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| 1.
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論文
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Haryanto ; Mukai, Kanae ; Nakajima, Yukari ; Okuwa, Mayumi ; Cau, Kim Jiu ; Sugama, Junko ; Nakatani, Toshio ; 向井, 加奈恵 ; 中島, 由加里 ; 大桑, 麻由美 ; 須釜, 淳子 ; 中谷, 壽男
概要:
金沢大学医薬保健研究域保健学系<br />The purpose of this study is to evaluate and clarify the effect of Indonesian honey, two types of J
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apanese honey and hydrocolloid dressing on wound healing process. Four groups of male mice were treated to produce two circular full-thickness skin wounds on the dorsum. They were then randomly allocated to receive daily Indonesian honey, Japanese honey (Buckwheat and Acacia honey) or hydrocolloid dressing as a control for treatment application. Macroscopic findings were observed from day 0 to 14 after wounding. Microscopic evaluation was assessed using qualitative analysis. The ratios of wound areas for honey groups on day 3 and 7 were smaller than those of the control group. Wound areas of honey groups gradually decreased to almost the same wound area as the control group on day 14, while the wound area of the control group peaked on day 5 and rapidly decreased until day 14. Microscopic finding that Indonesian honey was different with Japanese honey especially Buckwheat honey.
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| 2.
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Mukai, Kanae ; Komatsu, Emi ; Nakajima, Yukari ; Urai, Tamae ; Nasruddin ; Sugama, Junko ; Nakatani, Toshio ; 向井, 加奈恵 ; 中島, 由加里 ; 須釜, 淳子 ; 中谷, 壽男
概要:
金沢大学医薬保健研究域保健学系<br />Cutaneous wound healing is delayed by protein malnutrition (PM). On the other hand, estrogen promot
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es cutaneous wound healing by its anti-inflammatory and cell proliferation effects. Therefore, we hypothesized that estrogen administration in protein-malnourished ovariectomized (OVX) female mice might improve the inflammatory response and promote cutaneous wound healing as well as normal nutrition. To test this hypothesis, we used full-thickness excisional wounds in Control SHAM, PM SHAM, PM OVX and PM OVX+17β-estradiol mice. The Control diet included 200 g/kg protein and the PM diet included 30 g/kg protein. The ratio of wound area in the Control SHAM group was significantly smaller than those in the three PM groups. In addition, microscopic findings also showed that the ratio of collagen fibers, the ratio of myofibroblasts and the number of new blood vessels in the Control SHAM group were significantly greater than those in the three PM groups. However, the number of Ym1-positive cells as an anti-inflammatory M2-like macrophage marker in the PM OVX+17β-estradiol group was significantly higher than those in the other three groups. These results indicate that the appearance of anti-inflammatory M2-like macrophages was promoted by estrogen administration; however, it could not promote cutaneous wound healing upon a low-protein diet. Therefore, it may be confirmed that nutrition is more important for promoting cutaneous wound healing than estrogen administration.
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| 3.
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Mukai, Kanae ; Komatsu, Emi ; Nakajima, Yukari ; Urai, Tamae ; Nasruddin ; Sugama, Junko ; Nakatani, Toshio ; 向井, 加奈恵 ; 中島, 由加里 ; 浦井, 珠恵 ; 須釜, 淳子 ; 中谷, 壽男
概要:
金沢大学医薬保健研究域保健学系<br />Topical estrogen application to wounds is effective in promoting cutaneous wound healing. However,
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whether it promotes cutaneous wound healing in delayed cutaneous wound healing associated with advanced age remains to be elucidated. This study aimed to evaluate the effect of topical estrogen application to wounds in cutaneous wound healing in 80-week-old female mice. C57BL/6J female mice aged 82–85 and 12 weeks old were submitted to two full-thickness wounds. Mice were divided into four groups: aged group, topical estrogen wound treatment aged group (aged-E), vehicle wound treatment aged group (aged-vehicle), and young group. Wound healing was observed until day 14. In the aged group, wound area ratio (wound area / initial wound area) was significantly higher on days 3–14, ratio of re-epithelialization was significantly lower on day 3 and tended to be lower on day 14, and neutrophil number was significantly higher on day 7 compared with the young group. In contrast, in the aged-E group, wound area ratio was significantly smaller on days 1–14, re-epithelialization ratio was significantly higher on days 3–14, and neutrophil and macrophage number was significantly lower on days 3 and 7 compared with the aged group. These results demonstrate that topical estrogen application to wounds in 80-week-old female mice promoted cutaneous wound healing by reducing wound area and inflammatory response and promoting re-epithelialization.
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| 4.
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Asano, Kimi ; Nakajima, Yukari ; Mukai, Kanae ; Urai, Tamae ; Okuwa, Mayumi ; Sugama, Junko ; Konya, Chizuko ; Nakatani, Toshio ; 浅野, きみ ; 中島, 由加里 ; 向井, 加奈恵 ; 浦井, 珠恵 ; 大桑, 麻由美 ; 須釜, 淳子 ; 紺家, 千津子 ; 中谷, 壽男
概要:
金沢大学医薬保健研究域保健学系<br />Background Previously, we showed that lymphatic vessels (LVs) formed detours after lymphatic obstru
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ction, contributing to preventing lymphedema. In this study, we developed detours using lymphatic ligation in mice and we identified the detours histologically. Methods and results Under anesthesia, both hindlimbs in mice were subcutaneously injected with Evans blue dye to detect LVs. We tied the right collecting LV on the abdomen that passes through the inguinal lymph node (LN) at two points. The right and left sides comprised the operation and sham operation sides, respectively. Lymphography was performed to investigate the lymph flow after lymphatic ligation until day 30, using a near-infrared fluorescence imaging system. Anti-podoplanin antibody and 5-ethynyl-2’-deoxyuridine (EdU) were used to detect LVs and lymphangiogenesis. Within 30 days, detours had developed in 62.5% of the mice. Detours observed between two ligation sites were enlarged and irregular in shape. Podoplanin+ LVs, which were located in the subcutaneous tissue of the upper panniculus carnosus muscle, connected to collecting LVs at the upper portion from the cranial ligation site and at the lower portion from the caudal ligation site. EdU+ cells were not observed in these detours. The sham operation side showed normal lymph flow and did not show enlarged pre-collecting LVs until day 30. Conclusions Detours after lymphatic ligation were formed not by lymphangiogenesis but through an enlargement of pre-collecting LVs that functioned as collecting LVs after lymphatic ligation. Further studies are required to explore the developmental mechanism of the lymphatic detour for treatment and effective care of lymphedema in humans. © 2020 Asano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 5.
学位論文 |
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中島, 由加里 ; Nakajima, Yukari
概要:
博士論文要旨Abstract 以下に掲載：Scientific Reports 8 pp.1-9 2018. Nature Research. 共著者：Yukari Nakajima, Kimi Asano, Kanae Mukai, Tamae Urai, Mayumi Okuwa, Junko Sugama, Toshio Nakatani
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中島, 由加里 ; Nakajima, Yukari
概要:
博士論文本文Full 以下に掲載：Scientific Reports 8 pp.1-9 2018. Nature Research. 共著者：Yukari Nakajima, Kimi Asano, Kanae Mukai, Tamae Urai, Mayumi Okuwa, Junko Sugama, Toshio Nakatani
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Nakajima, Yukari ; Asano, Kimi ; Mukai, Kanae ; Urai, Tamae ; Okuwa, Mayumi ; Sugama, Junko ; Nakatani, Toshio ; 中島, 由加里 ; 向井, 加奈恵 ; 大桑, 麻由美 ; 須釜, 淳子 ; 中谷, 壽男
概要:
金沢大学医薬保健研究域<br />Since lymphedema rarely develops in the mouse hindlimb, the underlying mechanisms remain unclear. We he
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rein investigated the resolution of chronic hindlimb lymphedema in mice using a Near-Infrared Fluorescence (NIRF) imaging system. Nineteen 7–28-week-old BALB/c male and female mice were injected with two dyes for lymphography and dissection. Lymphadenectomy was performed on six male mice to completely obstruct lymph flow in the hindlimb. Edematous changes in both hindlimbs were compared until 60 days after surgery. The NIRF imaging system detected three lymphatic collecting systems in the mouse hindlimb: superficial lateral, superficial medial, and deep medial. It also showed connections between the superficial and deep lymphatic systems in the inguinal region. Lymphadenectomy of the iliac, inguinal, and popliteal lymph nodes caused edematous changes. However, lymph flow in these operated areas restarted within 60 days and the severity of lymphedema appeared to be low. NIRF imaging showed that the deep medial system and a connection between the superficial and deep lymphatic systems in the inguinal region drain lymph from the hindlimb. This is the one reasons why lymphedema does not develop in the mouse hindlimb. The stable obstruction of lymph flow in these three systems is desired to develop chronic lymphedema.
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| 8.
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Urai, Tamae ; Nakajima, Yukari ; Mukai, Kanae ; Asano, Kimi ; Okuwa, Mayumi ; Sugama, Junko ; Nakatani, Toshio ; 中島, 由加里 ; 向井, 加奈恵 ; 大桑, 麻由美 ; 須釜, 淳子 ; 中谷, 壽男
概要:
金沢大学医薬保健研究域<br />It was unclear that wound healing was delayed in obesity without hyperglycemia. The purpose of this stu
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dy was to compare the wound healing process between obese and non-obese mice without hyperglycemia by attaching a splint. Three-week-old male mice (C57BL/6N) were fed high-fat diets (60% of calories from fat) in the obesity group, and commercial diets in the control group for 15 weeks. Two circular (4 mm in diameter) full-thickness wounds were made on the dorsal skin. Body weights and serum leptin levels were significantly higher in the obesity group than in the control group until day 15 after wounding. Fasting blood glucose levels before wounding were lower in the obesity group than in a hyperglycemic rodent model. The macrophage infiltration into subcutaneous fat before wounding in the obesity group was negligible. The ratios of the wound area were not significantly different between the two groups. No significant differences were observed in the number of neutrophils or macrophages or new blood vessels and ratio of myofibroblasts or collagen fibers between the two groups. Our results demonstrated that cutaneous wound healing was not delayed in the obesity group without hyperglycemia and macrophage infiltration into the subcutaneous fat and with high serum leptin levels.
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| 9.
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Mukai, Kanae ; Urai, Tamae ; Asano, Kimi ; Nakajima, Yukari ; Nakatani, Toshio ; 向井, 加奈恵 ; 中島, 由加里 ; 中谷, 壽男
概要:
金沢大学医薬保健研究域<br />Estrogen promotes cutaneous wound healing in ovariectomized (OVX) female mice. However, the effects of
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topical estrogen application on wounds remain unclear. Therefore, the aim of this study was to compare the effects of topical estrogen application on wounds with standard treatment methods. Eight-week-old C57BL/6J female mice underwent OVX and received two full-thickness wounds four weeks later. Mice were divided into three groups: topical estradiol benzoate (EB) (0.75 μg/g/day) wound treatment, subcutaneous estradiol (E2) pellets (0.05 mg, 21 days), and topical E2 (0.01 g/day) skin application. Wound healing was observed until day 14. Wound area ratios were significantly smaller in the topical EB wound treatment group than in the subcutaneous E2 pellet group on days 1-14 (p < 0.05) and topical E2 skin application group on days 1-9 (p < 0.05). Neutrophil and macrophage numbers were significantly smaller in the topical EB wound treatment group than in the subcutaneous E2 pellet and topical E2 skin application groups on day 7 (p < 0.05). Moreover, the number of new blood vessels and ratio of myofibroblasts were significantly larger in the topical EB wound treatment group than in the subcutaneous E2 pellet and topical E2 application skin groups on day 7 (p < 0.05). These results demonstrate that the application of estrogen to wounds reduced inflammatory responses and promoted angiogenesis and wound contraction more than the two other standard treatment methods. � 2016 Mukai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 10.
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論文
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中谷, 壽男 ; 向井, 加奈恵 ; 中島, 由加里 ; Nakatani, Toshio ; Mukai, Kanae ; Nakajima, Yukari
概要:
我々が行ってきた研究の内容の概要を記載する。Ⅰ．人体に見られる破格（変異， anatomical variation）, Ⅱ．リンパ管小孔（lymphatic stomata），Ⅲ．心膜孔（pericardial pores），Ⅳ．皮静脈注
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射（peripheral intravenous injection），Ⅴ．筋肉内注射（intramuscular injection）， Ⅵ．リン パ 浮 腫（lymphedema）， Ⅶ．皮 膚 創 傷 治 癒（cutaneous wound healing）である。破格を知ることで，臨床で利用できる。リンパ管小孔は特に横隔膜の腹膜に見られる構造で，漿液の吸収に関係している。心膜孔は人では見られないが，生き物の構造の面白さである。注射は，臨床で多用されている手技であるが，特に三角筋への筋注は，臨床で参考になると思われる。リンパ浮腫はリンパ節，リンパ管切除後に発生するが，齧歯類では浮腫が発生し難い理由が一部判明したので，人でも参考になるかと思われる。皮膚創傷治癒は，いろいろな条件を試すことで，創傷が早くかつ綺麗に治癒することの可能性を記載してあるので，参考になると思われる。
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