[Show abstract][Hide abstract] ABSTRACT: Nanosized-magnetite (MGT) is widely utilized in medicinal and industrial fields; however, its toxicological properties are not well documented. In our previous report, MGT showed genotoxicity in both in vitro and in vivo assay systems, and it was suggested that inflammatory responses exist behind the genotoxicity. To further clarify mechanisms underlying the genotoxicity, a comprehensive DNA adduct (DNA adductome) analysis was conducted using DNA samples derived from the lungs of mice exposed to MGT. In total, 30 and 42 types of DNA adducts were detected in the vehicle control and MGT-treated groups, respectively. Principal component analysis (PCA) against a subset of DNA adducts was applied and several adducts, which are deduced to be formed by inflammation or oxidative stress, as the case of etheno-deoxycytidine (εdC), revealed higher contributions to MGT exposure. By quantitative-LC-MS/MS analysis, εdC levels were significantly higher in MGT-treated mice than those of the vehicle control. Taken together with our previous data, it is suggested that inflammatory responses might be involved in the genotoxicity induced by MGT in the lungs of mice.
International Journal of Molecular Sciences 02/2015; 16(2):3474-3492. DOI:10.3390/ijms16023474 · 2.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recently, intraoperative fluorescence video angiography using indocyanine green (ICG) has been widely used in aneurysm surgery. This is a simple and useful method to confirm complete occlusion of the aneurysm lumen and preservation of blood flow in the arteries around the aneurysm. However, the observation field of ICG video angiography is limited under a microscope, making it difficult to confirm the flow in the arteries behind the parent arteries or aneurysm. The authors developed a new technique of intraoperative endoscopic ICG video angiography to assess the blood flow in perforating arteries hidden by the parent arteries or aneurysm. The endoscope emits excitation light with a wavelength of approximately 800 nm, and video images were obtained through a cut filter. The authors used this ICG fluorescence endoscope in treating 3 patients with unruptured cerebral aneurysms. During clip placement, the endoscope was inserted to confirm aneurysm occlusion. Then, ICG was intravenously administered, and the fluorescence in the vessels was observed via the endoscope as well as under the microscope. The blood flow in the perforating arteries was clearly identified, and no procedural complication occurred. The authors conclude that the technique is very useful and facilitates intraoperative real-time assessment of the patency of perforating arteries behind parent arteries or aneurysms.
Journal of Neurosurgery 06/2012; 117(2):302-8. DOI:10.3171/2012.5.JNS112300 · 3.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study examined the mutagenic activity of genistein after a nitrite treatment under acidic conditions. Nitrite-treated genistein exhibited mutagenic activity toward Salmonella typhimurium strains TA 100 and TA 98 with or without S9 mix. Nitrite-treated genistein was demonstrated by electron spin resonance to generate radicals. An instrumental analysis showed 3'-nitro-genistein to have been formed in the reaction mixture. However, 3'-nitro-genistein did not exhibit mutagenic activity toward the S. typhimurium strains, suggesting that other mutagens might also have been formed in the reaction mixture. The clastogenic properties of nitrite-treated genistein and 3'-nitro-genistein were examined by a micronucleus test with male ICR mice. Nitrite-treated genistein and 3'-nitro-genistein showed a significantly higher frequency of micronucleated reticulocytes in mice than in the control group. These results suggest that a daily oral intake of genistein and nitrite through foodstuffs might induce the formation of various mutagenic compounds in the body.
[Show abstract][Hide abstract] ABSTRACT: Multiple arterial dissections in the anterior circulation with simultaneous onset are extremely rare. We report a patient with infarctions caused by simultaneous arterial dissections in the right anterior cerebral artery and the left middle cerebral artery and discuss the characteristic feature of this vascular disorder. A 53-year-old woman presented with a severe headache and a mild aphasia. Magnetic resonance imaging revealed multiple acute cerebral infarctions in the left temporal and right frontal lobes. The initial angiographic findings revealed arterial dissections of the anterior cerebral, left middle cerebral, and right vertebral arteries. The follow-up angiographic examination found improvement of the stenosis in both the anterior cerebral and middle cerebral arteries. We have concluded that the lesion of the vertebral artery was not in an acute stage, because no interval change was seen during the radiologic evaluation. She underwent conservative therapy, and her symptoms disappeared. Multiple arterial dissections are rare, especially those developing simultaneously in different arteries. This is the first case of multiple arterial dissections of the different arteries in the anterior circulation manifesting cerebral infarction simultaneously.
Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 04/2012; 22(8). DOI:10.1016/j.jstrokecerebrovasdis.2012.03.004 · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract The genotoxic effects of multi-walled carbon nanotubes (MWCNTs) were examined by using in vitro and in vivo assays. MWCNTs significantly induced micronuclei in A549 cells and enhanced the frequency of sister chromatid exchange (SCE) in CHO AA8 cells. When ICR mice were intratracheally instilled with a single dose (0.05 or 0.2 mg/animal) of MWCNTs, DNA damage of the lungs, analysed by comet assay, increased in a dose-dependent manner. Moreover, DNA oxidative damage, indicated by 8-oxo-7,8-dihydro-2'-deoxyguanosine and heptanone etheno-deoxyribonucleosides, occurred in the lungs of MWCNT-exposed mice. The gpt mutation frequencies significantly increased in the lungs of MWCNT-treated gpt delta transgenic mice. Transversions were predominant, and G:C to C:G was clearly increased by MWCNTs. Moreover, many regions immunohistochemically stained for inducible NO synthase and nitrotyrosine were observed in the lungs of MWCNT-exposed mice. Overall, MWCNTs were shown to be genotoxic both in in vitro and in vivo tests; the mechanisms probably involve oxidative stress and inflammatory responses.
[Show abstract][Hide abstract] ABSTRACT: The signal transducers and activators of transcription 3 (STAT3) has been suggested to have neuroprotective roles. However, its role in ischemic preconditioning (PC) is still obscure. In this study, we examined the phosphorylation status of ser727-STAT3, which is necessary for activation of STAT3, and its roles in a rat global ischemia model with or without PC. PC was induced by 3 min of nonlethal ischemia 48 h before 5 min of lethal ischemia. Western blot analysis showed that phospho-ser727-STAT3 significantly increased from 8 to 48 h after nonlethal ischemia, while it increased only for 1h after lethal ischemia and returned to the baseline within 24h. In the preconditioned brains, phospho-ser727-STAT3 was induced at 1 to 4h after lethal ischemia, and decrease of its levels delayed compared to the nonconditioned brains. Immunohistochemistry revealed that phospho-ser727-STAT3 was expressed mainly in CA1 neurons after nonlethal ischemia. Additionally, STAT3 inhibitor peptide treatment prevented PC induced-neuroprotection. These results indicate that phosphorylation of ser727-STAT3 plays an important role in PC induced- neuroptotection.
Brain research 11/2011; 1422(2):39-45. DOI:10.1016/j.brainres.2011.08.076 · 2.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Experimental and clinical studies have revealed that angiotensin II type 1 receptor blocker has protective effects against ischemic brain injury, but the mechanism is still obscure. Angiotensin II type 1 receptor blocker may also have effects on neurogenesis through the activation of unblocked angiotensin II type 2 receptors. In this study, we showed that valsartan significantly suppressed superoxide production and cytochrome C release into the cytosol after transient forebrain ischemia and consequently attenuated ischemic neuronal damage without affecting the blood pressure in rats. However, valsartan has none of the expected effects on neurogenesis after ischemia. These results suggest that valsartan has neuroprotective effects on ischemic injury through the suppression of oxidative stress and mitochondrial injury.
[Show abstract][Hide abstract] ABSTRACT: Nanomaterials are being utilized for many kinds of industrial products, and the assessment of genotoxicity and safety of nanomaterials is therefore of concern. In the present study, we examined the genotoxic effects of fullerene (C60) and kaolin using in vitro and in vivo genotoxicity systems. Both nanomaterials significantly induced micronuclei and enhanced frequency of sister chromatid exchange (SCE) in cultured mammalian cells. When ICR mice were intratracheally instilled with these nanomaterials, DNA damage of the lungs increased significantly that of the vehicle control. Formation of DNA adducts in the lungs of mice exposed to nanomaterials were also analyzed by stable isotope dilution LC-MS/MS. 8-Oxodeoxyguanosine and other lipid peroxide related adducts were increased by 2- to 5-fold in the nanomaterial-exposed mice. Moreover, multiple (four consecutive doses of 0.2 mg per animal per week) instillations of C60 or kaolin, increased gpt mutant frequencies in the lungs of gpt delta transgenic mice. As the result of mutation spectrum analysis, G:C to C:G transversions were commonly increased in the lungs of mice exposed to both nanomaterials. In addition, G:C to A:T was increased in kaolin-exposed mice. In immunohistochemical analysis, many regions of the lungs that stained positively for nitrotyrosine (NT) were observed in mice exposed to nanomaterials. From these observations, it is suggested that oxidative stress and inflammatory responses are probably involved in the genotoxicity induced by C60 and kaolin.
Genes and Environment 01/2011; 33(1):14-20. DOI:10.3123/jemsge.33.14
[Show abstract][Hide abstract] ABSTRACT: In this report, a rare case of dysembryoplastic neuroepithelial tumor (DNET) initially presented as a small white matter lesion with calcification adjacent to the lateral ventricle and extending to the frontal cortex after 7 years. This 1-year-old boy initially suffered from partial seizures. Initial CT revealed a small, low-density area surrounding a tiny calcified mass in the deep white matter of the left frontal lobe. Seven years later, his seizures had become intractable to antiepileptic agents, and MR imaging demonstrated a relatively large mass extending from the calcified lesion up to the adjacent cortical surface. He underwent surgery and the tumor was subtotally removed. Histological examination of the tumor verified it as a DNET consisting of clusters of small oligodendrocytes with floating neurons in the mucoid background. The pattern of the tumor progression in this case suggests that a DNET in the cortex originates from the subependymal germinal layer near the ventricle.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
Manufactured nano/microparticles, CB, C60 and kaolin, were shown to be genotoxic in in vitro and in vivo assay systems.