Improved antimony--antimony (III) oxide pH electrodes.
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We have recently demonstrated that the hepatobiliary transport of arsenic is glutathione-dependent and is associated with a profound increase in biliary excretion of glutathione (GSH), hepatic GSH depletion and diminished GSH conjugation (Gyurasics A, Varga F and Gregus Z, Biochem Pharmacol 41: 937-944 and Gyurasics A, Varga F and Gregus Z, Biochem Pharmacol 42: 465-468, 1991). The present studies in rats aimed to determine whether antimony and bismuth, other metalloids in group Va of the periodic table, also possess similar properties. Antimony potassium tartrate (25-100 mumol/kg, i.v.) and bismuth ammonium citrate (50-200 mumol/kg, i.v.) increased up to 50- and 4-fold, respectively, the biliary excretion of non-protein thiols (NPSH). This resulted mainly from increased hepatobiliary transport of GSH as suggested by a close parallelism in the biliary excretion of NPSH and GSH after antimony or bismuth administration. Within 2 hr, rats excreted into bile 55 and 3% of the dose of antimony (50 mumol/kg, i.v.) and bismuth (150 mumol/kg, i.v.), respectively. The time courses of the biliary excretion of these metalloids and NPSH or GSH were strikingly similar suggesting co-ordinate hepatobiliary transport of the metalloids and GSH. However, at the peak of their excretion, each molecule of antimony or bismuth resulted in a co-transport of approximately three molecules of GSH. Diethyl maleate, indocyanine green and sulfobromophthalein (BSP), which decreased biliary excretion of GSH, significantly diminished excretion of antimony and bismuth into bile indicating that hepatobiliary transport of these metalloids is GSH-dependent. Administration of antimony, but not bismuth, decreased hepatic GSH level by 30% and reduced the GSH conjugation and biliary excretion of BSP. These studies demonstrate that the hepatobiliary transport of trivalent antimony and bismuth is GSH-dependent similarly to the hepatobiliary transport of trivalent arsenic. Proportionally to their biliary excretion rates, these metalloids generate increased biliary excretion of GSH probably because they are transported from liver to bile as unstable GSH complexes. The significant loss of hepatic GSH into bile as induced by arsenic or antimony may compromise conjugation of xenobiotics with GSH.
Antimony electrodes are widely used for gastro-oesophageal pH monitoring. They are also sensitive to oxygen, however, especially at low PO2 levels, which are known to shift recorded values in the alkaline direction. This study, which compares antimony and glass electrodes for oesophageal pH monitoring in six adults, shows that values recorded by antimony electrodes are 2.1 +/- 0.8 pH units (mean +/- SD) higher than by glass electrodes (p < 0.001; n = 7642). A further 52 patients with suspected gastro-oesophageal reflux were investigated by 24-h pH monitoring by means of antimony electrodes. In these patients the oesophageal pH was higher than 8.0 for 7% of the time (range, 0-60%). The alkaline periods recorded with antimony electrodes were all protracted in time, smoothly increasing from a neutral pH, and did not correspond to a sudden increase in pH, which would be expected if alkaline reflux had occurred. It is concluded that high pH values obtained by antimony electrodes are due to the oxygen sensitivity of the electrodes. The diagnosis of alkaline reflux seems to be valid only when pH monitoring is performed with glass electrodes or when values obtained with antimony electrodes are adjusted for the influence of the oxygen tension in the oesophagus.
Although unresponsiveness to antimonial drugs in human leishmaniasis appears to be increasing, resistance to antimony in Leishmania is not well documented. Treatment of leishmaniasis in dogs, the domestic reservoir of L. infantum, with meglumine antimoniate (Glucantime) is a common practice in many Mediterranean countries. The dogs, however, remain highly infective to the phlebotomine vectors, even after several courses of treatment. A study was therefore carried out to test the comparative susceptibility to meglumine antimoniate of L. infantum stocks isolated from four naturally-infected dogs, before (BT) and after treatment (AT) with three to six courses of the drug, and used to infect Balb/c mice. Significant differences in suppression between the BT and AT stocks were observed in the infected mice when they were given the drug at a rate of 0.01-10 mg kg-1 day-1 for five days. Each AT stock was between eight and 41 times more resistant to meglumine antimoniate than the BT stock from the same dog, in terms of the ratios of the AT ED50 values to the corresponding BT values, which were calculated as indices of resistance. This result underlines the futility and danger of repeated antimonial treatments of dogs with signs of leishmaniasis, as these may produce a permanent reservoir of parasites unsusceptible to the drugs in human clinical use.
This report concerns the investigation of the sensitivity, temperature dependence, accuracy, and the standard electrode potential EO of an antimony thin film pH electrode which was prepared with electron beam evaporation techniques. The air-formed oxide film on antimony thin film electrodes has been proved by both the cathodic reduction method and electron spectroscopy for chemical analysis (ESCA). The antimony thin film electrode responded rapidly to pH changes and its sensitivity was slightly changed depending on the buffer composition. The accuracy of this electrode was compared with that of the glass electrode. Temperature had some influence on the function of this electrode. The standard electrode potential of this electrode was discussed together with that of other forms of antimony electrodes. The structure and thickness of the surface oxide on antimony thin film electrodes was confirmed by cathodic reduction and ESCA. It was clear that the surface oxide governs the electrode reactions. Possible applications of the antimony thin film electrode are discussed stating some limitations in the use.
A new technique for manufacturing single-barreled and double-barreled antimony pH microelectrodes is described. The results of investigations into the accuracy of antimony as a pH sensor disclosed that the pH-voltage response is: 1) within the physiologic range, principally the result of the hydrogen ion activity of the solution in which the voltage is being developed, 2) in part, qualitatively anion-dependent, 3) modified by the presence of significant amounts of at least carbon dioxide, oxygen, and nitrogen gases, and 4) markedly offset by fluctuations in temperature. Our results further indicate that the accuracy of antimony as a pH sensor is determined by the quality of the calibration procedure. We conclude that if the antimony electrode is to accurately determine the pH of a biological fluid, the pH calibration solutions must closely resemble the unknown biological fluid with respect to temperature, PO2, PN2, and types of buffering anions. A calibration procedure is described which can minimize errors with antimony pH estimations when measuring the pH of proximal tubular fluid of the mammalian kidney.
The features of antimony excretion by sweat glands were studied in normal subjects and patients with chronic bronchitis, chronic gastritis, chronic nephritis and calculous pyelonephritis, visceral leishmaniasis, living in some biogeochemical provinces of Fergana Valley. A micromethod based on the coloured reaction of the element with brilliant green was worked out to detect antimony in sweat. Sweat antimony elimination was proved to play a significant role in health and disease. The workers engaged in antimony production, the inhabitants of antimony biogeochemical regions should have their sweat excretion tested to score the Sb level. It is recommended as an additional test for screening and controlling the effects of visceral leishmaniasis chemotherapy by solusurmine in patients with kidney disorders.
BALB/c mice with an acute or chronic Leishmania donovani infection were treated with intravenous sodium stibogluconate solution and the parasite suppressions determined in the spleen, liver and femur bone marrow. Antimony concentrations in these and other tissues were determined by hydride generation-atomic absorption spectrophotometry. There was little correlation between tissue antimony levels one hour after treatment and drug efficacy. It would appear that the peak tissue antimony concentration achieved soon after dosing, rather than the lower concentrations which are readily sustained in most tissues, is the most important factor in the antileishmanial activity of stibogluconate. A high peak antimony concentration occurred in the liver, where parasites were significantly suppressed, and was not observed in the two other sites of infection, where the parasites were apparently less susceptible to stibogluconate therapy.
The electrocardiographic (ECG) changes in Bolivian patients with mucocutaneous leishmaniasis, treated with meglumine antimoniate and allopurinol, were evaluated. Electric changes due to the antimonial compound appeared in 45% of the patients, and consisted of repolarization alteration, principally affecting the T wave and the S-T segment. The changes disappeared within 2 months following the end of the antimonial treatment. In patients with associated Chagas disease and leishmaniasis, antimonial therapy did not aggravate the ECG changes characteristic of Chagasic cardiopathy.
Antimony microelectrodes were calibrated at 37 degrees C in phosphate buffers, in different bicarbonate solutions at various CO2-partial pressures and in buffers like TRIS1, TES2, MES3 and malonic acid. By use of the latter buffers (with exception of malonic acid) the most reliable calibration curves were obtained ("normal values"). The usual calibration in 67 mmol/l standard phosphate buffers turned out to be unacceptable because the obtained mV-values were too high (negative) in comparison to all other buffers. Different calibration curves resulted from the use of pure bicarbonate solution whether the pH-values were changed by variation of pCO2 or of the bicarbonate concentration. Low bicarbonate concentrations in combination with low pCO2 gave mV-values which were too low relative to the other buffers. Both the increase of pCO2 as well as of the bicarbonate concentration caused a shift of the potential of the antimony electrodes toward "normal values". In solutions containing other buffers the influence of bicarbonate and pCO2 became negligible with increasing buffer concentration. Decreasing oxygen partial pressure was found to cause an increase of the potential of the antimony electrodes. The influence of liquid junction potentials at the reference electrode is discussed.
A subacute toxicity study of pentavalent antimony (Sb) compounds, sodium stibogluconate (SSG) and meglumine antimoniate (MA) was carried out in rats. Three groups of 10 rats each were treated with saline (control group), 300 mg Sb kg-1 d-1 or 900 mg Sb kg-1 d-1 of SSG for 30 d. A parallel study of similar type was conducted for MA. Compared with controls, drug-treated rats showed an impairment of feeding habits and retardation of weight gain (P less than 0.01) during the treatment period. In both SSG- and MA-treated rats there was a dose-related reduction in haemoglobin concentration (P less than 0.001), and hematocrit (P less than 0.001). Red cell count was reduced in SSG-treated rats only. Both drugs, however, significantly raised the white cell count (P less than 0.05). These changes were more pronounced with SSG them with MA. There was no change in MCV, MCH and MCHC. SSG, 900 mg Sb kg-1 d-1, significantly raised AST (P less than 0.005), ALT (P less than 0.01) and alkaline phosphatase activity (P less than 0.01). SSG-treated rats also had raised BUN (P less than 0.01) and creatinine (P less than 0.001), but no significant change in bilirubin levels. MA significantly raised AST (P less than 0.01), ALT (P less than 0.01), BUN (P less than 0.001) and serum creatinine levels (P less than 0.001), but had no appreciable effect on bilirubin and alkaline phosphatase levels. Both SSG and MA decreased blood glucose levels (P less than 0.01) and induced proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)
When T-cell deprived CBA mice, infected with Schistosoma mansoni, were treated orally with potassium antimony tartrate, the reduction in size of their worm burdens was less than in similarly treated, immunologically-intact animals. The defect in deprived mice could be restored by the administration of serum obtained from S. mansoni-infected normal mice simultaneously with the drug, but by a different route. A serum component, probably immunoglobulin, obtained from rabbits which had been injected with an extract from S. mansoni adult worms was also found to act synergystically with the antimonial in the chemotherapeutic eradication of S. mansoni worms from immunologically intact mice.
An electrothermal atomic absorption method for the determination of antimony in biological fluids, derived from Triostam or Pentostam, is described. Comparison of the results obtained by this method has been made with hydride generation atomic absorption and by measuring the gamma emission of 125Sb-Pentostam. Using electrothermal atomic absorption, the concentrations and distributions of the pentavalent and trivalent antimony drugs, either in free or liposome-entrapped forms, have been determined in vitro after incubation with human blood. The effect of entrapping Pentostam within liposomes has also been studied in vivo in mice, and its concentration and distribution compared with results obtained using the free drug.
A 20 d drug regimen of aminosidine (= paromomycin) at 12 mg/kg/d in combination with sodium stibogluconate at 20 mg/kg/d proved efficacious and well-tolerated in patients with visceral leishmaniasis in the State of Bihar, India. Eighteen of 22 evaluable patients achieved an ultimate cure. The remaining 4 patients, although not cleared of parasites, had their parasite grade reduced and also improved clinically. This confirms prior findings in Kenyan patients with kala-azar, and indicates that this regimen is a valid alternative to antimonial compounds alone in the State of Bihar, where cases of kala-azar not responding to antimonial drugs and intolerant of pentamidine are increasingly recorded.
The color reaction of cholesterol with trichloracetic acid and antimony trichloride was examined to elucidate its reaction mechanism. 3,5-Cholestadiene, 3,3'bis(3,5-cholestadiene), 3,3'bis(2,4-cholestadiene), and cholesteryl trichloroacetate were isolated as the reaction products from the colored reaction mixture of cholesterol, and the first three compounds were found to be responsible for the coloration. It was assumed that cholesterol was dehydrated to 3,5-cholestadiene and 2,4-cholestadiene, which were dimerized to 3,3'-bis(3,5-cholestadiene) and 3,3'-bis(2,4-cholestadiene), respectively, and 3,3'-bis(2,4-cholestadiene) was in part converted to 3,3'-bis(3,5-cholestadiene) in trichloroacetic acid and antimony trichloride. The free radicals were detected in the colored solutions of choelsterol, 3,5-cholestadiene, 3,3'-bis(3,5-cholestadiene), and 3,3'-bis(2,4-cholestadiene), and inferred to be the radical cations of the steroids. The radical cation was postulated to be responsible with respect to the mechanism of the coloration. The relationship between the color reagent and the formation of dimeric steroids was described.
A review of sampling and analytical procedures for antimony and its compounds is presented. Emphasis has been placed on those methods which have application to personal air or biological samples in industrial hygiene. Two analytical techniques in particular have been used most frequently--colorimetric and atomic absorption. A need for research to develop satisfactory solid sorbent sampling techniques for stibine and other volatile antimony compounds is evident.
Simultaneous separation and quantitation of arsenic(III) and antimony(III) can be achieved by extraction with lithium bis(trifluoroethyl)dithiocarbamate followed by supercritical fluid chromatographic (SFC) analysis. Arsenic(V) and antimony(V) are extracted after reduction with potassium iodide and sodium thiosulfate. Detection limits of 7 pg As and 11 pg Sb are achieved using this extraction method and SFC. Application to natural water and biological sample analysis is discussed.
In vitro comparison of 99Tc(m) antimony sulphide colloid and 99Tc(m) stannous phytate as well as in vivo studies in six rabbits and seven patients indicate disparity in the colloidal properties and localization of these two agents. The variability in lymphatic uptake and the relatively poor quality of scintigraphic images following interstitial injection of 99Tc(m) stannous phytate, when compared with 99Tc(m) antimony sulphide colloid, provide evidence of the unsuitability of this agent for lymphoscintigraphy. Maintenance of the diagnostic quality of the lymphoscintigraphic image and adherence to interpretive criteria already established therefore preclude the routine use of 99Tc(m) stannous phytate for interstitial lymphoscintigraphy.