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Cyanide poisoning poses a significant threat to burn patients exposed to smoke in residential or workplace fires, leading to central nervous system dysfunction, hemodynamic instability, cardiovascular collapse, and death. Prompt administration of an effective antidote is critical. Hydroxocobalamin, a form of vitamin B12, is the gold standard treatment for cyanide toxicity, by binding to cyanide molecules and converting them into non-toxic cyanocobalamin that is eliminated by the kidneys. This mechanism is distinct from previous cyanide antidotes, which induce the formation of methemoglobin to bind to cyanide. Recent case studies have reported elevated methemoglobin levels after hydroxocobalamin administration, raising concerns regarding its safety. The current study investigates smoke inhalation patients treated with hydroxocobalamin at a single institution Burn Unit in hopes of enhancing our understanding of the complexities surrounding cyanide antidote therapy. After Institutional Board Approval, a retrospective cohort study was conducted. Our sample comprised burn patients with inhalation injury admitted to a single institution from 2013 to 2023 and treated with hydroxocobalamin for suspected cyanide toxicity. We also analyzed a matched control cohort of similar patients with inhalation injury not treated with hydroxocobalamin. We analyzed changes and peaks in methemoglobin levels, lactate levels, blood urea nitrogen (BUN) and creatinine, ventilator days, % total body surface area (TBSA), various types of medications and dressings, and mortality. Statistical analyses included t-tests, chi-square, linear and logistic regressions, and correlation analysis. In the study, 36 patients with suspected inhalation injury were treated with hydroxocobalamin at the Los Angeles General (LAG) Burn Unit from 2013 to 2023, who were matched to 32 control patients with inhalation injury who were not treated with hydroxocobalamin. Demographic and baseline characteristics showed no statistically significant differences between the groups, including age, gender, BMI, and %TBSA. No significant differences were found in initial, final, peak, or change in methemoglobin levels. The study also revealed no significant disparities in initial lactate levels, mortality, kidney function tests, ventilator days, surgeries, or use of medications/treatments (e.g., Silvadene dressings, Vitamin C) between the two groups. When controlling for covariates, multiple linear regression analysis (age, gender, and %TBSA) indicated that hydroxocobalamin administration was not significantly associated with changes in methemoglobin or mortality. Increased %TBSA, however, was linked to elevated lactate levels. Our investigation sought to assess the potential risks associated with hydroxocobalamin administration in burn patients with concomitant inhalation injury. Contrary to our initial hypothesis, we found no statistically significant differences in methemoglobinemia, lactate levels, mortality, or kidney function. The influence of other factors, such as methemoglobinemia-inducing drugs or hydroxocobalamin's interference with co-oximetry, adds complexity. Although elevated methemoglobin levels were observed in some cases, their clinical significance was limited. However, this study's limitations, particularly the rarity of inhalation injury cases with concern for cyanide toxicity, warrant consideration. Further research is required to comprehensively elucidate the impact of hydroxocobalamin administration on burn patients' outcomes. • Hydroxocobalamin is a common antidote for suspected inhalation injury in burn patients. • Hydroxocobalamin does not lead to methemoglobinemia or increased mortality. • Hydroxocobalamin does not lead to significant changes in outcomes for burn patients. [ABSTRACT FROM AUTHOR]

To evaluate variations in diagnostic criteria and management recommendations for smoke inhalation injury (SII) amongst the burn networks of England, Scotland, and Wales. A descriptive cross-sectional study examining SII guidelines provided by adult burn units and centres in England, Scotland and Wales. All 16 adult burn units and centres responded. Fourteen (87.5 %) had guidelines. Due to sharing of guidelines, ten unique guidelines were assessed. Diagnostic criteria showed variability with no universal criterion shared amongst guidelines. Bronchoscopy was recommended by 90 % of guidelines, but the timing varied. The use of bronchoscopic scoring systems was recommended by four guidelines. Bronchoalveolar lavage (BAL) was recommended by four, with considerable variation in frequency and choice of lavage fluid. All guidelines advised at least one nebulised agent: heparin (n = 8); N-acetyl cysteine (NAC) (n = 8); or salbutamol (n = 8). All guidelines included advice on carbon monoxide poisoning; however, carboxyhaemoglobin (COHb) cut-off levels for treatment varied (5 % [n-4], 10 % [n = 3], 15 % [n = 1]). All recommended high-flow oxygen. Seven (70 %) guidelines offered guidance on cyanide poisoning. Reduced/altered consciousness was the only consistent diagnostic criterion. Five (50 %) guidelines provided intubation guidance, emphasising the role of a 'senior clinician' as the intubator. Ventilatory guidance appeared in eight guidelines, focusing on lung protective ventilation (n = 8); oxygenation goals (n = 3); and permissive hypercapnia (n = 3). Within lung-protective ventilation, advice on tidal volume (6, or 6–8 ml/kg) and plateau pressures (>30 cmH2O) were presented most commonly (n = 7). This study has outlined the substantial variations in guidance for the management of SII. The results underscore the need for a national guideline outlining a standardised approach to the diagnosis and management of SII, within the limitations of the current evidence. • No diagnostic criterion was shared amongst guidelines. • Considerable variability of guidance for bronchoscopy and bronchoalveolar lavage. • All guidelines advised at least one nebulised agent. • Carboxyhaemoglobin (COHb) cut-off levels for treatment varied greatly. • Lung protective ventilation was the focus of ventilatory guidance. [ABSTRACT FROM AUTHOR]

Multiple organ failure (MOF) is the leading cause of death in patients with burns requiring ICU admission. Quantifying the evolution of MOF, with the SOFA score, over the first few days after a severe burn may provide useful prognostic information. This retrospective cohort study aimed at evaluating the association between the evolution of the SOFA score between day 0 and day 3 and in-hospital mortality. All patients admitted for severe burns at the burn ICU of the Tours University Hospital between 2017 and 2020 and who stayed 3 days or more were included. Severe burns included: total body surface area burned (TBSA) ≥ 20 % or burns of any surface associated with one or more of the following items: (1) organ failure, (2) clinically significant smoke inhalation and/or cyanide poisoning, (3) severe preexisting comorbidities, (4) complex and specialized burn wound care. DeltaSOFA was defined as day 3 minus day 0 SOFA. One hundred and thirty-six patients were included. Median age was 52 years (38−70), median TBSA burned was 24 % (20−38), median day 0 SOFA was 2 (0−4) and median day 3 SOFA was 1 (0−5). In-hospital mortality was 10 %. There was a significant association between deltaSOFA and mortality that persisted after adjustment for age and TBSA (HR 1.37, 95 %CI 1.09–1.72, p < 0.01). Area under the receiver operating characteristics curve for the prediction of mortality by day 0 SOFA and deltaSOFA were 0.79 (95 %CI 0.69–0.89) and 0.83 (95 %CI 0.70–0.95) respectively. After exclusion of patients with TBSA burned< 15 %, deltaSOFA remained independently associated with mortality (HR 1.42 95 %CI 1.09–1.85, p < 0.01). In addition, SOFA variations allowed the identification of subgroups of patients with either very low or very high mortality. In patients with severe burns, SOFA score evolution between day 0 and day 3 may be useful for individualized medical and ethical decisions. Further multicenter studies are required to corroborate the present results. • SOFA score variation is associated with in-hospital mortality in patients with severe burns. • SOFA score variation identifies subgroups with low mortality in patients with severe burns. • SOFA score variation may help for ethical decisions in patients with severe burns. [ABSTRACT FROM AUTHOR]

Melanoma is the most common form of skin cancer. Given its high metastasis and high recurrence, its therapies are constantly updated. The study aims to prove the efficacy of sodium thiosulfate (STS), an antidote to cyanide or nitroprusside poisoning, in melanoma treatment. We tested the effect of STS by culturing melanoma cells (B16 and A375) in vitro and establishing melanoma mouse models in vivo. The proliferation and viability of melanoma cells were measured by the CCK-8 test, cell cycle assay, apoptosis analysis, wound healing assay, and transwell migration assay. The expression of apoptosis-related molecules, epithelial-mesenchymal transition (EMT)-associated molecules, and the Wnt/β-catenin signaling pathway-related molecules were determined by Western blotting and immunofluorescence. The high metastasis of melanoma is considered to be linked to the EMT process. The scratch assay using B16 and A375 cells also showed that STS could inhibit the EMT process of melanoma. We demonstrated that STS inhibited the proliferation, viability, and EMT process of melanoma by releasing H 2 S. STS-mediated weakening of cell migration was related to the inhibition of the Wnt/β-catenin signaling pathway. Mechanistically, we defined that STS inhibited the EMT process via the Wnt/β-catenin signaling pathway. These results suggest that the negative effect of STS on melanoma development is mediated by the reduction of EMT via the regulation of the Wnt/β-catenin signaling pathway, which provides a new clue to treating melanoma. • STS treatment can inhibit melanoma cell proliferation, viability, and EMT process. • STS inhibits melanoma development via releasing H 2 S. • STS inhibits the EMT process via downregulating the activity of the Wnt/β-catenin signaling pathway. [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]

Cyanide induces acute lethal poisoning resulting from inhibition of cytochrome c oxidase located in the complex IV (Complex IV) of mitochondria. However, current therapies for cyanide poisoning using hydroxocobalamin and nitrous acid compounds remain a clinical issue. Here, we show that liposome-encapsulated methemoglobin (metHb@Lipo), nanosized biomimetic red blood cells, replicate the antidotal mechanism of nitrous acid compounds against cyanide poisoning, achieving superior efficacy and fast action with no adverse effects. The structure of metHb@Lipo, which consists of concentrated methemoglobin in its aqueous core and a lipid membrane resembling the red blood cell membrane, provides favorable characteristics as a cyanide antidote, such as binding properties and membrane permeability. Upon cyanide exposure, metHb@Lipo maintained the mitochondrial function in PC12 cells, resulting in a cell viability comparable to treatment with nitrous acid compounds. In a mouse model of cyanide poisoning, metHb@Lipo treatment dramatically improved mortality with a rapid recovery from the symptoms of cyanide poisoning compared to treatment with nitrous acid compounds. Furthermore, metHb@Lipo also possesses satisfactory pharmacokinetic properties without long-term bioaccumulation and toxicity. Our findings showed a novel concept to develop drugs for cyanide poisoning and provide a promising possibility for biomimetic red blood cell preparations for pharmaceutical applications. [Display omitted] • metHb@Lipo is encapsulated methemoglobin in liposome, which mimics red blood cell. • metHb@Lipo replicates the antidotal mechanism of nitrite against cyanide poisoning. • metHb@Lipo possesses superior antidotal effect than nitrite and hydroxocobalamin. • metHb@Lipo has favorable pharmacokinetic properties and biocompatibility. [ABSTRACT FROM AUTHOR]

Cyanide is a typical toxic reducing agent prevailing in wastewater with a well-defined chemical mechanism, whereas its exploitation as an electron donor by microorganisms is currently understudied. Given that conventional denitrification requires additional electron donors, the cyanide and nitrogen can be eliminated simultaneously if the reducing HCN/CN− and its complexes are used as inorganic electron donors. Hence, this paper proposes anaerobic cyanides oxidation for nitrite reduction, whereby the biological toxicity and activity of cyanides are modulated by bimetallics. Performance tests illustrated that low toxicity equivalents of iron-copper composite cyanides provided higher denitrification loads with the release of cyanide ions and electrons from the complex structure by the bimetal. Both isotopic labeling and Density Functional Theory (DFT) demonstrated that CN−-N supplied electrons for nitrite reduction. The superposition of chemical processes reduces the biotoxicity and enhances the biological activity of cyanides in the CN−/Fe3+/Cu2+/ NO 2 – coexistence system, including complex detoxification of CN− by Fe3+, CN− release by Cu2+ from [Fe(CN) 6 ]3−, and NO release by nitrite substitution of −CN groups. Cyanide is the smallest structural unit of C/N-containing compounds and serves as a probe to extend the electron-donating principle of anaerobic cyanides oxidation to more electron-donor microbial utilization. [Display omitted] • A novel anaerobic cyanides oxidation and its metabolic pathway were found. • Complex detoxification of coexisting systems facilitates cyanide metabolisms. • Bimetallic modulation promotes the cyanide detoxification and electron release. • The probing role of cyanides reveals the bioavailability of N-containing compounds. [ABSTRACT FROM AUTHOR]

• Hydroxocobalamin is a cyanide poisoning antidote. • The drug turns plasma and urine red but does not trigger hemolysis index flagging. • Drug spiking studies reveal significant interference on a broad range of tests. • Sample identification & handling and result reporting protocols were developed. • Close communication with ED and ICU are required for identification of samples. Hydroxocobalamin (OHCob) is an antidote for cyanide poisoning in patients rescued from house fires and is known to cause interference with certain laboratory tests. Consensus is lacking on the extent of this interference and on how to handle these samples. The objectives of this study were to characterize OHCob interference across a wide range of laboratory tests and to develop protocols for identifying and reporting these samples. Patient plasma samples (n = 5) were spiked with OHCob (1.5 mg/mL) and compared to controls without this drug. A series of analytes were measured using chemistry, urinalysis, coagulation, hematology, and blood gas instruments. Dose-response testing was performed on a subset of assays that showed interferences ≥10%. Of the 77 analytes evaluated, 27 (35%) showed interference from OHCob, with chemistry and coagulation analytes showing the greatest effects. Of those affected, 22 analytes had a positive interference, whereas 5 analytes had negative interference. Dose-response studies showed dose-dependent increases and/or decreases consistent with initial spiking studies. Although red in colour, plasma samples with OHCob did not trigger hemolysis index flags, necessitating a special sample identification and reporting protocol. OHCob had significant effects on several analytes across different instruments. These findings led to the development of special sample handling and reporting protocols to identify OHCob samples and ensure only accurate results are released. It is vital for emergency departments to document and notify their laboratories whenever blood samples from these patients are drawn. [ABSTRACT FROM AUTHOR]

Smoke inhalation injury is common in victims of domestic fires, among whom children are the most vulnerable. Cyanide poisoning may occur in addition to carbon monoxide poisoning and is challenging to diagnose. In France, the recommended antidotes are hydroxocobalamin for cyanide and hyperbaric oxygen for carbon monoxide. We managed a 26-month-old girl who sustained smoke inhalation injury with both carbon monoxide and cyanide poisoning during a house fire. Despite hydroxocobalamin and sodium thiosulfate therapy combined with hyperbaric oxygen, she had residual neurological impairments 3 months after the injury. The treatment challenges and detailed neurological follow-up data are described. [ABSTRACT FROM AUTHOR]

This work clarifies the pyrite oxidation mechanism in the Cu2+–NH 3 –S 2 O 3 2− system and provides a theoretical basis for the regulation and control of gold leaching reagents therein. [Display omitted] • The mechanism of electrochemical pyrite oxidation in the Cu2+–NH 3 –S 2 O 3 2− system is probed by LSV, CV, EIS, AFM, XPS, and Raman spectroscopy. • The rate of pyrite surface reactions increased with increasing applied potential. • Thiosulphate concentration is shown to influence the dissolution of bulk pyrite by affecting its surface properties. • This work provides a theoretical basis for the regulation and control of gold leaching reagents therein. The nontoxicity, low cost, and environmental friendliness of the Cu2+–NH 3 –S 2 O 3 2− gold leaching system make it a viable alternative to cyanide-based systems. However, the strong influence of certain sulphide minerals (e.g., pyrite) on the performance of the former system complicates its compositional regulation. Herein, the mechanism of electrochemical pyrite oxidation in the Cu2+–NH 3 –S 2 O 3 2− system is probed by electrochemical techniques combined with surface analysis techniques. The results indicate that the anodic oxidation of pyrite can be assigned to active, passive, or transpassive regions, depending on the applied potential, with high potentials accelerating the reactions on the pyrite surface. Thiosulphate concentration is shown to influence the surface properties and the rate of surface reactions of pyrite. AFM images indicated that the morphological changes on the pyrite electrode surface became much rougher with increasing potential. Moreover, Raman spectroscopy and XPS provided strong evidence for the analysis of the surface species of pyrite surface oxidation. Our work will further explain and provide a mechanism for the oxidation of pyrite in the Cu2+–NH 3 –S 2 O 3 2− system. More importantly, this study is expected to be able to provide a theoretical basis for guiding the regulation and control of gold leaching reagent in the Cu2+–NH 3 –S 2 O 3 2− system. [ABSTRACT FROM AUTHOR]

Cyanide (both HCN and CN− are represented by CN) has multiple industrial applications, is commonly found in some foods, and is a component of fire smoke. Upon exposure, CN blocks production of adenosine triphosphate, causing cellular hypoxia and cytotoxic anoxia, which can eventually result in death. Considering CN's quick onset of action and the long analysis times associated with current techniques, the objective of this study was to develop and validate a rapid and field-portable sensor to detect blood CN concentrations focusing on both concentration and diagnostic accuracy. The sensor takes advantage of the chemical properties of CN by converting it exclusively to HCN via acidification of whole blood. High-speed headspace transfer is used to deliver HCN to a capture solution where it is reacted with naphthalene dialdehyde and taurine to produce a fluorescent β-isoindole product. Simple spectrofluorometric analysis of the product provides quantitative analysis of CN from whole blood in 60 s and requires only 25 μL of blood (obtainable via fingerstick). A limit of detection of 5 μM, a linear range of 10–200 μM (with ≥15 μM considered CN exposed), and excellent accuracy (100 ± 15%) and precision (≤15.2% relative standard deviation) were obtained. To evaluate the diagnostic accuracy of the sensor, rabbit blood samples (N = 190, including 24 blinded samples) were analyzed by both the sensor and a lab-based spectrophotometric method. An excellent positive correlation was obtained between the sensor and the lab-based method (R2 ˃ 0.995) confirming the concentration accuracy of the CN sensor. Moreover, the sensor produced no false positives or negatives when diagnosing CN poisoning. Image 1 • A rapid and field-portable sensor was developed for blood cyanide (CN) analysis. • The sensor analyzes blood CN concentrations within 60 s, requiring 25 μL of blood. • Exposed and non-exposed rabbit blood (N = 190) were analyzed with the CN sensor. • The sensor produced 100% diagnostic accuracy with no false positives or negatives. • The CN sensor was validated using lab-based spectrophotometric and GC-MS methods. [ABSTRACT FROM AUTHOR]

In recent years, Cobinamide (Cbi) has shown promise as a therapeutic for cyanide poisoning. There are several forms of Cbi based on the identity of the ligands bound to the cobalt in Cbi and these different forms of Cbi have divergent behavior (e.g., the aquo and hydroxo forms of Cbi readily bind to proteins, limiting their distribution significantly, whereas [Cbi(CN) 2 ] does not). While current analysis techniques only measure total Cbi, methods to elucidate the behavior of 'available' Cbi versus cyanide-complexed Cbi would be valuable for biomedical and pharmacokinetic studies. Therefore, a method was developed for the analysis of cyanide-complexed Cbi in plasma via liquid chromatography tandem mass spectrometry (LC-MS-MS). Plasma samples were prepared by denaturing proteins with 10% ammonium hydroxide in acetonitrile. The resulting mixture was centrifuged, and the supernatant was removed, dried, and reconstituted. Cyanide-complexed Cbi was then analyzed via LC-MS-MS. The limit of detection was 0.2 μM, and the linear dynamic range was between 1 and 200 μM. The accuracy was 100 ± 17% and the precision, measured by relative standard deviation (%RSD), was ≤18.5%. Carryover, a severe problem when analyzing Cbi via liquid chromatography was eliminated using a polymeric-based stationary phase (PLRP-S) and a controlled washing protocol. The method allowed evaluation of the cyanide-bound and 'available' Cbi from treated animals and, when paired with a method for total Cbi analysis, allows for estimation of Cbi utilization when treating cyanide poisoning. • This method is the first to analyze cyanide-bound cobinamide directly as opposed to total cobinamide • This work definitively showed, for the first time, that the mechanism of cobinamide protection is direct binding of cyanide • A detailed cleaning procedure was shown to eliminate the well-known problem of cobinamide carryover in chromatography systems • Combination of this method with total cobinamide analysis allowed for estimation of the available cobinamide [ABSTRACT FROM AUTHOR]

The study of non-precious metal catalysts (NPMCs) as alternatives to platinum for oxygen reduction is crucial if the use of fuel cells is to become more widespread. Among NPMCs, pyrolyzed catalysts (Fe-N-C) are particularly promising in both basic and acid media. The characterization of active sites and the understanding of the oxygen reduction reaction (ORR) mechanism are crucial for the design of active Fe-N-C catalysts. In this study, we have tested the involvement of the metal centre in the ORR process at pH 13 for two pyrolyzed iron porphyrins. The pyrolyzed catalysts present a FeN4 active site structure similar to that of the porphyrin precursors. Regarding the mechanism, we have found evidence for the crucial role of the Fe(II) centres. There is a direct relation between the Fe(III)/(II) redox transition of the catalysts and the onset potential of the ORR, showing that the electrogeneration of Fe(II) from Fe(III)OH– controls the catalysis. The poisoning of iron centres with CN− induces a decrease in the ORR activity. However, the onset potential for H 2 O 2 generation remains unchanged. The Tafel plots show two different slopes at high and low overpotentials. Based on these results, we propose two different mechanisms, both dependent on the redox potential of the catalysts and the Fe O 2 binding energy. Unlabelled Image • Fe-N-C catalysts show a connection between the redox potential, Fe(III)/(II), with the onset potential of the ORR at pH 13. • Two Tafel slopes are found, the changes in slopes take place close to the redox potential of the catalysts. • The residual H 2 O 2 production is due to the nitrogen and oxidized groups present in the carbon matrix. • Two mechanisms are proposed, both dependent on the redox potential of the catalysts and the Fe(II)-O 2 binding energy. [ABSTRACT FROM AUTHOR]

Highlights • Innovative hydrophilic interaction d-SPE protocol for ATCA was proposed. • d-SPE protocols for ATCA on MCX and MIP sorbents were optimized. • Higher clean-up ability and efficiency of recovery was noted for MCX. • MCX and MIP surfaces in silico models were used for analysis of ATCA interactions. • Analytical method for ATCA analysis in post mortem blood was validated. Abstract In this paper, we proposed an innovative hydrophilic interaction dispersive solid-phase extraction (HI-d-SPE) protocol suitable for the isolation of the potential cyanide intoxication marker, 2-aminothiazoline-4-carboxylic acid (ATCA), from such complicated matrix as post-mortem blood. To create an optimal HI-d-SPE protocol, two sorbents were used: a molecularly imprinted polymer (MIP) and commercially available Oasis-MCX®. The latter sorbent was identified as more recovery-efficient with higher clean-up abilities in a carefully optimized process. Computational analysis was employed to provide insight into the adsorption mechanism of the two selected sorbents. The theoretical results were in agreement with the experiment regarding the efficiency of the sorbent. HI-d-SPE was successfully applied to the analysis of ATCA in 20 post-mortem blood samples using LC–MS/MS. The analytical performance of the method was finally compared to prior existing methods, in turn revealing its superiority. [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]

The purpose of this research work was to prepare nanosized formulation of alpha ketoglutarate as dry powder inhaler for cyanide poisoning. Nanosizing can be approached by solid phase and liquid phase method. The different conditions encountered in both these approaches can greatly affect the particle characteristics. In this study milling and precipitation technique were compared to study their effect on α-KG particles characteristics. Differences in choice of stabilizers were observed between the two processing techniques. Sonication processes followed by HPH produced small sized particles in which Pluronic F68 was employed as stabilizing agent. Precipitation approach produced ultrafine drug particles by utilizing combination of stabilizers (PVA + PEG 400). Amongst the two sonication processes, probe sonication process produced well stabilized small sized particles. The designed particles showed 43.13 ± 2.36% lung deposition when compared with ultrasonication and precipitation technique that showed 31.69% and 21.67% respirable fraction. The MMAD of the designed particles was found suitable for deep alveolar deposition. Clinical studies (Phase-I trial) showed whole lung deposition of 52.51% for DPI. The P/C ratio was found to be 1.02 suggesting uniform distribution of particles in different lung compartments. [ABSTRACT FROM AUTHOR]

Cyanide tailings are the bulk solid waste generated by the production processes of gold mines. Since the highly toxicity of cyanide affects its disposal and comprehensive utilization, a decyanation treatment is needed. However, wide-ranging industrial uses of the current decyanation methods are restricted due to the treatment effects and costs. Based on the natural degradation method, the cyanide treatment effect was enhanced by raising the treatment temperature, increasing the ultraviolet (UV) irradiation and turning the pile periodically. Using the Arrhenius equation, the activation energies of the cyanide hydrolysis reactions were calculated as 52.22 kJ/mol and 34.59 kJ/mol for heating alone and for heating combined with UV irradiation, respectively. At 60 ℃, the cyanide tailings reached the discharge standard (leachate, total cyanide (CNt)< 5 mg/L) after 8 h of treatment. Moreover, after adding UV irradiation (with an intensity of 120 μW/cm2) and a hydrogen peroxide spray (spraying intensity, 2 mL/kg) to the above conditions and shortening the treatment time to 7 h, the cyanide tailings reached the standard for use in building materials (leachate, CN t <0.5 mg/L). Based on these results, UV irradiation, ventilation, spraying and pile-turning were integrated into the solar drying room to form an enhanced natural degradation system, which was applied in the semi-industrial scale treatment of the cyanide tailings. The results showed that the cyanide tailings consistently met the standards for discharge and use in building materials, successfully verified the conditions and effects of the laboratory treatment, and reduced the treatment cost by more than 50 %. [Display omitted] • Cyanide was mainly distributed in the liquid of the tailings and was removed by volatilization and hydrolysis. • The effects of temperature, UV intensity, turning and reagent spraying on cyanide removal were investigated. • The equation and activation energy of cyanide hydrolysis under heating and UV irradiation were analyzed. • Two methods were designed to meet the different standard requirements for treating cyanide tailings. • Designed an enhanced natural degradation system and completed semi-industrial validation tests. [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]

Cyanide is a metabolic poison that inhibits cytochrome c oxidase. Its broad applications in manufacturing and history as an agent of warfare/terror highlight the limitations in approved cyanide antidotes for mass casualties. Sulfanegen, a pre-clinical antidote for cyanide poisoning, exploits an endogenous detoxification pathway and should be amenable to mass-casualty scenarios. Because human studies are unethical, determination of appropriate animal species as models in translational studies for FDA approval under the “Animal Rule” are critical. Here, we compared the specific activities of mercaptopyruvate sulfurtransferase (MST, required for sulfanegen’s activity), across common laboratory models of cyanide intoxication, and humans. Human MST activities in erythrocytes (measured as micromole pyruvate/min/10 6 rbc) were closest to those of Swiss-Webster mice and NZW rabbits. Similar species were selected for a more detailed tissue-specific comparison of MST activities. NZW Rabbits were closest to humans in the liver and kidney mitochondrial fractions, the Swiss-Webster mouse was closest to humans in the liver cytosolic fraction, while C57BL/6 mouse was closest in the kidney cytosolic fraction. These data comparing MST activities in animal models will help justify the use of those specific animals per the animal rule. Interestingly, statistically significant differences were found in MST activities of liver mitochondria between human smokers and non-smokers (p = 0.0030). [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]

Using a matched case-control design, we sought to determine whether the odds of konzo, a distinct spastic paraparesis associated with food (cassava) cyanogenic exposure in the tropics, were associated with lower cyanide detoxification rates (CDR) and malnutrition. Children with konzo (N = 122, 5-17 years of age) were age- and sex-matched with presumably healthy controls (N = 87) and assessed for motor and cognition performances, cyanogenic exposure, nutritional status, and cyanide detoxification rates (CDR). Cyanogenic exposure was ascertained by thiocyanate (SCN) concentrations in plasma (P-SCN) and urine (U-SCN). Children with a height-for-age z-score (HAZNCHS) < -2 were classified as nutritionally stunted. CDR was measured as time required to convert cyanide to SCN, and expressed as ms/μmol SCN/mg protein or as mmolSCN/ml plasma/min. Mean (SD) U-SCN in children with konzo was 521.9 (353.6) μmol/l and was, significantly higher than 384.6 (223.7) μmol/l in those without konzo. Conditional regression analysis of data for age- and sex-matched case-control pairs showed that konzo was associated with stunting (OR: 5.8; 95% CI: 2.7-12.8; p < 0.01; N = 83 paired groups) and higher U-SCN (OR: 1.1; 95% CI: 1.02-1.20 per 50-μmol increase in U-SCN; p = 0.02; N = 47 paired groups). After adjusting for stunting and U-SCN, the odds of developing konzo was reduced by 63% (95% CI: 11-85%, p = 0.03; N = 41 paired groups) for each 5 mmol SCN/(ml plasma/min)-increase in CDR. Linear regression analysis indicated a significant association between BOT-2 or KABC-II scores and both the HAZNCHS z-score and the U-SCN concentration, but not the CDR. Our findings provide evidence in support of interventions to remove cyanogenic compounds from cassava prior to human consumption or, peharps, enhance the detoxification of cyanide in those relying on the cassava as the main source of food. [ABSTRACT FROM AUTHOR]

The antidotal potency of dimethyl trisulfide (DMTS) against cyanide poisoning was discovered and investigated in our previous studies. Based on our results it has better efficacy than the Cyanokit and the Nithiodote therapies that are presently used against cyanide intoxication in the US. Because of their absence in the literature, the goal of this work was to develop analytical methods for determining DMTS from blood and brain that could be employed in future pharmacokinetic studies. An HPLC-UV method for detection of DMTS from blood, a GC–MS method for detection of DMTS from brain, and associated validation experiments are described here. These analytical methods were developed using in vitro spiking of brain and blood, and are suitable for determining the in vivo DMTS concentrations in blood and brain in future pharmacokinetic and distribution studies. An important phenomenon was observed in the process of developing these methods. Specifically, recoveries from fresh blood spiked with DMTS were found to be significantly lower than recoveries from aged blood spiked in the same manner with DMTS. This decreased DMTS recovery from fresh blood is important, both because of the role it may play in the antidotal action of DMTS in the presence of cyanide, and because it adds the requirement of sample stabilization to the method development process. Mitigation procedures for stabilizing DMTS samples in blood are reported. [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]

Introduction: Hydroxocobalamin has been available for use for suspected cyanide toxicity in smoke inhalation patients in the United States since 2006. Our study compares outcomes of patients who received hydroxocobalamin to historical controls who did not.Methods: In this retrospective review, patients administered hydroxocobalamin (2008-2014) were compared to historical controls (2002-2008). Patients <18 years, patients who received an alternate antidote, and patients without suspicion of smoke inhalation injury were excluded. Mortality was the primary outcome. Secondary outcomes evaluated were 7-day change in creatinine, culture-proven pneumonia, days on mechanical ventilation, ventilator- free days (VFD), ICU length of stay (ICU LOS), and hospital length of stay (HLOS).Results: A total of 138 patients in the hydroxocobalamin group and 135 in the control group were identified. Mortality rate was similar between both groups (29% vs. 28%, p=0.90). Hydroxocobalamin was associated with lower pneumonia rate (23% vs. 49%, p<0.01), less ventilator days (4 days vs. 7 days, p<0.01), and increased VFD (20 days vs. 11 days, p=0.01) compared to controls. Shorter ICU LOS (6 days vs. 10 days, p=0.03) and a trend toward lower HLOS (7 day vs. 11 days, p=0.06) were also found in patients who received hydroxocobalamin.Conclusions: Routine administration was associated with lower rate of pneumonia, faster liberation from the ventilator, and reductions in intensive care unit stay. Burn centers should consider its empiric use in suspected smoke inhalation patients. [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]

• ATCA is a promising marker of cyanide intoxication. • ATCA in postmortem dried blood spot sample was analyzed by LC/ESI − MS/MS. • Dried blood spot is a powerful tool for forensic toxicological testing. 2-Aminothiazoline-4-carboxylic acid (ATCA), which is produced by the reaction of cyanide with endogenous cystine, is a promising biomarker of cyanide exposure because of its physicochemical stability. Analysis of more stable metabolite than the toxic gas itself is sometimes useful for postmortem diagnosis of gas poisoning. Here, we developed and validated an approach that uses liquid chromatography coupled with electrospray ionization−tandem mass spectrometry for quantifying ATCA in dried blood spot (DBS) samples. The linearity of the calibration curve was good in the concentration range of 20–1500 ng/mL. Our method allows for repeatable and the accurate quantification of ATCA, with intra- and inter assay coefficients of variation of below 7.8 % and below 9.3 %, respectively. In addition, the concentration of ATCA in DBSs remained stable for at least one month when stored at −20°C. Our results indicated that our analytical approach can be used to determine past exposure to higher doses of cyanide. In a comparison of ATCA concentrations in DBSs obtained from cadavers with various causes of death, significantly higher ATCA concentrations were observed in fire victims than in non-fire victims, confirming that fire victims inhale large amounts of cyanide gas. Thus, here we extended the possible uses of DBS for quantification of ATCA to forensic toxicological testing for cyanide poisoning. [ABSTRACT FROM AUTHOR]

[Display omitted] • A facile and rapid SERS method for conjugated cyanide in blood using a gold coating nanoporous AAO membrane was developed. • The functionalized Au/AAO membrane exhibited high enhancement for SERS detection of cyanide. • The whole analysis could be finished in 2 min using a drop fingertip blood with LOD of 10 ng/mL. • The novel approach would be beneficial to diagnosis of cyanide poisoning in clinical and forensic applications. Rapid and sensitive detection of cyanide (free and conjugated) in blood samples is of vital significance for the clinical treatments and forensic verifications of cyanide poisoning. To overcome the disadvantages of conventional in-field detection methods, a facile, rapid and sensitive surface enhanced Raman spectroscopy (SERS) method for the analysis of free and conjugated cyanide using functionalized nanoporous anodic aluminium oxide (AAO) membrane coupled with hand-held Raman spectrometer has been developed in this study. A gold coating nanoporous AAO membrane with a high specific surface area, appropriate surface roughness and super-hydrophobicity has been prepared. The significant SERS signals enhancement benefiting from the high enrichment capacity and strong plasmonic hot-spots effects of the membrane has been achieved for hydrocyanic acid (HCN). Optimal parameters, including substrate modification, dissociation and capture conditions for blood samples have been investigated. The conjugated cyanide in the fingertip blood could be effectively liberated by the addition of H 3 PO 4 and NaBH 4 , followed by the capture of HCN on the membrane and analyzed based on SERS. The whole detection procedure only needed 2 min, and the limit of detection could reach 10 ng/mL in only ∼ 50 μL fingertip blood. Therefore, this approach is expected to be a powerful point of care testing (POCT) tool for the diagnosis of cyanide poisoning in clinical and forensic applications. [ABSTRACT FROM AUTHOR]

The current suite of Food and Drug Administration (FDA) approved antidotes (i.e., sodium nitrite, sodium thiosulfate, and hydroxocobalamin) are effective for treating cyanide poisoning, but individually, each antidote has major limitations (e.g., large effective dosage or delayed onset of action). To mitigate these limitations, next-generation cyanide antidotes are being investigated, including 3-mercaptopyruvate (3-MP) and cobinamide (Cbi). Analytical methods capable of detecting these therapeutics individually and simultaneously (for combination therapy) are essential for the development of 3-MP and Cbi as potential cyanide antidotes. Therefore, a liquid chromatography–tandem mass-spectrometry method for the simultaneous analysis of 3-MP and Cbi was developed. Sample preparation of 3-MP consisted of spiking plasma with an internal standard ( 13 C 3 -3-MP), precipitation of plasma proteins, and derivatizing 3-MP with monobromobimane to produce 3-mercaptopyruvate-bimane. Preparation of Cbi involved denaturing plasma proteins with simultaneous addition of excess cyanide to convert each Cbi species to dicyanocobinamide (Cbi(CN) 2 ). The limits of detection for 3-MP and Cbi were 0.5 μM and 0.2 μM, respectively. The linear ranges were 2–500 μM for 3-MP and 0.5–50 μM for Cbi. The accuracy and precision for 3-MP were 100 ± 9% and <8.3% relative standard deviation (RSD), respectively. For Cbi(CN) 2 , the accuracy was 100 ± 13% and the precision was <9.5% RSD. The method presented here was used to determine 3-MP and Cbi from treated animals and may ultimately facilitate FDA approval of these antidotes for treatment of cyanide poisoning. [ABSTRACT FROM AUTHOR]

• ATCA has been proposed as a stable diagnostic marker of cyanide poisoning. • Blood ATCA concentrations are affected by both age and sex in non-fire victims. • In fire victims, ATCA concentrations were correlated with increasing CO-Hb. Recently, 2-aminothiazoline-4-carboxylic acid (ATCA), a cyanide (CN) metabolite, has been proposed as a stable diagnostic marker of CN poisoning. In this study, liquid chromatography coupled with electrospray ionization – tandem mass spectrometry was used to quantify ATCA concentrations in human postmortem blood samples, and differences in ATCA concentrations according to age and sex were determined. Both age and sex had significant effects on blood ATCA concentrations. Although ATCA concentrations exhibited an inverted U shape with increasing age in men, in women ATCA concentrations plateaued at around 40–59 years of age. There were significant differences between the sexes in ATCA concentrations for the 20–39 and 40–59 year age groups (P < 0.05 and P < 0.01, respectively). Correlations between ATCA concentrations and carboxyhemoglobin (CO-Hb) saturation were also examined in fire victims. ATCA concentrations increased significantly with increasing CO-Hb saturation (r = 0.382, P < 0.01). In addition, ATCA concentrations were also correlated to CN concentrations (r = 0.309, P < 0.05). The results of our study may provide novel information about the contribution of CN poisoning to the cause of death at fire scenes. [ABSTRACT FROM AUTHOR]

• Cbi(AT) 2 is a potent antidote for cyanide, hydrogen sulfide and methanethiol. • The developed method is the first to analyze Cbi(AT) 2 in any biological matrix. • The method is sensitive (LOD = 0.3 μM) and has a wide dynamic range (2 – 500 μM). • Cbi(AT) 2 was easily detected in the plasma of Cbi(AT) 2 -treated swine. • Day-to-day carryover, a major problem for Cbi analysis, was eliminated in < 1 h. Cyanide, hydrogen sulfide, and methanethiol are common toxic inhalation agents that inhibit mitochondrial cytochrome c oxidase and result in cellular hypoxia, cytotoxic anoxia, apnea, respiratory failure, cardiovascular collapse, seizure and potentially death. While all are occupational gas exposure hazards that have the potential to cause mass casualties from industrial accidents or acts of terrorism, only cyanide has approved antidotes, and each of these has major limitations, including difficult administration in mass-casualty settings. While bisaminotetrazole cobinamide (Cbi(AT) 2) has recently gained attention because of its efficacy in treating these metabolic poisons, there is no method available for the analysis of Cbi(AT) 2 in any biological matrix. Hence, in this study, a simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the analysis of Cbi(AT) 2 in swine plasma. The method is extremely simple, consisting of protein precipitation, separation and drying of the supernatant, reconstitution in an aqueous solvent, and LC-MS/MS analysis. The method produced an LOD of 0.3 μM with a wide dynamic range (2 – 500 μM). Inter- and intraassay accuracies (100 ± 12 % and 100 ± 19 %, respectively) were acceptable and the precision (<12 % and < 9 % relative standard deviation, respectively) was good. The developed method was used to analyze Cbi(AT) 2 from treated swine and the preliminary pharmacokinetic parameters showed impressive antidotal behavior, most notably a long estimated elimination half-life (t 1/2 = 37.5 h). This simple and rapid method can be used to facilitate the development of Cbi(AT) 2 as a therapeutic against toxic cyanide, hydrogen sulfide and methanethiol exposure. [ABSTRACT FROM AUTHOR]

Abstract: Background: Historically, methylene blue (MB) has been used for multiple purposes, including as an antidote for toxin-induced and hereditary methemoglobinemia, ifosfamide-induced encephalopathy, and ackee fruit and cyanide poisoning; as an aniline dye derivative, antimalarial agent, and antidepressant. Discussion: Most recently, the use of MB has been advocated as a potential adjunct in the treatment of shock states. Our article reviews the role of MB in septic shock, anaphylactic shock, and toxin-induced shock. MB is proposed to increase blood pressure in these shock states by interfering with guanylate cyclase activity, and preventing cyclic guanosine monophosphate production and vasodilatation. Summary: MB may be an adjunct in the treatment of septic shock, anaphylactic shock, and toxin-induced shock. [Copyright &y& Elsevier]

Highlights: [•] The toxicokinetic behavior of α-KgCN in swine was investigated. [•] Measuring plasma α-KgCN provides definitive confirmation of cyanide exposure. [•] Treatment of cyanide poisoning with cobinamide renders α-KgCN an ineffective diagnostic marker. [ABSTRACT FROM AUTHOR]

Abstract: Development of nano alpha-ketoglutarate (A-KG) nebulization formulation for neutralization of inhaled cyanide ion toxicity. Objectives of the present study were to (a) develop a novel A-KG nebulization formulation against cyanide poisoning, particularly hydrogen cyanide gas (b) validate its respiratory fraction in vitro and in vivo, and (c) create its pharmacokinetic data in human volunteers. The formulation was optimized on the basis of particle size of aerosolized droplets after nebulization in 6 volunteers. Gamma scintigraphy was used to quantify total and regional lung deposition of nebulized A-KG after radiolabeling it with Technetium-99m. The formulation was optimized using 30% ethanol–saline with particle size in the range of 300–500nm. In vitro and in vivo studies showed that drug nebulization resulted in a significant respirable fraction of 65±0.6% with whole lung deposition of 13±1%. Human pharmacokinetic data was derived in 6 healthy human volunteers with peak serum concentration (C max) of 39±3μg/ml, while the area under curve (AUC) after inhalation was 376±23μg×h/ml indicating that the drug was rapidly and completely absorbed when targeted directly to lungs. Significant lung deposition of A-KG was achieved with the developed formulation. The formulation appears to have several advantages, including the potential of neutralizing inhaled CN− ions in the lungs themselves. It is a safe and efficacious procedure, suitable for hospital or ambulance use in accidental cyanide poisoning cases, or as a preventive approach for fire-rescue teams. [Copyright &y& Elsevier]

Abstract: Cassava contains cyanogenic glucosides which are hydrolysed by an enzyme linamarase to produce cyanohydrins which breakdown to toxic cyanide. Cyanide ingestion from bitter cassava can cause cyanide poisoning sometimes leading to death and also konzo, an irreversible paralysis of the legs which occurs mainly in children and young women. In 2005 we developed a simple wetting method that reduces the total cyanide content of cassava flour 3–6-fold. It involves wetting the flour, spreading it in a thin layer in the shade for 5h and using it the same day to make traditional thick porridge (ugali). The method was readily accepted by rural women and requires no additional equipment or water. Laminated, illustrated posters describing the method are available for free in ten languages, see http://online.anu.edu.au/BoZo/CCDN/. An equally effective treatment method is to expose wet flour in a thin layer in the sun for 2h. Projects for rehabilitation and prevention of konzo occurred in Mozambique in 2007 and in 2008–2009 in Tanzania, funded by AusAID. The Ministry of Health in Mozambique is now using our posters in Macua. In Uvira DRC, the wetting method has been taught in many villages and over 1200 posters distributed. [Copyright &y& Elsevier]

Abstract: Hydroxocobalamin, a precursor of vitamin B12, has a history of use in the prehospital setting in France for cyanide poisoning, particularly that associated with smoke inhalation. Because cyanide poisoning by ingestion is less common than smoke inhalation-associated cyanide poisoning, less information is available on prehospital use of hydroxocobalamin to treat cyanide poisoning by ingestion. This report describes a case of prehospital use of hydroxocobalamin for poisoning by ingestion of cyanide. The case supports the efficacy of hydroxocobalamin for acute cyanide poisoning caused by ingestion of a cyanide salt. No adverse events attributed to hydroxocobalamin were observed. [ABSTRACT FROM AUTHOR]

Abstract: In 2005 a simple wetting method was developed that reduced total cyanide content of cassava flour 3–6-fold. The method involved spreading wet flour in a thin layer and standing in the shade for five hours to allow evolution of HCN gas. We found that breakdown of linamarin catalysed by linamarase to acetone cyanohydrin, followed by its spontaneous decomposition to HCN and acetone was greatly increased by standing the wet flour in the sun. Treatment for two hours in the sun gave the same amount of total cyanide remaining as five hours in the shade. This rapid treatment in the sun may be more acceptable to rural women in Democratic Republic of Congo, than five hours in the shade. The two methods are offered as alternatives for use in rural Africa. With adequate linamarase present the residual cyanogen remaining after the wetting treatment was acetone cyanohydrin. [Copyright &y& Elsevier]

Abstract: Background: Inhalation of hydrogen cyanide from smoke in structural fires is common, but cardiovascular function in these patients is poorly documented. Objective: The objective was to study the cardiac complications of cyanide poisoning in patients who received early administration of a cyanide antidote, hydroxocobalamin (Cyanokit®; Merck KGaA, Darmstadt, Germany [in the United States, marketed by Meridian Medical Technologies, Bristol, TN]). Methods: The medical records of 161 fire survivors with suspected or confirmed cyanide poisoning were reviewed in an open, multicenter, retrospective review of cases from the Emergency Medical Assistance Unit (Service d''Aide Médical d''Urgence) in France. Results: Cardiac arrest (61/161, 58 asystole, 3 ventricular fibrillation), cardiac rhythm disorders (57/161, 56 supraventricular tachycardia), repolarization disorders (12/161), and intracardiac conduction disorders (5/161) were observed. Of the total 161 patients studied, 26 displayed no cardiac disorder. All patients were given an initial dose of 5 g of hydroxocobalamin. Non-responders received a second dose of 5 g of hydroxocobalamin. Of the patients initially in cardiac arrest, 30 died at the scene, 24 died in hospital, and 5 survived without cardiovascular sequelae. Cardiac disorders improved with increasing doses of hydroxocobalamin, and higher doses of the antidote seem to be associated with a superior outcome in patients with initial cardiac arrest. Conclusions: Cardiac complications are common in cyanide poisoning in fire survivors. [Copyright &y& Elsevier]

The oxygen demands of the human body require the constant circulation of blood carrying an enormous concentration of hemoglobin (Hb). Oxygen transport depends not only on the amount of Hb, but also on the control over the affinity of the protein for the gas, which can be optimized for the environmental conditions by changes in the concentration of effectors (hydrogen ions, chloride, CO2, and DPG) inside the red cell. Some pathological conditions affecting Hb may benefit from pharmacological interventions to increase or decrease its affinity for oxygen, or otherwise modify its properties, or alter its biosynthesis. Examples of such conditions include sickle cell anemia, thalassemias and inherited hemoglobinopathies. Effective and safe drugs such as voxelotor, bezafibrate and efaproxiral are available that significantly increase or decrease Hb oxygen affinity. Some medical conditions not directly affecting the blood or its oxygen carrying capacity may also be relieved by the manipulation of Hb. For example, the standard treatment of acute cyanide poisoning requires the oxidation of a fraction of the Hb in the bloodstream so that it efficiently scavenges cyanide. Tumors are often extremely hypoxic and therefore strongly resistant to radiotherapy; the sensitivity of cancerous tissue to X-rays may be increased by improved oxygenation through drugs binding Hb. This review attempts to provide a systematic exploration of the pharmacology of Hb, its molecular basis, and its intended and possible uses. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hydroxocobalamin (OHCbl) and cyanocobalamin (CNCbl) are dark-red colored analogs of vitamin B-12. OHCbl is used as an alternate antidote for cyanide poisoning. Due to the strong red color, if uncorrected, these cobalamins interfere with hemoglobin measurements and can introduce errors in spectrophotometric assay on co-oximeters. The impact of cobalamins on commonly used co-oximetry systems was compared to evaluate the accuracy of hemoglobin measurements and to further assess the ability of the instruments to detect and flag cobalamin interference. Methods: Blood samples spiked with varying concentrations of hydroxocobalamin or cyanocobalamin (0–2 g/l), were measured on 3 GEM Premier 4000 s, 3 IL 682 CO-Oximeter, 1 Radiometer ABL 735 and 1 Siemens Rapidpoint 405 analyzer. The effect of OHCbl or CNCbl interference on total hemoglobin and hemoglobin derivatives is evaluated using the measured difference between the control sample and the spiked sample. Results: Spectral measurements, blood measurements and delta spectral data confirmed that hemoglobin measurement accuracy is affected by the presence of OHCbl or CNCbl and that the source of interference is from errors in measurement algorithms, and not due to cobalamin induced hemoglobin changes. Conclusions: Among the 4 co-oximeters tested in this evaluation, GEM Premier 4000 and Rapidpoint 405 analyzer showed minimal impact for hydroxocobalamin concentrations around 0.5 g/l. Cyanocobalamin displayed similar interference effect on co-oximetry measurements as OHCbl. The error detection system in the GEM Premier 4000 appropriately detected and flagged interferences on sample measurements. [Copyright &y& Elsevier]

Abstract: A 35-year-old female ingested a lethal dose of potassium cyanide in a suicide attempt. She survived following antidote therapy and intensive care. Following artificial coma she presented with an agitative state for several days followed by akinetic mutism, buccofacial and ideomotoric aphasia. Severe rigid-akinetic syndrome, dysarthria, dysphagia and generalized dystonia developed weeks later. MRI revealed lesions in the caudate and lentiform nuclei, precentral cortex, and cerebellum. SPECT by [123-I] 2β-carbomethoxy-3-β-(4-iodophenyl)-Tropan on two occasions revealed progressive loss of dopamine transporter suggestive of nigral neuronal apoptosis. Striatal and frontal hypometabolism and hypoperfusion were found by FDG-PET and HMPAO SPECT. [Copyright &y& Elsevier]

[Display omitted] Liposome-encapsulated methemoglobin (metHb@Lipo) has been developed as a novel antidote for cyanide poisoning. Antidotes for lethal acute poisoning should be capable of being easily stored as ready-to-use formulations without temperature restrictions. Here, we investigated the pharmaceutical stability of the metHb@Lipo suspension after one-year storage as a ready-to-use formulation at 4 °C, room temperature (23–28 °C) and 37 °C. The liposomal integrity of metHb@Lipo was observed after one year of storage at all storage temperatures with no physicochemical change or methemoglobin leakage outside the liposome. Furthermore, the encapsulated methemoglobin remained intact without aggregation, fragmentation, denaturation, or dissociation of heme. Fresh and stored metHb@Lipo were equivalent in their binding affinity against cyanide. Moreover, all one-year stored metHb@Lipo suspensions improved the mortality rates of lethal cyanide poisoning mice comparable to fresh metHb@Lipo suspension. Additionally, all stored metHb@Lipo suspensions preserved high biocompatibility, including blood compatibility and the lack of organ toxicity. In conclusion, the metHb@Lipo suspension was a pharmaceutically stable antidote for cyanide poisoning for at least one year without any temperature restrictions. [ABSTRACT FROM AUTHOR]

Rigid polyurethane foam (RPUF) is widely used for thermal and sound insulation owing to their low thermal conductivity and light weight. However, they have serious disadvantages, including flammability and toxic gas generation, which can cause chemical asphyxia during a fire. Carbon monoxide (CO) and hydrogen cyanide (HCN) are representative toxic gases formed by incomplete combustion and HCN, in particular, is closely related to polyurethane product fires. In this study, the risk of inhalation of toxic gases such as CO, HCN and NO2 during RPUF fires was demonstrated convincingly through the analysis of carboxyhemoglobin (COHb), cyanide (CN-) and methemoglobin (MetHb) in the postmortem blood samples of 38 victims of RPUF fires. To better understand the toxic gas poisoning and chemical asphyxia, we classified all cases into two groups based on the extent of injuries and location where the victim was found. Mean concentrations of COHb and cyanide in group 1 without injuries were approximately two times higher than in group 2 with severe injuries, while concentrations of free MetHb showing possibility of NO2 inhalation were approximately six times lower than in group 2. Furthermore, we presumed concentrations of cyanide at the time of death and five cases showed the possibility of cyanide poisoning. [ABSTRACT FROM AUTHOR]

• Dimethyl disulfide is a soil fumigant which can cause serious health problems. • A sensitive method (LOD = 30 nM) was developed for DMDS analysis from blood. • The method is selective and has a wide linear range (0.1 – 200 μM). • The method detected low DMDS concentrations in dimethyl trisulfide-treated swine. Plant parasites and soilborne pathogens directly reduce the overall yield of crops, vegetables, and fruits, negatively impacting the market demand for these products and their net profitability. While preplant soil fumigation helps maintain the consistent production quality of high-value cash crops, most soil fumigants are toxic to off-target species, including humans. Dimethyl disulfide (DMDS) has recently been introduced as a relatively low toxicity soil fumigant. Although DMDS exhibits low toxicity compared to other soil fumigants, it is volatile and exposure can cause eye, nasal, and upper respiratory tract irritation, skin irritation, nausea, dizziness, headache, and fatigue. While there is one analysis method available for DMDS from biological matrices, it has significant disadvantages. Hence, in this study, a dynamic headspace gas chromatography–mass spectroscopy (DHS-GC-MS) method was developed for the analysis of DMDS in swine whole blood. This method is highly sensitive and requires only three steps: 1) acid denaturation, 2) addition of internal standard, and 3) DHS-GC-MS analysis. The method produced a wide linear range from 0.1 – 200 µM with an excellent limit of detection of 30 nM. Intra- and interassay accuracy (100±14% and 100±11%, respectively) and precision (<5% and <6% relative standard deviation, respectively) were also excellent. The method worked well to quantify the DMDS levels in the blood of dimethyl trisulfide (DMTS)-treated swine (i.e., DMDS is a byproduct of DMTS treatment) with no interfering substances at or around the retention time of DMDS (i.e., 2.7 min). This simple, rapid, and extremely sensitive method can be used for the quantification of DMDS levels in blood to verify exposure to DMDS or to monitor levels of DMDS following DMTS treatment (e.g., for cyanide poisoning). [ABSTRACT FROM AUTHOR]