was investigated by estimating cell lethality in rat thymocytes. Cells were incubated with ferrous sulfate (FeSO4) and hydrogen peroxide (H2O2), or pre-incubated with FeSO4 and then H2O2 was added after medium was replaced to remove iron ions or after the medium was not replaced. Cell lethality in rat thymocytes was estimated by measuring cell sizes using flow cytometry. High extracellular concentrations of FeSO4 exerted protective effects against H2O2-induced cell death instead of enhancing cell lethality. The pre-incubation of cells with FeSO4 enhanced cell lethality induced by H2O2, whereas a pre-incubation with a high concentration of FeSO4 exerted protective effects. FeSO4 distributed extracellularly or on the surface of cells neutralized H2O2 outside cells. Cytotoxicity was only enhanced when the Fenton reaction, i.e., the generation of •OH, occurred inside cells. An assessment of plasmid DNA breakage showed that •OH induced by the Fenton reaction system did not break DNA. Therefore, the main target of intracellularly generated •OH does not appear to be DNA.

6.
J Clin Biochem Nutr ; 70(3): 213-221, 2022 May.
Article in English | MEDLINE | ID: mdl-35692674

ABSTRACT

The quantitative measurement of free radicals in liquid using an X-band electron paramagnetic resonance (EPR) was systematized. Quantification of free radicals by EPR requires a standard sample that contains a known spin amount/concentration. When satisfactory reproducibility of the sample material, volume, shape, and positioning in the cavity for EPR measurements can be guaranteed, a sample tested and a standard can be directly compared and the process of quantification can be simplified. The purpose of this study was to simplify manual quantitative EPR measurement. A suitable sample volume for achieving a stable EPR intensity was estimated. The effects of different solvents on the EPR sensitivity were compared. The stability and reproducibility of the EPR intensity of standard nitroxyl radical solutions were compared among different types of sample tubes. When the sample tubes, sample volumes, and/or solvents were the same, the EPR intensity was reproduced with an error of 2% or less for µM samples. The quantified sample and the standard sample in the same solvent and the same volume drawn into the same sample tube was able to be directly compared. The standard sample for quantification should be measured just before or after every daily experiment.

7.
Geriatr Gerontol Int ; 22(5): 441-448, 2022 May.
Article in English | MEDLINE | ID: mdl-35355401

ABSTRACT

AIM: Diabetes confers a high risk of developing poor health in later life in women. Based on the Developmental Origins of Health and Disease theory, the present study was undertaken to investigate the efficacy of perinatal fat restriction in maternal high-fat-exposed female offspring to maintain glucose homeostasis in later life between adulthood and aging. METHODS: Low-fat dietary intervention during either gestation or lactation was performed using a high-fat diet-induced maternal obesity mouse model (HFD mice). Physiological metabolic parameters, including body weight and serum levels of total cholesterol and triglycerides, were monitored. Glucose tolerance test and insulin sensitivity test were performed in 12- and 70-week-old offspring. Insulin-positive islet cells were also observed using immunohistochemical staining. RESULTS: HFD significantly induced abnormal weight gain, hyperlipidemia and impairment of both glucose tolerance and insulin sensitivity in offspring. Standard diet intake after weaning improved weight gain, serum total cholesterol level and glucose tolerance, but not insulin sensitivity, in 70-week-old offspring. Only perinatal fat restriction during both gestation and lactation, followed by standard food intake for the rest of their life, provided adequate efficacy to restore insulin sensitivity in aging female progeny. CONCLUSIONS: Perinatal low-fat intervention may prevent deterioration of glucose metabolism. To improve the health status over a female's lifespan, appropriate nutritional intervention during the early developmental stage may reset the disease trajectory and prevent the onset and development of diabetes. Geriatr Gerontol Int 2022; 22: 441-448.


Subject(s)
Insulin Resistance , Adult , Aging , Animals , Cholesterol , Female , Glucose/metabolism , Humans , Insulin/metabolism , Mice , Pregnancy , Weight Gain
8.
Antioxidants (Basel) ; 11(2)2022 Feb 09.
Article in English | MEDLINE | ID: mdl-35204222

ABSTRACT

Pterostilbene (PTS), a methylated analog of resveratrol (RSV), has recently attracted much attention due to its enhanced bioavailability compared to RSV. However, little is known about the radical-scavenging mechanism of PTS. In this study, we investigated the effect of Mg(ClO4)2 on the scavenging reaction of galvinoxyl radical (GO•) by PTS in acetonitrile (MeCN). GO• was used as a model for reactive oxygen radicals. The second-order rate constant (kH) for the GO•-scavenging reaction by PTS was more than threefold larger than that by RSV, although thermodynamic parameters, such as the relative O-H bond dissociation energies of the phenolic OH groups, ionization potentials, and HOMO energies calculated by the density functional theory are about the same between PTS and RSV. The oxidation peak potential of PTS determined by the cyclic voltammetry in MeCN (0.10 M Bu4NClO4) was also virtually the same as that of RSV. On the other hand, no effect of Mg (ClO4)2 on the kH values was observed for PTS, in contrast to the case for RSV. A kinetic isotope effect of 3.4 was observed when PTS was replaced by a deuterated PTS. These results suggest that a one-step hydrogen-atom transfer from PTS to GO• may be the rate-determining step in MeCN.

9.
J Nutr Biochem ; 104: 108971, 2022 06.
Article in English | MEDLINE | ID: mdl-35196575

ABSTRACT

The long-term effect of changes in maternal dietary composition during pregnancy on the offspring's metabolic homeostasis is uncertain. We aimed to investigate the long-term effects of maternal balanced low-fat interventions on metabolic homeostasis of the offspring using a mouse model of gestational obesity induced by a high-fat diet (HFD). Male newborns in the balanced low-fat intervention group had significantly lower serum insulin and higher serum adiponectin levels than those in the HFD group. Changes in maternal dietary composition improved glucose tolerance in pups at 3 and 12 weeks of age. We also performed transcriptomic analysis of the liver in neonatal and 3-week-old pups. Genes in the peroxisome proliferator-activated receptor signaling pathway were significantly down-regulated in neonates in the balanced low-fat intervention group compared with the HFD group. A maternal balanced low-fat diet fully compensated for the detrimental effects of a maternal HFD on glucose metabolism, insulin tolerance, circulating insulin, dyslipidemia, and body weight gain in male offspring by changing the gene expression profile. These data suggest that maternal balanced low-fat intervention is critical for improving the metabolic health of future generations.


Subject(s)
Prenatal Exposure Delayed Effects , Body Weight , Diet, High-Fat/adverse effects , Female , Homeostasis , Humans , Infant, Newborn , Insulin/metabolism , Male , Obesity/metabolism , Pregnancy , Prenatal Exposure Delayed Effects/genetics
10.
Molecules ; 27(3)2022 Jan 18.
Article in English | MEDLINE | ID: mdl-35163857

ABSTRACT

The linear-density (number of molecules on an arbitrary distance) of X-ray-induced markedly dense hydroxyl radicals (•OH) in water was estimated based on EPR spin-trapping measurement. A lower (0.13 mM-2.3 M) concentration series of DMPO water solutions and higher (1.7-6.0 M) concentration series of DMPO water solutions plus neat DMPO liquid (8.8 M as DMPO) were irradiated with 32 Gy of X-rays. Then, the yield of DMPO-OH in DMPO water solutions and the total spin-adduct of DMPO in neat DMPO were quantified. For the higher concentration DMPO series, the EPR peak area was estimated by double integration, and the baseline correction of the integral spectrum is necessary for accurate estimation of the peak area. The preparation of a suitable standard sample corresponding to the electric permittivity according to DMPO concentration was quite important for quantification of DMPO-OH, especially in DMPO concentration beyond 2 M. The linear-density of •OH generation in water by X-ray irradiation was estimated from the inflection point on the plot of the DMPO-OH yield versus DMPO linear-density. The linear-density of X-ray-induced markedly dense •OH was estimated as 1168 µm-1, which was converted to 0.86 nm as the intermolecular distance and 2.6 M as the local concentration.

11.
Free Radic Res ; 55(6): 714-719, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34519601

ABSTRACT

Linear energy transfer (LET) dependence of yields of O2-dependent and O2-independent hydrogen peroxide (H2O2) in water irradiated by ionizing radiation was investigated. The radiation-induced hydroxyl radical (•OH) generation in an aqueous solution was reported to occur in two different localization densities, the milli-molar (relatively sparse) and/or molar (markedly-dense) levels. In the milli-molar-level •OH generation atmosphere, •OH generated at a molecular distance of ∼7 nm are likely unable to interact. However, in the molar-level •OH generation atmosphere, several •OH were generated with a molecular distance of 1 nm or less, and two •OH can react to directly make H2O2. An aliquot of ultra-pure water was irradiated by 290-MeV/nucleon carbon-ion beams at the Heavy-Ion Medical Accelerator in Chiba (HIMAC, NIRS/QST, Chiba, Japan). Irradiation experiments were performed under aerobic or hypoxic (<0.5% oxygen) conditions, and several LET conditions (13, 20, 40, 60, 80, or >100 keV/µm). H2O2 generation in irradiated samples was estimated by three methods. The amount of H2O2 generated per dose was estimated and compared. O2-independent H2O2 generation, i.e. H2O2 generation under hypoxic conditions, increased with increasing LET. On the other hand, the O2-dependent H2O2 generation, i.e. subtraction of H2O2 generation under hypoxic conditions from H2O2 generation under aerobic conditions, decreased with increasing LET. This suggests that the markedly-dense •OH generation is positively correlated with LET. High-LET beams generate H2O2 in an oxygen-independent manner.


Subject(s)
Carbon/chemistry , Hydrogen Peroxide/metabolism , Ions/chemistry , Linear Energy Transfer/physiology , Oxygen/chemistry , Water/chemistry
12.
J Clin Biochem Nutr ; 68(2): 123-130, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33879963

ABSTRACT

Relatively young (4-week-old) selenium deficient (SeD) mice, which lack the activity of selenium-dependent glutathione peroxidase (GSH-Px) isomers, were prepared using torula yeast-based SeD diet. Mice were fed the torula yeast-based SeD diet and ultra-pure water. Several different timings for starting the SeD diet were assessed. The weekly time course of liver comprehensive GSH-Px activity after weaning was monitored. Protein expression levels of GPx1 and 4 in the liver were measured by Western blot analysis. Gene expression levels of GPx1, 2, 3, 4, and 7 in the liver were measured by quantitative real-time PCR. Apoptotic activity of thymocytes after hydrogen peroxide (H2O2) exposure was compared. Thirty-day survival rates after whole-body X-ray irradiation were estimated. Pre-birth or right-after-birth starting of the SeD diet in dams was unable to lead to creation of SeD mice due to neonatal death. This suggests that Se is necessary for normal birth and healthy growing of mouse pups. Starting the mother on the SeD diet from 2 weeks after giving birth (SeD-trial-2w group) resulted in a usable SeD mouse model. The liver GSH-Px activity of the SeD-trial-2w group was almost none from 4 week olds, but the mice survived for more than 63 weeks. Protein and gene expression of GPx1 was suppressed in the SeD-trial-2w group, but that of GPx4 was not. The thymocytes of the SeD-trial-2w group were sensitive to H2O2-induced apoptosis. The SeD-trial-2w group was sensitive to whole-body X-ray irradiation compared with control mice. The SeD-trial-2w model may be a useful animal model for H2O2/hydroperoxide-induced oxidative stress.

13.
Free Radic Res ; 55(4): 450-460, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33729087

ABSTRACT

Quantification and local density estimation of radiation-induced reactive oxygen species (ROS) were described focusing on our recent and related studies. Charged particle radiation, i.e. heavy-ion beams, are currently utilized for medical treatment. Differences in ROS generation properties between photon and charged particle radiation may lead to differences in the quality of radiation. Radiation-induced generation of ROS in water was quantified using several different approaches to electron paramagnetic resonance (EPR) techniques. Two different densities of localized hydroxyl radical (•OH) generation, i.e. milli-molar and molar levels, were described. Yields of sparse •OH decreased with increasing linear energy transfer (LET), the yield total •OH was not affected by LET. In the high-density, molar level, •OH environment, •OH can react and directly make hydrogen peroxide (H2O2), and then possible to form a high-density H2O2 cluster. The amount of total oxidation reactions caused by oxidative ROS, such as •OH and hydroperoxyl radial (HO2•), was decreased with increasing LET. Possibilities of the sequential reactions were discussed based on the initial localized density at the generated site. Water-induced ROS have been well investigated. However, little is known about radiation-induced free radical generation in lipidic conditions. Radio-chemistry to understand the sequential radio-biological effects is still under development.


Subject(s)
Hydrogen Peroxide/metabolism , Hydroxyl Radical/metabolism , Reactive Oxygen Species/metabolism , Electron Spin Resonance Spectroscopy , Hydrogen Peroxide/chemistry , Hydroxyl Radical/chemistry , Linear Energy Transfer , Oxidation-Reduction , Reactive Oxygen Species/chemistry
14.
Free Radic Res ; 55(4): 481-489, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32896187

ABSTRACT

The density of hydroxyl radical (•OH) generation by degeneration of hydrogen peroxide (H2O2) during UVB irradiation and in a Fenton reaction system was estimated. The purpose of this study was to evaluate whether these reaction systems generate spatially uniform or inhomogeneous •OH from H2O2 in the reaction mixture. A series of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) solutions of several concentrations (0.13‒1661 mM) were prepared. For UVB irradiation, 1 µl of 98 mM, 980 mM, or 9.8 M H2O2 solution was added to a 100-µl aliquot of DMPO solution, and the reaction mixture was irradiated with UVB. For the Fenton reaction, 1 µl of 98 mM H2O2 and 1 µl of 100 mM FeSO4 were added to a 100-µl aliquot of DMPO solution. After UVB irradiation or adding FeSO4, the entire volume of the reaction mixture was drawn into PTFE tubing and measured by X-band EPR. The DMPO-OH concentration in the reaction mixture was plotted versus the molecular density of DMPO, and the density of •OH generation was estimated from an inflection point on the plotted profile. The local densities of the UV-induced •OH in the H2O2 water solutions depended on the concentration of H2O2 in the solution, and were likely localized. The energy absorption process of photons was suspected to occur in a step-wise manner in a limited volume. •OH generation in the Fenton reaction system was expected to be uniformly distributed, but inhomogeneous •OH generation was observed at the molecular level.


Subject(s)
Cyclic N-Oxides/chemistry , Hydrogen Peroxide/chemistry , Hydroxyl Radical/chemical synthesis , Ultraviolet Rays , Hydroxyl Radical/chemistry , Molecular Structure , Solutions
15.
Laryngoscope ; 131(4): E1287-E1295, 2021 04.
Article in English | MEDLINE | ID: mdl-32835430

ABSTRACT

OBJECTIVE: Identification of undefined risk factors will be crucial for the development of therapeutic strategies in hearing impairment. Platelets are likely to affect the development of sudden sensorineural hearing loss, which is a primary risk factor for permanent hearing impairment. This implies that abnormal platelets might contribute to long-term hearing loss. This study investigated the role of platelets in the development of hearing impairment over a 5-year period. METHODS: This study was a retrospective cohort study and consisted of a population-based survey, which was performed for 1,897 participants in 2014 to 2019. To evaluate the effect of platelet level on hearing ability, the subjects were divided into two groups: a high-normal platelet group (25 ∼ 40 × 104 cells/µL) and a low-normal platelet group (15 ∼ 25 × 104 cells/µL). Subjects were defined as having hearing impairment when pure tone audiometry was over 25 dB HL in either ear (tested in 2017 and 2019). Incidence of hearing impairment was analyzed. RESULTS: Incidence of hearing impairment at low frequencies was significantly higher in the low-normal platelet group than in the high-normal group year over year. Low-normal platelet count associated with low-frequency hearing impairment (LFHI) incidence (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.15-4.76). In the low-normal platelet group, subjects whose counts declined from baseline developed more LFHI than those whose counts increased over time. Further, decreasing platelets appeared to be an independent risk factor contributing to the incidence of LFHI (OR, 2.10; 95%CI, 1.09-4.06) in the low-normal platelet group. CONCLUSION: Both a low-normal platelet and a declining platelet count were independently associated with the incidence of LFHI. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E1287-E1295, 2021.


Subject(s)
Hearing Loss, Sudden/blood , Platelet Count , Adult , Female , Hearing Loss, Sudden/epidemiology , Humans , Japan/epidemiology , Male , Prevalence , Retrospective Studies , Risk Factors
16.
J Clin Biochem Nutr ; 67(2): 174-178, 2020 Sep.
Article in English | MEDLINE | ID: mdl-33041515

ABSTRACT

To clarify a possible index for long-term and low-dose irradiation, the effects of repeated low-dose X-ray irradiation on the amount of melanin-derived radicals in mouse hair and tail skin were investigated. Eight-week-old female C3H/HeSlc mice were irradiated by X-rays at a dose of 100 mGy/day 5 days/week for 12 weeks. Similarly, a 4-week irradiation experiment was carried out at 500 mGy/day for C3H/HeSlc mice, or at 10, 100, and 500 mGy/day for 8-week-old female C57BL/6NCrSlc mice. The hair sample (~10 mg) was weighed accurately and stuffed into a plastic tube. The 2-cm tip of the tail was sampled and lyophilized. Melanin-derived radicals in hair and tail samples were measured by X-band electron paramagnetic resonance spectrometry. After X-ray irradiation at 100 mGy/day for 12 weeks, no difference was found in the amount of melanin-derived radicals in the hair of the irradiated and non-irradiated groups. X-ray irradiation at 500 mGy/day for 4 weeks increased the amount of melanin-derived radicals in hair compared with the non-irradiated group, but the baseline amount of melanin-derived radicals in hair was varied. The amount of melanin-derived radicals in the tail skin dose-dependently increased. Melanin-derived radicals in skin may be an endogenous marker for long-term and low-dose irradiation.

17.
Free Radic Res ; 54(5): 360-372, 2020 May.
Article in English | MEDLINE | ID: mdl-32450709

ABSTRACT

The formation of highly concentrated hydrogen peroxide (H2O2) clusters (localized circumstance) in an aqueous solution during X-ray irradiation was demonstrated. The relationship between H2O2 concentration and hydrogen donor-independent reduction of nitroxyl radicals was examined. The method to measure the distance between the clusters (localized circumstance) was assessed by comparing the simulation and the experimental results. Reaction mixtures containing a nitroxyl redox probe, 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) and 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CmP) at 0.1 mM were prepared containing several different concentrations (1.0 mM‒9.8 M) of H2O2. The reaction mixture was irradiated by 12000 µW/cm2 UVB for 2 min, and reduction of the electron paramagnetic resonance (EPR) signal of the nitroxyl radicals was measured. An aliquot (2 µL) of 200 mM K3[Fe(CN)6] or FeCl3 solution was added to 200 µL of the reaction mixture, and the time course of the EPR signal of the nitroxyl radicals was measured. To estimate the distance between the H2O2 clusters, a series of nitroxyl radical solutions with several different concentrations (0.06 µM‒2.28 mM) was irradiated with X-rays, and the degree of reduction of nitroxyl radicals in each sample was measured. UVB, K3[Fe(CN)6], or FeCl3-induced EPR signal loss of the nitroxyl radicals was observed with H2O2 concentrations greater than 10 mM or 100 mM, respectively. The EPR signal loss of nitroxyl radicals, TEMPOL or CmP, may occur in highly concentrated H2O2 circumstances after oxidative stimulation. Plotting the X-ray-induced reduction of nitroxyl radicals versus their density revealed the high-concentration H2O2 clusters to be separated by 40‒47 nm. Ionizing irradiation of an aqueous solution creates a localized highly concentrated H2O2 environment.


Subject(s)
Hydrogen Peroxide/analysis , Water/chemistry , Hydrogen Peroxide/chemical synthesis , Molecular Structure , Nitrogen Oxides/chemistry , Solutions , X-Rays
18.
World Neurosurg ; 139: 196-199, 2020 07.
Article in English | MEDLINE | ID: mdl-32311552

ABSTRACT

BACKGROUND: Incidence of chronic subdural hematoma (CSH) associated with metastases of extraneural malignancies is rare. We report a rare case of CSH wherein most of the CSH cavity was occupied with metastatic cancer cells; in addition, we review the literature. CASE DESCRIPTION: A 68-year-old man with a history of gastric cancer presented to our hospital with dysarthria and shoulder paralysis; CSH was diagnosed from preoperative imaging findings. When the hematoma was removed via a small craniotomy, besides the hematoma, we observed an abnormal mass of tissue in the capsule. Pathologically, the mass was consistent with the findings of metastatic gastric cancer. Although the symptoms immediately disappeared postoperatively, a symptomatic acute subdural hematoma with midline shift was observed on postoperative day 27. Emergency craniotomy and hematoma and tumor removal were performed. Pathologic examination showed hemorrhagic necrosis in the tumor, which had not been initially observed. The postoperative course progressed without hematoma recurrence. CONCLUSIONS: To the best of our knowledge, this is the first report of a CSH accompanied by tumor metastasis in most of the CSH cavity. Although rare, if a patient with cancer has CSH, the CSH should be treated considering the possibility of metastasis.


Subject(s)
Adenocarcinoma/secondary , Central Nervous System Neoplasms/secondary , Hematoma, Subdural, Acute/surgery , Hematoma, Subdural, Chronic/surgery , Stomach Neoplasms/pathology , Adenocarcinoma/complications , Adenocarcinoma/surgery , Aged , Central Nervous System Neoplasms/complications , Central Nervous System Neoplasms/surgery , Craniotomy , Drainage , Hematoma, Subdural, Acute/etiology , Hematoma, Subdural, Chronic/etiology , Humans , Male , Recurrence
19.
J Diabetes Investig ; 11(6): 1643-1650, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32298536

ABSTRACT

AIMS/INTRODUCTION: Low birthweight is reportedly associated with type 2 diabetes mellitus; however, this association has not been confirmed in the Japanese population, and whether high birthweight is associated with type 2 diabetes mellitus is controversial. We aimed to investigate the association between birthweight and type 2 diabetes mellitus among a general Japanese population. MATERIALS AND METHODS: Overall 1,135 middle- to old-aged Japanese men and women were enrolled in the Toon Health Study. A 75-g oral glucose tolerance test was used to diagnose type 2 diabetes mellitus, and a questionnaire survey about birthweight was administered. The association between birthweight and the prevalence of type 2 diabetes mellitus in later life of the participants was examined using multivariable logistic regression analysis. Stratified analysis by current body mass index was also carried out. RESULTS: The mean age was 56.5 ± 12.2 years. Type 2 diabetes mellitus was observed in 9.3% of the participants in this study. Compared with the reference group (2,500-3,999 g), the adjusted odds ratio of the low-birthweight group (<2,500 g) for type 2 diabetes mellitus was 2.46 (95% confidence interval 1.48-4.10). The association between the high-birthweight group (≥4000 g) and type 2 diabetes mellitus was not significant after including family history of diabetes in the multivariable model. The odds ratio of the low-birthweight group for type 2 diabetes mellitus was higher in the overweight/obese group than in the non-overweight group. CONCLUSIONS: Low birthweight was associated with an increased risk of type 2 diabetes mellitus in a Japanese population, especially in overweight/obese individuals.


Subject(s)
Birth Weight , Body Mass Index , Diabetes Mellitus, Type 2/epidemiology , Adult , Aged , Biomarkers/analysis , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Infant, Low Birth Weight , Infant, Newborn , Japan/epidemiology , Male , Middle Aged , Prognosis , Prospective Studies , Risk Factors
20.
Clin Neurol Neurosurg ; 194: 105831, 2020 07.
Article in English | MEDLINE | ID: mdl-32294578

ABSTRACT

OBJECTIVES: Infected subdural hematoma (ISH) is a rare type of subdural empyema, with fewer than 50 cases reported to date. Its radiological features have not been adequately described, making diagnosis challenging. At our institution, two adults presented with ISH, which exhibited a characteristic shape on preoperative imaging. PATIENTS AND METHODS: This study examined ISH cases and chronic subdural hematoma (CSH) cases that underwent surgery at the Ishikawa Prefectural Central Hospital between January 2016 and March 2018. To distinguish ISH from CSH, we focused on three specific radiological features: the biconvex shape of the hematoma, presence of a high-density region at the lower end of the hematoma on plain computed tomography (CT), and presence of a hyper-intense signal within the hematoma on diffusion weighted imaging (DWI). RESULTS: We analyzed 30 ISH (current and previously reported) and 102 CSH cases in our study. We found no statistically significant associations between the hematoma type (ISH or CSH) and the presence of a high-density region at the lower end of the hematoma on plain CT (p = 0.13) or the presence of hyperintensity in the hematoma on DWI (p = 1.00). Conversely, a statistically significant association was found between the hematoma type and the biconvex shape of the hematoma (p < 0.01). CONCLUSION: These results suggest that the shape of the hematoma on imaging provides valuable information that can be used to differentiate ISH from CSH and optimize therapeutic approaches.


Subject(s)
Central Nervous System Infections/diagnostic imaging , Hematoma, Subdural, Chronic/diagnostic imaging , Hematoma, Subdural/diagnostic imaging , Aged, 80 and over , Central Nervous System Infections/psychology , Central Nervous System Infections/surgery , Cognition Disorders/etiology , Cognition Disorders/psychology , Diagnosis, Differential , Diffusion Magnetic Resonance Imaging , Fatal Outcome , Hematoma, Subdural/psychology , Hematoma, Subdural/surgery , Hematoma, Subdural, Chronic/surgery , Humans , Male , Neurosurgical Procedures , Tomography, X-Ray Computed , Treatment Outcome
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