肘の内外反変形に伴う尺骨神経の伸長度変化に関する生体力学的研究

Background: Cubital tunnel syndrome can be caused by overtraction and dynamic compression in elbow deformities. The extent to which elbow deformities contribute to ulnar nerve strain is unknown. Here, we investigated ulnar nerve strain caused by cubitus valgus/varus deformity using fresh-frozen cadavers. Methods: We used six fresh-frozen cadaver upper extremities. A strain gauge was placed on the ulnar nerve 2 cm proximal to the medial epicondyle of the humerus. For the elbow deformity model, osteotomy was performed at the distal humerus, and plate fixation was performed to create cubitus valgus/varus deformities (10°, 20°, and 30°). Ulnar nerve strain caused by elbow flexion (0–125°) was measured in both the normal and deformity models. The strains at different elbow flexion angles within each model were compared, and the strains at elbow extension and at maximum elbow flexion were compared between the normal model and each elbow deformity model. However, in the cubitus varus model, the ulnar nerve deflected more than the measurable range of the strain gauge; elbow flexion of 60° or more were considered effective values. Statistical analysis of the strain values was performed with Friedman test, followed by the Williams’ test (the Shirley‒Williams’ test for non-parametric analysis). Results: In all models, ulnar nerve strain increased significantly from elbow extension to maximal flexion (control: 13.2%; cubitus valgus 10°: 13.6%; cubitus valgus 20°: 13.5%; cubitus valgus 30°: 12.2%; cubitus varus 10°: 8.3%; cubitus varus 20°: 8.2%; cubitus varus 30°: 6.3%, P < 0.001). The control and cubitus valgus models had similar values, but the cubitus varus models revealed that this deformity caused ulnar nerve relaxation. Conclusions: Ulnar nerve strain significantly increased during elbow flexion. No significant increase in strain 2 cm proximal to the medial epicondyle was observed in the cubitus valgus model. Major changes may have been observed in the measurement behind the medial epicondyle. In the cubitus varus model, the ulnar nerve was relaxed during elbow extension, but this effect was reduced by elbow flexion.博士（医学）・甲第865号・令和5年3月15

凍結保存骨形成細胞シートの骨再建における有用性

Skeletal diseases, such as nonunion and osteonecrosis, are now treatable with tissue engineering techniques. Single cell sheets called osteogenic matrix cell sheets (OMCSs) grown from cultured bone marrow-derived mesenchymal stem cells show high osteogenic potential; however, long preparation times currently limit their clinical application. Here, we report a cryopreservation OMCS transplantation method that shortens OMCS preparation time. Cryopreserved rat OMCSs were prepared using slow- and rapid-freezing methods, thawed, and subsequently injected scaffold-free into subcutaneous sites. Rapid- and slow-frozen OMCSs were also transplanted directly to the femur bone at sites of injury. Slow-freezing resulted in higher cell viability than rapid freezing, yet all two cryopreservation methods yielded OMCSs that survived and formed bone tissue. In the rapid- and slow-freezing groups, cortical gaps were repaired and bone continuity was observed within 6 weeks of OMCS transplantation. Moreover, while no significant difference was found in osteocalcin expression between the three experimental groups, the biomechanical strength of femurs treated with slow-frozen OMCSs was significantly greater than those of non-transplant at 6 weeks post-injury. Collectively, these data suggest that slow-frozen OMCSs have superior osteogenic potential and are better suited to produce a mineralized matrix and repair sites of bone injury.博士（医学）・甲第650号・平成28年3月15日Copyright © 2016 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0

Emerging Technologies for Telemedicine

This paper focuses on new technologies that are practically useful for telemedicine. Three representative systems are introduced: a Digital Video Transport System (DVTS), an H.323 compatible videoconferencing system, and Vidyo. Based on some of our experiences, we highlight the advantages and disadvantages of each technology, and point out technologies that are especially targeted at doctors and technicians, so that those interested in using similar technologies can make appropriate choices and achieve their own goals depending on their specific conditions

動物モデルにおける骨髄間質細胞シートの乱軸型皮弁の延長効果

BACKGROUND: Bone marrow stromal cells can be applied therapeutically to enhance angiogenesis; however, the use of bone marrow stromal cell suspensions reduces efficiency because of low-level attachment. The authors hypothesized that bone marrow stromal cell sheets would facilitate cell fixation, thus enhancing angiogenesis. The authors investigated flap survival area and enhancement of angiogenic factors in a rat random-pattern skin flap model after application of bone marrow stromal cell sheets. METHODS: Bone marrow stromal cell sheets (prepared from 7-week-old rat femurs) were cultured under four different hypoxic conditions. Sheets with the highest angiogenic potential, determined by an in vitro pilot study, were injected into subcutaneous layers of the rat dorsum (bone marrow stromal cell sheet group). A control group (phosphate-buffered saline only) was included. On day 2 after injection, caudally based random-pattern skin flaps (12 × 3 cm) were elevated. On day 7 after elevation, surviving skin flap areas were measured. Skin samples were harvested from each flap and gene expression levels of vascular endothelial growth factor and basic fibroblast growth factor were measured by quantitative real-time polymerase chain reaction. RESULTS: Skin flap survival area (71.6 ± 2.3 percent versus 51.5 ± 3.3 percent) and levels of vascular endothelial growth factor and basic fibroblast growth factor were significantly higher in the bone marrow stromal cell sheet group than in the control group (p < 0.05). CONCLUSIONS: Implantation of bone marrow stromal cell sheets increased the survival area of random-pattern skin flaps. Expression of angiogenic factors may have contributed to the increased flap survival.博士（医学）・甲第658号・平成28年11月24日Copyright © 2015 American Society of Plastic SurgeonsThe definitive version is available at " http://dx.doi.org/10.1097/PRS.0000000000001679

Anti-neutrophilic inflammatory activity of ASP3258, a novel phosphodiesterase type 4 inhibitor

a b s t r a c t a r t i c l e i n f o Neutrophil-dominant pulmonary inflammation is an important feature of chronic obstructive pulmonary disease (COPD). Here, we evaluated the in vitro and in vivo anti-neutrophilic inflammatory activities of ASP3258, a novel, orally active, and selective phosphodiesterase (PDE) 4 inhibitor with anti-inflammatory potency comparable to that of second-generation compound roflumilast but with lower emetic activity in vivo. In in vitro experiments using human peripheral blood neutrophils, PDE4 inhibitors ASP3258, cilomilast, and roflumilast inhibited fMLP-induced superoxide production in a concentration-dependent manner with IC50 values of 5.0, 96, and 4.7 nM, respectively. ASP3258, cilomilast, and roflumilast also attenuated fMLPinduced neutrophil chemotaxis in a concentration-dependent manner with IC30 values of 18, 270, and 9.7 nM, respectively. In contrast, the glucocorticoid prednisolone inhibited neither superoxide production nor chemotaxis up to 1 μM. In a rat model of lipopolysaccharide (LPS)-induced lung inflammation, orally administered ASP3258, cilomilast, roflumilast, and prednisolone (at 10 or 30 mg/kg) dose-dependently attenuated pulmonary accumulation of neutrophils. The inhibitory effect of ASP3258 was more potent than cilomilast and almost the same as roflumilast and prednisolone. Treatment with ASP3258 inhibited the elevation of TNF-α in the bronchoalveolar lavage fluid following LPS instillation. Histological examination revealed significant inhibition of neutrophil and macrophage infiltration into alveoli by ASP3258. Overall, these findings suggest that ASP3258 has therapeutic potential for treating neutrophilic inflammation such as COPD, partly through direct inhibition of neutrophil activation as well as possibly through inhibition of the TNF-α-mediated pathway

Increased Ratio of Non-mercaptalbumin-1 Among Total Plasma Albumin Demonstrates Potential Protein Undernutrition in Adult Rats

The redox state of plasma albumin shifts in response to dietary protein intake in growing rats, and the shift is more sensitive than that of plasma albumin level, a classical marker of protein nutritional status. While it has been suggested that plasma albumin redox state could be useful as a novel marker of protein nutritional status, the above animal model is highly sensitive to dietary protein intake and the observation may not be extrapolated widely to humans. This study aimed to investigate whether albumin redox state also reflects protein nutritional status in adult rats, which have a lower dietary protein requirement and are less responsive to protein intake. Male adult rats were placed on AIN-93M diet (14% casein), or AIN-93M-based low protein diets (10 or 5% casein) ad libitum for 24 weeks. Whereas there was no significant difference in body weight between the groups at the end of the experimental period, the 5% casein diet group had the smallest gastrocnemius muscle weight among the groups, which was significantly lower than that of the 10% casein diet group. Plasma albumin level was also lower in the 5% casein diet group compared with the other groups, but the differences were limited and inconsistent during the experimental period. Among the albumin redox isoforms such as mercaptalbumin, non-mercaptalbumin-1, and non-mercaptalbumin-2, the ratio of non-mercaptalbumin-1 among total albumin was significantly higher in the 5% casein diet group, and the increase remained constant throughout the experimental period. Increased non-mercaptalbumin-1 ratio would thus demonstrate the presence of potential protein undernutrition in adult rats, as manifested only by a decreased gain in a specific type of skeletal muscle; non-mercaptalbumin-1 among total albumin ratio could be useful as a robust marker of protein nutritional status, contributing to prevention of protein undernutrition-related diseases such as frailty and sarcopenia

Plasma Albumin Redox State Is Responsive to the Amino Acid Balance of Dietary Proteins in Rats Fed a Low Protein Diet

We recently reported that plasma albumin redox state, which correlates with albumin synthesis rate, could be associated with the quality of dietary protein. Aiming to elucidate the association between them, plasma albumin redox state was investigated in rats fed various kinds of AIN-93G-based low protein diets. Plasma albumin redox state was shifted to a more oxidized state in rats fed 3% casein (CN) diet than those fed 3% whey protein or 3% wheat gluten diet, while supplementing 3% CN diet with cystine reversed it to a more reduced state, indicating that cystine would complement the shortage of cysteine in CN, thereby increasing albumin synthesis rate. Supplementation with glutathione, a cysteine-containing antioxidative tripeptide, normalized hepatic glutathione redox state modulated by ingestion of 3% CN diet, but it only reversed the oxidized shift of plasma albumin redox state to an extent similar to cystine alone or the constituting amino acid mixture of glutathione (i.e., glutamic acid, cystine, and glycine), indicating that glutathione would primarily serve as a source of cysteine rather than exert its antioxidative activity. Plasma albumin would thus be influenced by amino acid balance in dietary proteins, and it could be useful as a biomarker that contributes to prevention of protein under-nutriton, caused by not only insufficient protein intake but also ingestion of poor-quality protein