Takako Chikenji

Comparison of Different Fixation Methods of the Suture-Button Implant for Tibiofibular Syndesmosis Injuries

Background: Suture-button fixation for tibiofibular syndesmosis injuries is a relatively new surgical technique thought to provide semirigid dynamic stabilization. However, adequate information is still not available and there are controversies as to whether it provides enough fixation for syndesmosis injuries. Hypothesis: Optimally directed suture-button fixation brings physiologic dynamic stabilization of the ankle syndesmosis. Study Design: Controlled laboratory study. Methods: Stabilization of the ankle syndesmosis fixed by a suture-button construct was examined using 6 normal fresh-frozen cadaver legs. After initial tests of intact and injured models, suture-button fixation and screw surgical techniques were performed sequentially for each specimen, with single suture-button fixation, double suture-button fixation, anatomic suture-button fixation, and metal screw. Anterior and medial traction forces, as well as external rotation force, were applied to the tibia; the diastasis of the syndesmosis and the rotational angle of the fibula related to the tibia were measured using a magnetic tracking system. Results: Each traction and rotation force significantly increased the diastasis and fibular rotational angles in the created injury models. With single fixation, the diastases increased significantly compared with the intact model with an anterior traction force (P < .001), a medial traction force (P = .005), and an external rotation force (P = .015). The fibular rotational angles increased significantly with a medial traction force (P = .005) and an external rotation force (P < .001). With double fixation, the diastases increased significantly with a medial traction force (P = .004) and an external rotation force (P = .012). The fibular rotational angles increased significantly with a medial traction force (P = .035) and an external rotation force (P = .002). With anatomic fixation, there were no significant differences compared with the intact model. With the metal screw, the diastases decreased significantly with an external rotation force (P = .037). Conclusion: Neither single nor double fixation for syndesmosis injuries provided multidirectionally stabilizing syndesmosis. Anatomic fixation directed from the posterior cortex of the fibula to the anterolateral edge of the tibia allowed dynamic stabilization of intact cadaver specimens. The metal screw provided very rigid fixation. Clinical Relevance: Optimal direction of the suture button can provide adequate stabilization of the ankle and could benefit athletes with syndesmosis injuries.

Bone marrow-derived mesenchymal stem cells improve diabetes-induced cognitive impairment by exosome transfer into damaged neurons and astrocytes

The incidence of dementia is higher in diabetic patients, but no effective treatment has been developed. This study showed that rat bone marrow mesenchymal stem cells (BM-MSCs) can improve the cognitive impairments of STZ-diabetic mice by repairing damaged neurons and astrocytes. The Morris water maze test demonstrated that cognitive impairments induced by diabetes were significantly improved by intravenous injection of BM-MSCs. In the CA1 region of the hippocampus, degeneration of neurons and astrocytes, as well as synaptic loss, were prominent in diabetes, and BM-MSC treatment successfully normalized them. Since a limited number of donor BM-MSCs was observed in the brain parenchyma, we hypothesized that humoral factors, especially exosomes released from BM-MSCs, act on damaged neurons and astrocytes. To investigate the effectiveness of exosomes for treatment of diabetes-induced cognitive impairment, exosomes were purified from the culture media and injected intracerebroventricularly into diabetic mice. Recovery of cognitive impairment and histological abnormalities similar to that seen with BM-MSC injection was found following exosome treatment. Use of fluorescence-labeled exosomes demonstrated that injected exosomes were internalized into astrocytes and neurons; these subsequently reversed the dysfunction. The present results indicate that exosomes derived from BM-MSCs might be a promising therapeutic tool for diabetes-induced cognitive impairment.

Mesenchymal stem cell therapy ameliorates diabetic nephropathy via the paracrine effect of renal trophic factors including exosomes

Bone marrow-derived mesenchymal stem cells (MSCs) have contributed to the improvement of diabetic nephropathy (DN); however, the actual mediator of this effect and its role has not been characterized thoroughly. We investigated the effects of MSC therapy on DN, focusing on the paracrine effect of renal trophic factors, including exosomes secreted by MSCs. MSCs and MSC-conditioned medium (MSC-CM) as renal trophic factors were administered in parallel to high-fat diet (HFD)-induced type 2 diabetic mice and streptozotocin (STZ)-induced insulin-deficient diabetic mice. Both therapies showed approximately equivalent curative effects, as each inhibited the exacerbation of albuminuria. They also suppressed the excessive infiltration of BMDCs into the kidney by regulating the expression of the adhesion molecule ICAM-1. Proinflammatory cytokine expression (e.g., TNF-α) and fibrosis in tubular interstitium were inhibited. TGF-β1 expression was down-regulated and tight junction protein expression (e.g., ZO-1) was maintained, which sequentially suppressed the epithelial-to-mesenchymal transition of tubular epithelial cells (TECs). Exosomes purified from MSC-CM exerted an anti-apoptotic effect and protected tight junction structure in TECs. The increase of glomerular mesangium substrate was inhibited in HFD-diabetic mice. MSC therapy is a promising tool to prevent DN via the paracrine effect of renal trophic factors including exosomes due to its multifactorial action.

Transforming growth factor-β (TGF-β) expression is increased in the subsynovial connective tissues of patients with idiopathic carpal tunnel syndrome.

Non‐inflammatory fibrosis of the subsynovial connective tissue (SSCT) is a hallmark of carpal tunnel syndrome (CTS). The etiology of this finding and its relationship to the development of CTS remain poorly understood. Recent studies have found that transforming growth factor‐β (TGF‐β) plays a central role in fibrosis. The purpose of this study was to investigate the expression of TGF‐β and connective tissue growth factor (CTGF), a downstream mediator of TGF‐β, in the pathogenesis of CTS. We compared SSCT specimens from 26 idiopathic CTS patients with specimens from 10 human cadaver controls with no previous diagnosis of CTS. Immunohistochemistry was performed to determine levels TGF‐β1, CTGF, collagen 1(Col1) and collagen 3 (Col3) expression. TGF‐β1 (p < 0.01), CTGF (p < 0.01), and Col3 (p < 0.01) were increased in SSCT of CTS patients compared with control tissue. In addition, a strong positive correlation was found between TGF‐β1 and CTGF, (R2 = 0.80, p < 0.01) and a moderate positive correlation between Col3 and TGF‐β1 (R2 = 0.49, p < 0.01). These finding suggest that there is an increased expression of TGF‐β and CTGF, a TGF‐β regulated protein, and that this TGF‐β activation may be responsible for SSCT fibrosis in CTS patients.

Skeletal muscle and bone marrow derived stromal cells: A comparison of tenocyte differentiation capabilities

This study investigated the comparative ability of bone marrow and skeletal muscle derived stromal cells (BMSCs and SMSCs) to express a tenocyte phenotype, and whether this expression could be augmented by growth and differentiation factor‐5 (GDF‐5). Tissue harvest was performed on the hind limbs of seven dogs. Stromal cells were isolated via serial expansion in culture. After four passages, tenogenesis was induced using either ascorbic acid alone or in conjunction with GDF‐5. CD44, tenomodulin, collagen I, and collagen III expression levels were compared for each culture condition at 7 and 14 days following induction. Immunohistochemistry (IHC) was performed to evaluate cell morphology and production of tenomodulin and collagen I. SMSCs and BMSCs were successfully isolated in culture. Following tenocytic induction, SMSCs demonstrated an increased mean relative expression of tenomodulin, collagen I, and collagen III at 14 days. BMSCs only showed increased mean relative expression of collagen I, and collagen III at 14 days. IHC revealed positive staining for tenomodulin and collagen I at 14 days for both cell types. The morphology of skeletal muscle derived stromal cells at 14 days had an organized appearance in contrast to the haphazard arrangement of the bone marrow derived cells. GDF‐5 did not affect gene expression, cell staining, or cell morphology significantly. Stromal cells from either bone marrow or skeletal muscle can be induced to increase expression of matrix genes; however, based on expression of tenomodulin and cell culture morphology SMSCs may be a more ideal candidate for tenocytic differentiation.

The effect of lubricin on the gliding resistance of mouse intrasynovial tendon.

The purpose of this study was to investigate the role of lubricin on the gliding resistance of intrasynovial tendons by comparing lubricin knockout, heterozygous, and wild type mice. A total of thirty-six deep digital flexor (DDF) tendons in the third digits of each hind paw from eighteen adult mice were used, including six lubricin knockout mice (Prg4 –/–), six heterozygous mice (Prg4 +/–), and six wild type mice (Prg4 +/+). The tendon gliding resistance was measured using a custom-made device. Tendon structural changes were evaluated by scanning electron and light microscopy. The gliding resistance of intrasynovial tendons from lubricin knockout mice was significantly higher than the gliding resistance of either wild type or heterozygous mice. The surface of the lubricin knockout tendons appeared to be rougher, compared to the wild type and heterozygous tendons. Synovial hyperplasia was found in the lubricin knockout mice. Cartilage-like tissue was found in the tendon and pulley of the lubricin knockout mice. Our findings confirm the importance of lubricin in intrasynovial tendon lubrication. This knockout model may be useful in determining the effect of lubricin on tendon healing and the response to injury.

Distribution of nerve endings in human distal interphalangeal joint and surrounding structures

PURPOSE To examine the distribution of encapsulated nerve endings called mechanoreceptors in the human distal interphalangeal (DIP) joint and surrounding structures. METHODS We processed 12 right index finger DIP joints and surrounding structures from fresh cadavers for immunohistochemistry of the anti-protein gene product 9.5 (PGP9.5) and silver staining to detect encapsulated nerve endings. Serial transverse sections were cut throughout the whole specimen and divided into 3 regions along the longitudinal axis: distal, middle, and proximal. Each of the transverse sections was partitioned into dorsal capsule (DC), radial capsule (RC), ulnar capsule (UC), volar plate (VP), and radial and ulnar assemblage nuclei (RAN and UAN); the RAN and UAN are located on both the radial and ulnar side of the VP. The C3 pulley contained the proximal region of the RAN and UAN, whereas the A5 pulley contained the middle and distal. The accessory collateral ligament contained all the regions of the RAN and UAN. We analyzed and compared the density of encapsulated nerve endings among the 18 different regions. RESULTS According to the modified Freeman and Wyke classification, we identified type I (eg, Ruffini-like endings) and type II (eg, Pacini-like endings) nerve endings. The density of type II nerve endings in the proximal region of the RAN and UAN was considerably higher than that in the proximal region of the VP, RC, UC and DC, and that in the proximal region of the VP, RC, UC, and DC, respectively. CONCLUSIONS Our examination of the distribution of type I and type II nerve endings provides new information on the sensory systems of the DIP joints and surrounding structures.

Wrist Positioning and Muscle Activities in the Wrist Extensor and Flexor during Piano Playing

Objective Musicians tend to suffer from playing-related musculoskeletal problems over the forearm muscles. Lateral epicondylitis of the elbow is the most common disease of pianists. The purpose of this study was to measure by electromyography (EMG) the wrist extensor and flexor to clarify the burden of forearm muscles during piano playing with various wrist positions. Methods Fourteen female piano students and 14 novice females participated in this study. Surface EMG was conducted during piano playing in nine conditions that combined three wrist positions with three degrees of loudness. Results The muscle activities increased with the increase of loudness in both groups. Muscle activities for both the wrist extensor and flexor were the smallest in the neutral wrist position. There were no differences of the muscle activities between the piano-student and the control groups. Conclusion The neutral position of the wrist should be recommended for reduction of play ingrelated musculoskeletal burden during piano playing.

Activated forms of astrocytes with higher GLT-1 expression are associated with cognitive normal subjects with Alzheimer pathology in human brain

Although the cognitive impairment in Alzheimer’s disease (AD) is believed to be caused by amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), several postmortem studies have reported cognitive normal subjects with AD brain pathology. As the mechanism underlying these discrepancies has not been clarified, we focused the neuroprotective role of astrocytes. After examining 47 donated brains, we classified brains into 3 groups, no AD pathology with no dementia (N-N), AD pathology with no dementia (AD-N), and AD pathology with dementia (AD-D), which represented 41%, 21%, and 38% of brains, respectively. No differences were found in the accumulation of Aβ plaques or NFTs in the entorhinal cortex (EC) between AD-N and AD-D. Number of neurons and synaptic density were increased in AD-N compared to those in AD-D. The astrocytes in AD-N possessed longer or thicker processes, while those in AD-D possessed shorter or thinner processes in layer I/II of the EC. Astrocytes in all layers of the EC in AD-N showed enhanced GLT-1 expression in comparison to those in AD-D. Therefore these activated forms of astrocytes with increased GLT-1 expression may exert beneficial roles in preserving cognitive function, even in the presence of Aβ and NFTs.

Effects of different temperatures, velocities and loads on the gliding resistance of flexor digitorum profundus tendons in a human cadaver model

The purpose of this study was to investigate the effects of temperature, velocity and load on the gliding resistance (GR) of flexor digitorum profundus (FDP) tendons in a human cadaver model. A total of 40 FDP tendons from the index through small digits of ten human cadavers were tested to assess the effect of temperature (4, 23 or 36 °C), velocity (2, 4, 6, 8, 10 or 12 mm/s) and load (250, 500, 750, 1000, 1250 and 1500 g) on GR. The mean GR at 4 °C was significantly higher than the mean GR at 36 °C (p<0.0066). There was no significant difference in the mean GR of the tested velocities. The mean GR was proportional to load, with each successive load having significantly higher GR than the loads before it (all p<0.001). There was no significant difference in the mean GR by digit. In this in vitro model, we have demonstrated that tendon gliding resistance is proportional to load, independent of velocity and somewhat affected by temperature. We conclude that it is important to specify these conditions when reporting gliding resistance, especially load and temperature.