Analysis of anticholinesterase-induced neuromuscular transmission failure

To define the underlying mechanism of neuromuscular transmission failure induced by anticholinesterases, we simultaneously performed surface recordings of compound muscle action potentials (CMAPs) and intracellular recordings of miniature end-plate potentials (MEPPs), miniature end-plate current (MEPCs), and end-plate potential (EPPs) in rat diaphragms exposed in vitro to 1 × 10^?4 to 2 × 10^?2 mmol/L neostigmine methylsulfate. At low concentrations of neostigmine, repetitive stimulation of the phrenic nerve resulted in decrement followed by complete recuperation of CMAP amplitudes. This bimodal pattern was associated with maximal end-plate depolarization at the beginning of the stimulation period, increased MEPP amplitudes, and prolonged time constants of MEPC decays. Higher concentrations of neostigmine resulted in a unimodal decline of amplitudes of CMAPs and EPPS, reduced MEPP amplitudes, and a double exponential time course of MEPC decays. These results indicate that low concentrations of anticholinesterases impaired neuromuscular transmission by producing transient depolarization of the end-plate region. Higher concentrations induced desensitization and direct blockade of the end-plate receptor channel, probably in its open conformation. © 1993 John Wiley & Soncs, Inc.     

急性有机磷中毒动物血糖及胆碱酯酶活力的动态监测研究

目的：动态监测急性有机磷中毒动物在急性有机磷中毒及解救过程中血浆的乙酰胆碱酯酶活性和血糖值变化，依据此两项指标与中毒程度的相关性，为临床救治提供新的方法以及实验依据。方法：通过耳缘静脉注射5％敌百虫溶液（2mL／kg）先后对12只家兔建立急性有机磷中毒模型，分别在模型动物处于正常、轻、中、重度中毒和救治的时段采血，动态监测血浆乙酰胆碱酯酶活力和血糖两项指标变化。结果：在急性有机磷中毒过程中，血糖值升高与乙酰胆碱酯酶活力降低相比较，血糖浓度动态变化与中毒轻重程度相关性较好，并能体现机体对中毒的应激程度。结论：血糖浓度能较好地反映有机磷中毒深度以及机体应激程度，可作为临床评估危重程度的动态性快速诊断指标。     

Antibodies to the pesticide interaction sites of parathion hydrolase and cutinase

Monoclonal antibodies are able to provide information on the surface topography of biopolymers. Antibodies capable of inhibiting the activities of cutinase and parathion hydrolase have been identified in order to probe the sites of pesticide inhibition. Kinetic studies were employed to determine whether organophosphate pesticide binding was directly prevented by antibody binding. Prior binding of chlorfenvinphos and methyl paraoxon to cutinase inhibited subsequent binding by the monoclonal anti‐cutinase antibodies. The role of antibodies in probing enzyme structure is discussed.     

有机磷农药敌敌畏和对硫磷所致大鼠循环衰竭时的血流动力学特征

目的：在胆碱酯酶抑制剂（ChEI）类有机磷农药敌敌畏、对硫磷所致大鼠循环衰竭模型上，观察循环衰竭前后大鼠血流动力学及心电图变化，旨在阐明有机磷农药中毒引起的循环衰竭的血流动力学特征。方法:健康Wistar雄性大鼠，体重（320±20） g，腹腔注射累积染毒，直至平均动脉压（MBP）降至45 mmHg为循环衰竭标准。观察循环衰竭前后血流动力学指标及心电图变化。结果:2种农药所致大鼠循环衰竭时，收缩压（SBP）、舒张压（DBP）、平均血压（MBP）、心率（HR）、左室内压上升段最大变化速率（+dp/dt_max）、心肌纤维缩短速度（Vpm）以及+dp/dt_max与等容收缩期压力（IP）的比值（+dp/dt_max/IP）均显著低于染毒前，反映心脏舒张功能的左室舒张压（LVDP)、左室内压下降段最大变化速率（-dp/dt_max）、IP均显著高于染毒前（P<0.01）;心电图显示心率缓慢，心律失常。结论:有机磷农药导致大鼠循环衰竭时心率、心脏收缩功能和舒张功能均显著下降，心脏起搏与传导功能受损。     

Delayed neurotoxicity of diisopropylfluorophosphate (DFP): autoradiographic localization of high-affinity [3H]DFP binding sites in the chicken spinal cord

The delayed neurotoxic organophosphate, diisopropylfluorophosphate (DFP) binds with high affinity to membrane-bound proteins from chicken nerve tissues. The autoradiographic distribution of [³H]DFP binding sites in spinal cord sections of chicken showed higher concentrations of binding sites in gray matter than in white matter. In the cervical region, fairly high densities of [³H]DFP binding sites were found in laminae X and to a lesser extent, in the ventral horn gray matter. To identify the membrane-associated DFP-binding proteins, detergent-solubilized membranes were labeled widi 5-10nM [³H]DFP (10pmol/mg protein) for 70 min at 37°C. Gel-exclusion chromatography of the [³H]DFP-radiolabeled membranes indicated at least two major radioactive proteins with apparent molecular weights of 150-670 kDa and 40-129 kDa. Although we could not identify the high affinity DFP binding proteins, the autoradiographic experiments clearly demonstrated that the DFP binding proteins localized on gray matter of chicken spinal cord.     

Neuropsychiatric evaluation in subjects chronically exposed to organophosphate pesticides.

Long-term exposure to low levels of organophosphate pesticides (OP) may produce neuropsychiatric symptoms. We performed clinical, neuropsychiatric, and laboratory evaluations of 37 workers involved in family agriculture of tobacco from southern Brazil who had been exposed to OP for 3 months, and in 25 of these workers, after 3 months without exposure to OP. Plasma acetylcholinesterase activity levels of all subjects were within the normal range (3.2 to 9.0 U/l) and were not different between on- and off-exposure periods (4.7 +/- 0.9 and 4.5 +/- 1.1 U/l, respectively). Clinically significant extrapyramidal symptoms were present in 12 of 25 subjects, which is unexpected in such a population. There was a significant reduction of extrapyramidal symptoms after 3 months without exposure to OP, but 10 subjects still had significant parkinsonism. Mini-mental and word span scores were within the expected range for this population and were not influenced by exposure to OP. Eighteen of the 37 subjects (48%) had current psychiatric diagnoses in the first interview (13 with generalized anxiety disorder and 8 with major depression). Among the 25 subjects who completed both evaluations, the total number of current psychiatric diagnoses, after 3 months without using OP, dropped from 24 to 13 and the number of affected individuals with any psychiatric diagnosis dropped from 11 to 7. In conclusion, this study reinforces the need for parameters other than acetylcholinesterase activity to monitor for chronic consequences of chronic low-dose OP exposure, and it suggests that subjects have not only transient motor and psychiatric consequences while exposed, but may also develop enduring extrapyramidal symptoms.     

院前系统救治对重度急性有机磷农药中毒预后的影响

目的探讨口服重度急性有机磷农药中毒(SAOPP)患者服毒至救治时间(无治疗期)的长短与患者预后的关系。方法选择经过院前系统救治后接回医院的174例SAOPP患者作为治疗组,自行前往医院或拒绝院前洗胃者160例为对照组。两组治疗方法为洗胃、应用氯磷定、阿托品及对症治疗等综合措施。统计患者无治疗期的长短与死亡、严重并发症的发生情况;观察症状消失时间、全血乙酰胆碱酯酶(AChE)活力恢复至正常时间、阿托品化时间、阿托品用量、氯磷定用量、纳洛酮用量与住院天数等指标。结果治疗组无治疗期时间为(1.2±0.3)h,而对照组为(2.8±0.5)h,差异有统计学意义(P<0.01);治疗组死亡11例(死亡率6.32%),对照组死亡36例(死亡率22.50%),差异有统计学意义(P<0.01);治疗组呼吸衰竭、心脏损害、脑损害、阿托品中毒、中间综合征、肝损害发生率分别为12.64%、5.75%、8.62%、1.72%、4.60%、5.17%,与对照组(25.63%、13.75%、17.50%、6.25%、7.50%、9.38%)的差异有统计学意义(P<0.05或P<0.01);治疗组的中毒症状消失时间、阿托品化时间、AChE恢复至正常时间、阿托品用量、氯磷定用量、纳络酮用量、住院天数各指标均明显优于对照组,差异有统计学意义(P<0.05或P<0.01)。结论院前系统救治可改善SAOPP患者的预后,值得推广应用。     

快速测试有机磷和氨基甲酸酯成分的方法研究

目的快速检测市售卫生杀虫剂中是否含有机磷或氨基甲酸酯成分。方法用农药速测卡测试稀释后的卫生杀虫剂提取液。结果将检测结果用气相色谱法验证,蚊香准确率88.9%、灭蚊片100%、气雾剂33.3%,15个电热灭蚊片样品中没有发现含有机磷或氨基甲酸酯的产品。结论此方法可用于蚊香和灭蚊片初筛检测是否含有机磷或氨基甲酸酯。     

Neurochemical effects of repeated gestational exposure to chlorpyrifos in developing rats.

The neurochemical effects in developing rats exposed during gestation to the anticholinesterase organophosphorus insecticide chlorpyrifos (CPS) were determined. Pregnant rats were dosed daily with CPS (0, 3, or 7 mg/kg) in corn oil from gestation days (GD) 6-20. Pups were euthanized on postnatal days (PND) 1, 3, 6, 9, 12, and 30 for the determination of brain cholinesterase (ChE) and choline acetyltransferase (ChAT) activities, along with muscarinic receptor (mAChR) densities, the levels of the high-affinity choline uptake (HACU) system, and the vesicular acetylcholine transporter (VAChT). ChE activities were inhibited about 15 and 30% on PND 1, in the low- and high-dosage groups, respectively, and were not different from control values by PND 6. mAChR densities on PND 1 were reduced in the high-dosage group by about 18, 21, and 17%, using 3H-N-methylscopolamine, 3H-quinuclidinyl benzilate, and 3H-4-DAMP, respectively, as ligands, and were not different from control levels by PND 6. ChAT activity was decreased by approximately 12% in the high-dosage group on PND 9, 12, and 30. HACU levels, using 3H-hemicholinium-3 as the ligand, were reduced by approximately 25% on PND 6 in the low- and high-dosage groups, and by approximately 14 and 21% on PND 12 and 30, only in the high-dosage group. Levels of the VAChT were reduced by a range of 13-31% on PND 3 through 30 in the high-dosage group, using 3H-AH5183 (vesamicol) as the ligand. These data suggest that gestational exposure to 7 mg/kg/day CPS results in long-term alterations of presynaptic cholinergic neurochemistry.     

急性有机磷农药中毒162例的流行病学分析

目的调查本地区有机磷农药中毒患者流行病学资料，为防治有机磷农药中毒提供依据。方法经过培训的专人登记我院急诊科2003年1月1日～2007年1月1日收治的所有确诊为急性有机磷农药中毒患者的年龄、性别、职业、中毒时间、中毒地点、中毒原因、中毒途径、住院天数和治疗转归等临床资料。结果共入选急性有机磷农药中毒患者162例，年龄14～78岁，平均（39．2±15）岁，男女患者比例为2：3，20～40岁患者占50．6％；女性患者20～40岁占59．6％；男性患者20～30、50～60岁共占62．5％；6～9月份中毒患者为50．7％；农民占50％，其次为学生（17．5％）、离退休老人（12．5％）、无业人员（11．1％）；服毒自杀占85．3％，其中因夫妻吵架或其他家庭问题自杀占60．5％，其次为喷洒农药和食用农药污染食物中毒；住．院时间为1～17天，平均（6．2±3．7）天，死亡率5．5％。结论本地区有机磷农药中毒发病率女性于高于男性，20～40岁是女性中毒高发年龄；男性20～30、50～60岁是中毒高发年龄；6～9月份是发生中毒事件高峰季节；中毒原因主要为自杀，多因家庭纠纷引起；农民、学生为主要中毒职业分布；中毒患者住院时间较长、死亡率较高。