Feasibility of measuring zinc in human nails using portable x-ray fluorescence.

A variety of adverse health effects have been identified as resulting from zinc deficiency. Zinc supplementation may therefore be indicated for certain individuals or populations. A rapid and straightforward means of assessing zinc status in humans would be of considerable medical benefit. In this study, the feasibility of measuring zinc levels in human fingernails or toenails using a portable x-ray fluorescence technique was assessed. Whole nail models (or phantoms) were constructed from resin, and dosed with various concentrations of zinc. These different concentration "nails" were cut into small slices of 4.4 ±â€¯0.2 mm width. The combination of these various slices into different arrangements allowed the modeling of different time-dependent zinc exposure scenarios. A portable x-ray fluorescence device was tested using an "open beam" configuration having a beam diameter of ∼9 mm, and using a "weld mask" configuration with the beam width reduced to 2.9 mm. Minimum detection limits were determined to be 0.15 ±â€¯0.01 ppm for the open beam, and 1.13 ±â€¯0.08 ppm when using the weld mask. By scanning across the length of the model nails, it was demonstrated that differences in zinc levels deposited over time could be detected, and that the weld mask configuration was better suited to resolving spatial changes. The x-ray fluorescence approach was found to be highly sensitive for detecting zinc in nail, and capable of differentiating patterns of zinc uptake over time.

Neurotoxic zinc translocation into hippocampal neurons is inhibited by hypothermia and is aggravated by hyperthermia after traumatic brain injury in rats.

Hypothermia reduces excitotoxic neuronal damage after seizures, cerebral ischemia and traumatic brain injury (TBI), while hyperthermia exacerbates damage from these insults. Presynaptic release of ionic zinc (Zn2+), translocation and accumulation of Zn2+ ions in postsynaptic neurons are important mechanisms of excitotoxic neuronal injury. We hypothesized that temperature-dependent modulation of excitotoxicity is mediated in part by temperature-dependent changes in the synaptic release and translocation of Zn2+. In the present studies, we used autometallographic (AMG) and fluorescent imaging of N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) staining to quantify the influence of temperature on translocation of Zn2+ into hippocampal neurons in adult rats after weight drop-induced TBI. The central finding was that TBI-induced Zn2+ translocation is strongly influenced by brain temperature. Vesicular Zn2+ release was detected by AMG staining 1 h after TBI. At 30 degrees C, hippocampus showed almost no evidence of vesicular Zn2+ release from presynaptic terminals; at 36.5 degrees C, the hippocampus showed around 20% to 30% presynaptic vesicular Zn2+ release; and at 39 degrees C vesicular Zn2+ release was significantly greater (40% to 60%) than at 36.5 degrees C. At 6 h after TBI, intracellular Zn2+ accumulation was detected by the TSQ staining method, which showed that Zn2+ translocation also paralleled the vesicular Zn2+ release. Neuronal injury, assessed by counting eosinophilic neurons, also paralleled the translocation of Zn2+, being minimal at 30 degrees C and maximal at 39 degrees C. We conclude that pathological Zn2+ translocation in brain after TBI is temperature-dependent and that hypothermic neuronal protection might be mediated in part by reduced Zn2+ translocation.

Protective effects of zinc chelation in traumatic brain injury correlate with upregulation of neuroprotective genes in rat brain.

Chelation of excessive neuronal zinc ameliorates zinc neurotoxicity and reduces subsequent neuronal injury. To clarify the molecular mechanisms of this neuroprotective effect, we used a focused cDNA array of stress-response genes with zinc chelation (calcium EDTA) in our rat model of fluid percussion brain injury at 2 h, 24 h, and 7 days after injury. In parallel experiments, we compared neuronal cell death in TUNEL-stained brain sections in traumatized rats with and without calcium EDTA treatment. Zinc chelation induced the expression of several neuroprotective genes; neuroprotective gene expression correlated with substantially decreased numbers of TUNEL-positive cells.

Clioquinol effects on tissue chelatable zinc in mice.

Recent evidence for the involvement of zinc in the formation of beta-amyloid plaques in the brain in Alzheimer's disease has led to the establishment of new therapeutic strategies for the degenerative disorder based on metal chelation. The present experiment was conducted on a membrane-permeable zinc chelator, clioquinol (CQ), that has shown potential in initial studies on a mouse model of Alzheimer's disease [1]. The degree of chelatable zinc in mice treated with CQ, delivered by two different routes, was measured using complementary protocols for identifying chelatable zinc: 6-methoxy-8-quinolyl- p-toluenesulfonamide (TSQ) histofluorescence, and selenite autometalography. Mice injected intraperitoneally with CQ showed a dramatic reduction in chelatable zinc in brain, testis, and pancreas. In contrast, mice given CQ orally showed no significant change in levels of chelatable zinc in these tissues. This suggests that CQ administered orally to patients with Alzheimer's disease should not significantly perturb chelatable zinc levels in key organs and may be used over long periods without adverse endocrinological and reproductive effects related to zinc deficiency. In contrast, CQ injected intraperitoneally may be used not only as a tool for investigating chelatable zinc pools but also in a clinical context. For example, injected CQ could be employed in situations requiring the rapid buffering of excessive chelatable zinc following ischemic episodes or brain trauma. Thus, our findings indicate that CQ has considerable potential as a versatile scientific and clinical tool used for selective modulation of zinc pools.