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At least 19 recordsLinked to original sources
PubMed2004

Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress.

alpha-Lipoic acid (LA), a naturally occurring dithiol compound, has long been known as an essential cofactor for mitochondrial bioenergetic enzymes. Aside from its enzymatic role, in vitro and in vivo studies suggest that LA also acts as a powerful micronutrient with diverse pharmacologic and antioxidant properties. Pharmacologically, LA improves glycemic control, polyneuropathies associated with diabetes mellitus, and effectively mitigates toxicities associated with heavy metal poisoning. As an antioxidant, LA directly terminates free radicals, chelates transition metal ions (e.g. iron and copper), increases cytosolic glutathione and vitamin C levels and prevents toxicities associated with their loss. These diverse actions suggest that LA acts by multiple mechanisms both physiologically and pharmacologically, many of which are only now being explored. Herein, we review the known biochemical properties of LA with particular reference to how LA may be an effective agent to ameliorate certain pathophysiologies of many chronic diseases.

Animals↗
PubMed2001

Blood levels of toxic and essential metals in motor neuron disease.

Toxic and essential metals have been implicated in the pathogenesis of sporadic motor neuron disease (SMND), but attempts to measure blood levels of these metals have led to contradictory results. We, therefore, measured blood levels of various metals using paired SMND/controls. In 20 subjects with SMND (15 males, five females, mean age 56.8 years) and 20 partner controls (15 females, five males, mean age 55.0 years) cadmium, lead, mercury, copper, zinc and selenium levels were measured in blood, plasma and red cells with inductively coupled plasma mass spectrometry and manganese levels with atomic absorption spectrophotometry. Results were analysed using non-parametric tests. Hypo-osmotic red blood cellfragility was estimated in six SMND/control pairs to see if hemolysis could account for increased metal levels. The plasma cadmium level was significantly raised in SMND cases (P = 0.005), but with considerable overlap between SMND and controls. No other metal levels were significantly different, though plasma lead in SMND had a tendency to be higher than controls. No difference in red cell fragility was found between groups. In conclusion, plasma levels of cadmium were raised in this SMND group, but the biological significance of this is uncertain. The measurement of metals in the blood of SMND cases seems unwarrranted for routine diagnostic testing.

Adult↗
PubMed2005

Time-resolved monitoring of heavy-metal intoxication in single hair by laser ablation ICP-DRCMS.

The potential of laser ablation inductively coupled plasma mass spectrometry for the time-resolved analysis of heavy-metal intoxication in human bodies by analysis of hair is demonstrated. As application, we analyzed forensic samples from one individual after Hg intake and from one treated with a Pt-containing cytostatic remedy. Single hairs were analyzed from the hair root to the tip by laser ablation ICP-MS with a spatial resolution of 20 mum (corresponding to approx. 2 h growth of the hair). Sulfur was used as internal standard and was analyzed by using oxygen as reaction gas in the dynamic reaction cell of the ICP-DRCMS. The detection limits for Hg and Pt were found to be 0.3 microg g(-1) and 0.5 ng g(-1), respectively. Standard uncertainties for the quantification results were 10% for Hg and approximately 15 % for Pt. The analyzed hair samples reflected the forensic evidence in both cases. A significant increase of Hg concentration, by a factor of 50, at the time of HgO administration could be shown, and variation of Pt in the hair strands could be used to monitor the time and relative amount of Pt intake by the patient. The investigations also revealed that the concentrations in the outer and the inner parts of the hair varied similarly with time, even though the concentration in the core of the hair is approximately 0.25 that at the surface for both Pt and Hg.

Forensic Medicine↗
PubMed2001

Effect of process parameters upon the dopamine and lipid peroxidation activity of selected MIG welding fumes as a marker of potential neurotoxicity.

There is growing concern over the neurotoxic effects of chronic occupational exposure to metal fume produced by welding. Elevated iron and manganese levels in the brain have been linked to an increase in lipid peroxidation, dopamine depletion and predisposition to the development of a Parkinson's type condition in advanced cases. Chemical and toxicological analysis of selected welding fumes, generated by model processes, were used in order to evaluate their potential to release solutes that promote oxidation of dopamine and peroxidation of brain lipids in cell free assays. This study compared the effect of shield gas, electrode type and voltage/currect upon the dopamine and brain lipid peroxidation potential of selected welding fume, obtained from metal inert gas (MIG) welding systems. Overall, fume extracts were found to enhance dopamine oxidation and inhibit lipid peroxidation. Significant differences were also found in the oxidising potential of fume generated under differing process conditions; it may therefore be possible to determine the potential neurotoxicity of fumes using this system.

Animals↗
PubMed2004

[Nervous system involvement in three children poisoned with thallium].

Three children, aged 5, 10 and 16 years, poisoned with thallium were hospitalized. Two of them suffered from sensory-motor and third from sensory polyneuropathy and additionally in the youngest child severe encephalopathy was observed. The correlations between serum and urine thallium levels and the severity of the symptoms in the course of the disease were positive. The most severe symptoms and the highest thallium level were observed in the youngest child.

Adolescent↗
PubMed2005

Ependymal epithelium disruption after vanadium pentoxide inhalation. A mice experimental model.

The blood-brain barrier (BBB) protects the CNS against chemical insults. Regulation of blood-brain tissue exchange is accomplished by ependymal cells, which possess intercellular tight junctions. Loss of BBB function is an etiologic component of many neurological disorders. Vanadium (V) is a metalloid widely distributed in the environment and exerts potent toxic effects on a wide variety of biological systems. The current study examines the effects of Vanadium pentoxide (V2O5) inhalation in mice ependymal epithelium, through the analysis of the brain metal concentrations and the morphological modifications in the ependymal cells identified by scanning and transmission electron microscopy after 8 weeks of inhalation, in order to obtain a possible explanation about the mechanisms that V uses to enter and alter the CNS. Our results showed that V2O5 concentrations increase from the first week of study, stabilizing its values during the rest of the experiment. The morphological effects included cilia loss, cell sloughing and ependymal cell layer detachment. This damage can allow toxicants to modify the permeability of the epithelium and promote access of inflammatory mediators to the underlying neuronal tissue causing injury and neuronal death. Thus, understanding the mechanisms of BBB disruption would allow planning strategies to protect the brain from toxicants such as metals, which have increased in the atmosphere during the last decades and constitute an important health problem.

Administration, Inhalation↗
PubMed2000

An uncommon cause of lower limb weakness.

We describe a case of a severely mentally disabled patient diagnosed as suffering from Guillain-Barré syndrome and treated with repeated plasma exchange. However, the abrupt onset of a cardiovascular collapse prompted a more in-depth diagnostic workup which demonstrated that the neurologic symptoms were likely to be ascribed to poisoning with heavy metals from a large number of ingested coins and other metallic items.

Aluminum↗
PubMed2005

Analyses of neurobehavioral screening data: benchmark dose estimation.

Zhu et al. (Zhu, Y., Wessel, M., Liu, T., Moser, V.C., 2005. Analyses of neurobehavioral screening data: dose-time-response modeling of continuous outcomes. Regul. Toxicol. Pharmacol. 41, 240-255) have recently applied dose-time-response models to longitudinal or time-course neurotoxicity data, and have illustrated the modeling process using continuous data from a functional observational battery (FOB). Following the work of these authors, the purpose of this paper is to show that the benchmark dose (BMD) method for single time point dose-response data can be generalized and applied to longitudinal data such as those generated in neurotoxicity studies. We propose a statistical procedure called bootstrap method for computing the lower confidence limits for the BMD. We demonstrate the method using three previously published FOB datasets of triethyltin (Moser, V.C., Becking, G.C., Cuomo, V., Frantik, E., Kulig, B., MacPhail, R.C., Tilson, H.A., Winneke, G., Brightwell, W.S., DeSalvia, M.A., Gill, M.W., Haggerty, G.C., Hornychova, M., Lammers, J., Larsson, J., McDaniel, K.L., Nelson, B.K., Ostergaard, G., 1997a. The IPCS study on neurobehavioral screening methods: results of chemical testing. Neurotoxicology 18, 969-1056.) and the models of Zhu et al. (Zhu, Y., Wessel, M., Liu, T., Moser, V.C., 2005. Analyses of neurobehavioral screening data: dose-time-response modeling of continuous outcomes. Regul. Toxicol. Pharmacol. 41, 240-255).

Algorithms↗