Influence of ROM Exercise on the Joint Components during Immobilization

13301乙第2046号博士（保健学）金沢大学博士論文要旨Abstract 要約Outline 以下に掲載：Journal of Physical Therapy Science 25(12) pp.1547-1551 2013. The Society of Physical Therapy Science. 共著者：Taro Matsuzaki, Shinya Yoshida, Satoshi Kojima, Masanori Watanabe, Masahiro Hos

Hinode Calibration for Precise Image Co-alignment between SOT and XRT (November 2006 -- April 2007)

To understand the physical mechanisms for activity and heating in the solar atmosphere, the magnetic coupling from the photosphere to the corona is an important piece of information from the Hinode observations, and therefore precise positional alignment is required among the data acquired by different telescopes. The Hinode spacecraft and its onboard telescopes were developed to allow us to investigate magnetic coupling with co-alignment accuracy better than 1 arcsec. Using the Mercury transit observed on 8 November 2006 and co-alignment measurements regularly performed on a weekly basis, we have determined the information necessary for precise image co-alignment and have confirmed that co-alignment better than 1 arcsec can be realized between Solar Optical Telescope (SOT) and X-Ray Telescope (XRT) with our baseline co-alignment method. This paper presents results from the calibration for precise co-alignment of CCD images from SOT and XRT.Comment: 8 pages, 9 figures, accepted for publication in PASJ (Hinode Special issue

Histopathological changes in surrounding tissue of the sciatic nerve after spinal cord injury in rats

[Purpose] The purpose of this study was to examine histopathological changes in tissue surrounding the sciatic nerve after spinal cord injury (SCI) in rats. [Subjects and Methods] Thirty adult, nine-week-old, female Wistar rats were used in this study. Fifteen experimental rats underwent spinal cord transection at the level of Th8-9 and the other fifteen control rats were raised normally. Animals were assessed at 1, 2, 4, 8, and 12 weeks following surgery. After the experimental period, we obtained tissue surrounding the sciatic nerve of the thigh after hematoxylin and eosin staining under a microscope. [Results] Adherence between the nerve bundle and perineural innermost layer was observed in tissue surrounding the sciatic nerve in the SCI group. Adherence among the interperineurium was evident at 2 weeks after SCI. It had declined at 4 weeks after SCI, but was still evident at 8 and 12 weeks after SCI. [Conclusion] Histopathological findings in the SCI model may be related to compression of the nerve bundle and neurogenic contracture of tissue surrounding the nerve bundle.Thesis of Ippei Kitade / 北出 一平 博士論文 金沢大学医薬保健学総合研究科（保健学専攻

関節可動域運動はラット関節拘縮モデルにおける関節包の筋線維芽細胞増生を抑制する

Objective: Immobilization of the rat knee joint causes fibrosis of the joint capsule, andmyofibroblasts have been implicated as the cause. This study aimed to perform range ofmotion exercises on a rat knee joint contracture model and clarify changes in the jointrange of motion and changes in the joint capsule using α -SMA-positive cells.Subjects and Methods: Eighteen male Wistar rats were used and randomly divided intothe following three groups: control, immobilized, and exercise. The right hindlimb kneejoints of rats in the immobilized and exercise groups were immobilized with externalfixation at 120 degrees of flexion, and range of motion exercises were started for theanimals in the exercise group the day after the joint immobilization. After a two-weekexperimental period, the knee joint extension restriction angles were measured, and theknee joints were collected as specimens. To observe the posterior joint capsules of the ratknee joints, hematoxylin and eosin staining and double immunostaining for α -SMA andCD34 were performed.Results: Differences in knee extension restriction angles were significant between allgroups, and differences in the number of α -SMA-positive cells were significant betweenthe control and immobilization groups.Conclusion: These results suggest that joint immobilization leads to the proliferationof myofibroblasts, and that range-of-motion exercises may inhibit the proliferation ofmyofibroblasts

Long-term histopathological developments in knee-joint components in a rat model of osteoarthritis induced by monosodium iodoacetate

[Purpose] This study was performed to evaluate the long-term histopathological changes in knee-joint components including synovial membrane and joint capsule in a rat model of osteoarthritis (OA) induced by monosodium iodoacetate (MIA). [Subjects and Methods] Fifty male rats were used. OA was induced through intra-articular injection of MIA, and ten rats were randomly allocated to each of five groups induced with OA for 1, 2, 4, 6, or 8 weeks. At the end of each period, the knee components were examined histopathologically. [Results] After 1 and 2 weeks, chondrocytes were weakly stained. After 4 weeks, fibrillation, fissuring, and eburnation were observed, whereas after 6 weeks, chondrocyte clustering and osteophyte formation were detected. In the synovial membrane, the proliferation of spindle-shaped cells and a multilayered structure of the surface cells were observed at 1 and 2 weeks, but the degree of these changes decreased over time. In the joint capsule, a narrowing of the space between collagen fiber bundles was observed at 4–8 weeks. [Conclusion] The long-term histopathological changes of the joint components observed in a rat model of OA induced by MIA were similar to those detected in OA, but differed at specific times and tissues.出版者照会後に全文公

非荷重でのラット後肢膝関節の不動による関節構成体の変化

The purpose of this study was to establish a method of knee immobilization associated with hindlimb unloading, and to investigate the histopathological changes of the knee joint components after immobilization and unloading.Forty male Wistar rats were randomly divided into four groups: control group, unweighting group, knee immobilization group, and unweighting + joint immobilization group. The knee immobilization was performed using external fixation. For the hindlimb unweighting, a Kirschner wire was inserted at the rat’s caudal vertebra and a stainless steel wire was attached to the Kirschner wire to allow hindlimb suspension by the tail.After two weeks of intervention, the body weight and knee range of motion were measured, and the histopathological changes in the articular cavity and joint capsule were examined. There was no significant difference between the body weight and the range of joint motion among the 4 groups before the intervention. After the experimental period, the average body weight was no statistically significant between them.The knee range of joint motion was no significant different between unweighting group and control group, however, immobilized groups had significant decrease in comparison with non-immobilized groups. In unweighting groups, the cartilage was directly exposed to the articular cavity, and the surface of the articular cartilage was smooth. Conversely, invasion and adhesion of the granulation-like tissue into the joint cavity were observed in joint immobilization groups. Joint capsule of control groups and unweighting groups was typically composed of coarse and relatively loose fibrous connective tissues. The immobilized groups presented dense collagen bundles with narrow interstitial spaces and congested blood vessels in all cases. In the knee immobilization associated with unweighting group, the increase in collagen fiber density was less obvious in comparison with that observed in animals of immobilized group.Although the Kirschner wire insertion is an invasive intervention, the animals in our study showed increasing body weight compared to the baseline weight. In addition, no suspension failing episodes were observed across the study, thus there was no need to re-suspend or drop-out animals. Therefore, the tail suspension technique using Kirschner wire reported in this study, could be safer and a less stressful technique of hindlimb suspension compared to other conventional techniques.We also concluded the method described in this study does not allow weight bearing during joint immobilization resulting in better simulation of the joint contracture observation in clinical practice.今回の実験の目的は、ラット後肢を非荷重としたまま飼育する方法を確立すること、および荷重の有無が関節不動による関節構成体の変化にどのように影響するのかを調査することである。　40 匹の Wistar 系雄性ラットを使用し、無作為に 4 群に分けた。それぞれ対照群、非荷重群、関節不動群、不動と非荷重群とした。関節不動は創外固定を用いて後肢膝関節を屈曲 120 度で不動化した。非荷重群はラットの尾骨に Kirschner 鋼線を刺し、ステンレスワイヤを用いて尾部を懸垂し、足部が接地しないようにした。　介入の 2 週後、体重と関節可動域を測定した後に関節腔と関節後方の関節包を病理組織学的に観察した。　実験後の体重には各群に差は見られなかった。関節可動域は対照群および非荷重群に対し不動群、関節不動と非荷重群で有意に減少していた。また、不動と非荷重群と比較して関節不動群では有意な可動域の減少が見られた。関節腔では対照群、懸垂群は軟骨が直接関節腔に露出していたが、関節不動群、不動と非荷重群では肉芽様組織の関節腔内の侵入，関節軟骨表層の膜様組織との癒着が観察され，不動と非荷重群では軟骨表層の膜様組織は限局的であった。関節包は対照群、非荷重群ではコラーゲン線維間に間隙を認め，比較的疎性であったが，関節不動群ではコラーゲン線維束はやや組硬化し，線維素区間が狭まり密生化しており，全例でうっ血像が観察された。不動と非荷重群では線維の密生化は見られたものの関節不動群と比較して軽度であった。　今回の手技は侵襲はあるものの懸垂が外れることはなく、より臨床での関節拘縮に近い研究を行う一助となると考えられる

Phosphorylated Smad2 in Advanced Stage Gastric Carcinoma

<p>Abstract</p> <p>Background</p> <p>Transforming growth factor β (TGFβ) receptor signaling is closely associated with the invasion ability of gastric cancer cells. Although Smad signal is a critical integrator of TGFβ receptor signaling transduction systems, not much is known about the role of Smad2 expression in gastric carcinoma. The aim of the current study is to clarify the role of phosphorylated Smad2 (p-Smad2) in gastric adenocarcinomas at advanced stages.</p> <p>Methods</p> <p>Immunohistochemical staining with anti-p-Smad2 was performed on paraffin-embedded specimens from 135 patients with advanced gastric adenocarcinomas. We also evaluated the relationship between the expression levels of p-Smad2 and clinicopathologic characteristics of patients with gastric adenocarcinomas.</p> <p>Results</p> <p>The p-Smad2 expression level was high in 63 (47%) of 135 gastric carcinomas. The p-Smad2 expression level was significantly higher in diffuse type carcinoma (p = 0.007), tumours with peritoneal metastasis (p = 0.017), and tumours with lymph node metastasis (p = 0.047). The prognosis for p-Smad2-high patients was significantly (p = 0.035, log-rank) poorer than that of p-Smad2-low patients, while a multivariate analysis revealed that p-Smad2 expression was not an independence prognostic factor.</p> <p>Conclusion</p> <p>The expression of p-Smad2 is associated with malignant phenotype and poor prognosis in patients with advanced gastric carcinoma.</p

The histological effect of immobilization and unloading/reloading on articular cartilage of rat knee joint

これまで、ラット膝関節の不動化による関節周囲組織の組織学的変化が報告されているが、臨床の場においてギプス固定がなされる場合には非荷重の状態となることが多い。荷重の除去が長期に及ぶと膝半月板内の機械受容器数が減少し、長期臥床や免荷直後は関節損傷の危険性が高いとの報告もある。今回ラット膝関節をギプス固定するだけでなく、後肢懸垂法を用いて非荷重モデルと非荷重の後に再荷重を加えたモデルを作成し、荷重の有無による影響を調査した。　 ２ 週間片側下肢のギプス固定と後肢懸垂を行った群 ( ２ IS 群 )、 4 週間片側下肢のギプス固定と後肢懸垂を行った群 ( 4 IS 群 )、 ２ 週間片側下肢のギプス固定と後肢懸垂を行い、その後 ２ 週間ケージ内にて自由飼育とし再荷重を行った群 ( ２ IS+IL 群 )、 ２ 週間通常飼育の対照群( ２C 群)、4 週間通常飼育の対照群( 4C 群)で比較した。　 ２ IS 群では膝関節軟骨表面の不整が確認され、 4 IS 群では軟骨表面の変化はさらに進行していた。 ２ IS+IL 群では関節軟骨と周囲組織の癒着は確認されず、軟骨表面の変化は２ IS 群よりも軽減していた。　不動と非荷重が組み合わさった際には膝関節軟骨組織の変化について相加的な影響をもたらす可能性が明らかになり、再荷重により関節軟骨は修復されうることが考えられる。関節軟骨の正常状態維持には適切な関節運動と荷重が必要である。Purpose: Joint movement and loading are thought to maintain articular cartilage. In this study, we performed histological examination of the effects of immobilization and unloading/reloading on articular cartilage in the rat knee joint.　Materials and Methods: Twenty-five adult, 9-week-old, male rats were used in this study. The animals were randomly divided into five groups of equal size: two-week caged control (２C), 4-week caged control (4C), ２-week hind limb suspension with cast immobilization (２IS), 4-week hind limb suspension with cast immobilization (4IS), and ２-week hind limb suspension with cast immobilization and ２-week reloading with cast immobilization (２IS+IL). Rats in the experimental groups had one knee joint immobilized for ２ or 4 weeks in maximum flexion with a plaster cast of our own making and aluminum wire netting. After the end of each experimental period, tissue specimens of the knee joint were prepared for observation in the sagittal plane and examined under a light microscope with hematoxylin-eosin staining.　Results: In the control groups (２C or 4C), the surface of the articular cartilage was smooth and continuous. On the other hand, the surface of the femoral articular cartilage was irregular in the experimental groups. The pathological changes in the cartilage surfaces showed greater progression in the 4IS group than that the ２IS group. We observed adhesions between the cartilage surface layer and synovial membrane in some specimens in the 4IS group. The pathological changes in the cartilage surfaces were less severe in the ２IS+IL group than the ２IS group.　Conclusion: Immobilization and unloading caused irregularity of the femoral articular cartilage surface as well as adhesions between the cartilage surface layer and synovial membrane in some specimens. Reloading may be related to cartilage repair

Destruction of Dopaminergic Neurons in the Midbrain by 6-Hydroxydopamine Decreases Hippocampal Cell Proliferation in Rats: Reversal by Fluoxetine

Background Non-motor symptoms (e.g., depression, anxiety, and cognitive deficits) in patients with Parkinson disease (PD) precede the onset of the motor symptoms. Although these symptoms do not respond to pharmacological dopamine replacement therapy, their precise pathological mechanisms are currently unclear. The present study was undertaken to examine whether the unilateral 6-hydroxydopamine (6-OHDA) lesion to the substantia nigra pars compacta (SNc), which represents a model of long-term dopaminergic neurotoxicity, could affect cell proliferation in the adult rat brain. Furthermore, we examined the effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine and the selective noradrenaline reuptake inhibitor maprotiline on the reduction in cell proliferation in the subgranular zone (SGZ) by the unilateral 6-OHDA lesion. Methodology/Principal Findings A single unilateral injection of 6-OHDA into the rat SNc resulted in an almost complete loss of tyrosine hydroxylase (TH) immunoreactivity in the striatum and SNc, as well as in reductions of TH-positive cells and fibers in the ventral tegmental area (VTA). On the other hand, an injection of vehicle alone showed no overt change in TH immunoreactivity. A unilateral 6-OHDA lesion to SNc significantly decreased cell proliferation in the SGZ ipsilateral to the 6-OHDA lesion, but not in the contralateral SGZ or the subventricular zone (SVZ), of rats. Furthermore, subchronic (14 days) administration of fluoxetine (5 mg/kg/day), but not maprotiline significantly attenuated the reduction in cell proliferation in the SGZ by unilateral 6-OHDA lesion. Conclusions/Significance The present study suggests that cell proliferation in the SGZ of the dentate gyrus might be, in part, under dopaminergic control by SNc and VTA, and that subchronic administration of fluoxetine reversed the reduction in cell proliferation in the SGZ by 6-OHDA. Therefore, SSRIs such as fluoxetine might be potential therapeutic drugs for non-motor symptoms as well as motor symptoms in patients with PD, which might be associated with the reduction in cell proliferation in the SGZ