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Experimental study of iron effect on the liver function.

The effect of iron on the liver function was studied in rats. A total of 40 rats were divided into four groups. Group 1 was given iron; Group 2, carbon tetrachloride; Group 3, a combination of iron and carbon tetrachloride; and Group 4 was the control. The changes in liver function were evaluated by using hepatobiliary and liver scintigraphy as the index of hepatocyte function and reticuloendothelial system function, respectively. Determination of liver CT number and a histological study were made at the same time. The administration of iron activated the reticuloendothelial system function per unit of liver weight. However, because of the decrease in liver weight, the total reticuloendothelial system function did not change at all. In the group given iron and carbon tetrachloride, liver cirrhosis and siderosis in the reticuloendothelial system occurred. Dysfunction in the reticuloendothelial system was more severe in this group than in the group given carbon tetrachloride only, by hepatocyte dysfunction was more mild. It is doubtful that the administration of iron after liver dysfunction had developed, which caused acceleration of fibrosis and reduction of liver blood flow, led to the enhancement of the reticuloendothelial system dysfunction.

Animals↗

Inhibition of human gingival gelatinases (MMP-2 and MMP-9) by metal salts.

OBJECTIVES: The interaction between metal ions and the oral environment is a major subject matter in dental research. Matrix metalloproteinases (MMPs) have been implicated in several pathologic oral processes such as periodontal tissue destruction, root caries, tumour invasion and temporomandibular joint disorders. The aim of this work was to test the effect of Zn, Cu, Sn and Hg ions on the activity of the major gingival gelatinolytic MMPs. METHODS: Gingival explants were cultured overnight in DMEM and the activity of secreted enzymes was analyzed by gelatin zymography in buffers containing different metal ion concentrations. The major gelatinolytic proteinases present in the conditioned media were characterized as MMP-2 and MMP-9 by immunoprecipitation with specific antibodies. The eletrophoretic bands were scanned and the transmittance values were analyzed with the Sigmagel software (Sigma). RESULTS: ZnSO4 was a strong inhibitor of MMP-2 (I50 = 15 microM) and MMP-9 (I50 = 40 microM), whereas CuSO4, HgSO4 and SnCl2 showed less efficient inhibition potential. SIGNIFICANCE: Our findings show that the activity of oral tissue MMPs may be modulated by metal ions present in the oral environment. Therefore, the accumulation of metals in connective tissue may interfere with the formation and resorption of the extracellular matrix components.

Adult↗

Preparation of [186Re]Re-DMSA and its bio-distribution studies.

99mTc(V)-DMSA is widely used for imaging medullary carcinoma and hence 186/188Re(V)-DMSA is suggested as a potential agent for treating medullary carcinoma. In the present paper, we report the work carried out for the preparation of [186Re]Re(V)-DMSA and it's bio-distribution studies in Wistar rats. The complex was prepared by reducing 186Re (100 micrograms, 0.54 microM, approximately 150 MBq) in the presence of DMSA (2 mg, 11 microM) with stannous chloride (0.4 mg, 2.2 microM) in acidic medium at pH 2. The reaction was taken to completion by heating the complex in a boiling water bath for 30 min. Bio-distribution studies carried out revealed that pharmacological behaviour of 186Re(V)-DMSA is similar to that of 99mTc(V)-DMSA except that the kidney uptake is marginally higher. The kidney uptake reduced significantly when the pH of the complex was adjusted to 8 prior to injection. The in vitro stability studies of this complex suggest that the product formed is stable and could be used for clinical trials.

Animals↗

Carrier effect on radiolabeling the polynuclear pentavalent rhenium-186 complex of dimercaptosuccinic acid at alkaline pH: 186Re(V)-DMS.

Radiolabeling with rhenium (Re-186, Re-188), a tumor agent to resemble the pentavalent polynuclear technetium complex of dimercaptosuccinic acid (99mTc[V]-DMS) has been reported for radiotherapeutical use. Nevertheless, despite the periodic analogies between both radiometals, differences in the redox potential and the carrier concentration have made the radiolabeling of the rhenium counterpart difficult. In the present study, the effect of the carrier contained in the reactor-produced Re-186 was estimated as an important factor relevant to the Re-186 radiolabeling of DMS at an alkaline pH. Great effect of the carrier Re with an inverse correlation with the stannous ion was an interesting phenomenon relevant for an assumption on the Sn participation in the complex. Under strict control of various labeling parameters, the 186Re(V)-DMS was made available with high yield (93-97%) at an alkaline pH and at room temperature. The great effect of carrier offers support to the polymeric or polynuclear nature of the rhenium complex of DMS as depicted in the drug design basis of its parent Tc(V)-DMS. The biodistribution studies of Re(V)-DMS showed mimetic characteristics with its parent Tc(V)-DMS drug.

Animals↗

EXAFS study of Sn(IV) immobilization by hardened cement paste and calcium silicate hydrates.

In this study, the immobilization mechanisms of Sn(IV) onto calcium silicate hydrates (C-S-H) and hardened cement paste (HCP) have been investigated by combining wet chemistry experiments with X-ray absorption spectroscopy (XAS). Evidence is presented which demonstrates the formation of a Sn(IV) inner-sphere surface complex on C-S-H with a CaO/SiO2 weight ratio of 0.7. Two possible structural models, implying a corner sharing between the Sn octahedra and Q1 or Q2b Si tetrahedra, have been developed based on the experimentally determined structural parameters. In HCP, the formation of a different type of Sn(IV) inner-sphere complex has been observed, indicating that C-S-H may not be the uptake-controlling phase for Sn(IV) in the cement matrix. An alternative structural model for Sn(IV) binding in HCP has been developed, assuming that ettringite is the uptake-controlling phase. At high Sn(IV) concentrations, Sn(IV) immobilization in HCP occurs due to the formation of CaSn(OH)6.

Calcium Compounds↗

Selective determination of inorganic mercury and methylmercury in tissues by continuous flow and cold vapor atomic absorption spectrometry.

A method has been developed for the determination of inorganic (InHg) and methylmercury (MeHg) in solubilized tissues with continuous-flow (flow injection) cold vapor atomic absorption spectrometry. Kidney, liver, and brain tissues were spiked with MeHg and InHg and solubilized at an elevated temperature in a solution containing 90 g/L NaOH, 2 g/L L-cysteine, and 4 g/L NaCl. Total mercury determination was achieved by continuous-flow cold vapor atomic absorption spectrometry using an inlet system containing a flow through photo-oxidation reactor and sodium borohydride as the mercury reductant. InHg was selectively determined in the presence of MeHg with this method when using stannous chloride as the reductant. MeHg concentrations were computed as the difference between the values obtained from the two analyses. Recoveries for spiked tissues were above 95% for InHg and MeHg. Quantitation limits for InHg and total mercury in tissues were 0.4 and 0.6 microgram/g, respectively. MeHg chloride levels from kidney tissues of exposed rats were evaluated using the present method in comparison with another method in which MeHg was measured using solvent extraction and capillary gas chromatography with electron capture detection.

Animals↗

The role of Tc-99m IDA hepatobiliary and Tc-99m colloid hepatic imaging in primary biliary cirrhosis.

To assess the presence of primary biliary cirrhosis, 15 patients at various histopathologic stages were studied by Tc-99m IDA hepatobiliary and/or Tc-99m colloid hepatic imaging. In the earlier stages (I and II), seven of eight patients (88%) showed uniform hepatic retention of Tc-99m IDA. Of seven patients in the same stage, however, four (57%) showed no abnormality on Tc-99m colliod imaging. In three of these four negative patients (75%), uniform hepatic retention of Tc-99m IDA was noted. In the later stages (III and IV), all seven patients showed decreased clearance with or without delayed tracer appearance in the intestine and prominent hepatic retention on Tc-99m IDA imaging; with Tc-99m colloid imaging there was enlargement of the spleen and increased activity in the spleen and bone marrow. Thus, Tc-99m IDA imaging is considered to be more useful in revealing this functional disorder at the earlier stage of primary biliary cirrhosis and in evaluating progression from an earlier to a later stage of disease. Tc-99m colloid imaging also effectively evaluated progression.

Bone Marrow↗

A novel method for labelling human immunoglobulin-G with 99Tcm suitable for inflammation scintigraphy.

An amount of 1.0 mg human immunoglobulin G (hIgG) treated with ascorbic acid at a molar ratio of 1:5000 for 16 h at 4-7 degrees C was mixed with 250 micrograms GHA and 5 micrograms stannous chloride dihydrate in normal saline. Radiolabelling of hIgG (> 98%) was achieved instantly when mixed with 99Tcm-pertechnetate. The preparation was sufficiently stable in serum at 37 degrees C. The competitive binding assay and gel electrophoresis of the native and reduced hIgG did not show any measurable loss in immunoreactivity and intactness due to its reduction. There was no significant decrease in the radiolabel of labelled hIgG when incubated with diethylenetriaminepentaacetate (DTPA) (50-fold), in contrast with about 9% loss of the radiolabel by treating it with a similar concentration of cysteine. Blood clearance of labelled hIgG in rabbits was biphasic with about 78 min and 8 h as T1/2 of the fast and slow phases. Biodistribution of the radiotracer in mice at 4 h showed its uptake by liver (10.2%), kidneys (5.39%), intestines (7.33%) and muscles (3.9%), which altered to 5.63, 3.20, 4.03 and 6.73%, respectively, at 24 h. The radiotracer was excreted through both renal and hepatobiliary routes. High accumulation of the radiolabelled hIgG in inflammatory lesions of the patients confirmed the clinical usefulness of the method developed.

Animals↗

The effect of Glucantime on the labeling of blood constituents with technetium-99m.

PURPOSE: The labeling of red blood cells (C) with 99mTc is employed in clinical nuclear medicine for a variety of diagnostic procedures. Drugs can alter this labeling method and modify the disposition of the radiopharmaceuticals. In this paper, the influence of glucantime on the labeling of blood constituents with 9mTc was reported. METHODS: Blood was withdrawn from rats and incubated with glucantime. Stannous chloride and 99mTc were added. After centrifugation, plasma (P) and (C) were isolated. Samples of P and C were precipitated with TCA 5%, centrifuged and insoluble (IF) and soluble fractions (SF) separated. The percentages of total activity injected (%ATI) in C, IF-P and IF-C were calculated (p < 0.05). RESULTS: The %ATI on C decreased from control to following concentrations of glucantime (6.25%; 12.5%; 25%; 50%; 100%), respectively: 94.06 +/- 1.29 (control) to 77.15 +/- 2.79; to 76.68 +/- 1.88; to 75.15 +/- 2.79; to 72.64 +/- 4.40 and to 63.05 +/- 3.84. On IF-C the %ATI decreased from control to all the concentrations of glucantime (3.125%;6.25%; 12.5%; 25%; 50%; 100%), respectively: 93.34 +/- 1.18 (control) to 78.81 +/- 2.76; to 74.76 +/- 4.82; to 74.02 +/- 5.32; to 64.35 +/- 4.82; to 62.81 +/- 1.97 and to 54.55 +/- 3.58. CONCLUSIONS: This effect was probably due to products present in this drug that may complex with ions (Sn(+2) and 99mTcO4) or have a direct or indirect effect on intracellular stannous ion concentration.

Animals↗

Treatment of metastatic bone pain with tin-117m Stannic diethylenetriaminepentaacetic acid: a phase I/II clinical study.

The physical characteristics of Sn-117m combined with the biodistribution of the compound tin-117m (Stannic, 4+) diethylenetriaminepentaacetic acid (Sn-117m DTPA) suggest that it should be an excellent agent for the palliation of pain from bony metastases. Prior work has established the dosimetry and the safety for the material in human beings. The presence of low-energy conversion electrons should result in the relative sparing of the bone marrow while delivering a high radiation dose to sites of bony metastatic disease. Forty-seven patients with painful bone metastases from various malignancies were treated with Sn-117m DTPA. The patients were assigned to five different dose levels ranging from 2.64 to 10.58 MBq (71-286 microCi) per kg of body weight. Follow-up included review of pain diaries, performance scores, analgesic requirements, blood chemistries, and hematological assessment. Three patients received a second treatment. There was an overall response rate for relief of pain of 75% (range, 60-83%) in the 40 treatments that could be evaluated. No correlation was apparent in this limited series between response rate and the five dose levels used. The relief was complete in 12 patients (30%). The time to onset of pain relief was 19 +/- 15 days with doses < or = 5.29 MBq/kg and 5 +/- 3 days with doses > or = 6.61 MBq/kg. Myelotoxicity was minimal, with only one patient having a marginal grade 3 WBC toxicity. On the basis of our data, Sn-117m DTPA should be an effective and safe radiopharmaceutical for palliation of painful bony metastases. A large-scale trial is warranted to evaluate it in comparison to other similar agents.

Bone Marrow↗

[Study of the molluscocid properties of lead triphenylacetate].

The molluscicide and biocide properties of lead triphenylacetate (4,5 p p m, on Biomphalaria glabraia and Bulinus contortus) are not so great that the toxic action of tin tributiloxyde, on the same snails (2 p p m). Still the prices of the organic salts of lead are not so expensive as tin organic salts.

Lead↗

In vitro studies on tin-dithiocarbamates.

Organotin compounds have been studied for their biological properties, whereas very little is known about the effects of tin-inorganic derivatives on biological systems. Owing to our interest in the dithiocarbamate moiety in relation to metal redistribution in the body and to its biological import, we performed in vitro cytotoxicity experiments on dithiocarbamates. Preliminary results obtained with five tin-dithiocarbamates, where DDTC is the diethyldithiocarbamate anion, indicate some very promising compounds.

Animals↗

Comparison of azo dye degradation efficiency using UV/single semiconductor and UV/coupled semiconductor systems.

This study examined degradation of azo dyes using photocatalytic oxidation (UV/semiconductor). The model substrates employed in this work were Procion Red MX-5B and Amaranth, while the photocatalysts were TiO2, ZnO, and SnO2. UV-Vis spectrum analysis demonstrated that the band gap energies of TiO2, ZnO, and SnO2 were 3.17, 2.92, and 4.13 eV, respectively. The band gap energy of SnO2 is insufficient to initiate photocatalytic reaction after UV irradiation (365 nm). The reaction rate constants fit a first-order reaction model and the reaction rate constant of Procion Red MX-5B for TiO2+SnO2 (0.31 h-1) is larger than that of TiO2 (0.24 h-1) and SnO2 at pH 10. The difference between the conduction bands of SnO2 and TiO2 enables the former to act as a sink for the photogenerated electrons. Most of the reaction rate constants had higher values at pH 10 than pH 7, and thus the OH attack could be assumed to represent the main reaction in this investigation. The quantities of sulfate and chloride ions released are below stoichiometry during the degradation. Owing to the sulfonate groups of Amaranth exceeding Procion Red MX-5B, Amaranth had larger electrostatic attraction than Procion Red MX-5B with the surface of ZnO, and also had higher adsorption percentage than Procion Red MX-5B on the surface of ZnO. The trend of adsorption is consistent with the reaction rate constant at pH 7, namely Amaranth>Procion Red MX-5B. The sulfate dissociation rate constant of Amaranth in UV/ZnO at pH 7 (0.49 h-1) approaches the overall rate constant (0.53 h-1); therefore, the first step involved in Amaranth can be suggested to the cleavage of the bonds of the C-S in Amaranth, causing sulfate ion formation.

Azo Compounds↗

Effect of extract of medicinal plants on the labeling of blood elements with Technetium-99m and on the morphology of red blood cells: I--a study with Paullinia cupana.

Drugs can alter the labeling and the morphology of red blood cells. As Paullinia cupana is used in popular medicine, we evaluated its influence on the labeling process using technetium-99m (Tc-99m). Blood was incubated with P. cupana, stannous chloride and Tc-99m. Samples were centrifuged and plasma (P) and blood cells (BC) were separated and precipitated with trichloroacetic acid. Soluble (SF) and insoluble fractions (IF) were isolated. The morphology of the blood cells was evaluated under an optical microscope. The results showed a significant (P = 0.05) decrease in the uptake of radioactivity for the RBC (97.93 +/- 0.74 to 36.90 +/- 4.71%), in IF-P and in IF-BC due to P. cupana extract. The study of the morphology of the RBC revealed alterations in the shape of these cells. We suggest that the P. cupana effect could be explained by an inhibition of the stannous and pertechnetate ions or oxidation of the stannous ion or by damages in the plasma membrane.

Animals↗

Capillary electrophoretic analysis of ethylene dicysteine, a precursor of the radiopharmaceutical 99mTc ethylene dicysteine.

L,L-Ethylene dicysteine (EC) is a ligand used in nuclear medicine for the preparation of 99mTc-L,L-EC, a tracer agent for renal function studies. A capillary zone electrophoretic method is described which allows us to monitor the purity of ethylene dicysteine, for which no other suitable method has been reported to date. A fused-silica capillary (L = 70 cm, l = 62 cm, 75 microns i.d.) was used with 10 mM sodium tetraborate, pH 10.0, as the background electrolyte. The voltage applied was 20 kV and the temperature was 25 degrees C. Benzyl alcohol served as the internal standard. The limit of detection was 0.07% and the limit of quantitation was 0.15%.

Buffers↗