Transition and post-transition metals in exhaled breath condensate.

Water vapor in expired air, as well as dispersed non-volatile components, condense onto a cooler surface after exiting the respiratory tract. This exhaled breath condensate (EBC) provides a dilute sampling of the epithelial lining fluid. Accordingly, the collection of EBC imparts a capacity to provide biomarkers of injury preceding clinical disease. Concentrations of transition and post-transition metals in EBC are included among these endpoints. Iron and zinc are the metals with the highest concentration and are measurable in all EBC samples from healthy subjects; other metals are most frequently either at or below the level of detection in this group. Gender, age, and smoking can impact EBC metal concentrations in healthy subjects. EBC metal concentrations among patients diagnosed with particular lung diseases (e.g. asthma, chronic obstructive disease, and interstitial lung disease) have been of research interest but no definite pattern of involvement has been delineated. Studies of occupationally exposed workers confirm significant exposure to specific metals, but such EBC metal measurements frequently provide evidence redundant with environmental sampling. Measurements of metal concentrations in EBC remain a research tool into metal homeostasis in the respiratory tract and participation of metals in disease pathogenesis. The quantification of metal concentrations in EBC is currently not reliable for clinical use in either supporting or determining any diagnosis. Issues that must be addressed prior to the use of EBC metal measurements include the establishment of both standardized collection and measurement techniques.

Recognition- and reactivity-based fluorescent probes for studying transition metal signaling in living systems.

Metals are essential for life, playing critical roles in all aspects of the central dogma of biology (e.g., the transcription and translation of nucleic acids and synthesis of proteins). Redox-inactive alkali, alkaline earth, and transition metals such as sodium, potassium, calcium, and zinc are widely recognized as dynamic signals, whereas redox-active transition metals such as copper and iron are traditionally thought of as sequestered by protein ligands, including as static enzyme cofactors, in part because of their potential to trigger oxidative stress and damage via Fenton chemistry. Metals in biology can be broadly categorized into two pools: static and labile. In the former, proteins and other macromolecules tightly bind metals; in the latter, metals are bound relatively weakly to cellular ligands, including proteins and low molecular weight ligands. Fluorescent probes can be useful tools for studying the roles of transition metals in their labile forms. Probes for imaging transition metal dynamics in living systems must meet several stringent criteria. In addition to exhibiting desirable photophysical properties and biocompatibility, they must be selective and show a fluorescence turn-on response to the metal of interest. To meet this challenge, we have pursued two general strategies for metal detection, termed "recognition" and "reactivity". Our design of transition metal probes makes use of a recognition-based approach for copper and nickel and a reactivity-based approach for cobalt and iron. This Account summarizes progress in our laboratory on both the development and application of fluorescent probes to identify and study the signaling roles of transition metals in biology. In conjunction with complementary methods for direct metal detection and genetic and/or pharmacological manipulations, fluorescent probes for transition metals have helped reveal a number of principles underlying transition metal dynamics. In this Account, we give three recent examples from our laboratory and collaborations in which applications of chemical probes reveal that labile copper contributes to various physiologies. The first example shows that copper is an endogenous regulator of neuronal activity, the second illustrates cellular prioritization of mitochondrial copper homeostasis, and the third identifies the "cuprosome" as a new copper storage compartment in Chlamydomonas reinhardtii green algae. Indeed, recognition- and reactivity-based fluorescent probes have helped to uncover new biological roles for labile transition metals, and the further development of fluorescent probes, including ones with varied Kd values and new reaction triggers and recognition receptors, will continue to reveal exciting and new biological roles for labile transition metals.

Improved identification of transition metals in airborne aerosols by SEM-EDX combined backscattered and secondary electron microanalysis.

The SEM EDX backscattered electron (BSE) atomic number contrast has been largely used in this work, in combination with conventional secondary electron microanalysis, to investigate the presence of metal particles in airborne particulate collected at three sites (industrial, residential, and rural background) in the Po Valley (Italy). Individual particle x-ray microanalysis was used for this aim. In many cases, the presence of metal particles was not evident by secondary electron imaging and it was instead revealed by BSE detection. Metal particles were observed either as isolated (not clustered to other particles), or gathered together (homogeneous clusters). In addition, the BSE microanalysis put on evidence two main types of association of metals to other particulate components: heterogeneous clusters and metals embedded or enclosed in other materials. In this study, the first association (heterogeneous clusters) was observed mostly between Fe-bearing metallic particles and soot aggregates (or other carbonaceous particles) and it was found in the particulate matter (PM) of all studied sites. The second association, conversely, seems to be characterized by more selective relationships between composition/size of metal particles and type of other particulate components. These associations could be evidenced only when using the BSE Z-contrast and mainly concern three cases: (1) unusual silicate-carbonate mixed aggregates were observed at the industrial site only. In these aggregates, embedded Mn, Cr, Co, Bi, W, and Zr fine particles were selectively observed. (2) Ni and V rich ultrafine particles were only observed as embedded particles in the surface structure of carbon cenospheres. (3) Pb or Pb-Zn bearing fine and ultrafine particles were largely detected only in oxygenated organic aerosols in the ultrafine PM.

Design and synthesis of an on-off "click" fluorophore that executes a logic operation and detects heavy and transition metal ions in water and living cells.

We have designed and synthesized a novel fluorescent molecular probe using the Cu(i)-catalyzed Huisgen cycloaddition of 1,3-diethynyl-6-fluoroisoquinoline with 1-(2-azidoethyl)pyrrolidine. This water soluble "click" fluorescent chemosensor displays good sensitivity towards heavy and transition metal ions. It shows pronounced fluorescence enhancement and high selectivity for Zn(2+) over other biologically relevant metal ions in water at pH 7.0. The fluorescence response of the bis-triazole derivative in the presence of Zn(2+) is switchable and reversible as a function of pH. The chemosensor also exhibits fluorescence quenching with Fe(2+) and Cu(2+) in water at pH 7.0. A modified YES logic gate property has been proposed using the "turn-on" and "turn-off" behavior of the bis-triazole with Zn(2+) and Fe(2+). The sensor is cell membrane permeable and applicable for intracellular Zn(2+) imaging.

Nickel(II) and iron(III) selective off-on-type fluorescence probes based on perylene tetracarboxylic diimide.

Two novel "turn-on" fluorescent probes with perylene tetracarboxylic diimide (PDI) as the fluorophore and two different di-(2-picolyl)-amine (DPA) groups as the metal ion receptor (PDI-1 and PDI-2) were successfully synthesized with satisfactory yields. PDI-1 exhibited high selectivity toward Ni(2+) in the presence of various other metal cations including Zn(2+), Cd(2+) and Cu(2+) which were expected to interfere significantly. A 1 : 2 stoichiometry was found for the complex formed by PDI-1 and Ni(2+) by a Job's plot and by non-linear least square fitting of the fluorescence titration curves. By introducing an extra diamino ethylene group between DPA and the phenyl bridge, the receptor was modified and the high selectivity of the sensor toward Ni(2+) shifted to Fe(3+). The enhancement factor of the fluorescence response of PDI-2 to Fe(3+) was as high as 138. The binding behavior of the receptors in these two compounds is affected significantly by the PDI fluorophores. Most interestingly, both Ni(2+) and Fe(3+) are paramagnetic metal ions, which are known as fluorescence quenchers and are rarely targeted with "turn-on" fluorescence probes. This result suggests that PDIs are favorable fluorophores for a "turn-on" fluorescence probe for paramagnetic transition metal ions because of their high oxidation potential.

Ratiometric and turn-on monitoring for heavy and transition metal ions in aqueous solution with a fluorescent peptide sensor.

A novel fluorescent peptide sensor containing tryptophan (donor) and dansyl fluorophore (acceptor) was synthesized for monitoring heavy and transition metal (HTM) ions on the basis of metal ion binding motif (Cys-X-X-X-Cys). The peptide probe successfully exhibited a turn on and ratiometric response for several heavy metal ions such as Hg(2+), Cd(2+), Pb(2+), Zn(2+), and Ag(+) in aqueous solution. The enhancements of emission intensity were achieved in the presence of the HTM ions by fluorescent resonance energy transfer (FRET) and chelation enhanced fluorescence (CHEF) effects. The detection limits of the sensor for Cd(2+), Pb(2+), Zn(2+), and Ag(+) were lower than the EPA's drinking water maximum contaminant levels (MCL). We described the fluorescent enhancement, binding affinity, and detection limit of the peptide probe for HTM ions.

Functionalized CdS quantum dots-based luminescence probe for detection of heavy and transition metal ions in aqueous solution.

Strong luminescence CdS quantum dots (QDs) have been prepared and modified with l-cysteine by a facile seeds-assistant technique in water. They are water-soluble and highly stable in aqueous solution. CdS QDs evaluated as a luminescence probe for heavy and transition metal (HTM) ions in aqueous solution was systematically studied. Five HTM ions such as silver(I) ion, copper(II) ion, mercury(II) ion, cobalt(II) ion, and nickel(II) ion significantly influence the photophysics of the emission from the functionalized CdS QDs. Experiment results showed that the fluorescence emission from CdS QDs was enhanced significantly by silver ion without any spectral shift, while several other bivalent HTM ions, such as Hg(2+), Cu(2+), Co(2+), and Ni(2+), exhibited effective optical quenching effect on QDs. Moreover, an obvious red-shift of emission band was observed in the quenching of CdS QDs for Hg(2+) and Cu(2+) ions. Under the optimal conditions, the response was linearly proportional to the concentration of Ag(+) ion ranging from 1.25 x 10(-7) to 5.0 x 10(-6)molL(-1) with a detection limit of 2.0 x 10(-8)molL(-1). The concentration dependence of the quenching effect on functionalized QDs for the other four HTM ions could be well described by typical Stern-Volmer equation, with the linear response of CdS QDs emission proportional to the concentration ranging from 1.50 x 10(-8) to 7.50 x 10(-7)molL(-1) for Hg(2+) ion, 3.0 x 10(-7) to 1.0 x 10(-5)molL(-1) for Ni(2+) ion, 4.59 x 10(-8) to 2.295 x 10(-6)molL(-1) for Cu(2+) ion, and 1.20 x 10(-7) to 6.0 x 10(-6)molL(-1) Co(2+) ion, respectively. Based on the distinct optical properties of CdS QDs system with the five HTM ions, and the relatively wide linear range and rapid response to HTM ions, CdS QDs can be developed as a potential identified luminescence probe for familiar HTM ions detection in aqueous solution.

Quantification of transition metals in biological samples and its possible impact on ferro-alloy workers.

Increased risk of ill-health and diseases has been associated with employment in the ferro-alloy factory. Since measurement of transition metals in human blood and hair along with respective exposure rates, provides a means of assessing individual risk, it has been the most important part of the study. In the study majority of the elements in the transition series, such as, vanadium (V), chromium (Cr), iron (Fe), manganese (Mn), cobalt, (Co) nickel (Ni), copper (Cu), zinc (Zn), molybdenum (Mo) and cadmium (Cd) were considered which are randomly emitted from the source, that is, manganese ore (used during ferro-alloy manufacturing process). The commonly available transition, metals, observed in biological samples of ferro-alloy workers, were found to be Fe, Zn, Co, Ni, Cu, Cr, Cd, V Mn and Mo in blood, while in hair, Mn, Fe, Zn, Co, Ni, Cu, Cr, Cd, V and Mo were present in decreasing order Surveillance of bio-concentration of these metals in workers, exposed to close proximity of the coke-ovens and smelting furnaces, revealed that the workers were prone to several physical disorders.

The London Underground: dust and hazards to health.

AIMS: To assess hazards associated with exposure to dust in the London Underground railway and to provide an informed opinion on the risks to workers and the travelling public of exposure to tunnel dust. METHODS: Concentrations of dust, as mass (PM2.5) and particle number, were measured at different underground stations and in train cabs; its size and composition were analysed; likely maximal exposures of staff and passengers were estimated; and in vitro toxicological testing of sample dusts in comparison with other dusts was performed. RESULTS: Concentrations on station platforms were 270-480 microg/m3 PM2.5 and 14,000-29,000 particles/cm3. Cab concentrations over a shift averaged 130-200 microg/m3 and 17,000-23,000 particles/cm3. The dust comprised by mass approximately 67% iron oxide, 1-2% quartz, and traces of other metals, the residue being volatile matter. The finest particles are drawn underground from the surface while the coarser dust is generated by interaction of brakes, wheels, and rails. Taking account of durations of exposure, drivers and station staff would have maximum exposures of about 200 microg/m3 over eight hours; the occupational exposure standard for welding fume, as iron oxide, is 5 mg/m3 over an eight hour shift. Toxicology showed the dust to have cytotoxic and inflammatory potential at high doses, consistent with its composition largely of iron oxide. DISCUSSION: It is unjustifiable to compare PM2.5 exposure underground with that on the surface, since the adverse effects of iron oxide and combustion generated particles differ. Concentrations of ultrafine particles are lower and of coarser (PM2.5) particles higher underground than on the surface. The concentrations underground are well below allowable workplace concentrations for iron oxide and unlikely to represent a significant cumulative risk to the health of workers or commuters.

[Determination of chromium, manganese and nickel in six biological agents].

The determination of chromium, manganese and nickel in biological agents has obtained by flame atomic absorption spectrometry. The results show that three trace elements of body necessary are the most rich in ant factor injection liquid. The chromium content is slightly lower in the brain cell activator injection liquid, the nickel content is slightly lower in the shift factor injection liquid and the manganese is the lowest in the marrow factor injection liquid. In this paper, we have studied three trace element contents in six biological agents. It provides, useful data for clinical treatment to some trace-element-lacking diseases.