{"created":"2023-06-19T07:19:18.785897+00:00","id":5344,"links":{},"metadata":{"_buckets":{"deposit":"3ea0e545-bb11-4680-90ea-a5e4403bd716"},"_deposit":{"created_by":4,"id":"5344","owners":[4],"pid":{"revision_id":0,"type":"depid","value":"5344"},"status":"published"},"_oai":{"id":"oai:az.repo.nii.ac.jp:00005344","sets":["370:15:391"]},"author_link":["23016"],"item_10006_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2019-03-15"}]},"item_10006_degree_grantor_9":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"麻布大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"32701","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_10006_degree_name_8":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(獣医学)"}]},"item_10006_description_22":{"attribute_name":"Abstract","attribute_value_mlt":[{"subitem_description":"Introduction\n　Epilepsy is one of the most common chronic neurological disorders that affects both dogs and humans. The type of epilepsy affecting about half of the epileptic dogs is idiopathic epilepsy (IE). There is no standardized definitive treatment for IE, and most of the dogs affected by this disease need to be medicated with an anti-epileptic drug (AED) throughout their lifespans to prevent epileptic seizures. Despite being administered adequate doses of AEDs, 20–30% of the epileptic dogs remain inadequately treated for seizure control. Seizures deteriorate the quality of life of both the affected animals and the owners of these animals. Therefore, in Chapter 1, the author retrospectively investigated the clinical data corresponding to dogs with IE in Japan to search for predisposing factors to this condition and to identify problem areas in the treatment of IE that have the potential to be improved upon for further investigation. In Chapter 2, the author focused on potassium bromide (KBr), which is an effective AED to control seizures in dogs; however, there are problems associated with administering this treatment in some clinical cases. Next, in Chapter 3, a search was conducted for the risk loci of IE in a dog breed that was overrepresented in the retrospective study (Chapter 1) using a genome-wide association study (GWAS) and a direct sequence method.\n\nChapter 1: A retrospective study of canine idiopathic epilepsy in referral centers in Japan\n　The aim of this chapter was to describe the clinical data associated with dogs affected by IE in Japan and to search for predisposing factors responsible for this condition. Furthermore, another purpose was to address the problems encountered with the AED treatments administered to dogs with epilepsy. The medical records and clinical information corresponding to dogs diagnosed with IE at 2 referral centers between April 2013 and March 2016 were retrospectively reviewed. The review was conducted according to the consensus statements published by the International Veterinary Epilepsy Task Force. The data of a total of 70 dogs that had a median (minimum –maximum) weight of 5.15 (1.85–79.85) kg and were at a median age of 4.2 (0.3–11.8) years at the initial onset of epileptic seizures were used. Forty-four of these dogs were male, and 26 were female. Toy poodles were overrepresented in the present study indicating that this breed may be predisposed to IE and would be a good candidate for a gene study to elucidate the cause of IE in dogs. Moreover, the cases suspected to be refractory among these were being administered 2 or more AEDs. Since 67 % of the dogs with a poor therapeutic outcome were on potassium bromide (KBr), it was hypothesized that optimizing the KBr treatment would contribute to the improvement of the therapeutic outcome.\n \nChapter 2: The effects of chloride in the diet on serum bromide concentrations in dogs\n　Since it is known that a high chloride intake decreases the serum bromide concentration, it was considered that elucidating the relationship that exists between these parameters would provide useful data. Therefore, in this chapter, the author clarifies the relationship between the dietary chloride intake and serum bromide concentrations. Steady-state serum bromide concentrations were measured using a gold chloride method in 23 dogs treated with KBr. The content of dietary chloride (per 1 g) was measured using the Mohr’s method or calculated from the ingredients label provided by the manufacturer of the dog food. A regression analysis was used to evaluate the relationship between dietary chloride intake (mg/kg/day) and the serum bromide concentration per dose (μg/ml per mg/kg). Dogs with a higher chloride intake had lower serum bromide concentrations. A strong negative correlation was observed between the dietary chloride intake (mg/kg/day) and the serum bromide concentration per dose (μg/ml per mg/kg) (P < 0.01). These results suggest the importance of considering the dietary chloride content for KBr-treated dogs and may also assist clinicians with the selection of KBr doses and appropriate diets for dogs treated with KBr.\n\nChapter 3: The investigation of the candidate gene associated with IE in toy poodles\n　Since toy poodles were overrepresented in the investigation conducted in Chapter 1, it was indicated that this breed may be predisposed to developing IE and, hence, would be a candidate for the gene study to elucidate the cause of IE in dogs. Therefore, in this chapter, the author tried to locate the loci that are related to IE in toy poodles. Using 10 and 22 toy poodles with and without IE, respectively, a genome wide association study (GWAS) was performed. The identified candidate variant was validated using a standard PCR, followed by Sanger sequencing in an additional sample of 39 toy poodles (23 affected and 16 unaffected). The GWAS and confirmation study revealed a significant variant single nucleotide polymorphism (SNP), rs22063361, in chromosome 10. Exonic sequencing was performed on 1 of the candidate genes, ELFN2, and its potential to be involved in the pathogenesis of IE in dogs was evaluated. The analysis of the coding region of ELFN2 did not reveal a causative mutation responsible for IE. Therefore, further investigation is needed to elucidate the relative gene responsible for IE in this breed.\n\nConclusion\n　The author described the clinical data corresponding to canine IE in Japan, elucidated the relationship that exists between the dietary chloride intake and serum bromide concentration. Although the present study could not reveal the association between specific candidate gene and toy poodle with IE, these findings of the present study act as a resource to assist clinicians in treating dogs with IE and provide multiple basic data to facilitate further investigations of canine IE."}]},"item_10006_dissertation_number_12":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第154号"}]},"item_10006_textarea_23":{"attribute_name":"Rights","attribute_value_mlt":[{"subitem_textarea_value":"本論文の一部は以下のとおり公表されている。(Part of this dissertation has been published as follows.) \n1. Togawa G, Saito M, Uebayashi I, Onishi Y, Yamazoe H. 2018. A Retrospective study of canine idiopathic epilepsy in referral centers in Japan. J Azabu Univ. (In Press).\n2. Togawa G, Saito M, Iwata S, Watanabe N, Orito K. 2018. Effects of chloride in the diet on serum bromide concentration in dogs. Inter J Appl Res Vet Med. 16 197–202.\n"}]},"item_10006_version_type_18":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"十川, 剛"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-02-07"}],"displaytype":"detail","filename":"diss_dv_kou0154.pdf","filesize":[{"value":"1.6 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"diss_dv_kou0154","url":"https://az.repo.nii.ac.jp/record/5344/files/diss_dv_kou0154.pdf"},"version_id":"0c50dadf-f59d-4515-87e5-a3a91dfca435"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2019-03-22"}],"displaytype":"detail","filename":"diss_dv_kou0154_jab&rev.pdf","filesize":[{"value":"194.2 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"diss_dv_kou0154_jab&rev.pdf","url":"https://az.repo.nii.ac.jp/record/5344/files/diss_dv_kou0154_jab&rev.pdf"},"version_id":"f9db1fd4-e27e-4f11-94ce-cf6f30fe8233"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis"}]},"item_title":"犬の特発性てんかんの発症の素因および治療に関する研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"犬の特発性てんかんの発症の素因および治療に関する研究"},{"subitem_title":"Risk Factors and Treatments of Idiopathic Epilepsy in Dogs","subitem_title_language":"en"}]},"item_type_id":"10006","owner":"4","path":["391"],"pubdate":{"attribute_name":"公開日","attribute_value":"2019-04-23"},"publish_date":"2019-04-23","publish_status":"0","recid":"5344","relation_version_is_last":true,"title":["犬の特発性てんかんの発症の素因および治療に関する研究"],"weko_creator_id":"4","weko_shared_id":4},"updated":"2023-06-19T07:41:06.646202+00:00"}