Kinetic analysis of anaerobic metabolism in rats during acute cyanide poisoning

In order to investigate the changes in energy metabolism during acute anoxia, blood levels of various metabolites were analysed in cyanide-poisoned rats. After intraperitoneal injection of a sublethal dose of potassium cyanide (5 mg/kg), blood samples were obtained by cervical dislocation at intervals of 5 min until 30 min. Lacatate and lactate/pyruvate ratio (L/P) in plasma concomitantly changed with cyanide; increased rapidly at 5 min, remained fairly constant until 20 min and then began to decrease at 25 min. In contrast, the products of ATP degradation, oxypurines and inorganic phosphate (Pi), increased gradually until 25 min and then began to decrease at 30 min. Allantoin in plasma scarcely increased throughout the experiments. The results indicate that the rapid activation of anaerobic ATP formation by glycolysis was followed by the increase in ATP degradation in cyanide-poisoned rats. Thus, increase in plasma oxypurines could be regarded as an indicator for severe anoxic states in tissues with massive ATP degradation.     

Kinetic analysis of the shift of aerobic to anaerobic metabolism in rats during acute cyanide poisoning

Blood concentrations of cyanide, lactate, glucose, oxypurines and allantoin were determined in rats sampled at 10 min after the intraperitoneal administration of various concentrations of potassium cyanide. Lactate and oxypurines in plasma increased biquadratically with increase in the cyanide concentration in blood. The concentrations of cyanide for half maximal effect were 1.63 μg/ml for lactate and 2.09 μg/ml for oxypurines. Plasma glucose increased quadratically with increase in the cyanide concentration, and the marked increase was observed where plasma lactate concentration became near maximal. Plasma allantoin concentrations were not significantly changed throughout the experiments. The present results indicate that determination of plasma oxypurines as well as lactate is an excellent parameter for tissue hypoxia.     

Methadone poisoning due to accidental contamination of prescribed medication.

Two infants presented with fever and signs of brainstem dysfunction, including impaired consciousness, miosis, absence of oculocephalic responses, respiratory depression and a very peculiar tremor of the tongue and floor of the mouth. They were found to have methadone poisoning caused by accidental contamination of prescribed antibiotics in the same pharmacy, which was a dispensing centre for a methadone maintenance program. They recovered with supportive treatment only.     

Acute oral toxicity of sodium cyanide in birds

Sensitivities of six avian species, black vulture (Coragyps atratus), American kestrel (Falco sparverius), Japanese quail (Coturnix japonica), domestic chicken (Gallus domesticus), eastern screech-owl (Otus asio), and European starling (Sturnus vulgaris), to acute poisoning by sodium cyanide (NaCN) were compared by single dose LD50's. Three species, domestic chickens, black vultures, and turkey vultures (Cathartes aura), were dosed with NaCN to determine cyanide residues in those that died and also in survivors, in addition to postmortem fate. Three flesh-eating species (black vulture, American kestrel, and eastern screech-owl; LD50's 4.0-8.6 mg/kg) were more sensitive to NaCN than three species (Japanese quail, domestic chicken, and European starling; LD50's 9.4-21 mg/kg) that fed predominantly on plant material. Elevated concentrations of cyanide were found in the blood of birds that died of cyanide poisoning; however, concentrations in birds that died overlapped those in survivors. Blood was superior to liver as the tissue of choice for detecting cyanide exposure. No gross pathological changes related to dosing were observed at necropsy.     

血液净化治疗毒鼠强急性中毒的临床研究

目的 观察血液净化治疗对毒鼠强急性中毒的疗效.方法 在内科常规治疗的基础上,采用血液净化救治急性毒鼠强中毒10例,并与单纯常规治疗的12例对照,比较两组的平均住院天数、治愈率以及APACHE Ⅲ评分变化.结果 血液净化治疗组平均住院天数较常规治疗组明显缩短(P＜0.05),治愈率明显提高(P＜0.05);两组治疗后APACHEⅢ评分均较治疗前降低,其中血液净化组治疗后APACHEⅢ评分降低尤为明显(P＜0.05).结论 血液净化是救治毒鼠强急性中毒的有效方法.     

Pseudomonas aeruginosa PAO1 kills Caenorhabditis elegans by cyanide poisoning

In this report we describe experiments to investigate a simple virulence model in which Pseudomonas aeruginosa PAO1 rapidly paralyzes and kills the nematode Caenorhabditis elegans. Our results imply that hydrogen cyanide is the sole or primary toxic factor produced by P. aeruginosa that is responsible for killing of the nematode. Four lines of evidence support this conclusion. First, a transposon insertion mutation in a gene encoding a subunit of hydrogen cyanide synthase (hcnC) eliminated nematode killing. Second, the 17 avirulent mutants examined all exhibited reduced cyanide synthesis, and the residual production levels correlated with killing efficiency. Third, exposure to exogenous cyanide alone at levels comparable to the level produced by PAO1 killed nematodes with kinetics similar to those observed with bacteria. The killing was not enhanced if hcnC mutant bacteria were present during cyanide exposure. And fourth, a nematode mutant (egl-9) resistant to P. aeruginosa was also resistant to killing by exogenous cyanide in the absence of bacteria. A model for nematode killing based on inhibition of mitochondrial cytochrome oxidase is presented. The action of cyanide helps account for the unusually broad host range of virulence of P. aeruginosa and may contribute to the pathogenesis in opportunistic human infections due to the bacterium.     

Limitations and challenges in treatment of acute chemical warfare agent poisoning

Recent news from Syria on a possible use of chemical warfare agents made the headlines. Furthermore, the motivation of terrorists to cause maximal harm shifts these agents into the public focus. For incidents with mass casualties appropriate medical countermeasures must be available. At present, the most important threats arise from nerve agents and sulfur mustard. At first, self-protection and protection of medical units from contamination is of utmost importance. Volatile nerve agent exposure, e.g. sarin, results in fast development of cholinergic crisis. Immediate clinical diagnosis can be confirmed on-site by assessment of acetylcholinesterase activity. Treatment with autoinjectors that are filled with 2 mg atropine and an oxime (at present obidoxime, pralidoxime, TMB-4 or HI-6) are not effective against all nerve agents. A more aggressive atropinisation has to be considered and more effective oximes (if possible with a broad spectrum or a combination of different oximes) as well as alternative strategies to cope with high acetylcholine levels at synaptic sites should be developed. A further gap exists for the treatment of patients with sustained cholinergic crisis that has to be expected after exposure to persistent nerve agents, e.g. VX. The requirement for long-lasting artificial ventilation can be reduced with an oxime therapy that is optimized by using the cholinesterase status for guidance or by measures (e.g. scavengers) that are able to reduce the poison load substantially in the patients.