Showing papers on "Cyanide published in 1982"

A Clinical Trial of Amygdalin (Laetrile) in the Treatment of Human Cancer

Abstract: One hundred seventy-eight patients with cancer were treated with amygdalin (Laetrile) plus a "metabolic therapy" program consisting of diet, enzymes, and vitamins. The great majority of these patients were in good general condition before treatment. None was totally disabled or in preterminal condition. One third had not received any previous chemotherapy. The pharmaceutical preparations of amygdalin, the dosage, and the schedule were representative of past and present Laetrile practice. No substantive benefit was observed in terms of cure, improvement or stabilization of cancer, improvement of symptoms related to cancer, or extension of life span. The hazards of amygdalin therapy were evidenced in several patients by symptoms of cyanide toxicity or by blood cyanide levels approaching the lethal range. Patients exposed to this agent should be instructed about the danger of cyanide poisoning, and their blood cyanide levels should be carefully monitored. Amygdalin (Laetrile) is a toxic drug that is not effective as a cancer treatment.

Production of superoxide and activity of superoxide dismutase in rabbit epididymal spermatozoa.

Abstract: Mature rabbit spermatozoa from the cauda epididymidis suspended in potassium Tris phosphate buffer at 24 degrees C produced O2.-, as measured by reduction of acetylated ferricytochrome c, with an intrinsic rate of 0.20 nmol/min per 10(8) cells. This rate increased to 1.80 nmol/min per 10(8) cells in the presence of 10 mM cyanide. These spermatozoa contain 2.8 units per 10(8) cells of superoxide dismutase activity, 95% of which is sensitive, and 5% of which is insensitive, to cyanide inhibition. These activities correspond to the cytosolic Cu-Zn form and the mitochondrial Mn form of the dismutase, respectively. Only the cyanide-sensitive form is released from the sperm on hypo-osmotic treatment or sonication. Hypo-osmotically treated rabbit epididymal spermatozoa produced O2.- with an intrinsic rate of 0.24 nmol/min per 10(8) cells, which increased to 0.58 nmol/min per 10(8) cells in the presence of 10 mM cyanide. Both intact and hypo-osmotically treated cells react with O2.- in a second order reaction as inferred from the hyperbolic dependence on cell concentration of O2.- production rate in both the absence and presence of cyanide. The second order rate constant for this reaction with intact cells, kS, was calculated to be 22.9 X 10(-8) (cells/ml)-1 min-1 in its absence. For hypo-osmotically treated cells, the values of kS were 10.8 X 10(-8) (cells/ml)-1 min-1 and 8.2 X 10(-8) (cells/ml) -1 min-1, respectively. Since hypo-osmotically treated cells have lost much of their plasma membrane, the lower value of kS for the treated cells implies that this membrane is one site of reaction of O2.- with the cells. The increase in kS in the presence of cyanide, which inhibits superoxide dismutase and so increases O2.- production, suggests that the cells become more reactive with O2.- as its production rate increase, as would be expected for the occurrence of radical chain oxidation. This in turn suggests that superoxide dismutase plays a major role in protecting rabbit sperm against damage from lipid peroxidation.

Electrochemical preparation of a Prussian blue analog: iron-ruthenium cyanide

Abstract: Eine durch Reaktion von K4.Ru(CN)6 mit PbO2 erhaltene Losung von Hexacyanoruthenat(III) im Gemisch mit Fe,(SO4 )3 wird unter Verwendung von SnO" Pt oder glasigem Kohlenstoff als kathodisch polarisierten Elektroden und Pt als Gegenelektrode elektrolysiert.

Nitrogenase reactivity: cyanide as substrate and inhibitor.

Abstract: We have examined the reduction of cyanide by using the purified component proteins of nitrogenase (Av1 and Av2). The previously reported self-inhibition phenomenon was found to be an artifact. One of the two species present in cyanide solutions, CN-, was shown to be a potent reversible inhibitor (Ki = 27 microM) of total electron flow, apparently uncoupling MgATP hydrolysis and electron transfer. There appears to be no differential effect of CN- on the specific activities of Av1 and Av2 nor is there any apparent irreversible physical damage to Av2. CN- inhibition is completely reversed by low levels of CO, implying a common binding site. Azide partially relieves the inhibitory effect, but other substrates and inhibitors (N2, C2H2, N2O, H2) have no effect. The other species present in cyanide solutions, HCN, was shown to be the substrate (Km = 4.5 mM at Av2/Av1 = 8), and extrapolation of the data indicates that at high enough HCN concentration H2 evolution can be eliminated. The products are methane plus ammonia (six electrons), and methylamine (four electrons). There is an excess (relative to methane) of ammonia formed, which, according to electron balance studies, may arise from a two-electron intermediate. Both nitrous oxide and acetylene (but not N2) influence the distribution of cyanide reduction products, implying simultaneous binding. HCN appears to bind to and be reduced at an enzyme state more oxidized than the one responsible for either H2 evolution or N2 reduction.

Respiratory physiology and energy conservation efficiency of Campylobacter jejuni.

Abstract: A study of the electron transport chain of the human intestinal pathogen Campylobacter jejuni revealed a rich complement of b- and c-type cytochromes. Two c-type cytochromes were partially purified: one, possibly an oxidase, bound carbon monoxide whereas the other, of high potential was unreactive with carbon monoxide. Respiratory activities determined with membrane vesicles were 50- to 100-fold higher with formate and hydrogen than with succinate, lactate, malate, or NADH as substrates. Evidence for three terminal respiratory components was obtained from respiratory kinetic studies employing cyanide, and the following Ki values for cyanide were determined from Dixon plots: ascorbate + reduced N,N,N', N'-tetramethyl-p-phenylenediamine, K1 + 3.5 muM; malate, K1 = 55 muM; and hydrogen, K1 = 4.5 muM. Two oxidases (K1 = 90 muM, 4.5 mM) participated in the oxidation of succinate, lactate, and formate. Except with formate, 37 muM HQNO inhibited respiration by approximately 50%. Carbon monoxide had little inhibitory effect on respiration except under low oxygen tension (less than 10% air saturation). The stoichiometry of respiratory-driven proton translocation (H+/O) determined with whole cells was approximately 2 for all substrates examined except hydrogen (H+/) = 3.7) and formate (H+/O = 2.5). The higher stoichiometries observed with hydrogen and formate are consistent with their respective dehydrogenase being located on the periplasmic face of the cytoplasmic membrane. The results of this study suggest that the oxidation of hydrogen and formate probably serves as the major sources of energy for growth.

Fire deaths in the Glasgow area: III. The role of hydrogen cyanide.

Abstract: An assessment is presented of the importance of cyanide in fire deaths in the United Kingdom during the period 1976–79. Concentrations of cyanide and its principal metabolite in man, thiocyanate, were measured in 139 fire fatalities and for comparison purposes, in groups of non-fatal fire casualties, firemen and controls. Cyanide levels were found to be significantly elevated in fatalities and non-fatal casualties but not in firemen when compared to controls and in addition, smokers showed higher blood levels of cyanide than non-smokers. 78 per cent of the fatalities had elevated cyanide levels. 31 per cent had levels which would have caused toxic effects and of these, 12 per cent were likely to have shown symptoms of severe cyanide poisoning. No additive or synergistic effects were observed in fatalities between cyanide and other factors including carbon monoxide, alcohol, the age of the victim and the presence of heart disease. Thiocyanate levels in fatalities showed some correlation with the cyanide le...

Cyanide toxicity of sodium nitroprusside in therapeutic use with and without sodium thiosulphate

Abstract: Sodium nitroprusside (SNP) as a mono-infusion was administered to 51 patients for periods of a few hours. A further group of 19 patients received SNP for periods of several days as a combination solution of SNP mixed with sodium thiosulphate. The concentrations of cyanide and of thiocyanate in the blood of all patients were measured. In seven of the patients the level of thiosulphate was also measured. Infusion of SNP on its own at levels exceeding 2 microgram/kg/min led to the rising of cyanide levels in the blood being proportional to dosage. Infusion of SNP mixed with thiosulphate showed no such accumulation of cyanide in any patient, irrespective of dosage level and duration. The efficacy at lowering blood pressure was fully maintained in the mixed infusion. The elimination half-life for thiosulphate was 16.5 min. Pharmacokinetic calculation of the rise in cyanide level showed that mono-infusions of 5-10 micrograms SNP/kg/min could within 5-10 h cause a life-threatening cyanide level in the blood. By contrast, mixed infusion of SNP together with thiosulphate, for which light-opaque syringes and tubing must be used, is a procedure free of danger and should become the technique of choice when therapeutically administering SNP in order to lower blood pressure.

Synthesis of ribosyl and arabinosyl cyanides by reaction of 1-O-acyl sugars with trimethylsilyl cyanide

Abstract: A new procedure is described for the synthesis of glycosyl cyanides by reaction of 1-O-acyl sugars with trimethyl-silyl cyanide in a polar aprotic solvent and in the presence of a Lewis acid as catalyst. A variety of ribosyl and arabinosyl cyanides have been made in this way from sugar derivatives having acyl, chloro, or methoxy leaving groups at the anomeric position, furanose or pyranose rings, and acyl or benzyl protecting groups. The 1,2-Trans-glycosyl cyanide was formed when the starting sugar had a participating 2-O-acyl substituent. A mixture of cyanide anomers was obtained when the starting sugar was protected with non-participating benzyl groups.

Electron transport components involved in hydrogen oxidation in free-living Rhizobium japonicum.

Abstract: Membranes from free-living Rhizobium japonicum were isolated to study electron transport components involved in H2 oxidation. The H2/O2 uptake rate ratio in membranes was approximately 2. The electron transport inhibitors antimycin A, cyanide, azide, hydroxylamine, and 2-n-heptyl-4-hydroxyquinoline-N-oxide (HQNO) inhibited H2 uptake and H2-dependent O2 uptake significantly. H2-reduced minus O2-oxidized absorption difference spectra revealed peaks at 551.5, 560, and 603 nm, indicating the involvement of cytochromes c, b, and a-a3, respectively. H2-dependent cytochrome reduction was completely inhibited in the presence of 0.15 mM HQNO. This inhibition was relieved by the addition of 0.1 mM menadione. Evidence is presented for the involvement of two b-type cytochromes in H2 oxidation. One b-type cytochrome was not reduced by ascorbate and had an absorption peak at 560 nm. The reduction of this cytochrome by H2 was not inhibited by cyanide. A second b-type cytochrome, cytochrome b', was not reduced by H2 in the presence of cyanide. This cytochrome had an absorption peak at 558 nm. Carbon monoxide difference spectra with H2 as reductant provided evidence for the involvement of cytochrome o as well as cytochrome a3 in H2 oxidation. H2 uptake activity in cell-free extracts was inhibited by UV light irradiation. Most of the activity of the UV-treated extracts was restored with the addition of ubiquinone. The restored activity was inhibited by cyanide. A branched electron transport pathway from H2 to O2 is proposed.

Metabolism of phencyclidine. The role of iminium ion formation in covalent binding to rabbit microsomal protein.

Abstract: Incubation of phencyclidine (PCP) with rabbit liver microsomes and Na14CN resulted in the metabolically dependent formation of a 14C-labeled cyano adduct of the drug. After isolation by HPLC, this compound was identified as the alpha-aminonitrile [1-(1-phenylcyclohexyl)-2-cyanopiperidine] derivative of PCP by use of chemical-ionization and gas-chromatographic coupled electron-impact mass spectrometry. Synthetic alpha-aminonitrile exhibited identical chemical properties and comigrated in HPLC and GLC with the metabolism derived cyano adduct. Molecular identification of the adduct formed by cyanide trapping provided evidence for the formation of an iminium ion during PCP metabolism. Quantitative estimation by HPLC demonstrated that the alpha-aminonitrile accounted for over 50% of the PCP metabolized in 30 min by hepatic microsomes in vitro. Metabolism-dependent covalent binding of [3H]PCP to rabbit liver microsomal proteins was inhibited by cyanide ion in a concentration-dependent manner with an IC50 value of 57 microM. The concentrations of cyanide ion used in these experiments did not significantly inhibit the metabolism of PCP. These results support our suggestions that iminium ion formation may represent an important intermediary step in the metabolism of PCP and that such a reactive electrophilic species may be capable of covalent interactions with nucleophilic groupings on microsomal macromolecules.

Ionic regulation of the unicellular green algadunaliella tertiolecta

Abstract: Different techniques were investigated in order to determine the Na, K and Cl concentrations ofDunaliella tertiolecta cells adapted to a large range of salinity (20 to 1640 mM NaCl). The K cell concentrations were 6 to 13 times higher than the K concentration of the external medium (11 mM). The The Na and Cl cell concentrations, on the other hand, were lower than in the external medium at all salinities tested. Considerable differences in the absolute values of Na and Cl were, however, found according to the technique employed. These results are interpreted in terms of compartmentalization of the cells (at least two compartments). It is postulated that the larger compartment regulates its ion concentrations, maintaining low Na and Cl and high K concentrations, whereas the second compartment equilibrates with the external medium. The cation permeability of the membrane limiting the regulating compartment is altered by the antibiotics nystatin and monensin. Incubation of cells in K-free medium leads to a decrease of K and to an increase of the cell Na, this effect being reversed by addition of KCl to the medium. A good correlation is found between gain of K and loss of Na, suggesting a stoichiometric exchange of these two ions. The magnitude of this apparent Na/K exchange increases as the salinity increases. The external K concentration necessary to mediate half-saturation of the Na/K exchange is a function of the NaCl concentration of the adaptation medium. This Na/K exchange is partially light-dependant and inhibited by cold, cyanide and DCCD. It is suggested that this mechanism helps in the regulation of the ionic composition ofDunaliella cells.

Application of the trickle tower to problems of pollution control. II. The direct and indirect oxidation of cyanide

Abstract: The direct and indirect oxidation of cyanide at concentrations typical of those found in plating wash water have been investigated in a bipolar trickle-tower reactor. It has been found that the oxidation by hypochlorite generatedin situ was faster than direct oxidation or oxidation in the presence of base, but that the CN− concentration was easily reduced by any of these methods. Scaling-up experiments were performed by using different numbers of layers of bipoles, different electrolyte flow rates and different applied voltages. It is shown that the overall rate is determined by the mass-transport-limited generation of oxidant.

Malate Oxidation, Rotenone-Resistance, and Alternative Path Activity in Plant Mitochondria

Abstract: The effect of cyanide and rotenone on malate (pH 6.8), malate plus glutamate (pH 7.8), citrate, α-ketoglutarate, and succinate oxidation by cauliflower (Brassica oleracea L.) bud, sweet potato (Ipomoea batatis L.) tuber, and spinach (Spinacia oleracea and Kalanchoe daigremontiana leaf mitochondria was investigated. Cyanide inhibited all substrates equally with the exception of malate plus glutamate; in this case, inhibition of O2 uptake was more severe due to an effect of cyanide on aspartate aminotransferase. Azide and antimycin A gave similar inhibitions with all substrates. Subsequent addition of NAD had no effect with any substrate. Providing that oxalacetate accumulation was prevented, rotenone inhibited all NAD-linked substrates equally and caused ADP:O ratios to decrease by one-third. Addition of succinate to mitochondria oxidizing malate stimulated oxygen uptake, but adding citrate and α-ketoglutarate did not. These results indicate that there is no direct link between malic enzyme and the rotenone- and cyanide-resistant respiratory pathways, and that there is no need to postulate separate compartmentation of malic enzyme and the other NAD-linked enzymes in the matrix.

Electrochemical preparation of a prussian blue analog: iron‐ruthenium cyanide

Abstract: Eine durch Reaktion von K4.Ru(CN)6 mit PbO2 erhaltene Losung von Hexacyanoruthenat(III) im Gemisch mit Fe,(SO4 )3 wird unter Verwendung von SnO" Pt oder glasigem Kohlenstoff als kathodisch polarisierten Elektroden und Pt als Gegenelektrode elektrolysiert.

Simultaneous determination of cyanide and thiocyanate by high performance liquid chromatography.

Abstract: A sensitive, simple and specific method was developed for the simultaneous determination of cyanide and thiocyanate by high performance liquid chromatography with a strong base anion exchanger column. For detection, colorimetry based on the Konig reaction was employed with chloramine T, pyridine and barbituric acid as reagents. This method was applied to the determination of cyanide and thiocyanate in human urine.

Metabolic Inhibitors Block ABA-Induced Stomatal Closure

Abstract: Closure of stomata of Commelina communis L. leaf epidermis caused by abscisic acid (ABA) was inhibited by sodium azide, potassium cyanide and hypoxic conditions. Azide was more effective than cyanide at low concentrations, but the cyanide effect could be enhanced by addition of salicylhydroxamic acid, providing indirect evidence for cyanide-resistant respiration in epidermal tissue. Azide also inhibited ABA-induced closure of 'isolated' stomata and shrinkage of guard cell protoplasts. The results indicate that metabolic energy is required for ABA action involving solute loss from the guard cells. Possible mechanisms of action are discussed.

Comparison of hydroxylamine, 4-dimethylaminophenol and nitrite protection against cyanide poisoning in mice.

Abstract: Intraperitoneal doses of 4-dimethylaminophenol hydrochloride (DMAP), hydroxylamine hydrochloride (H2NOH) and sodium nitrite (NaNO2) were found where each converted a maximum of about 37% of the total circulating hemoglobin in mice to methemoglobin. Those doses in mmol/kg were: 0.29 for DMAP, 1.1 for H2NOH, and 1.1 for NaNO2. For DMAP and H2NOH the peak was sharp and at about 7 min after injection whereas for NaNO2 the peak was much broader and at about 40 min. The i.p. LD50's in mmol/kg were: 0.48 for DMAP, 1.8 for H2NOH and 2.3 for NaNO2. When mice pretreated with each of the methemoglobin-generating agents were challenged with sodium cyanide, the ratios of the LD50's in protected mice to those in control mice (protection index, PI) were 1.5 for H2NOH, 2.0 for DMAP and 3.1 for NaNO2. When sodium thiosulfate was also given in combination with each of the three methemoglobin-generating agents, the protective effect was at least additive. The PI against sodium sulfide was also significantly greater in mice pretreated with NaNO2 than in mice given H2NOH. Methemoglobins generated from human and mouse hemoglobins by either NaNO2 or by H2NOH had identical binding affinities (dissociation constants) for cyanide. When human red cells containing methemoglobin generated by exposure to either NaNO2 or H2NOH were injected into the peritoneal cavity of mice and then followed by cyanide challenges, there was no difference in the PI for the two kinds of methemoglobin. Not only was the PI the same in each case with human cells, but it was also identical with that in mice given NaNO2 systemically to generate the same total amount of methemoglobin. The difference in PI between NaNO2 and H2NOH (or DMAP) in mice appears to be related to the high rate of methemoglobin reductase activity in mouse RBC. It appears likely that cyanmethemoglobin is a substrate for mouse methemoglobin reductase activity, and that NaNO2 is an inhibitor of mouse methemoglobin reductase. No differences in cyanide antagonism between NaNO2 and H2NOH would be anticipated in humans because of the slow rates of methemoglobin reduction in human red cells.

STO-3G MO calculations on structures and internal rotational barriers of phenol, benzoyl X(X = H, F, CH3, CN, OCH3), acetyl fluoride, acetyl cyanide, and carbonyl cyanide

Abstract: The side chain geometry and some adjacent bond lengths and angles of the ring are optimized at the STO-3G level of molecular orbital theory for the planar and orthogonal forms of benzoyl X(X = H, F, CN, CH3, OCH3). Similar calculations are reported for acetyl fluoride, acetyl cyanide, and carbonyl cyanide, for which experimental structures and reliable internal barriers are available. The calculated barriers for the benzoyl compounds suggest steric hindrance by X in the ground state as a major cause of the variation in the barrier magnitudes. Good agreement between calculated and experimental geometries for acetyl cyanide and carbonyl cyanide, as well as for the internal rotational barrier in the former, are taken to imply a reliable calculated geometry for benzoyl cyanide. A total geometry optimization for phenol agrees fairly well as for the internal rotational barrier in the ture and also with the direction and magnitude of the dipole moment. Optimization of the ring geometry does not lower the calculated internal rotation barrier.