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Calciphylaxis is a rare and devastating condition with important systemic ramifications. This second-part of our CME aims to educate the practicing dermatologist on the current standard of care once a diagnosis of calciphylaxis is confirmed or highly suspected. The key pathologic findings, as well as the role and limitations of biopsy, are reviewed. We aim to guide readers through the complex hospitalization and posthospitalization management of these medically vulnerable patients. Collaboration with other specialists will be discussed. Experimental and developing treatments are discussed, and the outlook of the condition is reported. [ABSTRACT FROM AUTHOR]

Pseudoxanthoma elasticum (PXE) is a multisystem ectopic mineralization disorder caused by pathogenic variants in the ABCC6 gene. Though complications of the disease can be treated, PXE itself remains currently intractable. A strategy for rapid and cost-effective discovery of therapeutic drugs would be to perform chemical compound screening using zebrafish, but this approach remains to be validated for PXE. In this paper, we validate a stable CRISPR/Cas9 abcc6a knockout zebrafish model–which has spinal column hypermineralization as its primary phenotypic feature–as a model system for compound screening in ectopic mineralization. We evaluated the anti-mineralization potential of five compounds, which had (anecdotal) positive effects reported in Abcc6 knockout mice and/or PXE patients. Abcc6a knockout zebrafish larvae were treated from 3 to 10 days post-fertilization with vitamin K1, sodium thiosulfate, etidronate, alendronate or magnesium citrate and compared to matching controls. Following alizarin red S staining, alterations in notochord sheath mineralization were semiquantified and found to largely congrue with the originally reported outcomes. Our results demonstrate that the use of this abcc6a knockout zebrafish model is a validated and promising strategy for drug discovery against ectopic mineralization. [ABSTRACT FROM AUTHOR]

Dewatering of sludge is a key problem that must be solved in the sewage sludge disposal industry. In this study, a series of process optimization tests were conducted to learn how to improve sludge treatment. The optimum process of sludge leaching treatment was studied in a specially designed 100-L reactor system. Four factors were investigated and nine batches of bioleaching tests were run at three levels of these factors. Orthogonal experiments showed that the effect of sludge return ratio and aeration rate on the sludge moisture content was significant and hydraulic retention time (HRT) had a clear effect, but nutrient types had a reduced effect on the moisture content of sludge. The primary and secondary order of each factor is reflux ratio > aeration rate > HRT > nutrient type. Under the optimal process, three batches of sludge were processed and the moisture content of the filter press cake was reduced to less than 60%, the organic matter content reduced to below 5%, and the concentration of heavy metals (Cu, Zn, Pb, and Cr) was much lower than the agricultural standard limit, which is suitable for landscaping, composting, and incineration power generation and other resource applications.

Wojciech Danysz,1 Bartosch Nowag,1 Thomas Hengl,1 Peter Kreymerman,2 Céline Furne,3 Elise Madeuf,4 Christoph Höennscheidt,1 Deanne Mraz Robinson5,6 1R&D, Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany; 2Medical Affairs, Merz North America, Raleigh, NC, USA; 3NAMSA, Chasse sur Rhône, France; 4Preclinical Studies, Voxcan, Marcy L´Etoile, France; 5Modern Dermatology of Connecticut, Westport, CT, USA; 6Yale-New Haven Hospital, New Haven, CT, USACorrespondence: Wojciech DanyszMerz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, Frankfurt am Main 60318, GermanyEmail Wojciech.danysz@merz.deIntroduction: Calcium hydroxylapatite microspheres suspended in a gel carrier of sodium carboxymethylcellulose (CaHA; Radiesse®) has demonstrated safe and effective restoration of facial volume in clinical trials, as well as collagen biostimulation leading to skin quality improvement. The potential with CaHA, as with any filler, to produce overcorrection and subsequent complications has led to the search for a reversal agent. Sodium thiosulfate (STS) was proposed based on experience with it as a chelating agent to treat calciphylaxis. Previous pilot studies with small sample sizes have suggested its efficacy in the reduction of CaHA volume and nodule formation. The present study focuses on the verification of this effect using various readout methods in preclinical experiments.Methods: We use both in vitro (co-incubation of STS with CaHA) and in vivo (injections in farm pig) methods with readout techniques such as 3D camera analysis, micro-computed tomography ex vivo (μCT), computed tomography in vivo (CT), histopathology and scanning electron microscopy.Results: We did not obtain any indications of CaHA degradation by STS, either in vitro or in vivo. 3D-camera analysis also did not show any decreasing effect of STS on CaHA. However, histology, μCT ex vivo, and CT in vivo indicated a decrease of Radiesse amount/volume after STS treatment, which could be attributed to dispersion effect. It should be noted that necrosis and haemorrhages were observed after STS treatment.Discussion: Results suggest no indication of CaHA microspheres degradation with STS and that the STS mechanism of action on CaHA is consistent with a dispersion effect. Observed necrosis is a further obstacle in the use of STS.Keywords: calcium hydroxylapatite, sodium thiosulfate, dispersion effect, computed tomography, histology, 3D camera

Background/Aims: Arterial stenosis activates the renin-angiotensin-aldosterone system subsequently resulting in renovascular hypertension (RVHT) and renal oxidative injury. We explored the effect of sodium thiosulfate (STS, Na2S2O3), a developed antioxidant in clinical trial, on RVHT-induced hypertension and renal oxidative injury in rats. Methods: We induced RVHT in male Wistar rats with bilaterally partial ligation of renal arteries in the 2-kidney 2-clip model. We evaluated the STS effect on RVHT-induced oxidative injury and apoptosis by a chemiluminescence amplification method, Western blot, and immunohistochemistry. Results: We found STS displayed a dose-dependent antioxidant H2O2 activity and adapted the maximal scavenging H2O2 activity of STS at the dosage of 0.1 g/kg intraperitoneally 3 times/week for 4 weeks in RVHT rats. RVHT induced a significant elevation of arterial blood pressure, blood reactive oxygen species amount, neutrophil infiltration, 4-HNE and NADPH oxidase gp91 expression, Bax/Bcl-2/poly(ADP-ribose) polymerase (PARP)-mediated apoptosis formation, blue Masson-stained fibrosis, and urinary protein level. STS treatment significantly reduced hypertension, oxidative stress, neutrophil infiltration, fibrosis, and Bax/Bcl-2/PARP-mediated apoptosis formation and depressed the urinary protein level in the RVHT models. Conclusion: Our results suggest that STS treatment could ameliorate RVHT hypertension and renal oxidative injury through antioxidant, antifibrotic, and antiapoptotic mechanisms.

Background: Intralesional injection of sodium thiosulfate has emerged as a promising therapy for calcinosis cutis, but to our knowledge there are no randomized controlled trials evaluating its efficacy as a treatment. Objective: Conduct a prospective, double-blinded investigation of intralesional sodium thiosulfate versus normal saline in the treatment of dystrophic calcinosis cutis. Methods: This prospective pilot study injected normal saline or sodium thiosulfate at 0.1 mL/cm2 into lesions at baseline and at 1- and 2-month follow-up. Subjects were followed for a total of 12 weeks. An in-person Physician Global Assessment score was assigned by the injecting physician at each visit and was repeated by an independent observer. Results: Of 4 subjects who completed the study, only 1 experienced improvement in the size and Physician Global Assessment score of the lesion. By 3-month follow-up, there was no difference between the average size of the treatment and control lesions (P = .39). Limitations: This was a small single-center study with limited demographic diversity and a short follow-up period. Only dystrophic calcinosis cutis subjects were included, and subjects received only 3 monthly injections of sodium thiosulfate. Conclusions: With only 1 positive response, our results highlight the need for further study of sodium thiosulfate treatment for dystrophic calcinosis.

Summary: Background: Intimal hyperplasia (IH) remains a major limitation in the long-term success of any type of revascularisation. IH is due to vascular smooth muscle cell (VSMC) dedifferentiation, proliferation and migration. The gasotransmitter Hydrogen Sulfide (H2S), mainly produced in blood vessels by the enzyme cystathionine- γ-lyase (CSE), inhibits IH in pre-clinical models. However, there is currently no H2S donor available to treat patients. Here we used sodium thiosulfate (STS), a clinically-approved source of sulfur, to limit IH. Methods: Low density lipoprotein receptor deleted (LDLR−/−), WT or Cse-deleted (Cse−/−) male mice randomly treated with 4 g/L STS in the water bottle were submitted to focal carotid artery stenosis to induce IH. Human vein segments were maintained in culture for 7 days to induce IH. Further in vitro studies were conducted in primary human vascular smooth muscle cells (VSMCs). Findings: STS inhibited IH in WT mice, as well as in LDLR−/− and Cse−/− mice, and in human vein segments. STS inhibited cell proliferation in the carotid artery wall and in human vein segments. STS increased polysulfides in vivo and protein persulfidation in vitro, which correlated with microtubule depolymerisation, cell cycle arrest and reduced VSMC migration and proliferation. Interpretation: STS, a drug used for the treatment of cyanide poisoning and calciphylaxis, protects against IH in a mouse model of arterial restenosis and in human vein segments. STS acts as an H2S donor to limit VSMC migration and proliferation via microtubule depolymerisation. Funding: This work was supported by the Swiss National Science Foundation (grant FN-310030_176158 to FA and SD and PZ00P3-185927 to AL); the Novartis Foundation to FA; and the Union des Sociétés Suisses des Maladies Vasculaires to SD, and the Fondation pour la recherche en chirurgie vasculaire et thoracique.

Background: Calciphylaxis is a rare, often fatal disease resulting from calcification of dermal arterioles and capillaries. Usually diagnosed in patients with end-stage renal disease, this disorder typically presents as necrotic, nonhealing ulcers in acral or adipose areas. Here we report the case of an elderly man who was found to have calciphylaxis of the distal digits and penis, the latter of which is an uncommon site of disease that carries a particularly poor prognosis.Case Presentation: A 73-year-old African American man with multiple medical comorbidities including dialysis-dependent end-stage renal disease presented with worsening painful, necrotic lesions on his glans penis and several distal digits over the last 2 months. The wound on the glans was foul smelling with overlying purulence and had been unsuccessfully treated with amoxicillin-clavulanic acid. Discovery of diffuse intravascular calcification on computed tomography, in addition to a markedly elevated calcium-phosphate product immediately prior to the onset of his ulcers, led to the diagnosis of calciphylaxis. The patient was initiated on sodium thiosulfate without improvement in his lesions, and he died 3 months later after another prolonged hospitalization.Conclusions: While calciphylaxis is a rare disease, involvement of the distal digits and especially the penis is even more uncommon and portends a particularly poor prognosis: 6-month mortality rates are reportedly as high as 70%. This suggests that prompt recognition and management of the disease is required; however, despite receiving standard therapy, our patient failed to experience improvement in his disease and instead developed several more fingertip ulcers at blood glucose sample points during his hospitalization. A corollary of the case presented here is the need for more effective management of calciphylaxis, especially for patients in whom uncommon sites, such as the penis, are involved. [ABSTRACT FROM AUTHOR]

Background: Calciphylaxis, or calcific uremic arteriolopathy (CUA), is a rare, fatal disorder of microvascular calcification and thrombosis that typically affects patients with end-stage renal disease (ESRD) receiving long-term dialysis. Fewer reports describe calciphylaxis in peritoneal dialysis patients than hemodialysis patients as per a literature review. To date, there are no clear guidelines for CUA diagnosis and treatment. While sodium thiosulfate (STS) has been increasingly used for treatment in recent years, there have also been reports of severe side effects. There is no uniform standard for its usage and dosage, especially for peritoneal dialysis patients.Case Presentation: We present a case of a 40-year-old Chinese male patient with ESRD on peritoneal dialysis who developed calciphylaxis with severe painful cutaneous ulcers on the fingers and toes that were managed successfully for 6 months with comprehensive treatment composed mainly of small-dose fractionated sodium thiosulfate.Conclusions: Our experience suggests that the treatment of calciphylaxis requires timely and multi-angle intervention. Treatment with small-dose fractionated sodium thiosulfate has proven effective and tolerated in this patient. [ABSTRACT FROM AUTHOR]

Bovine ringworm is a serious public and veterinary health problem worldwide. Many antifungals and antibiotics have been evaluated in the past in an attempt to identify a suitable agent for the topical treatment of bovine ringworm. The objective of this study was to highlight the epidemiology of ringworm in cattle in North of Mosul; and to evaluate three types of antifungals. The study included examination of 508 cows and calves of various ages that were spread across 17 fields in Mosul, Iraq. Clinical investigations and laboratory diagnoses were recorded during 2018-2020. Three topical antifungals including sodium thiosulfate, Whitefield ointment and Iodine preparation were evaluated. Of the 508 animals examined126 (24.8%) were naturally infected with ringworm caused by Trichophyton verrucosum, and highest prevalence of infection was observed in Al-Abbasiya fields (46.6%). Furthermore, the incidence was higher in young calves under one year old (54.76%), and it was more common in males than females (67.46% and 32.53%, respectively). Significant differences (P≤0.01) were observed between the groups of treated animals (10 animals in each group)which were treated with Sodium thiosulfate solution 25% (7 healing days) and the group which was treated with Whitefield's ointment 30 g (14 healing days), with iodine solution 5% (21 days). [ABSTRACT FROM AUTHOR]

Abstract Background This study aims to evaluate the ability of sodium thiosulfate (STS) to neutralize the adverse effect of sodium hypochlorite (NaOCl) on dentin micro-hardness. Methods Fifty single-rooted teeth were longitudinally sectioned. The samples divided into a control and four sample groups (n = 20). All the samples were immersed in different solutions as follows, Control: Normal saline for 15 min, G1and G2: 2.5% NaOCl for 15 min, G3: 2.5% NaOCl for 15 min, followed by 5% STS for 10 min, G4: Normal saline for 15 min followed by 5% STS for 10 min. All groups except G1 incubated for one week before the test. The micro-hardness of samples was measured. Data were analyzed using the Kruskal–Wallis test for pairwise comparisons. A p value

Sarju Panchal,1 Kirstie Holtermann,2 Namrita Trivedi,1 Hariharan Regunath,3 Preethi Yerram4 1Department of Internal Medicine, Hospital of University of Pennsylvania, Philadelphia, PA 19146, USA; 2Department of Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USA; 3Department of Medicine – Divisions of Pulmonary, Critical Care and Infectious Diseases, University of Missouri School of Medicine, Columbia, MO 65212, USA; 4Department of Medicine – Division of Nephrology, University of Missouri School of Medicine, Columbia, MO 65212, USACorrespondence: Preethi YerramDepartment of Medicine - Division of Nephrology, University of Missouri School of Medicine, One Hospital Drive, Columbia, MO 65212, USATel +1 573 882 7992Email yerramp@umsystem.eduBackground: Calciphylaxis is a rare but severe complication mostly affecting patients with end-stage renal disease (ESRD) and is associated with high morbidity and mortality. The natural history, concomitant factors, pathogenesis, and treatment for calciphylaxis remain equivocal.Methods: We conducted a retrospective study on patients diagnosed with calciphylaxis in a tertiary care center between January 1, 2012, and December 31, 2017. We describe demographics, co-morbidities, laboratory parameters, effectiveness of sodium thiosulfate treatment and outcomes.Results: Of the 30 patients (age 65.6 ± 12.79 years, male:female = 8:22), 23 (76.67%) had ESRD and were either on hemodialysis (15 [65.22%], median duration 22.5 months [range 0.2– 96 months]) or peritoneal dialysis (8 [34.78%], duration 29± 10 months). Predisposing home medications: 8 (28%) had calcium supplements, 10 (36%) had warfarin, 16 (57%) had vitamin D and 5 (18%) had iron supplements. The median parathyroid hormone (PTH) level was 239.8 pg/mL (range 4.7– 2922). Calciphylaxis was found on extremities in 21 (70%) and on torso in 6 (20%) patients. Sodium thiosulfate (STS) was given for treatment in 20 (67%) patients and 3 were cured in < 2.25 months. One-year survival for all patients with calciphylaxis was 26% (29% for STS group and 20% for those that did not receive STS) and following any surgical treatment regardless of STS use was 14%.Limitations: Retrospective design, absence of a control group and low power.Conclusion: Calciphylaxis was more common among females with a predilection for extremities over the torso. Elevations in PTH and inflammatory markers were common. Treatment with STS did not show a statistically significant improvement in survival. Those who were cured, were treated with STS up to three months.Keywords: calciphylaxis, sodium thiosulfate, calcific uremic arteriolopathy, calcification, non-uremic calciphylaxis

Objective: To compare the anti-proliferative effect of sodium thiosulfate on human colorectal cancer cells (HT-29) and normal small intestine cells (IEC6). Methods: Cells (HT-29 and IEC6) were treated with different concentrations of sodium thiosulfate ranging from 0.5 mM to 80 mM for 24 h. Cell viability was measured via crystal violet and MTT assays. HT-29 cells were further treated in the presence and absence of mitochondrial electron transport chain (ETC) inhibitors, KATP channel opener and closer and H2S inhibitors for 24 h followed by sodium thiosulfate in order to study their respective roles in the anti-proliferative activity of sodium thiosulfate. Results: The IC50 values of sodium thiosulfate on HT-29 cells were 40.93 mM and 42.45 mM by crystal violet and MTT assay whereas, in the case of IEC6 cells, the values were 45.17 mM and 47.22 mM. The inhibition of endogenous H2S enzymes and KATP channel induced no change in the anti-proliferative capacity of sodium thiosulfate. However, the anti-proliferative activity of sodium thiosulfate was enhanced in the presence of mitochondrial ETC inhibitors. Conclusions: HT-29 cell growth is effectively attenuated by sodium thiosulfate and the anti-proliferative activity of sodium thiosulfate is enhanced in the presence of mitochondrial ETC inhibitors.

Abstract Hydrogen sulfide (H2S) has long been known as a toxic environmental hazard. Discovery of physiological roles of H2S as a neurotransmitter by Kimura and colleagues triggered an intensive research in the biological roles of H2S in the past decades. Manipulation of H2S levels by inhibiting H2S synthesis or administration of H2S-releasing molecules revealed beneficial as well as harmful effects of H2S. As a result, it is now established that H2S levels are tightly controlled and too much or too little H2S levels cause harm. Nonetheless, translation of sulfide-based therapy to clinical practice has been stymied due to the very low therapeutic index of sulfide and the incomplete understanding of endogenous sulfide metabolism. One potential strategy to circumvent this problem is to use a safe and stable sulfide metabolite that may mediate effects of H2S. Alternatively, endogenous sulfide levels may be controlled using specific sulfide scavengers. In this review article, the role of endogenous H2S production and catabolism will be briefly reviewed followed by an introduction of thiosulfate and H2S scavengers as novel pharmacological tools to control H2S-dependent signaling.

Objectives This study aimed to compare the efficacy of intravenous sodium thiosulfate (IV STS) with that of loratadine in the treatment of uremic pruritus in hemodialysis (HD) patients. Methods This retrospective study included 44 HD patients with pruritus aged over 18 years between June 2018 and January 2020 at the Aerospace Center Hospital of China. Twenty-four HD patients received 3.2 g IV STS treatment three times per week at the end of each HD session for 8 weeks. Twenty HD patients received loratadine (10 mg/day) for 8 weeks. Pruritus intensity was measured using a visual analog scale (VAS) and the detailed pruritus score (DPS) at three time points. The safety of STS was evaluated according to adverse event symptoms and biological variable changes. Results There was no significant difference between the STS and loratadine groups in age, sex, characteristics of pruritus, or other clinical variables before treatment. After 8 weeks of treatment, the VAS score (7.07 ± 2.56 and 2.67 ± 2.01) and DPS (30.72 ± 4.81 and 8.04 ± 2.86) decreased significantly in the STS group (p 0.05). There were no morbidities or mortalities associated with the use of either drug. All biological variables remained stable after therapy. Conclusions STS can improve uremic pruritus in HD patients. However, literature on the subject remains lacking. Close monitoring for adverse effects is advised.

Background Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to provide benefits in the management of peritoneal metastasis. Cisplatin (CDDP) is one of the most frequently used drugs for peritoneal infusion. A major restriction is that CDDP causes renal toxicity and acute renal failure, sometimes leading to chronic renal failure. The aim of the present study was to assess the impact of sodium thiosulfate (ST) in preventing renal impairment (RI) following HIPEC with CDDP. Methods This prospective study assessed the RI rates for all patients who underwent HIPEC with CDDP during two successive periods: without ST (nST Period; from November 2016 to September 2017) and with ST (ST Period; from October 2017 to March 2018). During the ST Period, patients received an ST infusion at 9 mg/m2 prior to HIPEC and at 12 mg/m2 at the end of the procedure. RI was defined by postoperative serum creatinine >1.6 times elevation of baseline value. The impact of ST treatment was evaluated by comparison of the RI rates between the two periods. Results During ST Period, none of 38 patients (0%) developed RI versus 11/35 patients (31.4%) during the nST Period (p

Calcinosis cutis is defined as the deposition of calcium salts in the skin. The dystrophic form is the most common and usually occurs in chronic inflammatory processes associated with collagenoses. Therapeutic options include surgical excision as well as a few pharmacological treatments. Overall, the evidence for the known therapeutic interventions is very limited and there is a lack of valid recommendations. Intravenous sodium thiosulfate has been used successfully in the treatment of calciphylaxis. In our case series, five patients with dystrophic calcinosis cutis received intravenous sodium thiosulfate for at least six cycles on five consecutive days per month, with single doses of 12.5 g and 25.0 g, respectively. A reduction in the calcified lesions could not be proven with certainty, but stable disease conditions were achieved. Intravenous sodium thiosulfate may counteract the progression of calcinosis cutis. The successful use of epicutaneously applied sodium thiosulfate, as described in the literature, suggests that a higher cutaneous bioavailability can be achieved to exert a lytic effect on calcinosis cutis. This is further supported by the reported efficacy of high-dose sodium thiosulfate in the treatment of calciphylaxis., (© 2024 The Author(s). Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Competing Interests: None disclosed.

The use of sodium thiosulfate has emerged as a promising treatment for calciphylaxis, albeit inconclusively in terms of efficacy and variable outcomes. Research in this field has been limited by a paucity of samples due to the rarity of the disease. We herein discuss eight calciphylaxis patients' responses to STS, the potential predictive factors affecting outcomes and compare our results with previously published literature. We are able to show that lesion severity, concomitant drugs, and dialysis duration may be predictive factors of outcomes. Further, improvement of the wound site may be a clinically relevant prognostic determinant. [ABSTRACT FROM AUTHOR]

The ongoing epidemic caused by SARS-CoV-2 infection led to the search for fundamentally new ways and means to combat inflammation and other pathologies caused by this virus. Using a cellular model of lipopolysaccharide (LPS)-induced sepsis (human promonocytes), we showed that both a hydrogen sulfide donor (sodium thiosulfate, STS) and a recombinant Heat shock protein 70 (rHsp70) effectively block all major inflammatory mediators when administrated before and after LPS challenge. The protective anti-inflammatory effect of rHsp70 and H2S was also confirmed in vivo using various animal models of pneumonia. Specifically, it was found that rHsp70 injections prevented the development of the acute respiratory distress syndrome in highly pathogenic pneumonia in mice, increased animal survival, and reduced the number of Programmed death-1 (PD-1)-positive T-lymphocytes in peripheral blood. Based on our model experiments we developed a combined two-phase therapeutic approach for the treatment of COVID-19 patients. This procedure includes the inhalation of hot helium–oxygen mixtures for induction of endogenous Hsp70 in the first phase and STS inhalation in the second phase. The use of this approach has yielded positive results in COVID-19 patients, reducing the area of lung lesions, restoring parameters of innate immunity and T-cell immune response against coronavirus infection, and preventing the development of pulmonary fibrosis and immune exhaustion syndrome.

IntroductionIn the immunology of sepsis microcirculatory and mitochondrial dysfunction in the gastrointestinal system are important contributors to mortality. Hydrogen sulfide (H2S) optimizes gastrointestinal oxygen supply and mitochondrial respiration predominantly via K(ATP)-channels. Therefore, we tested the hypothesis that sodium thiosulfate (STS), an inducer of endogenous H2S, improves intestinal and hepatic microcirculation and mitochondrial function via K(ATP)-channels in sepsis.MethodsIn 40 male Wistar rats colon ascendens stent peritonitis (CASP) surgery was performed to establish sepsis. Animals were randomized into 4 groups (1: STS 1 g • kg-1 i.p., 2: glibenclamide (GL) 5 mg • kg-1 i.p., 3: STS + GL, 4: vehicle (VE) i.p.). Treatment was given directly after CASP-surgery and 24 hours later. Microcirculatory oxygenation (µHBO2) and flow (µflow) of the colon and the liver were continuously recorded over 90 min using tissue reflectance spectrophotometry. Mitochondrial oxygen consumption in tissue homogenates was determined with respirometry. Statistic: two-way ANOVA + Dunnett´s and Tukey post - hoc test (microcirculation) and Kruskal-Wallis test + Dunn’s multiple comparison test (mitochondria). p < 0.05 was considered significant.ResultsSTS increased µHbO2 (colon: 90 min: + 10.4 ± 18.3%; liver: 90 min: + 5.8 ± 9.1%; p < 0.05 vs. baseline). Furthermore, STS ameliorated µflow (colon: 60 min: + 51.9 ± 71.1 aU; liver: 90 min: + 22.5 ± 20.0 aU; p < 0.05 vs. baseline). In both organs, µHbO2 and µflow were significantly higher after STS compared to VE. The combination of STS and GL increased colonic µHbO2 and µflow (µHbO2 90 min: + 8.7 ± 11.5%; µflow: 90 min: + 41.8 ± 63.3 aU; p < 0.05 vs. baseline), with significantly higher values compared to VE. Liver µHbO2 and µflow did not change after STS and GL. GL alone did not change colonic or hepatic µHbO2 or µflow. Mitochondrial oxygen consumption and macrohemodynamic remained unaltered.ConclusionThe beneficial effect of STS on intestinal and hepatic microcirculatory oxygenation in sepsis seems to be mediated by an increased microcirculatory perfusion and not by mitochondrial respiratory or macrohemodynamic changes. Furthermore, the effect of STS on hepatic but not on intestinal microcirculation seems to be K(ATP)-channel-dependent.

Laterite ore is one of the important sources of nickel (Ni). However, it is difficult to liberate Ni from ore structure during reduction roasting. This paper provided an effective way for a robust recovery of Ni from laterite ore by H2 reduction using sodium thiosulfate (Na2S2O3) as a promoter. . It was found that a Ni content of 9.97% and a Ni recovery of 99.24% were achieved with 20 wt% Na2S2O3 at 1,100°C. The promoting mechanism of Na2S2O3 in laterite ore reduction by H2 was also investigated. The thermogravimetric results suggested the formation of Na2Mg2SiO7, Na2SO3, Na2SO4, and S during the pyrolysis of laterite with Na2S2O3, among which the alkali metal salts could destroy the structures of nickel-bearing silicate minerals and hence release Ni, while S could participate in the formation of the low-melting-point eutectic phase of FeS-Fe. The formation of low-melting-point phases were further verified by the morphology analysis, which could improve the aggregation of Ni-Fe particles due to the capillary forces of FeS-Fe as well as the enhanced element migration by the liquid phase of sodium silicates during reduction.

Thin films of zinc sulphide (ZnS) were prepared by a facile, economical, and scalable electrochemical method as a buffer layer for a CdS/CdTe based solar cell. Herein, a three-electrode cell in a complexing agent-free electrolyte containing 0.1 mol/L Na2S2O3 and 0.1 mol/L ZnSO4 was employed for the deposition of ZnS. The electrodeposition conditions (temperature: 30°C, pH: 4.2, cathodic potential: −1.10 V and deposition time: 90 min) were identified to grow an ideal thin film of ZnS on fluorine-doped tin oxide (FTO)-coated glass substrate, applying moderate stirring of 60 rpm. In material characterization of heat-treated samples (300°C, 10 min), the optical absorption measurement depicted a direct energy bandgap of 3.64 eV with low light absorbance and a blueshift from bulk ZnS. Scanning electron microscopy and atomic force microscopy studies demonstrated the uniform distribution of ZnS grains over the FTO glass substrate, and x-ray diffraction analysis revealed an amorphous structural nature of ZnS. The charge carrier density and flat-band potential of the ZnS material were determined as 1.19 × 10−19 cm−3 and −0.59 V, respectively, by Mott–Schottky analysis. [ABSTRACT FROM AUTHOR]

Calcinosis cutis (CC) is defined as the deposition of calcium salts on the skin and subcutaneous tissue. It is associated with different conditions, including some autoimmune diseases, and it can generate significant inflammation, pain, and functional impairment. Different therapies have been tried with limited results. Intralesional sodium thiosulfate seems a promising therapeutic option. We report a patient with diffuse systemic sclerosis who presented with two symmetrical plaques on both axillae, which caused pain and skin retraction. The clinical diagnosis was consistent with CC, which was confirmed by skin biopsy and ultrasound. The patient was treated with a 250 mg/ml solution of sodium thiosulfate injected into the plaques. Complete resolution was achieved after three monthly sessions. The only reported adverse effect was a transient burning sensation during the injections. Given its effectiveness and safety, we believe that intralesional sodium thiosulfate could become a valid first-line option for the treatment of CC. [ABSTRACT FROM AUTHOR]

Computed tomography (CT) scanning is being increasingly employed in the study of natural history, particularly to investigate the internal anatomy of unique specimens in museum collections. Different techniques to enhance the contrast between tissues have been developed to improve the quality of the scans while preserving the integrity of these rare specimens. Diffusible iodine‐based contrast enhanced computed tomography (diceCT) was found to be particularly effective and reversible for staining tissues in formalin preserved specimens. While it can also be effectively employed to stain ethanol‐preserved specimens of small size, the reversibility of this process and the applicability to large‐bodied animals has never been thoroughly tested. Here, we describe a novel diceCT protocol developed to stain and de‐stain ethanol‐preserved prenatal specimens of baleen whales (Mysticeti, Cetacea). These large (10–90 cm in length only considering early fetal stages) specimens present unique challenges as they are rare in collections and irreplaceable, therefore it is imperative to not damage them with the staining process. Before trying this protocol on baleen whales' specimens, we conducted a pilot study on commercially available fetal pigs using the same parameters. This allowed us to optimize the staining time to obtain the best results in CT scanning and to test first‐hand the effect of de‐staining on ethanol‐based specimens. External coloration of the specimens is also a concern with iodine‐staining, as stained specimens assume a bright red color that needs to be removed from both internal and external tissues before they can be stored. To test the reversibility of the stain in ethanol‐preserved specimens with fur, we also conducted a small experiment using commercially acquired domestic mice. After these trials were successful, we applied the staining and de‐staining protocol to multiple fetal specimens of mysticetes up to 90 cm in length, both ethanol‐ and formalin‐preserved. Specimens were soaked in a solution of 1% pure iodine in 70% ethanol for 1–28 days, according to their size. After scanning, specimens are soaked in a solution of 3% sodium thiosulfate in 70% ethanol that is able to completely wash out the iodine from the tissues in a shorter time frame, between a few hours and 14 days. The same concentrations were used for formalin‐preserved specimens, but DI water was used as solvent instead of ethanol. The staining technique proved particularly useful to enhance the contrast difference between cartilage, mineralized bone, teeth, and the surrounding soft tissues even when the specimens where scanned in medical‐grade CT scans. The specimens did not suffer any visible damage or shrinkage due to the procedure, and in both the fetal samples and in the mice the color of the stain was completely removed by the de‐staining process. We conclude therefore that this protocol can be safely applied to a variety of ethanol‐preserved museum specimens to enhance the quality of the CT scanning and highlight internal morphological features without recurring to dissection or other irreversible procedures. We also provide tips to best apply this protocol, from how to mix the solutions to how to minimize the staining time. [ABSTRACT FROM AUTHOR]

Introduction: In the immunology of sepsis microcirculatory and mitochondrial dysfunction in the gastrointestinal system are important contributors to mortality. Hydrogen sulfide (H2S) optimizes gastrointestinal oxygen supply and mitochondrial respiration predominantly via K(ATP)-channels. Therefore, we tested the hypothesis that sodium thiosulfate (STS), an inducer of endogenous H2S, improves intestinal and hepatic microcirculation and mitochondrial function via K(ATP)-channels in sepsis. Methods: In 40 male Wistar rats colon ascendens stent peritonitis (CASP) surgery was performed to establish sepsis. Animals were randomized into 4 groups (1: STS 1 g • kg-1 i.p., 2: glibenclamide (GL) 5 mg • kg-1 i.p., 3: STS + GL, 4: vehicle (VE) i.p.). Treatment was given directly after CASP-surgery and 24 hours later. Microcirculatory oxygenation (µHBO2) and flow (µflow) of the colon and the liver were continuously recorded over 90 min using tissue reflectance spectrophotometry. Mitochondrial oxygen consumption in tissue homogenates was determined with respirometry. Statistic: two-way ANOVA + Dunnett´s and Tukey post - hoc test (microcirculation) and Kruskal-Wallis test + Dunn's multiple comparison test (mitochondria). p < 0.05 was considered significant. Results: STS increased µHbO2 (colon: 90 min: + 10.4 ± 18.3%; liver: 90 min: + 5.8 ± 9.1%; p < 0.05 vs. baseline). Furthermore, STS ameliorated µflow (colon: 60 min: + 51.9 ± 71.1 aU; liver: 90 min: + 22.5 ± 20.0 aU; p < 0.05 vs. baseline). In both organs, µHbO2 and µflow were significantly higher after STS compared to VE. The combination of STS and GL increased colonic µHbO2 and µflow (µHbO2 90 min: + 8.7 ± 11.5%; µflow: 90 min: + 41.8 ± 63.3 aU; p < 0.05 vs. baseline), with significantly higher values compared to VE. Liver µHbO2 and µflow did not change after STS and GL. GL alone did not change colonic or hepatic µHbO2 or µflow. Mitochondrial oxygen consumption and macrohemodynamic remained unaltered. Conclusion: The beneficial effect of STS on intestinal and hepatic microcirculatory oxygenation in sepsis seems to be mediated by an increased microcirculatory perfusion and not by mitochondrial respiratory or macrohemodynamic changes. Furthermore, the effect of STS on hepatic but not on intestinal microcirculation seems to be K(ATP)-channel-dependent. [ABSTRACT FROM AUTHOR]

Familial hyperphosphatemic tumoral calcinosis is a rare disorder characterized by hyperphosphatemia with recurrent ectopic periarticular calcifications, in addition to other visceral and vascular manifestations, without any inflammatory or neoplastic disorder. The available treatment strategies are limited. Here we report an eight year old female patient with recurrent lesions under the chin, and bilateral hips which are painful and improving of the size of the lesions and hyperphosphatemia. The patient was started to the treatment with peroral acetazolamide however the lesion did not regress but a new lesion appeared then we added sevelamer and topical sodium thiosulfate treatment for three months. After the three months of the combination treatment the lesions, there were no pain, no hyperphospahtemia regression/disappearance of the lesions. This combination treatment or topical sodium thiosulfate use only may be a novel treatment strategy for the patients prospective controlled trials are needed. [ABSTRACT FROM AUTHOR]

Cornelia Erfurt-Berge, Regina Renner Department of Dermatology, University Hospital Erlangen, Erlangen 91054, GermanyCorrespondence: Cornelia Erfurt-BergeDepartment of Dermatology, University Hospital Erlangen, Ulmenweg 18, Erlangen 91054, GermanyTel + 49 9 131 853 5000Email Cornelia.Erfurt-Berge@uk-erlangen.deAbstract: Calciphylaxis (CP) is a rare disorder presenting with painful ischemic skin ulcerations. Its association with end-stage renal disease, but also non-uremic cases have been described. Several risk factors, like metabolic syndrome, calcium-phosphate imbalance, anticoagulative medication and female gender have been discussed. Multidisciplinary therapeutic approaches are necessary since evidence-based guidelines are missing due to lack of pathophysiological understanding of the disease and the absence of studies with large patient cohorts. However, strategies for local wound therapy, reduction of risk factors and systemic therapies are being developed. Changes in duration, frequency and method of hemodialysis and specific medication to lower the calcium upload can be effective in uremic CP cases. Systemic treatments with cinacalcet, sodium thiosulfate or bisphosphonates have been applied successfully in CP patients, but large placebo-controlled randomized trials are still needed to gather better insight into this fatal disease.Keywords: calciphylaxis, calcific uremic arteriolopathy, non-uremic calciphylaxis, calcification, treatment, sodium thiosulfate

Abstract Background Cisplatin-induced hearing loss is frequent and severe. Antioxidants such as sodium thiosulfate (STS) can neutralize the effects of cisplatin. The objective of the trial was to test the efficacy of trans-tympanic injections of a STS gel to prevent cisplatin-induced ototoxicity. Methods Eligible participants were newly diagnosed patients with stage III or IV squamous cell carcinoma of the mouth, oropharynx, hypopharynx, or larynx and scheduled to be treated by concurrent chemoradiation (CCR). Patients with asymmetric hearing were not eligible. The planed treatment included cisplatin 100 mg/m2 at days 1, 22 and 43. A baseline pre-treatment complete audiometric evaluation (pure tone at frequencies ranging from 0.5 to 14 kHz, bone conduction at 0.5–4 kHz and DPOAEs) was performed. Adverse effects were noted according to CTCAE. On the day before the beginning of CCR, eligible and consenting patients were randomized to receive a trans-tympanic injection of the gel either in the left ear or in the right ear. A final post-treatment complete audiometric evaluation was scheduled to be performed 1 month after the end of CCR by audiologists kept blind to the ear assignment. For the main outcome, the permanent threshold shift (PTS) in decibel (dB) was calculated as the difference between the final and baseline measures at all pure tone frequencies at 0.5–14 kHz for each patient and for each ear. The main outcome was assessed blindly in a mixed linear model with the PTS as the dependent variable and intervention, frequency, their interaction and radiation dose to the cochlea as independent variables. Results Between January 2015 and April 2016, 13 patients were randomized. The trial was stopped in June 2016 for poor accrual. The average loss of hearing over all frequencies was 1.3 dB less for treated ears compared to control ears. Although not statistically (p = 0.61) nor clinically significant, the difference was in favor of the treated ears for all frequencies between 3 and 10 kHz. Conclusions Our trial suggests that STS deposited on the round window was safe for the middle and inner ears. More work is needed to improve the efficacy of trans-tympanic injections of cisplatin antidotes. Trial registration ClinicalTrials.gov, NTC02281006, Registered 3 November 2014.

Introduction: The use of Sodium Hypochlorite (NaOCl) as an endodontic irrigant changes the properties of dentine and lowers the bond strength of resin cements to dentine. But it can be reversed by the use of antioxidants. Aim: To evaluate the effect of different antioxidants for restoring adhesion potential/reversal of microtensile bond strength of dentin of the pulp chamber treated with NaOCl and Ethylenediaminetetracetic Acid (EDTA). Materials and Methods: It was a laboratory based experimentalinvitro study in which 40 freshly extracted human incisors were selected and cut to expose the pulp chamber dentin. The specimens were distributed into five groups: Group I samples were irrigated with 5.25% NaOCl for 30 minutes followed by 17% EDTA for 3 minutes and final rinse was done with 5.25% NaOCl (Positive control). Group II samples were treated with distilled water only (Negative control). In Group III, samples were treated same as in group I followed by 10% Sodium Ascorbate (SA) for 10 minute. Samples of group IV samples were also treated as in group I followed by application of 5% solution of Alpha tocopherol with for 10 minutes. Group V samples were treated same as in group I followed by rinse with 5% solution of Sodium Thiosulphate (Na2 S2 O3 ) for 10 minutes. Composite resin build up was performed and interface was tested by using Universal testing machine for Microtensile bond strength. The resulting data was analysed by one-way Analysis of Variance (ANOVA) and Mann-Whitney U test (p

Introduction: The use of Sodium Hypochlorite (NaOCl) as an endodontic irrigant changes the properties of dentine and lowers the bond strength of resin cements to dentine. But it can be reversed by the use of antioxidants. Aim: To evaluate the effect of different antioxidants for restoring adhesion potential/reversal of microtensile bond strength of dentin of the pulp chamber treated with NaOCl and Ethylenediaminetetracetic Acid (EDTA). Materials and Methods: It was a laboratory based experimental in-vitro study in which 40 freshly extracted human incisors were selected and cut to expose the pulp chamber dentin. The specimens were distributed into five groups: Group I samples were irrigated with 5.25% NaOCl for 30 minute followed by 17% EDTA for 3 minutes and final rinse was done with 5.25% NaOCl (Positive Control). Group II samples were treated with distilled water only (Negative Control). In Group III, samples were treated same as in group I followed by 10% Sodium Ascorbate (SA) for 10 minute. Samples of group IV were also treated as in group I then application of 5% solution of Alpha tocopherol with for 10 minutes. Group V samples were treated same as in group I then 5% solution of Sodium Thiosulphate (Na2S2O3) for 10 minutes. Composite resin build up was performed and interface was tested by using the universal testing machine for Microtensile bond strength. The resulting data were analysed by one-way analysis of variance ANOVA and Mann-Whitney U test (p<0.05). Results: The results demonstrated that irrigation with 5.25% NaOCl and 17% EDTA produce significant (p<0.05) reduction in resin dentin bond strength but this can be reversed by application of 5% Na2S2O3. Highest bond strength was observed in group V (22.38±0.84) and lowest for group I (15.38±1.22). Conclusion: Dentin bond strength was significantly reduced when bonding was performed immediately after use of NaOCl. Use of antioxidants after final irrigation with NaOCl can be recommended for better bonding of composite resin. [ABSTRACT FROM AUTHOR]

Although traditionally observed in patients with end-stage renal disease and secondary hyperparathyroidism, calciphylaxis has been reported in patients with normal renal and parathyroid function. There is no evidence-based therapy available. The use of sodium thiosulfate (STS) has been increasingly described. Herein we describe two patients who responded well to this treatment.

Background/Aims: Arterial stenosis activates the renin-angiotensin-aldosterone system subsequently resulting in renovascular hypertension (RVHT) and renal oxidative injury. We explored the effect of sodium thiosulfate (STS, Na2S2O3), a developed antioxidant in clinical trial, on RVHT-induced hypertension and renal oxidative injury in rats. Methods: We induced RVHT in male Wistar rats with bilaterally partial ligation of renal arteries in the 2-kidney 2-clip model. We evaluated the STS effect on RVHT-induced oxidative injury and apoptosis by a chemiluminescence amplification method, Western blot, and immunohistochemistry. Results: We found STS displayed a dose-dependent antioxidant H2O2 activity and adapted the maximal scavenging H2O2 activity of STS at the dosage of 0.1 g/kg intraperitoneally 3 times/week for 4 weeks in RVHT rats. RVHT induced a significant elevation of arterial blood pressure, blood reactive oxygen species amount, neutrophil infiltration, 4-HNE and NADPH oxidase gp91 expression, Bax/Bcl-2/poly(ADP-ribose) polymerase (PARP)-mediated apoptosis formation, blue Masson-stained fibrosis, and urinary protein level. STS treatment significantly reduced hypertension, oxidative stress, neutrophil infiltration, fibrosis, and Bax/Bcl-2/PARP-mediated apoptosis formation and depressed the urinary protein level in the RVHT models. Conclusion: Our results suggest that STS treatment could ameliorate RVHT hypertension and renal oxidative injury through antioxidant, antifibrotic, and antiapoptotic mechanisms. [ABSTRACT FROM AUTHOR]