Effects of DC Magnetic Fields on Magnetoliposomes.

The potential use of magnetic nanoparticles (MNPs) in biomedicine as magnetic resonance, drug delivery, imagenology, hyperthermia, biosensors, and biological separation has been studied in different laboratories. One of the challenges on MNP elaboration for biological applications is the size, biocompatibility, heat efficiency, stabilization in physiological conditions, and surface coating. Magnetoliposome (ML), a lipid bilayer of phospholipids encapsulating MNPs, is a system used to reduce toxicity. Encapsulated MNPs can be used as a potential drug and a gene delivery system, and in the presence of magnetic fields, MLs can be accumulated in a target tissue by a strong gradient magnetic field. Here, we present a study of the effects of DC magnetic fields on encapsulated MNPs inside liposomes. Despite their widespread applications in biotechnology and environmental, biomedical, and materials science, the effects of magnetic fields on MLs are unclear. We use a modified coprecipitation method to synthesize superparamagnetic nanoparticles (SNPs) in aqueous solutions. The SNPs are encapsulated inside phospholipid liposomes to study the interaction between phospholipids and SNPs. Material characterization of SNPs reveals round-shaped nanoparticles with an average size of 12 nm, mainly magnetite. MLs were prepared by the rehydration method. After formation, we found two types of MLs: one type is tense with SNPs encapsulated and the other is a floppy vesicle that does not show the presence of SNPs. To study the response of MLs to an applied DC magnetic field, we used a homemade chamber. Digitalized images show encapsulated SNPs assembled in chain formation when a DC magnetic field is applied. When the magnetic field is switched off, it completely disperses SNPs. Floppy MLs deform along the direction of the external applied magnetic field. Solving the relevant magnetostatic equations, we present a theoretical model to explain the ML deformations by analyzing the forces exerted by the magnetic field over the surface of the spheroidal liposome. Tangential magnetic forces acting on the ML surface result in a press force deforming MLs. The type of deformations will depend on the magnetic properties of the mediums inside and outside the MLs. The model predicts a coexistence region of oblate-prolate deformation in the zone where χ = 1. We can understand the chain formation in terms of a dipole-dipole interaction of SNP.

Neurotoxic character of thimerosal and the allometric extrapolation of adult clearance half-time to infants.

The decomposition rate of organomercurials and the potency of the blood-brain barrier increase with the size of the organic radical. Thus methylmercury damages the brain more than thimerosal does, and when intake limits set for methylmercury are applied to thimerosal the safety margin is increased even if the clearances were the same. However, the clearance half-time of ethylmercury in adults is about one-third of the 50 days' clearance half-time of methylmercury given for 60 kg body weight. Moreover, because metabolic rates (e.g. basal metabolism, daily loss of mercury in per cent of body burden) in different weight groups are related to the fractional power of body weight (rule of allometry), mercury clears from the infant body faster than from the adult body. Blood mercury concentrations observed after vaccination showed agreement with allometrically extrapolated concentrations.

Three cases of methylmercury intoxication which eluded correct diagnosis.

Three casual workers engaged in the production of mercuric acetate were admitted to hospital within 22 calendar days of each other, respectively 30, 48 and 5 days after their last working day. The workers served the same reactor in which elemental mercury was oxidized by peroxide and mercuric acetate was formed by the reaction of mercuric oxide with acetic acid. The diagnosis of mercury vapour intoxication of the first two patients was made 21 and 16 days after their admission when the third patient was admitted and hospitals were informed about their exposure. This diagnosis was made without considering: (a) that the observed signs were characteristic of methylmercury intoxication and are rarely present in mercury vapour intoxication; (b) the degree of deterioration after removal from exposure implicated methylmercury; (c) that blood mercury concentrations extrapolated to the last day at work were in the range, which had been associated with severe intoxication in the Iraq methylmercury epidemic; (d) at the time of the first blood mercury estimations the blood urinary mercury concentration ratios were 11.2, 5.4 and 2.4 while this ratio is below 0.5 in mercury vapour intoxication or in workers exposed to mercury vapour.

Lead poisoning from retained lead projectiles. A critical review of case reports.

Case reports demonstrate that embedded lead projectiles (bullets, pellets) have the potential to cause lead poisoning. They also show that the relationship between blood lead concentration and lead poisoning is the same as in lead poisonings of occupational origin and that latent periods between lodgement and the onset of lead poisoning varies from less than a half year to several decades. Nevertheless neither the quantitative relationships between projectiles and blood concentrations nor the number at risk and the number affected are known. The aim of this review is to show the limitations of case studies through the analysis of negative and positive case reports, diagnostic and monitoring methods, differences between bullets and pellets, and factors affecting the disintegration of projectiles and the distribution of released lead.

Epidemiological and experimental aspects of metal carcinogenesis: physicochemical properties, kinetics, and the active species.

The carcinogenic properties of selected metals and their compounds are reviewed to provide a useful reference for existing knowledge on relationships between physical and chemical forms, kinetics and carcinogenic potential and between epidemiology, bioassays, and short-term tests. Extensive consideration is given to arsenic, beryllium, cadmium, chromium, lead, and nickel. Other metals such as antimony, cobalt, copper, iron, manganese, selenium, and zinc are discussed briefly.

A versatile mercury vapour generating system suitable for long-term inhalation experiments.

A mercury vapour generating system is described that is based on the reduction of HgCl2 by SnCl2 in the input airstream of the inhalation chamber. The solutions of the two chemicals are pumped by peristaltic pumps from reservoirs through a miniature mixing chamber into the upper part of a sloping glass tube (reduction chamber) through which air is sucked into the inhalation assembly. The liquid flows down the slope and through a port into a Quickfit flask. Reservoirs can be filled and the collecting flask emptied without interruption of exposure. The desired vapour concentration is achieved by varying the rate of mercury injection and the rate of airflow. Concentration in the inhalation chamber can be measured by passing air through a mercury vapour monitor or by radioactivity when 203HgCl2 is used and a known volume of air is passed through a hopcalite absorber. Operation instructions and an experimental example with mice are given.

The effects of dose of elemental mercury and first-pass circulation time on exhalation and organ distribution of inorganic mercury in rats.

The lung plays a major role in the removal of dissolved elemental mercury (Hg0) from the bloodstream. During the first passage through the lung after an intravenous dose of Hg0 dissolved in aqueous buffer, from 10 to 17% was exhaled depending on the dose (0.11 or 1.1 micrograms Hg/rat) and the injection site (jugular versus tail vein). Furthermore, evidence is presented that subsequent exhalation over the next 50 s, before the rats were killed and the mercury determined in the lung at that time, was largely Hg0-extracted during the first pass. The total mercury extracted during the 60 s period was in the range of 40-49% of the dose. The oxidation of Hg0 to Hg2+ in red cells is important in limiting the availability of Hg0 to certain tissues. Thus, after a short residence time in blood (0.6 s after jugular vein injection), 12.9-17% is exhaled in the first pass as compared to 10.4-12.2% with a longer residence time (1.8 s after tail vein injection). Furthermore, there was a general tendency, even at 60 s after dosing, for certain tissues - lung, brain, and heart - to have higher values after dosing from the jugular vein. It was estimated that the half-time for oxidation was 3.3 s. Our results confirm previous observations that the form of inorganic mercury greatly influences the short-term deposition in certain tissues. Thus as compared to Hg2+, administration of Hg0 increases lung levels 5-10-fold; brain, 4-fold; and heart, 3-fold. Blood levels are lower after Hg0, particularly after the higher dose. Such findings are consistent with a model wherein Hg0 is in part oxidized by red blood cells, the remainder rapidly diffusing in tissues where it is also oxidized to Hg2+.

Persistent mercury in nerve cells 16 years after metallic mercury poisoning.

A male subject, after exposure to mercury metal at work in 1968, developed classical signs of mercurialism from which he made a slow clinical recovery. He subsequently developed psychoneurotic symptoms and became an alcoholic; he never returned to work and died in 1984. No histological changes relevant to mercury intoxication were found in the brain, but staining by Danscher & Schroeder's method for mercury showed many positively staining lysosomal dense bodies in a large proportion of nerve cells, and the presence of mercury was confirmed by elemental X-ray analysis. The mercury content of the brain was increased, much of it being present in colloidal form.

The effect of sodium chromate pretreatment on mercuric chloride-induced nephrotoxicity.

Sodium chromate (20 mg/kg, s.c.), which in male rats inflicted necrotic damage mainly in the P1 region (proximal part of the proximal convoluted tubules), protected against proximal tubular necrosis induced by 0.5 or 3.0 mg Hg2+/kg in the P2 (distal part of the proximal convoluted tubules) and P3 (pars recta part of the proximal tubules) regions. Histochemical staining for mercury indicated that chromate increased mercury deposition in those cells of the P1 region which were unaffected by chromate (had intact brush border) but did not decrease mercury deposition in the most severely affected P3 region. Chromate pretreatment actually increased mercury deposition in the kidneys of animals killed 24 h after the injection of 0.5 mg Hg2+. The protective effect was mutual. Cellular proliferation and fibrosis observed 4-5 days after chromate were prevented by injecting 0.5 mg Hg2+/kg 3 days after chromate treatment.

Comparison of the protection given by selenite, selenomethionine and biological selenium against the renotoxicity of mercury.

The protective effect of selenite, seleno-dl-methionine and biological selenium against the renotoxicity of mercury was tested in rats. As the source of biological selenium, the liver soluble fraction of rats given 60 mumoles/kg selenite 3 days before sacrifice was used. The aim of the experiments was to test whether protective efficiency follows the reported order of ability to form HgSe. Mercury was given subcutaneously in doses of 2.5, 5.0 and 7.5 mumoles/kg HgCl2 and selenium was given in equimolar doses at the same time as Hg2+. Liver soluble fraction, biological selenium or liver soluble fraction supplemented with selenite or seleno-dl-methionine were given orally, while in experiments without liver soluble fraction the two selenium compounds were given subcutaneously. Biological selenium was tested only at the two lower dose levels. Both biological selenium and seleno-dl-methionine decreased the urinary excretion of mercury in the first 48 h, but less so than selenite and only selenite decreased the renal content of mercury at the end of this period. Urinary alkaline phosphatase activity and plasma urea nitrogen at the 2.5 and 5.0 mumoles/kg dose levels decreased in the order of no selenium greater than biological selenium greater than seleno-dl-methionine greater than selenite. As the reported HgSe formation increases in the same order, the experiments support the role of HgSe formation in the protective effect. The degree of necrotic damage in the P2 and P3 regions of the proximal tubular cells increased in the same order as the biochemical indicators at the 5.0 and 7.5 mumoles/kg dose levels.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of treatment with selenite before and after the administration of [75Se]selenite on the exhalation of [75Se]dimethylselenide.

The exhalation of dimethylselenium, as indicated by the respiratory loss of 75Se from injected Na75SeO3, depends not only on the dose, but also on previous exposure. Three days pretreatment with 1.2 mumol/100 g unlabelled selenite increased exhalation of 75Se from 0.1 or 1.2 mumol/100 g Na2 75SeO3 and decreased the retention of 75Se in blood and liver from the higher dose. Similarly the injection of 1.2 mumol/100 g unlabelled selenite 24 h after the last of 3 daily doses of 1.2 mumol/100 g labelled selenite increased the exhalation of 75Se in the following 24 h period. Thus, pre-exposure to selenium increased the exhalation of 75Se by making a higher proportion of the newly injected dose accessible for methylation. The exhaled dimethylselenide, however, is not derived solely from the injected dose, since in pretreated animals, it is possible to demonstrate exchange between injected and deposited selenium.

The potentiation of the non-behavioural effects of amphetamine by carbon disulphide.

In agreement with the inhibition of dopamine-beta-hydroxylase by exposure to CS2, the extension of exposure time from 4 to 16 h increased dopamine concentrations in the hypothalmus and adrenals, and decreased noradrenaline concentration in the hypothalmus. The extension of exposure time also increased the toxicity of amphetamine. In conscious animals the stereotypic activity produced by 6.0 mg/kg and even that of 3.0 mg/kg amphetamine sulphate was suppressed by severe hyperthermia resulting in exhaustion, prostration and eventually death. A 16 h exposure to CS2 did not increase the lethal or hyperthermic effects of amphetamine in rats anaesthetized with 60 mg/kg sodium pentobarbitone. In fact the CS2 exposed rats became more hypothermic than non-exposed rats.

The stimulation and inhibition of the exhalation of volatile selenium.

Administration of methylmercury (1.5-24 mumol kg-1; s.c.) to female rats simultaneously with Na2 75SO3 (0.25 or 24 mumol kg-1; s.c.) causes a dose-dependent increase in the exhalation of dimethylselenide. At the low selenite dose level, exhalation of 75Se over a 24 hr period is about fourfold greater after treatment with 24 mumol kg-1 methylmercury than that (approximately 0.75% of the dose) in the controls, but excretion by other routes (urine, faeces) and the liver and kidney contents of 75Se are not affected significantly. At the higher selenite dose level (24 mumol kg-1) exhalation of 75Se is correlated with the log dose of methylmercury. The faecal and urinary excretion remains essentially unaffected, and in rats treated with 24 mumol kg-1 methylmercury the 75Se contents of the liver, kidneys and blood are reduced by 78%, 86% and 18% respectively. The effects of the alkylmercurial are not specific since, at this selenite dose level, ethylmercury increases the exhalation and decreases the liver and kidney contents of 75Se approximately to the same extent as an equimolar dose of methylmercury. In methylmercury-treated and control animals dosed with 24 mumol kg-1 Na 75SeO3 the exhalation of 75Se is inhibited to the same extent by periodate-oxidized adenosine (PAD; 15 mumol kg-1, i.p.) in the first 6 hr. Later inhibition is less pronounced in methylmercury-treated rats. Under these conditions PAD has little effect on the renal content, but increases the hepatic content of 75Se. It seems, therefore, that the methylation of selenite occurs mainly in the liver and in both control and methylmercury-treated animals, S-adenosylmethionine is the major methyl donor. It is possible that methylmercury does not affect directly the methylation enzyme system but, by competition for protein sulphydryl groups, increases the availability of the intermediary selenide anion.