Toxic action/toxicity

Some six or so physiological systems, essential to normal mammalian life, are involved in poisoning; an intoxication that causes severe injury to any one of them could be life threatening. Reversible chemical reactions showing Scatchard-type binding are exemplified by CO, CN- and cyclodiene neurotoxin insecticide intoxications, and by antigen-antibody complex formation. Haemoglobin (Hb) molecular biology accounts for the allosteric co-operativity and other characteristics of CO poisoning, CN- acts as a powerful cytochrome oxidase inhibitor, and antigen binding in a deep antibody cleft between two domains equipped with epitopes for antigen-binding groups explains hapten-specific immune reactions. Covalent chemical reactions with second-order (SN2) kinetics characterize Hg and Cd poisonings, the reactions of organophosphates and phosphonates with acetylcholinesterase and neurotoxic esterase and the reaction sequence whereby Paraquat accepts electrons and generates superoxide under aerobic conditions. Indirect carcinogens require cytochrome P450 activation to form DNA adducts in target-organ DNA and cause cancer, but a battery of detoxifying enzymes clustered with the P450 system must be overcome. Thus, S-metabolism competes ineffectively with target DNA for reactive vinyl chloride (VC) metabolites, epoxide hydrolase is important to the metabolism and carcinogenicity of alfatoxins and polycyclic aromatic hydrocarbons (benzo[a]pyrene, etc.), and the non-toxic 2-naphthylhydroxylamine N-glucuronide acts as a transport form in 2-naphthylamine bladder cancer. VC liver-cancer pathogenesis is explicable in terms of the presence of the glutathione S-transferase detoxifying system in hepatocytes and its absence from the fibroblastic elements, and of the VC concentrations reaching the liver by different administrative routes. In VC carcinogenicity, chemical reactions give imidazo-cyclization products with nucleoside residues of target DNA, and in benzene leukaemia, Z,Z-muconaldehyde forms cyclic products containing a pyrrole residue linked to purine. Increased HbCO concentrations reduce the O2-carrying capacity of the blood, and the changed shape of the O2-Hb dissociation curve parallels disturbance in O2 unloading. CN- acts on electron transport and paralyses respiration. In telodrin poisoning, preconvulsive glutamine formation abstracts tricarboxylic acid intermediates incommensurately with normal cerebral respiration. Antigen-antibody complexing depletes the antibody titre, available against infection. At high doses of Cd, Cd-thionein filtered through the kidneys is reabsorbed and tubular lesions produced. Some organophosphate insecticides promote irreversible acetylcholinesterase phosphorylation and blockade nerve function, and others react with neurotoxic esterase to cause delayed neuropathy. The evidence for Paraquat pulmonary poisoning suggests a radical mechanism involving three interrelated cyclic reaction stages. The action of N- and O8 (O substituent in 6-position of the purine) demethylases explains deletion mechanisms for DNA-alkyl adducts. DNA-directed synthesis in the presence of ultimate carcinogens provides for an estimation of misincorporations, which implicate the same transversions as those found by direct mutagenicity testing. Chemical carcinogens recognize tissue-sensitive cells and modify their heritable genetic complement. Oncoproteins encoded by activated oncogenes signal the transformation of normal cells into cancer cells. The importance of the H-ras oncogene and p53 tumour-suppressor gene is stressed. Antidotal action is analysed; for example, parenteral glutamine administration to telodrin-intoxicated rats restores the depleted cerebral glutamate level and prevents seizures. Glutamate acts as anticonvulsant in petit mal epilepsy. In general, therefore, the reaction of the toxicant-related substance with the relevant target-tissue macromolecule accounts for the biochemical/biological events at a cellular level a     

不同血液净化方式对中毒所致多器官功能障碍的临床效果比较

目的:探讨两种不同的血液净化方式对中毒所致的多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)的临床治疗效果。方法:回顾性分析2015年9月至2018年9月我院收治的41例中毒所致的多器官功能障碍综合征患者,按照采取血液净化方式的不同将其分为实验组(序贯性净化)和对照组(单种净化)。比较两组患者在住院期间的一般住院指标(住院时间、费用等)及治疗后的主要血液指标、APACHE Ⅱ (acute physiology and chronic health evaluationⅡ)评分和生存率。结果:治疗后第5天,实验组的丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)等生化指标显著低于对照组(P0.05)。治疗第5天时,实验组的APACHE Ⅱ评分显著低于对照组(P0.05),总住院费用高于对照组(P0.05),总住院时间及病死率与对照组比较差异无统计学差异(P0.05)。结论:相对于单种血液净化方式而言,序贯性治疗可显著改善肝功指标,降低APACHE Ⅱ评分,且不增加总住院时间,但增加了治疗费用。     

Characterization and comparison of toxin‐producing isolates of Dinophysis acuminata from New England and Canada

Following the identification of the first toxic isolate of Dinophysis acuminata from the northwestern Atlantic, we conducted detailed investigations into the morphology, phylogeny, physiology, and toxigenicity of three isolates from three sites within the northeastern U.S./Canada region: Eel Pond and Martha's Vineyard, Massachusetts, and the Bay of Fundy. Another isolate, collected from the Gulf of Mexico, was grown under the same light, temperature, and prey conditions for comparison. Despite observed phenotypic heterogeneity, morphometrics and molecular evidence classified the three northwestern Atlantic isolates as D. acuminata Claparède & Lachmann, whereas the isolate from the Gulf of Mexico was morphologically identified as D. cf. ovum. Physiological and toxin analyses supported these classifications, with the three northwestern Atlantic isolates being more similar to each other with respect to growth rate, toxin profile, and diarrhetic shellfish poisoning (DSP) toxin content (okadaic acid + dinophysistoxin 1/cell) than they were to the isolate from the Gulf of Mexico, which had toxin profiles similar to those published for D. cf. ovum F. Schütt. The DSP toxin content, 0.01–1.8 pg okadaic acid (OA) + dinophysistoxin (DTX1) per cell, of the three northwestern Atlantic isolates was low relative to other D. acuminata strains from elsewhere in the world, consistent with the relative scarcity of shellfish harvesting closures due to DSP toxins in the northeastern U.S. and Canada. If this pattern is repeated with the analyses of more geographically and temporally dispersed isolates from the region, it would appear that the risk of significant DSP toxin outbreaks in the northwestern Atlantic is low to moderate. Finally, the morphological, physiological, and toxicological variability within D. acuminata may reflect spatial (and/or temporal) population structure, and suggests that sub‐specific resolution may be helpful in characterizing bloom dynamics and predicting toxicity.     

竹叶青蛇咬伤中毒机制及临床研究新进展

竹叶青的毒素成分主要为血液毒素.被竹叶青蛇咬伤后的主要临床表现为出凝血功能障碍,其中最突出的表现是纤维蛋白原(Fib)严重消耗.根据2018年中国蛇伤救治专家共识,在治疗竹叶青蛇咬伤时,主要治疗措施有抗蛇毒血清的应用以及消肿止痛、预防破伤风、使用糖皮质激素等,并根据患者纤维蛋白原情况使用血制品如"新鲜冰冻血浆"及"冷沉...     

血液透析对急性百草枯中毒的临床疗效分析

目的:探讨血液透析(hemodilalysis,HD)治疗急性百草枯中毒的临床疗效,为临床应用HD治疗急性百草枯中毒提供依据。方法:选择我院2003年3月~2012年7月收治的百草枯中毒患者40例,根据患者使用是否行透析治疗分为透析组(A组17例)和非透析组(B组23例),比较分析两组患者治疗后的肝功能、肾功能、肺功能及心肌酶学指标的变化,治疗效果及存活情况。结果:两组患者入院后前3天ALT、AST、BUN、CR、CK、CK-MB水平均呈上升趋势,且非透析组患者以上指标的水平高于透析组患者,但差异无统计学意义(P0.05),入院后第7天,两组以上指标的比较亦无统计学差异(P0.05);两组患者之间入院时和入院后72小时内最低的SPO2%、血气分析中PaO2和PaCO2水平比较无统计学意义(P0.05);透析组和非透析组患者的病死率分别为70.6%和69.6%,差异无统计学意义(P0.05)。结论:百草枯溶液中毒的患者预后差、病死率高,血液透析治疗并不能显著提高急性百草枯中毒患者的生存率。     

急性一氧化碳中毒致心肌损害临床研究

目的研究急性一氧化碳（CO）中毒对心脏的损害。方法选择急诊入院的急性CO中毒患者102例,分为轻度、中度和重度中毒组,同时在健康体检人群中随机选择100例健康人为对照组。中毒组的病例入院24h采静脉血测定心肌酶及行心电图检查;对照组清晨抽空腹静脉血．测定心肌酶并完成12导联心电图描记。结果急性CO中毒患者中有63例血清心肌酶谱改变,占61.77％。中、重度中毒者多有不同程度的心肌酶升高,与健康对照组相比,差异有统计学意义（P〈0．01）;重、中度中毒组相比。差异亦有统计学意义（P〈0．01）。心电图异常改变有70例．占68．63％。经治疗,除2例病重无康复外．其余100例均康复出院．在CO中毒纠正后心肌酶和心电图均恢复正常。蛄论急性CO中毒不仅对神经系统造成损害．对心脏的损害也较严重,需要给予相应的治疗.     

扎兰屯地区酵米面中毒的病原菌研究

本文报告从两起酵米面食物中毒的酵米面中分离出2株非发酵革兰氏阴性杆菌,经系统生物学特征的鉴定,确认这2株菌为酵米面假单胞菌。与国外的椰毒假单胞菌为同一个种。对小白鼠、狗有致病性,实验动物脏器有不同程度的病理改变,表明这2株菌有较强的毒力。     

Development of antidotes for sodium monofluoroacetate (1080)

Baits containing sodium monofluoroacetate (1080) are commonly used in New Zealand during feral pest control operations. However, each year, a number of domestic dogs are unintentionally killed during these control operations, and a suitable antidote to 1080 intoxication is required. The primary toxic mechanism of 1080 is well known. However, as with other pathologies where energy deprivation is the main effect of intoxication, the cascade of effects that arises from this primary mechanism is complex. At present, putative antidotes for 1080 are generally unable to address the primary mechanism of intoxication but such agents may be able to control the cascade of secondary effects, which can result during intoxication. Part of the reason for this is that targeting the cascade can provide a longer window of time for antidote success. We have undertaken studies that identified some of the central nervous system (CNS) and systemic pathophysiological cascades caused by 1080 intoxication. Using this information we designed antidotes, on the basis of preventing different steps in this cascade. In the chicken model targeting systemic changes, in particular reducing effects of nitric oxide derivatives generated in cardiac muscle, proved successful in reducing fatality associated with 1080. In rats and sheep, targeting the CNS with a number of compounds including: glutamate; calcium and dopamine antagonists; gamma amino butyric acid agonists, and astressin-like compounds reduced fatalaties. However, to be successful in the rat and sheep model a given antidote needed to move quickly from systemic circulation across the blood brain barrier and into the CNS. The work also suggests ways in which specific biomarkers of 1080 exposure may be developed with respect to different species.