Trace elements profile in the blood of Huntington' disease patients.

Huntington' disease (HD) is an autosomal dominant neurodegenerative disease characterized by progressive motor, psychiatric, and cognitive deterioration. HD is, together with spinocerebellar ataxias, spinobulbar muscular atrophy and dentatorubral-pallido- luysian atrophy, one of the nine disorders caused by an expansion of glutamine residues in the causative protein where the polyglutamine expansion cause aberrant protein folding. Since an excessive metal's accumulation in organs may induce protein misfolding and oxidative stress, we have studied the blood concentration of essential (Cr, Co, Cu, Fe, Mn, Mo, Ni, Se, Zn) and nonessential (As, Cd, Sb, Sn, V) trace elements in HD patients. We found increased levels of the essential elements iron, chromium, selenium and zinc and of the nonessential element arsenic in the blood of HD patients. Since alteration in metals homeostasis may contribute to the pathogenesis of neurodegenerative disease and could eventually constitute a target for therapy, we may suggest the utilize of the blood metal profile as a further in vivo tool to study and characterize Huntington disease.

Urinary trimethyl tin reflects blood trimethyl tin in workers recycling organotins.

AIM: Our recent case report of organotin intoxication showed higher ratio of urinary trimethyl tin (TMT) to dimethyl tin (DMT) than those of the previous cases exposed to only DMT, suggesting co-exposure to DMT and TMT occurred. The present study investigated how urinary TMT and DMT reflect blood TMT and DMT, respectively, to evaluate them as biomarkers for TMT/DMT exposure. METHODS: DMT and TMT from blood collected at different time points from three patients intoxicated with organotins were measured with HPLC-ICP/MS. Previously published data of urinary DMT and TMT were used for comparison. Regression analyses were conducted with dependent variable of blood DMT and TMT and independent variable of urinary DMT and TMT, respectively. Multiple regression analysis with dummy variables of individual was also conducted. RESULTS: Regression analysis did not show significant relation of urinary TMT to blood TMT or relation of urinary DMT to blood DMT, although the former was marginal. Multiple regression analysis showed significantly positive relation of urinary TMT to blood TMT. CONCLUSIONS: The study shows that urinary TMT reflects blood TMT. In co-exposure to TMT and DMT, urinary TMT can be an internal exposure marker of TMT, which might be not only derived from external exposure to TMT but also converted from DMT in human body.

Kinetics and tissue distribution of bismuth, tin and lead after implantation of miniature shotgun alloy pellets in rats.

INTRODUCTION: Shotgun pellets containing bismuth (Bi) as substitute for lead (Pb) are increasingly being used due to environmental concerns. Information on toxicokinetics of Bi is lacking for the assessment of humans accidentally shot by Bi-containing shotgun alloy pellets. METHODS: Male Wistar rats were exposed to miniature alloy pellets containing Bi, tin (Sn) and minor amounts of Pb by implantation in muscle tissues of the hind legs. RESULTS: The concentrations of Bi in whole blood and urine increased up to 53 weeks after implantation. The highest concentrations of Sn in whole blood were observed three weeks after implantation, then declining to background levels 53 weeks after implantation. Lead in whole blood increased up to 13 weeks of exposure, and declined for the remaining observation period. Bismuth and Sn accumulated mainly in kidney, but also in liver, testicle and brain. Analytical field emission scanning electron microscopy of post-implant pellets showed depletion of Pb towards the pellet surface. Oxygen and chlorine accumulated in Sn rich lamellas in areas next to the pellet surface. The distribution of Bi remained visually unaffected as compared to pre-implant pellets. CONCLUSION: The concentration of Bi increased during the whole observation period in blood, urine, kidney, brain, testicle and liver. The decline in the concentrations of Pb and Sn in blood and urine after reaching the peak concentration may be related to alterations in the chemical composition and element distribution of the implanted alloy pellets.

Serum concentration of several trace metals and physical training.

BACKGROUND: The aim of this study was to observe the concentrations of trace metals boron, lithium, rubidium, antimony, tin and strontium in the serum of athletes from different modalities and sedentary subjects and the possible influence that different energy sports training modalities can have on their concentration. METHODS: Eighty professional athletes and 31 sedentary males participated in the present survey. All of them were living in Cáceres (Spain). Serum boron, lithium, rubidium, antimony, tin and strontium analysis was performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). RESULTS: The results show higher concentrations in athletes on tin (p < 0.01), rubidium and antimony (p < 0.001) than the control group. In the case of tin, this item had the highest concentrations only in aerobic sports modalities. Regarding rubidium and antimony, the highest concentrations are found in athletes with lower oxygen consumption (aerobic-anaerobic) (p < 0.001), followed by anaerobic group (p < 0.001). CONCLUSION: Our research shows that, probably due to increased water and air intake, especially, trace elements rubidium, antimony and tin reveal major differences in serum concentration of athletes in relation to sedentary subjects. On the other hand, physical training does not change the serum concentration of Boron, Lithium and strontium.

Tributyltin chloride induces renal dysfunction by inflammation and oxidative stress in female rats.

Tributyltin chloride (TBT) is an organometallic pollutant that is used as a biocide in antifouling paints. TBT induces several toxic and endocrine-disrupting effects. However, studies evaluating the effects of TBT on renal function are rare. This study demonstrates that TBT exposure is responsible for improper renal function as well as the development of abnormal morphophysiology in mammalian kidneys. Female rats were treated with TBT, and their renal morphophysiology was assessed. Morphophysiological abnormalities such as decreased glomerular filtration rate and increased proteinuria levels were observed in TBT rats. In addition, increases in inflammation, collagen deposition and α-smooth muscle actin (α-SMA) protein expression were observed in TBT kidneys. A disrupted cellular redox balance and apoptosis in kidney tissue were also observed in TBT rats. TBT rats demonstrated reduced serum estrogen levels and estrogen receptor-α (ERα) protein expression in renal cortex. Together, these data provide in vivo evidence that TBT is toxic to normal renal function and that these effects may be associated with renal histopathology complications, such as inflammation and fibrosis.

Correlation between long-term in vivo amalgam restorations and the presence of heavy elements in the dental pulp.

PROJECT: To measure the levels of heavy metals (Hg, Sn) in the dental pulp and blood samples of patients with long-term amalgam restorations. PROCEDURE: 12 amalgam restored and 12 non-restored, sound teeth were chosen and access cavity preparation to the pulp chamber was made. The contents were transferred and dissolved in 5mL of concentrated nitric acid followed by placement in an oven at 180°C for tissue digestion. After cooling the tubes each digested sample was transferred to an atomic absorption system to measure the levels of heavy metals. The blood samples of five patients in each group were randomly analyzed to determine the levels of these heavy metals in the blood and if there were a correlation between these levels in blood and pulp. Data were analyzed by t-test at a P<0.05 level of significance. RESULTS: No significant difference was seen between the levels of Hg and Sn in pulp tissues (P>0.05); however, the blood analysis showed higher level of Hg amalgam group (P=0.009). The analysis between the pulp and blood samples showed positive correlations for both Hg and Sn elements in dental pulp and the blood (P=1.000) (P=0.900). CONCLUSIONS: The long-term presence of dental amalgam (at least 5 years) did not result in any remarkable changes in the levels of mercury and tin in the pulp tissue; however, there were increases in the level of mercury in the blood circulation even five years following the placement of the restoration.

Direct determination of tin in whole blood and urine by GF AAS.

OBJECTIVE: The aim of this work was to develop a procedure for the determination of tin in whole blood and urine by GF AAS with a minimum sample pre-treatment, using Pd/Mg as chemical modifier. DESIGN AND METHODS: The analyses of tin were conducted using an atomic absorption spectrometer with Zeeman background correction. The laboratory staff volunteered blood and urine samples for the experimental studies and application of the methodology. RESULTS: Samples were just diluted with 0.2% v/v Triton X-100, and pyrolysis and atomization temperatures of 1300 and 2200 °C were used. External calibration was performed with matrix matched calibration solutions. Limits of detection of 2.7 and 0.8 µgL(-1) were reached for blood and urine, respectively. The method was applied to the determination of Sn in blood and urine of eleven subjects not occupationally exposed, working in a laboratory of toxicology in a large Brazilian city, and the results ranged from 7.4 to 11.2 µgL(-1) and ≤0.8 to 2.2 µgL(-1), for blood and urine, respectively. Accuracy was assessed by analysis of standard reference materials for tin in blood (Contox I, lot TM144-1097, Kaulson Laboratories, USA) and urine (Seronorm, lot 0511545, Sero AS, Norway). CONCLUSIONS: Results showed good agreement between experimental and reference values according to the Student's t test at 95% of confidence.

Concentration of metals in blood of Maine children 1-6 years old.

Blood lead concentrations are higher in young children than in other age groups, whereas little is known regarding concentrations of other metals in young children. We measured the concentrations of a suite of metals in the blood of children 1-6 years of age, and assessed potential differences by age, season, or region of Maine. We used blood submitted to the Maine State Health and Environmental Testing Laboratory for blood lead analysis to determine the concentrations of arsenic (As), antimony (Sb), cadmium (Cd), manganese (Mn), mercury (Hg), selenium (Se), tin (Sn), and uranium (U) in 1350 children 1-6 years of age. The essential metals Mn and Se were detected in all samples, and As and Sb were detected in >90% of samples. Hg was detected in approximately 60% of samples. U and Cd were less often detected in blood samples, at approximately 30% and 10% of samples, respectively. Sn was not detected in any sample. Concentrations of As, Hg, and Se increased with age, whereas Sb decreased with age. Concentrations also varied by season and region for some though not all metals. Significant pairwise correlations were observed for a number of metals. Blood is a reasonable compartment for measurement of most of these metals in young children. The use of convenience samples provided a cost-effective mechanism for assessing exposure of young children in Maine.

Análise de especiação de estanho em plasma de trabalhadores expostos / Speciation analysis of tin in plasma of exposed workers

O estanho (Sn) é um elemento natural na crosta terrestre obtido a partir do minério cassiterita. Devido à sua utilização em processos industriais, é encontrado distribuído pelo ambiente, e sendo um potencial contaminante. Na natureza, aparece nas formas inorgânicas e orgânicas, e quanto menor a cadeia orgânica associada ao metal, maior toxicidade do composto. Compostos organoestânicos de cadeia curta, como trimetil e trietil Sn, são bem absorvidos no trato gastrointestinal. Compostos organoestânicos podem penetrar nas membranas celulares, causando danos celulares e nas mitocôndrias, e ainda interromper a fosforilação oxidativa. Desta forma, podem ser imuno e genotóxicos. O interesse na especiação dos compostos de Sn é devido à toxicidade ser dependente da espécie. O plasma sanguíneo contém a fração biodisponível do analito e pode intermediar a predição de algumas formas de toxicidade crônica. No entanto, há poucos trabalhos sobre como o Sn se encontra no plasma. Portanto, a caracterização dos constituintes que se ligam e / ou transportam esse elemento ajustam na compreensão de seu metabolismo, elucidação dos mecanismos de toxicidade, uma melhor compreensão da distribuição de Sn na célula e sua de posição nos tecidos. Neste estudo, foi desenvolvido um método analítico para separação das espécies de Sn no plasma sanguíneo de trabalhadores que beneficiam o minério de cassiterita, através de cromatografia líquida por filtração em gel, enquanto a concentração do Sn nas frações coletadas foi determinada por espectrometria de absorção atômica por forno de grafite. O uso de Sepharose CL-4B, uma coluna com altura de 1 m, fase móvel de 50 milimolares (mM) Tris-HCl + 30 mM NaHCO3, pH 7,4, fluxo de 0,7 militros por minuto (ml min-1), volumes de plasma injetado e frações coletadas iguais a 2 ml cada,apresentou melhor separação das proteínas, com o aparecimento de três picos...

Tin is a natural element in the earth's crust and is obtained from cassiterite ores. Owing to their wide use in industrial processes, tin is relatively distributed in the environment. In nature, it occurs in both inorganic and organic forms and shorter organic chainassociated to the metal, higher the toxicity of the compound. Short-chain organotin compounds such as trimethyl and triethyl tin are well absorbed in the gastrointestinal tract. Organotin compounds can penetrate cell membranes causing damage to cell andmitochondria, as well as interrupt oxidative phosphorylation. Thus organic compounds can be immunotoxic and genotoxic. The interest on speciation of the organotin compounds is due to species-dependent toxicity. The blood plasma contains the bioavailable fraction of the analyte and can mediate the prediction of some forms ofchronic toxicity. However, very few species of tin existing in the plasma are known. Therefore, the characterization of the constituents that bind to and / or transporting the element of interest is critical to full understanding of metabolism, elucidation of themechanisms of toxicity, a better understanding of the distribution of tin in the cell and its deposition in tissues. In this study, we developed an analytical method for theseparation of tin species in blood plasma using gel filtration liquid chromatography while tin concentration in the collected fractions was determined by graphite furnace atomic absorption spectrometry. The use of Sepharose CL-4B, height of 1 m, mobilephase of 50mM Tris-HCl + 30mM NaHCO3, pH 7,4, flow 0,7 ml min-1, fractions collected volume of 2 ml, plasma injected volume of 2 ml, showed the best protein separation with three peaks. For the determination of tin, pyrolisis and atomization...

Synthesis and characterization of Sn(IV) complexes of lower rim 1,3-diacid derivative of calix[4]arene and their protective effects on tissue oxidative stress and essential metal concentration in lead exposed male Wistar rats.

The two Sn(IV) complexes synthesized using calix[4]arene-1,3-di-acid derivative were characterized by analytical, (1)H, (13)C and (119)Sn NMR, matrix assisted laser desorption ionization mass, and (119)Sn Mossbauer techniques and found that the complexes are tetranuclear possessing structurally two different types of tin centers. These complexes were evaluated for their protective value against blood and tissue oxidative stress in lead exposed male albino rats of Wistar strain. The results suggest that the two tin complexes significantly protect changes in lead induced biochemical variables indicative of heme synthesis pathway and exhibit only moderate effect on tissue oxidative stress. The beneficial effects could be attributed mainly to the ability of Sn(IV) complexes in preventing absorption of lead to the target sites/tissues.

Comparison of the predicted in vivo behaviour of the Sn(II)-APDDMP complex and the results as studied in a rodent model.

In a quest for more effective radiopharmaceuticals for pain palliation of metastatic bone cancer, this paper relates results obtained with ((117m)Sn labelled) Sn(II) complexed to the bone seeking bisphosphonate, N,N-dimethylenephosphonate-1-hydroxy-3-aminopropylidenediphosphonate (APDDMP). APDDMP is synthesised from the known bone cancer pain palliation agent 1-hydroxy-3-aminopropylidenediphosphonate (APD, Pamindronate). This work is performed to utilise the idea that the low bone marrow radio toxicity of (117m)Sn could afford a highly effective radiopharmaceutical in pain palliation but also in the curative treatment of bone metastasis. Complex-formation constants of APDDMP with the important blood plasma metal-ions, Ca(2+), Mg(2+), Zn(2+) as well as the added metal ion, Sn(2+) were measured by glass electrode potentiometry at 25 degrees C and I = 150 mM. Blood plasma models were constructed using the computer code ECCLES and the results compared with those gathered from tests on a rodent model. The ((117m)Sn-labelled) Sn(II)-APDDMP complex was found to have only some liver and bone uptake although a high trabecular to normal bone ratio was recorded. From the blood plasma model this was shown to be primarily due to the high affinity of APDDMP for Ca(II) causing some of the Sn(II)-APDDMP complex to dissociate. High kidney uptake and excretion as well as high bladder uptake was recorded which was shown to be due to the dissociation of the Sn(II)-APDDMP complex in blood plasma. Animal model observations could be explained by the blood plasma modelling.

Clinical application of spontaneous red blood cell labeling with Tc-99m sodium pertechnetate.

Red blood cells (RBC) may be labeled with Tc-99m after Tc-99m sodium pertechnetate is injected in the presence of a reducing agent, such as stannous chloride. Thus, spontaneous RBC labeling with Tc-99m is expected to be seen in patients with a high plasma concentration of tin. Spontaneous RBC labeling with Tc-99m was obtained in a 73-year-old woman who was clinically diagnosed with tin intoxication and proved to have a high concentration of plasma tin. The RBC labeling rate was calculated as 96% with blood sampling. Spontaneous RBC labeling with Tc-99m is a very simple method for proving a high plasma tin concentration and is adaptable to clinical diagnosis.

Plasma trace elements concentrations in trained subjects after exposure to hypokinesia and daily hyperhydration.

The objective of this investigation was to evaluate the effect of a daily intake of fluid and salt supplementation (FSS) on blood plasma trace elements concentrations in physically healthy volunteers after exposure to 364 d of hypokinesia (decreased number of steps per day). The studies were performed after exposure to 364 d of Hypokinesia (HK) on 30 long-distance runners of volunteers who had a VO2 max 67 mL/kg/min and were ranging in the age of 19-24 yrs. Prior to their exposure to HK all volunteers were on an average of 10,000 steps/d. For the simulation of the hypokinetic effect the volunteers were kept under an average of 3000 steps/d. All volunteers were divided into three equal groups. The first group of volunteers subjected to HK and received daily FSS (water 26 mL/kg body wt and sodium chloride 0.16 g/kg body wt.), the second groups of volunteers submitted only to HK, and the third group of volunteers underwent a normal ambulatory life and served as control. The content of manganese, calcium, magnesium, iron, lead, copper, tin, nickel, zinc and cobalamine were determined in blood plasma of volunteers. By the end of the hypokinetic period the blood plasma concentration of microelements increased significantly in the hypokinetic subjects (second group), whereas in the hyperhydrated subjects (first group) decreased. It was concluded that prolonged restriction of motor activity induced significant increases in blood trace elements concentrations whereas daily hyperhydration had a normalizing effect on their concentration in blood plasma. This indicates that daily hyperhydration may be used to normalize blood plasma concentrations of micro-elements in physically healthy volunteers subjected to prolonged restriction of motor activity.

Effect of subchronic bis(tri-n-butyltin)oxide (TBTO) oral administration on haematological parameters in monkeys: a preliminary report.

A preliminary study was conducted on adult male crab-eating monkeys (Macaca fascicularis) orally exposed to bis(tri-n-butyltin)oxide (TBTO) at doses of 0 and 160 micrograms/kg/day, 6 days/wk, for 22 wk. No treatment-related signs of toxicity or changes in body weight gain were detected during the course of the study. The haematological analyses performed every 2 wk indicated a decrease in total leucocyte count in the treated animals with significant values in wk 8, 10 and 22 of treatment. No differences from controls were noted in clinical chemistry and total tin concentration in blood. These preliminary data on the toxicity of TBTO in the primate model are intended to be an initial contribution towards a better evaluation of the potential toxicological hazard of TBTO to humans.

The role of the rat submandibular gland in the excretion of bis (tributyltin) oxide: electron microscopy, X-ray microanalysis and atomic absorption analysis.

The role of the submandibular glands in the excretion of parenterally administered bis (tributyltin) oxide (TBTO) was studied. Fine structural alterations of the submandibular glands were observed with an electron microscope. Accumulation sites of TBTO were determined with an X-ray microanalyzer and tin concentrations in saliva and blood were measured by atomic absorption spectrophotometry.

Tin and fatty acids in dementia.

Serum elements and fatty acids of red cell and plasma phospholipids, cholesterol esters and high density lipoproteins, were studied in patients with Alzheimer's disease (SDAT) and with multi-infarct dementia (MID). Increased 20:4n6 in MID was the finding most consistent in the different tissues. The red cell phospholipids were more unsaturated in MID than in SDAT but in SDAT the plasma phospholipids were more saturated. Serum Al, Sn and V concentrations were higher in SDAT than in MID while serum Mn concentrations were higher in MID. Sn and V correlated negatively with the unsaturation index of the red cell phospholipids and Sn showed a striking pattern of correlations with the red cell phospholipid fatty acids in SDAT: it was significantly positively correlated with 16:0 and 18:1n-9 and negatively correlated with 20 and 22 carbon n-3 and n-6 essential fatty acids. Since we have shown elevated tin levels in patients with Alzheimer's disease, and since organic tin compounds given to animals produce a syndrome with similarities to Alzheimer's disease, there is a need for investigation of the role of tin in lipid metabolism in dementia.

Determination of tin in human blood serum by radiochemical neutron activation analysis.

A method was developed for the determination of tin in human serum by radiochemical neutron activation analysis, using the long-lived radioisotope Sn(T1/2 = 115.09 days). This radioisotope decays to a daughter isotope 113mIn, the most suitable nuclide for counting (T1/2 = 1.658 h, gamma-ray of 391.7 keV). Experience showed that, with the exception of the serum samples with the lowest tin levels, in the experimental conditions of the present study tin could mostly also be determined by using its radioisotope 117mSn(T1/2 = 13.61 days, gamma-ray of 158.5 keV). Samples were collected and prepared by using the procedure elaborated by the authors, which proved its effectiveness in preventing significant sample contamination on several occasions. Because samples had to be irradiated at 10(14) n.cm-2.s-1, dry ashing was necessary. After irradiation, tin was separated by solvent extraction of tin(IV) iodide from a sulfuric acid-ammonium iodide solution with toluene. The dry ashing and solvent extraction steps were exhaustively tested by means of radioactive tracer experiments whereas the accuracy and precision of the analytical method were thoroughly checked by analyzing biological reference materials (Bowen's kale powder, the NBS' bovine liver, the NBS' nonfat milk powder, and the "second-generation" biological reference material--freeze-dried human serum--for trace element determinations, developed by the authors).(ABSTRACT TRUNCATED AT 250 WORDS)

Simple determination of tin in biological materials by atomic absorption spectrometry with a graphite furnace.

A simple and rapid determination of tin in biological materials (blood, brain, liver, kidney, etc,) by atomic absorption spectrometry (AAS) with a graphite furnace is described. Suppression of interferences by direct addition of ascorbic acid in wet-ashed biological materials was investigated for the determination of tin. This method involves no extraction with organic solvent for removal of the interferences, and therefore it is neither time consuming nor error prone, and is suitable for large sample sizes and small sample volumes. The limit of detection of this method is 0.002 microgram/mL, equivalent to a limit of detection in the materials of 0.02 microgram/g. The calibration graph is linear up to 1 microgram/mL of tin.

Autonomic nervous system dysfunction in workers exposed to lead, zinc, and copper in relation to peripheral nerve conduction: a study of R-R interval variability.

Quantitative assessment of the autonomic neurotoxicity due to lead was undertaken by measuring variability in the electrocardiographic R-R interval (CVRR) in 16 male workers exposed to lead, zinc, copper, and tin and in 16 unexposed control subjects. Two component coefficients of variation in the R-R interval, the C-CVRSA (respiratory sinus arrhythmia) and C-CVMWSA (Mayer wave related sinus arrhythmia), were examined; these indices are considered to reflect parasympathetic and sympathetic activities, respectively. Maximal motor and sensory conduction velocities (MCV and SCV) in the median nerve were also measured. In the 16 exposed workers, blood lead concentrations ranged from 16 to 60 (mean 34) micrograms/dl. The CVRR and C-CVRSA were found to be significantly reduced in the workers with elevated lead, zinc, and copper absorption as compared to unexposed control subjects; also, the MCV and SCV were significantly slowed. The C-CVMWSA was not significantly reduced, and was positively related to plasma zinc concentrations. No significant relationships were found between indicators of lead and copper absorption and these electrophysiological measurements. These data suggest that subclinical toxicity of lead occurs in the parasympathetic component of the autonomic nervous system as well as in the peripheral nerves. Zinc may antagonize the autonomic nervous dysfunction caused by lead.