Changes in thallium distribution in the scalp hair after an intoxication incident.

In cases of criminal thallium poisoning, forensic investigation is required to identify the amount and time of thallium exposure. Usually, blood and urine thallium levels are respectively used as biomarkers. Additionally, hair has the unique potential to reveal retrospective information. Although several studies have attempted to clarify how thallium is distributed in hair after thallium poisoning, none have evaluated the time course of changing thallium distribution. We investigated changes in the distribution of thallium in hair at different time points after exposure in five criminal thallotoxicosis patients. Scalp hair samples were collected twice, at 2.6 and 4.2-4.5months after an exposure incident by police. Results of our segmented analysis, a considerable amount of thallium was detected in almost all hair sample segments. The thallium exposure date estimated from both hair sample collections matched the actual exposure date. We found that determination of thallium amounts in hair samples divided into consecutive segments provides valuable information about exposure period even if a considerable time passes after exposure. Moreover, when estimating the amount of thallium exposure from a scalp hair sample, it is necessary to pay sufficient attention to individual differences in its decrease from hair.

Electropermeabilization of cells by closely spaced paired nanosecond-range pulses.

Decreasing the time gap between two identical electric pulses is expected to render bioeffects similar to those of a single pulse of equivalent total duration. In this study, we show that it is not necessarily true, and that the effects vary for different permeabilization markers. We exposed individual CHO or NG108 cells to one 300-ns pulse (3.7-11.6 kV/cm), or a pair of such pulses (0.4-1000 µs interval), or to a single 600-ns pulse of the same amplitude. Electropermeabilization was evaluated (a) by the uptake of YO-PRO-1 (YP) dye; (b) by the amplitude of elicited Ca2+ transients, and (c) by the entry of Tl+ ions. For YP uptake, applying a 600-ns pulse or a pair of 300-ns pulses doubled the effect of a single 300-ns pulse; this additive effect did not depend on the time interval between pulses or the electric field, indicating that already permeabilized cells are as susceptible to electropermeabilization as naïve cells. In contrast, Ca2+ transients and Tl+ uptake increased in a supra-additive fashion when two pulses were delivered instead of one. Paired pulses at 3.7 kV/cm with minimal separation (0.4 and 1 µs) elicited 50-100% larger Ca2+ transients than either a single 600-ns pulse or paired pulses with longer separation (10-1000 µs). This paradoxically high efficiency of the closest spaced pulses was emphasized when Ca2+ transients were elicited in a Ca2+-free solution (when the endoplasmic reticulum (ER) was the sole significant source of Ca2+), but was eliminated by Ca2+ depletion from the ER and was not observed for Tl+ entry through the electropermeabilized membrane. We conclude that closely spaced paired pulses specifically target ER, by either permeabilizing it to a greater extent than a single double-duration pulse thus causing more Ca2+ leak, or by amplifying Ca2+-induced Ca2+ release by an unknown mechanism.

Criteria for the addition of prone imaging to myocardial perfusion single-photon emission computed tomography for inferior wall.

OBJECTIVE: Myocardial perfusion single-photon emission computed tomography (SPECT) is occasionally suspected to generate images that represent either ischemia or infarction for the inferior wall [right coronary artery (RCA) disease] or attenuation artifacts because of the diaphragm. We often encounter this. The application of prone imaging is advantageous in the differentiation of RCA disease because of attenuation artifacts. If decreased accumulation of radioisotopes is observed at the site with either RCA disease or attenuation artifacts, then a criterion that enables the addition of prone imaging should be implemented. Then, we evaluated sites where RCA disease and attenuation artifacts would likely appear and investigated the threshold of decreased accumulation that enables utilization of prone imaging. PATIENTS AND METHODS: The patients in this study were divided into two groups: group A (20 patients) suspected to have attenuation artifacts because of the diaphragm and group B (14 patients) with RCA disease. Additional evaluation by prone imaging was performed in all patients. We utilized a 20-segment quantitative perfusion SPECT polar map in the supine and prone positions to compare the percentage increase in Thallium chloride (Tl) in both groups. We then investigated the percent uptake (%uptake) value of decreased accumulation in the inferior wall for the addition of prone imaging. RESULTS: The highest %uptake was present in segments 3, 4, 5, and 10 in group A after the prone imaging. Detection of attenuation artifacts from the diaphragm was easy in segments 3, 4, 5, and 10, and we set the %uptake threshold at 62, 61, 71, and 76%, respectively, in the supine position for the addition of prone imaging. CONCLUSION: A decrease of the %uptake in segments 3, 4, 5, and 10 after supine imaging is presumed to result from attenuation artifact or RCA disease. We established evaluation criteria for the addition of prone imaging in patients with decreased accumulation in the inferior wall during supine imaging.

Bioaccumulation of thallium and other trace metals in Biscutella laevigata nearby a decommissioned zinc-lead mine (Northeastern Italian Alps).

The mineral body exploited in Salafossa (Eastern Dolomites) was one of the largest lead/zinc-containing mineral deposits in Europe. Both metals were mainly present as sulphides (sphalerite, ZnS and galena, PbS). Mining activity started around 1550, but it was only around 1960 that the richest veins of the minerals were discovered. The mine closed in 1985, and concentrations of several trace metals, such as thallium (Tl), iron (Fe), manganese (Mn), lead (Pb) and zinc (Zn), were detected in the soils and plant samples (Biscutella laevigata L.) that were collected from eighteen sites selected outside the mine. B. laevigata is a pseudometallophyta species, and it often grows near mining areas where the soil's metal concentrations are significantly higher than those of soil with a natural geochemical background. The total metal concentrations in the plant tissue (roots and leaves of Biscutella laevigata) and in the soil samples - both bulk-soil and the B. laevigata root system (rhizo-soil) - were determined through Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). The metal extractability and leachability of the soil samples were estimated using soil extractions with DTPA (Diethylenetriaminepentaacetic acid). In addition, metal mobility caused by rainwater runoff was estimated by using a leaching test with a dilute solution of H2SO4 and HNO3. The results showed that metals were present in a chemical form available for uptake by the plants' roots. In fact, high concentrations of the metals were also found in the plant tissue (roots and leaves) of B. laevigata, and these concentrations were higher than those whose soils present natural geochemical background levels in the corresponding rhizo-soil. Thus, B. laevigata has shown a marked ability to bioaccumulate trace metals, especially Tl and, to a lesser extent, Zn, Pb, Fe and Mn, and it can influence metal mobility in the rhizo-soil. To assess the uptake and translocation processes of the trace metals, resulting in their bioaccumulation, two different indices were calculated: the enrichment factor in roots (EFr), as the ratio between the metal concentration in belowground biomass and in the respective rhizo-soil, and the translocation factor (TF), as the ratio between the metal concentration in the leaves and the corresponding roots. For both indices, values > 1 denoted enrichment of the metal in the roots or its translocation to the upper tissues. The results showed that EFr and TF were considerably high only for Tl, reaching a maximum value of 60 for EFr and 11.6 for TF. Conversely, the other investigated metals did not show significant bioaccumulation (EFr < 1), and they showed TF > 1 only at a few sites.

Risk assessment and vertical distribution of thallium in paddy soils and uptake in rice plants irrigated with acid mine drainage.

The objective of this paper is to assess the influence of irritating paddy fields with acid mine drainage containing thallium (Tl) to rice plant-soil system and potential health risks for local residents. Vertical distribution of Tl, pH, organic matter (OM), and cation exchange capacity (CEC) in 24 paddy soil profiles around Yunfu pyrite mine area was investigated. Rice plant samples were collected from the corresponding soil sampling site. The results showed that Tl concentrations in paddy soils at 0-60 cm depth range from 3.07 to 9.42 mg kg-1, with a mean of 5.74 mg kg-1, which were significantly higher than the background value of soil in China (0.58 mg kg-1). On the whole, Tl contents in paddy soil profiles increased quickly with soil depth from 0 to 30 cm and decreased slowly with soil depth from 30 to 60 cm. The soil Tl content was significant negatively correlated with soil pH. The mean content of Tl in the root, stem, leaf, and rice was 4.36, 1.83, 2.74, and 1.42 mg kg-1, respectively, which exceeded the proposed permissible limits for foods and feedstuffs in Germany. The Tl content in various tissues of the rice plants followed the order root > leaf > stem (rice), which suggested that most Tl taken up by rice plants retained in the root, and a little migrated to the leaf, stem, and rice. Correlation analysis showed that Tl content in root was significant positively correlated with Tl content in leaf and rice. The ranges of hazard quotient (HQ) values were 4.08∼24.50 and 3.84∼22.38 for males and females, respectively. Males have higher health risk than females in the same age group. In childhood age groups (2 to <21 years) and adult age groups (21 to <70 years), the highest health risk level was observed in the 11 to 16 age group and 21 to 50 age group, respectively. The findings indicated that regular irrigation with Tl-bearing acid mine drainage led to considerable contamination of Tl in paddy soil and rice plant. Local government should take various measures to treat Tl contamination, especially the tailings.

Spatial patterns of neuronal activity in rat cerebral cortex during non-rapid eye movement sleep.

It is commonly assumed that cortical activity in non-rapid eye movement sleep (NREMS) is spatially homogeneous on the mesoscopic scale. This is partly due to the limited observational scope of common metabolic or imaging methods in sleep. We used the recently developed technique of thallium-autometallography (TlAMG) to visualize mesoscopic patterns of activity in the sleeping cortex with single-cell resolution. We intravenously injected rats with the lipophilic chelate complex thallium diethyldithiocarbamate (TlDDC) during spontaneously occurring periods of NREMS and mapped the patterns of neuronal uptake of the potassium (K+) probe thallium (Tl+). Using this method, we show that cortical activity patterns are not spatially homogeneous during discrete 5-min episodes of NREMS in unrestrained rats-rather, they are complex and spatially diverse. Along with a relative predominance of infragranular layer activation, we find pronounced differences in metabolic activity of neighboring neuronal assemblies, an observation which lends support to the emerging paradigm that sleep is a distributed process with regulation on the local scale.

Effects of exposure to high concentrations of waterborne Tl on K and Tl concentrations in Chironomus riparius larvae.

Thallium (Tl) is a non-essential metal which is released into the environment primarily as the result of anthropogenic activities such as fossil fuel burning and smelting of ores. The ionic radius of monovalent Tl⁺ is similar to that of K⁺ and Tl⁺ may thus interfere with K⁺-dependent processes. We determined that the acute (48 h) lethal concentration where 50% of the organisms do not survive (LC50) of Tl for 4th instar Chironomus riparius larvae was 723 µmol L⁻¹. Accumulation of Tl by the whole animal was saturable, with a maximum accumulation (Jmax) of 4637 µmol kg⁻¹ wet mass, and K(D) of 670 µmol Tl l⁻¹. Tl accumulation by the gut appeared saturable at the lowest four Tl concentrations, with a Jmax of 2560 µmol kg⁻¹ wet mass and a K(D) of 54.5 µmol Tl l⁻¹. The saturable accumulation at the gut may be indicative of a limited capacity for intracellular detoxification, such as storage in lysosomes or complexation with metal-binding proteins. Tl accumulation by the hemolymph was found to be linear and Tl concentrations in the hemolymph were ~75% of the exposure concentration at Tl exposures >26.9 µmol L⁻¹. There was not a significant decrease in whole animal, gut or hemolymph K during exposure to waterborne Tl at any of the concentrations tested (up to 1500 µmol L⁻¹). The avoidance of hypokalemia by C. riparius larvae may contribute to survival during acute waterborne exposures to Tl.

Factors affecting the myocardial activity acquired during exercise SPECT with a high-sensitivity cardiac CZT camera as compared with conventional Anger camera.

PURPOSE: Injected doses are difficult to optimize for exercise SPECT since they depend on the myocardial fraction of injected activity (MFI) that is detected by the camera. The aim of this study was to analyse the factors affecting MFI determined using a cardiac CZT camera as compared with those determined using conventional Anger cameras. METHODS: Factors affecting MFI were determined and compared in patients who had consecutive exercise SPECT acquisitions with (201)Tl (84 patients) or (99m)Tc-sestamibi (87 patients) with an Anger or a CZT camera. A predictive model was validated in a group of patients routinely referred for (201)Tl (78 patients) or (99m)Tc-sestamibi (80 patients) exercise CZT SPECT. RESULTS: The predictive model involved: (1) camera type, adjusted mean MFI being ninefold higher for CZT than for Anger SPECT, (2) tracer type, adjusted mean MFI being twofold higher for (201)Tl than for (99m)Tc-sestamibi, and (3) logarithm of body weight. The CZT SPECT model led to a +1 ± 26% error in the prediction of the actual MFI from the validation group. The mean MFI values estimated for CZT SPECT were more than twofold higher in patients with a body weight of 60 kg than in patients with a body weight of 120 kg (15.9 and 6.8 ppm for (99m)Tc-sestamibi and 30.5 and 13.1ppm for (201)Tl, respectively), and for a 14-min acquisition of up to one million myocardial counts, the corresponding injected activities were only 80 and 186 MBq for (99m)Tc-sestamibi and 39 and 91 MBq for (201)Tl, respectively. CONCLUSION: Myocardial activities acquired during exercise CZT SPECT are strongly influenced by body weight and tracer type, and are dramatically higher than those obtained using an Anger camera, allowing very low-dose protocols to be planned, especially for (99m)Tc-sestamibi and in non-obese subjects.

Low-dose single acquisition rest (99m)Tc/stress (201)Tl myocardial perfusion SPECT protocol: phantom studies and clinical validation.

PURPOSE: We developed and tested a single acquisition rest (99m)Tc-sestamibi/stress (201)Tl dual isotope protocol (SDI) with the intention of improving the clinical workflow and patient comfort of myocardial perfusion single photon emission computed tomography (SPECT). METHODS: The technical feasibility of SDI was evaluated by a series of anthropomorphic phantom studies on a standard SPECT camera. The attenuation map was created by a moving transmission line source. Iterative reconstruction including attenuation correction, resolution recovery and Monte Carlo simulation of scatter was used for simultaneous reconstruction of dual tracer distribution. For clinical evaluation, patient studies were compared to stress (99m)Tc and rest (99m)Tc reference images acquired in a 2-day protocol. Clinical follow-up examinations like coronary angiography (CAG) and fractional flow reserve (FFR) were included in the assessment if available. RESULTS: Phantom studies demonstrated the technical feasibility of SDI. Artificial lesions inserted in the phantom mimicking ischaemia could be clearly identified. In 51/53 patients, the image quality was adequate for clinical evaluation. For the remaining two obese patients with body mass index > 32 the injected (201)Tl dose of 74 MBq was insufficient for clinical assessment. In answer to this the (201)Tl dose was adapted for obese patients in the rest of the study. In 31 patients, SDI and (99m)Tc reference images resulted in equivalent clinical assessment. Significant differences were found in 20 patients. In 18 of these 20 patients additional examinations were available. In 15 patients the diagnosis based on the SDI images was confirmed by the results of CAG or FFR. In these patients the SDI images were more accurate than the (99m)Tc reference study. In three patients minor ischaemic lesions were detected by SDI but were not confirmed by CAG. In one of these cases this was probably caused by pronounced apical thinning. For two patients no relevant clinical follow-up information was available for evaluation. CONCLUSION: The proposed SDI protocol has the potential to improve clinical workflow and patient comfort and suggests improved accuracy as demonstrated in the clinical feasibility study.

Ion-selective microelectrode measurements of Tl⁺ and K⁺ transport by the gut and associated epithelia in Chironomus riparius.

Thallium (Tl) is a non-essential metal that is mobilized through industrial processes, subsequently entering aquatic environments where it can exert toxic effects. Although the aquatic larvae of the midge, Chironomus riparius, are exceptionally tolerant toward many waterborne non-essential metals, few studies have looked at the cellular mechanism of this tolerance. Tl⁺ and K⁺ share the same charge and have similar ionic radii, resulting in competition between these ions for K⁺ transporters. Using a recently developed Tl⁺-selective microelectrode in conjunction with the scanning ion selective electrode technique (SIET) and a two-microelectrode holder, measurements of K⁺ and Tl⁺ fluxes were made along the anal papillae and also along the isolated gut tract and Malpighian tubules (MTs) of C. riparius larvae. The MTs are a site of Tl⁺ secretion (i.e. from hemolymph into the tubule lumen). The major K⁺ transporting regions of the gut were the caecae, anterior midgut (AMG) and posterior midgut (PMG) in Tl⁺-naïve larvae, and Tl⁺ was also transported in the same direction at these locations. When the bathing saline concentration of Tl⁺ was increased to 50 µmol l⁻¹, K⁺ transport was inhibited at the AMG and PMG. Larvae exposed to 300 µmol l⁻¹ waterborne Tl⁺ for 48 h prior to ion flux measurements absorbed Tl⁺ (lumen to hemolymph) across the caecae, AMG and PMG. K⁺ secretion at the caecae was unaffected by Tl⁺ exposure, consistent with separate pathways for Tl⁺ and K⁺ transport across the caecae. By contrast, K⁺ flux at the AMG and PMG of Tl⁺-exposed larvae was impaired, suggesting that interference of Tl⁺ on K⁺ transport across these tissues may contribute to Tl⁺ toxicity.

Brain fluorodeoxyglucose positron emission tomography (¹8FDG PET) in patients with acute thallium intoxication.

OBJECTIVE: Thallium toxicity induces cellular injury through impaired Na-K-ATPase activity. The aim of this study was to investigate functional imaging and the long-term clinical-imaging correlations of thallium toxicity. MATERIALS AND METHODS: We measured thallium concentrations in blood, urine, stools, and hair of a 48-year-old woman and a 52-year-old man (patients 1 and 2) in the first 3 months after exposure to thallium containing water, and studied their neuropsychological functions. Using fluorodeoxyglucose positron emission tomography ((18)FDG PET) scans, we examined the brain involvement and correlated the image findings with the clinical presentations. RESULTS: On the 1st, 30th, and 61st days after exposure, the thallium concentrations in patient 1 were 2056, 311, and 7.5 µg/L in the blood, and 11400, 4570, and 36.4 µg/L in the urine. The concentrations in patient 2 were 956, 235, and 15.6 µg/L in the blood, and 11900, 2670, and 101 µg/L in the urine. On the 40th, 50th and 89th days after exposure, the thallium concentration in the stools were 21.6, 3.6, and 0.35 µg/g in patient 1, and 22.2, 3.2, and 0.37 µg/g in patient 2. Executive function, perceptual motor speed, and learning memory were initially abnormal but recovered particularly within the first year. The first (18)FDG PET studies of both patients disclosed a decreased uptake of glucose metabolism in the cingulate gyrus, bilateral frontal, and parietal lobes 2-5 months after exposure. The follow-up (18)FDG PET scan of patient 2 revealed a partial recovery. CONCLUSION: This study indicates that damage to the central nervous system after acute thallium poisoning may be reversible after a long-term follow-up. Brain (18)FDG PET demonstrated the brain involvement and was correlated with cognitive impairment.

Genetic toxicology of thallium: a review.

This review summarizes the current knowledge about the general toxicity of thallium (Tl) and its environmental sources, with special emphasis placed on its potential mutagenic, genotoxic, and cytotoxic effects on both eukaryotic and prokaryotic cells. Tl is a nonessential heavy metal that poses environmental and occupational threats as well as therapeutic hazards because of its use in medicine. It is found in two oxidation states, thallous (Tl(+)) and thallic (Tl(3+)), both of which are considered highly toxic to human beings and domestic and wild organisms. Many Tl compounds are colorless, odorless and tasteless, and these characteristics, combined with the high toxicity of TI compounds, have led to their use as poisons. Because of its similarity to potassium ions (K(+)), plants and mammals readily absorb Tl(+) through the skin and digestive and respiratory systems. In mammals, it can cross the placental, hematoencephalic, and gonadal barriers. Inside cells, Tl can accumulate and interfere with the metabolism of potassium and other metal cations, mimicking or inhibiting their action. The effects of Tl on genetic material have not yet been thoroughly explored, and few existing studies have focused exclusively on Tl(+). Both in vivo and in vitro studies indicate that Tl compounds can have a weak mutagenic effect, but no definitive effect on the induction of primary DNA damage or chromosomal damage has been shown. These studies have demonstrated that Tl compounds are highly toxic and lead to changes in cell-cycle progression.

A high-throughput screening campaign for detection of ca(2+)-activated k(+) channel activators and inhibitors using a fluorometric imaging plate reader-based tl(+)-influx assay.

The intermediate-conductance Ca(2+)-activated K(+) channel (KCa3.1) has been proposed to play many physiological roles, and modulators of KCa3.1 activity are potentially interesting as new drugs. In order to identify new chemical scaffolds, high-throughput screening (HTS) assays are needed. In the current study, we present an HTS assay that has been optimized for the detection of inhibitors as well as activators of KCa3.1 in a combined assay. We used HEK293 cells heterologously expressing KCa3.1 in a fluorescence-based Tl(+) influx assay, where the permeability of potassium channels to Tl(+) is taken advantage of. We found the combined activator-and-inhibitor assay to be robust and insensitive to dimethyl sulfoxide (up to 1%), and conducted an HTS campaign of 217,119 small molecules. In total, 224 confirmed activators and 312 confirmed inhibitors were found, which corresponded to a hit rate of 0.10% and 0.14%, respectively. The confirmed hits were further characterized in a fluorometric imaging plate reader-based concentration-response assay, and selected compounds were subjected to secondary testing in an assay for endogenous KCa3.1 activity using human erythrocytes (red blood cell assay). Although the estimated potencies were slightly higher in the RBC assay, there was an overall good correlation across all clusters. The campaign led to the identification of several chemical series of KCa3.1 activators and inhibitors, comprising already known pharmacophores and new chemical series. One of these were the benzothiazinones that constitute a new class of highly potent KCa3.1 inhibitors, exemplified by 4-{[3-(trifluoromethyl)phenyl]methyl}-2H-1,4-benzothiazin-3(4H)-one (NS6180).

Extracorporeal treatment for thallium poisoning: recommendations from the EXTRIP Workgroup.

BACKGROUND: The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatment (ECTR) in poisoning. To test and validate its methods, the workgroup reviewed data for thallium (Tl). METHODS: After an extensive search, the co-chairs reviewed the articles, extracted the data, summarized findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and RAND/UCLA Appropriateness Method to quantify disagreement. Blinded votes were compiled, returned, and discussed during a conference call. A second vote determined the final recommendations. RESULTS: Forty-five articles met inclusion criteria. Only case reports and case series were identified, yielding a very low quality of evidence for all recommendations. Data on 74 patients, including 11 who died, were abstracted. The workgroup concluded that Tl is slightly dialyzable and made the following recommendations: ECTR is recommended in severe Tl poisoning (1D). ECTR is indicated if Tl exposure is highly suspected on the basis of history or clinical features (2D) or if the serum Tl concentration is >1.0 mg/L (2D). ECTR should be initiated as soon as possible, ideally within 24-48 hours of Tl exposure (1D), and be continued until the serum Tl concentration is <0.1 mg/L for a minimal duration of 72 hours (2D). CONCLUSION: Despite Tl's low dialyzability and the limited evidence, the workgroup strongly recommended extracorporeal removal in the case of severe Tl poisoning.

Gamma radiation measurements and Monte Carlo computations following myocardial perfusion imaging with 201Tl.

In the current study, the time-dependent retention of (201)Tl-thallous chloride (111 MBq) was measured in a 56-y-old man undergoing myocardial perfusion imaging. For 23 d following the (201)Tl injection, total-body retained activity was measured by (i) in situ gamma spectrometry using a portable high-purity germanium (HPGe) detector and (ii) ex vivo urine radioassay using a shielded HPGe detector. The time-dependent decrease in total-body activity followed a monoexponential function, exp(-0.011 t), with an excellent correlation (R(2)=0.9988) between the experimental data and the fitted values. The effective half-life, Teff, of (201)Tl (physical half-life, Tph: 72.9 h) was therefore 63 h and the biological half-life, Tb, 463 h=19.3 d, identical to those measured in the same patient in 1997 (i.e. 14 y ago). The time-dependent decrease in the urine activity concentration, which followed a monoexponential function, exp(-0.0115 t), corroborated the foregoing results. The correlation (R(2)=0.9939) between the experimental data and the fitted values was again excellent. The effective half-life, Teff, was 60.26 h and the biological half-life, Tb, 348 h=14.5 d. Monte Carlo simulation using a simple model of the patient as a unit-density cylinder filled with water and containing a uniform distribution of (201)Tl yielded photon flux results in reasonable agreement with the measured data.

[Hair as a study object in case of poisoning with heavy metal salts].

The objective of the present work was to analyse the results of morphological studies of hair taken from the children with suspected thallium poisoning. The findings obtained by isoelectrofocusing, spectroscopy, and scanning electron microscopy were compared with the relevant literature data. Original investigations included a comparative microstructural study along the hair length and cross section. We failed to observe formation of black-purple structures in the hair bulb and root region of the shaft usually associated with thallium poisoning. It is concluded that thallium poisoning can not be diagnosed based on the presence of a black pigment, knob-like swellings, and spindle-shaped bulbs since they are normal elements of healthy hair. More sensitive methods for the determination of trace elements and their combination with morphological investigations are needed for the definitive diagnosis of thallium poisoning.

Additive effect of DL-penicillamine plus Prussian blue for the antidotal treatment of thallotoxicosis in rats.

DL-penicillamine (DL-P) and Prussian blue (PB) given alone or in combination were tested as possible treatments against acute thallium toxicity. Rats were intoxicated by i.p. injection of thallium (I) acetate at LD(50) (32 mg/kg). A day later, pharmacological treatment was administered until day 4 as follows: (1) vehicles, (2) PB 50mg/kg, by oral route, twice a day, (3) DL-P 25mg/kg i.p. route, twice daily and (4) PB+DL-P. The Estimated Probability Survival (EPS) was recorded during the experiment for each treatment. DL-P alone did not show a significant effect on survival. However, when it was used in combination with PB, it increased the survival significantly (EPS=0.8, P<0.05) as compared to the control group (EPS=0.4). In a different experiment, using 16 mg/kg of Thallium I acetate, the metal levels were analyzed in blood, body organs and brain regions after treatments. DL-P given alone decreased slightly the thallium content in blood, organs and brain. Meanwhile, its administration in combination with PB diminished the thallium levels significantly (P<0.05) in the majority of tissues, at levels lower than those achieved in the PB group. Those results indicate that DL-P administered alone did not prevent the mortality nor accumulation of the metal in body tissues. Its combination with PB could be considered an alternative antidotal treatment in thallium toxicity, because this chelating agent given alone did not cause thallium redistribution to the brain. When given in combination with PB it has an additive effect in the treatment of acute thallotoxicosis.

KCNQ2/3 openers show differential selectivity and site of action across multiple KCNQ channels.

KCNQ2/3 voltage-gated potassium channels conduct low-threshold, slowly activating and non-inactivating currents to repolarize the neuronal resting membrane potential. The channels negatively regulate neuronal excitability and KCNQ2/3 openers are efficacious in hyperexcited states such as epilepsy and pain. We developed and utilized thallium influx assays to profile novel KCNQ2/3 channel openers with respect to selectivity across KCNQ subtypes and on requirement for tryptophan 236 of KCNQ2, a critical residue for activity of the KCNQ opener retigabine. Using distinct chemical series of openers, a quinazolinone series showed relatively poor selectivity across multiple KCNQ channels and lacked activity at the KCNQ2(W236L) mutant channel. In contrast, several novel benzimidazole openers showed selectivity for KCNQ2/3 and KCNQ2 and retain activity at KCNQ2(W236L). Profiling of several hundred KCNQ2/3 openers across multiple diverse chemical series revealed that openers show differential degrees of selectivity across subtypes, with selectivity most difficult to achieve against KCNQ2. In addition, we report the significant finding that KCNQ openers can pharmacologically differentiate between homomeric and heteromeric channels containing subtypes in common. Moreover, most openers assayed were dependent on the W236 for activity, whereas only a small number appear to use a distinct mechanism. Collectively, we provide novel insights into the molecular pharmacology of KCNQ channels by demonstrating differential selectivity and site of action for KCNQ2/3 openers. The high-throughput thallium influx assays should prove useful for rapid characterization of KCNQ openers and in guiding efforts to identify selective compounds for advancement towards the clinic.

Effect of illite and birnessite on thallium retention and bioavailability in contaminated soils.

The influence of illite and birnessite (δ-MnO(2)) amendments on the retention and bioavailability of Tl in contaminated soils was investigated. The efficiency of both phases was evaluated using Tl uptake by white mustard (Sinapis alba L.), sequential extraction and sorption experiments. The obtained data demonstrate that the application of birnessite can effectively transform Tl from the labile (easily mobilizable) fraction to its reducible form, thus lowering Tl bioavailability in soil and subsequent accumulation by plants. The Mn oxide added to the soils reduced substantially Tl uptake; Tl levels in the plants decreased by up to 50%, compared to the non-amended soil. The effect of illite on the immobilization and uptake of Tl was less pronounced, and in the carbonate-rich Leptosol has not been proved at all, suggesting the importance of bulk soil mineralogy and nature of the soil sorption complex on the behavior of this amendment. Therefore, the general applicability of illite for Tl stabilization in soils seems to be limited and strongly dependent on soil composition. In contrast, the use of birnessite like soil additive might be an efficient and environment-friendly solution for soil systems contaminated with Tl.

[Transport of monovalent thallium across the membrane of oocyte of the lamprey Lampetra fluviatilis].

Mechanisms of transport of monovalent thallium across the membrane of oocyte of the lamprey Lampetra fluviatilis were studied by using 204Tl. Transport of Tl+ in lamprey oocytes has been shown to be realized by at least two pathways: through Na/K-pump and by the mechanism of Na,K,Cl-cotransport. In the standard Ringer solution (mM): 4 KCl, 140 NaCl, 0.5 CaCl2, 5 glucose, 10 Tris-HCl--in the presence of oubain, the coefficient of the 204Tl stationary distribution (cell/medium) was within the range of 2.3-2.5, while the time necessary to reach its 50 % value amounted to 40-5 min at 20 degrees C. In potassium-free media, transport of 204Tl via Na/K-pump was described by simple kinetis with saturation and was characterized by the value V(max) = 520 pmol/(cell x h) and K(M) = 0.3 mM. In the presence of 4 mM K+ and 0.1 mM/l Tl+, the oubain-sensitive Tl+ flow decreased to 75 pmol/(cell x h). At activation of the mechanism of Na,K,Cl-cotransport by the outer Na+ (in Na-NMDG media of different composition) the total inflow of Tl+ reached 193 +/- 20 pmol/(cell x h), while the butamenide-sensitive component--119 +/- 12 pmol/(cell x h) with K(M) for Na+ about 20 mM. In the incubation media with variable concentration of chloride ions (replacement of Cl- by NO3(-)) the total Tl+ flow reached 220 +/- 21, while via the mechanisms of Na,K,Cl-cotransport--87 +/- 8 pmol/(cell x h). Under our experimental conditions, mechanisms of active transport and Na,K,Cl-cotransport accounted for 94% of the Tl+ inflow. The potassium channels that usually are also permeable to monovalent thallium ions were not revealed.