Lead exposures and biological responses in military weapons systems: Aerosol characteristics and acute lead effects among US Army artillerymen: Final report

This study was to determine the concentration and chemical nature of lead (Pb) aerosols produced during the firing of artillery and to determine the exposures and biological responses of crew members exposed to lead aerosols during such firing. The concentrations of lead-containing aerosols at crew positions depended on wind conditions, with higher concentrations when firing into a head wind. Aerosol concentrations were highest in the muzzle blast zone. Concentrations of lead in the blood of crew members rose during the first 12 days of exposure to elevated airborne lead concentrations and then leveled off. There was no rapid decrease in blood lead concentrations after completion of firing. Small decreases in hematocrit and small increases in free erythrocyte porphyrin were correlated with increasing exposure to airborne lead. These changes were reversed by seven weeks after firing. Changes in nerve conduction velocity had borderline statistical significance to airborne lead exposure. In measuring nerve conduction velocity, differences in skin temperature must be taken into account

Antibacterial activity of traditional medicinal plants used by Haudenosaunee peoples of New York State

<p>Abstract</p> <p>Background</p> <p>The evolution and spread of antibiotic resistance, as well as the evolution of new strains of disease causing agents, is of great concern to the global health community. Our ability to effectively treat disease is dependent on the development of new pharmaceuticals, and one potential source of novel drugs is traditional medicine. This study explores the antibacterial properties of plants used in Haudenosaunee traditional medicine. We tested the hypothesis that extracts from Haudenosaunee medicinal plants used to treat symptoms often caused by bacterial infection would show antibacterial properties in laboratory assays, and that these extracts would be more effective against moderately virulent bacteria than less virulent bacteria.</p> <p>Methods</p> <p>After identification and harvesting, a total of 57 different aqueous extractions were made from 15 plant species. Nine plant species were used in Haudenosaunee medicines and six plant species, of which three are native to the region and three are introduced, were not used in traditional medicine. Antibacterial activity against mostly avirulent (<it>Escherichia coli, Streptococcus lactis</it>) and moderately virulent (<it>Salmonella typhimurium, Staphylococcus aureus</it>) microbes was inferred through replicate disc diffusion assays; and observed and statistically predicted MIC values were determined through replicate serial dilution assays.</p> <p>Results</p> <p>Although there was not complete concordance between the traditional use of Haudenosaunee medicinal plants and antibacterial activity, our data support the hypothesis that the selection and use of these plants to treat disease was not random. In particular, four plant species exhibited antimicrobial properties as expected (<it>Achillea millefolium, Ipomoea pandurata, Hieracium pilosella</it>, and <it>Solidago canadensis</it>), with particularly strong effectiveness against <it>S. typhimurium</it>. In addition, extractions from two of the introduced species (<it>Hesperis matronalis </it>and <it>Rosa multiflora</it>) were effective against this pathogen.</p> <p>Conclusions</p> <p>Our data suggest that further screening of plants used in traditional Haudenosaunee medicine is warranted, and we put forward several species for further investigation of activity against <it>S. typhimurium </it>(<it>A. millefolium, H. matronalis, I. pandurata, H. pilosella, R. multiflora, S. canadensis</it>).</p

Conjugation of a Ru(II) Arene Complex to Neomycin or to Guanidinoneomycin Leads to Compounds with Differential Cytotoxicities and Accumulation between Cancer and Normal Cells

A straightforward methodology for the synthesis of conjugates between a cytotoxic organometallic ruthenium(II) complex and amino- and guanidinoglycosides, as potential RNA-targeted anticancer compounds, is described. Under microwave irradiation, the imidazole ligand incorporated on the aminoglycoside moiety (neamine or neomycin) was found to replace one triphenylphosphine ligand from the ruthenium precursor [(η6-p-cym)RuCl(PPh3)2]+, allowing the assembly of the target conjugates. The guanidinylated analogue was easily prepared from the neomycin-ruthenium conjugate by reaction with N,N′-di-Boc-N″-triflylguanidine, a powerful guanidinylating reagent that was compatible with the integrity of the metal complex. All conjugates were purified by semipreparative high-performance liquid chromatography (HPLC) and characterized by electrospray ionization (ESI) and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and NMR spectroscopy. The cytotoxicity of the compounds was tested in MCF-7 (breast) and DU-145 (prostate) human cancer cells, as well as in the normal HEK293 (Human Embryonic Kidney) cell line, revealing a dependence on the nature of the glycoside moiety and the type of cell (cancer or healthy). Indeed, the neomycin-ruthenium conjugate (2) displayed moderate antiproliferative activity in both cancer cell lines (IC50 ≈ 80 μM), whereas the neamine conjugate (4) was inactive (IC50 ≈ 200 μM). However, the guanidinylated analogue of the neomycin-ruthenium conjugate (3) required much lower concentrations than the parent conjugate for equal effect (IC50 = 7.17 μM in DU-145 and IC50 = 11.33 μM in MCF-7). Although the same ranking in antiproliferative activity was found in the nontumorigenic cell line (3 2 > 4), IC50 values indicate that aminoglycoside-containing conjugates are about 2-fold more cytotoxic in normal cells (e.g., IC50 = 49.4 μM for 2) than in cancer cells, whereas an opposite tendency was found with the guanidinylated conjugate, since its cytotoxicity in the normal cell line (IC50 = 12.75 μM for 3) was similar or even lower than that found in MCF-7 and DU-145 cancer cell lines, respectively. Cell uptake studies performed by ICP-MS with conjugates 2 and 3 revealed that guanidinylation of the neomycin moiety had a positive effect on accumulation (about 3-fold higher in DU-145 and 4-fold higher in HEK293), which correlates well with the higher antiproliferative activity of 3. Interestingly, despite the slightly higher accumulation in the normal cell than in the cancer cell line (about 1.4-fold), guanidinoneomycin-ruthenium conjugate (3) was more cytotoxic to cancer cells (about 1.8-fold), whereas the opposite tendency applied for neomycin-ruthenium conjugate (2). Such differences in cytotoxic activity and cellular accumulation between cancer and normal cells open the way to the creation of more selective, less toxic anticancer metallodrugs by conjugating cytotoxic metal-based complexes such as ruthenium(II) arene derivatives to guanidinoglycosides

Lead exposures and biological responses in military weapons systems: Aerosol characteristics and acute lead effects among US Army artillerymen: Final report

This study was to determine the concentration and chemical nature of lead (Pb) aerosols produced during the firing of artillery and to determine the exposures and biological responses of crew members exposed to lead aerosols during such firing. The concentrations of lead-containing aerosols at crew positions depended on wind conditions, with higher concentrations when firing into a head wind. Aerosol concentrations were highest in the muzzle blast zone. Concentrations of lead in the blood of crew members rose during the first 12 days of exposure to elevated airborne lead concentrations and then leveled off. There was no rapid decrease in blood lead concentrations after completion of firing. Small decreases in hematocrit and small increases in free erythrocyte porphyrin were correlated with increasing exposure to airborne lead. These changes were reversed by seven weeks after firing. Changes in nerve conduction velocity had borderline statistical significance to airborne lead exposure. In measuring nerve conduction velocity, differences in skin temperature must be taken into account

Antimicrobial and antifungal activities of the extracts and essential oils of Bidens tripartita.

The aim of this study was to determine the antibacterial and antifungal properties of the extracts, subextracts and essential oils of Bidens tripartita flowers and herbs. In the study, twelve extracts and two essential oils were investigated for activity against different Gram-positive Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, Gram-negative bacteria Escherichia coli, E. coli (beta-laktamase+), Klebsiella pneumoniae (ESBL+), Pseudomonas aeruginosa and some fungal organisms Candida albicans, C. parapsilosis, Aspergillus fumigatus, A. terreus using a broth microdilution and disc diffusion methods. The results obtained indicate antimicrobial activity of the tested extracts (except butanolic extracts), which however did not inhibit the growth of fungi used in this study. Bacteriostatic effect of both essential oils is insignificant, but they have strong antifungal activity. These results support the use of B. tripartita to treat a microbial infections and it is indicated as an antimicrobial and antifungal agent, which may act as pharmaceuticals and preservatives