@misc{oai:niigata-u.repo.nii.ac.jp:00005325,
 author = {新井, 佐知子},
 month = {Sep},
 note = {Leg weakness in pigs is externally represented by an abnormal sign in the limb hoof. Leg weakness is a regressive disease mainly caused by Osteochondrosis (OC) and osteoarthritis (OA) as non-infective diseases. OC and OA induce lesions in cartilage poor in both blood vessels and pain sensation. Therefore, initial signs are difficult to detect, and sudden astasia or claudication occurs in the terminal stage. This locomotor disease causes large economic losses in pig farms in Japan and other countries. In this study, we clarified the status of leg weakness in pigs in general farms, and developed and evaluated a diagnostic technique for its early detection. To confirm the present status of the development of leg weakness in pigs in Japan, a present status survey and a follow-up survey were performed. As a result, leg weakness was present irrespective of the breeding form in general pig farms. Analysis using quantification theory classes III and II showed close associations between culling and the following 7 items: upright pasterns of forelegs/hind legs, weak pasterns of forelegs/hind legs, standing outwards of rear view, stiff locomotion, and swaying hindquarters. Therefore, there is a possibility that the number of growing pigs culled due to leg weakness can be reduced by checking the 7 items at the time of introduction of growing pigs as hogs for breeding. Animal models with leg weakness have already been produced in some animals, but no models using pigs, showing the highest incidence of leg weakness, have been reported. We produced a pig model of leg weakness using 5% papain solution, observed clinical signs, and evaluated the relationship between joint lesions and clinical signs. The day of papain administration was regarded as Day 0. Body temperature and clinical signs improved on Day 3 or later, while mild claudication was observed until Day 14. However, macroscopic lesions in cartilage were aggravated daily, resulting in extensive lesions involving fissures and erosion. Histological evaluation of these lesions showed thinning and detachment of the cartilage surface on Day 7 and the disappearance of glucosaminoglycan on the cartilage surface, disappearance of proteoglycan in deep cartilage areas, chondrocyte vacuolation, and chondrocyte clusters on Day 14. On Day 21, marked cartilage detachment and exfoliation and the disappearance of most cartilage were observed. Vacuolation in deep cartilage areas was enlarged by fusing with adjacent lesions. On Day 28, histological damage was relatively slight without detachment, but numerous chondrocyte clusters were present. Pigs as a model of leg weakness could be produced using 5% papain solution at a probability of 100%. There is a possibility that papain solution injection into the knee joint can play a major role in establishing diagnostic techniques for leg weakness due to OC or OA. As histological findings of leg weakness induced by papain injection, findings of OA were marked. Using this technique, we produced a breeding sow model of leg weakness and a pain scoring system for the objective evaluation of joint pain, and clinically observed the course from joint destruction. Blood was periodically collected after cannulation of the auricular vein, and changes in the concentration of keratan sulfateas a joint marker were determined. After autopsy, the distal end of the femur was collected, and the correlations between the blood keratan sulfate concentration and macroscopic/ pathological findings of the cartilage area or clinical signs were evaluated., Of the 3 sows with leg weakness, 1 showed clear signs and cartilage lesions. In this sow, the blood keratan sulfate level clearly increased after joint destruction, suggesting the acute detachment of cartilage components due to acute damage to cartilage. Another sow showed a decrease in the keratan sulfate concentration compared with the pre-administration value. We speculated that shortening of the standing time due to leg pain reduced cartilage metabolism, reducing the keratan sulfate concentration. Thus, it is ascertained that the keratan sulfate concentration changes with the pathological condition. As a method for the early diagnosis of leg weakness, C-reactive protein (CRP) as a biomarker, which increases in acute inflammation was evaluated for the objective monitoring of inflammation, ELISA kits for pigs are commercially available. However, to process a large quantity of samples more readily, pig CRP was measured with N-assay TIA CRP-S kits using the TIA method for humans. As a result, the mean CRP level was 2.56±1.9mng/dl. The CRP level tended to be slightly high at the age of 70 days (5.75±3.2 mg/dl), but the normal pig CRP level using the TIA method was considered to be ≤5 mg/dl. In addition, in the sows with leg weakness, CRP was monitored from the development of arthritis until autopsy, and inflammatory reactions could be confirmed sensitively. There was a slight dissociation between the plasma and serum CRP levels. The lower serum CRP level may have been because CRP was captured and removed by pig serum fibrin. The determination of the plasma CRP level with consideration being given to age (days) in pig leg weakness may allow the clear evaluation of acute inflammatory reactions in the body. In human medicine, for the diagnosis of rheumatoid arthritis and osteoarthrosis, measurement of joint markers (cartilage components in the blood) is performed in addition to radiography and diagnostic imaging. Among these markers, keratan sulfate is specific to the articu1ar cartilage and has already been measured in dogs and horses. However, there have been no reports of its measurement in pigs, and age-, sex-, and breed-associated differences in its level have also been unclear. Measurement of keratan sulfate in pigs showed a decrease with growth from the juvenile period in healthy pigs. The cartilage thickness was associated with the keratan sulfate concentration. There were no sex-related differences, but there were differences among breeds. The keratan sulfate level in sows decreased to about 1/10 of the level in piglets. This may have been because of a change in the breeding form to breeding in stalls specific to sows. Since the joints constantly do not move, cartilage metabolism may be impaired, In addition, in sows, and growing pigs for breeding, the keratan sulfate level decreased in the presence of leg weakness clinically observed. These results suggest that monitoring of lesions in the joint and early detection of the risk of leg weakness may be possible by identifying pigs at risk of leg weakness based on the state of the limb hoof and gait, and determining the blood CRP and keratan sulfate levels with consideration being given to the age and breeds., 学位の種類: 博士（農学）. 報告番号: 乙第2165号. 学位記番号: 新大博（農）乙第30号. 学位授与年月日: 平成24年9月20日, 新大博（農）乙第30号},
 title = {豚脚弱症の実態解明と臨床診断技術の開発},
 year = {2012}
}