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Background: Bone fragments are often found in ankles with anterior bony impingement. However, whether they are detached osteophytes or accessory bones remains unknown. Methods: Among the 66 continuously enrolled cases of ankles with anterior bony impingement, 32 had a fragment located at the anterior margin of the tibia. The cases of posterior impingement, lateral instability, osteochondral lesions, or free bodies simultaneously treated were excluded. The enrolled subjects were classified into 2 groups: ankles without (group A) and with remarkable spurs (group B). The patients’ backgrounds, location of the fragments, clinical scores, and other parameters required to resume sports were compared. The Japanese Society for Surgery of the Foot (JSSF) ankle rating scale was used to evaluate preoperative and postoperative ankle conditions, and the Self-Administered Foot Evaluation Questionnaire ( SAFE-Q ) was used to evaluate postoperative sports abilities. Results: Eight (seven subjects) and 11 ankles were classified into groups A and B, respectively, and the mean age of the 18 patients was 25.4 (range, 16-37) years. No statistical differences in patient backgrounds or fragment sizes between the groups existed. In group A, the fragments were located on the lateral plateau in 7 of the 8 ankles, whereas in group B, their locations varied. The patients were followed up for a median of 48 months (range, 24-168). No complications were observed. The postoperative JSSF and SAFE-Q sports activity scores were significantly higher in group A than in group B ( P

Therapeutic agents to the central nervous system (CNS) need to be efficiently delivered to the target site of action at appropriate therapeutic levels. However, a limited number of effective drugs for the treatment of neurological diseases has been developed thus far. Further, the pharmacological mechanisms by which such therapeutic agents can protect neurons from cell death have not been fully understood. We have previously reported the novel small-molecule compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS). One of the remarkable characteristics of WN1316 is that its efficacious doses in ALS mouse models are much less than those against oxidative injury in cultured human neuronal cells. It is also noted that the WN1316 cytoprotective activity observed in cultured cells is totally dependent upon the addition of fetal bovine serum in culture medium. These findings led us to postulate some serum factors being tightly linked to the WN1316 efficacy. In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. Notably, the removal of glycan chains from these molecules did not affect the WN1316 cytoprotective activity. Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy.

Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron degenerative disease. Given that oxidative stress and resulting chronic neuronal inflammation are thought to be central pathogenic, anti-oxidative agents and modulators of neuronal inflammation could be potential therapies for ALS. We report here that the novel small molecular compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) selectively suppresses oxidative stress-induced cell death and neuronal inflammation in the late-stage ALS mice. WN1316 has high blood-brain-barrier permeability and water solubility, and boosts both neuronal apoptosis inhibitory protein (NAIP) and NF-E2-related factor 2 (Nrf2) which governed glutathione (GSH)-related anti-oxidation pathway protecting motor neurons against oxidative injuries. Post-onset oral administration of low dose (1-100 µg/kg/day) WN1316 in ALS(SOD1(H46R)) and ALS(SOD1(G93A)) mice resulted in sustained improved motor function and post onset survival rate. Immunohistochemical analysis revealed less DNA oxidative damage and motor neuronal inflammation as well as repression of both microgliosis and astrocytosis, concomitant down regulation of interleukin-1β and inducible nitric oxide synthase, and preservation of the motoneurons in anterior horn of lumbar spinal cord and skeletal muscle (quadriceps femoris). Thus, WN1316 would be a novel therapeutic agent for ALS.

Purpose. To compare mid-term outcomes of hemi-resurfacing arthroplasty (HRA) and total resurfacing arthroplasty (TRA). Methods. Seven men and 5 women (16 hips) aged 33 to 72 (mean, 50) years underwent HRA, whereas 7 men and 3 women (16 hips) aged 23 to 52 (mean, 40) years underwent metal-on-metal TRA; all were for osteonecrosis of the femoral head. In the HRA and TRA groups respectively, 10 and 8 hips were steroid-induced, whereas 6 and 8 hips were related to alcohol abuse. Surgery for 12 and 4 hips entailed the posterolateral approach, whereas 4 and 12 hips entailed the Hardinge approach. Usually, HRA was performed for early stages of the disease, and TRA for more advanced stages. 12 and 6 hips were classified as JOA stages 1 to 3A, whereas 4 and 10 hips as stages 3B to 4. All the hips were JOA types C1 or C2. Results. In the HRA and TRA groups respectively, the mean follow-up period were 6.5 and 5.5 years. The mean total JOA hip scores were 57 and 54 preoperatively, 93 and 97 at one year, and 84 and 96 at the final follow-up (p