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Effects of cisplatin and thiosulfate upon auditory brainstem responses of guinea pigs.

Two side effects which limit the use of cisplatin in cancer chemotherapy are severe nephrotoxicity and ototoxicity. The concurrent administration of sodium thiosulfate with cisplatin reportedly protects from cisplatin nephrotoxicity, however, protection from ototoxicity has not been documented. The purpose of this study was to examine the efficacy of using thiosulfate to ameliorate the ototoxic effects of cisplatin. Toward this end, the effects of cisplatin alone, cisplatin administered concurrently with sodium thiosulfate (CIS/THIO), and sodium thiosulfate alone on the auditory brainstem response (ABR) of guinea pigs were compared. ABR waveforms, comparing latencies, amplitudes and response thresholds, were monitored before, immediately after, and 30 days post treatment. Sodium thiosulfate administered with cisplatin (CIS/THIO) consistently protected animals from hearing loss and surprisingly yielded significant increases in amplitude when compared to baseline and saline controls. However, ABRs of CIS/THIO animals returned toward baseline values after 30 days.

Animals↗

Sodium thiosulfate or hydroxocobalamin for the empiric treatment of cyanide poisoning?

Cyanide poisoning must be seriously considered in victims of smoke inhalation from enclosed space fires; it is also a credible terrorism threat agent. The treatment of cyanide poisoning is empiric because laboratory confirmation can take hours or days. Empiric treatment requires a safe and effective antidote that can be rapidly administered by either out-of-hospital or emergency department personnel. Among several cyanide antidotes available, sodium thiosulfate and hydroxocobalamin have been proposed for use in these circumstances. The evidence available to assess either sodium thiosulfate or hydroxocobalamin is incomplete. According to recent safety and efficacy studies in animals and human safety and uncontrolled efficacy studies, hydroxocobalamin seems to be an appropriate antidote for empiric treatment of smoke inhalation and other suspected cyanide poisoning victims in the out-of-hospital setting. Sodium thiosulfate can also be administered in the out-of-hospital setting. The efficacy of sodium thiosulfate is based on individual case studies, and there are contradictory conclusions about efficacy in animal models. The onset of antidotal action of sodium thiosulfate may be too slow for it to be the only cyanide antidote for emergency use. Hydroxocobalamin is being developed for potential introduction in the United States and may represent a new option for emergency personnel in cases of suspected or confirmed cyanide poisoning in the out-of-hospital setting.

Animals↗

Ion-pair chromatography of polythionates and thiosulfate with detection based on their catalytic effects on the postcolumn azide-iodine reaction.

The reduction of iodine with azide, catalyzed by polythionates (tri-, tetra-, penta- and hexathionate) and thiosulfate, has been utilized as a postcolumn reaction for chromatographic determination of these sulfur oxyanions. The method is based on the separation of polythionates and thiosulfate on an octadecylsilica column with an acetonitrile-water (20:80, v/v) mobile phase (pH 5.0) containing 3 mM tetrapropylammonium hydroxide and 6 mM acetic acid, followed by photometric measurement of the residual iodine (as triiodide) from the catalytic postcolumn azide-iodine reaction after mixing a reaction solution containing azide and iodine with the column effluent. Chromatograms obtained for the sulfur oxyanions showed negative peaks as a result of the decrease in absorbance of background. The conditions for the catalytic postcolumn reaction of the sulfur oxyanions in the column effluents were established by varying the concentrations of azide, iodine, iodide and acetic acid in the reaction solution, and varying the flow-rate, reaction temperature and length of the reaction tube. The detection limits (defined as SIN = 3) were 4.3 microM for trithionate, 0.10 microM for tetrathionate, 2.7 nM for pentathionate, 5.0 nM for hexathionate and 1.1 nM for thiosulfate. When compared with earlier methods, the proposed method gave a much higher sensitivity for the determination of two polythionates (penta- and hexathionate) and thiosulfate. This method was applied successfully to the analysis of polythionates and thiosulfate added to hot-spring water samples.

Azides↗

Rapid ion chromatography of L-ascorbic acid, nitrite, sulfite, oxalate, iodide and thiosulfate by isocratic elution utilizing a postcolumn reaction with cerium(IV) and fluorescence detection.

Rapid separation and determination of mixtures of L-ascorbic acid, nitrite, sulfite, oxalate, iodide and thiosulfate by conventional ion chromatography is often difficult due to incomplete separation of L-ascorbic acid and nitrite from the water peak when using eluents giving short elution times for iodide and thiosulfate. Separation of the six species within about 15 min has been achieved by isocratic elution using a resin-based ion-exchange column with a carbonate eluent containing a trace amount of 1,3,5-benzenetricarboxylic acid (BTA) and fluorescence measurement of cerium(III) formed via postcolumn reactions of the separated sample species with cerium(IV). Calibration plots of peak height versus concentration were linear up to 10.0 microM (1.76 ppm) for L-ascorbic acid, 8.0 microM (0.37 ppm) for nitrite, 8.0 microM (0.70 ppm) for oxalate, 80.0 microM (10.2 ppm) for iodide and 25.0 microM (2.80 ppm) for thiosulfate, whilst the sulfite calibration was linear up to 25.0 microM (2.00 ppm) when peak area was plotted against concentration. Detection limits (defined as S/N = 3) were 18 ppb for L-ascorbic acid, 4 ppb for nitrite, 16 ppb for sulfite, 7 ppb for oxalate, 72 ppb for iodide and 37 ppb for thiosulfate. The proposed method was applied successfully to the determination of L-ascorbic acid, nitrite, sulfite, oxalate, iodide or thiosulfate in water samples.

Anions↗

Thiosulfate enhances silver uptake by a green alga: role of anion transporters in metal uptake.

Short-term (< 1 h) silver uptake by the green alga Chlamydomonas reinhardtii was measured in the laboratory in defined inorganic media in the presence or absence of ligands (chloride and thiosulfate). In contradiction to the free-ion model of metal uptake, silver accumulation by the alga proved to be sensitive to the choice of ligand used to buffer the free silver concentration. For a low fixed free Ag+ concentration of 10 nM, silver uptake in the presence of thiosulfate (0.11 microM) was 2x greater than in the presence of chloride (4 mM). When sulfate was removed from the exposure medium (i.e., 81 microM-->0 microM), silver uptake in the presence of thiosulfate was even more markedly enhanced (more than 4x greater than in the presence of chloride). Varying the sulfate concentration in the exposure medium only affected silver uptake if thiosulfate was present. We conclude that silver-thiosulfate complexes are transported across the plasma membrane via sulfate/thiosulfate transport systems and that sulfate acts as a competitive inhibitor of this uptake mechanism.

Animals↗

Sodium thiosulfate solution spray for relief of irritation caused by Lugol's stain in chromoendoscopy.

BACKGROUND: Mucosal iodine staining is known to improve the endoscopic visualization of esophageal squamous dysplasia and cancer. However, it often causes mucosal irritation leading to retrosternal discomfort. The clinical usefulness of sodium thiosulfate solution (STS) for easing symptoms induced by mucosal staining with Lugol's solution was evaluated in this study. METHODS: One hundred twenty healthy men over 50 years of age were enrolled in the study. They each underwent esophagogastroscopy including the spraying of Lugol's iodine solution (10 mL) on the mid and distal esophagus and were subsequently randomized into three groups: (I) no treatment (n = 40), (II) spraying of 20 mL of aluminum-magnesium hydroxide gel (Maalox) by means of endoscopic catheter (n = 40), and (III) spraying of 20 mL of 5% sodium thiosulfate solution by means of endoscopic catheter (n = 40). An hour after the endoscopic examination the subjects were asked to complete a questionnaire that addressed adverse symptoms induced by Lugol's iodine staining. RESULTS: Sodium thiosulfate solution spray substantially reduced adverse symptoms that lasted more than 30 minutes after chromoendoscopy, compared with the no-treatment group. There was no significant difference in the proportion of subjects with symptoms between the Maalox and no-treatment groups. Cost of sodium thiosulfate solution spray per use was $0.15 (15 yen). CONCLUSIONS: Sodium thiosulfate solution is recommended for routine use after Lugol's staining.

Coloring Agents↗

Prevention of fetal and maternal cyanide toxicity from nitroprusside with coinfusion of sodium thiosulfate in gravid ewes.

Coadministration of sodium thiosulfate with sodium nitroprusside (SNP) to children and adults prevents increases in cyanide concentrations during anesthesia or long-term SNP infusions. We wondered whether maternally administered sodium thiosulfate would prevent increases in fetal red cell cyanide concentrations in gravid ewes receiving SNP infusions. Under anesthesia, the fetal head was delivered through a lateral hysterotomy for catheterization of the jugular vein; the fetus was left in utero. Six control ewes near term received SNP at 25 micrograms.kg-1.min-1 for 4 h. Norepinephrine was used to maintain maternal mean arterial pressure at 80% baseline values. Six experimental ewes received the same treatment except that sodium thiosulfate was infused with SNP (1 g sodium thiosulfate per 100 mg SNP). Serial red cell cyanide concentrations in ewes and fetuses were followed. One control fetal death resulted from abruptio placenta, and this ewe and fetus were excluded from analysis. An additional control ewe and fetus died from apparent cyanide poisoning late during the course of the experiment. While control ewes and fetuses suffered progressive increases in red cell cyanide concentrations into the toxic range, experimental ewes and fetuses never developed toxic red cell cyanide levels (ewes P < .003, fetuses P < .004). These data, if applicable to humans, suggest that coadministration of sodium thiosulfate with SNP to pregnant women at doses currently in use for nonpregnant patients will prevent fetal, as well as maternal, cyanide toxicity.

Animals↗

Dethiosulfovibrio peptidovorans gen. nov., sp. nov., a new anaerobic, slightly halophilic, thiosulfate-reducing bacterium from corroding offshore oil wells.

A strictly anaerobic thiosulfate-reducing bacterium was isolated from a corroding offshore oil well in Congo and was designated strain SEBR 4207T. Pure culture of the strain induced a very active pitting corrosion of mild steel, with penetration rates of up to 4 mm per year. This constitutes the first experimental evidence of the involvement of thiosulfate reduction in microbial corrosion of steel. Strain SEBR 4207T cells were vibrios (3 to 5 by 1 microns), stained gram negative, and possessed lateral flagella. Spores were not detected. Optimum growth occurred in the presence of 3% NaCl at pH 7.0 and 42 degrees C. Strain SEBR 4207T utilized peptides and amino acids, but not sugars or fatty acids. It fermented serine, histidine, and Casamino Acids, whereas arginine, glutamate, leucine, isoleucine, alanine, valine, methionine, and asparagine were only used in the presence of thiosulfate. Peptides were fermented to acetate, isobutyrate, isovalerate, 2-methylbutyrate, H2, and CO2. The addition of either thiosulfate or sulfur but not sulfate increased peptide utilization, growth rate, and biomass; during growth, H2S was produced and a concomitant decrease in H2 was observed. The addition of either thiosulfate or sulfur also reversed H2 inhibition. 16S rRNA sequence analysis indicates that strain SEBR 4207T is distantly related to members of the genus Thermoanaerobacter (83% similarity). Because the phenotypic and phylogenetic characteristics cannot be assigned to any described genus, strain SEBR 4207T is designated as a new species of a new genus, Dethiosulfovibrio peptidovorans gen. nov., sp. nov. Strain SEBR 4207T has been deposited in the Deutsche Sammlung von Mikroorganismen und zellkulturen GmbH (= DSM 11002).

Bacteriological Techniques↗

Inhibitory effects of sulfamic acid on three thiosulfate-oxidizing chemolithotrophs.

Sulfamate is an analogue of thiosulfate, and the sodium and potassium salts of sulfamic acid inhibited the chemolithoautotrophic growth on thiosulfate of Acidithiobacillus ferrooxidans and Halothiobacillus neapolitanus. The chemo-organotrophic growth of Paracoccus versutus on sucrose was similarly inhibited by sulfamate. Thiosulfate oxidation by suspensions of H. neapolitanus was, however, unaffected by sulfamate, showing that sulfamate did not directly affect thiosulfate uptake, activation or oxidation. Inhibition of P. versutus was not relieved by cysteine and methionine, indicating that sulfate uptake and sulfur amino acid biosynthesis were not directly affected by sulfamate. Sulfamate was not degraded by any of the bacteria, and so could not serve as an alternative to thiosulfate as an energy-yielding substrate. Sulfamate is also an analogue of ammonia and might act like hydrazine by inhibiting ammonium uptake or an essential enzyme activity.

Acidithiobacillus↗

The development and course of test reactions to gold sodium thiosulfate.

In our department, gold sodium thiosulfate has become the 2nd most common allergen in routinely patch tested dermatitis patients, with a rate around 10%. Test reactions to this compound often appear late, sometimes so late that active sensitization may be suspected. This study was performed to study the time course of the allergic reaction to gold sodium thiosulfate and to elucidate whether late test reactions mean active sensitization. 10 patients with contact allergy to gold sodium thiosulfate (0.5% pet.) were retested epicutaneously (e.c.) and intracutaneously (i.c.) with dilution series. The clinical course was followed for 2 months with initially short intervals, later more extended. During the entire study, 26 positive e.c. reactions were diagnosed. Within the 1st week, 17 (65%) were recorded. 12 reactions (46% of 26) were noted at the ordinary reading, 3 days after test application. After 10 days, another 9 reactions (35%) appeared. The patients with the latter reactions also had positive test reactions within the 1st week. After 2 months, 9 reactions remained. Out of 30 i.c. tests applied, 25 became positive within 1 week. 19 (76%) of these reactions changed in morphology from thin infiltrates to deep nodules. Another 4 nodules appeared in patients with previous negative i.c. tests. All 23 nodules remained after 2 months. E.c. and i.c. test reactions to gold sodium thiosulfate are long-lasting. Positive patch test reactions emerging after 10 days do not automatically imply active sensitization. To diagnose contact allergy to gold sodium thiosulfate, the ordinary reading at day 3 is insufficient; even reading at 1 week is insufficient and must be supplemented by a reading at 3 weeks. All the i.c. test reactions, however, appeared within 1 week and, in several, a dermal nodule was formed.

Allergens↗

Thiosulfate- and sulfide-dependent pyridine nucleotide reduction and gluconeogenesis in intact Thiobacillus neapolitanus.

Nicotinamide adenine dinucleotide phosphate (reduced form) is formed more rapidly after the addition of thiosulfate to suspensions of intact Thiobacillus neapolitanus in the absence of CO(2) than nicotinamide adenine dinucleotide (reduced form). Measurement of acid-stable metabolites shows this phenomenon to be the result of rapid reoxidation of nicotinamide adenine dinucleotide (reduced form) by 3-phosphoglyceric acid and other oxidized intermediates, which are converted to triose and hexose phosphates, and that, in reality, the rate of nicotinamide adenine dinucleotide (oxidized form) reduction exceeds that of nicotinamide adenine dinucleotide phosphate (oxidized form) by approximately 4.5-fold. The overall rate of pyridine nucleotide reduction by thiosulfate (264 nmol per min per mg of protein) is in excess of that rate needed to sustain growth. Pyridine nucleotide reduction, adenosine triphosphate synthesis, and carbohydrate synthesis are prevented by the uncoupler m-Cl-Carbonylcyanide phenylhydrazone. Sodium amytal inhibits pyridine nucleotide reduction and carbohydrate synthesis are prevented by the uncoupler m-Cl-carbonylcyanide observations are reproduced when sulfide serves as the substrate. The rate of pyridine nucleotide anaerobic reduction with endogenous substrates or thiosulfate is less than 1% of the aerobic rate with thiosulfate. We conclude that the principal, if not the only, pathway of pyridine nucleotide reduction proceeds through an energy-dependent and amytal-sensitive step when either thiosulfate or sulfide is used as the substrate.

Adenosine Triphosphate↗

Catabolic thiosulfate disproportionation and carbon dioxide reduction in strain DCB-1, a reductively dechlorinating anaerobe.

Strain DCB-1 is a strict anaerobe capable of reductive dehalogenation. We elucidated metabolic processes in DCB-1 which may be related to dehalogenation and which further characterize the organism physiologically. Sulfoxy anions and CO2 were used by DCB-1 as catabolic electron acceptors. With suitable electron donors, sulfate and thiosulfate were reduced to sulfide. Sulfate and thiosulfate supported growth with formate or hydrogen as the electron donor and thus are probably respiratory electron acceptors. Other electron donors supporting growth with sulfate were CO, lactate, pyruvate, butyrate, and 3-methoxybenzoate. Thiosulfate also supported growth without an additional electron donor, being disproportionated to sulfide and sulfate. In the absence of other electron acceptors, CO2 reduction to acetate plus cell material was coupled to pyruvate oxidation to acetate plus CO2. Pyruvate could not be fermented without an electron acceptor. Carbon monoxide dehydrogenase activity was found in whole cells, indicating that CO2 reduction probably occurred via the acetyl coenzyme A pathway. Autotrophic growth occurred on H2 plus thiosulfate or sulfate. Diazotrophic growth occurred, and whole cells had nitrogenase activity. On the basis of these physiological characteristics, DCB-1 is a thiosulfate-disproportionating bacterium unlike those previously described.

Acetates↗

Relation of the iron oxidizer, Thiobacillus ferrooxidans, to thiosulfate.

Colmer, Arthur R. (Louisiana State University, Baton Rouge). Relation of the iron oxidizer, Thiobacillus ferrooxidans, to thiosulfate. J. Bacteriol. 83:761-765. 1962.-A restudy has been made of Thiobacillus ferrooxidans secured from the acid drainage of some northern West Virginia coal mines. Cultures isolated from ferrous iron agar and then subcultured for 85 consecutive transfers in thiosulfate broth during a period of 14 months were able to use ferrous iron as their energy source when returned to ferrous iron broth. Thiosulfate utilization was quantitatively followed by iodine titration and pH change; ferrous iron oxidation was quantitatively determined by use of 1,10-phenanthroline.Characteristic colonial forms were produced by T. ferrooxidans growing on thiosulfate agar irrespective of whether the inoculum was from iron broth or thiosulfate broth.

Acidithiobacillus↗

Formation of thiosulfate from sulfite by Desulfovibrio vulgaris.

Crude extracts of Desulfovibrio vulgaris reduced sulfite to sulfide. Ammonium sulfate fractionation of crude extracts separated a thiosulfate-forming system from sulfite- and thiosulfate-reductase activities. Further purification by sucrose density centrifugation separated the thiosulfate-forming system into two components, both of which were required for the reaction. In addition to these two components, cytochrome c(3), ferredoxin, and hydrogenase were required to form thiosulfate from sulfite. By absorption spectra and from the effect of pH and substrate concentration, the ionic species acting as the substrate for thiosulfate-formation was concluded to be bisulfite.

Cell-Free System↗

[Thiosulfate oxidation by nonsulfur purple bacteria].

The capability to oxidize thiosulfate was studied in 11 cultures of purple bacteria belonging to Rhodomicrobium vannielii, Rhodopseudmonas viridis, Rh. sphaeroides, Rh. capsulata, and Rhodospirillum rubrum. All the bacteria oxidized thiosulfate under aerobic conditions in the dark. The strains 2R, 8259, A1, A2 and D1 of Rh. sphaeroides oxidized thiosulfate under anaerobic conditions in the light, and the process was coupled with carbon dioxide fixation. All the strains contained thiosulfate reductase, and the majority of them possessed also the activity of thiosulfate oxidase and sulfite oxidase.

Aerobiosis↗

Studies of sulfate utilization by algae: 8. The ubiquity of sulfate reduction to thiosulfate.

Cell-free extracts from several microorganisms, when prepared by methods originally devised for Chlorella pyrenoidosa (Emerson strain 3) and incubated anaerobically with ATP, Mg(2+), and 2, 3-dimercaptopropan-1-ol, are capable of reducing sulfate-(35)S to thiosulfate. These microorganisms include, in addition to C. pyrenoidosa (Emerson strain 3), several other strains of C. pyrenoidosa, Chlorella protothecoides, Chlorella vulgaris, Anacystis sp., Chlamydomonas reinhardi, Escherichia coli, Salmonella typhimurium, and baker's yeast. Three of these organisms, E. coli, S. typhimurium, and baker's yeast, were previously reported by others to reduce sulfate to sulfite. Moreover, three mutant strains of S. typhimurium (Ba-25, Ce-363, and Bc-482) previously reported by other workers to be unable to reduce sulfate to sulfite also cannot form thiosulfate, and one mutant strain (Cd-68) reportedly able to form sulfite can also form thiosulfate. Taken together, this suggests that thiosulfate-forming activity may be a common feature of sulfate-reducing systems, and it may be present in enzymatic systems previously thought to be forming sulfite. Reasonably conclusive identification of thiosulfate is provided by ion exchange chromatography and by paper electrophoresis; the ambiguities associated with other analytical methods are discussed.

Journal Article↗

Mixotrophic and Autotrophic Growth of Thiobacillus acidophilus on Glucose and Thiosulfate.

Mixotrophic growth of the facultatively autotrophic acidophile Thiobacillus acidophilus on mixtures of glucose and thiosulfate or tetrathionate was studied in substrate-limited chemostat cultures. Growth yields in mixotrophic cultures were higher than the sum of the heterotrophic and autotrophic growth yields. Pulse experiments with thiosulfate indicated that tetrathionate is an intermediate during thiosulfate oxidation by cell suspensions of T. acidophilus. From mixotrophic growth studies, the energetic value of thiosulfate and tetrathionate redox equivalents was estimated to be 50% of that of redox equivalents derived from glucose oxidation. Ribulose 1,5-bisphosphate carboxylase (RuBPCase) activities in cell extracts and rates of sulfur compound oxidation by cell suspensions increased with increasing thiosulfate/glucose ratios in the influent medium of the mixotrophic cultures. Significant RuBPCase and sulfur compound-oxidizing activities were detected in heterotrophically grown T. acidophilus. Polyhedral inclusion bodies (carboxysomes) could be observed at low frequencies in thin sections of cells grown in heterotrophic, glucose-limited chemostat cultures. Highest RuBPCase activities and carboxysome abundancy were observed in cells from autotrophic, CO(2)-limited chemostat cultures. The maximum growth rate at which thiosulfate was still completely oxidized was increased when glucose was utilized simultaneously. This, together with the fact that even during heterotrophic growth the organism exhibited significant activities of enzymes involved in autotrophic metabolism, indicates that T. acidophilus is well adapted to a mixotrophic lifestyle. In this respect, T. acidophilus may have a competitive advantage over autotrophic acidophiles with respect to the sulfur compound oxidation in environments in which organic compounds are present.

Journal Article↗

Pathways and microbiology of thiosulfate transformations and sulfate reduction in a marine sediment (kattegat, denmark).

Reductive and oxidative pathways of the sulfur cycle were studied in a marine sediment by parallel radiotracer experiments with SO(4), H(2)S, and S(2)O(3) injected into undisturbed sediment cores. The distributions of viable populations of sulfate- and thiosulfate-reducing bacteria and of thiosulfate-disproportionating bacteria were concurrently determined. Sulfate reduction occurred both in the reducing sediment layers and in oxidized and even oxic surface layers. The population density of sulfate-reducing bacteria was >10 cm in the oxic layer, high enough that it could possibly account for the measured rates of sulfate reduction. The bacterial numbers counted in the reducing sediment layers were 100-fold lower. The dominant sulfate reducers growing on acetate or H(2) were gas-vacuolated motile rods which were previously undescribed. The products of sulfide oxidation, which took place in both oxidized and reduced sediment layers, were 65 to 85% S(2)O(3) and 35 to 15% SO(4). Thiosulfate was concurrently oxidized to sulfate, reduced to sulfide, and disproportionated to sulfate and sulfide. There was a gradual shift from predominance of oxidation toward predominance of reduction with depth in the sediment. Disproportionation was the most important pathway overall. Thiosulfate disproportionation occurred only as cometabolism in the marine acetate-utilizing sulfate-reducing bacteria, which could not conserve energy for growth from this process alone. Oxidative and reductive cycling of sulfur thus occurred in all sediment layers with an intermediate "thiosulfate shunt" as an important mechanism regulating the electron flow.

Journal Article↗