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Brazilian Journal of Microbiology :... 2015Ten bacterial strains that utilize cyanide (CN) as a nitrogen source were isolated from cassava factory wastewater after enrichment in a liquid media containing sodium...
Ten bacterial strains that utilize cyanide (CN) as a nitrogen source were isolated from cassava factory wastewater after enrichment in a liquid media containing sodium cyanide (1 mM) and glucose (0.2% w/v). The strains could tolerate and grow in cyanide concentrations of up to 5 mM. Increased cyanide levels in the media caused an extension of lag phase in the bacterial growth indicating that they need some period of acclimatisation. The rate of cyanide removal by the strains depends on the initial cyanide and glucose concentrations. When initial cyanide and glucose concentrations were increased up to 5 mM, cyanide removal rate increased up to 63 and 61 per cent by Bacillus pumilus and Pseudomonas putida. Metabolic products such as ammonia and formate were detected in culture supernatants, suggesting a direct hydrolytic pathway without an intermediate formamide. The study clearly demonstrates the potential of aerobic treatment with cyanide degrading bacteria for cyanide removal in cassava factory wastewaters.
Topics: Ammonia; Bacillus; Biodegradation, Environmental; Bioreactors; Cyanides; Formates; Glucose; India; Manihot; Pseudomonas putida; RNA, Ribosomal, 16S; Wastewater
PubMed: 26413045
DOI: 10.1590/S1517-838246320130516 -
Journal of Medical Toxicology :... Dec 2016Cyanide is a major chemical threat, and cyanide ingestion carries a higher risk for a supra-lethal dose exposure compared to inhalation but provides an opportunity for...
INTRODUCTION
Cyanide is a major chemical threat, and cyanide ingestion carries a higher risk for a supra-lethal dose exposure compared to inhalation but provides an opportunity for effective treatment due to a longer treatment window and a gastrointestinal cyanide reservoir that could be neutralized prior to systemic absorption. We hypothesized that orally administered cobinamide may function as a high-binding affinity scavenger and that gastric alkalinization would reduce cyanide absorption and concurrently increase cobinamide binding, further enhancing antidote effectiveness.
METHODS
Thirty New Zealand white rabbits were divided into five groups and were given a lethal dose of oral cyanide poisoning (50 mg). The survival time of animals was monitored with oral cyanide alone, oral cyanide with gastric alkalinization with oral sodium bicarbonate buffer (500 mg), and in combination with either aquohydroxocobinamide or dinitrocobinamide (250 mM). Red blood cell cyanide concentration, plasma cobinamide, and thiocyanate concentrations were measured from blood samples.
RESULTS
In cyanide ingested animals, oral sodium bicarbonate alone significantly prolonged survival time to 20.3 ± 8.6 min compared to 10.5 ± 4.3 min in saline-treated controls, but did not lead to overall survival. Aquohydroxocobinamide and dinitrocobinamide increased survival time to 64 ± 41 (p < 0.05) and 75 ± 16.4 min (p < 0.001), respectively. Compared to aquohydroxocobinamide, dinitrocobinamide showed greater systemic absorption and reduced blood pressure. Dinitrocobinamide also markedly increased the red blood cell cyanide concentration. Under all conditions, the plasma thiocyanate concentration gradually increased with time.
CONCLUSION
This study demonstrates a promising new approach to treat high-dose cyanide ingestion, with gastric alkalinization alone and in combination with oral cobinamide for treating a supra-lethal dose of orally administered cyanide in rabbits.
Topics: Administration, Oral; Analysis of Variance; Animals; Antacids; Antidotes; Blood Pressure; Cobamides; Cyanides; Disease Models, Animal; Eating; Erythrocytes; Humans; Male; Rabbits; Sodium Bicarbonate; Spectrum Analysis; Survival Rate; Thiocyanates; Time Factors
PubMed: 27631586
DOI: 10.1007/s13181-016-0566-4 -
Clinical Toxicology (Philadelphia, Pa.) Aug 2010Cyanide is a rapidly acting cellular poison, primarily targeting cytochrome c oxidase, and is a common occupational and residential toxin, mostly via smoke inhalation....
CONTEXT
Cyanide is a rapidly acting cellular poison, primarily targeting cytochrome c oxidase, and is a common occupational and residential toxin, mostly via smoke inhalation. Cyanide is also a potential weapon of mass destruction, with recent credible threats of attacks focusing the need for better treatments, as current cyanide antidotes are limited and impractical for rapid deployment in mass casualty settings.
OBJECTIVE
We have used mouse models of cyanide poisoning to compare the efficacy of cobinamide (Cbi), the precursor to cobalamin (vitamin B(12)), to currently approved cyanide antidotes. Cbi has extremely high affinity for cyanide and substantial solubility in water.
MATERIALS AND METHODS
We studied Cbi in both an inhaled and intraperitoneal model of cyanide poisoning in mice.
RESULTS
We found Cbi more effective than hydroxocobalamin, sodium thiosulfate, sodium nitrite, and the combination of sodium thiosulfate-sodium nitrite in treating cyanide poisoning. Compared to hydroxocobalamin, Cbi was 3 and 11 times more potent in the intraperitoneal and inhalation models, respectively. Cobinamide sulfite (Cbi-SO(3)) was rapidly absorbed after intramuscular injection, and mice recovered from a lethal dose of cyanide even when given at a time when they had been apneic for over 2 min. In range-finding studies, Cbi-SO(3) at doses up to 2000 mg/kg exhibited no clinical toxicity.
DISCUSSION AND CONCLUSION
These studies demonstrate that Cbi is a highly effective cyanide antidote in mouse models, and suggest it could be used in a mass casualty setting, because it can be given rapidly as an intramuscular injection when administered as Cbi-SO(3). Based on these animal data Cbi-SO(3) appears to be an antidote worthy of further testing as a therapy for mass casualties.
Topics: Administration, Inhalation; Animals; Antidotes; Cobamides; Cyanides; Dose-Response Relationship, Drug; Hydroxocobalamin; Injections, Intramuscular; Lethal Dose 50; Male; Mice; Mice, Inbred C57BL
PubMed: 20704457
DOI: 10.3109/15563650.2010.505197 -
Journal of Medical Toxicology :... Jun 2016Cyanide toxicity is common after significant smoke inhalation. Two cases are presented that provide framework for the discussion of epidemiology, pathogenesis,... (Review)
Review
Cyanide toxicity is common after significant smoke inhalation. Two cases are presented that provide framework for the discussion of epidemiology, pathogenesis, presenting signs and symptoms, and treatment options of inhalational cyanide poisoning. An evidence-based algorithm is proposed that utilizes point-of-care testing to help physicians identify patients who benefit most from antidotal therapy.
Topics: Academic Medical Centers; Algorithms; Antidotes; Biomarkers; Combined Modality Therapy; Decision Trees; Evidence-Based Emergency Medicine; Fellowships and Scholarships; Female; Gas Poisoning; Humans; Hydrogen Cyanide; Hydroxocobalamin; Male; Massachusetts; Point-of-Care Testing; Smoke Inhalation Injury; Toxicology; Workforce
PubMed: 26831054
DOI: 10.1007/s13181-016-0533-0 -
Clinical Toxicology (Philadelphia, Pa.) Jan 2020Cyanide is a metabolic poison used in multiple industries and is a high threat chemical agent. Current antidotes require intravenous administration, limiting their...
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. 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. 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). 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 ( = 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 ( ≤ 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. Sodium tetrathionate significantly improves survival and clinical outcomes in a large, swine model of acute cyanide poisoning.
Topics: Animals; Antidotes; Cyanides; Disease Models, Animal; Female; Injections, Intramuscular; Swine; Tetrathionic Acid
PubMed: 31008657
DOI: 10.1080/15563650.2019.1602272 -
British Journal of Pharmacology Jul 19801 The effects of intracarotid (i.a.) injections of acetylcholine (ACh) and sodium cyanide (NaCN) on baroreceptor activity recorded from the sinus nerve have been...
1 The effects of intracarotid (i.a.) injections of acetylcholine (ACh) and sodium cyanide (NaCN) on baroreceptor activity recorded from the sinus nerve have been investigated in cats anaesthetized with pentobarbitone.2 Two types of baroreceptor unit were recorded. The predominant type discharged at least 3 to 4 spikes per pulse wave at normal BP; they are referred to as ;polyspike' units and may have been associated with A fibres. The other type discharged a maximum of 1 to 3 spikes per pulse wave, even at high BP; they are referred to as ;few-spike' units and may have been from C fibres.3 NaCN had no direct effect on either type of baroreceptor unit, even when injected in high doses (2.04 to 5.1 mumol i.a.) which cause maximal chemoreceptor stimulation, and it is concluded that as far as the cat's carotid baroreceptors and chemoreceptors are concerned, NaCN is a specific chemoreceptor stimulant.4 ACh had no direct effect on polyspike baroreceptor units unless very high doses (1.83 mumol i.a.) were injected, when there was occasionally a transient slight increase in discharge. This effect appeared to be secondary to muscle contraction caused by ACh since it was not seen when an adequate neuromuscular-blocking dose of gallamine had been administered.5 ACh stimulated the few-spike type of baroreceptor unit, an effect which was dose-related and lasted for up to 3 s; the threshold dose for baroreceptor stimulation was higher than that needed to excite chemoreceptor units. The increased discharge also occurred during experiments in which gallamine had been administered. Only five of these units were recorded during the investigation, despite an intensive search for them.6 There was a delayed increase in baroreceptor sensitivity following the administration of ACh in doses (37 to 366 nmol i.a.) which had no immediate direct effect on polyspike baroreceptor discharge. The effect was evidently not secondary to changes in sympathetic nerve activity to the sinus region since it was observed during an experiment in which the ganglioglomerular nerves had been cut. Whether the increased sensitivity resulted from direct or indirect actions of ACh remains to be determined.7 It is concluded that low doses of ACh or other drugs with nicotinic properties are unlikely to evoke baroreceptor reflexes on intracarotid injection, although they may cause delayed changes in baroreceptor sensitivity. Higher doses of ACh do not directly affect baroreceptor polyspike (A fibre) units, but transient baroreflex changes might result from stimulation of baroreceptor few-spike (C fibre) units. It is most unlikely that NaCN has any direct effect on baroreceptor reflex activity when injected into the carotid artery in doses used to elicit chemoreceptor reflexes.
Topics: Acetylcholine; Animals; Carotid Sinus; Cats; Cyanides; Female; Male; Pressoreceptors; Sodium Cyanide; Sympathetic Nervous System
PubMed: 7397453
DOI: 10.1111/j.1476-5381.1980.tb07032.x -
Toxicology Letters Dec 2007Historically, antidotal potencies of cyanide antagonists were measured as increases in the experimental LD(50) for cyanide elicited by the antidotes. This required the...
Historically, antidotal potencies of cyanide antagonists were measured as increases in the experimental LD(50) for cyanide elicited by the antidotes. This required the use of high doses of cyanide following pre-treatment with the putative antidote. Since IACUC guidelines at our institutions strongly discourage LD(50) determinations: we developed a new test paradigm that allowed for maximal survival of cyanide-treated animals with greatly reduced numbers of animals. Symptoms of cyanide toxicity include disruption of neuromuscular coordination, i.e., the righting reflex. Therefore, to establish a dose-response curve, the times required for recovery of this righting reflex with increasing doses of cyanide were measured. A cyanide dose that disrupted this righting reflex for approximately 1h with minimal deaths was then selected. Using this paradigm, the current cyanide antidotes, viz., nitrite plus thiosulfate and hydroxocobalamin, as well as some potential cyanide antidotes that we developed, were evaluated pre- and post-cyanide. This allowed, for the first time, the assessment of the post-cyanide effectiveness of the current antidotes against cyanide poisoning in a live animal. In addition, some prototype compounds were found to exhibit antidotal efficacy not only when injected i.p. following cyanide, but also when administered orally 30 min before cyanide. Pre-cyanide oral efficacy suggests that such compounds have the potential of being administered prophylactically before exposure to cyanide. This new test paradigm was found to be a powerful tool for assessing the efficacies of some novel antidotes against cyanide and should be equally applicable for evaluating putative antidotes for other neurotoxins.
Topics: Animals; Antidotes; Drug Therapy, Combination; Hydroxocobalamin; Male; Mice; Neurotoxins; Reflex; Sodium Cyanide; Sodium Nitrite; Thiosulfates; Treatment Outcome
PubMed: 18024011
DOI: 10.1016/j.toxlet.2007.10.001 -
The Journal of Biological Chemistry Sep 1982Light-dependent membrane potentials, ionic fluxes, and volume changes were measured in two kinds of Halobacterium halobium cell envelope vesicles: one containing...
Light-dependent membrane potentials, ionic fluxes, and volume changes were measured in two kinds of Halobacterium halobium cell envelope vesicles: one containing bacteriorhodopsin and another halorhodopsin. Bacteriorhodopsin-containing vesicles extruded protons by a primary electrogenic mechanism and an energized volume decrease was observed. This was shown to be the consequences of sodium extrusion via proton/sodium antiport (which recirculated protons) and the accompanying passive chloride extrusion. Halorhodopsin-containing vesicles, in contrast, exhibited a volume increase during illumination, apparently caused by primary inward transport of chloride, and accompanied by passive cation (sodium or potassium, and proton) uptake. It was demonstrated that the chloride transport will occur against both electrical and concentration gradients across the vesicle membrane. Moreover, chloride was required on the vesicle exterior for the light-dependent generation of membrane potential, pH change, and swelling. These observations are inconsistent with an earlier proposal that halorhodopsin is an outward directed sodium pump, but suggest very strongly that it is an inward directed chloride pump. Quantitative arguments from the present work rule out a significant role of sodium in the functioning of halorhodopsin.
Topics: Bacteriorhodopsins; Biological Transport, Active; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Carotenoids; Cell Membrane; Chlorides; Halobacterium; Halorhodopsins; Hydrogen-Ion Concentration; Kinetics; Light
PubMed: 7107607
DOI: No ID Found -
Anesthesia and Analgesia Nov 2019Cytochrome aa3, the terminal component of the electron transport chain, absorbs near-infrared radiation (NIR) differentially depending on its oxidation state (Cytox),... (Comparative Study)
Comparative Study
BACKGROUND
Cytochrome aa3, the terminal component of the electron transport chain, absorbs near-infrared radiation (NIR) differentially depending on its oxidation state (Cytox), which can in theory be measured using near-infrared spectroscopy (NIRS) by relating light absorption at specific wavelengths to chromophore concentrations. Some NIRS algorithms use discrete wavelengths, while others analyze a band of NIR (broadband NIRS). The purpose of this study was to test the ability of discrete wavelength and broadband algorithms to measure changes in Cytox (primary outcome), and to determine whether or not a discreet wavelength NIRS algorithm could perform similarly to a broadband NIRS algorithm for the measurement of Cytox in a staged hypoxia-cyanide model (hypoxia and cyanide have oppositional effects on tissue saturation, but both cause cytochrome reduction).
METHODS
Twenty Sprague-Dawley rats were anesthetized with isoflurane, intubated, and instrumented. Blood pressure, end-tidal carbon dioxide, and arterial oxygen saturation were measured. A halogen light source transmitted NIR transcranially. NIR from the light source and the skull was transmitted to 2 cooled charge-coupled device spectrometers. Rats were subjected to anoxia (fraction of inspired oxygen, 0.0) until arterial oxygen saturation decreased to 70%. After recovery, 5 mg/kg sodium cyanide was injected intravenously. The cycle was repeated until cardiac arrest occurred. Relative concentrations of hemoglobin and cytochrome aa3 were calculated using discreet wavelength and broadband NIRS algorithms.
RESULTS
Hypoxia led to an increase in calculated deoxyhemoglobin (0.20 arbitrary units [AUs]; 95% confidence interval [CI], 0.17-0.22; P < .0001), a decrease in calculated oxyhemoglobin (-0.16 AUs; 95% CI, -0.19 to -0.14; P < .0001), and a decrease in calculated Cytox (-0.057 AUs; 95% CI, -0.073 to 0.0040; P < .001). Cyanide led to a decrease in calculated deoxyhemoglobin (-0.037 AUs; 95% CI, 0.046 to -0.029; P < .001), an increase in calculated oxyhemoglobin (0.053 AUs; 95% CI, 0.040-0.065; P < .001), and a decrease in calculated Cytox (-0.056 AUs; 95% CI, -0.064 to -0.048; P < .001). The correlations between "discreet" wavelength algorithms (using 4, 6, 8, and 10 wavelengths) and the broadband algorithm for the measurement of calculated Cytox were 0.54 (95% CI, 0.52-0.56), 0.87 (0.87-0.88), 0.88 (0.88-0.89), and 0.95 (0.95-0.95), respectively.
CONCLUSIONS
The broadband and 10 wavelength algorithm were able to accurately track changes in Cytox for all experiments.
Topics: Algorithms; Animals; Electron Transport Complex IV; Hemoglobins; Male; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; Spectroscopy, Near-Infrared
PubMed: 29916864
DOI: 10.1213/ANE.0000000000003572 -
Annals of Emergency Medicine Apr 2010Exposure to cyanide in fires and industrial exposures and intentional cyanide poisoning by terrorists leading to mass casualties is an ongoing threat. Current treatments...
STUDY OBJECTIVE
Exposure to cyanide in fires and industrial exposures and intentional cyanide poisoning by terrorists leading to mass casualties is an ongoing threat. Current treatments for cyanide poisoning must be administered intravenously, and no rapid treatment methods are available for mass casualty cyanide exposures. Cobinamide is a cobalamin (vitamin B(12)) analog with an extraordinarily high affinity for cyanide that is more water-soluble than cobalamin. We investigate the use of intramuscular cobinamide sulfite to reverse cyanide toxicity-induced physiologic changes in a sublethal cyanide exposure animal model and determine the ability of an intramuscular cobinamide sulfite injection to rapidly reverse the physiologic effects of cyanide toxicity.
METHODS
New Zealand white rabbits were given 10 mg sodium cyanide intravenously over 60 minutes. Quantitative diffuse optical spectroscopy and continuous-wave near-infrared spectroscopy monitoring of tissue oxyhemoglobin and deoxyhemoglobin concentrations were performed concurrently with blood cyanide level measurements and cobinamide levels. Immediately after completion of the cyanide infusion, the rabbits were injected intramuscularly with cobinamide sulfite (n=6) or inactive vehicle (controls, n=5).
RESULTS
Intramuscular administration led to rapid mobilization of cobinamide and was extremely effective at reversing the physiologic effects of cyanide on oxyhemoglobin and within deoxyhemoglobin extraction. Recovery time to 63% of their baseline values in the central nervous system occurred within a mean of 1,032 minutes in the control group and 9 minutes in the cobinamide group, with a difference of 1,023 minutes (95% confidence interval 116 to 1,874 minutes). In muscle tissue, recovery times were 76 and 24 minutes, with a difference of 52 minutes (95% confidence interval 7 to 98 minutes). RBC cyanide levels returned toward normal significantly faster in cobinamide sulfite-treated animals than in control animals.
CONCLUSION
Intramuscular cobinamide sulfite rapidly and effectively reverses the physiologic effects of cyanide poisoning, suggesting that a compact cyanide antidote kit can be developed for mass casualty cyanide exposures.
Topics: Animals; Antidotes; Cobamides; Cyanides; Disease Models, Animal; Hemoglobins; Injections, Intramuscular; Oxyhemoglobins; Rabbits; Spectroscopy, Near-Infrared; Time Factors
PubMed: 20045579
DOI: 10.1016/j.annemergmed.2009.12.002