Antimoniotungstate (HPA 23) treatment of three patients with AIDS and one with prodrome.
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OBJECTIVE: To assess whether corrosion of tungsten coils is related to residual shunting and to evaluate whether elevated tungsten serum levels are associated with local or systemic toxicity. METHODS: Tungsten coils (SPI, Balt, France) were implanted into the subclavian artery of New Zealand white rabbits leading to a residual high-flow shunt in 5/10 rabbits. Serial serum tungsten levels, complete blood count and clinical chemistry were analysed prior to the implantation as well as 15 min, 2 and 4 months thereafter. After 4 months the rabbits underwent repeat angiography before they were sacrificed and the internal organs were evaluated histopathologically. RESULTS: Mean tungsten levels rose from 0.48 microg/l prior to the implantation to 12.4 microg/l 4 months post-implantation. The rise in serum tungsten levels was neither associated with residual shunting present at the time of implantation nor with residual shunting at the time of explantation. One animal had to be sacrificed because of non-resolving palsy of the upper extremity. The remaining animals had an uneventful clinical course with no signs of toxicity of the elevated tungsten levels. Histological examination revealed no evidence of local or systemic toxicity of the tungsten coils. CONCLUSION: Tungsten coils corrode and lead to a steady increase in serum tungsten levels starting as early as 15 min after implantation. Residual shunting does not seem to influence the kinetics of corrosion of tungsten coils. Despite markedly elevated serum tungsten levels 4 months after implantation degradation of tungsten coils is not associated with local or systemic toxicity.
The effects of dietary supplementation with ammonium tetrathiotungstate and dithiotungstate on copper metabolism in young rats have been investigated. The addition of WS4(2-) (4-32 mg W/kg diet) decreased growth rates and induced clinical and biochemical signs of Cu deficiency. These were overcome by increasing the dietary content of Cu. The intestinal absorption of 64Cu was impaired and the tissue distribution of absorbed Cu modified by the administration of WS4(2-). No clinical or biochemical defects indicative of Cu deficiency developed in rats receiving WO2S2(2-) in their diet at concentrations up to 32 mg W/kg. In contrast, this oxythioanion enhanced the content of Cu in plasma liver and kidney, especially when dietary Cu was increased. Most of the additional Cu retained by plasma and kidney was associated with albumin and metallothionein, respectively. The effects of these W sources are compared with those caused by their thio- and oxythiomolybdate analogs and are discussed in relation to the mechanisms whereby Mo induces Cy deficiency in ruminants.
Aqueous vanadate and aqueous tungstate have been known to mimic all or most of the actions of insulin in intact cell systems with respect to normalization of the blood glucose level. By carrying out oral administration in vivo experiments on the blood glucose level of streptozotocin (STZ)-induced diabetes (STZ mice), the insulin-mimetic (IM) effects of metal-oxide clusters of all-inorganic composition were examined using many types of polyoxometalates (POM) with and without vanadium substitution. Several homo-POM and vanadium-substituted POM showed hypoglycemic effects. The observed hypoglycemic effects indicated that POM with the Dawson structure [[alpha-P(2)W(18)O(62)](6-) (W-2), [alpha-P(2)W(17)V(V)O(62)](7-) (V-19) and [alpha-1,2,3-P(2)W(15)V(V)(3)O(62)](9-) (V-04)] are more effective than those with the Keggin structure [[alpha-PW(12)O(40)](3-) (W-1), [alpha-PW(11)V(V)O(40)](4-) (V-01), [alpha-1,2-PW(10)V(V)(2)O(40)](5-) (V-02), [alpha-1,2,3-PW(9)V(V)(3)O(40)](6-) (V-03) and [alpha-1,4,9-PW(9)V(V)(3)O(40)](6-) (V-13)]. The vanadate cluster [V(10)O(28)](6-) (V-15) also showed a hypoglycemic effect. (31)P and (51)V NMR measurements showed that the Dawson POM (W-2, V-04 and V-19) are stable in aqueous solution under the conditions used. The effect of all POM on the body weight of STZ mice was also examined. The decrease in body weight after administration of W-2 was much less than for V-19, V-04 and V-15. This suggests that not only monomeric tungstate and vanadate, but also the structure factors of tungstate and vanadate clusters, can play a significant role in their biological action.
Two gadolinium polyoxometalates, Gd(2)P(2)W(18)O(62) and K(15)[(GdO)(3)(PW(9)O(34))(2)], have been evaluated by in vivo as well as in vitro experiments as the candidates of tissue-specific magnetic resonance imaging (MRI) contrast agents. T(1)-relaxivities of 28.4 mM(-1).s(-1) for Gd(2)P(2)W(18)O(62) and 11.2 mM(-1).s(-1) for K(15)[(GdO)(3)(PW(9)O(34))(2)] (400 MHz, 25 degrees C) were higher than that of the commercial MRI contrast agent (GdDTPA). Their relaxivities in bovine serum albumin and human serum transferrin were also reported. The favorable liver-specific contrast enhancement and renal excretion capability in in vivo MRI with Sprague-Dawley rats after i.v. administration of K(15)[(GdO)(3)(PW(9)O(34))(2)] was demonstrated. In vivo and in vitro assay showed that K(15)[(GdO)(3)(PW(9)O(34))(2)] is a promising liver-specific MRI contrast agent. However, Gd(2)P(2)W(18)O(62) did not show the favorable quality in vivo as expected from its high relaxivity in vitro, which was attributed to low bioavailability, indicating that it is of limited value as tissue-specific MRI contrast agent.
The Timm's sulfide-silver method is frequently used for the demonstration of the mossy fiber bundle or sprouted mossy fibers in the normal or epileptic hippocampal dentate gyrus. Under the light microscope the results are excellent, but the ultrastructure is considerably impaired and the silver grains produced are too large as compared to the sizes of intra-synaptic structures. The present study was meant to test a series of physical developers containing, instead of gum arabic, sodium tungstate as protective colloid. One of them left the ultrastructure fairly intact and produced small, round silver grains, making it possible to precisely locate zinc in mossy terminals. With this method, it could be demonstrated that zinc is contained inside synaptic vesicles in the resting axon terminals of granule cells. As a consequence of prolonged sodium sulfide perfusion, zinc is released from synaptic vesicles and enters the synaptic cleft.
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OBJECTIVE: To assess the effect of different modes of fissure preparation and filling level on the quality of pits and fissure sealants. METHODS: Various modes of fissure preparation in combination with two filling levels were examined. A total of 90 caries-free extracted human molar teeth were divided into three groups according to fissure preparation: (a) no mechanical preparation; (b) mechanical preparation with a round carbide bur; and (c) mechanical preparation with a tapered fissure diamond bur. All fissures were acid-etched and each group was subdivided according to filling level, either to the border or overfilled, using Helioseal (Vivadent, Schaan, Lichtenstein) as a sealant material. A modified microleakage assay was performed, combining occlusal loading and thermocycling, prior to staining with 0.5% Basic Fuchsin. After sectioning, teeth were examined and photographed in a reflected light microscope, sealant retention was observed and recorded. Microleakage and sealant penetration depths were measured for each section. Two-way ANOVA was used for statistical analysis. RESULTS: Sealant penetration and retention were significantly improved by mechanical preparation compared to non-prepared fissures (p<0.0001), and preparation with a tapered fissure diamond bur was superior to the round carbide bur. Overfilled fissures caused significantly higher levels of microleakage (p<0.004). CONCLUSIONS: Based on the results of this in vitro study, it is suggested that fissure sealant quality may be improved by mechanical preparation, preferably with a tapered diamond bur, and filling just to the border. Overfilling of fissures should be avoided.
Cultured Catharanthus roseus cells exhibit transmembrane ferricyanide (FIC) reduction which is associated with a proton translocation and a decrease in the ATP content of the cells. The H+ efflux and the ATP consumption may be counteracted by vanadate, a specific inhibitor of the ATPase activity, and by Na2WO4 which prevents FIC reduction. From these data it is concluded that the redox chain could be coupled with ATP hydrolysis for electrogenic proton extrusion which may involve a redox control mechanism for the plasmamembrane ATPase.
Diadenosine 5',5'''-p1,p4-tetraphosphate (Ap4A) alpha, beta-phosphorylase from yeast Saccharomyces cerevisiae catalyzes two reactions: Ap4A cleavage and nucleoside diphosphate--phosphate (NDP-Pi) exchange. In both reactions phosphate can be substituted by arsenate, chromate, molybdate, tungstate or vanadate. In the presence of each anion, nucleoside 5'-monophosphate (NMP) always accumulates as a product of the reaction. This indicates that an unstable NMP anion is formed as an intermediate.
PURPOSE: Intracoronary radiation has shown the potential to inhibit neointimal proliferation in porcine models of restenosis. The objective of this study was to determine whether intracoronary radiation using a new coiled wire of tungsten-188 ((188)W), a pure beta emitter (half-life 69.4 days) is safe. In addition, a dose of 0 Gy, 18 Gy, or 25 Gy prescribed to 2 mm from the center of the source and delivered intraluminally is sufficient to prevent restenosis and free from adverse effects. METHODS AND MATERIALS: Ten domestic swine underwent 13-mm stent implantation (SI) into two arteries, left anterior descending plus either the left circumflex or right coronary artery. After SI, a closed-end lumen radiation catheter was inserted to the treated artery and a 40-mm coiled (188)W source was manually delivered to cover the stented segment and its margins. A total of 20 arteries were randomized to treatment with a radiation dose of 0, 18 Gy, or 25 Gy delivered to 2 mm depth from the center of the source. Four weeks after the procedure, the swine underwent angiography and intravascular ultrasound using automated pullback at 0.5 mm/s. before being killed and the arteries perfusion fixed. Histopathologic and histomorphometric analyses were performed at 28 days after injury and radiation. RESULTS: Irradiation with (188)W at a dose of 25 Gy after SI significantly inhibited neointima formation (intimal area: 1.05 +/- 0.64 vs. 2.75 +/- 0.99 mm(2), p < 0.01) and at an 18 Gy dose of radiation (intimal area: 1.73 +/- 0.49 vs. 2.75 +/- 0.99 mm(2)), as compared to controls. One artery receiving 18 Gy and two arteries receiving 25 Gy were totally occluded at follow-up due to thrombus formation but no edge stenosis was observed in any of the irradiated arteries. CONCLUSIONS: Intracoronary radiation therapy using a new coiled wire of (188)W source delivered after SI appeared to be safe and well tolerated. The radiation doses demonstrated efficacy in reducing neointima formation in the porcine coronary stent injury model.
Paracoccus pantotrophus grown anaerobically under denitrifying conditions expressed similar levels of the periplasmic nitrate reductase (NAP) when cultured in molybdate- or tungstate-containing media. A native PAGE gel stained for nitrate reductase activity revealed that only NapA from molybdate-grown cells displayed readily detectable nitrate reductase activity. Further kinetic analysis showed that the periplasmic fraction from cells grown on molybdate (3 microM) reduced nitrate at a rate of V(max)=3.41+/-0.16 micromol [NO(3)(-)] min(-1) mg(-1) with an affinity for nitrate of K(m)=0.24+/-0.05 mM and was heat-stable up to 50 degrees C. In contrast, the periplasmic fraction obtained from cells cultured in media supplemented with tungstate (100 microM) reduced nitrate at a much slower rate, with much lower affinity (V(max)=0.05+/-0.002 micromol [NO(3)(-)] min(-1) mg(-1) and K(m)=3.91+/-0.45 mM) and was labile during prolonged incubation at >20 degrees C. Nitrate-dependent growth of Escherichia coli strains expressing only nitrate reductase A was inhibited by sub-mM concentrations of tungstate in the medium. In contrast, a strain expressing only NAP was only partially inhibited by 10 mM tungstate. However, none of the above experimental approaches revealed evidence that tungsten could replace molybdenum at the active site of E. coli NapA. The combined data show that tungsten can function at the active site of some, but not all, molybdoenzymes from mesophilic bacteria.
Enterobacter cloacae SLD1a-1 is capable of reducing selenium oxyanions to elemental selenium under both aerobic and anaerobic conditions. In this study the enzyme that catalyses the initial reduction of selenate (SeO4(2-)) to selenite (SeO3(2-)) has been localised to isolated cytoplasmic membrane fractions. Experiments with intact cells have shown that the putative selenate reductase can accept electrons more readily from membrane-impermeable methyl viologen than membrane-permeable benzyl viologen, suggesting that the location of the catalytic site is towards the periplasmic side of the cytoplasmic membrane. Enzyme activity was enhanced by growing cells in the presence of 1 mM sodium molybdate and significantly reduced in cells grown in the presence of 1 mM sodium tungstate. Non-denaturing polyacrylamide gel electrophoresis (PAGE) gels stained for selenate and nitrate reductase activity have revealed that two distinct membrane-bound enzymes catalyse the reduction of selenate and nitrate. The role of this membrane-bound molybdenum-dependent reductase in relation to selenate detoxification and energy conservation is discussed.
Five poly(vinyl chloride) matrix membrane sensors responsive to some beta-blockers (atenolol, bisoprolol, metoprolol, propranolol and timolol) are described and characterized. The sensors are based on the use of the ion-association complexes of the beta-blocker cations with tungstophosphate anion as electroactive materials. The performance characteristics of these sensors, evaluated according to IUPAC recommendations, reveal fast, stable and near-Nernstian response for 10(-2)-2 x 10(-7) mol l(-1) of different beta-blockers over the pH range 2-9. Many inorganic and organic cations as well as drug excipients and diluents normally used in drug formulations do not interfere. The sensors are used for direct potentiometry of beta-blockers in some pharmaceutical preparations. Validation of the method according to the quality assurance standards shows suitability of the proposed sensors for use in the quality control assessment of these drugs. Results with an average recovery of 99.1% and a mean standard deviation of +/- 1.3% of the nominal are obtained which compare fairly well with data obtained using the British Pharmacopoeia method.
A methylene blue (MB) poly(vinyl chloride) membrane sensor based on MB-silicotungstate (SLT) ion association as electroactive material was described. The linear response covered the range 1 x 10(-3)-1 x 10(-6) mol x dm(-3) MB solution, with a slope 52.0+/-0.8 mV decade(-1) (pH range 3.0-10.0). The detection limit was 7.65 x 10(-7) mol x dm(-3). The electrode showed stability, good reproducibility and fast response. Interferences from common inorganic cations, some organic base were negligible. These characteristics of the electrode enabled it to be used successfully for the determination of MB in injection. There was a good agreement for the results of MB content in injection between potentiometric method and USP standard procedure.
In the last few years, orthodontic literature has shown particular interest in the interproximal enamel reduction technique described as stripping or slenderizing. Most researchers have shown, by scanning electron microscopy (SEM) studies, the difficulties encountered while attempting to remove coarse abrasions left after stripping with the first instrument. The objective of this SEM study was to compare the different polishing methods proposed in the literature and to assess the efficiency of our own procedure. For this purpose, 48 healthy human teeth (premolars and molars) were used after removal for orthodontic or periodontal reasons. The teeth were divided into eight groups of six teeth each (two molars and four premolars), and mounted on a typodont to simulate a clinical situation. Each group underwent stripping according to one of the following techniques: 16-blade tungsten carbide bur and fine and ultrafine diamond burs; coarse diamond bur and fine and ultrafine diamond burs; coarse diamond disk and Sof-Lex disks (Dental products/3M, St. Paul, Minn.); 16-blade tungsten carbide bur and phosphoric acid on finishing strip; and 8-straight blade tungsten carbide diamond bur and Sof-Lex disks. The SEM investigations demonstrated that it is not possible to eliminate, with normal polishing and cleaning methods, the furrows left on the enamel both by the diamond burs and the diamond disks and the 16-blade tungsten carbide burs. Mechanical and chemical stripping as well did not prove to be effective. By contrast, with the use of a 8-straight blade tungsten carbide bur followed by Sof-Lex disks for polishing the enamel, it is possible to obtain well-polished surfaces that many times appear smoother than the intact or untreated enamel.
Ischemia-reperfusion to the liver results in increased microvascular permeability in a nonischemic lung. We hypothesized that a circulatory mediator released from ischemic liver contributed to endothelial cell (EC) damage. Isolated rat livers, made ischemic for 2 h, were reperfused for 10 min. Bovine ECs were incubated for 5 h with pooled liver effluent collected before ischemia (Baseline) or after 10 min of reperfusion (Reperfusion). In the Reperfusion group, there was increased endothelial cell injury, as determined by release of 8-[14C]adenine, (39 +/- 2%) compared to the Baseline group (22 +/- 2%). Permeability of ECs to rhodamine B-labeled dextran (70,000 Mr) was also increased in the Reperfusion group by 54 +/- 9%. There was no significant attenuation in EC injury following incubation with reperfusion effluent stored for 24 h, supplementation with antioxidants (superoxide dismutase + catalase), or inhibition of xanthine oxidase with allopurinol or tungstate. We conclude that the reperfused liver releases a long-lived circulatory mediator of EC injury, which may produce the clinical microvascular injury observed following hepatic ischemia. The mechanism of injury in our model is independent of oxidants or oxidants generated from the circulating xanthine oxidase released from reperfused ischemic liver.
BACKGROUND: Polynucleotide phosphorylase (PNPase) is a polyribonucleotide nucleotidyl transferase (E.C.2.7.7.8) that degrades mRNA in prokaryotes. Streptomyces antibioticus PNPase also assays as a guanosine 3'-diphosphate 5'-triphosphate (pppGpp) synthetase (E.C.2.7.6.5). It may function to coordinate changes in mRNA lifetimes with pppGpp levels during the Streptomyces lifecycle. RESULTS: The structure of S. antibioticus PNPase without bound RNA but with the phosphate analog tungstate bound at the PNPase catalytic sites was determined by X-ray crystallography and shows a trimeric multidomain protein with a central channel. The structural core has a novel duplicated architecture formed by association of two homologous domains. The tungstate derivative structure reveals the PNPase active site in the second of these core domains. Structure-based sequence analysis suggests that the pppGpp synthetase active site is located in the first core domain. CONCLUSIONS: This is the first structure of a PNPase and shows the structural basis for the trimer assembly, the arrangement of accessory RNA binding domains, and the likely catalytic residues of the PNPase active site. A possible function of the trimer channel is as a contribution to both the processivity of degradation and the regulation of PNPase action by RNA structural elements.