Anti-proliferative potential of sodium thiosulfate against HT 29 human colon cancer cells with augmented effect in the presence of mitochondrial electron transport chain inhibitors

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, K

Anti-proliferative potential of sodium thiosulfate against HT 29 human colon cancer cells with augmented effect in the presence of mitochondrial electron transport chain inhibitors

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.

Calcifilaxis, a propósito de un caso / Calciphylaxis, about a case

Resumen La calcifilaxis es un síndrome caracterizado por la calcificación de la pared media de las arteriolas de pequeño y mediano calibre de dermis y tejido celular subcutáneo, que se caracteriza clínicamente por úlceras necróticas, intensamente dolorosas, que afectan sobre todo miembros inferiores. Existen factores de riesgo para su desarrollo, como insuficiencia renal crónica, hiperparatiroidismo, sexo femenino, raza caucásica, diabetes, uso de anticoagulantes, entre otros. Si bien no existe un protocolo estandarizado para su tratamiento, se ha propuesto el uso del tiosulfato sódico como primera elección. Se presenta el caso de una paciente de sexo femenino de 75 años de edad con diagnóstico de calcifilaxis.

Abstract Calciphylaxis is a syndrome characterized by calciphication of the media of small and medium vessels of dermis and subcutaneous celular tissue, clinically characterized by extremely painful, necrotic ulcers, that affects especially lower limbs. There are risk factors for its development, such as renal failure, hyperparathyroidism, female gender, caucasian race, diabetes, use of anticoagulants, among others. Although there is not a standarized protocol for the treatment, it has been proposed the use of sodium thiosulfate as first line. We report a case of a woman of 75 years old with calciphylaxis.

Sodium thiosulfate and pamidronate for treatment of calciphylaxis: case report / Tiosulfato de sodio y pamidronato para el tratamiento de calcifilaxis: reporte de caso

Abstract Introduction: Calciphylaxis is an infrequent disease that almost exclusively affects patients with chronic kidney disease, although cases have been observed in patients without renal function impairment. The diagnosis is mainly made by clinical manifestations and subsequently confirmed by radiological and histological study. The optimal treatment is not known, although there is a consensus that a multifactorial approach is required. Clinical Case: A 68-year-old woman on hemodialysis for 2 years, who presented a painful nodular lesion in the left thigh, a skin biopsy was performed resulting in a diagnosis of calciphylaxis. Treatment and Outcome: Treatment was started with intravenous sodium thiosulfate. Pamidronate is added intravenously, three months later, due to an unfavorable evolution. After 6 months of treatment, improvement in nodular lesions and healing of the ulcerated lesion was observed to be generally well tolerated treatment. Conclusion: The combined treatment of sodium thiosulfate, pamidronate and calcitomimetics has been effectiveand safe for the treatment of calciphylaxis, inducing complete remission.

Resumen: Introducción: La calcifilaxis es una enfermedad infrecuente que afecta casi exclusivamente a pacientes con insuficiencia renal, aunque se han observado casos en pacientes sin deterioro de la función renal. El diagnóstico es clínico confirmándose con estudio radiológico e histológico. No se conoce con exactitud el tratamiento óptimo, aunque hay consenso en que se requiere un abordaje multifactorial. Caso Clínico: Mujer de 68 años en hemodiálisis desde hace 2 años, que presenta una lesión nodular dolorosa en muslo izquierdo, resultando un diagnostico compatible con calcifilaxis, tras biopsia cutánea. Tratamiento y resultado: Inicia tratamiento con tiosulfato de sodio vía venosa. Tres meses más tarde y ante la evolución desfavorable, se añade al tratamiento pamidronato vía intravenosa. Tras 6 meses de tratamiento se observa mejoría de las lesiones nodulares y cicatrización de la lesión ulcerada, habiéndose experimentado buena tolerancia. Conclusión: El tratamiento combinado de tiosulfato de sodio, pamidronato y calcimiméticos ha resultado efectivo y seguro para el tratamiento de la calcifilaxis, induciendo su remisión completa.

Calcifilaxis / Calciphylaxis

La calcifilaxis es una vasculopatía caracterizada por isquemia y necrosis cutánea dolorosa debida a calcificación, fibroplastia de la íntima y trombosis de las arteriolas paniculares. Compromete más frecuentemente a pacientes con insuficiencia renal crónica terminal y tiene muy elevada mortalidad. La biopsia de las lesiones cutáneas se utiliza como método diagnóstico. No se han registrado hallazgos específicos de laboratorio. Las lesiones cutáneas generalmente comienzan en las extremidades a modo de moteado violáceo doloroso similar al livedo reticularis. La evolución natural es hacia úlceras y escaras. La primera línea de tratamiento consiste en el cuidado de las lesiones cutáneas y antibioticoterapia. El tiosulfato sódico se utiliza como tratamiento debido a su actividad como antioxidante y quelante. Se presentan dos casos clínicos.

Calciphylaxis is vasculopathy characterized by ischemia and painful skin necrosis due to calcification and intimal fibroplasia of thrombosis of the panicular arterioles. It most frequently compromises patients with terminal chronic renal failure and has a high mortality rate. Biopsy of skin lesions is used as a diagnostic method. No specific laboratory findings have been recorded. Skin lesions usually begin in the extremities like a painful purplish mottling similar to "livedo reticularis". The natural evolution is to ulcers and bedsores. The first line of treatment involves the care of skin lesions and antibiotic therapy. Sodium thiosulfate is used as treatment due to its antioxidant activity and as a chelating. Two clinical cases are here reported.

Antidotes of cyanide intoxication

Cyanide poisoning can occur from industrial disasters, smoke inhalation from fire, food, and multiple other sources. Cyanide inhibits mitochondrial oxidative phosphorylation by blocking mitochondrial cytochrome oxidase, which in turn results in anaerobic metabolism and depletion of adenosine triphosphate in cells. Rapid administration of antidote is crucial for life saving in severe cyanide poisoning. Multiple antidotes are available for cyanide poisoning. The action mechanism of cyanide antidotes include formation of methemoglobin, production of less or no toxic complex, and sulfane sulfur supplementation. At present, the available antidotes are amyl nitrite, sodium nitrite, sodium thiosulfate, hydroxocobalamin, 4-dimethylaminophenol, and dicobalt edetate. Amyl nitrite, sodium nitrite, and 4-dimethylaminophenol induce the formation of methemoglobin. Sodium thiosulfate supplies the sulfane sulfur molecule to rhodanese, allowing formation of thiocyanate and regeneration of native enzymes. Hydroxocobalamin binds cyanide rapidly and irreversibly to form cyanocobalamin. Dicobalt edetate acts as a chelator of cyanide, forming a stable complex. Based on the best evidence available, a treatment regimen of 100% oxygen and hydroxocobalamin, with or without sodium thiosulfate, is recommended for cyanide poisoning. Amyl nitrite and sodium nitrite, which induce methemoglobin, should be avoided in victims of smoke inhalation because of serious adverse effects.

Comparative research on the adverse reaction of the intravenous injection of sodium thiosulfate and calcium gluconate / 中国实用护理杂志

Objective To compare the incidence of adverse reaction,clinical manifestation and serious degree of adverse reaction and the intravenous injection time of the two different drugs,and provide references for the safe dosage of the drugs in clinic.Methods 200 patients from June 2009 to June 2010,who visited department of dermatology because of allergic dermatitis were chosen.They were randomly divided into the sodium thiosulfate group and the calcium gluconate group according to the drugs which were injected intravenouly.And incidence of adverse reaction,clinical manifestation and serious degree of adverse reaction and the intravenous injection time were compared between two groups.Results Compared with the calcium gluconate group,the rate of the adverse reaction of the sodium thiosulfate group is lower,and the average time needed is shorter,in addition,there is no serious adverse reaction during injection.Conclusions Intravenous injection of sodium thiosulfate has the advantage of lower incidence of adverse reaction,shorter time needed,and fewer serious adverse reaction,which is worthy of wide spread.

A Simple and Accurate Method for Determining Antioxidative Activity

Antioxidative activity is an important factor in inhibiting oxidative stress. The usual methods for determining antioxidative activity are time-consuming and cumbersome. They are also indirect processes that use biological material such as brain or liver microsome. This study therefore proposed a new method. Redoxpotential was determined using galvanic cell with or without the addition of various antioxidants or herbal extracts in zinc sulfate solution. The result was compared with the results from the TBA method and the peroxide value from sodium thiosulfate titration. All methods showed significant and dose-dependent enhancement of antioxidative activity by adding ascorbic acid, quercetin, ginseng, or gingko biloba extract. The result of redox potential using galvanic cell showed the smallest standard deviation and took the shortest time among the three methods. Therefore, the antioxidative potential of chemical substances and herbal extracts can be determined simply, directly and accurately in a short period of time using galvanic cell.

Effectiveness of Magnesium Oxide and Sodium Thiosulfate in Calcium Oxalate Crystallization / 대한비뇨기과학회지

We investigated the comparative effect of magnesium and thiosulfate on the calcium oxalate crystallization. Magnesium is a strong inhibitor of calcium oxalate crystallization and it is sported to inhibit calcium phophate by about 20%. Even if it's mechanism is not clearly known, thiosulfat can resolve 250~100,000 times more than other calcium salts when it is combined with calcium. Wistar rats were fed by 1.0% ethylene glycol (EG) mixed with water. 500mg of magnesium oxide (MgO) per 100gm chows and 10mMo1 of S2O3 per 100gm chows were provided by oral intake respectively. Forty eight wistar rats were divided into following 6 groups. Each group has equal 8 wistar rats; A group (normal chow and water), B group (normal chow and 1%EG), C group (MgO and 1%EG), D group (MgO and water), E group (S2O3 and 1%EG), and F group (S2O3 and water). First, we examined calcium oxalate crystallization on bladder aspiration urine for 6 groups before the experiment and every week for 4 weeks after the experiment. Second, we also examined the degree of formation of calcium oxalate crystallization in renal tissue under polarizing microscope. Calcium oxalate crystallization was found in all 8 wistar rats in B group while it was not round in A, D, F group. Calcium oxalate crystallization was also found in one out of 8 wistar rats in C group, and 5 out of 8 wistar rats in E group. In conclusion, we believe that both MgO and sodium thiosulfate are effective in preventing calcium oxalate stone, and we also believe MgO is more elective than sodium thiosulfate. We think that further researches on administrating methods, the side effects and dosage of these two agents in human are necessary.

“TWO-ROUTE CHEMOTHERAPY”USING AHIGH-DOSE OF HD-CISPLATINE IN ARTERIAL INFUSION / 昆明医科大学学报

Eight patients with malignant tumors, testified by pathological examination. were treated by " Two-Route Chemotherapy" using a high dose of HD-Cisp latine in arterial infusion (AI). Among them 5 cases were primary or metastatic liver carcinoma, 3 cases were Ⅲ-Ⅳ stage breast carcinoma.One or two courses were given in each patient. The dosage of DDP in the first course was 80 - 100mg/m~2. the second was 120-150mg/m~2 with STS Ⅳ as a protective agent. The total lasted 14 courses.When DDF was given alone in AI, the serum creatine level increased temporarily, but there was no significant increase when both DDP and sodi um thiosulfate were given.Results: Among 5 cases of liver carcinomas I was complete response 3 were partial response and 1 was stable. Among 3 cases of Ⅲ-Ⅳ stage of breast carcinomas, all were partial response, giving a response rate of 8 (?) (7/8).