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An alternative biomarker for assessing the cyanide levels in postmortem materials is crucial for investigating acute cyanide intoxication. Herein, an aptamer–ligand biorecognition system with high specificity was developed to detect acute cyanide poisoning via its secondary metabolite, 2-amino-2-thiazoline-4-carboxylic acid (ATCA). Potential aptamers were screened from a random library of 66-base single-stranded DNA using GO-SELEX, with individual aptamers being identified through single-stranded DNA sequencing. Molecular docking was employed to predict the affinity of these aptamers toward ATCA and selected counter-targets; these predictions were confirmed using thermodynamic analysis with an isothermal titration calorimeter. Owing to its label-free biomolecular binding interactions, Apt46 exhibited the highest affinity against ATCA and notable selectivity against structurally similar counter-targets. Thus, an amino-tagged Apt46 binding aptamer was attached to a carbon electrode modified with EDC–NHS-activated graphene oxide. The binding of Apt46 to ATCA was quantified by measuring current changes using differential pulse voltammetry. The aptasensor achieved a detection limit of 0.05 µg/mL and demonstrated suitability for detecting ATCA across various biological matrices, with the high recovery percentages ranging from 92.29 to 114.22%. Overall, the proposed ATCA aptasensor is promising for identifying ATCA metabolites in cases of acute cyanide exposure. [ABSTRACT FROM AUTHOR]

D-penicillamine is used as the mainstay of chelation therapy for Wilson's disease and for heavy metal intoxication. D-penicillamine itself has been noted to cause several systemic side effects as well as symptoms related to the skin. Common cutaneous side effects such as acute hypersensitivity reactions, elastic fiber abnormalities, and bullous diseases have been occasionally described. Herein, we report a case of a 23-year-old Thai female with gold intoxication who developed Stevens–Johnson syndrome (SJS) following the treatment of D-penicillamine. To our knowledge, D-penicillamine-induced SJS is exceptionally rare. To raise awareness of potentially fatal cutaneous adverse drug reaction triggered by D-penicillamine, published literature regarding SJS induced by this agent has also been reviewed. D-penicillamine should be regarded as a possible culprit in patients presenting with SJS following D-penicillamine administration and should be promptly discontinued. [ABSTRACT FROM AUTHOR]

Carbon monoxide (CO) and cyanide poisoning are frequent causes of morbidity and mortality in cases of house and industrial fires. The 14th edition of guidelines from the Undersea and Hyperbaric Medical Society does not recommend hyperbaric oxygen (HBO2) treatment in those patients who have suffered a cardiac arrest and had to receive cardiopulmonary resuscitation [1]. In this paper, we describe the case of a 31-year-old patient who received HBO treatment in the setting of cardiac arrest and survived. [ABSTRACT FROM AUTHOR]

Introduction: Cyanide exposure can occur in various settings such as industry and metallurgy. The primary mechanism of injury is cellular hypoxia from Complex IV (CIV) inhibition. This leads to decreased ATP production and increased reactive oxygen species production. The brain and the heart are the organs most affected due to their high metabolic demand. While the cardiac effects of cyanide are well known, the cerebral effects on cellular function are less well described. We investigated cerebral metabolism with a combination of brain respirometry, microdialysis, and western blotting using a rodent model of sub-lethal cyanide poisoning. Methods: Twenty rodents were divided into two groups: control (n = 10) and sub-lethal cyanide (n = 10). Cerebral microdialysis was performed during a 2 mg/kg/h cyanide exposure to obtain real-time measurements of cerebral metabolic status. At the end of the exposure (90 min), brain-isolated mitochondria were measured for mitochondrial respiration. Brain tissue ATP concentrations, acyl-Coenzyme A thioesters, and mitochondrial content were also measured. Results: The cyanide group showed significantly increased lactate and decreased hypotension with decreased cerebral CIV-linked mitochondrial respiration. There was also a significant decrease in cerebral ATP concentration in the cyanide group and a significantly higher cerebral lactate-to-pyruvate ratio (LPR). In addition, we also found decreased expression of Complex III and IV protein expression in brain tissue from the cyanide group. Finally, there was no change in acyl-coenzyme A thioesters between the two groups. Conclusions: The key finding demonstrates mitochondrial dysfunction in brain tissue that corresponds with a decrease in mitochondrial function, ATP concentrations, and an elevated LPR indicating brain dysfunction at a sub-lethal dose of cyanide. [ABSTRACT FROM AUTHOR]

Cassava is the world's most essential food root crop, generating calories to millions of Sub-Saharan African subsistence farmers. Cassava leaves and roots contain toxic quantities of the cyanogenic glycoside linamarin. Consumption of residual cyanogens results in cyanide poisoning due to conversion of the cyanogens to cyanide in the body. There is a need for acyanogenic cassava cultivars in order for it to become a consistently safe and acceptable food, and commercial crop. In recent years, the CRISPR/Cas system, has proven to be the most effective and successful genome editing tool for gene function studies and crop improvement. In this study, we performed targeted mutagenesis of the MeCYP79D1 gene in exon 3, using CRISPR/Cas9, via Agrobacterium-mediated transformation. The vector design resulted in knockout in cotyledon-stage somatic embryos regenerated under hygromycin selection. Eight plants were recovered and genotyped. DNA sequencing analysis revealed that the tested putative transgenic plants carried mutations within the MeCYP79D1 locus, with deletions and substitutions being reported upstream and downstream of the PAM sequence, respectively. The levels of linamarin and evolved cyanide present in the leaves of mecyp79d1 lines were reduced up to seven-fold. Nevertheless, the cassava linamarin and cyanide were not completely eliminated by the MeCYP79D1 knockout. Our results indicate that CRISPR/Cas9-mediated mutagenesis is as an alternative approach for development of cassava plants with lowered cyanide content. [ABSTRACT FROM AUTHOR]

Cyanide is a prevalent, lethal chemical. Possible sources of exposure include products of combustion, plant material, industry, chemical warfare and terrorism. Retrospective review of UK Poisons Information Database of telephone enquiries to the National Poisons Information Service between 1st January 2008 and 31st December 2019 where cyanide poisoning was considered a possibility. Data extracted included demographics, exposure source, clinical features, Poisoning Severity Score, lactate concentration and antidotes given. A total of 1,252 cases of suspected cyanide poisoning were identified, 239 (19%) involved children under 10 years. The commonest sources of exposure were ingestion of plant material (437 cases; 35%) and smoke inhalation (399; 32%). Smoke inhalation caused the majority of severe and fatal cases (139; 71%). Clinical features associated with fatal outcomes were cardiac arrest (OR 36.4; 95% CI 14.4–92.2), hypotension (15.8; 7.0–35.9), coma (10.8; 5.6–21.0) and lactic acidosis (7.8; 4.1–14.8). 110 patients (9%) were given an antidote and 40 patients (3%) died. Lactate concentrations correlate with Poisoning Severity Score category (r = 0.6, p < 0.0001). Serum lactate <2.0 mmol/L was associated with Poisoning Severity Score None or Minor (sensitivity 76%; specificity 86%) and >11.0 mmol/L was associated with fatal outcome (sensitivity 74%; specificity 80%). 61 cases (5%) had severe carboxyhaemoglobin toxicity (COHb >30%). This was associated with a fatal outcome (OR 7.0; 95% CI 1.5-33.7) and there was positive correlation between carboxyhaemoglobin and Poisoning Severity Score, r = 0.57, p < 0.0001. Most cases of ingestion of plant material involved children under five years and resulted in no or mild symptoms. In adults smoke inhalation was associated with the most severe poisoning. The lactate cut-off values associated with each severity score calculated in this study are lower than the values used by NPIS on TOXBASE. Analytical conformation of cyanide exposure was unavailable in the majority of case, limiting the strength of these conclusions. [ABSTRACT FROM AUTHOR]

Despite the risk of cyanide poisoning a suitable antidote that can be administered at a reasonable quantity to a large number of individuals is not yet available. This study was carried out to determine the possible hepatoprotective effect of ethanolic extract of Aframomum melegueta seed against cyanide-induced liver injury and its possible antidote effect. Thirty male rats divided into five groups were used for this study. Group 1, received neither cyanide nor the seed extract (Normal control), Groups 2-5 were administered cyanide orally by gavage in form of KCN at a concentration of 4 mg/kg body weight according to body weights as follows; Group 2, received cyanide only (positive control). Group 3 received cyanide and sodium thiosulphate (500 mg/kg body weight) a standard cyanide antidote. (Standard control). Group 4 and 5 were co-treated with cyanide and different doses of the extract three times weekly for the duration of the experiment. Cotreatment with A. melegueta restored the weight loss and the activities of AST, ALT. ALP to levels compared to that obtained in the normal control. In addition co-treatment with A. melegueta modulated the cyanide mediated depletion of the antioxidant capacities of the rats that were exposed to cyanide and the increasing lipid peroxidation profile. The results indicated that ethanolic extract of A.melegueta seed ameliorated cyanideinduced hepatoxicity in rats through their free radical-scavenging mechanisms. [ABSTRACT FROM AUTHOR]

Cyanide is a poison widely used in cases of suicide or homicide. Although various methods to identify and quantify this substance are reported in the literature, they are mainly validated on biological fluids (e.g., blood and urine). In the present study, the Anion‐Exchange Liquid Chromatography with Pulsed Amperometric Detection (IC‐PAD) method was validated on blood and, for the first time, on gastric content, and organs (brain, lung, and liver). For each matrix, linearity, accuracy, precision, limit of detection (LOD), lower limit of quantification (LLOQ), matrix interferences, and carryover were assessed. The samples were extracted by steam distillation in acid environment for the following analysis by IC‐PAD. Furthermore, cyanide values found in two real poisoning cases are reported. For each investigated matrix, the analytical method satisfied all acceptance criteria for validation: it showed a good precision and accuracy, selectivity, and sensitivity with no carryover and matrix interference. The extraction by steam distillation in acid environment REDUCED the interference of the matrices and ALLOWED to perform the analysis with good precision and accuracy. In case #1, analysis showed a blood cyanide concentration of 0.99 μg/ml. In case #2, cyanide concentrations were 1.3 μg/g in brain, 0.8 μg/g in lung, 1.6 μg/g in liver, and 1.2 μg/g in gastric content. The cyanide concentrations found in the two reported cases have been suitable to cause death by poisoning. [ABSTRACT FROM AUTHOR]

Hydrogen cyanide and methanethiol are two toxic gases that inhibit mitochondrial cytochrome c oxidase. Cyanide is generated in structural fires and methanethiol is released by decaying organic matter. Current treatments for cyanide exposure do not lend themselves to treatment in the field and no treatment exists for methanethiol poisoning. Sodium tetrathionate (tetrathionate), a product of thiosulfate oxidation, could potentially serve as a cyanide antidote, and, based on its chemical structure, we hypothesized it could react with methanethiol. We show that tetrathionate, unlike thiosulfate, reacts directly with cyanide in vitro under physiological conditions, and based on rabbit studies where we monitor cyanide poisoning in real-time, tetrathionate likely reacts directly with cyanide in vivo. We found that tetrathionate administered by intramuscular injection rescues >80% of juvenile, young adult, and old adult mice from exposure to inhaled hydrogen cyanide gas that is >80% lethal. Tetrathionate also rescued young adult rabbits from intravenously administered sodium cyanide. Tetrathionate was reasonably well-tolerated by mice and rats, yielding a therapeutic index of ∼5 in juvenile and young adult mice, and ∼3.3 in old adult mice; it was non-mutagenic in Chinese Hamster ovary cells and by the Ames bacterial test. We found by gas chromatography-mass spectrometry that both tetrathionate and thiosulfate react with methanethiol to generate dimethyldisulfide, but that tetrathionate was much more effective than thiosulfate at recovering intracellular ATP in COS-7 cells and rescuing mice from a lethal exposure to methanethiol gas. We conclude that tetrathionate has the potential to be an effective antidote against cyanide and methanethiol poisoning. [ABSTRACT FROM AUTHOR]

• Development of the simultaneous determination of cyanide, ethanol, and 1-propanol. • A simple method using HS–GC–MS/NPD was employed. • The two detectors were switched using the Deans switch in a single run. • The separation of 23 volatile compounds was investigated on three types of columns. Cyanide is a powerful and rapidly acting poison. In Japan, cyanide poisoning is rare, and regular cyanide testing can be costly and time consuming. In contrast, alcohol analysis is routinely performed in most forensic laboratories. In this study, we attempted to develop a method for the simultaneous quantification of cyanide and alcohols in blood using headspace gas chromatography (HS–GC). As nitrogen-phosphorus detection (NPD) is more sensitive to hydrogen cyanide than mass spectrometry (MS), a Deans switch was used to switch the detectors during a single run. The separation provided by three analytical columns, PoraBOND Q, CP-Sil 5 CB, and HP-INNOWax, was investigated, and PoraBOND Q was selected. The use of HS–GC–MS/NPD with a Deans switch enabled the simple and simultaneous quantification of cyanide, ethanol, and 1-propanol. Eighteen other volatile compounds were detected in the SIM/scan mode of the MS. [ABSTRACT FROM AUTHOR]

House fires can lead to cyanide poisoning and an associated elevated serum lactate level. Because of delays in obtaining serum cyanide levels, clinical symptoms and serum lactate are often used to guide clinical decision making and antidote administration. However, as this case report identifies, lower levels of serum lactate may in fact correlate with higher levels of serum cyanide that could benefit from treatment with an antidote. [ABSTRACT FROM AUTHOR]

Cyanide poisoning most commonly occurs from smoke inhalation, less commonly by oral ingestion for suicide or homicide. There are rare cases of intravenous or subcutaneous parenteral cyanide. We report a fatal case of intramuscular cyanide used as a homicidal agent. A 35-year-old female was assaulted and injected with an unknown substance in her left buttock using a syringe. She was unresponsive at ED arrival and underwent immediate endotracheal intubation. After near normal vital signs at arrival (BP 130/83 mmHg, HR 102 bpm), she rapidly became hypotensive and bradycardic with worsening acidosis (pH 6.95, lactate 7.7 mmol/L). Despite vasopressors, hydroxocobalamin, and sodium thiosulfate, she succumbed. Plasma cyanide concentrations from blood drawn 1 and 4 h post exposure were both in the lethal range (3.4 and 4.1 mg/L, respectively). Our case demonstrates that intramuscular injection can result in fatal cyanide poisoning, resulting in rapid absorption, severe toxicity, and death. [ABSTRACT FROM AUTHOR]

Cyanide is a rapid acting, lethal, metabolic poison and remains a significant threat. Current FDA-approved antidotes are not amenable or efficient enough for a mass casualty incident. The objective of this study is to evaluate short and long-term efficacy of intramuscular aqueous dimethyl trisulfide (DMTS) on survival and clinical outcomes in a swine model of cyanide exposure. Anesthetized swine were instrumented and acclimated until breathing spontaneously. Potassium cyanide infusion was initiated and continued until 5 min after the onset of apnea. Subsequently, animals were treated with intramuscular DMTS (n = 11) or saline control (n = 10). Laboratory values and DMTS blood concentrations were assessed at various time points and physiological parameters were monitored continuously until the end of the experiment unless death occurred. A subset of animals treated with DMTS (n = 5) were survived for 7 days to evaluate muscle integrity by repeat biopsy and neurobehavioral outcomes. Physiological parameters and time to apnea were similar in both groups at baseline and at time of treatment. Survival in the DMTS-treated group was 90% and 30% in saline controls (p = 0.0034). DMTS-treated animals returned to breathing at 12.0 ± 10.4 min (mean ± SD) compared to 22.9 ± 7.0 min (mean ± SD) in the 3 surviving controls. Blood collected prior to euthanasia showed improved blood lactate concentrations in the DMTS treatment group; 5.47 ± 2.65 mmol/L vs. 9.39 ± 4.51 mmol/L (mean ± SD) in controls (p = 0.0310). Low concentrations of DMTS were detected in the blood, gradually increasing over time with no elimination phase observed. There was no mortality, histological evidence of muscle trauma, or observed adverse neurobehavioral outcomes, in DMTS-treated animals survived to 7 days. Intramuscular administration of aqueous DMTS improves survival following cyanide poisoning with no observed long-term effects on muscle integrity at the injection site or adverse neurobehavioral outcomes. [ABSTRACT FROM AUTHOR]

Malicious, commercial or retaliatory poisoning of wildlife is increasing across Africa, including the killing of elephants ( Loxodonta africana) to supply the illegal ivory trade. Regional differences exist in the types of poisons used by poachers and in Zimbabwe cyanide has become more commonly employed in recent years -- sourced illegally from its commercial use in the gold mining industry. Cyanide is potent, so can be rapidly lethal in small quantities and is also not too difficult or costly to source illegally. It is therefore a relatively low-risk option for any ivory poacher, even individuals not involved with criminal syndicates. On the positive side, however, cyanide has far fewer bio-accumulative and cycling properties in ecosystems than more frequently used poisons like pesticides. Detection and subsequent proof in a court of law, of the illegal use of cyanide in elephant carcasses, can be problematic to distinguish conclusively from other causes of sudden death. Therefore, proactive strategies to combat wildlife poisons are far more successful and the one proposed here against cyanide provides a good model. It encourages the establishment of strong intelligence networks to enable the arrest of poachers in possession of poisons before they are deployed in the field, and effective application of laws which now facilitate convictions for poaching. A key element in prosecution under recently revised Zimbabwean laws is proving that illegal possession of cyanide in the relevant circumstances includes the intent to use itfor ivory poaching. Zimbabwe's legal experience in this respect could prove especially valuable to other countries facing similar threats of poison being used illegally to kill any wildlife species. [ABSTRACT FROM AUTHOR]

Acetone cyanohydrin (ACH), an organic cyanide, is mainly used in the production of methyl methacrylate (MMA), and it also exists in cassava roots, the main calorie source in some tropical countries. ACH can decompose spontaneously or enzymatically into acetone and highly toxic hydrogen cyanide (HCN) and be potentially toxic to its contacts. Given that limited forensic studies and case reports on fatal ACH poisoning are available, herein, we present a report of two fatal cases of ACH poisoning in which the two victims, with postmortem cyanide blood concentrations of 4.22 μg/ml and 4.07 μg/ml, suffered from acute poisoning of ACH due to a traffic accident. Furthermore, a literature review of cyanide poisoning case reports from 2000 to 2020 was carried out, and 28 subjects with cyanide poisoning were presented, including the age, sex, cause of poisoning, autopsy findings and the cyanide concentration in the blood. ACH poisoning lacks specific and reliable autopsy findings for diagnosis, and relevant toxicological studies are necessary. Due to the chemical properties of ACH that allow it to easily decompose, the toxicological analysis of acetone and cyanide in biological samples is essential for the diagnosis of ACH poisoning. [ABSTRACT FROM AUTHOR]

Cyanogenic glycosides including amygdaline are naturally occurring herbal toxins. Apple seeds contain amygdalin, a potentially toxic compound. Orally amygdalin is hydrolyzed to cyanide with beta-glucuronidase in the small intestine and leads to cyanide poisoning. Suicidal attempts which are rarely used and involve complex methods are particularly important and oral intake of toxins that can turn into cyanide can also be considered in this context. Personality disorders are frequently diagnosed in cases presenting with suicid attempt and borderline personality disorder is one of the highest risk in terms of suicid attempt in the community. In this case report, a patient who attempted suicid with apple kernels and considered borderline personality disorder is presented. It is aimed to demonstrate that the early recognition and treatment of signs and symptoms of cyanide toxicity is vital for a successful clinical outcome and to draw attention to rare suicidal methods and possible risk factors, especially in patients with personality disorders. [ABSTRACT FROM AUTHOR]

In this proof-of-concept study, the aim was to evaluate the short-term clinical effectiveness of isosorbide dinitrate (ISDN) oral spray in non-anaesthetized cyanide-poisoned swine. A comparative study was conducted using domestic swine. Animals were intravenously poisoned with potassium cyanide (KCN), either 2 mg/kg or 4 mg/kg dose. Two control groups (one for each cyanide dose) were not further treated. Two other groups (one for each cyanide dose) were treated within 1 min after poisoning with ISDN oral spray: 3 spray actuations (averaging a total of 3.75 mg) after the lower cyanide dose and 4 spray actuations (averaging a total of 5.0 mg) after the higher dose. The study outcomes were clinical score, time to death, and blood tests including pH, lactate, and methemoglobin levels. All the animals started to convulse within 20 to 30 sec after KCN poisoning, then became unresponsive and hemodynamically depressed after another 20 to 30 sec. After the KCN 2 mg/kg dose, 3 of 4 control animals survived, while all treated animals survived. Compared with control animals, ISDN-treated animals displayed significantly better clinical scores starting 5 min after KCN poisoning. Acidosis was significantly more pronounced in the untreated animals. After the KCN 4 mg/kg dose, similar survival rates were observed for control and ISDN-treated groups (1/4), but treated animals had longer time to death and better pH and lactate levels. ISDN oral spray administration following KCN poisoning in this porcine model did not result in statistically significant increased survival. However, based on clinical scores and clinical laboratory values, ISDN may benefit as a bridging countermeasure until currently-available specific cyanide antidotes can be administered. Further research is warranted to better characterize this potential role of ISDN in cyanide poisoning. [ABSTRACT FROM AUTHOR]

Azide is a highly toxic chemical agent to human being. Accidental, but also intentional exposure to azide occurs. To be able to confirm azide ingestion, we developed a method to identify and quantify azide in biological matrices. Cyanide was included in the method to evaluate suggested in vivo production of cyanide after azide ingestion. Azide in biological matrices was first derivatized by propionic anhydride to form propionyl azide. Simultaneously, cyanide was converted into hydrogen cyanide. After thermal rearrangement of propionyl azide, ethyl isocyanate was formed, separated together with hydrogen cyanide by gas chromatography (GC) and detected using a nitrogen phosphorous detector (NPD). The method was linear from 1.0‐100 µg/mL for both analytes, and azide was stable in human plasma at −20°C for at least 49 days. Azide was measured in the gastric content of two cases of suspected azide ingestion (case 1:1.2 mg/mL, case 2:1.5 mg/mL). Cyanide was only identified in the gastric content of case 1 (approximately 1.4 µg/mL). Furthermore, azide was quantified in plasma (19 µg/mL), serum (24 µg/mL), cell pellet (21 µg/mL) and urine (3.0 µg/mL) of case 2. This method can be used to confirm azide and cyanide exposure, and azide concentrations can be quantified in several biological matrices. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Pediatric Emergency & Intensive Care Medicine / Çocuk Acil ve Voğun Bakım Dergisi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Cuarzo (REC) is the property of Fundacion Universitaria Juan N. Corpas and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cyanide (C≡N) can lead to blood, cardiovascular system, and nervous system disorders owing to the acute and chronic toxicity; thus, aiming at the group or individual poisoning incidents, it is necessary to develop the sensitive and credible method for rapid on-site detection of poisons cyanide. Surface-enhanced Raman spectroscopy (SERS) with the advantages of providing fingerprint information of target molecules and single-molecules sensitivity has been widely used in on-site analysis; however, the SERS measurements always suffer from the problem of the stability of substrates. Here, the polyvinylpyrrolidone (PVP)-stabilized Au NPs (PVP-Au NPs) have been assembled through the simple, convenient evaporation-induced strategy with the large-scale hotspots substrates. The presence of PVP can not only facilitate the assembly of Au NPs but also prevent the corrosion of CN− towards the Au NPs with the formation of [Au (CN)2]−1, providing high stable and reproducible SERS signals. Moreover, the PVP-Au NPs have been assembled on the Si wafer to fabricate the portable SERS chip for rapid on-site detection of CN− with an RSD of 5.8% and limitation of 100 ppb. Furthermore, by coupling a portable Raman spectrometer, the SERS spectra of CN− spiked into different specimens to simulate the poison samples have been collected and analyzed on SERS chips with the recovery of 89–103% and RSD not higher than 11.3%. Consequently, the fabricated SERS chip with assembled PVP-Au NPs can provide sensitive and credible detection for CN− in different specimens, and then would satisfy the rapid on-site evaluation of CN− in poisoning incidents with the portable Raman spectrometer. [ABSTRACT FROM AUTHOR]

Background: Dicobalt edetate and hydroxocobalamin are widely used to treat hydrogen cyanide poisoning. However, comparative and quantitative efficacy data are lacking. Although post-exposure treatment is typical, it may be possible to administer these antidotes before exposure to first attenders entering a known site of cyanide release, as supplementary protection to their personal protective equipment. Methods: We established an anaesthetised Gottingen minipig model of lethal bolus potassium cyanide (KCN) injection to simulate high dose hydrogen cyanide inhalation. Doses were similar to human lethal doses of KCN. Dicobalt edetate and hydroxocobalamin were administered shortly before KCN and their effect on metabolic and cardiovascular variables and survival time were measured. Results: Increases in arterial lactate were similar after 0.08 and 0.12 mmol/kg KCN. KCN 0.08 mmol/kg was survived by 4/4 animals with moderate cardiovascular effects, while the 0.12 mmol/kg dose was lethal in 4/4 animals, with a mean time to euthanasia of 28.3 (SEM: 13.9) min. Administration of dicobalt edetate (0.021 mmol/kg, 8.6 mg/kg) or hydroxocobalamin (0.054 mmol/kg, 75 mg/kg) at clinically licenced doses had modest effect on lactate concentrations but increased survival after administration of KCN 0.12 mmol/kg (survival: dicobalt edetate 4/4, hydroxocobalamin 2/4) but not 0.15 mmol/kg (0/4 and 0/4, respectively). In a subsequent larger study, doubling the dose of hydroxocobalamin (0.108 mmol/kg, 150 mg/kg) was associated with a modest but inconsistent increased survival after 0.15 mmol/kg KCN (survival: control 0/8, 75 mg/kg 1/10, 150 mg/kg 3/10) likely due to variable pharmacokinetics. Conclusions: In this porcine study of cyanide exposure, with pre-exposure antidote administration, licenced doses of dicobalt edetate and hydroxocobalamin were effective at just lethal doses but ineffective at less than twice the estimated LD50. The efficacy of a rapidly-administered double-dose of hydroxocobalamin was limited by variable pharmacokinetics. In clinical poisoning scenarios, with delayed administration, the antidotes are likely to be even less effective. New antidotes are required for treatment of cyanide exposures appreciably above the minimum lethal dose. [ABSTRACT FROM AUTHOR]

Chromolaena odorata is an invasive plant which is acclaimed to have cyanide remediation potential from contaminated sites. This examination means to decide the impact of ethanol concentrates of C. odorata (ECO), sodium thiosulphate and a mix of both on hematological parameters and blood lipid profile of rodents presented to potassium cyanide. (KCN). A sum of thirty five male Wistar rats partitioned into seven groups of five units were used. KCN Group rats were administered with KCN alone. Rats in 100ECO, 150ECO, 200ECO groups were administered with 100, 150 and 200 mg/kg body weight of ECO respectively. Rats under Na2sS2O3 and Na2S2O3+ECO groups were administered 200 mg/kg sodium thiosulphate and sodium thiosulphate with ECO at 200 mg/kg respectively. The trial was done in about a month. Toward the finish of the investigation, the packed cell volume (PCV), hemoglobin level (Hb), Red blood cells (RBC) and white blood cells (WBC) were resolved utilizing known biochemical methodology. The outcomes demonstrated a noteworthy increment (p < 0.05) in PCV, Hb, RBC and WBC level of remedial groups when contrasted with the cyanide group. Total cholesterol (TC), and triglyceride (TG) were altogether lower while HDL-cholesterol was fundamentally expanded in all the treated groups when contrasted and the untreated group given cyanide alone. However, no significant difference in LDL-cholesterol was indicated in all therapeutic groups compared with the cyanide group. The study revealed that C. odorata at the tested doses was able to improve the hematological parameters and lipid profile in cyanide exposed rats. [ABSTRACT FROM AUTHOR]

Cyanide, a metabolic poison, is a rising chemial threat and ingestion is the most common route of exposure. Terrorist organizations have threatened to attack the USA and international food and water supplies. The toxicokinetics and toxicodynamics of oral cyanide are unique, resulting in high-dose exposures, severe symptoms, and slower onset of symptoms. There are no FDA-approved therapies tested for oral cyanide ingestions and no approved intramuscular or oral therapies, which would be valuable in mass casualty settings. The aim of this review is to evaluate the risks of oral cyanide and its unique toxicokinetics, as well as address the lack of available rapid diagnostics and treatments for mass casualty events. We will also review current strategies for developing new therapies. A review of the literature using the PRISMA checklist detected 7284 articles, screened 1091, and included 59 articles or other reports. Articles referenced in this review were specific to risk, clinical presentation, diagnostics, current treatments, and developing therapies. Current diagnostics of cyanide exposure can take hours or days, which can delay treatment. Moreover, current therapies for cyanide poisoning are administered intravenously and are not specifically tested for oral exposures, which can result in higher cyanide doses and unique toxicodynamics. New therapies developed for oral cyanide exposures that are easily delivered, safe, and can be administered quickly by first responders in a mass casualty event are needed. Current research is aimed at identifying an antidote that is safe, effective, easy to administer, and has a rapid onset of action. [ABSTRACT FROM AUTHOR]

Cyanides are highly toxic compounds that have been used as weapons of terrorism throughout history. Cyanide (CN) is acutely toxic by all routes of administration; however, inhalation is the main exposure route. To adequately test effective countermeasures against inhalational CN threats, robust and well-characterized animal models are needed. This paper describes the initial development of a hydrogen cyanide (HCN) exposure swine model for documenting the physiological effects and toxicological profile during and after HCN inhalation exposure. Animals were implanted with telemetry transmitters for heart rate (HR), blood pressure, and electrocardiogram monitoring, and vascular access ports for serial blood collections. Nine female swine were exposed to HCN concentrations of 500 ± 6 ppm while breathing parameters were monitored real-time. Inhaled HCN doses ranged from 2.02 to 2.83 mg/kg. Clinical signs included vocalization, agitation, salivation, respiratory distress and apnea. After HCN exposure initiation, systemic arterial pressure fell dramatically with a concomitant increase in HR. Blood samples were collected to determine CN blood levels using LC-MS/MS and blood gas analysis. In summary, the developed HCN inhalation swine model permitted documentation of the physiological effects associated with CN poisoning. This model could be used to evaluate potential CN medical countermeasures in the event of a public health emergency stemming from inhalational CN threats. [ABSTRACT FROM AUTHOR]

Mine tailings and wastewater generate man-made environments with several selective pressures, including the presence of heavy metals, arsenic and high cyanide concentrations, but severe nutritional limitations. Some oligotrophic and pioneer bacteria can colonise and grow in mine wastes containing a low concentration of organic matter and combined nitrogen sources. In this study, Pseudomonas mendocina P6115 was isolated from mine tailings in Durango, Mexico, and identified through a phylogenetic approach of 16S rRNA, gyrB, rpoB, and rpoD genes. Cell growth, cyanide consumption, and ammonia production kinetics in a medium with cyanide as sole nitrogen source showed that at the beginning, the strain grew assimilating cyanide, when cyanide was removed, ammonium was produced and accumulated in the culture medium. However, no clear stoichiometric relationship between both nitrogen sources was observed. Also, cyanide complexes were assimilated as nitrogen sources. Other phenotypic tasks that contribute to the strain’s adaptation to a mine tailing environment included siderophores production in media with moderate amounts of heavy metals, arsenite and arsenate tolerance, and the capacity of oxidizing arsenite. P. mendocina P6115 harbours cioA/cioB and aoxB genes encoding for a cyanide-insensitive oxidase and an arsenite oxidase, respectively. This is the first report where P. mendocina is described as a cyanotrophic and arsenic oxidizing species. Genotypic and phenotypic tasks of P. mendocina P6115 autochthonous from mine wastes are potentially relevant for biological treatment of residues contaminated with cyanide and arsenic. [ABSTRACT FROM AUTHOR]

Background: Ingestion of cyanide may not manifest immediately in acute life-threatening symptoms. This delay presents an opportunity for recognition and appropriate management. Case Report: A 23 -year-old male purchased sodium cyanide through an internet order for suicidal gesture. He mixed sodium cyanide (5 grams) with cola soft drink (350 mL) to produce hydrogen cyanide. The patient inhaled cyanide gas for 30 minutes, however, he did not lose consciousness. He then drank the entire solution, causing him to vomit. The patient presented to the emergency medicine department about two hours after ingestion. He was conscious, and his vital signs were normal. Blood chemistries revealed wide anion gap metabolic acidosis (anion gap 16 mmol/L). Arterial blood gas and venous blood gas on arrival demonstrated no acidosis but narrow arterial and venous oxygen saturation gap (3%). He was treated with 12.5 grams of sodium thiosulfate intravenously, 5 0 grams of activated charcoal administered orally, and other supportive care. The patient condition improved clinically and laboratory. The narrow arterial-venous oxygen saturation gap was resolved (52%) at four hours post treatment. Hydrogen cyanide levels in patient's plasma and urine samples were confirmed by Gas Chromatography Mass Spectrometry methods. Conclusion: The patient was a confirmed case of acute cyanide poisoning, exhibiting the early signs of cyanide poisoning, and was successfully treated with sodium thiosulfate alone. [ABSTRACT FROM AUTHOR]

Objective: The aim of this systematic review was to identify isolated acute cyanide poison cases and to identify reported signs, symptoms, and laboratory findings. Methods: We searched MEDLINE, Cochrane Reviews, and Web of Science case reports and series using a number of MeSH descriptors pertaining to cyanide, toxicity, and poisonings. We excluded studies on plants, laboratory analyses, smoke inhalation poisonings, animals as well as non-English language articles and those in which data were not available. Data extracted included demographics, exposure characteristics, acute signs/symptoms, and medical management and outcome. Results: From the initial 2976 articles retrieved, 65 articles (52 case reports, 13 case series) met inclusion criteria and described 102 patients. Most patients were unresponsive (78%), hypotensive (54%), or had respiratory failure (73%); other signs and symptoms included cardiac arrest (20%), seizures (20%), cyanosis (15%), cherry red skin (11%), and had an odor present (15%). Medical management included cyanide antidote kit (20%), sodium thiosulfate (40%), and hydroxocobalamin (29%). The majority of cases (66%) required intubation with mechanical ventilation and a substantial number (39%) developed refractory hypotension requiring vasopressor support. Conclusions: Contrary to general reviews published on cyanide toxicity, reports of cherry red skin and bitter almond odor were rare among published cyanide cases. Consistent with other studies, metabolic acidosis with significant lactic acidosis were the laboratory values consistently associated with cyanide toxicity. Healthcare providers may overlook cyanide toxicity in the differential diagnosis, if certain expected characteristics, such as the odor of almonds or a cherry red color of the skin are absent on physical examination. [ABSTRACT FROM AUTHOR]

Cyanide leaching is the predominant process of gold extraction in large scale mining. Current initiatives for reducing the use of mercury in small scale and artisanal mining tend towards the cyanide technology as the only feasible alternative. Thus, the deliberate handling in consideration of the hazardous nature of cyanide compounds is an issue of particular importance. The hydrogen cyanide volatilised during the leaching process and from the tailings solutions after the gold extraction is reported to be destroyed by oxidation and photolysis from the surrounding atmosphere of gold mines and the sunlight. Cyanide solutions, drained into the surrounding waterbodies are stated to volatilise at a high rate, thus detoxifying them and releasing hydrogen cyanide to the air. In this study laboratory experiments and field tests were conducted to deliver basic data for the volatilisation and destruction of cyanide in the environment. In our laboratory tests we observed neither oxidation by the oxygen of air nor photolysis by UV-irradiation of cyanides after volatilisation from water. The whole amount of volatilised cyanide was found in the exhaust gas after absorption in a strong basic solution. Field experiments in Segovia (Colombia) could confirm these findings. Cyanide concentrations in a range 17 to 30 mg/L were measured in a local creek. Hydrogen cyanide amounts of 5 ppm were found in the atmosphere surrounding cyanide leaching facilities. With the findings of this study we want to point out that the concentrations of cyanide in the surrounding of cyanide leaching facilities exceed uncritical limits and a destruction via oxidation and photolysis is not detectable. These conclusions should result in initiatives to protect workers and the surrounding population of gold mines from contaminations of cyanide treatments. [ABSTRACT FROM AUTHOR]

We examined the feasibility of using handheld mid-infrared (MIR) Fourier-Transform infrared (FT-IR) instrumentation for detecting and analysing cyanide (CN) contamination in field contaminated soils. Cyanide spiking experiments were first carried out, in the laboratory, to test the sensitivity of infrared Fourier transform (DRIFT) spectrometry to ferro- and ferricyanide compounds across a range of reference soils and minerals. Both benchtop and handheld diffuse reflectance infrared spectrometers were tested. Excellent results were obtained for the reference soils and minerals, with the MIR outperforming the near-infrared (NIR) range. Spectral peaks characteristic of the –C≡N group were observed near 2062 and 2118 cm -1 in the MIR region for the ferro- and ferricyanide compounds spiked into soils/minerals, respectively. In the NIR region such peaks were observed near 4134 and 4220 cm -1 . Cyanide-contaminated samples were then collected in the field and analyzed with the two spectrometers to further test the applicability of the DRIFT technique for soils containing aged CN residues. The prediction of total CN in dry and ground contaminated soils using the handheld MIR instrument resulted in a coefficient of determination (R 2 ) of 0.88–0.98 and root mean square error of the cross-validation (RMSE) of 21–49 mg kg -1 for a CN range of 0–611 mg kg -1 . A major peak was observed in the MIR at about 2092 cm -1 which was attributed to “Prussian Blue” (Fe 4 [Fe(CN) 6 ] 3 · x H 2 O). These results demonstrate the potential of handheld DRIFT instrumentation as a promising alternative to the standard laboratory method to predict CN concentrations in contaminated field soils. [ABSTRACT FROM AUTHOR]

Electrochemiluminescence (ECL) emission of gold nanoparticles (Au NPs) loaded graphitic carbon nitride nanosheets (Au-CNN nanohybrids) can be modulated by the Au content. On the basis, a signal-on ECL sensor for detecting cyanide, a widespread toxic chemical, has been developed in this work. The sensor utilizes cyanide-mediated etching of Au NPs to recover the ECL emission of Au-CNN nanohybrids initially inhibited by Fӧrster resonance energy transfer (FRET) from CNNs to Au NPs. The ECL sensor has a sensitive response to cyanide in the range of 50 nM to 1 mM with a detection limit of 50 nM, and shows high specificity due to the high affinity of Au-cyanide complex. The proposed FRET modulated ECL sensor may prove valuable in future environmental monitoring. [ABSTRACT FROM AUTHOR]

Context:Acetonitrile (ACN) is a solvent rapidly absorbed through lungs and intestinal tract, and is slowly metabolized to cyanide (CN) by enzymatic processes mediated by CYP2E1. Objective:To describe the clinical and laboratory evolution, ACN elimination half-life, and its presence in breast milk in a nursing mother who attempted suicide. Case details:A 25-year-old 2-month nursing mother ingested an estimated dose of 2.1 g/kg of ACN. Blood and urine samples were collected 24 h later for ACN, CN and thiocyanate analysis, and 12.5 g sodium thiosulfate i.v. in 1-h infusion was started and repeated every 24 h for 4 days. ACN results showed 200 mg/L in blood and 235 mg/L in urine. ACN analysis in the breast milk at Day 6 showed level of 21 mg/L compared to 27 mg/L in blood collected at the same time, suggesting a possible relationship of 1.3:1.0 ratio. An elimination half-life of 40.4 h was calculated, compared to 32 and 36 h showed in other studies. Discussion:The clinical management must involve the use of CN antidotes for more than 24 h depending on the symptoms and blood levels of ACN. Furthermore, our data showed the possible existence of a close relationship between plasma and breast milk levels. [ABSTRACT FROM AUTHOR]

In recent times, a lot attention has been focused on the clinical importance of herbal medicines and there has been an ongoing research on plant extracts and their ability to ameliorate the toxicity of various heavy metals. In this study, the protective effects of Vernonia amydalina (bitter leaf) on the liver and kidney enzyme function of rats exposed to cyanide was investigated. A total of twenty four (24) male albino Wister rats weighing between 150 to 200g were used for the experiment and were randomly assigned to four (4) groups. Rats in group 1 (Control) received only normal feed and water, while rats in group 2 (cyanide) received cyanide (9mgCN/kg b.w.) in drinking water). Rats in group 3 and 4 received cyanide as those in group two, but were pretreated with 100mg and 200mg/kg b.w bitter leaf extract for 14 days respectively before cyanide administration. The experiment lasted for 28 days after which the rats were sacrificed and blood and tissues harvested for biochemical assays. A significant decrease (P>0.05) was indicated in Aspartate aminotransferase (AST), Alanine aminotransferase, (ALT) and Alkaline aminotransferase (ALP) activities in all the groups treated with aqueous bitter leaf extract (BLE) when compared with the untreated group given cyanide only. Aqueous extract of the bitter leaf also significantly reduced (P>0.05) Total protein, urea and creatinine concentration in all the treated rats. Among the treated groups the group given the higher dose of BLE gave significantly lower values. The results indicate that Vernonia amydalina possesses hepato- and nephro-protective effects which is dose dependent and that its consumption may help in the reduction of cyanide-induced damage to the liver and kidney. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effects of a blockade of nitric oxide (NO) synthesis on hyperbaric oxygen (HBO2) therapy during cyanide (CN) intoxication. Methods: 39 anesthetized female Sprague-Dawley rats were exposed to CN intoxication (5.4 mg/kg intraarterially) with or without previous nitric oxide synthase (NOS) inhibition by L-NG-nitroarginine methyl ester (L-NAME) injection (40 mg/kg intraperitoneally). Subsequently, either HBO2 therapy (284 kPa/90 minutes), normobaric oxygen therapy (100% oxygen/90 minutes) or nothing was administered. Intracerebral microdialysis was used to measure the interstitial brain concentration of lactate, glucose, glycerol and lactate/pyruvate ratios. Results: L-NAME potentiated CN intoxication by higher maximum and prolonged lactate (in mM: 0. 5+/- 0.3 vs. 0.7 +/- 0.4, P < 0.005) concentrations compared with solely CN-intoxicated rats. The same trend was found for mean glucose, glycerol and lactate/pyruvate ratio levels. During HBO2 treatment a sustained reduction occurred in mean lactate levels (in mM: 0.5 +/- 0.5 vs. 0.7 +/- 0.4, P < 0.01) regardless of NOS blockade by L-NAME. The same trend was found for mean glucose and glycerol levels. Conclusion: The results suggest that blocking NOS using L-NAME can worsen acute CN intoxication. HBO2 treatment can partially overcome this block and continue to ameliorate CN intoxication. [ABSTRACT FROM AUTHOR]

The high toxicity of cyanide, along with its widespread industrial use, has fuelled interest in the development of analytical methods for its determination in complex matrices. In this study, we propose a novel approach for the measurement of total cyanide in soil samples based on single-step derivatization with pentafluorobenzyl bromide (F 5 Bn−Br) followed by quantitation with gas chromatography mass spectrometry in negative chemical ionization mode. The reaction between CN − and F 5 Bn−Br resulted in the identification of several derivatives such as F 5 Bn−CN, (F 5 Bn)(F 5 Ph)CH−CN, and (F 5 Bn) 2 (F 5 Ph)C−CN. The relative proportion between such compounds was dependent on experimental conditions. When a 100 μL aliquot of an alkaline-aqueous extract was reacted with 700 μL of 1.3% F 5 Bn−Br in acetone, the tri-alkylated derivative was the most abundant. In such conditions a detection limit of 0.5 ng/g of CN − was attained. Soil samples were initially spiked with an alkaline solution of K 13 C 15 N internal standard and suspended in 7.5% aqueous NaOH. Determination of total cyanide was achieved by digestion of the alkaline extract with H 3 PO 4 to produce HCN which was then trapped in 0.1% NaOH in a sealed double vial system, followed by reaction with F 5 Bn−Br. Isotope dilution calibration was chosen for quantitation, and the validity of the novel method was demonstrated by analysis of soil Certified Reference Materials (CRMs) and by spike recovery tests. [ABSTRACT FROM AUTHOR]

Background: Better and safer antidotes against cyanide poisoning are needed. Prior study has shown a favorable effect of isosorbide dinitrate (ISDN) on the survival of cyanide-poisoned rabbits when administered as early as 1 min after poisoning. The aim of the current study was to further evaluate the efficacy of intravenous ISDN administered in clinically relevant timing for first responders. Methods: A comparative animal study using 24 rabbits in 4 randomized study groups was performed. Animals were poisoned with intravenous potassium cyanide (1 mg/kg). Animals in Group 1 served as controls and received no treatment. Groups 2-4 animals were treated intravenously with ISDN (50 μg/kg) after poisoning; one group after 3 min, another group after 5 min and the last after 7 min. Animals were observed for 30 min after poisoning. The study endpoints included survival rate, clinical status, blood pressure, pulse per minute, blood lactate and pH. Results: Five of 6 animals (83.3%) from every treatment group survived the whole observation period while all control untreated animals died. All the rabbits collapsed immediately after exposure, showing rapidly deteriorated vital signs with lactic metabolic acidosis (peak blood lactate levels of 18.1 to 19.0 mmol/L on average at 10 min post exposure). Vital signs, clinical scores, and blood gases of treated rabbits gradually improved. Conclusion: Poisoned rabbits showed improved short-term survival following the administration of ISDN up to 7 min after lethal cyanide poisoning of. We see a potential for ISDN as an antidote against cyanide poisoning. [ABSTRACT FROM AUTHOR]

Sodium nitrite (NaNO 2) is a universal antidote for patients with cyanide poisoning. However, its use has serious drawbacks in terms of efficacy and safety. Herein, we present a promising antidote: methemoglobin (metHb)-albumin clusters. The metHb-albumin cluster is made by a metHb core wrapped by covalently bound human serum albumin. Spectral analyses proved that the metHb-albumin clusters possessed cyanide-binding properties similar to those of naked metHb. In vitro cell experiments showed that metHb-albumin clusters prevented the cyanide-induced inhibition of cytochrome c oxidase activity, resulting in a strong cytoprotective effect. In mice subjected to cyanide poisoning, metHb-albumin clusters reduced mortality and alleviated metabolic acidosis, while maintaining the activity of cytochrome c oxidase in organs; their efficacy was better than that of NaNO 2. Furthermore, the oxygen carrying capacity was maintained in poisoned mice treated with metHb-albumin clusters and was low in those treated with NaNO 2. These results indicate that metHb-albumin clusters could be a more effective and safer antidote against cyanide poisoning than NaNO 2. • Methemoglobin-albumin clusters are more effective antidotes than sodium nitrite. • Methemoglobin-albumin clusters protect cytochrome c oxidase. • Combination use of thiosulfate potentiated the efficacy of metHb-albumin clusters. [ABSTRACT FROM AUTHOR]

Cyanide is a highly toxic chemical compound in all forms and used in many metallurgical and chemical synthesis methods. A huge amount of cyanide is discharged in effluents from different industries. Therefore, the removal of cyanide from aqueous solution by boron nitride (BN) nanotube as a membrane was investigated through molecular dynamics simulations. The considered system comprised a BN nanotube inserted between two graphene nanosheets and water containing cyanide ions. External pressure and electric fields were used for the removal of cyanide ions. Four types of armchair BN nanotubes were used with different diameter from 6.90 Å to 11.07 Å. Nanotubes performance relative to permeation of cyanide and water was different and the amount of species passing was dependent on the applied pressures, electric fields and the diameter of nanotubes. [ABSTRACT FROM AUTHOR]

Production of cyanide through biological and environmental processes requires the detoxification of this metabolic poison. In the 1960s, discovery of the β-cyanoalanine synthase ( β-CAS) pathway in cyanogenic plants provided the first insight on cyanide detoxification in nature. Fifty years of investigations firmly established the protective role of the β-CAS pathway in cyanogenic plants and its role in the removal of cyanide produced from ethylene synthesis in plants, but also revealed the importance of this pathway for plant growth and development and the integration of nitrogen and sulfur metabolism. This review describes the β-CAS pathway, its distribution across and within higher plants, and the diverse biological functions of the pathway in cyanide assimilation, plant growth and development, stress tolerance, regulation of cyanide and sulfide signalling, and nitrogen and sulfur metabolism. The collective roles of the β-CAS pathway highlight its potential evolutionary and ecological importance in plants. [ABSTRACT FROM AUTHOR]

Introduction:Dicobalt edetate is one of a number of cobalt compounds that have been studied in the treatment of cyanide poisoning, their efficacy being based upon the fact that cyanide combines with cobalt to form relatively non-toxic complexes. Inorganic cobalt salts are quite toxic (cyanide and cobalt antagonise one another's toxicity) and complexes such as dicobalt edetate were studied with the aim of identifying compounds that were less acutely toxic, but which retained the antidotal properties of cobalt salts. The proprietary preparation, Kelocyanor™, contains free cobalt and glucose as well as dicobalt edetate. Objective:The aim of this study was to evaluate the published evidence for the efficacy and adverse effects of dicobalt edetate. Methods:A Pubmed search was undertaken for the period 1961–September 2015. The search terms were “dicobalt edetate”, “cobalt edetate” and “Kelocyanor”, which produced 24 relevant citations. A review of the references in four relevant books (L'intoxication cyanhydrique et son traitement,Clinical and Experimental Toxicology of Cyanides,Antidotes for Poisoning by CyanideandAntidotes) produced three further relevant papers, making a total of 27 papers. Efficacy of dicobalt edetate:There is evidence from animal pharmacodynamic studies that dicobalt edetate is an effective cyanide antidote in experimental animals. Some 39 cases of human poisoning treated with dicobalt edetate have been reported, but in only nine cases were blood cyanide concentrations measured, although administration of dicobalt edetate procured survival in four of the seven patients with concentrations in the lethal range (>3.0 mg/L). It is unlikely that death in any of the adequately documented fatal cases was attributable to treatment failure with dicobalt edetate, as it is probable that they all had suffered anoxic brain damage before treatment could be initiated. Furthermore, in one case, acute gold toxicity contributed substantially to death. Adverse effects of dicobalt edetate:Adverse effects reported have included hypertension, tachycardia, nausea, retrosternal pain, sweating, palpebral, facial and laryngeal oedema, vomiting, urticaria and/or a feeling of impending doom. Such effects appear to be more prevalent where the antidote has been administered without evidence of substantial systemic poisoning or where other antidotes have been used which might have been expected also to combine with cyanide. Although the adverse effects observed were doubtless unpleasant, and some were severe, no fatal reactions were found. Conclusions:Dicobalt edetate is an effective cyanide antidote when given to patients with systemic cyanide poisoning, but it has the potential to give rise to adverse reactions, particularly when administered in the absence of intoxication. [ABSTRACT FROM AUTHOR]

Potassium cyanide (KCN) is an inhibitor of cytochrome C oxidase causing rapid death due to hypoxia. A well-characterized model of oral KCN intoxication is needed to test new therapeutics under the Food and Drug Administration Animal Rule. Clinical signs, plasma pH and lactate concentrations, biomarkers, histopathology, and cyanide and thiocyanate toxicokinetics were used to characterize the pathology of KCN intoxication in adult and juvenile mice. The acute oral LD50s were determined to be 11.8, 11.0, 10.9, and 9.9 mg/kg in water for adult male, adult female, juvenile male, and juvenile female mice, respectively. The time to death was rapid and dose dependent; juvenile mice had a shorter mean time to death. Juvenile mice displayed a more rapid onset and higher incidence of seizures. The time to observance of respiratory signs and prostration was rapid, but mice surviving beyond 2 hours generally recovered fully within 8 hours. At doses up to the LD50, there were no gross necropsy or microscopic findings clearly attributed to administration of KCN in juvenile or adult CD-1 mice from 24 hours to 28 days post-KCN challenge. Toxicokinetic analysis indicated rapid uptake, metabolism, and clearance of plasma cyanide. Potassium cyanide caused a rapid, dose-related decrease in blood pH and increase in serum lactate concentration. An increase in fatty acid-binding protein 3 was observed at 11.5 mg/kg KCN in adult but not in juvenile mice. These studies provide a characterization of KCN intoxication in adult and juvenile mice that can be used to screen or conduct preclinical efficacy studies of potential countermeasures. [ABSTRACT FROM AUTHOR]

Cyanide poisoning by accidental or intentional exposure poses a severe health risk. The current Food and Drug Administration approved antidotes for cyanide poisoning can be effective, but each suffers from specific major limitations concerning large effective dosage, delayed onset of action, or dependence on enzymes generally confined to specific organs. Dimethyl trisulfide (DMTS), a sulfur donor that detoxifies cyanide by converting it into thiocyanate (a relatively nontoxic cyanide metabolite), is a promising next generation cyanide antidote. Although a validated analytical method to analyze DMTS from any matrix is not currently available, one will be vital for the approval of DMTS as a therapeutic agent against cyanide poisoning. Hence, a stir bar sorptive extraction (SBSE) gas chromatography – mass spectrometry (GC–MS) method was developed and validated for the analysis of DMTS from rabbit whole blood. Following acid denaturation of blood, DMTS was extracted into a polydimethylsiloxane-coated stir bar. The DMTS was then thermally desorbed from the stir bar and analyzed by GC–MS. The limit of detection of DMTS using this method was 0.06 μM with dynamic range from 0.5–100 μM. For quality control standards, the precision, as measured by percent relative standard deviation, was below 10%, and the accuracy was within 15% of the nominal concentration. The method described here will allow further investigations of DMTS as a promising antidote for cyanide poisoning. [ABSTRACT FROM AUTHOR]