拟除虫菊酯对大鼠神经细胞凋亡的诱发作用

在发现拟除虫菊酯（Ｐｙ）可使大鼠脑组织谷氨酸含量升高，并使突触前膜谷氨酸释放增加的基础上，观察了Ｐｙ对大鼠神经细胞凋亡的诱发作用。结果发现，溴氰菊酯（ＤＭ）可以使分离的神经细胞ＤＮＡ受到损伤，出现类似凋亡的形态学改变；同时用流式细胞仪进行检测，发现ＤＭ和氯菊酯（ＰＭ）可以使大鼠脑组织皮层、海马和小脑部位ＤＮＡ片段化的细胞数明显增加。说明Ｐｙ可以损伤神经细胞的ＤＮＡ，有可能诱发神经细胞的凋亡。     

拟除虫菊酯诱导大鼠脑组织神经生长因子的表达

目的　为了探讨拟除虫菊酯对中枢神经系统损害的机理。方法　用逆转录 聚合酶链反应 (RT PCR) ,斑点杂交 ,流式细胞术及免疫组织化学技术同时检测了氯菊酯 (PM )和溴氰菊酯 (DM )对大鼠脑组织中神经生长因子 (NGF)表达的影响。结果4种方法检测结果均表明 1次大剂量 (PM1组 ,4 0 0mg·kg- 1)和连续 5d较小剂量 (PM2组 ,2 0 0mg·kg- 1)PM处理后大鼠脑组织NGF的mRNA和蛋白表达增多。其中RT PCR和斑点杂交结果表明各组大鼠大脑皮层和海马的NGFmRNA水平均有显著升高 ;其蛋白表达水平的变化与mRNA升高基本一致。而DM对NGF的影响与PM稍有不同 ,虽然大剂量(DM1组 ,2 5 .0mg·kg- 1) 1次ip和连续 5d较小剂量 (DM2组 ,12 .5mg·kg- 1)ip均可引起NGFmRNA表达的增加 ,流式细胞术结果却表明DM2组海马的NGF蛋白表达水平无明显的增加 ;免疫组化亦表明DM2组皮层及海马各区NGF的蛋白表达均无明显升高。结论　两型拟除虫菊酯对NGF蛋白表达的诱导作用不同 ,而NGF表达的增加可能在其神经损伤修复中有重要意义     

拟除虫菊酯对中枢神经系统谷氨酸递质信号转导过程影响的机理

拟除虫菊酯对中枢神经系统谷氨酸递质信号转导过程影响的机理石年刘毓谷（同济医科大学环境毒理学教研室，武汉４３００３０）对谷氨酸兴奋性递质在拟除虫菊酯神经毒性发生中的作用及其可能的机理进行了系统的研究．结果表明，拟除虫菊酯可明显干扰哺乳动物中枢神经系统兴...     

固相萃取-高效液相色谱法测定桔梗中拟除虫菊酯的农药残留

目的:建立桔梗中甲氰菊酯、高效氯氟氰菊酯、溴氰菊酯、氰戊菊酯、氯菊酯、联苯菊酯共6个拟除虫菊酯类农药残留的提取、净化及其残留量测定的方法。方法:样品运用石油醚提取,商品CARB/NH2小柱净化,乙腈-二氯甲烷(5∶95)洗脱,HPLC-DAD检测。色谱条件:采用Hypersil BDS C18(250 mm×4.6 mm,5μm)色谱柱,流动相为乙腈-水(70∶30),流速1 mL.min-1,检测波长230 nm。结果:样品4水平添加时的6个拟除虫菊酯类化合物回收率在75.63%～107.5%范围内,RSD在2.3%～9.9%范围内,可以满足农药残留分析的要求。结论:该方法灵敏度高,选择性强,操作简单、快速,净化效果好。可应用于桔梗药材中痕量农药残留的检测。     

拟除虫菊酯农药的毒性研究进展

拟除虫菊酯农药是70年代迅速发展起来的新型农药，由于它高效、低毒而替代有机氯农药在室内和农业广泛应用。根据拟除虫菊酯化学结构的不同可将其分为不含α-氰基的Ⅰ型以氯菊酯为代表和含α-氰基的Ⅱ型以氯氰菊酯、溴氰菊酯和氰戊菊酯等为代表。由于Ⅱ型的广谱性和高效性，广泛用于农林害虫和卫生害虫的防治，现在以Ⅱ型使用最多，对此的研究报道也较多。     

国内对拟除虫菊酯类农药的毒性毒理研究概况

拟除虫菊酯类农药是70年代迅速发展起来的新型农药,具有广谱、高效、低毒、低残留的优点,日益广泛应用于农业、林业、仓储和卫生等部门的害虫防治。 二氯菊酯(商品名除虫精)是国内由江苏省农药研究所最早合成的拟除虫菊酯农药之一。1978年江苏省又相继合成了氰戊菊酯(商品名速灭菊酯)     

拟除虫菊酯农药急性中毒的诊断与治疗

目前国内拟除虫菊酯（Pyrethroid）杀虫剂在不断发展,新品种不断涌现。这类杀虫剂具有广谱、高效、低残留、光稳定和易生物降解等优点。适宜防治农业害虫,对蚊、蝇、蟑螂和头虱等卫生害虫也有相当满意的效果。这类农药应用数量大、使用面积广、接触人群多。在我国,特别是农村,此类农药中毒常有发生。为了加强对这类农药的防治,本文对拟除虫菊酯急性中毒的诊断和治疗加以综述。     

HPLC-ECD法测定大鼠脑组织中单胺类神经递质的含量

目的:建立测定大鼠脑组织中的单胺类神经递质含量的方法。方法:采用高效液相色谱-电化学法,以2,5-二羟基苯甲酸为内标,测定大鼠大脑皮层、小脑、海马组织、下丘脑、嗅球中以去甲肾上腺素(NE)和5-羟色胺(5-HT)为代表的单胺类神经递质的含量。色谱柱为DIKMAC18,流动相为缓冲盐溶液(醋酸钠、庚烷磺酸钠、乙二胺四乙酸二钠和柠檬酸)-甲醇(梯度洗脱),流速为1.0 ml/min,工作电压为+0.7 V。结果:NE、5-HT的检测质量浓度线性范围分别为0.084⁴.2μg/ml(r=0.999 9)和0.0054.2μg/ml(r=0.999 9)和0.005⁰.25μg/ml(r=0.999 1),平均加样回收率分别为98.85%(RSD=2.89%,n=3)和101.5%(RSD=2.41%,n=3),日内(n=5)和日间(n=3)RSD均不大于3%;NE在小脑中的含量最低[(0.343±0.14)mg/g],在下丘脑中含量最高[(3.062±1.51)mg/g];5-HT在小脑中的含量最低[(0.059±0.04)mg/g],在大脑皮层中含量最高[(0.383±0.21)mg/g]。结论:本方法灵敏、简便、快速,可用于大鼠脑组织中NE、5-HT含量的测定。     

有机磷与拟除虫菊酯农药联合作用的毒性评价

目的 探讨农药混配后农药之间发生的相互作用,为合理混配农药提供参考依据。方法 用等毒剂量法评价有机磷类与拟除虫菊酯类农药混剂对大鼠急性经口毒性的联合作用。结果 辛酸磷＋溴氰菊酯、辛硫磷＋高效氯氰菊酯、甲基对硫磷＋高效氯氰菊酯和水胺硫磷＋甲氰菊酯毒性增加非常明显呈协高作用。辛硫磷＋氰戊菊酯虽属相加作用,但毒性是相加作用的１．５倍,唯独敌敌畏＋溴氰菊酯虽属相加作用,但毒性略有降低。结论 有机磷与拟除虫     

一氧化碳对幼龄大鼠脑单胺类神经递质代谢的影响

幼龄Wistar大鼠,分别给以一氧化碳 0(对照)、5、25和125ppm染毒4小时,结果125ppm染毒组5-羟色胺明显减少。用250ppm CO染毒的幼龄大鼠给以腹腔注射单胺氧化酶抑制剂优降宁100mg/kg,1小时后去肾上腺素的更新率比对照组明显降低。腹腔注射囊泡摄取阻断剂利血平5mg/kg耗竭单胺后,去甲肾上腺素、多巴胺和5-羟色胺明显增多。说明CO可使鼠脑单胺类神经递质的合成和降解受到抑制。     

Effects of piracetam on brain monoamine metabolism and serum prolactin levels in the rat

Levels of monoamine metabolites in three different regions of the rat brain were determined following treatment with piracetam (0.5 and 5 g/kg, i.p.). The concentration of prolactin in serum was also measured.Piracetam, at 5 g/kg, increased the levels of dihydroxyphenylacetic acid, homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol, whereas 5-hydroxyindoleacetic acid was unaffected. The drug also increased prolactin concentrations in serum. The level of dopamine was unchanged in the olfactory tubercle and the striatum. These effects are different from those obtained with amphetamine-like drugs. The results would seem to indicate that piracetam accelerates brain catecholamine (CA) turnover via a blockade of CA receptors, as suggested for neuroleptic drugs. This effect could be responsible for the therapeutic action of piracetam on psychotic symptoms in psycho-organic disorders of old age. A blockade of brain CA receptors by piracetam is not compatible with facilitated learning, which seems to be mediated via other neuron systems than CA pathways.     

The effect of CO2 on monoamine metabolism in rat brain

Summary White male albino rats were exposed to artificial atmosphere containing 20% of O₂ and 5, 10 and 15% of CO₂, for periods of time ranging from 30 min to 2 h. Monoamine synthesis in different dissected brain areas was measured by estimating Dopa and 5-hydroxytryptophan (5-HTP) accumulation after inhibition of their decarboxylation with the L-aromatic aminoacid decarboxylase inhibitor NSD 1015 (3-hydroxybenzylhydrazine). Endogenous levels of noradrenaline (NA), dopamine (DA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), and NA and DA levels after inhibition of catecholamine synthesis with -methyltyrosine (-MT) were measured in dissected areas and whole brain.The synthesis of all three monoamines was found to be increased in all the cerebral regions. Endogenous dopamine levels with or without -MT treatment were increased while NA levels decreased. 5-HT decreased in at least one area and 5-HIAA increased in several brain areas. These observations indicate that the utilization of NA and 5-HT is increased and that of DA is diminished in acidosis, presumably as a consequence of a corresponding change in nerve impulse flow.The similarity between the monoamine changes induced by hypercarbia and by GABA are pointed out. It is suggested that GABA-ergic activity is elevated in acidosis and that GABA may be involved in the pH dependence of seizure thresholds, as well as in the increased tendency to respiratory depression induced by central nervous system depressant drugs in patients with chronic respiratory failure.     

无机汞对大鼠脑单胺类神经递质代谢的影响

用大鼠脑组织匀浆、游离脑细胞和脑细胞亚组分作实验材料，较全面地观察了氯化汞对单胺类神经递质含量及其合成、释放、摄取、降解等重要代谢环节的影响。结果表明，汞通过抑制脑线粒体外膜单胺氧化酶使得脑组织中５－羟色胺、多巴胺、去甲肾上腺素含量增高，５－羟吲哚乙酸含量下降，呈良好的剂量－效应关系；汞还明显改变了游离脑细胞对单胺类神经递质的释放和摄取能力。     

Inhibition of rat brain monoamine oxidase enzymes by fluoxetine and norfluoxetine

Fluoxetine and its primary metabolite, norfluoxetine, are inhibitors of neuronal uptake of 5-hydroxytryptamine. While fluoxetine has also been reported to inhibit monoamine oxidase (MAO) in vitro at concentrations much lower than those measured in brain following chronic fluoxetine treatment, neurochemical profiles are not consistent with substantial MAO inhibition in vivo. In an attempt to explain this inconsistency, we have examined the interactions of fluoxetine and norfluoxetine with rat brain MAO-A and -B by a radiochemical assay method.Fluoxetine and norfluoxetine were competitive inhibitors of MAO-A in vitro, with K_i values of 76.3 M and 90.5 M, respectively. Both compounds were non competitive or uncompetitive inhibitors of MAO-B in vitro. Inhibition of MAO-B was time-dependent and was very slowly reversible by dialysis. IC₅₀ values versus metabolism of 50 M, -phenylethylamine were 17.8 M (fluoxetine) and 18.5 M (norfluoxetine). Analysis of the time-dependence of MAO-B inhibition by fluoxetine revealed that an initial competitive interaction between the enzyme and the inhibitor (K_i 245 M) was followed by tight-binding enzyme inactivation (k_inact 0.071 min^–1).Following administration of fluoxetine (20 mg kg^–1 day^–1]) for 7 days, the cortical concentration of fluoxetine + norfluoxetine was estimated by gas-liquid chromatography to be 700 M. Such drug treatment reduced MAO-A activity by 23% in 1:8 (w/v) cortical homogenates, but not in 1:80 homogenates. Inhibition of MAO-B in 1:8 homogenates was modest (12%) and was not significantly reduced by homogenate dilution. The concentration of 5-hydroxyindole-3-acetic acid, measured by high pressure liquid chromatography, was reduced by 47% in cortices from drug-treated rats, while concentrations of 5-hydroxytryptamine, noradrenaline, dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid were unchanged. These results suggest that, following chronic drug administration leading to relatively high tissue concentrations of fluoxetine and norfluoxetine, inhibition of either form of MAO would be restricted by competition for the enzyme with intraneuronal amine substrates.     

Effect of isopropanol on rat brain monoamine levels

Changes in monoamines were studied in discrete areas of brain with varying dose of isopropanol. Acute administration of isopropanol (0.463 g/kg, 0.925 g/kg and 1.85 g/kg) decreased dopamine level in hypothalamus, pons medulla and cerebral cortex and whereas it was increased in striatum and cerebellum. Noradrenaline level was reduced in all the brain areas studied. Adrenaline level was increased in hypothalamus, striatum, midbrain and pons medulla, and decreased in hippocampus and cerebral cortex. Serotonin level was increased in hypothalamus, midbrain, pons-medulla and cerebral cortex, and decreased in striatum and hippocampus. These changes were dose-dependent. It is concluded that isopropanol causes changes in brain monoamine content that this effect is not the same in all the regions of the brain.     

Interactions of methylenedioxymethamphetamine with monoamine transmitter release mechanisms in rat brain slices

Summary This study investigates the effects of methylenedioxymethamphetamine (MDMA) and amphetamine on monoamine release from rat superfused brain slices in both the presence and absence of vesicular stores of transmitter. MDMA caused the release of radioactivity from slices incubated with [³H]5-hydroxytryptamine, [³H]noradrenaline or [³H]dopamine with EC₅₀ values of 1.9 mol/l (95% confidence limits 1.5–2.3 mol/l), 4.5 mol/l (2.3–8.7 mol/l), and greater than 30 mol/l, respectively. In contrast, amphetamine (0.1–300 mol/l) was more effective in releasing radioactivity from slices incubated with [³H]dopamine than [³H]noradrenaline or [³H]5-hydroxytryptamine. When Ca²⁺ was excluded from the superfusion fluid, the MDMA induced release of radioactivity from slices incubated with [³H]dopamine was unaltered, but that from slices incubated with [³H]noradrenaline or [³H]5-hydroxytryptamine was enhanced. MDMA (10 mol/l) facilitated the stimulation-induced (5 Hz, 1 min) outflow of radioactivity from slices incubated with [³H]noradrenaline or [³H]5-hydroxytryptamine to 7.5-fold and 2.1-fold of control values, respectively, but had no effect on that from slices incubated with [³H]dopamine. Amphetamine (1 mol/l) increased the stimulation-induced outflow from slices incubated with [³H]noradrenaline, but not that from slices incubated with [³H]5-hydroxytryptamine or [³H]dopamine.Inhibition of monoamine oxidase by a 30-min incubation with pargyline (100 mol/l) enhanced the releasing action of MDMA on all three monoamines. Pargyline (100 mol/l) also enhanced the facilitation caused by MDMA, of the stimulation-induced outflow of radioactivity from slices incubated with [³H]noradrenaline, [³H]5-hydroxytryptamine or [³H]dopamine.In some experiments, slices were obtained from reserpinised rats (2.5 mg/kg s.c. 24 h prior) and pre-exposed for 30 min to the monoamine oxidase inhibitor pargyline (100 mol/l). Under these conditions, electrical stimulation evoked a small residual stimulation-induced outflow of radioactivity from slices incubated with [³H]noradrenaline, and failed to evoke an outflow of radioactivity from slices incubated with [³H]5-hydroxytryptamine or [³H]dopamine. However, a Ca²⁺-dependent stimulation-induced outflow of radioactivity was evoked in the presence of either MDMA (10 mol/l) or amphetamine (1 mol/l) from slices incubated with either [³H]dopamine or [³H]noradrenaline, but not from slices incubated with [³H]5-hydroxytryptamine. The stimulation-induced outflow of radioactivity from slices incubated with [³H]noradrenaline was enhanced in the presence of desipramine (1 mol/l), however this enhancement was less than that caused by 10 mol/l MDMA or 1 mol/l amphetamine. The Ca²⁺-dependent response to electrical stimulation in the presence of MDMA from slices incubated with [³H]noradrenaline was greatly reduced when rats were pretreated with a higher dose of reserpine (10 mg/kg s.c.).This study demonstrates that MDMA and amphetamine release radioactivity from brain slices incubated with [³H]noradrenaline, [³H]dopamine and [³H]5-hydroxytryptamine, but their order or potency as releasers of brain monoamines differs. The results also suggest that MDMA and amphetamine have significant effects on the exocytotic release of monoamines and may interact with both vesicular and cytoplasmic monoamines. Correspondence to J. J. Reid at the above address     

The effect of methanol on rat brain monoamine levels

The variations in brain monoamine levels after methanol administration were studied in discrete areas of rat brain. Acute methanol administration (2 g/kg and 4 g/kg) significantly decreased Dopamine (DA) level in striatum and increased it in hypothalamus. Nor-Epinephrine (NE) and Epinephrine (E) levels were reduced in most of the areas studied. Serotonin (5HT) level was increased in hypothalamus, midbrain and cortex with corresponding increase in 5 Hydroxy Indole Acetic Acid (5 HIAA) level. It was concluded that central monoaminergic neurons were specifically influenced either directly or indirectly after methanol administration and that the effect of methanol differed according to the brain area and its action on different monoaminergic systems were quite different.     

Effect of chronic deuterated and non-deuterated phenelzine on rat brain monoamines and monoamine oxidase

Summary The effects of phenelzine and 1,1-dideuterophenelzine (0.5 or 2.5 mg/kg/day) administered s.c. via miniosmotic pumps for 13 days were compared. Striatal levels of p-tryrosine and tryptophan were unaffected by either treatment. The concentrations of DOPAC, HVA and 5-HIAA were dose-dependently decreased by phenelzine and deuterated phenelzine; furthermore, the deuterated compound decreased the amounts of these acids more than the same dose of phenelzine. Dopamine levels were increased by a rather small amount by all drug treatments; no effects of drug dose or drug type (deuterated or nondeuterated) were observed. With the exception of phenylethylamine, qualitatively similar effects were found with all other amines measured; their amounts were increased dose-dependently and the effects of deuterated phenelzine were greater than those of phenelzine. Rat cerebral MAO activity was inhibited dose-dependently by phenelzine and by deuterated phenelzine. Type A MAO was inhibited more than type B, and deuterated phenelzine inhibited both types more than did phenelzine. The present study shows that the efficacy of phenelzine was increased about 5-fold by deuteration, that deuterated phenelzine increased tryptamine, m-tyramine and p-tyramine levels much more than it did the other monoamines, that phenylethylamine levels were least affected by the drug treatments, and that deuterated phenelzine inhibited MAO more than did phenelzine.Abbreviations D deuterium - DOPAC 3,4-dihydroxyphenylacetic acid - 5HIAA 5-hydroxyindole acetic acid - HVA homovanillic acid - MAO monoamine oxidase - 3MT 3-methoxytyramine - 5-HT 5-hydroxytryptamine Send offprint requests to L. E. Dyck     

Structure-activity relationships of some pyrethroids in rats

The intravenous toxicity to the rat of 36 pyrethroids has been examined. With two exceptions they cause either (1) T-syndrome, consisting of aggressive sparring, sensitivity to external stimuli, fine progressing to gross whole body tremor and prostration or (2) CS-syndrome, consisting of pawing and burrowing behaviour, salivation, coarse tremor, progressing to sinuous writhing (choreoathetosis) and clonic seizures. The two exceptions presented a TS-syndrome with salivation associated with the T-syndrome. No clearcut relationship between chemical structure and symptoms of poisoning has emerged through some generalisations are discussed.