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PURPOSE: To investigate the effect of bilateral reaching, with/without inertial loading on the unaffected arm, on hemiparetic arm motor control in stroke. METHODS: Twenty unilateral stroke patients were recruited. A three-dimensional optical motion capture system was used to measure the movement trajectory of the hemiparetic arm while performing three tasks: affected limb reaching forward; two-limb reaching forward; and two-limb reaching forward with inertia loading of 25% upper limb weight on the unaffected limb, respectively. Kinematical parameters were utilized to quantify the reaching performance of the affected arm. RESULTS: No matter whether loading was applied on the unaffected arm or not, the bilateral reaching task did not significantly facilitate smoother and faster movement. Furthermore, during bilateral reaching task with/without loading on the unaffected arm, stroke patients showed slower movement, lower maximal movement velocity, feedback control dominant and discontinuous movements in the affected arm than the same task with unilateral reaching. Subjects showed the greatest active upper extremity range of motion in proximal joints during the bilateral reaching task without unaffected arm loading. The amount of trunk movement also increased during bilateral reaching either with or without loading on the unaffected arm. Patients with moderate upper extremity motor impairment performed more discontinuous movements and less active elbow range of motion during bilateral reaching tasks; however, those with mild upper extremity motor impairment performed smoother movements and demonstrated greater active elbow range of motion during bilateral reaching tasks. CONCLUSIONS: Bilateral reaching tasks with/without loading on the unaffected arm could be considered as adding challenges during motor control training. Training with bilateral arm movements may be considered as a treatment strategy, and can be incorporated in stroke rehabilitation to facilitate greater arm active movement and improve motor control performance in the affected arm. [ABSTRACT FROM AUTHOR]

Examines the cloning and functional characteristics of low molecular weight thaumatin-like protein WRTLP2 from a cDNA library of winter rye. Amino acid sequence of WRTLP2; Overexpression of WRTLP2 in Escherichia coli; Antifungal activity of the cDNA clone.

Real-world data on the effectiveness of glecaprevir/pibrentasvir (GLE/PIB) for patients with HCV infection and compensated cirrhosis is limited, especially for the 8-week regimen and in an Asian population. This retrospective study enrolled 159 consecutive patients with HCV and compensated cirrhosis who were treated with GLE/PIB at a single center in Taiwan. Sustained virological response (SVR) and adverse events (AEs) were evaluated. Among the 159 patients, 91 and 68 were treated with GLE/PIB for 8 and 12 weeks, respectively. In the per protocol analysis, both the 8- and 12-week groups achieved 100% SVR (87/87 vs. 64/64); and in the evaluable population analysis, 95.6% (87/91) of the 8-week group and 94.1% (64/68) of the 12-week group achieved SVR. The most commonly reported AEs, which included pruritus (15.4% vs. 26.5%), abdominal discomfort (9.9% vs. 5.9%), and skin rash (5.5% vs. 5.9%), were mild for the 8- and 12-week groups. Two patients in the 8-week group exhibited total bilirubin elevation over three times the upper normal limit. One of these two patients discontinued GLE/PIB treatment after 2 weeks but still achieved SVR. Both 8- and 12-week GLE/PIB treatments are safe and effective for patients of Taiwanese ethnicity with HCV and compensated cirrhosis., Competing Interests: The authors have declared that no competing interests exist.

Clinical trials showed pangenotypic direct-acting antivirals' (DAAs) excellent efficacy and safety when treating hepatitis C virus (HCV). Two pangenotypic regimens were examined, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), in a real-world Taiwanese setting, including all HCV patients treated with GLE/PIB or SOF/VEL from August 2018 to April 2020. The primary endpoint was sustained virologic response 12 weeks after treatment cessation (SVR12), including adverse events (AEs). A total of 1,356 HCV patients received pangenotypic DAA treatment during the study: 742 and 614 received GLE/PIB and SOF/VEL, respectively. The rates of SVR12 for GLE/PIB and SOF/VEL were 710/718 (98.9%) and 581/584 (99.5%), respectively, by per-protocol analysis, and 710/742 (95.7%) and 581/614 (94.6%), respectively, by evaluable population analysis. Eleven (GLE/PIB: 8, SOF/VEL: 3) did not achieve SVR12. The most common AEs for GLE/PIB and SOF/VEL were pruritus (17.4% vs. 2.9%), abdominal discomfort (5.8% vs. 4.4%), dizziness (4.2% vs. 2%), and malaise (3.1% vs. 2.9%). Laboratory abnormalities were uncommon; only < 1% exhibited elevated total bilirubin or aminotransferase levels with both regimens. Five drug discontinuations occurred due to AEs (bilirubin elevation: 3; dermatological issues: 2). Pangenotypic DAAs GLE/PIB and SOF/VEL are effective and well tolerated, achieving high SVR12 rates for patients with all HCV genotypes.

Bakground: The objective of this study is to investigate the prognostic values of median nerve strain and applied pressure measurement for the assessment of clinical recovery after carpal tunnel release., Methods: Forty-five wrists, from 45 idiopathic carpal tunnel syndrome patients who treated with open carpal tunnel release, were evaluated by ultrasound. Median nerve strain, pressure applied to the skin, and ratio of pressure-strain were measured at the proximal part of the carpal tunnel. In addition, distal latencies in the motor and sensory nerve conductions studies and cross-sectional area of median nerve were measured. The parameters were compared before and after the open carpal tunnel release. According to patient recovery, the receiver operating characteristic curves were generated to evaluate the prognostic values of the parameters. The areas under the receiver operating characteristic curves were compared among parameters., Results: There was a significant increase in the median nerve strain, and significant decreases in the pressure applied to the skin and ratio of pressure-strain after carpal tunnel release (P < 0.01). There were significant decreases in the distal latencies and the cross-sectional area after carpal tunnel release (P < 0.01). The areas under the curves were 0.689, 0.773, 0.811, 0.668, 0.637, and 0.562 for the pressure, strain, pressure-strain ratio, motor latency, sensory latency, and area, respectively., Conclusions: The results suggest that elasticity of the median nerve and pressure around the nerve recover quickly after carpal tunnel release. Pressure-strain ratio was the most reliable parameter to reflect clinical recovery. The measurement of strain and applied pressure can be useful indicators to evaluate effectiveness of the carpal tunnel release., Trial Registration: Registered as NCT04027998 at ClinicalTrials.gov. Retrospectively registered on July 22, 2019.

The purpose of this study was to evaluate the reliability of ultrasound assessment of the displacement-force relationships for distal radioulnar joint (DRUJ) stability. Non-dominant wrists of 10 healthy male subjects were evaluated by force-monitor ultrasonography. This apparatus was developed to apply cyclic compression to the wrist with pre-determined transducer displacement conditions in the range of 0.1-3.0 mm. The subject's wrist was placed on the table with the forearm in the pronated position. The transducer was placed on the dorsal surface of the distal radius and ulna, perpendicular to the long axis of the forearm. The center of the ulnar head was at the DRUJ level. The distance between the dorsal surface of the distal radius and the ulnar head was measured at an initial and a pressed-down position. Changes in radioulnar displacement, force to the wrist and the displacement/force ratio were evaluated. The measurements were performed independently by two raters. The intra-class correlation coefficients (ICCs) for the radioulnar displacement were 0.76, 0.68, and 0.93, in the 1.0, 2.0, and 3.0 mm transducer displacement conditions, respectively. The ICCs for the force to the wrist were 0.18, 0.67, and 0.34, in different transducer displacement conditions, respectively. The ICCs for the displacement/force ratios were 0.68, 0.67, and 0.97, in different transducer displacement conditions, respectively. The highest ICC for the radioulnar displacement and the displacement/force ratio was observed in the 3.0 mm displacement condition. This assessment of displacement-force relationships may be useful to quantify DRUJ stability. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2053-2060, 2019., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: To assess the usefulness of three-dimensional (3D) digital pre-operative planning, we compared the radiographic parameters of the distal radius from 3D planning and conventional planning after osteosynthesis of distal radius fractures. We hypothesized that the use of 3D digital planning may improve radiographic outcomes for reduction and decrease the risk of correction loss. Methods: Sixty wrists of 60 distal radius fracture patients were randomly divided into two groups according to the order of hospital visits. Thirty wrists were treated with 3D preoperative planning as the plan group. Another thirty wrists were treated with conventional preoperative planning as the control group. Both groups were treated with volar locking plates. In the plan group, 3D digital preoperative planning and a surgical simulation were performed in order to determine the reduction and placement of the implants in addition to the plate/screw size prior to surgery. In the control group, conventional preoperative planning was performed. Ulnar variance, volar tilt, and radial inclination were measured at one week, three and six months after surgery. Difference of the measurement of radiographic parameters between operated and healthy side wrists were compared between plan and control groups at one week after surgery. Loss of corrections for radiographic parameters were compared between plan and control groups. Results: The differences between the operated and healthy side wrists were significantly smaller in the plan group compared to the control group for the volar tilt and radial inclination (p < 0.05).The loss of corrections for ulnar variance and volar tilt were significantly smaller in the plan group compared to the control group at six months after surgery (p < 0.05). Conclusions: 3D preoperative planning offers better reduction accuracy and reduces correction loss in the osteosynthesis of distal radius fractures.

Background: Diagnosing distal radioulnar joint (DRUJ) instability remains a challenge as it relies on physical examination. To quantitatively assess DRUJ stability, a pressure-monitor ultrasound system was developed. The objective of this study was to evaluate the force-displacement relationship of DRUJ in normal subjects., Methods: Nine wrists of 9 asymptomatic volunteers were evaluated. The pressure-monitor ultrasound system was developed to apply pressure to the tissue with a pre-determined cycle and displacement of the transducer. Each subject was imaged sitting with the elbow flexed and forearm pronated. The dorsal surface of the distal radius and the center of the ulnar head were displayed at DRUJ level. The pressure toward palmar direction was applied to the distal ulna with different levels of transducer displacements, i.e., 1 mm, 2 mm, and 3 mm. The distance between the dorsal surface of the ulnar head and the dorsal surface of the distal radius was measured. The first measurement was performed at the initial position, and the second measurement was performed when the transducer pressed down the ulna to the degree that the ulnar head had shifted to the most palmar position. At the same time, the pressure to the transducer was measured. The changes of radioulnar distance (=the measurement at the most palmar position-the measurement at the initial position) and pressure, and pressure/distance ratio were compared among the different transducer displacements., Results: The pressure was significantly increased as the transducer displacement became larger (P < 0.01). The changes of radioulnar distance were smaller in the 1 mm displacement condition compared to the 2 and 3 mm displacement conditions (P < 0.05). The pressure/distance ratio was larger in the 1 mm displacement condition compared to the 2 and 3 mm displacement conditions (P < 0.05)., Conclusions: A method to assess DRUJ stability by measuring changes in radioulnar distance and force application was developed. It was found that the application of 2 mm displacement and 200 g force was the critical stress for the capsuloligamentous structures to start stabilizing DRUJ. This methodology and the indices may be clinically useful to investigate the mechanical properties of patients with DRUJ instability.

A three-dimensional (3D) digital preoperative planning system for the osteosynthesis of distal radius fractures was developed for clinical practice. To assess the usefulness of the 3D planning for osteosynthesis, we evaluated the reproducibility of the reduction shapes and selected implants in the patients with distal radius fractures. Twenty wrists of 20 distal radius fracture patients who underwent osteosynthesis using volar locking plates were evaluated. The 3D preoperative planning was performed prior to each surgery. Four surgeons conducted the surgeries. The surgeons performed the reduction and the placement of the plate while comparing images between the preoperative plan and fluoroscopy. Preoperative planning and postoperative reductions were compared by measuring volar tilt and radial inclination of the 3D images. Intra-class correlation coefficients (ICCs) of the volar tilt and radial inclination were evaluated. For the implant choices, the ICCs for the screw lengths between the preoperative plan and the actual choices were evaluated. The ICCs were 0.644 (p < 0.01) and 0.625 (p < 0.01) for the volar tilt and radial inclination in the 3D measurements, respectively. The planned size of plate was used in all of the patients. The ICC for the screw length between preoperative planning and actual choice was 0.860 (p < 0.01). Good reproducibility for the reduction shape and excellent reproducibility for the implant choices were achieved using 3D preoperative planning for distal radius fracture. Three-dimensional digital planning was useful to visualize the reduction process and choose a proper implant for distal radius fractures. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2646-2651, 2017., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Objectives: Characterization of the changes of ultrasound parameters after carpal tunnel release may be useful for clarifying the effectiveness or the recovery process of the carpal tunnel syndrome treatment. We evaluated strain and morphological changes of the median nerve before and after carpal tunnel release in carpal tunnel syndrome patients., Methods: Twenty-two wrists of 20 idiopathic carpal tunnel syndrome patients who underwent open carpal tunnel release were evaluated by ultrasound. Cross-sectional images of the median nerve were obtained at the proximal carpal tunnel. The cross-sectional area, perimeter, aspect ratio of the minimum enclosing rectangle, and strain of the median nerve were measured and compared before and after carpal tunnel release. According to the patient's recovery, the areas under the receiver operating characteristic curves (AUCs) were compared among the parameters., Results: After carpal tunnel release, the area and perimeter significantly decreased, and the strain significantly increased compared with before carpal tunnel release. There were no significant changes in the aspect ratio after carpal tunnel release. The AUCs were 0.663, 0.643, 0.543, and 0.731 for the area, perimeter, aspect ratio, and strain, respectively., Conclusions: Significant decreases in median nerve area and perimeter as well as significant increases in median nerve strain were observed after carpal tunnel release. The results of this study may be useful when considering how the median nerve recovers after carpal tunnel release., (© 2017 by the American Institute of Ultrasound in Medicine.)

The objective of this study was to evaluate the diagnostic utility of strain and applied-pressure measurements of the median nerve in carpal tunnel syndrome (CTS). Thirty-five wrists of 23 idiopathic CTS patients and 30 wrists of 15 normal patients were examined. Median nerve strain, pressure to the skin and the pressure/strain ratio were measured at the proximal carpal tunnel level. Parameters were compared between CTS patients and controls. The areas under the receiver operating characteristic curves (AUCs) were compared for the parameters. Median nerve strain was significantly lower in the patients than in the controls (p < 0.01). Pressure and pressure/strain ratio were significantly higher in the patients than in the controls (p < 0.05: pressure, p < 0.01: ratio). The AUCs were 0.926, 0.681 and 0.937 for strain, pressure and pressure/strain ratio, respectively. Pressure/strain ratio is useful for evaluating the condition of the median nerve with respect to the hardness of the surrounding structures in CTS., (Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Forceful activities of the wrist were considered to be a risk factor for the epicondylitis. However, there are still conflicting evidence concerning work-relatedness of epicondylitis. The main problem is that there is little information about which forearm postures are capable of withstanding higher torque loads and the extent of the differences in the torques generated by different forearm postures. The objective of this study was to investigate the differences in wrist flexion and extension torques among different forearm positions in healthy subjects., Methods: Twenty wrists of 10 asymptomatic volunteers were evaluated. The apparatus to measure the wrist torque consisted of a handle with a force sensor and a table to place the forearm in different positions. The direction of the handle can change when measuring different forearm positions. The forearm of the examinee was secured to the table. The participants were asked to exert themselves in maximal isometric contraction for wrist flexion or extension, and to maintain it for 5 s. Each evaluation of the flexion and extension torque was conducted twice. Three forearm positions were evaluated: neutral, pronation, and supination. The intra-class correlation coefficients between first and second measurements were evaluated for the maximum torque. The maximum torques and flexion/extension ratio were compared among the positions. In addition, the agility and endurance for the wrist extension/flexion torques were compared among the positions., Results: The intra-class correlation coefficients between first and second measurements were 0.928 and 0.866 for the wrist flexion and extension measurements, respectively. The highest torques for the wrist flexion and extension were observed in the supination and pronation positions, respectively (P < 0.01). There was a higher extension/flexion ratio in the supination position compared to the other positions (P < 0.05). There was a superior agility for the wrist flexion in the supination position compared to the pronation position., Conclusions: The normal balance of the wrist flexion-extension torques in different forearm positions were characterized. This information might aid the provision of advice regarding the optimal positions for performing specific tasks and could help to elucidate the pathophysiology of epicondylitis.

To assess the biomechanical effect of carpal tunnel release (CTR), we evaluated the deformation and displacement patterns of the median nerve before and after CTR in carpal tunnel syndrome (CTS) patients. Sixteen wrists of 14 idiopathic CTS patients who had open CTR and 26 wrists of 13 asymptomatic volunteers were evaluated by ultrasound. Cross-sectional images of the carpal tunnel during motion from full finger extension to flexion were recorded. The area, perimeter, aspect ratio of a minimum enclosing rectangle, and circularity of the median nerve were measured in finger extension and flexion positions. Deformation indices, determined by the flexion-extension ratio for each parameter, were compared before and after CTR. After CTR, the deformation indices of perimeter and circularity became significantly larger and the aspect ratio became significantly smaller than those before CTR (p < 0.05). Those differences were more obvious when comparing the values between the patients before CTR and the controls. Since the deformation indices after CTR are similar to the patterns of normal subjects, the surrounding structures and environment of the median nerve may be normalized upon CTR. This may be a way to tell how the median nerves recover after CTR., (© 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The objective of this study was to detect differences in median nerve strain between patients with carpal tunnel syndrome and healthy controls using cyclic compression apparatus. Twenty-eight patients with idiopathic carpal tunnel syndrome and 30 normal patients were examined by ultrasound elastography. Median nerve strain, strain ratio of reference coupler and median nerve area and perimeter were measured. The areas under receiver operating characteristic curves were compared among the parameters. Median nerve strains of the patients were significantly smaller than those of the controls (p < 0.001). Strain ratios, areas and perimeters were significantly larger in the patients than in the controls (p < 0.001). The areas under curves were 0.963, 0.917, 0.759 and 0.706 for strain, strain ratio, area and perimeter, respectively. The median nerve strain had the highest area under the curve. The ultrasonic strain measurements of the median nerve provided by the cyclic compression apparatus were superior to morphologic assessment in diagnosing carpal tunnel syndrome., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to evaluate the correlations between deformation and displacement of median nerve and flexor tendons during finger motion in the carpal tunnel for both carpal tunnel syndrome (CTS) patients and healthy controls. Sixty-two wrists of 31 asymptomatic volunteers and fifty-one wrists of 28 idiopathic CTS patients were evaluated by ultrasound. The displacement of the median nerve and the middle finger flexor digitorum superficialis (FDS) tendon, as well as area, perimeter, aspect ratio of a minimum enclosing rectangle, and circularity of the median nerve were measured in finger extension and flexion positions. Deformation indices were defined as the ratios of indices in finger extension and flexion positions. The correlations between displacement and deformation indices were evaluated. There were significant correlations between nerve palmar-dorsal displacement and deformation indices (p < 0.05). The aspect ratio deformation index showed the strongest correlation to palmar-dorsal displacement of the nerve (-0.572, p < 0.01). This study showed that there is a relationship between median nerve deformation indices and nerve palmar-dorsal displacement in the carpal tunnel. Since the highest correlations were between palmar-dorsal nerve displacement direction and aspect ratio deformation index, these parameters may be helpful to understand the pathophysiology of CTS., (© 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The extensor tendon forces required to overcome the catching flexors in trigger fingers are unknown. A biomechanical model with moment equilibrium equations and method of least squares was developed for estimating the tendon force at triggering in trigger fingers. Trigger fingers that exhibited significant catching and sudden release during finger extension were tested. A customized "pulling tester" was used to pull the finger from flexion to extension and provide synchronic measurement of the pulling force. The displacement of the tested finger was measured by a motion capture system. This preliminary study presents kinematic and kinetic data at triggering of 10 trigger fingers. The distal and proximal interphalangeal (PIP) joints presented sudden release while the metacarpophalangeal (MCP) joint started extension in the early phase of finger extension. The tendon tension of flexor digitorum profundus was greater than that of flexor digitorum superficialis (FDS) in six fingers, and less than that of FDS in three fingers. The tension of two flexor tendons was almost equal in one finger. At the PIP and MCP joints, 1.54 times the force of flexors was needed for the extensors to overcome the catching flexors in trigger fingers. This biomechanical model provides clinicians with a clearer idea of the tendon force at triggering. The quantitative results may help in the understanding of movement characteristics of trigger fingers. These findings are useful to better understand the etiology and nature of trigger finger development, and thus aid in further development of better assessments and treatments related to this., (Copyright © 2013 Orthopaedic Research Society.)

Indole-3-carbinol (I3C), a potential anticancer substance, can be found in cruciferous (cabbage family) vegetables, mainly cauliflower and Chinese cabbage. However, the bioactivity of I3C on the apoptotic effects of murine leukemia WEHI-3 cells and promotion of immune responses in leukemia mice model are unclear. In this study, we investigated the effect of I3C on cell-cycle arrest and apoptosis in vitro and immunomodulation in vivo. I3C decreased the viable WEHI-3 cells and caused morphological changes in a concentration- and time-dependent manner. I3C also led to G0/G1 phase arrest, decreased the levels of cyclin A, cyclin D, and CDK2, and increased the level of p21(WAF1/CIP1). Flow cytometric analyses further proved that I3C promoted ROS and intracellular Ca(2+) production and decreased the levels of ΔΨ(m) in WEHI-3 cells. Cells after exposure to I3C for 24 h showed DNA fragmentation and chromatin condensation. Comet assay also indicated that I3C induced DNA damage in examined cells. I3C increased the levels of cytochrome c, FADD, GADD153, GRP78, and caspase-12 as well as induced activities of caspase-3, -8, and -9. Moreover, I3C attenuated NF-κB DNA binding activity in I3C-treated WEHI-3 cells as shown by EMSA and Western blotting analyses. In the in vivo study, we examined the effects of I3C on WEHI-3 leukemia mice. Results showed that I3C increased the level of T cells and decreased the level of macrophages. I3C also reduced the weights of liver and spleen, and it promoted phagocytosis by macrophages as compared to the nontreated leukemia mice group. On the basis of our results, I3C affects murine leukemia WEHI-3 cells both in vitro and in vivo.

Novel amphipathic derivative of chitosan (carboxymethyl-hexanoyl chitosan, CHC) was made into mats of nanofibers (approximately 100 nm) via electrospinning. The resulting mats were further cross-linked with genipin. The morphology of CHC nanofibers was examined using a field emission scanning electron microscope (FESEM). The optimum parameters of CHC nanofiber was achieved when the CHC concentration was 4 wt% and electrospinning was conducted with a voltage of 20 kV over a distance of 10 cm. The characterizations of biocompatibility, hemocompatibility, and anti-bacterial activity of the nanofibers were also investigated. The results show that CHC nanofibers still preserved antibacterial activity and thrombogeneicity owing to those residual amino groups of chitosan and exhibit high biocompatibility for L929 fibroblast test. Thus CHC exhibited the potential to serve as a novel wound dressing and surgical implants application by these advanced features.

Nanotherapeutic strategy is well recognized as the therapeutic approach of the future. Numerous reports have demonstrated the use of nanoparticulate drug carriers for the development of targeted nanotherapeutics by, for instance, incorporation of a moiety that specifically targets certain diseased cells. However, systematic investigation of this aspect has been inadequate, especially with regard to nanosystems with remotely controlled drug delivery. The authors previously designed a magnetic-responsive core-shell drug delivery nanosystem which proved to be technically feasible in vitro. In the present study, this nanosystem is modified for targeted delivery of an anticancer agent (encapsulated camptothecin (CPT)) to cancer cells overexpressing epithelial growth factor receptor (EGFR) with accurate intracellular drug release. The endocytosis of the nanocarriers by cancer cells, the pathway of cellular uptake and the subsequent intracellular controlled drug delivery were systematically investigated. It was found that the modified nanocarriers showed reasonably high drug load efficiency for CPT and a high uptake rate by cancer cells overexpressing EGFR through clathrin-mediated endocytosis. The intracellular release of the CPT molecules via an external magnetic stimulus proved to be technically successful and ensured much higher therapeutic efficacy than that obtained with the free drug. This study employs multiple functions for nanotherapeutic treatment of specific target cells, i.e. cell-specific targeting, controlled cellular endocytosis and magnetic-responsive intracellular drug release., (Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Prostatic small cell carcinoma (SCC) is a rare variant of prostate cancer. It is extremely aggressive and resistant to available therapies with a median survival range of 5-17 months. No standard chemotherapeutic regimen has been established for its treatment. In search of a new therapeutic approach, we examined the response of patient-derived prostatic SCC tissue xenografts to irinotecan, a topoisomerase I inhibitor., Methods: A tumor tissue line was established from a patient's prostatic SCC by subrenal capsule grafting using NOD-SCID mice. Mice carrying subcutaneous transplants of the tumor line were then treated for 2 weeks with irinotecan alone and in combination with cisplatin. The effect on tumor volume, histopathology, and apoptosis were determined., Results: The prostatic SCC tissue line resembled the donor tissue in morphologic and immunohistochemical features. Irinotecan (20 mg/kg/day; days 1-3, 8-10) completely arrested xenograft growth with a small reduction in tumor volume and only minor weight loss of the hosts (7%); irinotecan (12 mg/kg; same schedule) + cisplatin (2.5 mg/kg/day; days 1 and 8) had a similar effect, but with lower weight loss. While the growth inhibition involved apoptosis, it was also associated with a marked increase in autophagy., Conclusions: Tumor tissue lines established via subrenal capsule xenografting provide models with clinical relevance and the present study suggests that irinotecan could be useful for therapy of refractory prostatic SCC, in particular in combination with cisplatin., (Copyright © 2010 Wiley-Liss, Inc.)

Financial volatility refers to the intensity of the fluctuations in the expected return on an investment or the pricing of a financial asset due to market uncertainties. Hence, volatility modeling and forecasting is imperative to financial market investors, as such projections allow the investors to adjust their trading strategies in anticipation of the impending financial market movements. Following this, financial volatility trading is the capitalization of the uncertainties of the financial markets to realize investment profits in times of rising, falling and side-way market conditions. In this paper, an intelligent straddle trading system (framework) that consists of a volatility projection module (VPM) and a trade decision module (TDM) is proposed for financial volatility trading via the buying and selling of option straddles to help a human trader capitalizes on the underlying uncertainties of the Hong Kong stock market. Three different measures, namely: (1) the historical volatility (HV), (2) implied volatility (IV) and (3) model-based volatility (MV) of the Hang Seng Index (HSI) are employed to quantify the implicit volatility of the Hong Kong stock market. The TDM of the proposed straddle trading system combines the respective volatility measures with the well-established moving-averages convergence/divergence (MACD) principle to recommend trading actions to a human trader dealing in HSI straddles. However, the inherent limitation of the MACD trading rule is that it generates time-delayed trading signals due to the use of moving averages, which are essentially lagging trend indicators. This drawback is intuitively addressed in the proposed straddle trading system by applying the VPM to compute future projections of the volatility measures of the HSI prior to the activation of the TDM. The VPM is realized by a self-organising neural-fuzzy semantic network named the evolving fuzzy semantic memory (eFSM) model. As compared to existing statistical and computational intelligence based modeling techniques currently employed for financial volatility modeling and forecasting, eFSM possesses several desirable attributes such as: (1) an evolvable knowledge base to continuously address the non-stationary characteristics of the Hong Kong stock market; (2) highly formalized human-like information computations; and (3) a transparent structure that can be interpreted via a set of linguistic IF-THEN semantic fuzzy rules. These qualities provide added credence to the computed HSI volatility projections. The volatility modeling and forecasting performances of the eFSM, when benchmarked to several established modeling techniques, as well as the observed trading returns of the proposed straddle trading system, are encouraging., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The development of the mammalian neocortex relies heavily on subplate. The proportion of this cell population varies considerably in different mammalian species. Subplate is almost undetectable in marsupials, forms a thin, but distinct layer in mouse and rat, a larger layer in carnivores and big-brained mammals as pig, and a highly developed embryonic structure in human and non-human primates. The evolutionary origin of subplate neurons is the subject of current debate. Some hypothesize that subplate represents the ancestral cortex of sauropsids, while others consider it to be an increasingly complex phylogenetic novelty of the mammalian neocortex. Here we review recent work on expression of several genes that were originally identified in rodent as highly and differentially expressed in subplate. We relate these observations to cellular morphology, birthdating, and hodology in the dorsal cortex/dorsal pallium of several amniote species. Based on this reviewed evidence we argue for a third hypothesis according to which subplate contains both ancestral and newly derived cell populations. We propose that the mammalian subplate originally derived from a phylogenetically ancient structure in the dorsal pallium of stem amniotes, but subsequently expanded with additional cell populations in the synapsid lineage to support an increasingly complex cortical plate development. Further understanding of the detailed molecular taxonomy, somatodendritic morphology, and connectivity of subplate in a comparative context should contribute to the identification of the ancestral and newly evolved populations of subplate neurons.

Background: Clinical diagnosis and classification of trigger fingers is traditionally based on physical examinations and certain obvious symptoms. However, it might lack quantitative evidence to describe the different graded trigger digits. This study provides quantitative evidence of kinematics and functional differences among different graded trigger fingers based on Froimson's classification., Methods: Forty-seven patients with fifty-five trigger fingers and graded twenty-three, eleven, and twenty-one fingers as grades II, III, and IV, respectively. The QuickDASH questionnaire evaluated the subject's self-perception of hand symptoms and functions. The study measured maximal workspace of the fingertip motion and range of motion of the finger joints during an assigned tendon-gliding task using an electromagnetic tracking device. In addition, R(alpha), defined as the ratio range of angular acceleration during finger extension to the range during finger flexion of each joint, quantified the triggering effect., Findings: The QuickDASH score results show that functional performances have significant differences among three grades (P<0.05). Workspace, range of motion of proximal interphalangeal joint and R(alpha) of proximal interphalangeal and distal interphalangeal joint of trigger fingers also significantly differ among three grades (P<0.05). These findings quantitatively show that trigger fingers in different impairment levels have different kinematics and functional performances., Interpretation: The results serve as evidence-based knowledge for clinics. The more practical and immediate application of this study would be to facilitate the assessment, design and execution of rehabilitation for patients with trigger fingers., (Crown Copyright (c) 2010. Published by Elsevier Ltd. All rights reserved.)

Background: Trigger finger is most common in the ring finger, but the reason for this is not known. We hypothesized that the compliance of the A1 pulley might be one of the factors responsible for this phenomenon. The purpose of this study was therefore to compare the compliance of the normal A1 pulley of the thumb, index, middle, ring and little fingers using human cadavers., Methods: Eight normal thumbs, index, middle, ring and little fingers from eight fresh frozen human hand cadavers were used in this experiment. The compliance of the A1 pulley was measured by the resistance when passing a tapered metal rod through the A1 pulley. The slopes of the linear region of radial force/increasing area ratio curve were calculated and analyzed., Findings: The mean slope of the linear region of the radial force/increasing area ratio curve was significantly different among the five digits (p<0.05). Post hoc analysis indicated that the mean slope for the middle finger A1 pulleys was larger than the thumb and little finger A1 pulleys (p<0.05)., Interpretation: The findings did not support our clinical hypothesis that A1 pulley stiffness would parallel the relative frequency of trigger finger by digit., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

The purpose of this study was to measure the compliance of the carpal tunnel in candidate animal models of carpal tunnel syndrome (CTS), by measuring the resistance when passing a tapered metal rod through the carpal tunnel. Forepaws from 10 dogs, 10 rabbits, and 10 rats with intact carpal tunnels, and 10 fresh frozen human wrist cadavers were used. The slopes of the linear part of the force-displacement curve (a measure of stiffness), normal force, and increasing area ratio (InAR) were significantly different among the four species (p<0.05). Post hoc analysis indicated that the mean slopes for the human carpal tunnel were the largest, indicating the least compliance, whereas those of the rat were the least (p<0.05). The features of the compliance for the dog carpal tunnel were closest to the human. The development of animal models of CTS should consider the compliance of the carpal tunnel, as it will be more difficult to increase pressure in a more compliant tunnel., (Copyright (c) 2009 Orthopaedic Research Society.)

Fuzzy rule-based systems (FRBSs) have been successfully applied to many areas. However, traditional fuzzy systems are often manually crafted, and their rule bases that represent the acquired knowledge are static and cannot be trained to improve the modeling performance. This subsequently leads to intensive research on the autonomous construction and tuning of a fuzzy system directly from the observed training data to address the knowledge acquisition bottleneck, resulting in well-established hybrids such as neural-fuzzy systems (NFSs) and genetic fuzzy systems (GFSs). However, the complex and dynamic nature of real-world problems demands that fuzzy rule-based systems and models be able to adapt their parameters and ultimately evolve their rule bases to address the nonstationary (time-varying) characteristics of their operating environments. Recently, considerable research efforts have been directed to the study of evolving Tagaki-Sugeno (T-S)-type NFSs based on the concept of incremental learning. In contrast, there are very few incremental learning Mamdani-type NFSs reported in the literature. Hence, this paper presents the evolving neural-fuzzy semantic memory (eFSM) model, a neural-fuzzy Mamdani architecture with a data-driven progressively adaptive structure (i.e., rule base) based on incremental learning. Issues related to the incremental learning of the eFSM rule base are carefully investigated, and a novel parameter learning approach is proposed for the tuning of the fuzzy set parameters in eFSM. The proposed eFSM model elicits highly interpretable semantic knowledge in the form of Mamdani-type if-then fuzzy rules from low-level numeric training data. These Mamdani fuzzy rules define the computing structure of eFSM and are incrementally learned with the arrival of each training data sample. New rules are constructed from the emergence of novel training data and obsolete fuzzy rules that no longer describe the recently observed data trends are pruned. This enables eFSM to maintain a current and compact set of Mamdani-type if-then fuzzy rules that collectively generalizes and describes the salient associative mappings between the inputs and outputs of the underlying process being modeled. The learning and modeling performances of the proposed eFSM are evaluated using several benchmark applications and the results are encouraging.

We present evidence of kinematic and functional improvements of the trigger digit after sonographically assisted percutaneous release using quantitative motion analyses and functional assessments, respectively. Twenty-two patients with idiopathic trigger digits, who received the surgery, were recruited. A motion tracking system was used to measure the assigned kinematics parameters at the presurgical visit and at 1, 4, and 12 weeks after surgery. The hand strength and functional outcome were also obtained using dynamometer and self-report questionnaire assessments. The hand strength, maximal workspace, and joint range of motion of the involved digit were significantly smaller than that of the intact finger on the contralateral hand before surgery. The triggering phenomenon of the involved digit was significantly higher than that of the corresponding finger in the intact hand using a subscribed angular acceleration factor. The repeated measures showed that the workspace, joint range of motion, hand strength, and triggering effect of the involved hand significantly improved in follow-up examinations after the surgical intervention. Painful movement or insufficient tendon excursion of the trigger digit can cause loss of movement and strength, thus interfering with functional performance. After the disappearance of the pain and triggering by sonographically assisted percutaneous release, improvements in kinematics and function were objectively quantified in this study.

Objective: To analyze the effects of conventional rehabilitation combined with bilateral force-induced isokinetic arm movement training on paretic upper-limb motor recovery in patients with chronic stroke., Design: Single-cohort, pre- and postretention design., Setting: Rehabilitation department at a medical university., Participants: Twenty subjects who had unilateral strokes at least 6 months before enrolling in the study., Intervention: A training program (40min/session, 3 sessions/wk for 8wk) consisting of 10 minutes of conventional rehabilitation and 30 minutes of robot-aided, bilateral force-induced, isokinetic arm movement training to improve paretic upper-limb motor function., Main Outcome Measures: The interval of pretest, post-test, and retention test was set at 8 weeks. Clinical arm motor function (Fugl-Meyer Assessment [FMA], upper-limb motor function, Frenchay Arm Test, Modified Ashworth Scale), paretic upper-limb strength (grip strength, arm push and pull strength), and reaching kinematics analysis (peak velocity, percentage of time to peak velocity, movement time, normalized jerk score) were used as outcome measures., Results: After comparing the sets of scores, we found that the post-test and retention test in arm motor function significantly improved in terms of grip (P=.009), push (P=.001), and pull (P=.001) strengths, and FMA upper-limb scale (P<.001). Reaching kinematics significantly improved in terms of movement time (P=.015), peak velocity (P=.035), percentage of time to peak velocity (P=.004), and normalized jerk score (P=.008). Improvement in reaching ability was not sustained in the retention test., Conclusions: Preliminary results showed that conventional rehabilitation combined with robot-aided, bilateral force-induced, isokinetic arm training might enhance the recovery of strength and motor control ability in the paretic upper limb of patients with chronic stroke.

The cerebellum is a brain region important for a number of motor and cognitive functions. It is able to generate error correction signals to drive learning and for the acquisition of memory skills. The cerebellar model articulation controller (CMAC) is a neural network inspired by the neurophysiologic theory of the cerebellum and is recognized for its localized generalization and rapid algorithmic computation capabilities. The main deficiencies in the basic CMAC structure are: (1) it is difficult to interpret the internal operations of the CMAC network and (2) the resolution (quantization) problem arising from the partitioning of the input training space. These limitations lead to the synthesis of a fuzzy quantization technique and the mapping of a fuzzy inference scheme onto the CMAC structure. The discrete incremental clustering (DIC) technique is employed to alleviate the quantization problem in the CMAC structure, resulting in the fuzzy CMAC (FCMAC) network. The Yager inference scheme (Yager), which possesses firm fuzzy logic foundation and maps closely to the logical implication operations in the classical (binary) logic framework, is subsequently mapped onto the FCMAC structure. This results in a novel fuzzy neural architecture known as thefuzzy cerebellar model articulation controller-Yager (FCMAC-Yager) system. The proposed FCMAC-Yager network exhibits learning and memory capabilities of the cerebellum through the CMAC structure while emulating the human way of reasoning through the Yager. The new FCMAC-Yager network employs a two-phase training algorithm consisting of structural learning based on the DIC technique and parameter learning using hebbian learning (associative long-term potentiation). The proposed FCMAC-Yager architecture is evaluated using an extensive suite of real-life applications such as highway traffic-trend modeling and prediction and performing as an early warning system for bank failure classification and medical diagnosis of breast cancer. The experimental results are encouraging.

Objective: Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood, representing nearly one third of all pediatric cancers. Currently, the treatment of pediatric ALL is centered on tailoring the intensity of the therapy applied to a patient's risk of relapse, which is linked to the type of leukemia the patient has. Hence, accurate and correct diagnosis of the various leukemia subtypes becomes an important first step in the treatment process. Recently, gene expression profiling using DNA microarrays has been shown to be a viable and accurate diagnostic tool to identify the known prognostically important ALL subtypes. Thus, there is currently a huge interest in developing autonomous classification systems for cancer diagnosis using gene expression data. This is to achieve an unbiased analysis of the data and also partly to handle the large amount of genetic information extracted from the DNA microarrays., Methodology: Generally, existing medical decision support systems (DSS) for cancer classification and diagnosis are based on traditional statistical methods such as Bayesian decision theory and machine learning models such as neural networks (NN) and support vector machine (SVM). Though high accuracies have been reported for these systems, they fall short on certain critical areas. These included (a) being able to present the extracted knowledge and explain the computed solutions to the users; (b) having a logical deduction process that is similar and intuitive to the human reasoning process; and (c) flexible enough to incorporate new knowledge without running the risk of eroding old but valid information. On the other hand, a neural fuzzy system, which is synthesized to emulate the human ability to learn and reason in the presence of imprecise and incomplete information, has the ability to overcome the above-mentioned shortcomings. However, existing neural fuzzy systems have their own limitations when used in the design and implementation of DSS. Hence, this paper proposed the use of a novel neural fuzzy system: the generic self-organising fuzzy neural network (GenSoFNN) with truth-value restriction (TVR) fuzzy inference, as a fuzzy DSS (denoted as GenSo-FDSS) for the classification of ALL subtypes using gene expression data., Results and Conclusion: The performance of the GenSo-FDSS system is encouraging when benchmarked against those of NN, SVM and the K-nearest neighbor (K-NN) classifier. On average, a classification rate of above 90% has been achieved using the GenSo-FDSS system.

Bank failure prediction is an important issue for the regulators of the banking industries. The collapse and failure of a bank could trigger an adverse financial repercussion and generate negative impacts such as a massive bail out cost for the failing bank and loss of confidence from the investors and depositors. Very often, bank failures are due to financial distress. Hence, it is desirable to have an early warning system (EWS) that identifies potential bank failure or high-risk banks through the traits of financial distress. Various traditional statistical models have been employed to study bank failures [J Finance 1 (1975) 21; J Banking Finance 1 (1977) 249; J Banking Finance 10 (1986) 511; J Banking Finance 19 (1995) 1073]. However, these models do not have the capability to identify the characteristics of financial distress and thus function as black boxes. This paper proposes the use of a new neural fuzzy system [Foundations of neuro-fuzzy systems, 1997], namely the Generic Self-organising Fuzzy Neural Network (GenSoFNN) [IEEE Trans Neural Networks 13 (2002c) 1075] based on the compositional rule of inference (CRI) [Commun ACM 37 (1975) 77], as an alternative to predict banking failure. The CRI based GenSoFNN neural fuzzy network, henceforth denoted as GenSoFNN-CRI(S), functions as an EWS and is able to identify the inherent traits of financial distress based on financial covariates (features) derived from publicly available financial statements. The interaction between the selected features is captured in the form of highly intuitive IF-THEN fuzzy rules. Such easily comprehensible rules provide insights into the possible characteristics of financial distress and form the knowledge base for a highly desired EWS that aids bank regulation. The performance of the GenSoFNN-CRI(S) network is subsequently benchmarked against that of the Cox's proportional hazards model [J Banking Finance 10 (1986) 511; J Banking Finance 19 (1995) 1073], the multi-layered perceptron (MLP) and the modified cerebellar model articulation controller (MCMAC) [IEEE Trans Syst Man Cybern: Part B 30 (2000) 491] in predicting bank failures based on a population of 3635 US banks observed over a 21 years period. Three sets of experiments are performed-bank failure classification based on the last available financial record and prediction using financial records one and two years prior to the last available financial statements. The performance of the GenSoFNN-CRI(S) network as a bank failure classification and EWS is encouraging.

Neural fuzzy networks proposed in the literature can be broadly classified into two groups. The first group is essentially fuzzy systems with self-tuning capabilities and requires an initial rule base to be specified prior to training. The second group of neural fuzzy networks, on the other hand, is able to automatically formulate the fuzzy rules from the numerical training data. Examples are the Falcon-ART, and the POPFNN family of networks. A cluster analysis is first performed on the training data and the fuzzy rules are subsequently derived through the proper connections of these computed clusters. This correspondence proposes two new networks: Falcon-FKP and Falcon-PFKP. They are extensions of the Falcon-ART network, and aimed to overcome the shortcomings faced by the Falcon-ART network itself, i.e., poor classification ability when the classes of input data are very similar to each other, termination of training cycle depends heavily on a preset error parameter, the fuzzy rule base of the Falcon-ART network may not be consistent Nauck, there is no control over the number of fuzzy rules generated, and learning efficiency may deteriorate by using complementarily coded training data. These deficiencies are essentially inherent to the fuzzy ART, clustering technique employed by the Falcon-ART network. Hence, two clustering techniques--Fuzzy Kohonen Partitioning (FKP) and its pseudo variant PFKP, are synthesized with the basic Falcon structure to compute the fuzzy sets and to automatically derive the fuzzy rules from the training data. The resultant neural fuzzy networks are Falcon-FKP and Falcon-PFKP, respectively. These two proposed networks have a lean and efficient training algorithm and consistent fuzzy rule bases. Extensive simulations are conducted using the two networks and their performances are encouraging when benchmarked against other neural and neural fuzzy systems.

Existing neural fuzzy (neuro-fuzzy) networks proposed in the literature can be broadly classified into two groups. The first group is essentially fuzzy systems with self-tuning capabilities and requires an initial rule base to be specified prior to training. The second group of neural fuzzy networks, on the other hand, is able to automatically formulate the fuzzy rules from the numerical training data. No initial rule base needs to be specified prior to training. A cluster analysis is first performed on the training data and the fuzzy rules are subsequently derived through the proper connections of these computed clusters. However, most existing neural fuzzy systems (whether they belong to the first or second group) encountered one or more of the following major problems. They are (1) inconsistent rule-base; (2) heuristically defined node operations; (3) susceptibility to noisy training data and the stability-plasticity dilemma; and (4) needs for prior knowledge such as the number of clusters to be computed. Hence, a novel neural fuzzy system that is immune to the above-mentioned deficiencies is proposed in this paper. This new neural fuzzy system is named the generic self-organizing fuzzy neural network (GenSoFNN). The GenSoFNN network has strong noise tolerance capability by employing a new clustering technique known as discrete incremental clustering (DIC). The fuzzy rule base of the GenSoFNN network is consistent and compact as GenSoFNN has built-in mechanisms to identify and prune redundant and/or obsolete rules. Extensive simulations were conducted using the proposed GenSoFNN network and its performance is encouraging when benchmarked against other neural and neural fuzzy systems.

In contrast to the common impression that exposure to a magnetic field of low frequency causes mutations to organisms, we have demonstrated that a magnetic field can actually enhance the efficiency of DNA repair. Using Escherichia coli strain XL-1 Blue as the host and plasmid pUC8 that had been mutagenized by hydroxylamine as the vector for assessment, we found that bacterial transformants that had been exposed to a magnetic field of 50 Hz gave lower percentages of white colonies as compared to transformants that had not been exposed to the magnetic field. This result was indicative that the efficiency of DNA repair had been improved. The improvement was found to be mediated by the induced overproduction of heat shock proteins DnaK/J (Hsp70/40).

Like some naturally occurring environmental stress factors such as heat shock and UV irradiation, magnetic field exposure is also stimulatory to transposition activity. This feature could be illustrated by a bacterial conjugation study using an Escherichia coli strain that carries the transposable element Tn5 as the donor. When the donor cultures were exposed to a low-frequency (50 Hz) magnetic field of 1.2 mT, Tn5 located on the bacterial chromosome was stimulated to transpose and settled on the extrachromosomal episome, and eventually transferred to the recipient cell through conjugation. Such transposition activity stimulation was mediated by the induced synthesis and accumulation of the heat shock proteins DnaK/J., (Copyright 2000 Academic Press.)

Heat shock proteins not only can protect host cells against heat stress, they can also enable freeze tolerance as well. With respect to this unexpected feature, we are able to show that, at least in Escherichia coli, the heat shock proteins DnaK/DnaJ and GroEL play a very significant role. We found that the recovery rate of E. coli cultures that had been stored at -80 degreesC in the absence of any cryoprotectant was related to the abundance of these heat shock proteins accumulated before the freeze treatment. Before freezing, the DnaK in the bacterial cells was induced to accumulate to a level comparable to that produced in response to heat shock. After the freezing treatment, the recovery rate of the induced culture was very similar to that of the heat-shocked culture. Over production of GroEL was also protective but less effective. While freezing inevitably leads to protein denaturation, we propose that advance synthesis of DnaK/DnaJ and GroEL can accordingly prevent irreversible denaturation by chaperoning the unfolded polypeptides during freezing., (Copyright 1998 Academic Press.)

The activation of NK1 receptors on U373 MG human astrocytoma cells by substance P (SP) and related tachykinins was accompanied by an increase in taurine release and an accumulation of inositol phosphates. Both of these effects could be inhibited by spantide, a SP receptor antagonist. The relative potency of tachykinins in stimulating 3H-inositol phosphate accumulation correlated very well with their effects in stimulating the release of [3H]-taurine and inhibition 125I-Bolton-Hunter reagent-conjugated SP binding. The effect on [3H]taurine release was mimicked by a protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA). The inactive phorbol ester analogue 4-alpha-phorbol 12,13-didecanoate, however, was without effect. Both SP- and PMA-induced releases of [3H]-taurine were markedly inhibited by staurosporine, a potent PKC inhibitor. Pretreatment of U373 MG cells with 10 microM PMA for 19 h to down-regulate PKC activity also markedly inhibited both SP- and PMA-induced releases of [3H]-taurine. Treatment of cells with 100 nM SP induced a time-dependent translocation of PKC from the cytosolic fraction to the membrane fraction. These findings are consistent with the hypothesis that an activation of NK1 receptors on U373 MG cells results in the release of inositol phosphates and activation of PKC, which in turn may regulate the release of taurine.

Substance P (SP) stimulated [3H]taurine release from human astrocytoma cells (U-373 MG). This effect was concentration dependent and the EC50 was 0.3 nM. This stimulatory effect of SP can be inhibited by spantide, a SP receptor antagonist. The rank order of potencies of related tachykinins and their analogues in stimulating the release of [3H]taurine was SP much greater than neurokinin A much greater than neurokinin B and [Glp6,L-Pro9]SP (6-11) much greater than [Glp6, D-Pro9]SP (6-11) which conformed to that reported for the tachykinin NK-1 receptor. In addition to SP, isoproterenol, a beta-adrenergic agonist, can also increase the release of [3H]taurine from these cells and the effects of SP and isoproterenol were additive.