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Liu Z.-R.,Shanghai University | Tao J.,Shanghai University | Dong B.-Q.,Shanghai University | Ding G.,Xinhua Translational Institute For Cancer Pain | And 4 more authors.
Neuroscience Bulletin | Year: 2012

Objective: In this study, the pharmacological kinetics of Buthus martensi Karsch (BmK) AS, a specific modulator of voltage-gated sodium channel site 4, was investigated on Nav1.3 expressed in Xenopus oocytes. Methods: Twoelectrode voltage clamp was used to record the whole-cell sodium current. Results: The peak currents of Nav1.3 were depressed by BmK AS over a wide range of concentrations (10, 100, and 500 nmol/L). Most remarkably, BmK AS at 100 nmol/L hyperpolarized the voltage-dependence and increased the voltage-sensitivity of steady-state activation/inactivation. In addition, BmK AS was capable of hyperpolarizing not only the fast inactivation but also the slow inactivation, with a greater preference for the latter. Moreover, BmK AS accelerated the time constant and increased the ratio of recovery in Nav1.3 at all concentrations. Conclusion: This study provides direct evidence that BmK AS facilitates steady-state activation and inhibits slow inactivation by stabilizing both the closed and open states of the Nav1.3 channel, which might result from an integrative binding to two receptor sites on the voltage-gated sodium channels. These Results: may shed light on therapeutics against Nav1.3-targeted pathology. © Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2012.


Shen J.,Shanghai JiaoTong University | Huang C.-X.,Shanghai JiaoTong University | Yu Y.-L.,Shanghai JiaoTong University | Liu H.-X.,Shanghai JiaoTong University | And 2 more authors.
Chinese Journal of Tissue Engineering Research | Year: 2014

BACKGROUND: The anesthesia process is required strict in establishing rabbit models of ileal neobladder. It is required for cleaning operation field, quick postoperative recovery, and the choice of anesthetics and anesthesia does not influence smooth muscle peristalsis. OBJECTIVE: To compare the anesthetic effects between urethane and chloral hydrate in rabbits with ileal neobladder. METHODS: Eighteen rabbits were randomly assigned to urethane and chloral hydrate groups, and were respectively anesthetized with 20% urethane 5 mL/kg and 10% chloral hydrate 2 mL/kg through the ear vein. Double ureter was dissociated at 1 cm outside original bladder, and 15 cm-intestine obtained from 10 cm of ileocecal junction was implanted so as to establish models of ileal neobladder. RESULTS AND CONCLUSION: Heart rates were significantly lower compared with these before anesthesia in all cases (P ≤ 0.05), but no differences were detected between two groups (P > 0.05). Compared with the chloral hydrate group, the maintain time and recovery time were longer and the mortality rate was higher in the urethane group. Above data indicated that chloral hydrate is a safe long-acting anesthetic in establishing rabbit models of ileal neobladder. © 2014, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.


Ke M.,Shanghai JiaoTong University | Yinghui F.,Shanghai JiaoTong University | Yi J.,Nanjng Jinling Hospital | Xuehua H.,Shanghai JiaoTong University | And 4 more authors.
Pain Physician | Year: 2013

Background: Postherpetic neuralgia (PHN) is often refractory to existing treatments. Pulsed radiofrequency (PRF) is known to be effective for treating neuropathic pain. In common, the targets of PRF treatment were the segmental dorsal root ganglion (DRG) neurons responsible for the pain. A potential complication that can occasionally occur with PRF treatment is damage to the adjacent tissue and organ. The effectiveness of the angulus costae as a puncture site for PRF has not been tested in thoracic PHN treatment. Objective: The goal of this study was to investigate the therapeutic efficacy and safety of PRF for treating thoracic PHN through the puncture of the angulus costae. Study Design: Prospective, randomized, double-blinded study. Setting: Department of Anesthesiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine. Methods: Ninety-six patients with thoracic (T2-11) PHN were equally randomized assigned into 2 groups. The electrode needle punctured through the angulus costae of each patient guided by x-ray; PRF at 42°C for 120 seconds was applied after inducing paresthesia involving the affected dermatome area. PRF was applied in the PRF group (n = 48) twice. It was also applied in the sham group (n = 48) twice without radiofrequency energy output. The treatment was done once a week for 3 weeks. Tramadol was used for flare pain when the visual analog scale (VAS) ≥ 3. Outcomes Assessment: The therapeutic effect was evaluated by VAS, SF-36 health survey questionnaire, side effects (type, frequency, and onset time) before treatment, at days 3, 7, and 14, and at months one, 2, 3 and 6 after PRF. The average of tramadol (mg/d) administrated within the first month after treatment was also recorded. Results: The postprocedure VAS scores in the PRF group were significantly lower than those in the sham group and lasted for 6 months after treatment (P < 0.05). The SF-36 score, such as physical functioning, physical role, bodily pain, general health perceptions, social function, emotional role, and mental health index were significantly improved until 6 months after treatment in the PRF group compared to the sham group (P < 0.01- 0.05). The average dosage of tramadol administered (mg/d) within the first month after treatment was also significantly reduced in the PRF group compared to the sham group (P < 0.05). There were no obvious signs of pneumothorax, bleeding, infection, or other severe side effects in either group (P > 0.05). Limitations: Single center study, relatively small number of patients. Conclusions: The strategy that the angulus costae be used as the PRF puncture point of an electrode needle and the final localization of the needle tip as determined by sensory testing is an effective and safe therapeutic alternative for thoracic PHN treatment. Benefits include that the procedure is minimally invasive, provides short-term pain relief, and improves quality of life. Clinical Trial Registration: NO ISRCTN25588650.


Zhang H.,Shanghai University | Ji H.,Shanghai JiaoTong University | Ji H.,Xinhua Translational Institute For Cancer Pain | Liu Z.,Shanghai University | And 8 more authors.
Neuroscience Bulletin | Year: 2014

Bupivacaine ranks as the most potent and efficient drug among class I local anesthetics, but its high potential for toxic reactions severely limits its clinical use. Although bupivacaine-induced toxicity is mainly caused by substantial blockade of voltage-gated sodium channels (VGSCs), how these hydrophobic molecules interact with the receptor sites to which they bind remains unclear. Nav1.5 is the dominant isoform of VGSCs expressed in cardiac myocytes, and its dysfunction may be the cause of bupivacaine-triggered arrhythmia. Here, we investigated the effect of bupivacaine on Na v1.5 within the clinical concentration range. The electrophysiological measurements on Nav1.5 expressed in Xenopus oocytes showed that bupivacaine induced a voltage- and concentration-dependent blockade on the peak of INa and the half-maximal inhibitory dose was 4.51 μmol/L. Consistent with other local anesthetics, bupivacaine also induced a use-dependent blockade on Nav1.5 currents. The underlying mechanisms of this blockade may contribute to the fact that bupivacaine not only dose-dependently affected the gating kinetics of Nav1.5 but also accelerated the development of its open-state slow inactivation. These results extend our knowledge of the action of bupivacaine on cardiac sodium channels, and therefore contribute to the safer and more efficient clinical use of bupivacaine. © 2014 Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag.

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