Cyanide
David J. George in Poisons, 2017
The public is very much aware of the toxic potential of cyanide. During World War II, the Nazis used cyanide as an agent of genocide. Starting in the early 1920s, cyanide gas chambers were used for the execution of criminals sentenced to death in the United States. There was also a widely publicized mass suicide carried out in 1978 in Jonestown, Guyana by members of a religious organization utilizing a fruit-flavored cyanide drink; more than 900 cult members died, including men, women, and children. Exposures most commonly involve either hydrogen cyanide gas or potassium cyanide powder. Cyanide blocks the utilization of oxygen at the cellular level, resulting in metabolic asphyxiation. Early neurological manifestations of cyanide poisoning can include anxiety and confusion. The results from one laboratory were consistent with a cyanide poisoning cause of death; whereas the other laboratory's analytical results were more consistent with high normal cyanide levels.
Carbon-11 Labeled Amino Acid Analogs as Imaging Agents for
Friedman Mendel in Absorption and Utilization of Amino Acids, 2019
The medical cyclotron has been used for the production of various short-lived, positron emitting radionuclides including carbon-11, nitrogen-13, oxygen-15, and fluorine-18. The carbon-11 alpha-amino acids are generally prepared by reacting either precursor ketones or aldehydes with potassium cyanide in the presence of ammonium carbonate at high temperatures in sealed steel reaction vessels, with subsequent hydrolysis of the intermediate hydantoin using aqueous base. Carbon-11 amino acids have been developed as in vivo organ and tumor imaging agents. In particular, the pancreas has been studied using both natural and synthetic amino acids. It is becoming clear that amino acid utilization plays a vital role in tumor growth. Alteration in amino acid transport may be a useful parameter for both diagnosing and monitoring malignant growth. Carbon-11 amino acids have potential as organ and tumor imaging agents, as well as for the study of in vivo amino acid biochemistry.
Toxicokinetic aspects of thiocyanate after oral exposure to cyanide in female Wistar rats in different physiological states
Published in Drug and Chemical Toxicology, 2014
Altamir Benedito de Sousa, Silvana Lima Górniak
Cyanide (CN) is an ion that has been well studied in toxicology and has been associated with several intoxication episodes: the ingestion of contaminated foods and water, chemical war, suicides, homicides, occupational exposures and the use of certain medicines. The aim of the present study was to determine the toxicokinetic parameters of thiocyante (SCN), the main metabolite of CN, after oral administration of potassium cyanide (KCN) to female rats at diestrus, gestational and lactational periods. Female Wistar rats were divided into three equal groups: virgins in the diestrus phase of the estrus cycle, females at the 14th day of gestation and females at the 14th day of lactation. Each group of rats received 3.0 mg of potassium cyanide per kilogram (KCN/kg body weight) by gavage, and blood was collected at several time points. We also collected amniotic fluid from pregnant rats and milk from the nursing rats to analyze thiocyanate concentration. The results showed that SCN levels were significantly increased in serum, milk and amniotic fluid after administration of KCN. In conclusion, the results of the present study evidence that the metabolism of CN varies greatly considering the physiologic state of the female rat, being females at estrus probably more exposed by these substances than at gestation and lactation because in these states there are other compartments, fetus and milk, which may capture these substances, as demonstrated by the Vd values.
Hydroxocobalamin association during cell culture results in pink therapeutic proteins
Published in mAbs, 2013
Kenneth M Prentice, Ronald Gillespie, Nathan Lewis, Kiyoshi Fujimori, Rebecca McCoy, Julia Bach, Lisa Connell-Crowley, Catherine M Eakin
Process control of protein therapeutic manufacturing is central to ensuring the product is both safe and efficacious for patients. In this work, we investigate the cause of pink color variability in development lots of monoclonal antibody (mAb) and Fc-fusion proteins. Results show pink-colored product generated during manufacturing is due to association of hydroxocobalamin (OH-Cbl), a form of vitamin B12. OH-Cbl is not part of the product manufacturing process; however we found cyanocobalamin (CN-Cbl) in cell culture media converts to OH-Cbl in the presence of light. OH-Cbl can be released from mAb and Fc-fusion proteins by conversion with potassium cyanide to CN-Cbl, which does not bind. By exploiting the differential binding of CN-Cbl and OH-Cbl, we developed a rapid and specific assay to accurately measure B12 levels in purified protein. Analysis of multiple products and lots using this technique gives insight into color variability during manufacturing.
Intramuscular sodium tetrathionate as an antidote in a clinically relevant swine model of acute cyanide toxicity
Published in Clinical Toxicology, 2020
Tara B. Hendry-Hofer, Alyssa E. Witeof, Patrick C. Ng, Sari B. Mahon, Matthew Brenner, Gerry R. Boss, Vikhyat S. Bebarta
Background: Cyanide is a metabolic poison used in multiple industries and is a high threat chemical agent. Current antidotes require intravenous administration, limiting their usefulness in a mass casualty scenario. Sodium tetrathionate reacts directly with cyanide yielding thiosulfate and the non-toxic compound thiocyanate. Thiosulfate, in turn, neutralizes a second molecule of cyanide, thus, per mole, sodium tetrathionate neutralizes two moles of cyanide. Historical studies examined its efficacy as a cyanide antidote, but it has not been evaluated in a clinically relevant, large animal model, nor has it previously been administered by intramuscular injection. Objective: The objective of this study is to evaluate the efficacy of intramuscular sodium tetrathionate on survival and clinical outcomes in a large, swine model of severe cyanide toxicity. Methods: Anesthetized swine were instrumented for continuous monitoring of hemodynamics, then acclimated and breathing spontaneously prior to potassium cyanide infusion (0.17 mg/kg/min). At 6-min post-apnea (no breaths for 20 s), the cyanide infusion was terminated, and animals were treated with sodium tetrathionate (∼18 mg/kg) or normal saline control. Clinical parameters and laboratory values were evaluated at various time points until death or termination of the experiment (90 min post-treatment). Results: Laboratory values, vital signs, and time to apnea were similar in both groups at baseline and treatment. Survival in the sodium tetrathionate treated group was 100% and 17% in controls (p = 0.0043). All animals treated with sodium tetrathionate returned to breathing at a mean time of 10.85 min after antidote, and all but one control remained apneic through end of the experiment. Animals treated with tetrathionate showed improvement in blood lactate (p ≤ 0.002) starting at 30 min post-treatment. The average time to death in the control group is 63.3 ± 23.2 min. No systemic or localized adverse effects of intramuscular administration of sodium tetrathionate were observed. Conclusion: Sodium tetrathionate significantly improves survival and clinical outcomes in a large, swine model of acute cyanide poisoning.
Related Knowledge Centers
- Cellular Respiration
- Hydrogen Cyanide
- Nitriles
- Cn
- Cyanides
- Potassium Compounds
- Lactic Acidosis