二巯基丙磺酸钠治疗毒鼠强中毒的临床研究

目的 探讨二巯基丙磺酸钠(Na-DMPS)治疗毒鼠强(Tetramine)中毒的临床效果及作用机制：方法应用Na-DMPS静脉或肌肉注射治疗毒鼠强中毒，剂量因人而异；结果应用Na-DMPS治疗毒鼠强中毒的病例均取得良好的疗效，没有发现任何毒副作用；结论毒鼠强能阻断中枢神经系统的V-氨基丁酸(GABA)受体而引起惊阙，Na-DMPS能通过多种机制影响GABA受体，降低惊阙发作的程度。值得临床医师试用。     

二巯基丙磺酸钠治疗小儿急性毒鼠强中毒28例分析

目的探讨应用二巯基丙磺酸钠(Na-DMPS)治疗小儿急性毒鼠强中毒的疗效。方法28例患者随机分为2组,其他治疗相同,治疗组加用Na-DMPS治疗。结果治疗组治疗重度毒鼠强中毒疗效明显优于对照组,轻度中毒两组无明显区别。结论Na-DMPS是解救小儿急性重度毒鼠强中毒的有效药物。     

二巯基丙磺酸钠治疗急性毒鼠强中毒临床疗效观察

目的 观察二巯基丙磺酸钠（Na-DMPS)治疗急性毒鼠强中毒临床疗效。方法 将一年半以前给予常规治疗的50例急性毒鼠强中毒患做为对照组，近一年半以来收治的48例做为治疗组，除给予常规治疗外，别加Na-DMPS。观察血清组织释放酶开始下降时间，平均住院日，死亡例数，治愈率，并进行比较。结果 治疗组与对照组血清组织释放酶开始下降时间，平均住院日，死亡例数，治愈率比较差异均有显性（P＜0．05）。结论 Na-DMPS对急性毒鼠强中毒疗效明显，可降低抽搐强度，缩短抽搐持续时间，延长抽搐间隔时间，降低组织释放酶水平及缩短持续时间，从而减轻器官功能损伤，减少呼吸衰竭的发生，缩短住院时间，降低死亡率，提高治愈率。     

小儿毒鼠强中毒神经系统临床表现、治疗及预后

目的：观察小儿毒鼠强中毒的神经系统l临床表现、治疗及预后。方法：分析并随访15例小儿毒鼠强中毒的神经系统症状。对8例用苯巴比妥钠(PB)或妥泰(TPM)加氯硝安定(CZP)治疗的癫痫患儿随访半年至两年。结果：经治疗所有患儿得到有效控制。2年内症状均完全控制，EEG正常6例。结论：急性期洗胃，二巯基丙磺酸钠(Na-DMPS)和及时抗癫痫药等综合治疗，是临床上有效的治疗方法。     

火箭推进剂偏二甲基肼对大鼠γ—氨基丁酸受体的影响

目的研究偏二甲基肼急性中毒时大鼠γ-氨基丁酸(GABA)受体的变化。方法放射性配体结合试验。结果在体外试验中,偏二甲基肼可降低GABA与大鼠脑GABA受体蛋白的结合,与对照组比较,差异有显著意义(P＜0.05);在体内试验中,偏二甲基肼染毒大鼠后,在惊厥发生前染毒大鼠脑GABA受体蛋白与GABA结合明显低于对照组,脑受体结合放射性计数为408±63,对照组为809±210;在惊厥发生时染毒大鼠脑GABA受体与GABA结合明显高于对照组,脑受体结合放射性计数为837±100,对照组为630±141;两组相比,差异均有显著意义(P＜0.01)。结论偏二甲基肼急性中毒时GABA受体的改变可能是其中毒机制之一。     

急性毒鼠强中毒3例

目的:探讨急性毒鼠强中毒的药物治疗方法.方法:在采用传统洗胃、催吐、导泻等方法的基础上,对重症中毒者加用γ 氨基丁酸(γ GABA).结果:重症急性毒鼠强中毒患者在加用γ GABA后,其中枢兴奋症状明显好转.结论:γ GABA可抑制毒鼠强中毒患者的中枢兴奋性,疗效满意.     

毒鼠强中毒患儿的护理

毒鼠强 (四亚甲基二砜四胺 )为有机氮化合物[1,2 ] ,是一种神经毒性灭鼠药 ,该药毒性强 ,中毒剂量很小 ,极易中毒 ,具有强烈的脑干刺激作用及惊厥作用机制 ,可能是通过拮抗ＧＡＢＡ受体而出现中枢神经系统过度兴奋而导致惊厥 ,最近提出其可直接作用于交感神经[3 ] ,目前 ,毒鼠强中毒者主要为农村儿童 ,原因为家长把灭鼠药洒在食物上而误食。我院 2 0 0 0年 5月～ 2 0 0 2年 5月收治 2 6例毒鼠强中毒患儿 ,现将救治及护理情况报告如下 :1　资料与方法1 1　一般资料　男孩 18例 ,女孩 8例 ,年龄为 1～ 7岁 ,中毒途径均为胃肠道中毒 ,其中误食 …     

儿童毒鼠强中毒的诊治体会(附46例报告)

目的 :了解毒鼠强中毒的主要临床表现 ,提高诊断及抢救水平。方法 :对近 4a来收治的 4 6例急性毒鼠强中毒患儿的临床资料进行统计 ,分析误诊原因和抢救措施及其疗效。结果 :小儿毒鼠强中毒的临床表现主要为头晕、乏力、恶心、呕吐、腹痛、四肢阵发性强直性抽搐、昏迷、呼吸衰竭 ,急性肺水肿。本组病例因服毒病史不明确而误诊 17例 ,误诊率高。所有病例确诊后均给予彻底洗胃、控制惊厥及二巯基丙磺酸钠等药物治疗 ,有 7例死亡 ,均死于呼吸衰竭 ,其余临床治愈。结论 :儿童毒鼠强中毒因部分病史不清 ,容易误诊 ,应引起临床医生的重视。治疗的关键要及时确诊、早期洗胃、有效地控制惊厥及二巯基丙磺酸钠的应用。     

丙戊酸钠的合理使用

丙戊酸钠(VPA)是临床应用广泛的一线抗癫痫药物,在治疗偏头痛及顽固性呃逆等方面具有满意疗效,静脉注射可用于控制毒鼠强中毒惊厥持续状态[1],并可治疗双相情感障碍急性抑郁发作[2]。丙戊酸钠治疗指数窄,药物相互作用较多,患     

急性中毒1 098例院前急救分析

目的 提高急性中毒病人的院前急救水平,降低院前死亡率.方法 本文对1 098例急性中毒的病因、合并症、院前急救治疗进行分析.结果 1 098例除18例死亡多时无抢救意义外,其余1 080例经过抢救处理,有效率达96.6%,对202例重度急性中毒患者,联合应用纳洛酮和醒脑静治疗,收到显著疗效.结论 对18例毒鼠强中毒患者应用二巯基丙磺酸钠(Na-DMPS)解毒,取得一定效果.     

“毒鼠强”在鼠体的组织分布及二巯基丙磺钠的促排作用

目的研究"毒鼠强"在鼠体内的组织分布及二巯基丙磺钠的促排作用。方法建立高效液相色谱法测定小鼠体内血浆和组织中"毒鼠强"浓度的方法。结果所建立的高效液相色谱法测定小鼠体内血浆和组织中"毒鼠强"浓度的方法线性良好,回收率高,精密度好。结论口服"毒鼠强"后在体内各组织均有分布,二巯基丙磺钠没有明显的促排作用。     

Possibility for induction of convulsion by fleroxacin and its disposition in the central nervous system in animals

Fleroxacin and its metabolites were examined for their possibility of the induction of convulsion in mice, inhibitory activity on GABA receptor binding, and disposition in the central nervous system of mice, rats and dogs. No convulsion was evoked in mice at high oral combination doses of fleroxacin and fenbufen. Brain-to-serum concentration ratios of fleroxacin after oral dose were 0.13 in mice, 0.19 in rats and 0.28 in dogs. Rats showed no accumulation of fleroxacin in brain and similar elimination from brain to that from serum after the oral dose. Dogs exhibited the similar distribution of fleroxacin into various brain regions. The inhibitory effect of fleroxacin on GABA receptor binding was relatively weak and slightly potentiated in the presence of 4-biphenylacetic acid. Demethyl fleroxacin showed more potent inhibitory activity on GABA receptor binding and potentiation with 4-biphenylacetic acid. The combination of intravenous demethyl fleroxacin and oral fenbufen showed no convulsion in mice. Fleroxacin N-oxide showed only slight inhibitory activity on GABA receptor binding, being not influenced with 4-biphenylacetic acid.     

毛细管气相色谱-质谱联用法测定血中毒鼠强及其应用

目的建立毛细管气相色谱-质谱联用法（GC-MS法）定性检测血中毒鼠强的方法。方法血样经苯提取后,用DM-5弹性石英毛细管柱（Dikma公司,30m×0.25mm×0.25μm）,100℃～250℃程序升温,分别以全扫描模式和选择离子监测模式进样测定。结果毒鼠强的质谱特征碎片M/Z为240、212和121。结论所建立的方法简便、快速、灵敏、准确,可为临床相关急性中毒抢救工作提供科学的实验依据。     

6,2'-Dihydroxyflavone, a subtype-selective partial inverse agonist of GABAA receptor benzodiazepine site

Neuroactivity of a number of flavonoids is mediated by modulation of type A gamma-aminobutyric acid (GABA(A)) receptor function via benzodiazepine sites, mostly as partial agonists. In the present study, 6,2'-dihydroxyflavone (DHF) was characterized for potential inverse agonistic activity, and its mechanism of action was explored for receptor subtype selectivity. In whole-cell patch clamp studies on neuroblastoma IMR-32 cells expressing native GABA(A) receptors, DHF decreased GABA-induced currents, to an extent similar to that induced by the partial inverse agonist FG-7142, which could be blocked by flumazenil, a BZ site antagonist. In mouse behavioral models, DHF elicited significant anxiogenic-like effects in the elevated plus-maze test, and enhanced cognitive performance in the step-through passive avoidance test, as expected for an inverse agonist. However, DHF did not exhibit any proconvulsant effects, a typical action of inverse agonists. In electrophysiological studies on subtypes of recombinant GABA(A) receptors expressed in HEK 293T cells, DHF decreased GABA-induced currents in alpha(1)beta(3)gamma(2), alpha(2)beta(3)gamma(2), or alpha(5)beta(3)gamma(2), but not alpha(3)beta(3)gamma(2) receptors. The results demonstrated DHF as a partial inverse agonist-like modulator of GABA(A) receptors with selectivity in receptor subtypes as well as behavioral effects. The DHF subtype-selectivity suggested that alpha(3)-containing subtypes could be a mediator of the convulsion activities of GABA(A) receptor inverse agonists. Moreover, the pharmacological profile displayed in mouse behavioral models supported DHF as a useful lead compound for the development of cognition-enhancing agents devoid of convulsion side effects.     

Involvement of gamma-amino butyric acid (GABA) in the anticonvulsant action of methaqualone

The effects of methaqualone on isonicotinic acid hydrazide, 6-mercapto propionic acid, picrotoxin, and strychnine-induced convulsion were studied in mice and the results compared with diazepam. Methaqualone, like diazepam, was found to be a selective antagonist of isoniazid-induced convulsion and a much less effective inhibitor of strychnine convulsion.Methaqualone elicits muscle-relaxant, sedative, and anticonvulsant effects at different dose levels. At low, nonsedative doses the drug produces anticonvulsant effects, and at higher doses, muscle-relaxant and sedative effects. It appears that the mechanism(s) of action of methaqualone is on GABA deficiency or receptor blockade, rather than on glycine receptors.     

Benzodiazepines increase tonic component of postdecapitation convulsions in mice

The effects of benzodiazepines (BDZs) and GABA system on tonic and clonic component of postdecapitation convulsion (PDC) were studied in mice. Mice decapitated at the occipito-cervical junction, exerted biphasic convulsions, i.e., initially tonic and subsequently clonic convulsions. BDZs such as diazepam or clonazepam increased tonic and clonic components of PDC. These effects were not antagonized by Ro 15-1788, a benzodiazepine receptor antagonist. The increased tonic component was antagonized by the GABA receptor antagonists, bicuculline and picrotoxin, whereas the clonic component was augmented by them. Aminooxyacetic acid, which increases the endogenous GABA content by inhibiting the GABA-transaminase, increased the tonic component significantly; this increase was antagonized by both bicuculline and picrotoxin. Muscinol, a GABA agonist, however did not affect the tonic components but rather augmented the clonic component. Bicuculline and picrotoxin did not antagonize this effect of muscimol. These results indicate that endogenous GABA may play a crucial role in mediating the tonic component of PDC and the facilitation of this component by BDZs may also be due to the activation of GABA in the spinal cord. Furthermore, the mechanisms of the tonic component may be different from that of the clonic component.     

血液灌流在治疗急性毒鼠强中毒中的应用

目的 探讨血液灌流(hemoperfusion HP)救治急性毒鼠强中毒的疗效.方法 对30例急性毒鼠强中毒的患者进行血液灌流治疗与既往常规治疗的30例患者进行比较.结果 HP治疗后患者血液中的毒鼠强浓度明显减低,症状控制时间及住院天数的缩短,治愈率提高(血液灌流组治愈率87%,常规治疗组53%).结论 HP治疗急性毒鼠强中毒较常规治疗有明显疗效.     

左乙拉西坦对热性惊厥大鼠治疗作用的研究

目的观察左乙拉西坦对热性惊厥大鼠的治疗作用。方法通过热水浴建立热性惊厥大鼠模型,将40只SD幼龄热性惊厥大鼠随机分为模型组及左乙拉西坦低、中、高剂量组[100、200、300 mg/(kg·d)],分别于造模前灌胃,造模后进行47℃热水浴试验,每天惊厥1次,共惊厥5 d。观察每组大鼠惊厥潜伏期、惊厥持续时间、惊厥级别。采用TUNLE法检测各组大鼠海马神经元凋亡情况。试剂盒法检测海马组织中含半胱氨酸的天冬氨酸水解酶(Caspase 3)活性及谷氨酸(Glu)含量,Western blot检测γ-氨基丁酸(GABA蛋白)表达量。结果与模型组比较,左乙拉西坦低、中、高剂量组中大鼠惊厥潜伏期延长,惊厥持续时间缩短,惊厥严重程度降低,海马神经元凋亡率降低,Caspase 3活性及Glu含量降低,GABA表达量提高,差异均有统计学意义(P<0.01)。结论左乙拉西坦对热性惊厥大鼠具有显著治疗作用,可能与抑制神经元凋亡及调节Glu与GABA表达量有关。     

Inhibition of the rate of GABA synthesis in regions of rat brain following a convulsion.

1 The rate of synthesis of gamma-aminobutyric acid (GABA) in the cortex, hippocampus and striatum of rat brain was assessed by measuring the linear rate of accumulation of GABA following injection of amino-oxyacetic acid (AOAA). 2 Five min after a single electrically induced seizure there was a rise in GABA content in these brain regions and an almost total inhibition of the rate of synthesis. 3 Five min after seizure induced by the inhalant convulsant flurothyl there was no rise in GABA content in these brain regions but a similar marked degree of inhibition of GABA synthesis. 4 Two hours after the convulsion the rate of GABA synthesis had returned to control values in all three brain regions. 5 A single convulsion did not alter the glutamic acid decarboxylase activity in these brain regions either in the absence or presence of added co-factor (pyridoxal phosphate). 6 Evidence for an inhibition of GABA release following a convulsion which may be associated with the inhibition of GABA synthesis is presented in the following paper.