The rapid determination of bromadiolone in liver and blood plasma by in-injector pyrolysis gas chromatography - Ion trap tandem mass spectrometry.

The unintentional poisoning of off-target animals by bromadiolone, a second generation anticoagulant rodenticide, is an undesirable outcome requiring sensitive analytical methods. In this study, a rapid and sensitive method for the determination of bromadiolone in liver and blood plasma by means of gas chromatography coupled with tandem mass spectrometry without need for derivatization was developed. The method is based on the in-injector pyrolysis of bromadiolone and subsequent gas chromatography coupled with ion trap tandem mass spectrometry with electron ionization. Sample preparation includes extraction with methanol, evaporation under nitrogen stream, and dissolution in toluene. The pyrolysis of bromadiolone was carried out in an injector at 390°C. Chromatographic separation of the pyrolytical fragment of bromadiolone was achieved using a VF-5ms column with helium as the mobile phase. Tandem in-time mass spectrometry of the separated pyrolytical fragment of bromadiolone was carried out using an ion trap mass spectrometer after electron ionization. Recovery ranged from 94 to 98%. The method showed good linearity up to 1000µgkg-1 for liver and 1000µgL-1 for plasma. The limit of detection was 0.38µgkg-1 for liver and 0.26µgL-1 for plasma. The developed method was used successfully in several animal poisoning cases.

Intoxicaciones con rodenticidas superwarfarínicos / Superwarfarin rodenticide poisoning

Introducción: en la actualidad existe utilización masiva de rodenticidas y su venta no está restringida al público. Las etiologías de intoxicación por estos agentes son variadas pudiendo ser de tipo intencional o accidental. Objetivo: analizar estudios realizados en torno a intoxicaciones con rodenticidas superwarfarínicos en humanos con el propósito de reunir información que oriente a un adecuado tratamiento. Metodología: se realizó una revisión integradora en las bases de datos electrónicas PubMed, TripDataBase, Cochrane, además de Google Scholar y SciELO, libros de divulgación científica, documentos de convenciones, páginas web de instituciones públicas, privadas y artículos vinculados a efectos, cuadro clínico y tratamiento de exposiciones a rodenticidas en seres humanos. Se analizaron los documentos y la información se organizó en tres temáticas: toxicidad de los rodenticidas superwarfarínicos, cuadro clínico y tratamiento médico, y rodenticidas no anticoagulantes disponibles en Chile. Resultados: la dosis tóxica mínima reportada en adultos es de 1 mg de principio activo; en pacientes pediátricos ingestas accidentales rara vez producen síntomas. Los síntomas se observan de forma tardía y su toxicidad es variable. El examen de elección es el International Normalized Ratio (INR) y se realiza en todo paciente con factores de riesgo presentes. El antídoto no se administra de forma profiláctica y la dosis se ajusta individualmente. Conclusión: en niños las ingestas accidentales no son riesgosas por lo que pueden ser observados en el hogar. Pacientes con ingestas masivas requieren controles de INR por meses por lo que es importante que posterior al alta médica exista una óptima coordinación con nivel primario de atención.

Introduction: Currently there is a widespread use of rodenticides, unrestricted to the public. The exposure to these agents may varied being intentional or accidental. Objective: To analyze studies about superwarfarin poisoning in humans, with the purpose of gathering information to guide proper treatment. Methodology: It was conducted an integrative review in the electronic databases PubMed, TripDataBase, Cochrane, Google Scholar and SciELO, science books (reference textbooks), convention documents, websites from public and private institutions and articles about the effects, clinical manifestations and treatment of human exposures to rodenticides. Documents were analyzed and the information organized into three themes: superwarfarin toxicity, clinical features and medical treatment, and non-anticoagulant rodenticides available in Chile. Results: In adults, the minimum dose reported to cause toxicity is 1 mg of active ingredient. In pediatric patients, accidental intakes rarely produce symptoms. The symptoms of poisoning are usually delayed and its toxicity is variable. The test of choice is International Normalized Ratio (INR) and it is performed in all patients with risk factors. The antidote must not be administered prophylactically and the dose is adjusted individually. Conclusions: Accidental intakes in children are not risky and they can be observed at home. Patients with massive intakes require INR monitoring for months so, it is important that an optimal coordination with primary care facilities still exists after medical discharge.

Retrospective study of twenty-four patients with prolonged coagulopathy due to long-acting anti-vitamin K rodenticide poisoning.

Second generation anticoagulant rodenticides are now the most common rat killers used in China; however, poisoning incidents are frequently reported. The authors retrospectively reviewed 24 patients with vitamin K-dependent coagulation factor deficiency caused by rodenticide poisoning in the past 2 years. The main clinical presentation was hemorrhage, although intracranial bleeding and life-threatening symptoms were not seen. All patients responded to vitamin K, the specific antidote, along with fresh frozen plasma and cryoprecipitate, although prolonged treatment was sometimes required. To avoid such incidents, rodenticide should be safely stored and protective measures used during production and application. Once poisoning has occurred, vitamin K should be administered as soon as possible along with fresh frozen plasma and cryoprecipitate.

Differential antagonism of tetramethylenedisulfotetramine-induced seizures by agents acting at NMDA and GABA(A) receptors.

Tetramethylenedisulfotetramine (TMDT) is a highly lethal neuroactive rodenticide responsible for many accidental and intentional poisonings in mainland China. Ease of synthesis, water solubility, potency, and difficulty to treat make TMDT a potential weapon for terrorist activity. We characterized TMDT-induced convulsions and mortality in male C57BL/6 mice. TMDT (ip) produced a continuum of twitches, clonic, and tonic-clonic seizures decreasing in onset latency and increasing in severity with increasing dose; 0.4mg/kg was 100% lethal. The NMDA antagonist, ketamine (35mg/kg) injected ip immediately after the first TMDT-induced seizure, did not change number of tonic-clonic seizures or lethality, but increased the number of clonic seizures. Doubling the ketamine dose decreased tonic-clonic seizures and eliminated lethality through a 60min observation period. Treating mice with another NMDA antagonist, MK-801, 0.5 or 1mg/kg ip, showed similar effects as low and high doses of ketamine, respectively, and prevented lethality, converting status epilepticus EEG activity to isolated interictal discharges. Treatment with these agents 15min prior to TMDT administration did not increase their effectiveness. Post-treatment with the GABA(A) receptor allosteric enhancer diazepam (5mg/kg) greatly reduced seizure manifestations and prevented lethality 60min post-TMDT, but ictal events were evident in EEG recordings and, hours post-treatment, mice experienced status epilepticus and died. Thus, TMDT is a highly potent and lethal convulsant for which single-dose benzodiazepine treatment is inadequate in managing electrographic seizures or lethality. Repeated benzodiazepine dosing or combined application of benzodiazepines and NMDA receptor antagonists is more likely to be effective in treating TMDT poisoning.

Intoxication by large amounts of barium nitrate overcome by early massive K supplementation and oral administration of magnesium sulphate.

Suicide by ingestion of barium is exceptionally rare. Adverse health effects depend on the solubility of the barium compound. Severe hypokalemia, which generally occurs within 2 hours after ingestion, is the predominating feature of acute barium toxicity, subsequently leading to adverse effects on muscular activity and cardiac automaticity. We report one case of acute poisoning with barium nitrate, a soluble barium compound. A 75-year-old woman was hospitalized after suicidal ingestion of a burrow mole fumigant containing 12.375 g of barium nitrate. About 1 hour post-ingestion, she was only complaining of abdominal pain. The ECG recording demonstrated polymorphic ventricular premature complexes (VPCs). Laboratory data revealed profound hypokalemia (2.1 mmol/L). She made a complete and uneventful recovery after early and massive potassium supplementation combined with oral magnesium sulphate to prevent barium nitrate absorption.

Intento autolítico con superwarfarinas / Attempted autolysis with super warfain

No disponible

Keratinocyte growth factor attenuates lung leak induced by alpha-naphthylthiourea in rats.

OBJECTIVE: To investigate the effect of pretreatment with keratinocyte growth factor on acute permeability pulmonary edema. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: Specific pathogen-free Sprague-Dawley rats. INTERVENTION: Acute permeability pulmonary edema was induced with an injection of alpha-naphthylthiourea, and lung leak was assessed in an isolated perfused lung model over 180 mins. Leak was confirmed with wet/dry lung weight ratios, and the alveolar fluid protein concentration was measured after bronchoalveolar lavage. The effect of pretreatment with keratinocyte growth factor (injected intratracheally 48 hrs before the experiment) on alpha-naphthylthiourea-induced pulmonary edema was assessed (keratinocyte growth factor/alpha-naphthylthiourea group). Control groups (Control and keratinocyte growth factor/Control) were also studied. Histopathology was performed for each of the four groups. MEASUREMENTS AND MAIN RESULTS: The alpha-naphthylthiourea produced an acute permeability pulmonary edema detected by lung leak over the 180-min ex vivo period of monitoring the isolated perfused lung (leak = 8+/-mL; wet/dry weight ratio 14.7+/-2; lavage protein 3.1+/-1 mg/mL). Pretreatment with keratinocyte growth factor significantly attenuated these parameters (leak = 2.3+/-0.4 mL; wet/dry weight ratio 7.1 +/- 0.5; lavage protein 0.28 +/-0.03 mg/mL), which were not significantly different from the control group and the keratinocyte growth factor/control group. Histopathology showed abundant type II pneumocyte hyperplasia in the lungs of animals pretreated with keratinocyte growth factor, and marked pulmonary edema in animals pretreated with alpha-naphthylthiourea. Less edema was apparent in the keratinocyte growth factor/alpha-naphthylthiourea group. All data are expressed as mean +/- SEM. CONCLUSIONS: Pretreatment with keratinocyte growth factor significantly attenuates pulmonary edema induced by alpha-naphthylthiourea. The mechanisms of this protection are likely related to type II pneumocyte hyperplasia, but remain to be specifically elucidated.

Diabetes mellitus following rodenticide ingestion in man.

Ketotic, insulin-requiring diabetes mellitus and a severe peripheral neuropathy developed in a previously healthy 25-year-old man several days after he attempted suicide with rat poison containing N-3-pyridylmethyl N'-p-nitrophenyl urea. Study of islet-cell function ten months after ingestion showed a reduced disappearance rate of intravenous glucose and depressed C-peptide response to intravenous glucose when compared with a normal control but no impairment of glucagon release after intravenous arginine stimulation. Nerve conduction studies demonstrated severe sensory and mild motor neuropathy. Quadriceps capillary basement membrane thickness was in the diabetic range. Because at least 15 similar occurrences have been reported to the manufacturer, this agent appears to be diabetogenic in man, probably causing beta-cell destruction. Niacinamide, which can prevent glucose intolerance in both streptozocin- and alloxan-treated animals and prevents death in rats given this rodenticide, may be a useful antidote.