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Statistical evaluation of a quality control method for isolation of pathogenic Vibrio species on selected thiosulfate-citrate-bile salts-sucrose agars.

The recovery of Vibrio cholerae, Vibrio fluvialis, Vibrio parahaemolyticus, and Vibrio vulnificus, employing eight strains of each species, was studied by using four brands of thiosulfate-citrate-bile salts-sucrose (TCBS) agar prepared according to manufacturers' instructions and following a standardized procedure. A standardized broth inoculum of each strain was placed on duplicate plates of each brand of TCBS agar and also on tryptic soy agar (Difco Laboratories) containing 1% (wt/vol) NaCl, the latter serving as the control. Plates were inoculated in a sequence designed to compensate for bias associated with multiplication of the bacteria during the inoculation procedure. Colony counts and quality of growth were recorded after incubation for 18 h at 35 degrees C. The comparison procedure was repeated four times at weekly intervals. Data were analyzed by using an analysis of variance model. The recovery and quality of growth of each species varied significantly on the different brands of TCBS agar. Significant variability was also identified for some components of the inoculation procedure. Modifications of the inoculation procedure are suggested to minimize sources of variance. A simplified statistical procedure, based on the t test, is described for media quality control for laboratories routinely isolating pathogenic Vibrio spp.

Bacteriological Techniques↗

Enhancement by sodium chloride of the selectivity of thiosulfate citrate bile salts sucrose agar for isolating Vibrio cholerae biotype El Tor.

In this study we utilized the salt-tolerant characteristics of vibrios to develop a more selective medium by addition of NaCl to thiosulfate citrate bile salts sucrose (TCBS) agar. The effect of adding salt to TCBS agar varied greatly among brands of TCBS agar and between lots of the same brand. The addition of salt at concentrations as high as 1.5% (2.5% total NaCl) caused the inhibition of growth of three species of commonly encountered normal bowel flora and one strain of classical Vibrio cholerae but did not compromise the use of TCBS agar for isolation of V. cholerae biotype El Tor.

Agar↗

Sulfur isotope fractionation by Proteus vulgaris and Salmonella heidelberg during the reduction of thiosulfate.

Proteus vulgaris metabolized thiosulfate to H2S. The amount evolved and its sulfur isotope composition identified it solely with sulfane sulfur. In contrast, Salmonella heidelberg sequentially reduced the sulfane sulfur of S2O3(-2) with slight enrichment of the evolved sulfide in 32S and then reduced the sulfonate sulfur of S2O3(-2) with large isotopic selectivities and an inverse isotopic fractionation pattern. The inverse isotope fractionation pattern for the H2S derived from the sulfonate sulfur was almost identical to that observed during the reduction of high concentrations of sulfite by S. heidelberg.

Hydrogen Sulfide↗

[Therapy of peritoneal carcinosis with intraperitoneal administration of cis-diamminedichloroplatinum and systemic sodium thiosulfate protection. Clinical results of a pilot study and pharmacokinetics].

Six patients with peritoneal carcinosis and ascites received 13 courses of ip cis-platinum (c-DDP). C-DDP (170-250 mg in 2L saline, dwell 4 h) was administered via Pig-Tail-Cordis catheter with concurrent infusion of sodium thiosulfate (bolus 7.5 g/m2 followed by 2.13 g/m2/h for 12 h). The patients received pre- and post-therapy hydration (250 ml/h) and mannitol-induced diuresis. Courses were given in 4 weekly intervals. With a dwell time of 4 h 27.0% +/- 14.6% (mean +/- SD) of platinum were recovered. Total serum platinum peaked at 3.1 +/- 1.0 microgram/ml. The peritoneal/serum ratio of platinum concentration was 49.5 +/- 12.6 after 1 h, 7.4 +/- 1.7 after 5 h and 4.2 +/- 1.7 after 12 h. Within 12 h 30.9% +/- 10.0% of the administered dose were excreted in urine. In 4 patients the ascites had disappeared lasting 14+, 15+, 5+, 3+ months. 2 patients died within 1 month caused by systemic tumor progression. Following toxicity was observed: 9/13 nausea and vomiting grade 1 (WHO), 2/13 hematological toxicity grade 2, 1/13 sterile peritonitis, no renal or neurological toxicity. This pilot study demonstrates a pharmacokinetic advantage of ip chemotherapy with c-DDP and an effectiveness against peritoneal carcinosis.

Adenocarcinoma↗

Inactivation of cis-diamminedichloroplatinum (II) in blood by sodium thiosulfate.

The mode of inactivation of cis-diamminedichloroplatinum (II) (DDP) in the bloodstream by sodium thiosulfate (STS) was investigated experimentally and clinically by a bioassay system using the phytohemagglutinin stimulation assay of human peripheral blood mononuclear cells. Active DDP in the plasma of dogs after 3 mg/kg of DDP injection, assessed by the bioassay system, was almost completely inactivated, when the level of STS in the plasma was more than 500 times higher at molar STS/DDP ratios than that of DDP. In 6 patients with hepatic malignancies who were treated with hepatic artery infusion of 3 mg/kg DDP and systemic STS, active DDP in the plasma was not detectable in the concurrent presence of STS at molar ratios of more than 500. Severe DDP toxicity in these patients was completely protected. The results indicate that an inactivation of DDP in the bloodstream after DDP injection and, further, an effective protection against DDP toxicity can be achieved by the concurrent presence of STS at molar ratios of more than 500 in the plasma of these patients.

Animals↗

'Two-route chemotherapy' using cisplatin and its neutralizing agent, sodium thiosulfate, for intraperitoneal cancer.

The pharmacokinetics of intraperitoneal cisplatin (DDP) administered with simultaneous intravenous sodium thiosulfate (STS) were investigated by a bioassay system using the phytohemagglutinin (PHA) stimulation assay of human peripheral blood mononuclear cells (PBM). Active DDP in the plasma, assessed by the bioassay system, was almost completely inactivated, when the level of STS in the plasma was more than 500 times higher at molar STS/DDP ratios than that of DDP. However, the peak level of active DDP in the peritoneal cavity was not significantly decreased. Fourteen patients with intraperitoneal carcinoma were treated with intracavitary DDP chemotherapy in combination with STS in this setting. Of 8 patients with malignant ascites who were evaluable for response, 4 patients experienced complete disappearance of ascites and the remaining 4 patients responded with apparent decrease in the volume of their ascites. No serious drug-associated toxicity was encountered.

Adult↗

Chemolithoheterotrophy in a metazoan tissue: thiosulfate production matches ATP demand in ciliated mussel gills.

The ribbed mussel Geukensia demissa inhabits sulfide-rich coastal sediments with a distribution that suggests a preference for exposure to sulfide. Although sulfide is a respiratory poison, it is also a potent reductant. Geukensia demissa gill mitochondria can use sulfide as a respiratory substrate for ATP production, and the gills of this species exhibit sulfide-supported oxygen consumption that matches the energy demand of ciliary beating. Here, we demonstrate (i) that the major product of G. demissa gill sulfide oxidation is thiosulfate and (ii) that the rate of sulfide oxidation also matches the cellular energy demand, resulting in a ratio near unity of oxygen consumed to sulfide oxidized at both low and high ciliary beat frequencies. A value for this ratio of unity is consistent with electrons from sulfide oxidation entering the mitochondrial electron transport chain. In the gills of the blue mussel Mytilus edulis from sulfide-free conditions, this ratio is 3-5 times higher, indicating an uncoupling of oxygen consumption from sulfide oxidation. Whereas M. edulis gills exhibit anaerobic metabolism during sulfide exposure, G. demissa gills do not, indicating a difference in sulfide tolerance between the two mussel species.

Adenosine Triphosphate↗

Treatment of lung cancer with bronchial artery infusion of cisplatin and intravenous sodium thiosulfate rescue.

Forty-nine patients with primary lung cancer were treated with bronchial artery infusion of cisplatin and intravenous injection of and antidote, sodium thiosulfate. More than 50% reduction of tumor size (PR) was observed in 8 of 9 small cell carcinomas (SCLC) and in 16 of 40 non-small cell carcinomas (NSCLC). In NSCLC patients PR was obtained in 71% (12/17) after repeated infusion (greater than or equal to 200 mg cisplatin) and in 17% (4/23) after a single infusion (less than or equal to 150 mg cisplatin). There was a significant linear relationship between cisplatin dose and tumor reduction in this group. No severe adverse effects were encountered.

Adult↗

Rhodanese (thiosulfate:cyanide sulfurtransferase) distribution in the digestive tract of chicken.

In this study the level of rhodanese (thiosulfate:cyanide sulfurtransferase) activity in different regions of the digestive tract of chicken was determined and compared with that in the liver, heart, kidney, and lung. All tissues studied contained rhodanese. The highest specific activity of rhodanese was in the submucosal layer of proventriculus, followed by liver, heart, the mucosal layer of cecum, rectum, and kidney. The lowest level was present in lung. These results suggest that in the chicken part of the ingested cyanide is detoxified in the digestive tract, mainly by the proventriculus, and part of the absorbed cyanide is metabolized by hepatic rhodanese.

Animals↗

Automated detection of hydrogen sulfide release from thiosulfate by Salmonella spp.

Hydrogen sulfide production is used in conventional tests for identification and differentiation of Salmonella spp. from other species of Enterobacteriaceae, and a black precipitate on agar media is the indicator of the reaction. Selective liquid media were formulated for automated optical detection of H2S in salmonellae using the BioSys instrument. The media contained thiosulfate and ferric ammonium citrate, and production of H2S caused copious black pigmentation of the broth. Combination of the H2S indicators with dulcitol or xylose as fermentable carbohydrate, lysine, ornithine or arginine to induce decarboxylase activity, and Tergitol 4 as inhibitor selectively identified six Salmonella spp. by a sharp drop in transmittance at 585 nm. The time for detection of transmittance changes was inversely proportional to initial numbers of CFU in the media: 10 h for 10(5) CFU/ml and 17 h for 10(1) CFU/ml. No detection was observed in six non-Salmonella species of Enterobacteriaceae tested.

Carboxy-Lyases↗

Delayed administration of sodium thiosulfate in animal models reduces platinum ototoxicity without reduction of antitumor activity.

Platinum-based chemotherapeutic agents, such as carboplatin and cisplatin, are effective against many human tumors, but their use may be limited by a high incidence of ototoxicity. Delayed administration of the chemoprotective agent sodium thiosulfate (STS) reduces the ototoxicity of carboplatin in a guinea-pig model, when given up to 8 h after the chemotherapy, and also reduces hearing loss in patients given carboplatin with osmotic blood-brain barrier opening for treatment of brain tumors. We tested whether STS, given at times that achieved otoprotection, could impact the chemotherapeutic efficacy of carboplatin. The impact of STS was evaluated by measuring the onset of growth of LX-1 human small cell lung carcinoma s.c. xenografts in the nude rat. When STS was administered as two boluses, 2 and 6 h after treatment with carboplatin and etoposide, there was a decrease in the time to tumor progression. In contrast, when STS administration was delayed until 8 h after carboplatin/etoposide, there was no reduction in the antitumor cytotoxicity of the chemotherapy. STS infusion did not significantly affect ultrafilterable platinum pharmacokinetics in the guinea pig. To explore the potential wider applicability of STS, in a pilot study we tested its efficacy against cisplatin ototoxicity. Delayed administration of STS, 2 h after cisplatin, was protective against cisplatin-induced ototoxicity in the guinea pig model, as determined by electrophysiological measures. On the basis of these data, we suggest that delayed administration of STS may provide a mechanism to reduce the ototoxicity caused by administration of carboplatin or cisplatin for both central nervous system and systemic cancer chemotherapy.

Animals↗

Delayed sodium thiosulfate as an otoprotectant against carboplatin-induced hearing loss in patients with malignant brain tumors.

Carboplatin is effective in the treatment of malignant brain tumors. However, when administered in conjunction with osmotic opening of the blood-brain barrier (BBB), carboplatin is ototoxic. The purpose of this study was to determine whether delayed administration of sodium thiosulfate (STS), given after BBB closure, provided protection against carboplatin ototoxicity. Patients underwent monthly treatment with intra-arterial carboplatin (200 mg/m2/day x 2) in conjunction with osmotic opening of the BBB, for up to 1 year. Audiological assessment was conducted at baseline and within 24 h before each monthly treatment. STS was administered i.v. as one (20 g/m2) or two (20 g/m2 and 16 g/m2) 15-min doses, depending on baseline hearing status. The initial group received the first STS dose 2 h (or 2 and 6 h) after carboplatin (STS2) and a subsequent group received STS 4 h (or 4 and 8 h) after carboplatin (STS4). Audiological data were compared with a historical comparison group (HCG) treated with carboplatin without STS. Spearman correlation coefficients comparing STS 2 (n = 24), STS4 (n = 17), and HCG (n = 19) indicated significantly lower rates of ototoxicity with increased delay in STS (P = 0.0006). On the basis of the analysis of hearing levels, there were significant differences among the two STS groups and HCG at 8000 Hz (P = 0.0010) and at 4000 Hz (P = 0.0075). The log-rank test for time to ototoxicity indicated a significant difference between STS4 and HCG (P = 0.0018). Delayed STS was effective in protecting against carboplatin-induced hearing loss. STS delayed to 4 h after carboplatin significantly decreased time to development of ototoxicity and rate of ototoxicity when compared with HCG.

Adolescent↗

Chemoprotection profiles of sodium thiosulfate on methyl methanesulfonate-induced mutagenesis of bacteriophage T4.

BACKGROUND: The alkylation of nucleic acids is primarily responsible for chemical carcinogenesis. Even during disease treatment, several alkylating drugs interact with nucleic acids and cause severe toxic effects. Thus good chemoprotectants are necessary. For our study we chose a simple model organism, bacteriophage T4 (a nucleoprotenic particle), and alkylating agent methyl methanesulfonate (MMS) to study its lethal effects. Sodium thiosulfate (STS), used as a chemoprotectant, has been tested against alkylating drugs. MATERIAL/METHODS: Bacteriophage T4D(o) were exposed to different molarities of MMS for several pre-termination incubations. Alkylation reactions were stopped with different concentrations of STS at given pre-termination incubation periods and further incubated up to 24 hours. The viability (survival frequency) of phage T4 was studied at various post-termination intervals by plaque count assay. RESULTS: Our results show that the survival frequency is strongly influenced by MMS dosage and exposure time. However, the antidotal effect of STS on MMS-induced lethality directly corresponds to STS dosage. Survival frequencies with 1% quench solution were lower than with 5% quench solution at all molarities of MMS and at different pre- and post-termination periods. CONCLUSIONS: Our studies confirmed the role of STS in the cytoprotection of bacteriophage T4. In the presence of 1% STS, a moderate inhibition in cytotoxicity was observed, while 5% STS exhibited a significant inhibition against the cytotoxic activity of MMS, presumably due to a rapid covalent binding of the methyl group (carbocation - an electrophile) of MMS with the nucleophilic sulfur atom of STS.

Bacteriophage T4↗

[Use of zinc sulfate and sodium thiosulfate electrophoresis in treating patients with intestinal dysbacteriosis].

Electrophoresis of 2% zinc sulfate solution and 3% sodium thiosulfate solution was used in combined treatment of intestinal dysbiosis with high Candida proliferation in 79 patients. 77 controls received standard therapy. It is shown that such electrophoresis produced positive changes in the clinical picture of the disease, significantly suppressed growth of Candida fulgi, improved function of the liver as shown by a rise in the amount of total protein and hemoglobin, lower bilirubin concentrations in the blood.

Electrophoresis↗

A mechanism involved in the plaque enhancement effect of sodium thiosulfate for foot-and-mouth disease viruses.

A mechanism involved in the plaque enhancement effect of foot-and-mouth disease viruses (FMDV) by the addition of sodium thiosulfate (Hypo) in the agar overlay medium (AOM) previously reported was studied. It was experimentally proved that the diffusion of virus particles through agar overlay medium was enhanced when this salt was incorporated. Accordingly, the enlarged plaque formation was assumed to be caused by the enhanced diffusion of viral progenies produced in infectious centers during plaque assays.

Agar↗

[The effect of a single dose of nifedipine, intal, sodium thiosulfate and Essentiale on the blood level of calcium, hydroperoxides, thiol compounds and prostaglandins in bronchial asthma patients].

A study was made of the impact of a single intake of nifedipine, intal, sodium thiosulfate and essentiale on respiratory function, the blood content of ionized calcium, total calcium, hydroperoxides, total and non-protein thiol groups, and prostaglandins in bronchial asthma patients. All the drugs exerted an antioxidant action, which is supported by the lowering of the content of hydroperoxides after their administration and by an increase of the content of thiol groups. A rise of the level of PGE and a considerable reduction of blood serum PGF2 alpha, most remarkable after essentiale administration were also noted. In patients given nifedipine in a dose of 20 mg, an insignificant broncholytic effect was recorded in more than half the cases. An appreciable rise of blood ionized calcium was seen in all the cases. Obviously, this is a direct consequence of its limited supply to the cells via calcium channels. In contrast to patients who received other drugs, those given intal demonstrated the lowering of blood serum ionized calcium and the growth of the content of bound calcium, which may be accounted for the transformation of ionized calcium to the bound condition.

Antioxidants↗

[The clinical and pharmacokinetic evaluation of two-route chemotherapy with cisplatin and sodium thiosulfate in combination with angiotensin II].

Thirty-six courses of chemotherapy with cisplatin (CDDP) and sodium thiosulfate (STS) were performed in 31 patients with gynecologic cancer 2 weeks after operation under the hypertensive condition induced by angiotensin II (AT-II). One hundred-fifty mg of CDDP/body was intraperitoneally administered while the usual systolic blood pressure was increased to 130-140% by AT-II. The hypertension was maintained for 15 minutes after finishing CDDP infusion, then 8g of STS was intravenously infused immediately after the cessation of AT-II. The urinary Pt level measured 15 minutes after finishing CDDP infusion was extremely low at 1.37 +/- 0.47 micrograms/ml, in spite of the significantly high levels of plasma total Pt (7.83 +/- 0.85 micrograms/ml) and filtrable Pt (4.02 +/- 0.55 micrograms/ml). This suggests that, during renal vasoconstriction induced by AT-II, the renal blood flow as well as renal uptake of CDDP was decreased. Plasma filtrable Pt levels were measured at 15, 30, 60 and 120 minutes after intraperitoneal administration of CDDP. At 15 and 30 minutes a significantly higher blood concentration was found than in the control group (p less than 0.05). However, CDDP-induced toxicities of the bone marrow, liver, kidney and alimentary tract were not increased. The extreme vasoconstriction in the kidneys and other organs induced by AT-II might have protected these organs from the toxicities of CDDP despite the fact that STS infusion was delayed by 15 minutes after CDDP infusion. STS infused immediately after the cessation of AT-II could neutralize the CDDP preventing the occurrence of toxicities.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗