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Carboxyhaemoglobin and plasma thiocyanate: complementary indicators of smoking behaviour?

Carboxyhaemoglobin and plasma thiocyanate concentrations were measured in 79 non-smokers and 360 cigarette smokers. The mean levels were 0.73% and 7.09% carboxyhaemoglobin and 40 . 2 and 133 . 8 mumol thiocyanate/1 plasma respectively. With 1 . 6% carboxyhaemoglobin and 73 . 0 mumol thiocyanate/1 plasma as critical values the concentrations of carboxyhaemoglobin in 96.6% of subjects and of thiocyanate in 93.4% were compatible with reported smoking status. This difference between the two tests is significant (p less than 0 . 005). Statistical combination of the carboxyhaemoglobin and thiocyanate results, with the use of linear discrimination analysis, only marginally improved their diagnostic efficiency (96.8% of subjects were grouped correctly). This analysis did, however, successfully regroup 21 of 26 individuals with contradictory carboxyhaemoglobin and thiocyanate classifications. It is concluded that in this study determination of thiocyanate added little to the information obtained from carboxyhaemoglobin measurements alone.

Adult↗

Characteristics of Thiobacillus thioparus and its thiocyanate assimilation.

Thiocyanate-assimilatig bacterium, TK 21, was isolated from activated sludge used for the treatment of thiocyanate contained in coke-oven liquor. This organism oxidized thiosulfate and elemental sulfur, causing a decrease of pH of the medium. These facts indicated that it belongs to the genus Thiobacillus. Potassium thiocyanate (0.5 g/l) was completely assimilated during 60 h. Thiosulfate inhibited the assimilation of thiocyanate but elemental sulfur did not. This bacterium did not evolve cyanide as its oxidation product after the decomposition of thiocyanate. The isoalted bacterium was identified as Thiobacillus thioparus. Examination of the composition of cellular fatty acid of three strains of T. thioparus showed that they prossessed 3-hydroxy fatty acid of C10 and C12; saturated straight chains of C10, C12, C15, C16, C17, and C18; monounsaturated straight chains of C16 and C18; and cyclopropane acid of C17.

Fatty Acids↗

Thiocyanate inhibition of ATPase and its relationship to anion transport.

Adenosine triphosphatase activity not dependent on sodium or potassium but inhibited by thiocyanate is present in broken-cell homogenates of eel gill and rat kidney. This enzymatic property is predominantly associated with mitochondria, although thiocyanate-inhibited ATPase can also be detected in microsomes with little or no mitochondrial contamination as measured by the activity of the mitochondrial marker enzyme succinic dehydrogenase. When eels are transferred from fresh to salf water, thus increasing active outward transport of chloride across the gill, the thiocyanate-inhibited ATPase of gill microsomes does not change, though the activities of succinic dehydrogenase and Na-K-ATPase in gill homogenates are augmented. The thiocyanate-inhibited ATPase of homogenates of outer renal medulla does not differ from that of renal cortex, in contrast to Na-k-atpase which is higher in renal medulla than in cortex. The data do not support a role for thiocyanate-inhibited ATPase in active chloride transport by epithelial tissues.

Adenosine Triphosphatases↗

Chronic toxicity tests of sodium thiocyanate with sodium nitrite in F344 rats.

Sodium thiocyanate, a common environmental chemical, was found to increase the incidence of liver tumors in a group of rats treated with 0.08% in drinking water. To test the possibility that thiocyanate was catalyzing the formation of carcinogenic nitrosamines from amines and nitrite in the food, a group of 20 male and 20 female rats was given a higher dose of sodium thiocyanate (0.32%) together with sodium nitrite (0.2%) in drinking water. Similar groups of rats were given 0.32% sodium thiocyanate or 0.2% sodium nitrite in drinking water or were untreated. All treatments lasted most of the lifetime of the rats, at least 2 years. There was no difference between the groups, treated or untreated, in survival, or in the incidence of any tumor that could be related to the treatment. The results indicate that sodium thiocyanate is without carcinogenic activity in rats, alone or combined with sodium nitrite.

Animals↗

An improved method for determination of thiocyanate in plasma and urine.

An improved spectrophotometric method is described for the determination of thiocyanate in plasma and urine. Thiocyanate is adsorbed on a weak anion-exchange resin with strong affinity for chaotropic ions, and eluted with perchlorate. Thiocyanate is then chlorinated by hypochlorite and quantified according to the König (J Prakt Chem 1904; 69:105-37) reaction by use of isonicotinic acid and 1,3-dimethyl-barbituric acid. The method affords a simple, rapid and sensitive assay for thiocyanate and has a detection limit of 0.93 mumol/l. At thiocyanate concentrations of 107.1 and 167.4 mumol/l in plasma and urine the within-day CVs were 0.69% and 1.1% respectively, and the total imprecision measured for a period of 65 days was 0.98%. Analytical recoveries were quantitative both with urine and plasma samples.

Barbiturates↗

A combined experimental and quantum chemical study on the putative protonophoric activity of thiocyanate.

Inhibition of gastric acid secretion by thiocyanate is explained by a protonophoric mechanism assuming that thiocyanate induces a H(+) back flux from the acidic gastric lumen into the parietal cells of gastric mucosa. Protonophoric activity of thiocyanate was examined by swelling measurements using rat liver mitochondria and theoretically by quantum chemical methods. Mitochondria suspended in K-thiocyanate medium plus nigericin (an H/K-exchanger) swelled when the medium pH was acidic, indicating that SCN(-) initiates a transfer of H(+) across the inner membrane. To rationalize the protonophoric activity of thiocyanate, we considered the dehydration of SCN(-) to be critical for transmembranal H(+) transfer. For modeling this process, various hydrate clusters of SCN(-) and Cl(-) were generated and optimized by density functional theory (DFT) at the B3-LYP/6-311++G(d,p) level. The cluster hydration energy was lower for SCN(-) than for Cl(-). The total Gibbs free energies of hydration of the ions were estimated by a hybrid supermolecule-continuum approach based on DFT. The calculated hydration energies also led to the conclusion that SCN(-) is less efficiently solvated than Cl(-). Due to the easier removal of the hydration shell of SCN(-) relative to Cl(-), SCN(-) is favored in going across the membrane, giving rise to the protonophoric activity.

Adenosine Triphosphate↗

Kinetic determination of thiocyanate on the basis of its catalytic effect on the oxidation of methylene blue with potassium bromate.

This study reports a sensitive kinetic spectrophotometric method for the determination of trace amounts of thiocyanate. In acidic solution, Methylene Blue (MB) is oxidized by bromate to form a colorless compound. The reaction is accelerated by trace amounts of thiocyanate and can be followed by measuring the absorbance at 664 nm. The absorbance of the reaction decreased with an increase in the reaction time. Under the optimum experimental conditions (0.56 M of sulfuric acid, 3.9 x 10(-5) M of MB, 3.0 x 10(-3) M of bromate, 180 s, 25 degrees C), thiocyanate can be determined in the range 5.0 - 180 ng/ml. The relative standard deviations (n = 8) are 2.81 and 1.43% for 10.0 and 150 ng/ml thiocyanate, respectively. The detection limit of this method is (3sigma) 3.8 ng/ml. This method was successfully applied to the determination of thiocyanate in real samples.

Bromates↗

Effect of thyroid status and thiocyanate on absorption and excretion of iodine by cattle.

Effects of throidectomy or iodine-131, thyroprotein feeding, and thiocyanate dosing on radioiodine metabolism in the bovine were studied in 34 animals. Two thyroidectomized calves excreted 44% more radioiodine in urine and 38% less in feces than two thyroid-tact calves. Oral thiocyanate increased urinary radioiodine 32% in throidectomized and 46% in intact calves while reducing fecal radioiodine 48% in throidectomize and 11% in intact calves. Urninary radioiodine clearance of two heifers was increased 52% by thiocyanate, but urine flow was not affected. Percentages of radioiodine doses cycled through the abomasum daily and recovered from digestive tracts at slaughter, respectively, were: 12 thyroid-intact cows, 468 and 77; two intact cows fed 10 g sodium thiocyanate daily,64 and 41; 10 thyroid-damagedcows, 506 and 149; and four thyroid-damaged cows fed 8 g thyroprotein daily, 372 and 93. Thyroid damage had little effect on gastric radioiodine secretion but increased total digestive tract radioiodine because of greater volume of tract contents. Inhibition of gastric radioiodine secretion by thiocyanate reduced the digestive tract radioiodine pool. The digestive tract iodine pool may conserve iodine by reducing loss in urine.

Abomasum↗

Thiocyanate elution measurement of relative affinity of phage antibodies.

Human antibodies generated by phage antibody technology have been widely used in the immunotherapy of various diseases. Among the characteristics of these therapeutic antibodies, affinity is one of the most important determinants of their biological efficacy. The binding of an antibody and its corresponding antigen could be disrupted by thiocyanate solution of different concentrations, depend upon the affinity of the antibody. This mechanism has been adopted to determine the relative affinity of monoclonal or polyclonal antibodies in routine immunological practice. Correlation between the elution method and other techniques that measure the affinity such as equilibrium dialysis and biospecific interaction analysis (BIA) has been established. Here we describe the applications of the thiocyanate elution method in the determination of the relative affinity index (RAI) of phage antibodies (Phabs). Five clone antibodies, including 3 clones of anti-keratin antibodies (AK1, AK2 and AK3) and 2 clones of anti-HBsAg antibodies (HB1 and HB2) were selected to express Phabs and Fabs, and the RAI were determined by ELISA after thiocyanate elution. A HRP-conjugated anti-M13 was used as secondary antibody for Phabs and HRP-goat-anti-human Fab was used for Fabs. The affinity ranks of the Phabs were compared with that of the Fab fragments. The results showed that all the Phabs tested were tolerant to thiocyanate treatment. The relative affinity rank of 5 Phabs coincided well with that of their corresponding Fabs. We conclude that the thiocyanate elution can be used as an easy and rapid method to measure and compare the relative affinity of Phabs.

Antibodies↗

The anaerobic metabolism of verapamil in rat cecal contents forms nor-verapamil and thiocyanate.

The anaerobic metabolism of verapamil was studied to determine the role the intestinal flora may have on the disposition of verapamil. Metabolites produced by the flora could be the source of adverse reactions reported only with the p.o. controlled release formulations but not with immediate release formulations. Verapamil was found to be metabolized to thiocyanate, nor-verapamil and several more polar metabolites that were detected by either a specific assay for cyanide and thiocyanate or a high-performance liquid chromatography (HPLC) assay, respectively. The rate of thiocyanate formation with an initial substrate concentration of 2 mM verapamil was found to be 0.008 +/- 0.004 microgram/hr/ml of 1:10 cecal suspension. The N-demethylated metabolite, nor-verapamil, was detected in the cecal suspensions but it also disappeared with time. The rate of verapamil disappearance was dependent on the concentration of bacteria in the incubation mixture; the rate being most rapid with the highest concentration of bacteria. Acetonitrile and butyronitrile were also found to be metabolized by the cecal flora. Cyanide as well as thiocyanate were produced from both organo-nitriles. These results suggest that the cyano group of verapamil, acetonitrile and butyronitrile were all cleaved to form cyanide and/or thiocyanate. With verapamil, cleavage of the cyano group would form new chemical entities that could be pharmacologically active and serve as a source of some of the adverse reactions or side-effects reported.

Acetonitriles↗

[Studies on influence of thiocyanate on immune response by use of the hemolytic plaque technique (author's transl)].

Mice immunized with sheep red blood cells produce more direct plaque-forming cells, estimated with the hemolytic plaque-technique, during the primary immune response if they receive in that time 150 mg NaSCN/kg body mass with the drinking-water every day. The thiocyanate quantity of serum in immunized animals is higher than that in non-immunized animals. The titers of antibodies estimated by the hemagglutination test is about 1 titer step higher in thiocyanate-treated animals than in non-thiocyanate-treated animals. That applies also to the secondary immune response, in which course thiocyanate was not supplied. It is possible, that for instance a greater number of memory-cells was produced during the primary immune response in consequence of the thiocyanate application. Studies in similar arrangement with guinea-pigs confirm these statements in certain parameters.

Animals↗

Passive smoking and thiocyanate concentrations in pregnant women and newborns.

Serum thiocyanate concentrations have been used as a marker of cigarette exposure in both smokers and nonsmokers. The authors used this measure to estimate passive exposure in low-risk healthy pregnant women at term. Three groups were compared: smokers, passive smokers, and nonsmokers. The mean thiocyanate concentration (95 mumol/L) was significantly higher (P less than .001) in smokers than in passive smokers (35.9 mumol/L) or nonsmokers (32.3 mumol/L). The maternal and umbilical mean cord thiocyanate concentrations were similar in the smoking group (95 versus 72 mumol/L). Although the umbilical cord levels in the infants of passive smokers and nonsmokers were similar (26 versus 23 mumol/L), both levels were significantly lower than those of smokers. Most important, there was an inverse relationship between umbilical cord thiocyanate concentration and birth weight (P less than .001). The authors found no evidence that passive cigarette smoke exposure resulted in higher maternal or umbilical cord thiocyanate concentrations than found in nonsmokers.

Adult↗

[Thiocyanate toxicity arising from prolonged use of sodium nitroprusside in severe heart failure].

PURPOSE: To evaluate the toxicity of thiocyanate induced by the infusion of sodium nitroprusside in patients with severe congestive failure. METHODS: We studied 23 patients with congestive heart failure, in class IV (NYHA) under continuous infusion of sodium nitroprusside with doses varying between 0.5 and 5.5 micrograms/kg/min. Clinical evaluation, thiocyanate serum dosage and laboratorial evaluation of renal, hepatic and pulmonary functions were done. RESULTS: Seventeen patients (74%) presented toxic levels of thiocyanate (over 10 micrograms/ml), with the average of 29.9 +/- 4.4 micrograms/ml. Only renal function was related to the presence of intoxication. Clinical evaluation was not accurate to diagnose the thiocyanate toxicity in the patients. CONCLUSION: Sodium nitroprusside is potentially toxic, especially when the renal function is abnormal. Thiocyanate dosage is useful in diagnosing nitroprusside induced toxicity and then it contributes to an adequate treatment and prevention of clinical toxicity.

Adult↗

Interference in glucose and other clinical chemistry assays by thiocyanate and cyanide in a patient treated with nitroprusside.

A 3-year-old patient treated with nitroprusside for congestive heart failure had 6.5 mmol/L thiocyanate (toxic, >1.5 mmol/L) and 110 micromol/L cyanide (toxic, >5 micromol/L) present in her blood. At this time a whole-blood glucose concentration assayed on the Nova Stat Profile 5 Plus (Stat Profile) was 25.1 mmol/L. Plasma from that specimen analyzed on a Kodak Ektachem 700 analyzer (E700) indicated 5.2 mmol/L glucose. We investigated the potential interference of dissolved thiocyanate or cyanide on glucose and other routine assays. Toxic concentrations of thiocyanate increased Stat Profile glucose values and E700 total calcium, chloride, and creatinine values. Stat Profile ionized calcium values were decreased by toxic concentrations of thiocyanate. Cyanide (100 micromol/L) decreased alanine aminotransferase activity measured on the E700. Interference with the Stat Profile glucose assay may have been caused by thiocyanate oxidation at the glucose electrode.

Blood Chemical Analysis↗

Different oxidation states of copper(I, I/II, II) thiocyanate complexes containing 1,2,4-triazole as a bridging ligand: syntheses, crystal structures, and magnetic properties of 2-D polymer Cu I(admtrz)SCN, linear trinuclear [CuI2CuII(admtrz)6(SCN)2](ClO4)2, and triangular trinuclear [CuII3(admtrz)4(SCN)3(mu3-OH)(H2O)](ClO4)2.H2O (admtrz = 4-amino-3,5-dimethyl-1,2,4-triazole).

Copper thiocyanate compounds with three different oxidation states, Cu(I)(admtrz)SCN (1), [Cu(I)(2)Cu(II)(admtrz)(6)(SCN)(2)](ClO(4))(2) (2), and [Cu(II)(3)(admtrz)(4)(SCN)(3)(mu(3)-OH)(H(2)O)](ClO(4))(2).H(2)O (3), have been synthesized and characterized (admtrz = 4-amino-3,5-dimethyl-1,2,4-triazole). Compounds 1 and 3 crystallize in the space group Pbca of the orthorhombic system with eight formula units in cells of dimensions a = 8.0221(2) A, b = 32.3844(1) A, c = 13.5659(3) A, R1/wR2 = 0.0595/0.1674 for compound 1 and a = 21.501(3) A, b = 18.382(2) A, c = 21.526(2) A, R1/wR2 = 0.0638/0.1519 for compound 3. Compound 2 crystallizes in the space group C2/c of the monoclinic system with four formula units in cells of dimensions a = 18.772(4) A, b = 11.739(2) A, c = 22.838(5) A, beta = 91.11(3) degrees, R1/wR2 = 0.0482/0.1265. The layered-type structure of 1 can be regarded as constructed from the tetranuclear copper units double bridged by one of the two unique thiocyanate and admtrz ligands, which are bridged by the other unique thiocyanate ligands to form a two-dimensional layered structure along the a and b directions. The linear trinuclear copper cation in mixed-valence compound 2 consists of one two-valence copper and two one-valence copper atoms which are bridged by admtrz ligands, and the external copper(I) atoms are coordinated by terminal thiocyanate. The EPR spectra of 2 show the existence of localized mixed-valence copper ions. The triangle trinuclear copper cation in compound 3 has its Cu(3) triangle capped by one apical mu(3)-OH group, each edge bridged by a bridging admtrz ligand and each Cu atom coordinated by a N atom from the terminal thiocyanate, while one of the three edges is further bridged by another admtrz ligand and the opposite Cu1 atom is coordinated by a water molecule. The EPR and magnetic susceptibility of compound 3 were studied, showing antiferromagnetic behavior.

Journal Article↗

Competitive Substitution and Electron Transfer in Reactions between Haloamminegold(III) and Halocyanoaurate(III) Complexes and Thiocyanate.

Kinetics for reactions between thiocyanate and trans-Au(CN)(2)Cl(2)(-), trans-Au(CN)(2)Br(2)(-), and trans-Au(NH(3))(2)Cl(2)(+) in an acidic, 1.00 M perchlorate aqueous medium have been studied by use of conventional and diode-array UV/vis spectroscopy and high-pressure and sequential-mixing stopped-flow spectrophotometry. Initial, rapid formation of mixed halide-thiocyanate complexes of gold(III) is followed by slower reduction to Au(CN)(2)(-) and Au(NH(3))(2)(+), respectively. This is an intermolecular process, involving attack on the complex by outer-sphere thiocyanate. Second-order rate constants at 25.0 degrees C for reduction of trans-Au(CN)(2)XSCN(-) are (6.9 +/- 1.1) x 10(4) M(-)(1) s(-)(1) for X = Cl and (3.1 +/- 0.7) x 10(3) M(-)(1) s(-)(1) for X = Br. For reduction of trans-Au(CN)(2)(SCN)(2)(-) the second-order rate constant at 25.0 degrees C is (3.1 +/- 0.1) x 10(2) M(-)(1) s(-)(1) and the activation parameters are DeltaH() = (55 +/- 3) x 10(2) kJ mol(-)(1), DeltaS() = (-17.8 +/- 0.8) J K(-)(1) mol(-)(1), and DeltaV() = (-4.6 +/- 0.5) cm(3) mol(-)(1). The activation volume for substitution of one chloride on trans-Au(NH(3))(2)Cl(2)(+) is (-4.5 +/- 0.5) cm(3) mol(-)(1), and that for reduction of trans-Au(NH(3))(2)(SCN)(2)(+) (4.6 +/- 0.9) cm(3) mol(-)(1). The presence of pi-back-bonding cyanide ligands stabilizes the transition states for both substitution and reductive elimination reactions compared to ammine. In particular, complexes trans-Au(CN)(2)XSCN(-) with an unsymmetric electron distribution along the X-Au-SCN axis are reduced rapidly. The observed entropies and volumes of activation reflect large differences in the transition states for the reductive elimination and substitution processes, respectively, the former being more loosely bound, more sensitive to solvational changes, and probably not involving any large changes in the inner coordination sphere. A transition state with an S-S interaction between attacking and coordinated thiocyanate is suggested for the reduction. The stability constants for formation of the very short-lived complex trans-Au(CN)(2)(SCN)(2)(-) from trans-Au(CN)(2)X(SCN)(-) (X = Cl, Br) by replacement of halide by thiocyanate prior to reduction can be calculated from the redox kinetics data to be K(Cl,2) = (3.8 +/- 0.8) x 10(4) and K(Br,2) = (1.1 +/- 0.4) x 10(2).

Journal Article↗

The effect of pressure on the oxidation state of iron, iv. Thiocyanate and isothiocyanate ligands.

The effect of pressure on the Mössbauer resonance spectra of Fe(III) with thiocyanate (M-SCN) and isothiocyanate (M-NCS) ligands has been studied. Fe(NCS)(3).6H(2)O, which has the isothiocyanate structure, reduces with increasing pressure, reversibly, and with a pressure dependence for the conversion very similar to that shown by a wide variety of ionic ferric compounds. K(3)Fe(SCN)(6) has the thiocyanate structure. At low pressures, it exhibits a significantly larger reduction than the Fe(NCS)(3). With increasing pressure the thiocyanate complexes isomerize, each complex apparently exhibiting about the same degree of conversion at a given pressure. At 150 kb the isomerization is essentially complete. The reduction of the Fe(III) to Fe(II) is reversible but the isomerization is not, and the sample, when powdered and reloaded in the high-pressure cell, exhibits the isomer shift, quadrupole splitting, and Fe(III) to Fe(II) conversion characteristic of an isothiocyanate. Heating the thiocyanate to 110 degrees C at 5 kb yields a mixture of thiocyanate and isothiocyanate that converts with pressure completely to the isothiocyanate.

Journal Article↗

The conformational state of human alpha 2-macroglobulin influences its dissociation into half-molecules by sodium thiocyanate.

Sodium thiocyanate dissociates native human alpha 2-macroglobulin into half-molecules consisting of two disulfide-bonded subunits, when the salt concentration is equal to or exceeds 1.2 M. Incubation with 1.6 M sodium thiocyanate for 1 h at 22 degrees C dissociates about 90% of alpha 2-macroglobulin into half-molecules. The half-molecules remain stable when the concentration of sodium thiocyanate is reduced to 0.2 M or zero, demonstrating that reassociation does not occur under these conditions. The internal thiol esters of the half-molecules are intact because they can be exposed by treatment with methylamine or trypsin. The noncovalent interaction between the disulfide-bonded dimers is stronger in the "closed-trap" than in the "open-trap" conformation of alpha 2-macroglobulin. The cleavage in the bait region by trypsin makes alpha 2-macroglobulin completely stable toward dissociation, and alpha 2-macroglobulin remains in a tetrameric state in 2.2 M sodium thiocyanate even when trypsin is not covalently bound to it. The increase in fluorescence with time indicates that conformational changes occur as a consequence of dissociation.

Humans↗