Sixty-Year Old Concrete in a Marine Environment

The deterioration of concrete structures due to age, particularly in marine environments, has recently become a subject of great concern. In this study, the properties of 60-year old concrete in a marine environment are examined, taking the opportunity of the demolition of the northern breakwater of Muroran Port in 1984 to obtain samples. As a result of the study it was found that the concrete, which was made from blast furnace slag and volcanic ash and appeared to contain sea sand, had scarcely deteriorated at all, even though it had been exposed to sea water environment for 60 years

Effects of interfascial injection of bicarbonated Ringer’s solution, physiological saline and local anesthetic under ultrasonography for myofascial pain syndrome -Two prospective, randomized, double-blinded trials-

Myofascial pain syndrome (MPS) is a common clinical condition of muscle pain. Previous studies indicated that local injection of physiological saline (PS) into a muscle is equal to or more effective than a local anesthetic for MPS. We performed 2 randomized, double-blinded trials of interfascial injection under ultrasonography for outpatients with MPS over 3 months to assess the effects of PS (pH 6.0), 0.5% mepivacaine hydrochloride (MH) (pH 6.0), and bicarbonate Ringer’s solution (BRS) (pH 7.4), and to elucidate their action mechanisms. Maximum pain related to motion, time of pain relief, and pain related to injection (intensity and duration) were measured up to 72 hrs. The first trial showed that PS decreased maximum pain related to motion compared to MH (p < 0.05), although it increased pain related to injection compared to MH (p < 0.05). The second trial showed that BRS exhibited as much efficacy in relieving maximum pain related to motion as PS (p = 0.33), but decreased pain related to injection compared to PS (p < 0.05). In conclusion, the interfascial injection of PS has a greater analgesic effect on MPS but produced stronger pain related to injection compared to MH. BRS is equivalent to PS in analgesic effect and produced less pain related to injection compared to PS. These results indicate that BRS is the appropriate solution for an interfascial injection to treat MPS, and that the action mechanisms are not related to the pain intensity associated with the injections or the pharmacological anesthetic effect

Central administration of melanocortin agonist increased insulin sensitivity in diet-induced obese rats

AbstractIn this study, we examined the effects of intracerebroventricular administration of melanotan II (MTII), a melanocortin agonist, on insulin sensitivity in diet-induced obese (DIO) rats. Although MTII treatment significantly decreased food intake and body weight for 10 days, there was no significant difference in body weight between MTII and pair-fed groups. The insulin tolerance test showed that insulin sensitivity was significantly improved in the MTII group compared to the pair-fed group. Furthermore, MTII treatment increased the number of small-sized adipocytes in epididymal white adipose tissues, suggesting that MTII increased insulin sensitivity through action on the white adipose tissues in DIO rats

Vitreous preservation of articular cartilage from cryoinjury in rabbits

Frozen osteoarticular grafts treated with liquid nitrogen are utilized for joint reconstruction after tumor resection, but the joints may subsequently develop osteoarthritic changes. To preserve articular cartilage from cryoinjury, we modified a vitrification method utilized for embryo cryopreservation and demonstrated in vitro that our vitrification protocol was effective for protecting cartilage from cryoinjury. In this study, we investigated in vivo whether this vitrification method could protect against osteoarthritic changes in articular cartilage. Osteochondral plugs were obtained from the distal femur of rabbits. These grafts were divided into 3 groups: Fresh group (F-group), non-vitrification group (N-group), and vitrification group (V-group). After treatment, the plugs were re-implanted as autografts. Histological findings, chondrocyte viability, and ultrastructural examinations were examined 6, 12, and 24. weeks after implantation. Histological findings of chondrocytes for the V-group showed no significant difference from those of the F-group at any time point except at 24. weeks postimplantation at the non-weight bearing site (p<0.05). Viability of chondrocyte showed no significant difference from those of the F-group except at 12. weeks postimplantation at the bearing site (p<0.05). In contrast, viable cells disappeared from the N-group and histology and viability significantly differed between the N-group and the V-group. Transmission electron microscopy demonstrated preservation of chondrocyte structure in the V-group and the F-group, but chondrocytes of the N-group were abnormally electron dense. Our vitrification method was effective in protecting chondrocytes from cryoinjury that might lead to cartilage degeneration. Reconstructing joints with osteoarticular grafts containing living cartilage may help to avert osteoarthritic changes. Our vitrification method could prove useful for reconstruction with frozen tumor-containing autografts and for long-term storage of living cartilage for allografts. © 2012 Elsevier Inc

Inhibitory Effect of a Tankyrase Inhibitor on Mechanical Stress-Induced Protease Expression in Human Articular Chondrocytes

We investigated the effects of a Tankyrase (TNKS-1/2) inhibitor on mechanical stress-induced gene expression in human chondrocytes and examined TNKS-1/2 expression in human osteoarthritis (OA) cartilage. Cells were seeded onto stretch chambers and incubated with or without a TNKS-1/2 inhibitor (XAV939) for 12 h. Uni-axial cyclic tensile strain (CTS) (0.5 Hz, 8% elongation, 30 min) was applied and the gene expression of type II collagen a1 chain (COL2A1), aggrecan (ACAN), SRY-box9 (SOX9), TNKS-1/2, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), and matrix metalloproteinase-13 (MMP-13) were examined by real-time PCR. The expression of ADAMTS-5, MMP-13, nuclear translocation of nuclear factor-κB (NF-κB), and β-catenin were examined by immunocytochemistry and Western blotting. The concentration of IL-1β in the supernatant was examined by enzyme-linked immunosorbent assay (ELISA). TNKS-1/2 expression was assessed by immunohistochemistry in human OA cartilage obtained at the total knee arthroplasty. TNKS-1/2 expression was increased after CTS. The expression of anabolic factors were decreased by CTS, however, these declines were abrogated by XAV939. XAV939 suppressed the CTS-induced expression of catabolic factors, the release of IL-1β, as well as the nuclear translocation of NF-κB and β-catenin. TNKS-1/2 expression increased in mild and moderate OA cartilage. Our results demonstrated that XAV939 suppressed mechanical stress-induced expression of catabolic proteases by the inhibition of NF-κB and activation of β-catenin, indicating that TNKS-1/2 expression might be associated with OA pathogenesis

Evaluation of FGFR inhibitor ASP5878 as a drug candidate for achondroplasia

Ozaki T., Kawamoto T., Iimori Y., et al. Evaluation of FGFR inhibitor ASP5878 as a drug candidate for achondroplasia. Scientific Reports 10, 20915 (2020); https://doi.org/10.1038/s41598-020-77345-y.Achondroplasia is caused by gain-of-function mutations in FGFR3 gene and leads to short-limb dwarfism. A stabilized analogue of C-type natriuretic peptide (CNP) is known to elongate bone by interacting with FGFR3 signals and thus is a promising drug candidate. However, it needs daily administration by percutaneous injection. FGFR inhibitor compounds are other drug candidates for achondroplasia because they directly fix the mutant protein malfunction. Although FGFR inhibitors elongate the bone of model mice, their adverse effects are not well studied. In this study, we found that a new FGFR inhibitor, ASP5878, which was originally developed as an anti-cancer drug, elongated the bone of achondroplasia model male mice at the dose of 300 μg/kg, which confers an AUC of 275 ng·h/ml in juvenile mice. Although ASP5878 was less effective in bone elongation than a CNP analogue, it is advantageous in that ASP5878 can be administered orally. The AUC at which minimal adverse effects were observed (very slight atrophy of the corneal epithelium) was 459 ng·h/ml in juvenile rats. The positive discrepancy between AUCs that brought efficacy and minimal adverse effect suggests the applicability of ASP5878 to achondroplasia in the clinical setting. We also analyzed effects of ASP5878 in a patient-specific induced pluripotent stem cell (iPSC) model for achondroplasia and found the effects on patient chondrocyte equivalents. Nevertheless, cautious consideration is needed when referring to safety data obtained from its application to adult patients with cancer in clinical tests

Involvement of NGF in the Rat Model of Persistent Muscle Pain Associated With Taut Band

Myofascial pain syndrome (MPS) is an important clinical condition characterized by chronic muscle pain and a myofascial trigger point (MTrP) located in a taut band (TB). However, its pathogenic mechanism is still unclear. We developed an animal model relevant to conditions of MPS, and analyzed the mechanism of the muscle pain in this model. We applied eccentric contraction (EC) to a rat\u27s gastrocnemius muscle (GM) for 2 weeks, and examined the mechanical withdrawal thresholds, histological changes, and expressions and contents of nerve growth factor (NGF). The mechanical withdrawal threshold decreased significantly at the next day of first EC and continued up to 9 days after EC. TBs were palpable at 3 to 8 days after initiation of EC. In EC animals, necrotic and regenerating muscle cells were found significantly more than in control animals. In EC animals, NGF expressions in regenerating muscle cells and NGF contents of GM were significantly higher than control animals. Administration of NGF receptor (TrkA) inhibitor K252a showed significant suppression of mechanical hyperalgesia in EC animals. Repeated EC induced persistent mechanical muscle hyperalgesia associated with TB. NGF expressed in regenerating muscle cells may have an important role in persistent mechanical muscle hyperalgesia which might be relevant to pathogenesis of MPS. Perspective: The present study shows that NGF expressed in regenerating muscle cells is involved in persistent muscular mechanical hyperalgesia. NGF-TrkA signaling in primary muscle afferent neurons may be one of the most important and promising targets for MPS. © 2011 American Pain Society

Neurological Recovery after Posterior Spinal Surgery in Patients with Metastatic Epidural Spinal Cord Compression

Metastatic epidural spinal cord compression (MESCC) is a common complication in patients with a malignant tumor, but it is difficult to decide the proper time to perform the necessary surgery. Here we analyzed the prognostic factors for postoperative walking ability. We retrospectively reviewed the cases of 112 MESCC patients treated surgically at our institute and divided them into ambulatory (n＝ 88) and non-ambulatory (n＝24) groups based on their American Spinal Injury Association (ASIA) Impairment Scale grades at the final follow-up. We also classified the patients preoperatively using the revised Tokuhashi score. We assessed the correlation between preoperative or intraoperative factors and postoperative walking ability in both groups. Of the 10 patients classified preoperatively as grade A or B, 2 (20 ) were ambulatory at the final follow-up. Of the 102 patients classified preoperatively as grade C, D or E, 86 (84 ) were ambulatory at the final follow-up (p＜0.001). There were no significant differences between the groups in the average total Tokuhashi score. Our analysis revealed that the severity of paralysis significantly affects neurological recovery in patients with MESCC. Patients with MESCC should receive surgery before the preoperative ASIA Impairment Scale grade falls below grade C

Verification of Implant Surface Modification by a Novel Processing Method

Metals have been used clinically as biomaterials, especially in the orthopaedic and dental fields. Metals used as implants wear at contact surfaces, producing metal particles and metal ions that may be harmful. Newly developed metal implants and methods of implant surface modification are currently under scrutiny. We evaluated the use of electrolytic in-process dressing (ELID) as a surface finishing method for metal implants. Metal implants processed using the ELID method (ELID group) or not processed (Non-ELID group) were inserted surgically into rabbit femurs. The rabbits were sacrificed postoperatively over a 24-week period. We assessed the concentrations of the cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, the resistance to implant pull-out, and histopathology at the implant site. There was no significant difference between the groups regarding the cytokine concentrations or implant pull-out resistance. Many particles indicating wear around the implant were noted in the Non-ELID group (n=10) but not the ELID group (n=13), while a fibrous membrane adhering to the every implant was noted in the ELID group. The formation of a fibrous membrane rather than metal particles in the ELID group may indicate improved biocompatibility, and it suggests that ELID may prevent corrosion in the areas of contact