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Article: Time-course changes in DNA damage of corneal epithelial cells in rabbits following ocular instillation with genotoxic compounds.

Tahara, Haruna / Yamagiwa, Yoshinori / Haranosono, Yu / Kurata, Masaaki

Genes and environment : the official journal of the Japanese Environmental Mutagen Society

2022 Volume 44, Issue 1, Page(s) 14

Abstract: Background: In eye-drop drug development, the additional genotoxicity tests in some cases might be necessary to assess genotoxicity in the ocular surface since the ocular surface is exposed directly to high drug concentrations. Recently, an in vivo ... ...

Abstract	Background: In eye-drop drug development, the additional genotoxicity tests in some cases might be necessary to assess genotoxicity in the ocular surface since the ocular surface is exposed directly to high drug concentrations. Recently, an in vivo comet assay using corneal epithelial cells in rabbits following single ocular instillation was developed as an assay to evaluate genotoxicity in ocular tissues. In this study, we investigated the time-course changes in DNA damage after ocular instillation of genotoxic compounds to evaluate the optimal sampling timing for in vivo comet assay of the ocular surface tissue. Ethidium bromide (EtBr), methyl methanesulfonate (MMS), and 4-nitroquinoline 1-oxide (4-NQO) were administered to the eyes of the rabbits. Corneas were collected at 0.5, 2, 4, 6, and 24 h after administration, and the comet assay was performed. In addition, the in vitro comet assay was performed to assess the time-course changes in DNA damage induced by short-time exposure to the genotoxic compounds. Results: The mean % tail DNA, which is an indicator for DNA damage, in the corneal epithelial cells treated with all compounds exhibited statistically significant increases compared with those in the negative controls of saline at 0.5, 2, 4, and 6 h. There was a difference in the DNA damage response between EtBr and the other two compounds. In the 3% MMS- and 1% 4-NQO-treated eyes, the values of the % tail DNA were the highest at 0.5 h and then decreased gradually. In contrast, in the 1% EtBr-treated eyes, the highest value was noted at 4 h. The results of the in vitro comet assay showed that the % tail DNA increased in all groups. A further increase in the % tail DNA occurred in the EtBr-treated cells even after removing the compound but not in the MMS- and 4-NQO-treated cells. Conclusion: Relatively high values of the % tail DNA were maintained from 0.5 to 6 h after administration, suggesting that the optimal sampling time is any one point from 0.5 to 6 h in the comet assay of the corneal surface.
Language	English
Publishing date	2022-05-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2269162-5
ISSN	1880-7062 ; 1880-7046
ISSN (online)	1880-7062
ISSN	1880-7046
DOI	10.1186/s41021-022-00243-4
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Article ; Online: Histological Features of the Nasal Passage in Juvenile Japanese White Rabbits.

Yamagiwa, Yoshinori / Kurata, Masaaki / Satoh, Hiroshi

Toxicologic pathology

2022 Volume 50, Issue 2, Page(s) 218–231

Abstract: Rabbits are sometimes used for intranasal toxicology studies. We investigated the postnatal development of the nasal passage in juvenile Japanese white rabbits from just after birth to 6-week-old to provide information for conducting intranasal ... ...

Abstract	Rabbits are sometimes used for intranasal toxicology studies. We investigated the postnatal development of the nasal passage in juvenile Japanese white rabbits from just after birth to 6-week-old to provide information for conducting intranasal toxicological evaluation using juvenile animals. On postnatal day (PND) 1, the nasal passage consisted of the septum with mostly cartilaginous nasal wall and turbinates. The lining squamous, transitional, respiratory, and olfactory epithelia were already distributed similar to adults and were still underdeveloped. The nasal passage gradually expanded with age, as did the nasal wall, including the turbinates formed by endochondral ossification. The maxilloturbinate elongated, during which it branched complexly. The respiratory epithelium takes the form of columnar epithelium together with a reduction in goblet cells. In addition, the olfactory epithelium had clear cytoplasm in the ethmoturbinate, the olfactory nerve bundles thickened, and Bowman's gland acini increased in size and number. Other tissues, including the vomeronasal organ, nasal-associated lymphoid tissue, and nasolacrimal duct, also developed histologically with age. This investigation characterized the postnatal histological development of the nasal passage in Japanese white rabbits, providing basic knowledge regarding the histological examination and rationale for appropriate study design of intranasal toxicology studies in juvenile rabbits.
MeSH term(s)	Animals ; Epithelium ; Nasal Cavity/pathology ; Nasal Mucosa ; Olfactory Mucosa ; Rabbits
Language	English
Publishing date	2022-01-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	841009-4
ISSN	1533-1601 ; 0192-6233
ISSN (online)	1533-1601
ISSN	0192-6233
DOI	10.1177/01926233211068797
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Article ; Online: Presumed congenital nictitating membrane dysplasia in a Japanese white rabbit.

Masatsugu, Miki / Atsumi, Ikuyo / Yamagiwa, Yoshinori / Haranosono, Yu / Kurata, Masaaki

Veterinary medicine and science

2022 Volume 8, Issue 5, Page(s) 1946–1949

Abstract: Objective: The present report characterises a spontaneous nictitating membrane abnormality in a Japanese white rabbit.: Animal studied: The animal was a male Japanese white rabbit (Oryctolagus cuniculus, Kbs:JW, 10 weeks old at the time of purchase) ... ...

Abstract	Objective: The present report characterises a spontaneous nictitating membrane abnormality in a Japanese white rabbit. Animal studied: The animal was a male Japanese white rabbit (Oryctolagus cuniculus, Kbs:JW, 10 weeks old at the time of purchase) that had not received any treatment. A morphological abnormality of the nictitating membrane in the animal's right eye was detected. Procedures: Ophthalmological examinations, including slit-lamp biomicroscopy, corneal and conjunctival staining with fluorescein and lissamine green, fundoscopy, blinking rate measurement, Schirmer's tear test, and tonometry were performed. The animal was euthanised at 15 weeks of age, and histopathological examinations of the abnormal nictitating membrane, palpebral conjunctiva, eyelid and eyeball were performed. Results: The tip of the nictitating membrane adhered to the palpebral conjunctiva of the medial canthus. The eye and periocular tissues showed no abnormalities in the ophthalmological examinations, except for the structure of the nictitating membrane. Histopathological examination revealed that the adhered site of the nictitating membrane and the palpebral conjunctiva consisted of dense fibrous connective tissue that was consecutive to the conjunctiva adjacent to the eyelid margin and lamina propria of the nictitating membrane. The fibrous connective tissue was covered with stratified squamous epithelium. Conclusion: Based on these results, we diagnosed this abnormal finding as congenital nictitating membrane dysplasia. This paper is the first case report describing a congenital structural abnormality of the nictitating membrane in a Japanese white rabbit.
MeSH term(s)	Animals ; Conjunctiva/pathology ; Fluorescein ; Japan ; Male ; Nictitating Membrane ; Rabbits
Chemical Substances	Fluorescein (TPY09G7XIR)
Language	English
Publishing date	2022-05-19
Publishing country	England
Document type	Case Reports
ZDB-ID	2819409-3
ISSN	2053-1095 ; 2053-1095
ISSN (online)	2053-1095
ISSN	2053-1095
DOI	10.1002/vms3.844
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Article: In vivo comet assay in rabbit corneal epithelial cells following ocular instillation with genotoxic compounds.

Tahara, Haruna / Yamagiwa, Yoshinori / Haranosono, Yu / Kurata, Masaaki

Genes and environment : the official journal of the Japanese Environmental Mutagen Society

2021 Volume 43, Issue 1, Page(s) 11

Abstract: Background: The in vivo comet assay is used to evaluate the genotoxic potential of compounds by detecting DNA strand breaks in cells isolated from animal tissue. The comet assay of hepatocytes is well established; however, the levels of systemic drug ... ...

Abstract	Background: The in vivo comet assay is used to evaluate the genotoxic potential of compounds by detecting DNA strand breaks in cells isolated from animal tissue. The comet assay of hepatocytes is well established; however, the levels of systemic drug exposure following systemic administration are often insufficient to evaluate the genotoxic potential of compounds on the ocular surface following ocular instillation. To investigate the possibility of using the comet assay as a genotoxic evaluation tool for the ocular surface, we performed this assay on the corneal epithelial cells of rabbit eyes 2 h after the single ocular instillation of five genotoxic compounds, namely ethidium bromide, 1,1'-dimethyl-4,4'-bipyridinium dichloride (paraquat), methyl methanesulfonate (MMS), acrylamide, and 4-nitroquinoline 1-oxide (4-NQO). Results: The mean % tail DNA, as an indicator of DNA damage, in the corneal epithelial cells treated with ethidium bromide, MMS, and 4-NQO exhibited statistically significant increases compared with those in the negative controls (saline or 5 % dimethyl sulfoxide in saline). However, paraquat and acrylamide did not increase the mean % tail DNA, presumably because of the high antioxidant levels and low cytochrome P450 levels present in the corneal epithelium, respectively. Conclusions: The comet assay was able to detect genotoxic potential on the ocular surface following ocular instillation with genotoxic compounds. The study findings indicate that the in vivo comet assay may provide a useful tool for assessing the genotoxicity of compounds topically administrated on the ocular surface under mimicking clinical condition.
Language	English
Publishing date	2021-04-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2269162-5
ISSN	1880-7062 ; 1880-7046
ISSN (online)	1880-7062
ISSN	1880-7046
DOI	10.1186/s41021-021-00184-4
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Article ; Online: Histological Features of Postnatal Development of the Eye in White Rabbits.

Yamagiwa, Yoshinori / Kurata, Masaaki / Satoh, Hiroshi

Toxicologic pathology

2020 Volume 49, Issue 3, Page(s) 419–437

Abstract: Rabbits are frequently used in studies assessing the toxicity of ophthalmic drugs; however, the postnatal histological changes that occur in the rabbit eye have not been fully described. To characterize postnatal ocular development in white rabbits, a ... ...

Abstract	Rabbits are frequently used in studies assessing the toxicity of ophthalmic drugs; however, the postnatal histological changes that occur in the rabbit eye have not been fully described. To characterize postnatal ocular development in white rabbits, a histological investigation of the eyes and eyelids was sequentially performed between postnatal days (PNDs) 1 and 42. The eyes opened during PNDs10 to 12. Significant changes prior to eyelid opening included the proliferation of uveal and optic nerve cells, regression of the lenticular vasculature, and thinning of the retina with a decreasing number of retinal cells. After eyelid opening, several significant changes occurred in the anterior segment, including thickening of the cornea and the development of lacrimation-related tissues in the eyelid and conjunctiva. Additionally, the differentiation of retinal layer-derived cells and optic nerve thickening occurred. The lens size continued to increase throughout the postnatal period. The histological structure of the eyes and eyelids was nearly mature by PNDs28 to 42. This study characterizes the postnatal changes in the histological features of the eyes in juvenile white rabbits, providing fundamental knowledge on the appropriate design of histological studies of the eyes in juvenile rabbits, particularly ophthalmic drug evaluations.
MeSH term(s)	Animals ; Cornea ; Eye ; Eyelids ; Rabbits ; Retina
Language	English
Publishing date	2020-04-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	841009-4
ISSN	1533-1601 ; 0192-6233
ISSN (online)	1533-1601
ISSN	0192-6233
DOI	10.1177/0192623320915460
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Zs.A 1975: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Investigation of

Tahara, Haruna / Nemoto, Shingo / Yamagiwa, Yoshinori / Haranosono, Yu / Kurata, Masaaki

Cutaneous and ocular toxicology

2021 Volume 40, Issue 1, Page(s) 26–36

Abstract: Purpose: An unscheduled DNA synthesis (UDS) test is used for : Materials and methods: Five genotoxic agents - 1,1'-dimethyl-4,4'-bipyridinium dichloride (paraquat); acridine orange; ethidium bromide; acrylamide; and 4-nitroquinoline 1-oxide (4-NQO) - ...

Abstract	Purpose: An unscheduled DNA synthesis (UDS) test is used for Materials and methods: Five genotoxic agents - 1,1'-dimethyl-4,4'-bipyridinium dichloride (paraquat); acridine orange; ethidium bromide; acrylamide; and 4-nitroquinoline 1-oxide (4-NQO) - were instilled once onto both eyes of male Japanese white rabbits. Physiological saline or a general vehicle for ophthalmic solution were instilled as the negative controls. Dimethyl sulfoxide was instilled as the vehicle control. Isolated corneas were incubated with tritium-labelled thymidine and the number of sparsely labelled cells (SLCs, cells undergoing UDS) was counted by autoradiography. Results: Statistically significant increases in the mean appearance rates of SLCs in the corneal epithelium were noted in paraquat-, acridine orange-, ethidium bromide-, and 4-NQO-treated eyes compared with those of the controls. These increases generally appeared in a dose-dependent manner. Acrylamide did not induce an increase in the mean appearance rates of SLCs, presumably because it caused the generation of fewer metabolites in the cornea. Conclusions: UDS tests revealed DNA damage in the cornea epitheliums treated with well-known genotoxic agents. These results suggest that the UDS test is one of the useful tools for the assessment of
MeSH term(s)	4-Nitroquinoline-1-oxide/administration & dosage ; 4-Nitroquinoline-1-oxide/toxicity ; Acridine Orange/administration & dosage ; Acridine Orange/toxicity ; Acrylamide/administration & dosage ; Acrylamide/toxicity ; Administration, Ophthalmic ; Animals ; DNA/analysis ; DNA/biosynthesis ; DNA Damage/drug effects ; DNA Repair ; Dose-Response Relationship, Drug ; Epithelium, Corneal/drug effects ; Epithelium, Corneal/metabolism ; Ethidium/administration & dosage ; Ethidium/toxicity ; Feasibility Studies ; Male ; Models, Animal ; Mutagenicity Tests/methods ; Mutagens/administration & dosage ; Mutagens/toxicity ; Paraquat/administration & dosage ; Paraquat/toxicity ; Rabbits
Chemical Substances	Mutagens ; Acrylamide (20R035KLCI) ; 4-Nitroquinoline-1-oxide (56-57-5) ; DNA (9007-49-2) ; Ethidium (EN464416SI) ; Acridine Orange (F30N4O6XVV) ; Paraquat (PLG39H7695)
Language	English
Publishing date	2021-01-18
Publishing country	England
Document type	Journal Article
ZDB-ID	605635-0
ISSN	1556-9535 ; 1556-9527 ; 0731-3829
ISSN (online)	1556-9535
ISSN	1556-9527 ; 0731-3829
DOI	10.1080/15569527.2021.1874006
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Article: A case of frequent and inappropriate shock with a subcutaneous implantable cardioverter-defibrillator triggered by newly developed complete right bundle branch block.

Omura, Ayumi / Onuki, Tatsuya / Mase, Hiroshi / Kurata, Masaaki / Wakatsuki, Daisuke / Suzuki, Hiroshi

HeartRhythm case reports

2022 Volume 8, Issue 9, Page(s) 606–609

Language	English
Publishing date	2022-06-06
Publishing country	United States
Document type	Case Reports
ZDB-ID	2834871-0
ISSN	2214-0271
ISSN	2214-0271
DOI	10.1016/j.hrcr.2022.05.025
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Article ; Online: The characteristic of an abnormal p-wave axis in patients with atrial fibrillation.

Wakatsuki, Daisuke / Asano, Taku / Mase, Hiroshi / Kurata, Masaaki / Onuki, Tatsuya / Suzuki, Hiroshi

Journal of electrocardiology

2022 Volume 73, Page(s) 1–7

Abstract: Backgrounds: An adverse increased risk of atrial fibrillation (AF) can be detected by measuring the p-wave indices, including prolonged p-wave duration, the PR interval, abnormal p-wave terminal force, and abnormal p-wave axis (aPWA). Our purpose was to ...

Abstract	Backgrounds: An adverse increased risk of atrial fibrillation (AF) can be detected by measuring the p-wave indices, including prolonged p-wave duration, the PR interval, abnormal p-wave terminal force, and abnormal p-wave axis (aPWA). Our purpose was to characterize the AF patient population with an aPWA and to identify whether the aPWA was associated with recurrence after catheter ablation of AF. Methods: This study retrospectively included 249 patients with AF who underwent catheter ablation in our hospital from October 2015 to May 2019. We measured the p-wave indices and left atrial cavity size (LAVI) before the catheter ablation. A logistic regression analysis was performed to analyze the concurrent effects of various factors on the prevalence of AF recurrence over 12 months after the ablation. Results: An aPWA was observed in 35 patients (14%). There were significantly more patients with an aPWA in the non-PAF than PAF patients (26% versus 7%, p < 0.001). The patients with an aPWA had a significantly larger LAVI values (37 ± 12 versus 45 ± 11 ml/m2, p = 0.016). In a multivariate analysis, an aPWA (odds ratio, 4.27; 95% confidence interval, 1.75-10.4; p = 0.001) and the LAVI (odds ratio, 1.04; 95% confidence interval, 1.00-1.08; p = 0.032) were independently associated with recurrence after catheter ablation. Conclusions: Our results demonstrated that measuring the aPWA in patients with atrial fibrillation before ablation was useful for identifying patients at a higher risk of recurrence after catheter ablation of AF.
MeSH term(s)	Atrial Fibrillation ; Catheter Ablation/methods ; Electrocardiography ; Humans ; Recurrence ; Retrospective Studies ; Treatment Outcome
Language	English
Publishing date	2022-04-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	410286-1
ISSN	1532-8430 ; 0022-0736
ISSN (online)	1532-8430
ISSN	0022-0736
DOI	10.1016/j.jelectrocard.2022.04.003
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Zs.A 701: Show issues

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Article: Pharmacokinetics of Azithromycin, Levofloxacin, and Ofloxacin in Rabbit Extraocular Tissues After Ophthalmic Administration.

Sakai, Tatsuya / Shinno, Keisuke / Kurata, Masaaki / Kawamura, Akio

Ophthalmology and therapy

2019 Volume 8, Issue 4, Page(s) 511–517

Abstract: Introduction: Azithromycin demonstrates high tissue distribution and prolonged elimination half-life. In this study, we monitored the pharmacokinetics of a single ophthalmic administration of 1% azithromycin ophthalmic solution containing polycarbophil ... ...

Abstract	Introduction: Azithromycin demonstrates high tissue distribution and prolonged elimination half-life. In this study, we monitored the pharmacokinetics of a single ophthalmic administration of 1% azithromycin ophthalmic solution containing polycarbophil in the extraocular tissues, including the eyelid, and compared it with that of two commercial ophthalmic products, 1.5% levofloxacin ophthalmic solution and 0.3% ofloxacin ophthalmic ointment. Methods: Rabbits were treated with either a single topical administration of 1% azithromycin ophthalmic solution, 1.5% levofloxacin ophthalmic solution, or 0.3% ofloxacin ophthalmic ointment. The eyelid, conjunctiva, and cornea were collected at 0.25, 0.5, 1, 2, 4, 8, and 24 h post-administration. Tissue samples were pretreated for drug concentration measurements by ultra-performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined by non-compartmental analysis. Results: Azithromycin was rapidly absorbed, and its levels remained near the observed maximum concentrations for up to 24 h post-administration in all tissue. In contrast, extraocular tissue concentrations of levofloxacin and ofloxacin decreased with time. The maximum concentrations of azithromycin, levofloxacin, and ofloxacin were 35.6, 34.1, and 55.1 µg/g in the eyelid, 44.2, 46.8, and 20.4 µg/g in the conjunctiva, and 79.9, 18.0, and 2.21 µg/g in the cornea, respectively. The values of the area under the curve from 0 to 24 h after administration of azithromycin, levofloxacin, and ofloxacin were 602, 58.5, and 267 µg·h/g in the eyelid, 837, 43.2, and 51.9 µg·h/g in the conjunctiva, and 1250, 26.4, and 5.46 µg h/g in the cornea, respectively. Conclusion: The drug concentrations of azithromycin and levofloxacin were relatively comparable among the extraocular tissues following topical administration of the respective ophthalmic solutions, whereas the concentrations of ofloxacin varied following dosing of its ophthalmic ointment. The slow elimination profile in any extraocular tissue of rabbits was unique to azithromycin, and led to the demonstration of high exposures of azithromycin in all extraocular tissues after ophthalmic administration. Funding: This research and Rapid Service Fees were supported by Senju Pharmaceutical Co., Ltd.
Language	English
Publishing date	2019-08-01
Publishing country	England
Document type	Journal Article
ISSN	2193-8245
ISSN	2193-8245
DOI	10.1007/s40123-019-00205-0
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Article ; Online: Intramural needle ablation or repeated standard ablation in patients referred for repeat ablation of scar-related ventricular tachycardia.

Kurata, Masaaki / Batnyam, Uyanga / Tedrow, Usha B / Richardson, Travis D / Kanagasundram, Arvindh N / Hasegawa, Kanae / Uetake, Shunsuke / Manuelian, Deborah / Pellegrini, Christine / Stevenson, William G

Journal of cardiovascular electrophysiology

2024 Volume 35, Issue 5, Page(s) 994–1004

Abstract: Introduction: When ventricular tachycardia (VT) recurs after standard RF ablation (sRFA) some patients benefit from repeat sRFA, whereas others warrant advanced methods such as intramural needle ablation (INA). Our objectives are to assess the utility ... ...

Abstract	Introduction: When ventricular tachycardia (VT) recurs after standard RF ablation (sRFA) some patients benefit from repeat sRFA, whereas others warrant advanced methods such as intramural needle ablation (INA). Our objectives are to assess the utility of repeat sRFA and to clarify the benefit of INA when repeat sRFA fails in patients with VT due to structural heart disease. Methods: In consecutive patients who were prospectively enrolled in a study for INA for recurrent sustained monomorphic VT despite sRFA, repeat sRFA was considered first. INA was performed during the same procedure if repeat sRFA failed or no targets for sRFA were identified. Results: Of 85 patients enrolled, acute success with repeat sRFA was achieved in 30 patients (35%), and during the 6-month follow-up, 87% (20/23) were free of VT hospitalization, 78% were free of any VT, and 7 were lost to follow-up. INA was performed in 55 patients (65%) after sRFA failed, or no endocardial targets were found abolished or modified inducible VT in 35/55 patients (64%). During follow-up, 72% (39/54) were free of VT hospitalization, 41% were free of any VT, and 1 was lost to follow-up. Overall, 59 out of 77 (77%) patients were free of hospitalization and 52% were free of any VT. Septal-origin VTs were more likely to need INA, whereas RV and papillary muscle VTs were less likely to require INA. Conclusions: Repeat sRFA was beneficial in 23% (18/77) of patients with recurrent sustained VT who were referred for INA. The availability of INA increased favorable outcomes to 52%.
MeSH term(s)	Humans ; Tachycardia, Ventricular/surgery ; Tachycardia, Ventricular/physiopathology ; Tachycardia, Ventricular/diagnosis ; Tachycardia, Ventricular/etiology ; Male ; Female ; Middle Aged ; Aged ; Prospective Studies ; Recurrence ; Catheter Ablation/adverse effects ; Cicatrix/physiopathology ; Cicatrix/diagnosis ; Cicatrix/surgery ; Cicatrix/etiology ; Reoperation ; Time Factors ; Action Potentials ; Needles ; Heart Rate ; Risk Factors ; Treatment Outcome
Language	English
Publishing date	2024-03-19
Publishing country	United States
Document type	Journal Article ; Comparative Study
ZDB-ID	1025989-2
ISSN	1540-8167 ; 1045-3873
ISSN (online)	1540-8167
ISSN	1045-3873
DOI	10.1111/jce.16250
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