Adverse pulmonary effects after oral exposure to copper, manganese and mercury, alone and in mixtures, in a Spraque-Dawley rat model.

The rise in respiratory disease has been attributed to an increase in environmental pollution. Heavy metals contribute to environmental contamination via air, water, soil and food. The effects of atmospheric exposure to heavy metals on pulmonary structure and function have been researched, but the effects through drinking water have been neglected. The aim of this study was to investigate the potential in vivo alterations in the pulmonary tissue of male Sprague-Dawley rats after a 28-day oral exposure to copper (Cu), manganese (Mn) and mercury (Hg), alone and in mixtures, at 100 times the World Health Organization's (WHO) safety limit for each heavy metal in drinking water. Forty-eight male Sprague-Dawley rats were randomly divided into eight groups (n = 6): control, Cu, Mn, Hg, Cu + Mn, Cu + Hg, Mn + Hg and Cu, Mn + Hg. The morphology of lung tissue and the bronchioles were evaluated using light- and transmission electron microscopy. For all exposed groups, morphological changes included thickened inter- and intra-alveolar spaces, stratified epithelium, disrupted smooth muscle and early fibrosis and desquamation of the epithelia of the bronchioles to varying degrees. In all exposed groups, ultrastructurally, an increase in disarranged collagen and elastin fibers, nuclear membrane detachment, chromatin condensation, indistinct nucleoli and an increase in collagen fiber disarrangement was observed. This study has identified that oral exposure to Cu, Mn and Hg and as part of mixtures caused pathogenesis due to inflammation, cellular damage and fibrosis with Mn + Hg being the most potent heavy metal group.

Investigating the effect of the heavy metals cadmium, chromium and lead, alone and in combination on an endothelial cell line.

Heavy metals are natural elements characterized by their relatively large atomic mass as well as high density. It can be introduced into the ecosystem by the mining of heavy metals from deep within the earth's crust, thereby exposing the metals into air and water systems. Cigarette smoke is another source of heavy metal exposure and has been shown to have carcinogenic, toxic and genotoxic properties. Cadmium, lead, and chromium are the most abundant metals found in cigarette smoke. In response to tobacco smoke exposure, endothelial cells release inflammatory and pro-atherogenic cytokines that are linked to endothelial dysfunction. Endothelial dysfunction is directly related to the production of reactive oxygen species, leading to endothelial cell loss through necrosis and/or apoptosis. The current study aimed to investigate the effect of cadmium, lead, and chromium, alone and as part of metal mixtures, on endothelial cells. The EA.hy926 endothelial cell line was exposed to different concentrations of each of these metals and their combinations and analyzed using flow cytometric analyses with Annexin V. A clear trend was seen with the Pb + Cr as well as the triple combination group with the significant increase of early apoptotic cells. Scanning electron microscopy was used to study possible ultrastructural effects. Morphological changes observed with scanning electron microscopy included cell membrane damage and membrane blebbing at certain metal concentrations. In conclusion, the exposure of endothelial cells to cadmium, lead, and chromium, caused a disruption in cellular processes and morphology, possibly diminishing the protective ability of endothelial cells.

Adverse effects of copper, manganese and mercury, alone and in mixtures on the aorta and heart of Spraque-Dawley rats.

Cardiovascular diseases (CVD) are a common global cause of death and are therefore a major health concern. Inhaled or ingested environmental heavy metals contribute to the development of CVD. The aim of this study was to address the limited information available on the effect of relevant dosages of metals in mixtures. Three metals with reported effects on the cardiovascular system (CVS) were identified, and these metals were copper (Cu), manganese (Mn) and mercury (Hg). In Sprague-Dawley rats, the adverse effects of copper (Cu), manganese (Mn) and mercury (Hg), alone and as part of mixtures, on the blood parameters, the aorta and heart were investigated. Forty-eight male Sprague-Dawley rats were randomly divided into eight groups (n = 6): control, Cu, Mn, Hg, Cu + Mn, Cu + Hg, Mn + Hg and Cu, Mn + Hg. The seven experimental groups received the metal mixtures at 100 times the World Health Organisation (WHO) safety limit for drinking water (2 mg/L for Cu, 0.4 mg/L for Mn and 0.06 mg/L for Hg) via oral gavage for 28 days. After 28 days, compared with the control, red blood cell levels were increased for Cu + Hg. All other measured blood parameters were unchanged. Morphological changes in the tunica media were connective tissue deposition and an abundance of collagen type I in the metal exposed aortic tissues. In the cardiac tissue of metal-exposed rats, changes in the cardiomyocyte and myofibrillar arrangement, with an increase in collagen type I and III was observed. Ultrastructurally, the aortic collagen and elastin band arrangement and the cardiac mitochondrial and myofibrillar arrangement and structures were altered in the experimental groups. These changes indicated that exposure to these metals in rats caused minor changes in the blood parameters, however, the changes in tissue and cellular structure indicated an increased risk for the development of CVD.

Investigating the ultrastructural and viscoelastic characteristics of whole blood after exposure to the heavy metals cadmium, lead and chromium, alone and in combination.

In recent years, heavy metal exposure has become a serious health concern as more humans are being exposed to heavy metals on a daily basis. Most of the environmental contamination and human exposure result from anthropogenic activities such as mining and smelting. The industrial and agricultural sectors also play a big role. Cigarette smoke in particular contains trace amounts of heavy metals that put chronic smokers at serious risk. Previous studies have determined that there is a strong correlation between heavy metal exposure and adverse effects on the coagulation system. The aim of this study was to investigate the effect of cadmium, lead and chromium alone and in combination on erythrocytes and fibrin networks that form part of the coagulation system as well as the viscoelastic properties of thrombus formation by using thromboelastography®. The choice of metals for this study was based on a previous study that compared the levels of metals between smokers and nonsmokers and found significantly higher levels of cadmium, lead and chromium in the platelet-rich fibrin of smoking individuals. Scanning electron microscopy analysis revealed that the cadmium and chromium combination groups caused the highest degree of echinocyte formation and fibrin network alterations. These findings were supported by the thromboelastography® analysis that indicated a significant decrease in reaction-time and split point values for the chromium-containing group, suggesting a shorter initiation time for clot formation. The findings of this study support the hypothesis that the coagulation pathway is a potential target for heavy metal toxicity.

Whole blood ultrastructural alterations by mercury, nickel and manganese alone and in combination: An ex vivo investigation.

The distribution of metals across the environment is increasingly becoming a major concern as they not only pollute the environment but also pose a danger to humans and animals. Human exposure to heavy metals often occurs as a combination of metals the synergistic effects of which can be more toxic than a single metal. The aim of this study was to investigate the effects that the metals mercury (Hg), nickel (Ni) and manganese (Mn) alone and in combination have on erythrocyte morphology and other components of the coagulation system using the haemolysis assay, scanning electron microscopy (SEM), and confocal laser scanning microscopy. Human blood was exposed to the heavy metals ex vivo, and percentage haemolysis was determined. Ultrastructural analysis of erythrocytes, platelets and fibrin networks was performed using SEM. Analysis of phosphatidylserine (PS) flip-flop was determined using confocal laser scanning microscopy. At the highest concentration of 10,000× the World Health Organization safety limit, all the metals caused haemolysis. The results showed that the exposure of erythrocytes to Hg alone and in combination with other metals displayed more haemolysis compared to Ni and Mn alone and in combination. Components of the coagulation system showed ultrastructural changes, including the formation of echinocytes and the activation of platelets with all single metals as well as the combinations. Confocal laser scanning microscopy analysis showed the presence of PS on the outer surface of the echinocytes that were exposed to metals alone and in combination. It can, therefore, be concluded that these heavy metals have a negative impact on erythrocytes and the coagulation system.

Evidence against solar influence on nuclear decay constants.

The hypothesis that proximity to the Sun causes variation of decay constants at permille level has been tested and disproved. Repeated activity measurements of mono-radionuclide sources were performed over periods from 200 days up to four decades at 14 laboratories across the globe. Residuals from the exponential nuclear decay curves were inspected for annual oscillations. Systematic deviations from a purely exponential decay curve differ from one data set to another and are attributable to instabilities in the instrumentation and measurement conditions. The most stable activity measurements of alpha, beta-minus, electron capture, and beta-plus decaying sources set an upper limit of 0.0006% to 0.008% to the amplitude of annual oscillations in the decay rate. Oscillations in phase with Earth's orbital distance to the Sun could not be observed within a 10-6 to 10-5 range of precision. There are also no apparent modulations over periods of weeks or months. Consequently, there is no indication of a natural impediment against sub-permille accuracy in half-life determinations, renormalisation of activity to a distant reference date, application of nuclear dating for archaeology, geo- and cosmochronology, nor in establishing the SI unit becquerel and seeking international equivalence of activity standards.

The operation of an ionization chamber with depleted gas for radioactivity measurement: Calibration procedure and utilising normalized manufacturer's radionuclide factors.

At the National Metrology Institute of South Africa (NMISA) absolute activity measurements of γ-emitting radionuclides are maintained for longevity on a secondary standard ionization chamber. Because the ionization chamber has lower gas pressure than that normally produced by the manufacturer, this paper focuses attention on explaining a normalization scheme devised to allow NMISA to make use of the manufacturer's supplied radionuclide calibration factors when necessary. The applicability of the procedure is justified through analysis of some results from a comprehensive simulation of the chamber undertaken in an independent study. Comparisons of the derived normalized calibration factors against those obtained through measurement at NMISA are made for a variety of radionuclides.

Activity determination of 18F using liquid scintillation beta-efficiency extrapolation and non-extrapolation methods.

The absolute activity of 18F was determined using 4πß-γ liquid scintillation coincidence counting using beta-efficiency extrapolation. An ionization chamber factor was determined for use during a SIRTI comparison, for which results are presented. A non-extrapolation method based on a detection efficiency analysis was also employed using an adaptation of the double-phototube coincidence efficiency for a threshold above the second monopeak. Results and uncertainty budgets for the two methods are presented and discussed.

Oxidative and haemostatic effects of copper, manganese and mercury, alone and in combination at physiologically relevant levels: An ex vivo study.

Water contamination with metals due to anthropogenic activity is increasing and subsequent exposure increases the risk of associated toxicity. Exposure is not limited to a single metal but usually involves mixtures of different metals at different concentrations. Little is known about the contribution of this type of exposure, in humans, to the development of non-communicable diseases such as cardiovascular disease, and an increased risk to thrombosis. The World Health Organization has established limits for metal levels in drinking water and this includes levels for copper (Cu), manganese (Mn) and mercury (Hg). In this study, at 100X these limits, the ability of the metals' oxidative effects as catalysts of the Fenton reaction and/or ability to bind glutathione (GSH) were determined. The haemostatic effects of these metals, alone and in combination, at the World Health Organization limit were then evaluated. The ultrastructural and viscoelastic alterations of exposed ex vivo whole blood were also evaluated using scanning electron microscopy and thromboelastography® (TEG), respectively. Cu, alone and in combination with Mn and/or Hg, induced hydroxyl radical formation and reduced GSH levels. Ex vivo exposure caused deformation of erythrocytes and accelerated platelet activation especially for Cu, alone and in combination, with Mn. Reduction in the lysis potential of the clot was also observed for all combinations, especially Cu in combination with Hg as well as Mn alone. Although the TEG findings were not statistically significant, the trends indicate that the exposure to these metals, alone and in combination, adversely affects thrombus formation in ex vivo blood, thereby potentially increasing the risk in exposed individuals for thrombosis.

Activity determination of (59)Fe by 4π beta-gamma counting using liquid scintillation in the beta channel.

This paper reports on absolute activity measurements of iron-59 made at the National Metrology Institute of South Africa (NMISA) via 4π(LS)ß-γ coincidence counting. The exercise formed part of an Asia Pacific Metrology Program (APMP) regional key comparison. Source data were analysed by the extrapolation technique for a number of gamma-ray window settings. In addition, a feasibility study was undertaken on a second technique; a non-extrapolation method based on a detection efficiency analysis. The reported activity concentration of the (59)Fe solution was determined with a relative uncertainty of 0.28% (k=1), the uncertainty being due mainly to the rate vs. efficiency fitting process. The result from the non-extrapolation method was lower than that given by extrapolation by 0.33%, within two standard deviations. Possible reasons for the small discrepancy are discussed.

Weight and frequency effect on spinal loading in a bricklaying task.

In manual materials handling jobs a reduction in the weight of materials often concurs with an increase in handling frequency. The effect of weight and inversely related frequency on spinal load was studied in two bricklaying tasks: building the skin and the floor of a steel ladle. In both tasks five subjects laid bricks of varying weight and frequency (obtained from field observations). The load parameters investigated were peak values and time integrals of the compressive force on the L5-S1 motion segment and stature loss, which is assumed to reflect motion segment creep due to compression. Peak compression was found to increase at higher brick weights. No differences in integrated compression were observed among four out of five combinations of weight and frequency (both in skin and floor building). Laying bricks for a fixed period of 47 min yielded average stature losses of 2.0 3.6 mm. Differences in stature loss among weight-frequency conditions were not significant. In conclusion, at lower weights peak loads decrease, but the benefit of this should be doubted because the frequency of exposure to these peak loads was found to increase. Moreover, this increase was such that no effects were found on spinal load estimates that incorporate both magnitude and time aspects of the load, like time-integrated compression and stature loss.

Successful treatment by plasmapheresis of respiratory insufficiency in myasthenia gravis.

A 27-year-old man with myasthenia gravis developed a severe myasthenic crisis with respiratory insufficiency. In spite of high iv doses of pyridostigminebromide and corticosteroids, mechanical ventilation remained necessary. Treatment with plasma exchange grossly decreased the serum level of antibodies against acetylcholine receptor protein and caused an immediate clinical improvement. The respiratory assistance could be terminated and muscle strength increased substantially. Plasmapheresis seemed to be of definite benefit in the treatment of this acute crisis of myasthenia gravis.