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PubMed1982

A nuclear magnetic relaxation study of conformational changes induced by substrate and temperature in bovine liver thiosulfate sulfurtransferase and yeast hexokinase.

Nuclear magnetic relaxation studies have been performed on thiosulfate sulfurtransferase (EC 2.8.1.1) and hexokinase (EC 2.7.1.1). Observation of proton spin-lattice relaxation times T1 indicates that structural transitions occur in these enzymes in the range 0-40 degrees C and that there are different temperature-dependent forms of thiosulfate sulfurtransferase and hexokinase. Thermal transitions between these forms are affected by the binding of the substrates. The results may be due to changes in the interactions between the structural domains into which the single polypeptide chains of thiosulfate sulfurtransferase and hexokinase are folded.

Animals↗
PubMed1993

Protection against paraquat-induced toxicity with sulfite or thiosulfate in mice.

The toxicity of the herbicide paraquat in mice, measured by the single dose LD50 after 7 days, was significantly decreased by coinjection of thiosulfite (1 g/kg; one time per day for 3 days) or sulfite (0.2 g/kg; one time per day for 3 days). However, the toxicity of paraquat was not changed by coinjection of sulfate (1 g/kg; one time per day for 3 days). The body weight of mice was significantly decreased by paraquat treatment (30 mg/kg, i.p.). However, the decrease of body weight was abolished by coinjection of thiosulfate or sulfite but not by coinjection of sulfate. On the other hand, paraquat significantly decreased reduced glutathione contents in liver. The depletion of the glutathione contents was also abolished by coinjection of thiosulfate or sulfite but not by coinjection of sulfate. These results suggest that the preventive effect against paraquat-induced toxicity with thiosulfate or sulfite may involve the glutathione-dependent detoxication in mice.

Animals↗
PubMed1987

Hydroxycobalamin/sodium thiosulfate as a cyanide antidote.

Severe, acute cyanide poisoning is uncommon and can be very difficult to diagnose if a history of exposure is unavailable. Victims of smoke inhalation may have significant cyanide poisoning as well as carbon monoxide toxicity. The Lilly Cyanide Antidote Kit currently available in America unfortunately has its own inherent toxicity. An efficacious antidote lacking toxicity is desirable, especially in cases where the diagnosis of cyanide poisoning cannot be made with certainty. Hydroxycobalamin/sodium thiosulfate has been used in France since 1970. Both components have been shown to be safe and efficacious in animal studies. Case reports of human cyanide poisoning treated with hydroxycobalamin/sodium thiosulfate have been published only in French. Animal and human data on the use of this antidotal combination are reviewed. Hydroxycobalamin/sodium thiosulfate is an efficacious cyanide antidote with little inherent toxicity.

Acute Disease↗
PubMed2005

[Sodium thiosulfate for acute cyanide poisoning: study in a rat model].

Unlike practices in the United States where it is associated with other antidotes, sodium thiosulfate is not used for emergency therapy for cyanide poisoning in France. The purpose of this study was to develop a rat model using intraperitoneal injections of sodium thiosulfate at a dose of 225 mg/kg to test its therapeutic efficacy for acute cyanide poisoning. Efficacy was assessed directly by quantifying arterial blood cyanide and indirectly using markers of hypoxia: serum lactate and arteriolization of venous blood gases. Cyanide poisoning induced intense biological anomalies which were persistent (serum lactate) or transient (blood gases). Sodium thiosulfate was found to be an effective antidote in the rat enabling rapid normalization of hypoxia markers and clearing of cyanide from arterial blood.

Animals↗
PubMed1997

Kinetics of the conjugation of aniline mustards with glutathione and thiosulfate.

The rates of the non-enzymatic conjugation of the substituted aniline mustards, melphalan, chlorambucil and p-(N,N-bis(2-chloroethyl))toluidine with glutathione and thiosulfate were determined using nuclear magnetic resonance spectroscopy. Using this method, the disappearance of drug and the formation of both the mono-thioether and bis-thioether conjugates can be monitored directly. For glutathione conjugation, the rate constants for the formation of the first and second aziridinium intermediates were similar. With thiosulfate conjugation, the rate constant for the formation of the first aziridinium intermediate is greater than the rate constant for the formation of the second aziridinium. This demonstrates that the type of nucleophile has a significant influence on the overall alkylating activity of these bifunctional mustards. The bisthioether adduct formed from the reaction between p-(N,N-bis([2-13C]-2-chloroethyl))toluidine and glutathione and thiosulfate can be identified and scrambling of the 13C label in the product provides strong evidence that the alkylation must occur through an aziridinium intermediate.

Aniline Mustard↗
PubMed1998

Sulfur oxidation in rice field soil: activity, enumeration, isolation and characterization of thiosulfate-oxidizing bacteria.

In rice paddy fields the bulk soil is anoxic, but oxygenated zones occur in the surrounding of the rice roots to where oxygen is transported via the aerenchyma system of the rice plants. In the anaerobic soil compartments sulfate is consumed by sulfate-reducing bacteria. In the rhizosphere the reduced sulfur compounds can be reoxidized by sulfur-oxidizing bacteria. Measurements of the potential activity of thiosulfate-oxidizing bacteria in soil slurries derived from planted rice soil microcosms showed turnover rates of 2-6 mumol d-1 g-dw-1. Thiosulfate was oxidized to sulfate with tetrathionate as intermediate. Most probable number (MPN) enumeration with three aerobic media and one anaerobic nitrate-amended medium showed that thiosulfate-oxidizing bacteria were abundant in paddy soil and in rhizosphere soil at numbers of 10(5) to 10(6) per gram dry weight soil. Nine isolates of S-oxidizing bacteria were obtained from enrichment cultures or from the highest dilutions of the MPN series and were affiliated to four different phylogenetic groups. These isolates were characterized by physiological properties and by comparative 16S rDNA sequence analysis. Three isolates (TA1-AE1, TA1-A1 and TA12-21) were shown to be facultatively chemolithoautotrophic strains of Ancylobacter aquaticus. Three further isolates (Tv6-2b, Z2A-6A and Z4A-2A) were also facultatively chemolithoautotrophic and were affiliated with the Xanthobacter sp. group, probably representing new strains of X. flavus or X. tagetidis. Strain SZ-2111 was phylogenetically related to Bosea thiooxidans. However, the genus Bosea is described as obligately heterotrophic, whereas strain 5Z-2111 was able to grow autotrophically. The isolates 5Z-C1 and TBW3 were obligate chemolithoautotrophs and were closely affiliated with Thiobacillus thioparus. Our results showed that S-oxidizing bacteria were abundant and active in rice paddy soil and consisted of physiologically and phylogenetically diverse populations.

Anaerobiosis↗
PubMed2006

Intraperitoneal sodium thiosulfate for the treatment of calciphylaxis.

Calcific uremic arteriolopathy (or calciphylaxis) is a severe complication of renal failure characterized by subcutaneous calcification of the small arteries and tissue necrosis. We describe the case of a woman receiving continuous cycling peritoneal dialysis with calciphylaxis involving upper and lower extremities. After intolerance of intravenous sodium thiosulfate and limited intravenous access options, we administered sodium thiosulfate intraperitoneally and quantitated the amount of extra calcium removed. Intraperitoneal administration of sodium thiosulfate was well tolerated and led to removal of extra calcium with peritoneal dialysis.

Adolescent↗
PubMed2002

Structural basis for the oxidation of thiosulfate by a sulfur cycle enzyme.

Reduced inorganic sulfur compounds are utilized by many bacteria as electron donors to photosynthetic or respiratory electron transport chains. This metabolism is a key component of the biogeochemical sulfur cycle. The SoxAX protein is a heterodimeric c-type cytochrome involved in thiosulfate oxidation. The crystal structures of SoxAX from the photosynthetic bacterium Rhodovulum sulfidophilum have been solved at 1.75 A resolution in the oxidized state and at 1.5 A resolution in the dithionite-reduced state, providing the first structural insights into the enzymatic oxidation of thiosulfate. The SoxAX active site contains a haem with unprecedented cysteine persulfide (cysteine sulfane) coordination. This unusual post-translational modification is also seen in sulfurtransferases such as rhodanese. Intriguingly, this enzyme shares further active site characteristics with SoxAX such as an adjacent conserved arginine residue and a strongly positive electrostatic potential. These similarities have allowed us to suggest a catalytic mechanism for enzymatic thiosulfate oxidation. The atomic coordinates and experimental structure factors have been deposited in the PDB with the accession codes 1H31, 1H32 and 1H33.

Amino Acid Sequence↗
PubMedDate not supplied

Determination of thiosulfate in body fluids by GC and GC/MS.

A simple and sensitive method to determine thiosulfate in human blood and urine was devised. Thiosulfate was first alkylated with pentafluorobenzyl bromide, with L-ascorbic acid as the stabilizer and sodium chloride as the catalyst. The alkylated thiosulfate was oxidized with iodine to obtain bis(pentafluorobenzyl)disulfide, which was then subjected to gas chromatography and gas chromatography/mass spectrometry. Mass fragmentography was used to identify the disulfide, and gas chromatography with an electron capture detector was used for quantitative determination. The lower limit of detection was 0.003 mumol/mL.

Alkylation↗
PubMed1999

The lack of transplacental movement of the cyanide antidote thiosulfate in gravid ewes.

UNLABELLED: A previous study reported that the co-infusion of IV sodium thiosulfate (STS) with sodium nitroprusside (SNP) to near-term gravid ewes prevented both maternal and fetal cyanide toxicity. We questioned whether maternally administered STS crossed the ovine placenta to enhance fetal transulfuration of cyanide, or whether the fetus was dependent on maternal detoxification of cyanide after diffusion of cyanide into the maternal circulation. Ten anesthetized, near-term gravid ewes underwent hysterotomies with delivery of fetal heads for venous catheterization. Five control ewes received IV isotonic sodium chloride solution, whereas five experimental ewes received IV STS (50 mg/kg over 15 min). Serial plasma thiosulfate concentrations in ewes and fetuses were measured over 135 min. Areas under the time-plasma thiosulfate concentration curves were calculated for experimental and control ewes at 2758+/-197 and 508+/-74 min x mg(-1) x L(-1), respectively (P < 0.008). Mean areas under the curve for experimental and control fetuses were 236+/-34 and 265+/-23 min x mg(-1) x L(-1), respectively (P > 0.5). Maternally administered STS may prevent fetal cyanide poisoning from SNP administration without relying on STS crossing the placenta into the fetal circulation. Fetal cyanide may cross down a concentration gradient from fetal to maternal circulation, to be transulfurated to thiocyanate in maternal tissues. IMPLICATIONS: We evaluated the mechanism of action of sodium thiosulfide (STS) in sodium nitroprusside-induced cyanide toxicity in the ewe. Fetal cyanide poisoning is alleviated by maternal administration of STS, although this cyanide antidote apparently does not cross the placenta.

Animals↗
PubMed2001

Dethiosulfovibrio russensis sp. nov., Dethosulfovibrio marinus sp. nov. and Dethosulfovibrio acidaminovorans sp. nov., novel anaerobic, thiosulfate- and sulfur-reducing bacteria isolated from 'Thiodendron' sulfur mats in different saline environments.

Four strains of strictly anaerobic, sulfur- and thiosulfate-reducing bacteria, SR12T, SR13, SR15T and WS100T, were isolated from 'Thiodendron' sulfur mats obtained from different saline environments. All isolates were motile, Gram-negative, non-spore-forming curved rods with pointed or rounded ends. The sizes of cells varied from 0.9 x 3-5 microm for strains SR12T, SR13 and SR15T to 0.9 x 4.8 microm for strain WS100T. All strains could form long spiral filamentous cells up to 70-110 microm during the early stage of growth. All strains were motile by a tumbling movement and possessed lateral flagella arranged at the concave side of cells. Incomplete cross-septa were distinctive features of all strains. Growth occurred at temperatures of 10-40 degrees C with an optimum at 28 degrees C. The pH limits for growth were 5.5 to 8.0, with optimal growth at pH 6.5-7.0. All isolates were obligately anaerobic and slightly halophilic and grew in media containing 0.5-5% NaCl with an optimum at 2% NaCl. All strains were chemoorganoheterotrophic, having a fermentative type of metabolism and utilized proteins, peptides, amino acids and some organic acids, but not sugars, fatty acids or alcohols. Some organic substrates (isoleucine, valine, alanine, glutamate) were utilized only by strain SR12T in the presence of sulfur or thiosulfate. Fermentation of citrate yielded mainly acetate, CO2 and H2. Sulfur and thiosulfate were reduced to hydrogen sulfide during the fermentation of organic substances, which increased cell yields and growth rates. Sulfate, sulfite, fumarate, nitrate, Fe2O3, MnO2, DMSO and elemental selenium were not used as electron acceptors by these strains. The G+C contents of the DNA were 51 mol% for strains SR12T, SR13 and SR15T and 52 mol% for strain WS100T. Based on morphological, physiological and phylogenetic similarities, all four isolates could be assigned to three new species of the genus Dethiosulfovibrio, named Dethiosulfovibrio russensis (type strain DSM 12538T), Dethiosulfovibrio marinus (type strain DSM 12537T) and Dethiosulfovibrio acidaminovorans (type strain DSM 12590T).

Bacterial Typing Techniques↗
PubMed2002

Clostridium thiosulfatireducens sp. nov., a proteolytic, thiosulfate- and sulfur-reducing bacterium isolated from an upflow anaerobic sludge blanket (UASB) reactor.

A strictly anaerobic, gram-positive, sporulating rod (0.5-0.6 x 2.0-4.0 microm), designated strain Lup 21T, was isolated from an upflow anaerobic sludge blanket (UASB) reactor treating cheese-factory wastewater. Strain Lup 21T was motile by means of peritrichous flagella, had a G+C content of 31.4 mol% and grew optimally at 37 degrees C, pH 7.4, in the absence of NaCl. It is a heterotrophic micro-organism, utilizing proteinaceous compounds (gelatin, peptides, Casamino acids and various single amino acids) but unable to use any of the carbohydrates tested as a carbon and energy source. It reduced thiosulfate and elemental sulfur to sulfide in the presence of Casamino acids as carbon and energy sources. Acetate, butyrate, isobutyrate, isovalerate, CO2 and sulfide were end products from oxidation of gelatin and Casamino acids in the presence of thiosulfate as an electron acceptor. In the absence of thiosulfate, serine, lysine, methionine and histidine were fermented. On the basis of 16S rRNA similarity, strain Lup 21T was related to members of the low-G+C Clostridiales group, Clostridium subterminale DSM 6970T being the closest relative (with a sequence similarity of 99.4%). DNA-DNA hybridization was 56% with this species. On the basis of phenotypic, genotypic and phylogenetic characteristics, the isolate was designated as a novel species of the genus Clostridium, Clostridium thiosulfatireducens sp. nov. The type strain is strain Lup 21T (= DSM 13105T = CIP 106908T).

Anaerobiosis↗
PubMed2000

Novel activation of non-selective cationic channels by dinitrosyl iron-thiosulfate in PC12 cells.

Low molecular mass dinitrosyl iron complexes (DNICs) are nitrosating agents and it is known that the dinitrosyl iron moiety can be transferred to proteins. The aim of the present study was to determine if the formation of protein-bound dinitrosyl iron can modulate ionic channel activity. In PC12 cells, dinitrosyl iron-thiosulfate (50 microM) caused irreversible activation of a depolarizing inward current (IDNIC). IDNIC was partially inhibited by the metal chelator diethyldithiocarbamate (DETC, 1 mM), but not by the reducing/denitrosylating agent dithiothreitol (DTT, 5 mM). The activation of IDNIC was not reproduced by application of nitric oxide (NO., 100 microM), S-nitrocysteine (200 microM) or ferrous iron-thiosulfate (50 microM), and was not prevented by the irreversible guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4, 3-a]quinoxalin-1-one (ODQ, 1 microM). Similarly, intracellular perfusion of dinitrosyl iron-thiosulfate (100 microM) did not result in activation of IDNIC. Ion replacement experiments show that the DETC-sensitive component of IDNIC is a non-selective cationic current. In accordance, IDNIC was blocked by antagonists of receptor-operated calcium entry, gadolinium (25 microM) and SK&F 96365 (25 microM). Single-channel measurements from outside-out patches reveal that the DETC-sensitive component of IDNIC is an inward current carried by a cationic channel having a conductance of 50 pS. The present observations suggest that the formation of ion channel-bound dinitrosyl iron represents another mechanism of regulation of ion channel activity by NO.-related species, which may be particularly important in pathophysiological processes where NO. is overproduced.

Animals↗
PubMedDate not supplied

Long-term intravenous sodium thiosulfate in the treatment of a patient with calciphylaxis.

Calciphylaxis is a disabling and life-threatening complication that primarily affects patients who are dialysis dependent. This disease entity is characterized by calcification, intimal hypertrophy, and thrombosis of small vessels, which results in necrotizing, nonhealing ulcers. The development of these lesions portends a grim prognosis, as they are often accompanied by severe and sometimes fatal infectious complications. Although several strategies aimed at treating and preventing this affliction have been reported in the literature, the outcome for most patients with calciphylaxis remains quite poor. We describe an anuric hemodialysis patient who developed severe calciphylaxis that proved refractory to conventional treatment. Following extensive debridement of several wounds, intravenous sodium thiosulfate was utilized as an adjunctive therapy four times a week. Within 6 months, excellent wound healing ensued as well as a dramatic improvement in the lesions that were not previously resected. Aside from occasional nausea, these treatments were well tolerated, despite the development of an anion gap metabolic acidosis. After 34 months of continued treatment the patient remains free from disease recurrence and has demonstrated no untoward effect of prolonged therapy. In an effort to delineate the pharmacokinetics of this drug in a hemodialysis patient, serum thiosulfate levels were obtained 15 minutes after infusion as well as before and after subsequent dialysis treatments. Consistent with prior studies in anuric canines, we found measurable quantities of the drug more than 50 hours after treatment, in addition to a markedly elevated half life of 478 minutes. However, given the lack of significant toxicity, as well as a dramatic clinical improvement, we feel that sodium thiosulfate may have an important adjunctive role in the treatment of calciphylaxis in dialysis patients.

Anuria↗
PubMed2001

Phylogeny and distribution of the soxB gene among thiosulfate-oxidizing bacteria.

A PCR protocol for the detection of sulfur-oxidizing bacteria based on soxB genes that are essential for thiosulfate oxidation by sulfur-oxidizing bacteria of various phylogenetic groups which use the 'Paracoccus sulfur oxidation' pathway was developed. Five degenerate primers were used to specifically amplify fragments of soxB genes from different sulfur-oxidizing bacteria previously shown to oxidize thiosulfate. The PCR yielded a soxB fragment of approximately 1000 bp from most of the bacteria. Amino acid and nucleotide sequences of soxB from reference strains as well as from new isolates and environmental DNA from a hydrothermal vent habitat in the North Fiji Basin were compared and used to infer relationships of soxB between sulfur-oxidizing bacteria belonging to various 16S rDNA-based phylogenetic groups. Major phylogenetic lines derived from 16S rDNA were confirmed by soxB phylogeny. Thiosulfate-oxidizing green sulfur bacteria formed a coherent group by their soxB sequences. Likewise, clearly separated branches demonstrated the distant relationship of representatives of alpha-, beta-, and gamma-Proteobacteria including representative species of the former genus Thiobacillus (now Halothiobacillus - gamma-Proteobacteria, Thiobacillus - beta-Proteobacteria and Starkeya - alpha-Proteobacteria). This general picture emerged although apparent evidence for lateral transfer of the soxB gene is indicated and comparison of soxB phylogeny and 16S rDNA phylogeny points to the significance of this gene transfer in hydrothermal vent bacterial communities of the North Fiji Basin.

Cytochrome c Group↗
PubMed1995

Skin testing with gold sodium thiomalate and gold sodium thiosulfate.

Recently gold sodium thiosulfate was found to be the most common sensitizer after nickel sulfate in our routinely patch tested dermatitis patients. When patients hypertensive to gold sodium thiosulfate were tested with another monovalent gold salt, gold sodium thiomalate, at equimolar concentrations, in principle, no positive reactions were obtained. Gold sodium thiomalate is used for treatment of rheumatoid arthritis, a treatment with a high frequency of adverse skin reactions. To investigate whether the reactivity difference between the 2 gold salts was due to differences in bioavailability, some experiments were carried out. Intracutaneous tests with the 2 gold salts at equimolar concentrations yielded equivalent reactions. When the concentration of gold sodium thiomalate for epicutaneous testing was increased, all 12 gold-allergic patients reacted positively. Therefore, in our department, contact allergy to gold sodium thiomalate is probably as common as contact allergy to gold sodium thiosulfate.

Administration, Cutaneous↗
PubMed1997

Contact allergy to gold sodium thiosulfate. A comparative study.

During 1995, we added gold sodium thiosulfate and potassium dicyanoaurate to the patch test standard series. Our purpose was to compare the reactivity of the gold salts, to determine the frequency of contact allergy to gold in our country, to compare our results with those of the Malmö group and, finally to try to clarify the clinical relevance 2853 patients were routinely tested and 168 patients answered a questionnaire similar to that used by the Malmö group. Contact allergy to gold was found in 23 patients, all women: 22 to gold sodium thiosulfate (0.78%), only 1 to potassium dicyanoaurate and 2 to both salts. All reactors had their ears pierced and were exposed to gold jewelery (mainly earrings). Simultaneous allergies to nickel and cobalt were statistically significant in patients with positive patch tests to gold sodium thiosulfate. Atopy was no more common among these patients.

Chi-Square Distribution↗
PubMed2000

Thiosulfate disproportionation by Desulfotomaculum thermobenzoicum.

Desulfotomaculum thermobenzoicum, but not Desulfotomaculum nigrificans, Desulfotomaculum ruminis, or Desulfosporosinus orientis, grew by disproportionation of thiosulfate, forming stoichiometric amounts of sulfate and sulfide; sulfite was not disproportionated. The addition of acetate enhanced growth and thiosulfate disproportionation by D. thermobenzoicum compared to those observed with thiosulfate alone.

Anaerobiosis↗