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[Potentiometric methods for determining boron, hydrogen cyanide and hydrogen chloride compounds and their use in controlling the quality of manufacturing and natural environments].

The authors present basic science for, elaborate and set as methodic recommendations some potentiometric methods using ion-selective electrodes. Efficiency of those methods was proved in experiments with such substances as boron compounds, hydrogen cyanide, hydrogen chloride. High sensitivity, selectivity, accuracy and rapidity of the methods with handy technique make the facilities available for analysis of air at workplace, ambient atmosphere, water and biologic materials, detecting wide range of concentrations. Practical application of the methods enabled to specify measures to preserve health of workers and general population, helped in hygienic evaluation of work conditions in composition materials production, high-temperature soldering, optic glass industry.

Air Pollutants↗

Hydrogen cyanide generation by mu-opiate receptor activation: possible neuromodulatory role of endogenous cyanide.

Hydrogen cyanide, a gaseous molecule, is produced by white blood cells during phagocytosis. The present study examined the possibility that neuronal-like cells may also produce cyanide following activation. Rat pheochromocytoma (PC12) cells exhibited a low level of cyanide generation that was significantly increased by mu-opiate agonists (hydromorphone, morphine) and blocked by naloxone. A variety of other agonists including bradykinin, nicotine and glutamate did not generate cyanide in PC12 cells. Systemic administration of hydromorphone to rats increased brain cyanide levels by 61% after 15 min. Using microdialysis probes implanted in the cortical-hippocampal areas of the anesthetized rat or in the hypothalamus of the conscious hamster, a 2- to 5-fold increase in cyanide generation was seen after hydromorphone administration and this increase was blocked by naloxone. To determine whether cyanide release by hydromorphone has functional significance in a neuronal system, cyanide enhancement of N-methyl-D-aspartate (NMDA)-induced increased [Ca2+]i was measured in rat cerebellar granule cells. Hydromorphone enhanced the response to NMDA similar to cyanide and the hydromorphone effect was blocked by cyanide scavengers. These data show that cyanide generation is increased in neuronal tissue by a mu-opiate receptor agonist and it is proposed that endogenous cyanide may modulate the NMDA receptor response.

Analgesics, Opioid↗

Effects of pressure and temperature on the reactions of horseradish peroxidase with hydrogen cyanide and hydrogen peroxide.

Reactions of ferric horseradish peroxidase with hydrogen cyanide and hydrogen peroxide were studied as a function of pressure. Activation volumes are small and differ in sign (delta V = 1.7 +/- 0.5 ml/mol for peroxidase + HCN and -1.5 +/- 0.5 ml/mol for peroxidase + H2O2). The temperature dependence of cyanide binding to horseradish peroxidase was also determined. A comparison is made of relevant parameters for cyanide binding and compound I formation.

Enzyme Activation↗

Liberation of hydrogen cyanide and hydrogen chloride during high-temperature dispersion of CS riot control agent.

High temperature dispersion (greater than 700 degrees C) of the riot control agent orthochlorobenzylidenemalononitrile (CS) has previously been shown to produce a number of organic thermal degradation products through rearrangements and loss of cyano and chlorine substituents present on the parent CS compound. Until now the possibility that HCN and HCl might also be air contaminants produced during high temperature CS dispersion has not been examined. Air samples were collected to detect HCN and HCl as air contaminants released during high-temperature CS dispersion indoors. Sampling and analysis based on National Institute of Occupational Safety and Health methods 7904 and 6010 for HCN, and 7903 for HCl, showed evidence that both compounds were present in air samples collected. A reassessment of human health risks associated with exposure to CS riot control agent dispersed at high temperature should be conducted, and should consider the full range of contaminants produced during the dispersion process.

Environmental Exposure↗

Thermodynamics of hydrogen cyanide and hydrogen fluoride binding to cytochrome c peroxidase and its Asn-82-->Asp mutant.

The thermodynamics of binding of fluoride and cyanide to cytochrome c peroxidase (CCP) and its Asn-82-->Asp mutant (D82CCP) in phosphate and acetate buffer at an ionic strength of 0.15 mol.kg-1 from pH 5.0 to 7.1 were investigated by titration calorimetry at 289 and 297 K. The binding reactions are enthalpically driven. The fluoride-binding constants determined from the titration calorimetry results were in agreement with those determined from difference-spectroscopy measurements. For cyanide binding to CCP at 297.9 K, the binding constant decreased from 8.95 (+/- 0.83) x 10(5) M-1 at pH 7.0 to 4.04(+/- 0.23) x 10(5) M-1 at pH 5.0, and the binding enthalpy increased from -57.2 +/- 1.4 kJ.mol-1 at pH 7.0 to -48.6 +/- 1.8 kJ.mol-1 at pH 5.0. For fluoride binding to CCP, the binding constant increased from 8.41(+/- 0.54) x 10(3) M-1 at pH 7.0 to 3.11(+/- 0.09) x 10(5) M-1 at pH 5.0 and the binding enthalpy increased from -71.9 +/- 1.1 kJ.mol-1 at pH 7.0 to -67.0 +/- 1.9 kJ.mol-1 at pH 5.0. The binding enthalpies for D82CCP were about the same as those for CCP. However, the binding constants for cyanide and fluoride to D82CCP were respectively a factor of two less and at least an order of magnitude less than the corresponding binding constants of CCP. Decreased ligand-binding strength in the D82CCP mutant is thus entirely due to entropic effects.

Asparagine↗

Glycine metabolism by Pseudomonas aeruginosa: hydrogen cyanide biosynthesis.

Hydrogen cyanide (HCN) production by Pseudomonas aeruginosa in a synthetic medium is stimulated by the presence of glycine. Methionine enhances this stimulation but will not substitute for glycine as a stimulator of cyanogenesis. Threonine and phenylalanine are effective substitutes for glycine in the stimulation of HCN production. Glycine, threonine, and serine are good radioisotope precursors of HCN, but methionine and phenylalanine are not. Cell extracts of P. aeruginosa convert [14C]threonine to [14C]glycine. H14CN is produced with low dilution of label from either [1-14C]glycine or [2-14C]glycine, indicating a randomization of label either in the primary or secondary metabolism of glycine. When whole cells were fed [1,2-14C]glycine, cyanide and bicarbonate were the only radioactive extracellular products observed.

Carbon Radioisotopes↗

The origin of hydrogen cyanide in breath.

The excretion of hydrogen cyanide in breath and blood concentrations of cyanide were measured in eight normal subjects. There was no correlation between breath and blood levels of cyanide. Furthermore, breath cyanide concentrations calculated from blood values were much lower than measured values, which suggested a local production of hydrogen cyanide in the oropharynx. When saliva was incubated at 37 degrees C hydrogen cyanide was formed in the presence of air but not in a nitrogen atmosphere. No hydrogen cyanide was formed with boiled saliva and the production of hydrogen cyanide by native saliva was inhibited by catalase and by 6-n-propyl-thiouracil. Centrifugation of saliva resulted in a supernatant and a sediment, which were both required for the formation of hydrogen cyanide. Dialysis of the supernatant abolished its cyanide forming ability, which could be restored by addition of thiocyanate. We conclude that most of the hydrogen cyanide found in breath from normal human beings originates from oxidation of thiocyanate by salivary peroxidase in the oropharynx. As a consequence measurements of breath hydrogen cyanide can only be used to detect heavy exposure to cyanide.

Adult↗

An incident of hydrogen cyanide poisoning.

Seven cases of hydrogen cyanide gas poisoning which occurred in an industrial building in Hong Kong are presented here. Two of them were more severely injured and required specific antidotal treatment. The other five were mild and responded to supportive treatment alone. All except one patient recovered completely. Cyanide poisoning is relatively uncommon in urbanized area, so high index of suspicion is important for early diagnosis and treatment. We believe that prevention of cyanide poisoning can be achieved by proper storage of chemicals, and by enforcing rescuers to wear special chemical protective clothing to avoid systemic poisoning because of dermal absorption of hydrogen cyanide gas. As there are newer and safer cyanide antidotes available, each emergency department should have a stock of updated products such as hydroxocobalamin.

Adult↗

Hydrogen cyanide polymers, comets and the origin of life.

Hydrogen cyanide polymers--heterogeneous solids ranging in colour from yellow to orange to brown to black--could be major components of the dark matter observed on many bodies of the outer solar system including asteroids, moons, planets and, especially, comets. The presence on cometary nuclei of frozen volatiles such as methane, ammonia and water subjected to high energy sources makes them attractive sites for the ready formation and condensed-phase polymerization of hydrogen cyanide. This could account for the dark crust observed on Comet Halley in 1986 by the Vega and Giotto missions. Dust emanating from its nucleus would arise partly from HCN polymers as suggested by the Giotto detection of free hydrogen cyanide, CN radicals, solid particles consisting only of H, C and N, or only of H, C, N, O, and nitrogen-containing organic compounds. Further evidence for cometary HCN polymers could be expected from in situ analysis of the ejected material from Comet Tempel 1 after collision with the impactor probe from the two-stage Deep Impact mission on July 4, 2005. Even more revealing will be actual samples of dust collected from the coma of Comet Wild 2 by the Stardust mission, due to return to Earth in January 2006 for analyses which we have predicted will detect these polymers and related compounds. In situ results have already shown that nitriles and polymers of hydrogen cyanide are probable components of the cometary dust that struck the Cometary and Interstellar Dust Analyzer of the Stardust spacecraft as it approached Comet Wild 2 on January 2, 2004. Preliminary evidence (January 2005) obtained by the Huygens probe of the ongoing Cassini-Huygens mission to Saturn and its satellites indicates the presence of nitrogen-containing organic compounds in the refractory organic cores of the aerosols that give rise to the orange haze high in the atmosphere of Titan, Saturn's largest moon. Our continuing investigations suggest that HCN polymers are basically of two types: ladder structures with conjugated -C=N- bonds and polyamidines readily converted by water to polypeptides. Thermochemolysis GC-MS studies show that cleavage products of the polymer include alpha-amino acids, nitrogen heterocycles such as purines and pyrimidines, and provide evidence for peptide linkages. Hydrogen cyanide polymers are a plausible link between cosmochemistry and the origin of informational macromolecules. Implications for prebiotic chemistry are profound. Following persistent bolide bombardment, primitive Earth may have been covered by water and carbonaceous compounds, particularly HCN polymers which would have supplied essential components for establishing protein/nucleic acid life.

Cosmic Dust↗

Rapid sodium cyanide depletion in cell culture media: outgassing of hydrogen cyanide at physiological pH.

During the course of in vitro studies on cyanide exposure with SH-SY5Y human neuroblastoma cells, we found that sodium cyanide (NaCN) up to a concentration of 10 mM had no significant toxic effect under our culture conditions. Further investigation of this apparent cyanide resistance revealed that the sodium cyanide was being rapidly depleted from the cell culture medium. Cyanide was interacting with constituents of the cell culture medium and was somehow being detoxified or removed from solution. The reaction of cyanide with cell culture media in 96-well culture plates reduced cyanide concentrations rapidly (80-90% in 2 h at 37 degrees C). Running the same reaction in capped tubes significantly reduced cyanide loss from solution. Incubation of cyanide with individual constituents of the cell culture medium in solution showed that glucose, phenol red, and amino acids all acted to detoxify or remove cyanide from solution. When amino acids or buffers were incubated with sodium cyanide in aqueous solution at pH 7.4, hydrogen cyanide (HCN) was found to degas from the solutions. We compared HCN outgassing over a range of pH values. As expected, HCN remained very soluble at high pH, but as the pH was reduced to 7.0, the rate of HCN formation and outgassing increased dramatically. Acid-base reactions involving cyanide and proton donors, such as amino acids and other cell culture media constituents, at physiological pH result in rapid HCN outgassing from solution at 37 degrees C. These results indicate that previous in vitro cyanide toxicity studies done in standard culture media with prolonged incubation times using gas-exchanging culture containers might have to be reevaluated in light of the fact that the effective cyanide concentrations in the culture media were significantly lower than reported.

Culture Media↗

A study on house fire victims: age, carboxyhemoglobin, hydrogen cyanide and hemolysis.

Correlation among age, concentrations of carboxyhemoglobin and hydrogen cyanide, oxygen density and hemolysis were studied in 120 house fire victims. Victims aged over 60 years comprised approximately 50% of the pooled subjects. Blood samples were mainly collected from the left ventricle, but sometimes from both the right and left ventricles. The concentration of carboxyhemoglobin ranged from 1-95%, of which 71 persons (59.7%) died with carboxyhemoglobin concentrations below 60%. Carboxyhemoglobin concentrations below 10% were found in 9 persons (7.5%). Most of these cases involved the elderly persons. In this paper, we report on the death of elderly victims as a result of low carboxyhemoglobin concentrations. A significant correlation of blood carboxyhemoglobin concentrations existed between the right and left ventricles. The concentration of carboxyhemoglobin in the left ventricle was significantly higher than that in the right. Two out of 31 victims whose hydrogen cyanide concentrations were determined, succumbed to hydrogen cyanide poisoning, having a high concentration of hydrogen cyanide and a low concentration of carboxyhemoglobin. On analysis, oxygen density was found to be low in 13 persons. A negative correlation was shown between carboxyhemoglobin concentration and hemolysis. Inasmuch as hemolysis may indicate the extent of heat dissociation, hemolysis should provide an index of carbon monoxide dissociation from carboxyhemoglobin. In the present study of victims, possible causes of death i.e., carbon monoxide gas poisoning, hydrogen cyanide poisoning, oxygen deprivation, burning, shock due to burns and others were estimated. The survival time for elderly victims was considered to be short.

Adolescent↗

Hydrogen cyanide production by Pseudomonas aeruginosa at reduced oxygen levels.

Hydrogen cyanide production by Pseudomonas aeruginosa growing in a synthetic medium required aerobosis but operated efficiently at low dissolved oxygen concentration. Half maximum levels of cyanogenesis occurred at 0.015 microM oxygen; maximum cyanogenesis occurred over a wide range, 0.1-180 microM, of oxygen concentrations. These cells lost the ability to produce cyanide upon aerobic incubation in the absence of both the carbon energy source (L-glutamate) and the metabolic precursor of hydrogen cyanide (glycine). This loss of cyanogenesis was dependent on oxygen concentration; 1.0 microM oxygen produced no detectable loss, whereas 180 microM oxygen caused a rapid decline in cyanogenic ability. The endogenous cyanide production rate of cells in the presence of carbon energy source was not significantly influenced by oxygen concentration. During the batch culture cycle, the acquisition of the ability to produce HCN was preceded by oxygen reduction to growth-limiting levels. Cells which had lost the ability to produce hydrogen cyanide by oxygen treatment required protein synthesis before they could again become cyanogenic.

Glycine↗