N-Phenylethyl Amitriptyline in Rat Sciatic Nerve Blockade

Background: The antidepressant amitriptyline is commonly used orally for the treatment of chronic pain, particularly neuropathic pain, which is thought to be caused by high-frequency ectopic discharge. Among its many properties, amitriptyline is a potent Na+ channel blocker in vitro, has local anesthetic properties in vivo, and confers additional blockade at high stimulus-discharge rates (use-dependent blockade). As with other drug modifications, adding a phenylethyl group to obtain a permanently charged quaternary ammonium derivative may improve these advantageous properties.

Methods: The electrophysiologic properties of N-phenylethyl amitriptyline were assessed in cultured neuronal GH3 cells with the whole cell mode of the patch clamp technique, and the therapeutic range and toxicity were evaluated in the rat sciatic nerve model.

Results: In vitro, N-phenylethyl amitriptyline at 10 [mu]m elicits a greater block of Na+ channels than amitriptyline (resting block of approximately 90%vs. approximately 15%). This derivative also retains the attribute of amitriptyline in evoking high-degree use-dependent blockade during repetitive pulses. In vivo, duration to full recovery of nociception in the sciatic nerve model was 1,932 +/- 72 min for N-phenylethyl amitriptyline at 2.5 mm (n = 7) versus 72 +/- 3 min for lidocaine at 37 mm (n = 4; mean +/- SEM). However, there was evidence of neurotoxicity at 5 mm.     

An Unexplained Death: Hannah Greener and Chloroform

Background: Reports of major and minor sequelae following lidocaine spinal anesthesia have generated interest in an alternative short-acting intrathecal agent. Of the available anesthetics suitable for short-duration spinal anesthesia, prilocaine is perhaps the most promising agent. However, data comparing the neurotoxicity of these agents are lacking. Accordingly, the present experiments investigate whether prilocaine and lidocaine differ with respect to sensory impairment and histologic damage when administered intrathecally in the rat.

Methods: Ninety rats were divided into three groups to receive an intrathecal infusion of 2.5% prilocaine in saline, 2.5% lidocaine in saline, or normal saline. The animals were assessed for persistent sensory impairment 4 days after anesthetic administration using the tail-flick test. Three days later, the animals were killed, and specimens of the spinal cord and nerve roots were obtained for histopathologic examination.

Results: Prilocaine and lidocaine produced equivalent elevations in tail-flick latency that differed significantly from saline. Histologic injury scores with prilocaine were greater than with lidocaine, but this difference did not reach statistical significance.     

三叉神经痛显微血管减压术后的远期疗效观察

原发性三叉神经痛可能是由于桥小脑角区上血管神经复合体中相关的小脑动脉及静脉压迫三叉神经敏感区而发病。显微血管减压术治疗三叉神经痛已被广泛接受和应用，其治愈率是理想的。然而，从客观上讲还有一部分患者的疼痛未完全缓解，会复发或术后出现并发症，其结果不完全令人满意。但是患者主观满意度究竟怎样，患者亲身感受和对比手术前后的变化，包括复发疼痛的程度，     

广西医学院举办首届学校卫生医师培训班

广西医学院儿少卫生教研室受区卫生厅委托于1985年9月开始举办为期半年的学校卫生医师培训班。来自基层防疫站和学校的31名学     

印度生物技术企业欲与瑞典开展合作

Biocon公司是印度重要的生物技术公司之一,最近,该公司与Karolinska学院(瑞典最主要的医科大学)签署了一份协议,根据这项协议,双方将在研究、教育领域开展合作。此协议内容包括合作开发产品和共同研究规划。印度生物技术企业欲与瑞典开展合作@张亦农     

Cephalad Movement of Morphine and Fentanyl in Humans after Intrathecal Injection

Background: Despite decades of use, controversy remains regarding the extent and time course of cephalad spread of opioids in cerebrospinal fluid (CSF) after intrathecal injection. The purpose of this study was to examine differences between two often used opioids, morphine and fentanyl, in distribution in the CSF after intrathecal injection.

Methods: Eight healthy volunteers received intrathecal injection of morphine (50 [mu]g) plus fentanyl (50 [mu]g) at a lower lumbar interspace. CSF was sampled through a needle in an upper lumbar interspace for 60-120 min. At the end of this time, a sample was taken from the lower lumbar needle, and both needles were withdrawn. CSF volume was determined by magnetic resonance imaging. Pharmacokinetic modeling was performed with NONMEM.

Results: Morphine and fentanyl peaked in CSF at the cephalad needle at similar times (41 +/- 13 min for fentanyl, 57 +/- 12 min for morphine). The ratio of morphine to fentanyl in CSF at the cephalad needle increased with time, surpassing 2:1 by 36 min and 4:1 by 103 min. CSF concentrations did not correlate with weight, height, or lumbosacral CSF volume. The concentrations of morphine and fentanyl at both sampling sites were well described by a simple pharmacokinetic model. The individual model parameters did not correlate with the distance between the needles, CSF volume, patient height, or patient weight.     

GABAergic Interneurons at Supraspinal and Spinal Levels Differentially Modulate the Antinociceptive Effect of Nitrous Oxide in Fischer Rats

Background: The study hypothesizes that nitrous oxide (N2O) releases opioid peptide in the brain stem, which results in inhibition of [gamma]-aminobutyric acid-mediated (GABAergic) neurons that tonically inhibit the descending noradrenergic inhibitory neurons (DNIN), resulting in activation of DNIN. In the spinal cord, activation of DNIN leads to the release of norepinephrine, which inhibits nociceptive processing through direct activation of [alpha]2 adrenoceptor and indirect activation of GABAergic neurons through [alpha]1 adrenoceptor. Arising from this hypothesis, it follows that GABAergic neurons will modulate the antinociceptive effect of N2O in diametrically opposite directions at supraspinal and spinal levels. The authors have tested this tenet and further examined the effect of midazolam, a GABA-mimetic agent, on N2O-induced antinociceptive effect.

Methods: Adult male Fischer rats were administered muscimol (GABAA receptor agonist) intracerebroventricularly (icv), gabazine (GABAA receptor antagonist) intrathecally (intrathecal), or midazolam intraperitoneally (intraperitoneal). Fifteen minutes later, they were exposed to air or 75% N2O and were subjected to the plantar test after 30 min of gas exposure. In some animals administered with midazolam, gas exposure was continued for 90 min, and the brain and spinal cord were examined immunohistochemically.

Results: The N2O-induced antinociceptive effect, which was attenuated by icv muscimol, intrathecal gabazine, and intraperitoneal midazolam. Midazolam inhibited N2O-induced c-Fos expression (a marker of neuronal activation) in the pontine A7 and spinal cord.     

印度生物技术界试图开拓美国市场

印度生物技术主导企业协会(Biotechnology-LedEnterprisesofIndia)计划在美国设立分会,目的是为了在美国发展生物技术工业。美国当地商界有影响的权威人士Sartorious将担任该分会的名誉会长。印度生物技术界试图开拓美国市场@辛静     

免疫抑制剂致药物性肾损害

免疫抑制剂与类固醇激素一起用于器官移植、自身免疫疾病等疾病的治疗。目前作为免疫抑制剂应用的药物有硫唑嘌呤、环磷酰胺、环孢菌素（CyA）和他克莫司，还有日本开发、广泛应用的咪唑立宾（mizoribine，MZB）。近来，免疫抑制剂不仅用于器官移植，也成为肾脏领域肾病综合征以及自身免疫疾病的治疗中不可或缺的一部分。其中钙调神经磷酸酶抑制剂（calcineulin inhibitor，CNI）类免疫抑制剂的共同副作用为肾损害，特别是长期应用导致的慢性肾毒性已成为严重问题。