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1.
BMC Nephrol ; 23(1): 4, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979980

RESUMO

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.


Assuntos
Calciofilaxia/tratamento farmacológico , Quelantes/administração & dosagem , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Diálise Peritoneal , Tiossulfatos/administração & dosagem , Adulto , Calciofilaxia/diagnóstico por imagem , Calciofilaxia/etiologia , Humanos , Masculino , Diálise Peritoneal/efeitos adversos , Resultado do Tratamento
2.
N Engl J Med ; 378(25): 2376-2385, 2018 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-29924955

RESUMO

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 .).


Assuntos
Cisplatino/efeitos adversos , Perda Auditiva/prevenção & controle , Hepatoblastoma/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Tiossulfatos/uso terapêutico , Adolescente , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Quimioterapia Combinada , Feminino , Seguimentos , Taxa de Filtração Glomerular , Perda Auditiva/induzido quimicamente , Hepatoblastoma/mortalidade , Humanos , Incidência , Lactente , Neoplasias Hepáticas/mortalidade , Masculino , Método Simples-Cego , Análise de Sobrevida , Tiossulfatos/administração & dosagem , Tiossulfatos/efeitos adversos
3.
Invest New Drugs ; 38(5): 1463-1471, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157599

RESUMO

Cisplatin is a widely used chemotherapy for the treatment of certain solid tumors. Ototoxicity and subsequent permanent hearing loss remain a serious dose-limiting side effect associated with cisplatin treatment. To date, no therapies have been approved to prevent or treat cisplatin-induced hearing loss (CIHL). Sodium thiosulfate effectively inactivates cisplatin through covalent binding and may provide protection against cisplatin-induced ototoxicity. DB-020 is being developed as a novel formulation of sodium thiosulfate pentahydrate in 1% sodium hyaluronate for intratympanic injection (IT), enabling the delivery of high concentrations of thiosulfate into the cochlea prior to cisplatin administration. In the DB-020-002 phase 1a single-ascending dose study, healthy volunteers were enrolled into 5 cohorts to receive different doses of DB-020 via IT injection. Cohorts 1-4 received unilateral injections while Cohort 5 received bilateral injections. Plasma thiosulfate pharmacokinetics was measured, and safety and audiometric data were collected throughout the study. This study has demonstrated that intratympanic administration of DB-020 results in nominal systemic increases in thiosulfate levels, hence it should not compromise cisplatin anti-tumor efficacy. Furthermore, DB-020 was safe and well tolerated with most adverse events reported as transient, of mild-to-moderate severity and related to the IT administration procedure. These results support the design and execution of the ongoing proof-of-concept study, DB-020-002, to assess otoprotection using DB-020 in cancer patients receiving cisplatin without negatively impacting cisplatin anti-tumor efficacy.


Assuntos
Antineoplásicos/administração & dosagem , Perda Auditiva/prevenção & controle , Tiossulfatos/administração & dosagem , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/farmacocinética , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Perda Auditiva/induzido quimicamente , Humanos , Injeção Intratimpânica , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Tiossulfatos/efeitos adversos , Tiossulfatos/sangue , Tiossulfatos/farmacocinética , Adulto Jovem
4.
Pharmacol Res ; 151: 104536, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31734346

RESUMO

Controversial data are available on hydrogen sulfide (H2S) during hemorrhage and resuscitation, depending on timing, dosing, mode of application, and the H2S donor used. Sodium thiosulfate (Na2S2O3) is a recognized drug devoid of major side effects, which attenuated murine acute lung injury and cerebral ischemia/reperfusion injury. Therefore, we tested the hypothesis whether Na2S2O3 would mitigate organ dysfunction in porcine hemorrhage-and-resuscitation. We studied animals with pre-existing coronary artery disease because of the reduced coronary arterial expression of the H2S producing enzyme cystathionine-γ-lyase (CSE) in this prospective, randomized, controlled, blinded experimental study. 20 anesthetized and instrumented pigs underwent 3 h of hemorrhage (removal of 30 % of the blood volume and subsequent titration of mean arterial pressure to 40 mmHg). Resuscitation (72 h) comprised re-transfusion of shed blood, crystalloids, and continuous i.v. norepinephrine. Animals randomly received vehicle or Na2S2O3 (0.1 g·kg-1 h-1) for 24 h. Before, at the end of and every 24 h after shock, hemodynamics, metabolism, blood gases, lung, heart, kidney, and liver function and injury were evaluated together with cytokines and parameters of oxidative and nitrosative stress. Immediate post mortem lung, kidney, heart, and liver specimen were analyzed for marker proteins of inflammation and oxidative and nitrosative stress and mitochondrial respiratory activity in the heart, kidney, and liver. Immuno-histochemical analysis comprised lung extra-vascular albumin accumulation, nitrotyrosine formation, and CSE and glucocorticoid receptor (GCR) expression. Na2S2O3 significantly attenuated shock-induced impairment of lung mechanics and gas exchange (plateau and positive end-expiratory pressure at 72 h p = 0.0006/p = 0.0264; Horovitz index at 48 h p = 0.0261), which coincided with a higher tissue GCR expression (p = 0.0415). During resuscitation from hemorrhagic shock Na2S2O3 attenuated shock-induced acute lung injury in co-morbid swine, most likely due to a GCR expression related mechanism.


Assuntos
Antioxidantes/uso terapêutico , Aterosclerose/complicações , Choque Hemorrágico/complicações , Choque Hemorrágico/tratamento farmacológico , Tiossulfatos/uso terapêutico , Animais , Antioxidantes/administração & dosagem , Aterosclerose/patologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/patologia , Feminino , Masculino , Distribuição Aleatória , Ressuscitação , Choque Hemorrágico/patologia , Suínos , Tiossulfatos/administração & dosagem
5.
J Interv Cardiol ; 2020: 6014915, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33041696

RESUMO

BACKGROUND: In animal studies, hydrogen sulfide (H2S) has been shown to protect the heart from ischemia-reperfusion injury. This study evaluates the safety and tolerability of the H2S donor sodium thiosulfate (STS) in patients with acute coronary syndrome (ACS). METHODS: Eighteen patients, undergoing coronary angiography for ACS, received STS intravenously immediately after arrival at the catheterization laboratory according to a "3 + 3 dose-escalation design" with fixed dosing endpoint (0, 2.5, 5, 10, 12.5, and 15 grams). This first dose STS was combined with verapamil and nitroglycerin required for transradial procedures. A second dose STS was administered 6 hours later. Primary endpoint was dose-limiting toxicity, defined as significant hemodynamic instability or death up to 24 hours or before discharge from the coronary care unit. Secondary outcomes included the occurrence of anaphylaxis, nausea, vomiting, and systolic blood pressure (SBP) course. RESULTS: Sixteen patients received two dosages of STS and two patients one dosage. None of the patients reached the primary endpoint, nor experienced a serious adverse event. We observed a clinically well-tolerated decline in SBP 1 hour after administration of the first STS dose and concomitant verapamil/nitroglycerin. SBP for all patients together reduced 16.8 (8.1-25.5) mmHg (P = 0.0008). No significant decline in SBP occurred after the second dose. Mild nausea was observed in one patient. CONCLUSION: This is the first report on sodium thiosulfate administration in patients with acute coronary syndromes. Our data suggest that sodium thiosulfate was well tolerated in this setting. The potential benefit of this intervention has to be examined in larger studies.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Angiografia Coronária , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Tiossulfatos , Adulto , Angiografia Coronária/efeitos adversos , Angiografia Coronária/métodos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismo por Reperfusão Miocárdica/etiologia , Projetos Piloto , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/efeitos adversos , Tiossulfatos/administração & dosagem , Tiossulfatos/efeitos adversos
6.
J Am Acad Dermatol ; 82(2): 317-325, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31302187

RESUMO

BACKGROUND: We have limited data on the treatment of calcinosis cutis associated with systemic sclerosis and dermatomyositis. OBJECTIVE: To assess the efficacy and tolerance of available treatments for calcinosis cutis based on previously published studies. METHODS: We performed a systematic review of studies published in Medline, Embase, and the Cochrane library during 1980-July 2018. The strength of clinical data was graded according to the modified Oxford Centre for Evidence-Based Medicine levels of evidence. RESULTS: In all, 30 studies (288 patients) were included. Eleven therapeutic classes, surgery, and physical treatments were identified as potential treatment options for calcinosis cutis. On the basis of results of a small randomized controlled trial and 4 retrospective studies, low-dose warfarin should not be used for calcinosis cutis (level IB evidence). The results of several studies suggest diltiazem and bisphosphonates might be useful treatment options (level IV). Considering biologic therapies, rituximab has shown promising results in treating both dermatomyositis and systemic sclerosis, whereas tumor necrosis factor inhibitors might be useful for treating juvenile dermatomyositis (level IV). Intralesional sodium thiosulfate might be a promising alternative (level IV). LIMITATIONS: Few included studies had a high level of evidence. CONCLUSION: This study highlights the efficacy and tolerance profiles of available treatments for calcinosis cutis, with a focus on level of evidence.


Assuntos
Calcinose/terapia , Dermatomiosite/complicações , Escleroderma Sistêmico/complicações , Dermatopatias/terapia , Calcinose/etiologia , Procedimentos Cirúrgicos Dermatológicos , Dermatomiosite/terapia , Diltiazem/uso terapêutico , Humanos , Injeções Intralesionais , Modalidades de Fisioterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rituximab/uso terapêutico , Escleroderma Sistêmico/terapia , Dermatopatias/etiologia , Tiossulfatos/administração & dosagem , Resultado do Tratamento
7.
Ren Fail ; 42(1): 987-993, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32967516

RESUMO

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). The mean decrease in VAS score (6.89 ± 1.98 and 6.34 ± 2.35) and DPS (28.90 ± 3.24 and 26.92 ± 2.41) in the loratadine group was not statistically significant (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.


Assuntos
Prurido/tratamento farmacológico , Prurido/etiologia , Diálise Renal , Tiossulfatos/administração & dosagem , Uremia/complicações , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tiossulfatos/efeitos adversos , Uremia/sangue , Uremia/terapia , Escala Visual Analógica
8.
J Surg Oncol ; 120(7): 1220-1226, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31602673

RESUMO

BACKGROUND AND OBJECTIVES: Hyperthermic intrathoracic chemotherapy (HITOC) is used for the treatment of malignant pleural tumors. Although HITOC proved to be safe, postoperative renal failure due to nephrotoxicity of intrapleural cisplatin remains a concern. METHODS: This single-center study was performed retrospectively in patients who underwent pleural tumor resection and HITOC between September 2008 and December 2018. RESULTS: A total of 84 patients (female n = 33; 39.3%) with malignant pleural tumors underwent surgical cytoreduction with subsequent HITOC (60 minutes; 42°C). During the study period, we gradually increased the dosage of cisplatin (100-150 mg/m2 BSA n = 36; 175 mg/m2 BSA n = 2) and finally added doxorubicin (cisplatin 175 mg/m2 BSA/doxorubicin 65 mg; n = 46). All patients had perioperative fluid balancing. The last 54 (64.3%) patients also received perioperative cytoprotection. Overall 29 patients (34.5%) experienced renal insufficiency. Despite higher cisplatin concentrations, patients with cytoprotection showed significantly lower postoperative serum creatinine levels after 1 week (P = .006) and at discharge (P = .020). Also, they showed less intermediate and severe renal insufficiencies (5.6% vs 13.3%). CONCLUSIONS: Adequate perioperative fluid management and cytoprotection seem to be effective in protecting renal function. This allows the administration of higher intracavitary cisplatin doses without raising the rate of renal insufficiencies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Hipertermia Induzida/efeitos adversos , Mesotelioma/terapia , Néfrons/efeitos dos fármacos , Neoplasias Pleurais/terapia , Substâncias Protetoras/administração & dosagem , Insuficiência Renal Crônica/tratamento farmacológico , Amifostina/administração & dosagem , Cisplatino/administração & dosagem , Terapia Combinada , Creatinina/sangue , Citoproteção , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Pleurais/patologia , Cuidados Pós-Operatórios , Prognóstico , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Tiossulfatos/administração & dosagem , Cavidade Torácica/cirurgia
9.
Ann Emerg Med ; 74(3): 423-429, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31080026

RESUMO

STUDY OBJECTIVE: Cyanide is a deadly poison, particularly with oral exposure, in which larger doses can occur before any symptoms develop. Multiple governmental agencies highlight oral cyanide as an agent that can be used in a terrorist attack because it can be easily weaponized and is readily available. Currently, there are no Food and Drug Administration-approved antidotes specifically for oral cyanide. An oral countermeasure that can neutralize and prevent absorption of cyanide from the gastrointestinal tract after oral exposure is needed. The objective of this study is to determine if the combination of glycine and sodium thiosulfate administered orally is effective in reducing mortality in a large, swine model of oral cyanide toxicity. METHODS: Nine swine (45 to 55 kg) were instrumented, sedated, and stabilized. Potassium cyanide (at 8 mg/kg) in saline solution was delivered as a onetime bolus through an orogastric tube. Three minutes after cyanide administration, animals that were randomized to the treatment group received sodium thiosulfate (508.2 mg/kg, 3.25-M solution) and glycine (30 mg/kg, 3.5-M solution) through an orogastric tube. Survival at 60 minutes was the primary outcome. We compared survival between groups by log-rank Mantel-Cox analysis and trended laboratory results and vital signs. RESULTS: At baseline and treatment, all animals were similar. Survival at 60 minutes was 100% in treated animals compared with 0% in the control group (P=.003). By the study end, defined as death or 60 minutes after cyanide administration, there was a significant difference in the lactate concentration between the treatment and control groups (control 9.43 mmol/L [SD 4.08]; treatment 1.66 mmol/L [SD 0.82]; difference between means 7.69 mmol/L [SD 2.07]; 95% confidence interval difference -14.05 to -1.32). Mean arterial pressure was significantly different between the treatment and control groups at study end (control 26 mm Hg [SD 6.7]; treatment 81 mm Hg [SD 14]; difference between means 55.2 mm Hg [SD 7.1]; 95% confidence interval difference 37.8 to 72.6). pH and oxygen saturation were also significantly different between the treatment and control groups at study end. CONCLUSION: The combination of oral sodium thiosulfate and glycine significantly improved survival and physiologic parameters in a large-animal model of oral cyanide toxicity.


Assuntos
Antídotos/administração & dosagem , Glicina/administração & dosagem , Cianeto de Potássio/intoxicação , Tiossulfatos/administração & dosagem , Administração Oral , Animais , Antídotos/farmacocinética , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Glicina/farmacologia , Humanos , Venenos , Distribuição Aleatória , Suínos , Tiossulfatos/farmacologia , Fatores de Tempo
10.
Biosci Biotechnol Biochem ; 83(1): 114-122, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30200826

RESUMO

The present study describes the hair growth-promoting effects of sodium thiosulfate (STS), a widely used compound, in mice. STS accelerated hair growth in the "telogen model", suggesting that it stimulates telogen hair follicles to reenter the anagen phase of hair growth. In the same model, STS potentiated hair growth in an additive manner with minoxidil (MXD), a drug used for the treatment of androgenic alopecia. Furthermore, in the "anagen model", STS promoted hair growth, probably by promoting hair follicle proliferation. Since STS elevated the skin surface temperature, its hair growth-promoting activity may be partly due to vasorelaxation, similar to MXD. In addition, STS is known to generate a gaseous mediator, H2S, which has vasorelaxation and anti-inflammatory/anti-oxidative stress activities. Therefore, STS and/or provisionally its metabolite, H2S, may aid the hair growth process. Collectively, these results suggest that salts of thiosulfate may represent a novel and beneficial remedy for hair loss.


Assuntos
Folículo Piloso/efeitos dos fármacos , Folículo Piloso/crescimento & desenvolvimento , Modelos Animais , Tiossulfatos/farmacologia , Alopecia/tratamento farmacológico , Animais , Sinergismo Farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos C3H , Minoxidil/administração & dosagem , Minoxidil/efeitos adversos , Minoxidil/farmacologia , Modelos Biológicos , Temperatura Cutânea/efeitos dos fármacos , Sulfurtransferases/genética , Sulfurtransferases/metabolismo , Tiossulfatos/administração & dosagem , Tiossulfatos/efeitos adversos
11.
Br J Dermatol ; 178(6): 1412-1415, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28667747

RESUMO

Dystrophic calcinosis cutis is a debilitating condition of calcium salt deposition in the skin often occurring in association with connective tissue disease (CTD). Available treatments for calcinosis cutis are unsatisfactory, but given the recent use of topical and intralesional sodium thiosulfate (STS) to treat calcifying disorders, we sought to describe the use of intravenous (IV) STS for CTD-associated dystrophic calcinosis cutis. We report three patients with long-standing and extensive CTD-associated calcinosis cutis treated with IV STS after having failed multiple prior therapies. All three patients experienced fatigue and nausea with STS infusions, and none of the patients had notable clinical or symptomatic improvement of calcinosis. It remains to be seen whether the administration of IV STS earlier in the onset of calcinosis might be of benefit given that these patients all had long-standing and refractory CTD-associated calcinosis. Given the small number of patients in this series, further investigation into the use of IV STS in calcinosis cutis is warranted.


Assuntos
Calcinose/tratamento farmacológico , Doenças do Tecido Conjuntivo/complicações , Fármacos Dermatológicos/administração & dosagem , Dermatopatias/tratamento farmacológico , Tiossulfatos/administração & dosagem , Antioxidantes/administração & dosagem , Quelantes/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Resultado do Tratamento
12.
Dermatol Surg ; 44 Suppl 1: S5-S9, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30358629

RESUMO

BACKGROUND: A dissolving agent for calcium hydroxylapatite (CaHA, Radiesse) soft-tissue filler would be of value should inadvertent intravascular injection, vascular compromise, nodule formation, or overcorrection occur. METHODS: In a prospective, single-center, proof-of-concept study, 12 cadaveric porcine skin samples were injected with CaHA (0.4-0.8 mL). Samples were then randomized to intralesional injection of 0.2-mL sodium thiosulfate (STS, 12.5 g/50 mL); 1 to 2 g of topical sodium metabisulfite (SMB, 25% SMB in 120-mL gel) applied with occlusion, or both intralesional STS and topical SMB. Control samples were not treated after CaHA injection. A 4-mm punch biopsy was obtained 24 hours after treatment, and tissue sections were stained with hematoxylin and eosin and prepared for light microscopy. A board-certified dermatopathologist estimated the amount of CaHA present in each sample. RESULTS: Intralesional STS alone or combined with topical SMB completely dissolved CaHA in the porcine skin samples. Topical SMB treatment reduced, but did not entirely clear CaHA from the tissue samples. The control samples contained easily identifiable CaHA microspheres. CONCLUSION: This proof-of-concept study illustrates the potential reversibility of CaHA filler with intralesional STS, topical SMB, and the combination of both agents. Larger, in vivo, studies are now warranted to provide further insight.


Assuntos
Antídotos/química , Preenchedores Dérmicos/química , Durapatita/química , Sulfitos/química , Tiossulfatos/química , Administração Cutânea , Animais , Antídotos/administração & dosagem , Preenchedores Dérmicos/efeitos adversos , Durapatita/efeitos adversos , Feminino , Técnicas In Vitro , Injeções Intralesionais , Estudo de Prova de Conceito , Estudos Prospectivos , Distribuição Aleatória , Pele , Sulfitos/administração & dosagem , Suínos , Tiossulfatos/administração & dosagem
13.
Ann Emerg Med ; 69(6): 718-725.e4, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28041825

RESUMO

STUDY OBJECTIVE: The 2 antidotes for acute cyanide poisoning in the United States must be administered by intravenous injection. In the out-of-hospital setting, intravenous injection is not practical, particularly for mass casualties, and intramuscular injection would be preferred. The purpose of this study is to determine whether sodium nitrite and sodium thiosulfate are effective cyanide antidotes when administered by intramuscular injection. METHODS: We used a randomized, nonblinded, parallel-group study design in 3 mammalian models: cyanide gas inhalation in mice, with treatment postexposure; intravenous sodium cyanide infusion in rabbits, with severe hypotension as the trigger for treatment; and intravenous potassium cyanide infusion in pigs, with apnea as the trigger for treatment. The drugs were administered by intramuscular injection, and all 3 models were lethal in the absence of therapy. RESULTS: We found that sodium nitrite and sodium thiosulfate individually rescued 100% of the mice, and that the combination of the 2 drugs rescued 73% of the rabbits and 80% of the pigs. In all 3 species, survival in treated animals was significantly better than in control animals (log rank test, P<.05). In the pigs, the drugs attenuated an increase in the plasma lactate concentration within 5 minutes postantidote injection (difference: plasma lactate, saline solution-treated versus nitrite- or thiosulfate-treated 1.76 [95% confidence interval 1.25 to 2.27]). CONCLUSION: We conclude that sodium nitrite and sodium thiosulfate administered by intramuscular injection are effective against severe cyanide poisoning in 3 clinically relevant animal models of out-of-hospital emergency care.


Assuntos
Antídotos/administração & dosagem , Antídotos/uso terapêutico , Cianetos/intoxicação , Nitrito de Sódio/administração & dosagem , Nitrito de Sódio/uso terapêutico , Tiossulfatos/administração & dosagem , Tiossulfatos/uso terapêutico , Animais , Antídotos/farmacologia , Modelos Animais de Doenças , Injeções Intramusculares , Masculino , Camundongos , Coelhos , Distribuição Aleatória , Nitrito de Sódio/farmacologia , Sus scrofa , Tiossulfatos/farmacologia
14.
Cardiovasc Drugs Ther ; 31(5-6): 511-524, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28965151

RESUMO

PURPOSE: Sodium thiosulfate (STS) has of late been proven efficacious in models of urolithiasis and vascular calcification. However, its cardiovascular effects on ischemia reperfusion injury (IR) have not been revealed. Being an antioxidant and calcium chelator, it is assumed to play a vital role in IR as ROS production and calcium overload are major perpetrators of IR injury. METHODS: The cardioprotective effect of STS was evaluated in vitro using H9C2 cardiomyocytes and in vivo using both isolated rat heart and intact left anterior descending artery (LAD) occlusion models of ischemia reperfusion injury. Finally, in silico tools were utilized to establish its possible mode of action. Myocardial injury markers and expression of apoptotic proteins were studied along with myocardial histopathology. RESULTS: STS of 1 mM recovered H9C2 cells from glucose oxidase/catalase-induced apoptosis. The isolated rat heart treated with STS prior to IR injury improved its hemodynamics and reduced the infarct size to 9%. This was supported by the absence of derangement of cardiac fibers from H&E stained section of LAD-occluded rats. Plasma troponin levels decreased by 15% compared to IR and the myocardium showed diminished apoptotic proteins. An in silico docking analysis revealed higher binding affinity of STS for caspase-3 with a binding energy of - 60.523 kcal/mol for the complex. CONCLUSION: The effectiveness of STS as a cardioprotective agent is attributed to the reduction of apoptosis by binding to the active site of caspase-3 in silico, which was substantiated by the reduced expression of caspase-3 and poly ADP ribose polymerase levels.


Assuntos
Apoptose/efeitos dos fármacos , Cardiotônicos/uso terapêutico , Precondicionamento Isquêmico Miocárdico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Tiossulfatos/uso terapêutico , Animais , Cardiotônicos/administração & dosagem , Caspase 3/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Simulação de Acoplamento Molecular , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ligação Proteica , Ratos , Tiossulfatos/administração & dosagem
15.
J Intensive Care Med ; 32(9): 547-553, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27435907

RESUMO

PURPOSE: This study evaluated thiocyanate concentrations and factors associated with thiocyanate accumulation in intensive care unit patients receiving nitroprusside with and without sodium thiosulfate coadministration. MATERIALS AND METHODS: This retrospective study evaluated critically ill adults who received nitroprusside infusions and had at least one thiocyanate concentration. Patients with thiocyanate accumulation (concentrations ≥30 µg/mL) were compared to patients without accumulation. Factors associated with accumulation were determined by Spearman correlation and multivariate regression. RESULTS: Thiocyanate concentrations (n = 192) were obtained from 87 patients. Fourteen of the 87 (16%) patients experienced thiocyanate accumulation with a mean (SD) thiocyanate concentration of 44 ± 11 µg/mL. Patients with accumulation had received greater cumulative nitroprusside doses (28 vs 8.2 mg/kg, P < .01), greater cumulative sodium thiosulfate doses (16.8 vs 10.1 mg/kg, P < .01), and longer infusion durations (10.9 vs 6.0 days, P < .01), compared to patients without accumulation. Sodium thiosulfate coadministration resulted in greater thiocyanate concentrations (22.8 ± 16.7 vs 16.8 ± 14.9 µg/mL, P = .01), despite utilization of lower cumulative nitroprusside doses (10.2 vs 14.6 mg/kg, P = .03). Cumulative nitroprusside dose ( r2 .44, P < .001) and cumulative sodium thiosulfate dose ( r2 .32, P < .001) demonstrated a significant correlation with measured thiocyanate concentrations. Thiocyanate accumulation was independently associated with cumulative nitroprusside dose in mg/kg (regression coefficient 0.75, 95% CI 0.63-0.89; P < .01). No clinically significant adverse effects of cyanide or thiocyanate toxicity were observed. CONCLUSIONS: Cumulative nitroprusside dose was independently associated with thiocyanate accumulation. Despite elevated thiocyanate levels in 16% of patients, there was no clinical evidence of cyanide or thiocyanate toxicity. Routine monitoring of thiocyanate concentrations appears most warranted in patients receiving higher cumulative doses of nitroprusside.


Assuntos
Antídotos/efeitos adversos , Nitroprussiato/efeitos adversos , Tiocianatos/sangue , Tiossulfatos/efeitos adversos , Vasodilatadores/efeitos adversos , Adulto , Idoso , Antídotos/administração & dosagem , Cuidados Críticos/métodos , Estado Terminal/terapia , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Infusões Intravenosas , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nitroprussiato/administração & dosagem , Análise de Regressão , Estudos Retrospectivos , Estatísticas não Paramétricas , Tiossulfatos/administração & dosagem , Vasodilatadores/administração & dosagem
16.
Pediatr Dermatol ; 34(3): 356-358, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28382733

RESUMO

Calcinosis cutis is a term used to describe a group of disorders in which calcium salt deposits form in the skin and subcutaneous tissue. We report a 6-year-old boy with hypoparathyroidism after thyroidectomy who was admitted to the hospital for severe hypocalcemia being treated with calcium gluconate intravenous infusion through peripheral veins. Within a few days we made a diagnosis of iatrogenic calcinosis cutis and treatment with 10% topical sodium thiosulfate was prescribed; complete resolution of lesions was achieved after 6 months, with no local or systemic adverse effects. Because of the lack of noninvasive alternatives and the good tolerance of the treatment, especially in childhood, we suggest the topical use of this drug as an option for this condition.


Assuntos
Calcinose/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Tiossulfatos/administração & dosagem , Administração Tópica , Criança , Humanos , Doença Iatrogênica , Masculino , Dermatopatias/etiologia
17.
Jpn J Clin Oncol ; 46(1): 4-12, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26486825

RESUMO

Intra-arterial chemotherapy has been used to treat localized malignant neoplasms in patients with head and neck cancer for over 50 years as the head and neck region is particularly well suited to regional chemotherapy. Early intra-arterial chemotherapy did not prove its efficacy. In addition, the additional complications associated with establishing and maintaining arterial access have further dampened enthusiasm for this approach. Subsequent significant advances in vascular radiology techniques and the development of new devices, such as fluoroscopy units and angiographic catheters, have made possible safe, accurate and repeated superselective intra-arterial chemotherapy. Intra-arterial infusion of high-dose cisplatin with systemic neutralization by intravenous sodium thiosulfate (RADPLAT) is a theoretically attractive approach to the treatment of advanced head and neck cancer. However, a Dutch trial comparing intra-arterial and intravenous chemoradiotherapy for advanced head and neck cancer showed that RADPLAT was not superior to intravenous chemoradiotherapy. Therefore, further investigation of RADPLAT, including the refinement of the indications for its application, is needed.


Assuntos
Quimiorradioterapia , Cisplatino/administração & dosagem , Neoplasias de Cabeça e Pescoço/terapia , Tiossulfatos/administração & dosagem , Quimiorradioterapia/métodos , Cisplatino/efeitos adversos , Ensaios Clínicos como Assunto , Humanos , Infusões Intra-Arteriais , Japão , Pessoa de Meia-Idade , Substâncias Protetoras/administração & dosagem
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