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Key points Sodium thiosulfate (STS) is gaining increasing attention in research for its potential therapeutic applications across a spectrum of disease processes beyond its current uses. However, the precise mechanisms of action remain incompletely understood. We investigated the efficacy of STS in treating hyperglycaemia‐induced pronephros damage in zebrafish to gain further insight into the underlying mechanisms. Hyperglycaemia was induced in zebrafish by suppressing the pdx1 transcription factor, which plays a crucial role in maintaining physiological pancreatic function. STS was administered by introducing it into the medium of zebrafish larvae. The pronephros structure was analysed at 48 h post‐fertilization. Metabolomic profiling and RNA sequencing were conducted on groups exposed to various experimental conditions. Our findings reveal a downregulation of nitric oxide (NO) signalling in zebrafish with a knocked‐down pdx1 gene, both metabolomically and transcriptionally. Notably, treatment with STS led to a compensatory upregulation of the NO signalling, ultimately resulting in the rescue of the pronephros structure. Our study provides compelling evidence that targeting NO metabolism by the administration of STS offers a promising strategy for addressing hyperglycaemia‐induced organ damage. These findings underscore the potential of STS as a promising therapeutic agent for diabetic complications and warrant further investigation of its clinical applications. Sodium thiosulfate (STS) is increasingly drawing attention in research for its potential therapeutic applications across a spectrum of disease processes. Here, we demonstrate that STS treatment rescues hyperglycaemia‐induced pronephros damage in zebrafish. We identified upregulation of nitric oxide signalling as the major driver behind STS‐mediated rescue. Our data suggest that STS offers a promising strategy for addressing hyperglycaemia‐induced organ damage, including diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Objectives Escherichia coli can cause infections in the urinary tract and in normally sterile body sites leading to invasive E. coli disease (IED), including bacteraemia and sepsis, with older populations at increased risk. We aimed to estimate the theoretical coverage rate by the ExPEC4V and 9V vaccine candidates. In addition, we aimed at better understanding the diversity of E. coli isolates, including their genetic and phenotypic antimicrobial resistance (AMR), sequence types (STs), O-serotypes and the bacterial population structure. Methods Blood and urine culture E. coli isolates (n  = 304) were collected from hospitalized patients ≥60 years (n = 238) with IED during a multicentric, observational study across three continents. All isolates were tested for antimicrobial susceptibility, O-serotyped, whole-genome sequenced and bioinformatically analysed. Results A large diversity of STs and of O-serotypes were identified across all centres, with O25b-ST131, O6-ST73 and O1-ST95 being the most prevalent types. A total of 45.4% and 64.7% of all isolates were found to have an O-serotype covered by the ExPEC4V and ExPEC9V vaccine candidates, respectively. The overall frequency of MDR was 37.4% and ST131 was predominant among MDR isolates. Low in-patient genetic variability was observed in cases where multiple isolates were collected from the same patient. Conclusions Our results highlight the predominance of MDR O25b-ST131 E. coli isolates across diverse geographic areas. These findings provide further baseline data on the theoretical coverage of novel vaccines targeting E. coli associated with IED in older adults and their associated AMR levels. [ABSTRACT FROM AUTHOR]

Calcinosis cutis is a condition that is commonly associated with autoimmune connective tissue diseases. It is characterized by the deposition of insoluble calcium salts in the skin and subcutaneous tissue, which can cause pain, impair function, and have significant impacts on quality of life. Calcinosis cutis is difficult to manage because there is no generally accepted treatment: evidence supporting treatments is mostly comprised of case reports and case series, sometimes yielding mixed findings. Both pharmacologic and procedural interventions have been proposed to improve calcinosis cutis, and each may be suited to different clinical scenarios. This review summarizes current treatment options for calcinosis cutis, with discussion of recommendations based on patient-specific factors and disease severity. [ABSTRACT FROM AUTHOR]

Sodium thiosulfate has been used for decades in the treatment of calciphylaxis and cyanide detoxification, and has recently shown initial therapeutic promise in critical diseases such as neuronal ischemia, diabetes mellitus, heart failure and acute lung injury. However, the precise mechanism of sodium thiosulfate remains incompletely defined and sometimes contradictory. Although sodium thiosulfate has been widely accepted as a donor of hydrogen sulfide (H 2 S), emerging findings suggest that it is the executive signaling molecule for H 2 S and that its effects may not be dependent on H 2 S. This article presents an overview of the current understanding of sodium thiosulfate, including its synthesis, biological characteristics, and clinical applications of sodium thiosulfate, as well as the underlying mechanisms in vivo. We also discussed the interplay of sodium thiosulfate and H 2 S. Our review highlights sodium thiosulfate as a key player in sulfide signaling with the broad clinical potential for the future. [Display omitted] • The synthesis, biological properties and clinical applications of sodium thiosulfate are summarized. • The two current opposing views on the mechanism of sodium thiosulfate are also discussed in this paper. • Sodium thiosulfate is highlighted as a possible key player in sulfide signaling. [ABSTRACT FROM AUTHOR]

We assessed the effect of non-protein thiols (NPSH), reduced glutathione (GSH) and n-acetylcysteine (NAC), on resin shear bond strength (SBS) to hydrogen peroxide (H2O2)-treated dentin, and their effects on the characteristics of dentin in comparison to ascorbic acid (AA) and sodium thiosulfate (STS). H2O2-treated dentin was conditioned with 5% AA, GSH, NAC, or STS applied for 1 or 5 min. The positive control group received H2O2 without antioxidant application, and the first negative control group received distilled water (DW). The specimens received resin bonding immediately after treatment except for the second negative control group (delayed bonding). Microhardness, roughness, and topography were studied. The SBS values of all antioxidants were statistically greater than the positive control group (p < 0.05); however, NAC and AA applied for 1 min demonstrated the highest values, which were comparable to delayed bonding. All treatments removed the smear layer except DW, H2O2, and STS. The negative effect of H2O2 on resin–dentin bonding was mitigated by the application of the antioxidants; however, their efficiencies were dependent on the antioxidant type and time of application. NAC was more effective in optimizing resin bonding to bleached dentin compared to GSH at 1 min application and STS at both application times but was comparable to AA. Negligible negative effects on the substrate's roughness and microhardness were detected. The antioxidant properties of the agent and its capacity to remove the smear layer are the processes underpinning the ability of a certain antioxidant to reverse the effect of H2O2 on bonding. [ABSTRACT FROM AUTHOR]

Objectives To investigate the global distribution of an optrA -harbouring linezolid-resistant Enterococcus faecalis ST476 clonal lineage. Methods Comprehensive searches of the NCBI database were performed to identify published peer-reviewed articles and genomes of E. faecalis ST476. Each genome was analysed for resistome, virulome, OptrA variant and optrA genetic contexts. A phylogenetic comparison of ST476 genomes with publicly available genomes of other STs was also performed. Results Sixty-six E. faecalis ST476 isolates from 15 countries (China, Japan, South Korea, Austria, Denmark, Spain, Czech Republic, Colombia, Tunisia, Italy, Malaysia, Belgium, Germany, United Arab Emirates and Switzerland) mainly of human and animal origin were identified. Thirty available ST476 genomes compared with genomes of 591 STs indicated a progressive radiation of E. faecalis STs starting from ST21. The closest ancestral node for ST476 was ST1238. Thirty E. faecalis ST476 genomes exhibited 3–916 SNP differences. Several antimicrobial resistance and virulence genes were conserved among the ST476 genomes. The optrA genetic context exhibited a high degree of or complete identity to the chromosomal transposon Tn 6674. Only three isolates displayed an optrA -carrying plasmid with complete or partial Tn 6674. The WT OptrA protein was most widespread in the ST476 lineage. Conclusions Linezolid-resistant optrA -carrying E. faecalis of the clonal lineage ST476 is globally distributed in human, animal and environmental settings. The presence of such an emerging clone can be of great concern for public health. Thus, a One Health approach is needed to counteract the spread and the evolution of this enterococcal clonal lineage. [ABSTRACT FROM AUTHOR]

Ototoxicity is a devastating direct, irreversible side effect of platinum use in children with cancer, with its consequent effect on speech, language and social development, quality of life and adult productivity. Cisplatin, an essential chemotherapeutic agent for the treatment of solid tumors in children, is a DNA cross-linking agent. Which causes hearing loss in 50-70% of cisplatin treated children. Fortunately, to prevent hearing loss, sodium thiosulfate (STS), which binds to cisplatin, and reduces the superoxides in both tumor and outer hair cells of the cochlea has now been discovered to be an effective and safe otoprotectant if administered correctly. The aim of this perspective paper is to explore the key safety issues and challenges important for pediatric oncologists and pharmacists when considering the clinical use of STS as an otoprotectant for children and adolescents receiving cisplatin. These include: the choice of the formulation; the timing, both that of the STS in relation to cisplatin as well as the timing of the cisplatin infusion itself; the dosing; the challenge left by the definition of localized versus disseminated disease and the difference in indication for STS, between cisplatin treated patients and those receiving another platinum chemotherapeutic agent, carboplatin. [ABSTRACT FROM AUTHOR]

The dechlorination effect of sodium thiosulfate and the DCM model for wastewater dechlorination were investigated in order to achieve the automatic control of the dosage of dechlorination agent. Meanwhile，the model calibration was carried out by the nonlinear fitting. The automatic control system of the dosage of dechlorination agent was also developed. The results showed that sodium thiosulfate could be used for dechlorination in the influent of a waste water treatment plant （WWTP），and 90% of residual chlorine in the sewage could be removed within one minute of the dechlorination reaction. The dichlorination efficiencies were mainly determined by the dosage of sodium thiosulfate. The DCM model could be described by CtC0=k21+k1CR+k3. The DCM model curves had a good correlation with the test data. The square values of the fitting correlation coefficients were greater than 0.99，and the residual sums of square were less than 0.000 5. The imitative effect of the DCM model was best while the dechlorination time was one minute. Meanwhile，according to the DCM model，the automatic control of the dosage of dechlorination agent was described with programmable logic controller（PLC） as the main controller，with the on-line monitoring instrument of residual chlorine as the measuring element and with diaphragm pump as the executive equipment. The dosing point was set at the water-collecting well of influent pump station of the WWTP. The residual chlorine values of the influent in biological treatment unit were used for real-time feedback to determine whether the automatic control system of wastewater dechlorination was running correctly or not.

Abstract Background Up to now, there is no unequivocal intervention to mitigate vascular calcification (VC) in patients with hemodialysis. This network meta-analysis aimed to systematically evaluate the clinical efficacy of sodium thiosulfate, bisphosphonates, and cinacalcet in treating vascular calcification. Methods A comprehensive study search was performed using PubMed, Web of Science, the Cochrane Library, EMBASE and China National Knowledge Internet (CNKI) to collect randomized controlled trials (RCTs) of sodium thiosulfate, bisphosphonates, and cinacalcet for vascular calcification among hemodialysis patients. Then, network meta-analysis was conducted using Stata 17.0 software. Results In total, eleven RCTs including 1083 patients were qualified for this meta-analysis. We found that cinacalcet (SMD − 0.59; 95% CI [–0.95, -0.24]) had significant benefit on vascular calcification compared with conventional therapy, while sodium thiosulfate or bisphosphonates did not show such efficiency. Furthermore, as for ranking the efficacy assessment, cinacalcet possessed the highest surface under the cumulative ranking curve (SUCRA) value (88.5%) of lessening vascular calcification and was superior to sodium thiosulfate (50.4%) and bisphosphonates (55.4%). Thus, above results suggested that cinacalcet might be the most promising drug for vascular calcification treatment in hemodialysis patients. Mechanistically, our findings illustrated that cinacalcet reduced serum calcium (SMD − 1.20; 95% CI [–2.08, − 0.33]) and showed the tendency in maintaining the balance of intact Parathyroid Hormone (iPTH) level. Conclusions This network meta-analysis indicated that cinacalcet appear to be more effective than sodium thiosulfate and bisphosphonates in mitigating vascular calcification through decreasing serum calcium and iPTH. And cinacalcet might be a reasonable option for hemodialysis patients with VC in clinical practice. Systematic Review Registration [ http://www.crd.york.ac.uk/PROSPERO ], identifier [CRD42022379965].

One of the more common dechlorinated agents is Sodium thiosulfate. However, the toxicity on the aquatic animals was unknown, this study aims to determine the adverse effects of random usage and high sodium thiosulfate concentration in carp fish rearing in an earthen pond in Hawy -Al-Kanesa in Mosul city. The sodium thiosulfate used at 10 gm /L led to fish mortality of 80% through 96 days of exposure. The semi-quantities score analysis of histopathological alteration of gill represented a biological indicator for toxicity estimation, which reveals the significant alteration index (P≤0.05) in the vacuolar degeneration and hemorrhage while highly significant alteration index (P≤0.01) represented in the other vascular disturbances (edema, congestion, and aneurysm), hyperplasia, hyper trophy of cells, shortening, loss and fusion of secondary gills lamellae with abnormal cartilage morphology. Chloride and mucus cells were ++ and +++ for Periodic acid Schefft and Masson Trichrome, respectively, and apoptotic cells have been detected via caspase-3 activation, which was prominently detected mainly in the cells structure of the secondary gill lamella rather than primary filaments. This study concluded that sodium thiosulfate is toxic in high concentration to fish and leads to a pathological alteration in the vital organs such as gills. The semi-quantitative analysis is one of the modern techniques through which significant pathological changes are determined in histological sections of the gills and immunohistochemically and technique to determine programmed cell death.

Background Streptococcus suis is an important pig pathogen and an emerging zoonotic agent. In a previous study, we described a high proportion of penicillin-resistant serotype 9 S. suis (SS9) isolates on pig farms in Italy. Objectives We hypothesized that resistance to penicillin emerged in some SS9 lineages characterized by substitutions at the PBPs, contributing to the successful spread of these lineages in the last 20 years. Methods Sixty-six SS9 isolates from cases of streptococcosis in pigs were investigated for susceptibility to penicillin, ceftiofur and ampicillin. The isolates were characterized for ST, virulence profile, and antimicrobial resistance genes through WGS. Multiple linear regression models were employed to investigate the associations between STs, year of isolation, substitutions at the PBPs and an increase in MIC values to β-lactams. Results MIC values to penicillin increased by 4% each year in the study period. Higher MIC values for penicillin were also positively associated with ST123, ST1540 and ST1953 compared with ST16. The PBP sequences presented a mosaic organization of blocks. Within the same ST, substitutions at the PBPs were generally more frequent in recent isolates. Resistance to penicillin was driven by substitutions at PBP2b, including K479T, D512E and K513E, and PBP2x, including T551S, while reduced susceptibility to ceftiofur and ampicillin were largely dependent on substitutions at PBP2x. Conclusions Here, we identify the STs and substitutions at the PBPs responsible for increased resistance of SS9 to penicillin on Italian pig farms. Our data highlight the need for monitoring the evolution of S. suis in the coming years. [ABSTRACT FROM AUTHOR]

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Background: Up to now, there is no unequivocal intervention to mitigate vascular calcification (VC) in patients with hemodialysis. This network meta-analysis aimed to systematically evaluate the clinical efficacy of sodium thiosulfate, bisphosphonates, and cinacalcet in treating vascular calcification. Methods: A comprehensive study search was performed using PubMed, Web of Science, the Cochrane Library, EMBASE and China National Knowledge Internet (CNKI) to collect randomized controlled trials (RCTs) of sodium thiosulfate, bisphosphonates, and cinacalcet for vascular calcification among hemodialysis patients. Then, network meta-analysis was conducted using Stata 17.0 software. Results: In total, eleven RCTs including 1083 patients were qualified for this meta-analysis. We found that cinacalcet (SMD − 0.59; 95% CI [–0.95, -0.24]) had significant benefit on vascular calcification compared with conventional therapy, while sodium thiosulfate or bisphosphonates did not show such efficiency. Furthermore, as for ranking the efficacy assessment, cinacalcet possessed the highest surface under the cumulative ranking curve (SUCRA) value (88.5%) of lessening vascular calcification and was superior to sodium thiosulfate (50.4%) and bisphosphonates (55.4%). Thus, above results suggested that cinacalcet might be the most promising drug for vascular calcification treatment in hemodialysis patients. Mechanistically, our findings illustrated that cinacalcet reduced serum calcium (SMD − 1.20; 95% CI [–2.08, − 0.33]) and showed the tendency in maintaining the balance of intact Parathyroid Hormone (iPTH) level. Conclusions: This network meta-analysis indicated that cinacalcet appear to be more effective than sodium thiosulfate and bisphosphonates in mitigating vascular calcification through decreasing serum calcium and iPTH. And cinacalcet might be a reasonable option for hemodialysis patients with VC in clinical practice. Systematic Review Registration: [http://www.crd.york.ac.uk/PROSPERO], identifier [CRD42022379965]. [ABSTRACT FROM AUTHOR]

A Hypo helmet is a fabric hood soaked with an aqueous solution of two sodium salts for the detoxication of chlorine that was developed during the First World War. Herein, we report on a lecture, developed for non-chemistry majors that used the Hypo helmet to highlight the physical and chemical properties of chlorine. The lecture consisted of the following three components: (1) a brief introduction to the First World War (the Chemists’ War), (2) video demonstrations of the generation of chlorine by mixing bleaching powder and hydrochloric acid and the detoxication of chlorine using a dummy Hypo helmet, and (3) students’ written impressions of the lecture. The students’ written impressions revealed two things: the lecture on chlorine and the Hypo helmet was well received, and most of the students (71 %, N = 82) did not know that chlorine was used as a poisonous gas during the First World War.

Calciphylaxis is a rare and life-threatening condition in patients with end-stage kidney disease (ESKD). In this case report, we reported a 72-year-old female who had undergone aortic and mitral mechanical valve replacement 22 years ago due to rheumatic aortic and mitral stenosis. Following the valve replacement, she initiated warfarin treatment. Five years ago, she received a diagnosis of uremia and has since been undergoing regular hemodialysis. Ten months prior to her current admission, she experienced excruciating pain and was diagnosed with calciphylaxis. Additionally, an electrocardiogram revealed atrial fibrillation, while echocardiography indicated that the aortic and mitral mechanical valves were appropriately positioned, with normal perivalvular surroundings and good valve leaflet activity. No noticeable thrombosis was observed in the left atrium or left atrial appendage. Color Doppler imaging showed moderate stenosis in the lower extremity arteries, with no venous thromboembolism present. Extensive eggshell-like calcification within the arterial media was detected. The patient was managed with regular hemodialysis, symptomatic treatments (including anticoagulation and analgesia), and sodium thiosulfate. Unfortunately, symptomatic management provided limited relief, and during the one-month follow-up period, the patient passed away due to septic shock. Currently, there is insufficient conclusive evidence regarding alternative influential anticoagulants or appropriate prosthetic valve selection. For individuals with ESKD receiving maintenance hemodialysis, early identification, diagnosis, and treatment of calciphylaxis are of paramount importance. [ABSTRACT FROM AUTHOR]

A multimodality approach has been proposed as an effective treatment for calciphylaxis in patients with end-stage kidney disease. In this retrospective study, we report the cases of 12 end-stage kidney disease patients from l'Hôtel-Dieu de Québec hospital (Canada) who were diagnosed with calciphylaxis between 2004 and 2012 and treated with a multimodality clinical approach including sodium thiosulfate (STS). Statistical analyses were performed to evaluate the impacts of patients characteristics, the different interventions as well as therapy regimen on the therapeutic response. The majority of patients (n = 9) were hemodialyzed. The patients-associated comorbidities were consistent with previously reported risk factors for calciphylaxis: Diabetes (n = 11), calcium-based phosphate binders use (n = 10), warfarin use (n = 9), obesity (n = 7), female gender (n = 8) and intravenous iron use (n = 8). STS was given for a median duration of 81 days. 75% of the patients had a response (total or partial) including a complete response in 42% of patients. One-year mortality rate was low (25%). STS was used during a mean duration of 83.33 ± 41.52 days and with a total cumulating dose of 1129.00 ± 490.58 g. The recorded mean time before a complete response was 102.20 days (51-143). Pain improvement occurred after a mean time of 8.67 ± 10.06 days. None of the studied factors was statistically associated with a complete or a partial response to the multimodality approach. Although our data have a limited statistical power, they support treating calciphylaxis with a multimodality approach including STS as its effects are independent from important clinical variables. [ABSTRACT FROM AUTHOR]

Coronary artery calcification (CAC) is common in dialysis patients and is associated with a higher risk of future cardiovascular events. Sodium thiosulfate (STS) is effective for calciphylaxis in dialysis patients; however, the influence of STS on CAC in dialysis patients remains unclear. This systematic review and meta-analysis were conducted to evaluate the effects of STS on CAC in patients undergoing dialysis. PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched from inception to 22 March 2023 for controlled studies comparing the influence of STS versus usual care without STS on CAC scores in dialysis patients. A random effects model incorporating the potential influence of heterogeneity was used to pool the results. Nine studies, including two non-randomized studies and seven randomized controlled trials, were included in the meta-analysis. Among these, 365 patients on dialysis were included in the study. Compared with usual care without STS, intravenous STS for 3-6 months was associated with significantly reduced CAC scores (mean difference [MD] = -180.17, 95% confidence interval [CI]: -276.64 to -83.70, p < 0.001, I² = 0%). Sensitivity analysis limited to studies of patients on hemodialysis showed similar results (MD: -167.33, 95% CI: -266.57 to -68.09, p = 0.001; I² = 0%). Subgroup analyses according to study design, sample size, mean age, sex, dialysis vintage of the patients, and treatment duration of STS also showed consistent results (p for subgroup differences all > 0.05). In conclusion, intravenous STS may be effective in attenuating CAC in dialysis patients. [ABSTRACT FROM AUTHOR]

The results of identification of photolysis products of air-saturated aqueous solutions of Na2S2O3 irradiated with a KrCl excimer lamp are presented. Using spectrophotometry, HPLC, IR spectroscopy, and mass spectrometry, it has been shown that intermediate photolysis products are colloidal sulfur and tetrathionate and pentathionate ions, which photodegrade to form sulfur, sulfate ions, and hydrogen sulfide during further UV irradiation involving atmospheric oxygen and solvent molecules. Reactions for the formation of detected photolysis products have been proposed. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of sodium thiosulfate (STS) on serum calcification factors in patients undergoing maintenance hemodialysis. Methods: Forty‐four Patients were randomly divided into control group (n = 22) and observation group (n = 22) by envelope method (block 4 randomization). The control group received routine treatment while observation group was treated with STS on the basis of routine treatment. The biochemical indicators, including BUN, UA, SCr, Ca2+, P3−, calcium‐phosphorus product, PTH, hs‐CRP, TG, TC, HDL, LDL, and serum calcification factor MGP, FA, FGF‐23, and OPG levels were compared before and after treatment. Results: Control group had no statistically significant difference in the levels of vascular calcification factors MGP, FA, FGF‐23, and OPG before and after treatment (p > 0.05). Whereas observation group had higher levels of MGP and FA, and lower levels of FGF‐23 and OPG after treatment than before treatment (p < 0.05). The levels of MGP and FA in observation group were higher than those in control group, and FGF‐23 and OPG were lower than those in control group (p < 0.05). Conclusion: It is speculated that sodium thiosulfate can alleviate the progression of vascular calcification by changing the levels of calcification factors. [ABSTRACT FROM AUTHOR]

Ototoxicity is a devastating direct, irreversible side effect of platinum use in children with cancer, with its consequent effect on speech, language and social development, quality of life and adult productivity. Cisplatin, an essential chemotherapeutic agent for the treatment of solid tumors in children, is a DNA cross-linking agent. Which causes hearing loss in 50-70% of cisplatin treated children. Fortunately, to prevent hearing loss, sodium thiosulfate (STS), which binds to cisplatin, and reduces the superoxides in both tumor and outer hair cells of the cochlea has now been discovered to be an effective and safe otoprotectant if administered correctly. The aim of this perspective paper is to explore the key safety issues and challenges important for pediatric oncologists and pharmacists when considering the clinical use of STS as an otoprotectant for children and adolescents receiving cisplatin. These include: the choice of the formulation; the timing, both that of the STS in relation to cisplatin as well as the timing of the cisplatin infusion itself; the dosing; the challenge left by the definition of localized versus disseminated disease and the difference in indication for STS, between cisplatin treated patients and those receiving another platinum chemotherapeutic agent, carboplatin.

ContextHydrogen cyanide and methanethiol are two toxic gases that inhibit mitochondrial cytochrome c oxidase. Cyanide is generated in structural fires and methanethiol is released by decaying organic matter. Current treatments for cyanide exposure do not lend themselves to treatment in the field and no treatment exists for methanethiol poisoning. Sodium tetrathionate (tetrathionate), a product of thiosulfate oxidation, could potentially serve as a cyanide antidote, and, based on its chemical structure, we hypothesized it could react with methanethiol.ResultsWe show that tetrathionate, unlike thiosulfate, reacts directly with cyanide in vitro under physiological conditions, and based on rabbit studies where we monitor cyanide poisoning in real-time, tetrathionate likely reacts directly with cyanide in vivo. We found that tetrathionate administered by intramuscular injection rescues >80% of juvenile, young adult, and old adult mice from exposure to inhaled hydrogen cyanide gas that is >80% lethal. Tetrathionate also rescued young adult rabbits from intravenously administered sodium cyanide. Tetrathionate was reasonably well-tolerated by mice and rats, yielding a therapeutic index of ∼5 in juvenile and young adult mice, and ∼3.3 in old adult mice; it was non-mutagenic in Chinese Hamster ovary cells and by the Ames bacterial test. We found by gas chromatography-mass spectrometry that both tetrathionate and thiosulfate react with methanethiol to generate dimethyldisulfide, but that tetrathionate was much more effective than thiosulfate at recovering intracellular ATP in COS-7 cells and rescuing mice from a lethal exposure to methanethiol gas.ConclusionWe conclude that tetrathionate has the potential to be an effective antidote against cyanide and methanethiol poisoning.

Calciphylaxis is a rare and serious complication of chronic renal failure characterized by vascular calcium overload. It has a high mortality rate. Penile calciphylaxis is an extremely rare condition of penile necrosis due to calciphylaxis of the penile arterioles. Presented here is a severe case of systemic calciphylaxis initially presented as penile necrosis treated with sodium thiosulfate and amputation.

The modern period in the development of the world community and the Russian Federation in particular is characterized by the globalization of chemical danger. The increase of chemical hazards is determined by the growing potential of the chemical industry in developed countries, widespread use of highly toxic substances in industry, presence of not destroyed stockpiles of chemical weapons abroad, bolstering terrorist manifestations etc. In these circumstances one of the components of the concept of medical support for chemical safety is the existence of a scientifically based system for the development and application of medical technologies for the treatment and prophylaxis of chemical poisoning. The system of emergency specialized toxicological assistance that exists in the Russian Federation suggests the use of means of antidote therapy. However, the analysis of the reports of centers / departments of acute poisoning indicates the lack of significant means of specific pharmacotherapy there. Also there are no important antidotes to cyanides, irritants or alcohol substitutes on Russia's pharmaceutical market. After the analysis of the state of the scientific, technological and industrial base, as well as the analysis of the potential hazards of a chemical nature, it is necessary to underline, that the main directions for the optimization of the antidote therapy system in the Russian Federation should include experimental and clinical studies aimed at the development and creation of innovative antidotes (or adaptation and licensing of various pharmacopeial drugs). The short-term tasks of research, production and regulatory development of the antidote therapy system in the Russian Federation are connected with the completion of the development, registration and acceptance of domestic means of antidote therapy (antidotes to cyanides, combustion products, irritants, psychodisleptics), improvement of technical means of applying existing antidotes, legal regulations in the sphere of providing access to antidotes for medical units and organizations.

IntroductionCyanide is a deadly poison, particularly with oral exposure where larger doses can occur before symptoms develop. Prior studies and multiple governmentagencies highlight oral cyanide as an agent with the potential for use in a terrorist attack. Currently, there are no FDA approved antidotes specific to oralcyanide. An oral countermeasure that can neutralize and prevent absorption of cyanide from the GI tract after oral exposure is needed. Our objective was toevaluate the efficacy of oral sodium thiosulfate on survival and clinical outcomes in a large, swine model of severe cyanide toxicity.MethodsSwine (45-55kg) were instrumented, sedated, and stabilized. Potassium cyanide (8 mg/kg KCN) in saline was delivered as a one-time bolus via an orogastric tube. Three minutes after cyanide, animals randomized to the treatment group received sodium thiosulfate (510 mg/kg, 3.25 M solution) via orogastric tube. Our primary outcome was survival at 60 minutes after exposure. We compared survival between groups by log-rank, Mantel-Cox analysis and trended labs and vital signs.ResultsAt baseline and time of treatment all animals had similar weights, vital signs, and laboratory values. Survival at 60 min was 100% in treated animals compared to 0% in the control group (p=0.0027). Animals in the control group became apneic and subsequently died by 35.0 min (20.2,48.5) after cyanide exposure. Mean arterial pressure was significantly higher in the treatment group compared to controls (p=0.008). Blood lactate (p=0.02) and oxygen saturation (p=0.02) were also significantly different between treatment and control groups at study end.ConclusionOral administration of sodium thiosulfate improved survival, blood pressure, respirations, and blood lactate concentrations in a large animal model of acute oral cyanide toxicity.

Sulfur mustard was widely used during the Iran-Iraq war (1980–1988) and in other conflicts in the Middle East. Due to its availability, it can be used by terrorist organizations on the territory of the Russian Federation. Iran is the only country, against which mustard gas was used in modern warfare. The aim of this work is to analyze and summarize the experience of treating of sulfur mustard exposure, accumulated by Iranian specialists during the Iran-Iraq war (1980–1988). The UN official documents and materials, declassified CIA documents, articles of Iranian authors as well as other open sources have been used during its preparation. The Iraqi army used mustard gas in two aggregate states: liquid and dry. Dry mustard gas was a novelty of that war. It was a powdered silica steeped in mustard gas, with a particle size of less than 5 μm. The first signs and symptoms of poisoning could appear after 15 minutes, while acute poisoning effects of exposure to mustard gas vapour or liquid were typically delayed for several hours. The reasons for the severe mustard lesions of the servicemen were the lack of personal protective equipment, untimely evacuation from the mustard gas contamination zone, and the absence of mobile reserves of clean water and degassing installations in battle formations. Iranian experts consider 0.5% sodium hypochlorite solution to be the most effective decontaminant. The only safe antidote is sodium thiosulfate, administered within 60 minutes after exposure to mustard gas. During the evacuation of victims and their treatment in hospitals it is necessary, in severe cases, to insert an intravenous catheter, carry out a tracheotomy with the installation of a tracheotomy tube, and use bronchoscopy as early as possible to flush the bronchi. The treatment of skin and eye lesions should be conservative. In case of a corneal perforation, if its diameter is more than 2 mm – keratoplasty, if it is less – cyanoacrylate glue. Treatment of respiratory lesions aims to relieve symptoms and reduce the severity of complications. For this, bronchodilators, antitussives, mucolytics and, if necessary, antibiotics are used. The use of corticosteroids should be limited to the treatment of those patients with bronchospasm, who can not be treated by bronchodilators. The Iranians also consider gene therapy and treatment with mesenchymal stem cells to be the promising method used in the treatment of lung lesions.