Cisplatin chemotherapy and surgery are effective treatments for children with standard-risk hepatoblastoma but may cause considerable and irreversible hearing loss. This trial compared cisplatin with ...cisplatin plus delayed administration of sodium thiosulfate, aiming to reduce the incidence and severity of cisplatin-related ototoxic effects without jeopardizing overall and event-free survival.
We randomly assigned children older than 1 month and younger than 18 years of age who had standard-risk hepatoblastoma (≤3 involved liver sectors, no metastatic disease, and an alpha-fetoprotein level of >100 ng per milliliter) to receive cisplatin alone (at a dose of 80 mg per square meter of body-surface area, administered over a period of 6 hours) or cisplatin plus sodium thiosulfate (at a dose of 20 g per square meter, administered intravenously over a 15-minute period, 6 hours after the discontinuation of cisplatin) for four preoperative and two postoperative courses. The primary end point was the absolute hearing threshold, as measured by pure-tone audiometry, at a minimum age of 3.5 years. Hearing loss was assessed according to the Brock grade (on a scale from 0 to 4, with higher grades indicating greater hearing loss). The main secondary end points were overall survival and event-free survival at 3 years.
A total of 109 children were randomly assigned to receive cisplatin plus sodium thiosulfate (57 children) or cisplatin alone (52) and could be evaluated. Sodium thiosulfate was associated with few high-grade toxic effects. The absolute hearing threshold was assessed in 101 children. Hearing loss of grade 1 or higher occurred in 18 of 55 children (33%) in the cisplatin-sodium thiosulfate group, as compared with 29 of 46 (63%) in the cisplatin-alone group, indicating a 48% lower incidence of hearing loss in the cisplatin-sodium thiosulfate group (relative risk, 0.52; 95% confidence interval CI, 0.33 to 0.81; P=0.002). At a median of 52 months of follow-up, the 3-year rates of event-free survival were 82% (95% CI, 69 to 90) in the cisplatin-sodium thiosulfate group and 79% (95% CI, 65 to 88) in the cisplatin-alone group, and the 3-year rates of overall survival were 98% (95% CI, 88 to 100) and 92% (95% CI, 81 to 97), respectively.
The addition of sodium thiosulfate, administered 6 hours after cisplatin chemotherapy, resulted in a lower incidence of cisplatin-induced hearing loss among children with standard-risk hepatoblastoma, without jeopardizing overall or event-free survival. (Funded by Cancer Research UK and others; SIOPEL 6 ClinicalTrials.gov number, NCT00652132 ; EudraCT number, 2007-002402-21 .).
Aim
Calciphylaxis is a severe complication of advanced chronic kidney disease (CKD). Sodium thiosulphate (STS), an antioxidant and calcium chelating agent, has been used for the treatment of ...calciphylaxis. However, its efficacy and safety have not been systematically analysed and evaluated.
Methods
MEDLINE, EMBASE, and the Cochrane Library database were systematically searched for case report or cases series on use of STS for calciphylaxis published between July 1974 and October 2016. We extracted data on clinical characteristics, laboratory tests result and medication use. The effective treatment was defined as improvement in skin lesion cicatrisation or pain relief without death. Non‐responding effects were defined as stable skin lesions without remission or exacerbation of the disease in patients who remained alive. All‐cause mortality after STS treatment was defined as death due to exacerbations of calciphylaxis or other complications of advanced CKD. We compared the baseline parameters of the patients as well as the efficacy and mortality of the STS therapy between case report and multi‐case reports. Statistical analyses were performed using SPSS 19.
Results
A total of 83 papers were screened, 45 of them (n = 358) met the inclusion criteria, including 36 case reports (n = 64) and nine multi‐case reports (n = 294). The mean age of the patients with calciphylaxis was 58 ± 14 years (range 26–91 years). They were female predominant, accounting for 74.1%. Among the patients with calciphylaxis, 96.1% patients were on dialysis with median dialysis vintage of 44.5 months (range 24–84 months). STS was effective in 70.1% of patients, 37.6% patients died. The proportion of patients with sepsis was higher among those who received intravenous STS. There was no significant difference in efficacy between the different STS administration methods (P = 0.19).
Conclusion
Although the study was unable to assess the efficacy of sodium thiosulphate alone in the treatment of calciphylaxis, it still reveals a promising role of STS as an effective therapy for calciphylaxis. Further prospective studies to define the optimal therapy for calciphylaxis are needed.
Summary at a Glance
Calciphylaxis (or calcific uraemic arteriolopathy) is an uncommon condition that generally affects patients with chronic kidney disease. Management is challenging and there is a paucity of evidence‐based therapeutic options. This systematic review assesses the evidence (case reports and case series) for the use of sodium thiosulfate in the treatment of calciphylaxis.
Microbial sulfur metabolism contributes to biogeochemical cycling on global scales. Sulfur metabolizing microbes are infected by phages that can encode auxiliary metabolic genes (AMGs) to alter ...sulfur metabolism within host cells but remain poorly characterized. Here we identified 191 phages derived from twelve environments that encoded 227 AMGs for oxidation of sulfur and thiosulfate (dsrA, dsrC/tusE, soxC, soxD and soxYZ). Evidence for retention of AMGs during niche-differentiation of diverse phage populations provided evidence that auxiliary metabolism imparts measurable fitness benefits to phages with ramifications for ecosystem biogeochemistry. Gene abundance and expression profiles of AMGs suggested significant contributions by phages to sulfur and thiosulfate oxidation in freshwater lakes and oceans, and a sensitive response to changing sulfur concentrations in hydrothermal environments. Overall, our study provides fundamental insights on the distribution, diversity, and ecology of phage auxiliary metabolism associated with sulfur and reinforces the necessity of incorporating viral contributions into biogeochemical configurations.
Thiosulfate in the form of sodium thiosulfate (STS) is a major oxidation product of hydrogen sulfide (H2S), an endogenous signaling molecule and the third member of the gasotransmitter family. STS is ...currently used in the clinical treatment of acute cyanide poisoning, cisplatin toxicities in cancer therapy, and calciphylaxis in dialysis patients. Burgeoning evidence show that STS has antioxidant and anti-inflammatory properties, making it a potential therapeutic candidate molecule that can target multiple molecular pathways in various diseases and drug-induced toxicities. This review discusses the biochemical and molecular pathways in the generation of STS from H2S, its clinical usefulness, and potential clinical applications, as well as the molecular mechanisms underlying these clinical applications and a future perspective in kidney transplantation.
Increasing evidence has shown that light exists in a diverse range of deep‐sea environments. We unexpectedly found that blue light is necessary to produce excess zero‐valent sulfur (ZVS) in ...Erythrobacter flavus 21‐3, a bacterium that has been recently isolated from a deep‐sea cold seep. E. flavus 21‐3 is able to convert thiosulfate to ZVS using a novel thiosulfate oxidation pathway comprising a thiosulfate dehydrogenase (TsdA) and a thiosulfohydrolase (SoxB). Using proteomic, bacterial two‐hybrid and heterologous expression assays, we found that the light–oxygen–voltage histidine kinase LOV‐1477 responds to blue light and activates the diguanylate cyclase DGC‐2902 to produce c‐di‐GMP. Subsequently, the PilZ domain‐containing protein mPilZ‐1753 binds to c‐di‐GMP and activates TsdA through direct interaction. Finally, Raman spectroscopy and gene knockout results verified that TsdA and two SoxB homologs cooperate to regulate ZVS production. As ZVS is an energy source for E. flavus 21‐3, we propose that deep‐sea blue light provides E. flavus 21‐3 with a selective advantage in the cold seep, suggesting a previously unappreciated relationship between light‐sensing pathways and sulfur metabolism in a deep‐sea microorganism.
Synopsis
Blue light has been shown to affect metabolism in certain deep‐sea bacteria. Here, we show that blue light promotes the formation of zero‐valent sulfur (ZVS) in the deep‐sea cold‐seep bacterium Erythrobacter flavus 21‐3 via a pathway involving a light‐sensing LOV histidine kinase and downstream c‐di‐GMP production.
Blue light stimulates the production of zero‐valent sulfur (ZVS) in E. flavus 21‐3.
The light–oxygen–voltage histidine kinase LOV‐1477 phosphorylates the diguanylate cyclase DGC‐2902 and promotes the production of c‐di‐GMP.
mPilZ‐1753 binds c‐di‐GMP, activating thiosulfate dehydrogenase (TsdA) via a direct interaction.
Two thiosulfohydrolase (SoxB) homologs collaborate with TsdA to generate ZVS.
Blue light promotes sulfur metabolism in the deep‐sea cold seep bacterium Erythrobacter flavus 21‐3 via a pathway involving a light‐sensing LOV histidine kinase and c‐di‐GMP production.
Zero-valent sulfur (ZVS) has been shown to be a major sulfur intermediate in the deep-sea cold seep of the South China Sea based on our previous work, however, the microbial contribution to the ...formation of ZVS in cold seep has remained unclear. Here, we describe a novel thiosulfate oxidation pathway discovered in the deep-sea cold seep bacterium Erythrobacter flavus 21-3, which provides a new clue about the formation of ZVS. Electronic microscopy, energy-dispersive, and Raman spectra were used to confirm that E. flavus 21-3 effectively converts thiosulfate to ZVS. We next used a combined proteomic and genetic method to identify thiosulfate dehydrogenase (TsdA) and thiosulfohydrolase (SoxB) playing key roles in the conversion of thiosulfate to ZVS. Stoichiometric results of different sulfur intermediates further clarify the function of TsdA in converting thiosulfate to tetrathionate (
O
S-S-S-SO
), SoxB in liberating sulfone from tetrathionate to form ZVS and sulfur dioxygenases (SdoA/SdoB) in oxidizing ZVS to sulfite under some conditions. Notably, homologs of TsdA, SoxB, and SdoA/SdoB widely exist across the bacteria including in Erythrobacter species derived from different environments. This strongly indicates that this novel thiosulfate oxidation pathway might be frequently used by microbes and plays an important role in the biogeochemical sulfur cycle in nature.
Thiosulfate (S2O32-) is frequently used as an ozone (O3) quenching agent when investigating the ozonation of organic contaminants and the kinetics thereof. In this study, however, O3 is activated by ...S2O32-, resulting in a superfast degradation of O3-refractory contaminants. Therefore, the focus of this study is the exploration into the enhancing role of S2O32- in the degradation of refractory organic contaminants by O3, which has been overlooked thus far. Results obtained from scavenging experiments and electron paramagnetic resonance (EPR) spectra verify that •OH generated from the reaction of S2O32- with O3 is mainly responsible for the superfast degradation of O3-refractory contaminants. The •OH yield from the O3/S2O32- process is determined to be 0.216. A plausible mechanism for the generation of •OH from the O3/S2O32- process is proposed with the implementation of density functional theory (DFT). Initially, ozone reacts with a sulfur of S2O32- to form OOOSSO32-. The adduct then rearranges to OO(O)SSO32- or HOO(O)SSO32- in the presence of H+, which cleaves to give a sulfoxide radical cation and O2•-/HO2•. O2•-/HO2• is rapidly transformed into •OH by O3 through a series of steps. Degradation efficiency of O3-refractory contaminants of this process highly depends on the molar ratio of S2O32- and O3 (S2O32-:O3). The optimal S2O32-:O3 is pH dependent in synthetic water (e.g. 0.3 at pH 7). The presence of bicarbonate inhibits the degradation of refractory contaminants by the O3/S2O32- process. Humic acid exhibits a slight enhancing effect at low concentrations (0.1–0.2 mg-C/L), and an inhibiting effect at higher concentrations (≥0.4 mg-C/L). In addition, the efficacy of the O3/S2O32- process in real water matrices is also confirmed.
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•S2O32- appreciably accelerates the degradations of refractory contaminants by O3.•OH primarily contributed to the enhanced degradation of O3-refractory contaminants.•The .•OH yield of O3/S2O32- was determined to be 21.6%.•Degradation efficiency highly depends on the molar ratio of S2O32- and O3.•The potential mechanism of the of O3 with S2O32- was proposed.
The pore structure, high surface area and good conductivity are the key properties for the electrochemical double layer based supercapacitors. The activated carbons were produced from the waste tea, ...utilising microwave pretreatment with H
3
PO
4
and activation at 450°C. Sodium thiosulfate pentahydrate (Na
2
S
2
O
3
·5H
2
O) was used as sulphur doping agent at 800°C to enhance conductivity of the activated carbons. Supercapacitor electrodes were prepared from both the activated carbon (WTAC) and sulphur doped activated carbon (WTAC-S) samples and the electrochemical performances were tested in the presence of 6 M KOH and 1 M H
2
SO
4
as electrolytes. The activated carbon samples were characterised by Brunauer-Emmett-Teller (BET) surface area, Scanning Electron Microscopy/Energy Dispersive X-Ray Spectroscopy (SEM/EDS) and Fourier Transform Infrared Spectroscopy (FTIR) analysis techniques. The electrochemical performance analyses were performed by galvanostatic charge-discharge (GCD), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods. The specific capacitance values of the WTAC and WTAC-S samples under the 1 A g
−1
current density were found to be 89.3, 144.7 F g
−1
for KOH electrolyte and 73.8 and 101.9 F g
−1
for H
2
SO
4
electrolyte, respectively. The results show that the sulphur doping process enhances the electrochemical performance of activated carbon samples.
Thiosulfate oxidation by microbes has a major impact on global sulfur cycling. Here, we provide evidence that bacteria within various Roseobacter lineages are important for thiosulfate oxidation in ...marine biofilms. We isolate and sequence the genomes of 54 biofilm-associated Roseobacter strains, finding conserved sox gene clusters for thiosulfate oxidation and plasmids, pointing to a niche-specific lifestyle. Analysis of global ocean metagenomic data suggests that Roseobacter strains are abundant in biofilms and mats on various substrates, including stones, artificial surfaces, plant roots, and hydrothermal vent chimneys. Metatranscriptomic analysis indicates that the majority of active sox genes in biofilms belong to Roseobacter strains. Furthermore, we show that Roseobacter strains can grow and oxidize thiosulfate to sulfate under both aerobic and anaerobic conditions. Transcriptomic and membrane proteomic analyses of biofilms formed by a representative strain indicate that thiosulfate induces sox gene expression and alterations in cell membrane protein composition, and promotes biofilm formation and anaerobic respiration. We propose that bacteria of the Roseobacter group are major thiosulfate-oxidizers in marine biofilms, where anaerobic thiosulfate metabolism is preferred.
Thiosulfate leaching combined with ion-exchange resins is an innovative alternative for gold recovery. According to the properties of activated carbon, it could replace resins in the gold recovery ...process, improve efficiency, and reduce operating cost. In this research, the adsorption process of gold thiosulfate complex on thiol-modified activated carbon was studied. Thioglycolic acid (ATG) was impregnated in activated carbon, and its adsorption ability was tested with synthetic solutions of gold and sodium thiosulfate (Au 10 mg·L
, Na
S
O
0.1 mol·L
, pH = 10.0). Carbon was characterized by infrared spectroscopy, SEM-EDS, PZC titration, hardness number measures, and proximal analysis. Synthetic solutions were also characterized by UV-vis spectroscopy and cyclic voltammetry. The percentage of volatile material increased from 10.0 to 13.9% due to the impregnation process of ATG. Infrared spectra show characteristic bands of C-H, S-H, and C-S bonds. In the adsorption tests, the ATG-impregnated carbon achieved 91% of gold recovery, while the same amount of ATG in the liquid phase stirred with unmodified activated carbon reached 90% of gold recovery. The 44.9% of gold recovered with activated carbon impregnated with ATG was eluted with sodium cyanide (NaCN = 0.2 mol·L
; NaOH = 0.25 mol·L
; CH
CH
OH = 30%
/
; pH = 12.0; t = 24 h). These results suggest the gold transferred from the thiosulfate complex to a new gold thiolate complex.
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