Optimal placement for needle electromyography of the supinator muscle: Cadaveric studies.

INTRODUCTION/AIMS: The existing methods for needle electromyography are confusing as to which is the safest and most effective. Our aim was to identify the optimal and safest needle electromyographic insertion site in the supinator muscle. METHODS: We performed a two-step cadaveric dissection of the supinator muscle and related neurovascular structures. The study was performed using 18 upper limbs of 9 fresh adult cadavers (step 1) and 14 upper limbs of 7 fresh adult cadavers (step 2). In step 1, an imaginary line connecting the radial head (RH) and midpoint of the dorsal wrist (RW line) was drawn, and the distance from the RH to the point where the RW line and posterior interosseous nerve (PIN) intersect (L_CROSS) was measured on the RW line. In step 2, the needle was inserted 30 mm distal to the RH according to the results of step 1. After injection with India ink, dissection was performed to measure the distance between the needle insertion site and PIN (L_CROSS_Inj) on the RW line. RESULTS: The median L_CROSS was 51.4 (35.5-65.6) mm. Needle insertion spared the PIN in all cases during step 2, and the needle was inserted into the supinator muscle in all cases. The median L_CROSS_Inj was 27.4 (13.2-39.8) mm. DISCUSSION: A safe and accurate needle insertion site for the supinator muscle is approximately 30 to 40 mm distal to the RH along the RW line.

Triphenylphosphonium conjugation to a TRAP1 inhibitor, 2-amino-6-chloro-7,9-dihydro-8H-purin-8-one increases antiproliferative activity.

Tumor-necrosis-factor-receptor associated protein 1 (TRAP1), a mitochondrial paralog of heat shock protein 90 family proteins, is overexpressed in many cancer cells and supports tumorigenesis by rewiring vital metabolic and cell death pathways. The triphenylphosphonium moiety is used to deliver therapeutic cargo to increase drug uptake into mitochondria. Various aryl- or alkyl-substituted phosphonium analogs were conjugated with TRAP1-selective inhibitors 4a-c to optimize anticancer activity. Among these various phosphonium-conjugated compounds, (6-(2-amino-9-(4-bromo-2-fluorobenzyl)-6-chloro-8-oxo-8,9-dihydro-7H-purin-7-yl)hexyl)triphenylphosphornium (6a) was identified as a potential anticancer agent. Compound 6a had IC50 values of 0.30-3.24 µM in seven different cancer cell lines and potently suppressed tumor growth without any noticeable in vivo toxicity in a nude mouse model xenografted with PC3 prostate cancer cells.

Targeting the Mitochondrial Chaperone TRAP1 Alleviates Vascular Pathologies in Ischemic Retinopathy.

Activation of hypoxia-inducible factor 1α (HIF1α) contributes to blood-retinal barrier (BRB) breakdown and pathological neovascularization responsible for vision loss in ischemic retinal diseases. During disease progression, mitochondrial biology is altered to adapt to the ischemic environment created by initial vascular dysfunction, but the mitochondrial adaptive mechanisms, which ultimately contribute to the pathogenesis of ischemic retinopathy, remain incompletely understood. In the present study, it is identified that expression of mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 (TRAP1) is essential for BRB breakdown and pathologic retinal neovascularization in mouse models mimicking ischemic retinopathies. Genetic Trap1 ablation or treatment with small molecule TRAP1 inhibitors, such as mitoquinone (MitoQ) and SB-U015, alleviate retinal pathologies via proteolytic HIF1α degradation, which is mediated by opening of the mitochondrial permeability transition pore and activation of calcium-dependent protease calpain-1. These findings suggest that TRAP1 can be a promising target for the development of new treatments against ischemic retinopathy, such as retinopathy of prematurity and proliferative diabetic retinopathy.

Optimal Placement of Needle Electromyography in Extensor Indicis: A Cadaveric Study.

OBJECTIVE: To identify the center of extensor indicis (EI) muscle through cadaver dissection and compare the accuracy of different techniques for needle electromyography (EMG) electrode insertion. METHODS: Eighteen upper limbs of 10 adult cadavers were dissected. The center of trigonal EI muscle was defined as the point where the three medians of the triangle intersect. Three different needle electrode insertion techniques were introduced: M1, 2.5 cm above the lower border of ulnar styloid process (USP), lateral aspect of the ulna; M2, 2 finger breadths (FB) proximal to USP, lateral aspect of the ulna; and M3, distal fourth of the forearm, lateral aspect of the ulna. The distance from USP to the center (X) parallel to the line between radial head to USP, and from medial border of ulna to the center (Y) were measured. The distances between 3 different points (M1- M3) and the center were measured (marked as D1, D2, and D3, respectively). RESULTS: The median value of X was 48.3 mm and that of Y was 7.2 mm. The median values of D1, D2 and D3 were 23.3 mm, 13.3 mm and 9.0 mm, respectively. CONCLUSION: The center of EI muscle is located approximately 4.8 cm proximal to USP level and 7.2 mm lateral to the medial border of the ulna. Among the three methods, the technique placing the needle electrode at distal fourth of the forearm and lateral to the radial side of the ulna bone (M3) is the most accurate and closest to the center of the EI muscle.

Ultrasonographic Study of the Anatomical Relationship Between the Lateral Antebrachial Cutaneous Nerve and the Cephalic Vein.

OBJECTIVE: To define the anatomy of the lateral antebrachial cutaneous nerve (LABCN) and the cephalic vein (CV) in the anterior forearm region of living humans using ultrasonography for preventing LABCN injury during cephalic venipuncture. METHODS: Thirty forearms of 15 healthy volunteers were evaluated using ultrasonography to identify the point where the LABCN begins to contact with the CV, and the point where the LABCN separates from the CV. The LABCN pathway in the forearm in relation to a nerve conduction study was also evaluated. RESULTS: The LABCNs came in contact with the CV at a mean of 0.6±1.6 cm distal to the elbow crease, and separated from the CV at a mean of 7.0±3.4 cm distal to the elbow crease. The mean distance between the conventionally used recording points (point R) for the LABCN conduction study and the actual sonographic measured LABCN was 2.4±2.4 mm. LABCN usually presented laterally at the point R (83.3%). CONCLUSION: The LABCN had close proximity to the CV in the proximal first quarter of the forearm. Cephalic venipuncture in this area should be avoided, and performed with caution if needed.

Paralog Specificity Determines Subcellular Distribution, Action Mechanism, and Anticancer Activity of TRAP1 Inhibitors.

Although Hsp90 inhibitors can inhibit multiple tumorigenic pathways in cancer cells, their anticancer activity has been disappointingly modest. However, by forcing Hsp90 inhibitors into the mitochondria with mitochondrial delivery vehicles, they were converted into potent drugs targeting the mitochondrial Hsp90 paralog TRAP1. Here, to improve mitochondrial drug accumulation without using the mitochondrial delivery vehicle, we increased freely available drug concentrations in the cytoplasm by reducing the binding of the drugs to the abundant cytoplasmic Hsp90. After analyzing X-ray cocrystal structures, the purine ring of the Hsp90 inhibitor 2 (BIIB021) was modified to pyrazolopyrimidine scaffolds. One pyrazolopyrimidine, 12b (DN401), bound better to TRAP1 than to Hsp90, inactivated the mitochondrial TRAP1 in vivo, and it exhibited potent anticancer activity. Therefore, the rationale and feasible guidelines for developing 12b can potentially be exploited to design a potent TRAP1 inhibitor.

AMD3100 improves ovariectomy-induced osteoporosis in mice by facilitating mobilization of hematopoietic stem/progenitor cells.

Inhibition of an increase of osteoclasts has become the most important treatment for osteoporosis. The CXCR4 antagonist, AMD3100, plays an important role in the mobilization of osteoclast precursors within bone marrow (BM). However, the actual therapeutic impact of AMD3100 in osteoporosis has not yet been ascertained. Here we demonstrate the therapeutic effect of AMD3100 in the treatment of ovariectomy-induced osteoporosis in mice. We found that treatment with AMD3100 resulted in direct induction of release of SDF-1 from BM to blood and mobilization of hematopoietic stem/progenitor cells (HSPCs) in an osteoporosis model. AMD3100 prevented bone density loss after ovariectomy by mobilization of HSPCs, suggesting a therapeutic strategy to reduce the number of osteoclasts on bone surfaces. These findings support the hypothesis that treatment with AMD3100 can result in efficient mobilization of HSPCs into blood through direct blockade of the SDF-1/CXCR4 interaction in BM and can be considered as a potential new therapeutic intervention for osteoporosis.

Bone regeneration of mouse critical-sized calvarial defects with human mesenchymal stem cells in scaffold.

Combination of tissue engineering and cell therapy represents a promising approach for bone regeneration. Human mesenchymal stem cells (hMSCs) have properties that include low immunogenicity, high proliferation rate, and multi-differentiation potential; therefore, they are an attractive seeding source for tissue engineering therapy. Here we found that hMSCs with a scaffold did not affect cell viability and osteogenic differentiation. We also investigated regenerative effect of hMSCs with the scaffold in a calvarial bone defect model. Formation of new bone was evaluated by micro-CT, histology and expression of osteogenic markers. The results clearly showed interesting evidence indicating that hMSCs with scaffold increased the formation of new bone and expression of osteogenic markers, compared to the empty and scaffold only groups. Overall, our results suggest that hMSCs with scaffold are suitable for stimulation of intense bone regeneration in critical-sized bone defects.

Specific labeling of neurogenic, endothelial, and myogenic differentiated cells derived from human amniotic fluid stem cells with silica-coated magnetic nanoparticles.

Stem cell based cell therapies offer significant potential for the field of regenerative medicine. Human amniotic fluid stem cells (hAFSCs) are an attractive source for lineage-specific differentiated stem cell therapy since they have properties that are able to differentiate into cells representing all three germ layers. To better understand the fate and location of implanted hAFSCs, a means to monitor cells in living subjects is essential. Here, we showed that differentiated cells, such as neurogenic, endothelial, and myogenic cells, derived from hAFSCs can be effectively labeled by the FITC-incorporated silica-coated nanoparticles, MNPs@SiO2 (FITC), although the labeling efficacy and cytotoxicity were distinct depending on the differentiated cell type. In addition, we observed that MNPs@SiO2-labeled cells provided sufficient signals for detection by optical and confocal microscope imaging when transplanted into the mice. These results suggest that the fluorescent dye incorporated MNPs@SiO2 are a useful tool for the cell labeling and in vivo tracking of differentiated cells derived from hAFSCs.