•FQs inhibit growth of the Escherichia coli indicator organism at 1–10μg/L.•Eight FQ antibiotics in raw wastewater at inhibitory levels (2–3μg/L).•Several less-prescribed FQs (DIF, FLE, MOX, and ORB) ...were detected.•FQ removal negatively correlated to BOD removal, positively correlated to PO4 removal.
As annual sales of antibiotics continue to rise, the mass of these specially-designed compounds entering municipal wastewater treatment systems has also increased. Of primary concern here is that antibiotics can inhibit growth of specific microorganisms in biological processes of wastewater treatment plants (WWTPs) or in downstream ecosystems. Growth inhibition studies with Escherichia coli demonstrated that solutions containing 1–10μg/L of fluoroquinolones can inhibit microbial growth. Wastewater samples were collected on a monthly basis from various treatment stages of a 30 million gallon per day WWTP in Maryland, USA. Samples were analyzed for the presence of 11 fluoroquinolone antibiotics. At least one fluoroquinolone was detected in every sample. Ofloxacin and ciprofloxacin exhibited detection frequencies of 100% and 98%, respectively, across all sampling sites. Concentrations of fluoroquinolones in raw wastewater were as high as 1900ng/L for ciprofloxacin and 600ng/L for ofloxacin. Difloxacin, enrofloxacin, fleroxacin, moxifloxacin, norfloxacin, and orbifloxacin were also detected at appreciable concentrations of 9–170ng/L. The total mass concentration of fluoroquinolones in raw wastewater was in the range that inhibited E. coli growth, suggesting that concerns over antibiotic presence in wastewater and wastewater-impacted surface water are valid. The average removal efficiency of fluoroquinolones during wastewater treatment was approximately 65%; furthermore, the removal efficiency for fluoroquinolones was found to be negatively correlated to biochemical oxygen demand removal and positively correlated to phosphorus removal.
Induction of proinflammatory mediators by alveolar macrophages exposed to ambient air particulate matter has been suggested to be a key factor in the pathogenesis of inflammatory and allergic ...diseases in the lungs. However, receptors and mechanisms underlying these responses have not been fully elucidated. In this study, we examined whether TLR2, TLR4, and the key adaptor protein, MyD88, mediate the expression of proinflammatory cytokines and chemokines by mouse peritoneal macrophages exposed to fine and coarse PM. TLR2 deficiency blunted macrophage TNF-alpha and IL-6 expression in response to fine (PM2.5), while not affecting cytokine-inducing ability of coarse NIST Standard Reference Material (SRM 1648) particles. In contrast, TLR4(-/-) macrophages showed inhibited cytokine expression upon stimulation with NIST SRM 1648 but exhibited normal responses to PM2.5. Preincubation with polymyxin B markedly suppressed the capacity of NIST SRM 1648 to elicit TNF-alpha and IL-6, indicating endotoxin as a principal inducer of cytokine responses. Overexpression of TLR2 in TLR2/4-deficient human embryonic kidney 293 cells imparted PM2.5 sensitivity, as judged by IL-8 gene expression, whereas NIST SRM 1648, but not PM2.5 elicited IL-8 expression in 293/TLR4/MD-2 transfectants. Engagement of TLR4 by NIST SRM 1648 induced MyD88-independent expression of the chemokine RANTES, while TLR2-reactive NIST IRM PM2.5 failed to up-regulate this response. Consistent with the shared use of MyD88 by TLR2 and TLR4, cytokine responses of MyD88(-/-) macrophages to both types of air PM were significantly reduced. These data indicate differential utilization of TLR2 and TLR4 but shared use of MyD88 by fine and coarse air pollution particles.
•Size, metal and endotoxin content are reported for an interim PM2.5 reference material.•Cytokine and chemokine dose-response was characterized in A549 and RAW264.7 cells.•Physicochemical and ...biological data were compared to SRM 1648.•Results support a cytotoxic effect of PM2.5 and its possible role in inflammation.
The epidemiological association between exposure to fine particulate matter (PM2.5) and adverse health effects is well-known. Here we report the size distribution, metals content, endotoxin content, and biological activity of National Institute of Standards and Technology (NIST) Interim Reference Material (RM) PM2.5. Biological activity was measured in vitro by effects on cell viability and the release of four inflammatory immune mediators, from human A549 alveolar epithelial cells or murine RAW264.7 monocytes. A dose range covering three orders of magnitude (1–1000μg/mL) was tested, and biological activity was compared to an existing Standard Reference Material (SRM) for urban PM (NIST SRM 1648). Robust release of IL-8 and MCP-1 from A549 cells was observed in response to IRM PM2.5 exposures. Significant TNF-α, but not IL-6, secretion from RAW264.7 cells was observed in response to both IRM PM2.5 and SRM 1648 particle types. Cytokine or chemokine release at high doses often occurred in the presence of cytotoxicity, likely as a result of externalization of preformed mediator. Our results are consistent with a local cytotoxic and pro-inflammatory mechanism of response to exposure to inhaled ambient PM2.5 and reinforce the continued relevance of in vitro assays for mechanistic research in PM toxicology. Our study furthers the goal of developing reference samples of environmentally relevant particulate matter of various sizes that can be used for hypothesis testing by multiple investigators.
OBJECTIVE:To characterize systemic metal exposures from retained fragments in a cohort of war-injured US Veterans enrolled in the Department of Veterans Affairs’ Embedded Fragment Registry.
...METHODS:Five hundred seventy nine registry-enrolled Veterans submitted an exposure questionnaire and urine sample for analyses of 14 metals often found in fragments. Urine metal results were compared with reference values of unexposed populations to identify elevations.
RESULTS:55% of Veterans had normal urine metal values. When observed, tungsten and zinc were the metals most frequently elevated, followed by cobalt; however, cobalt levels were not associated with a fragment source, but with surgical implants present.
CONCLUSIONS:Though most metal elevations observed are not significantly outside the normal range, on-going accrual of metal burdens in these Veterans over time recommends continued surveillance which may inform future medical management.
Environmental metal exposure, as well as dietary metals, may adversely affect semen quality even as others play an essential role in normal spermatogenesis and fertility. Measures of seminal fluid ...metals have therefore been of high interest in the last several decades but have shown inconsistent results in correlations with some semen quality parameters. As well, environmental metal measures across various body fluid matrices have not been consistently correlated contrary to what one might hypothesize based on a systemic body burden of metal. This may be due to the body fluid matrices assessed and to other differences in laboratory methods and sample preparation. Measures of uranium, a potentially toxic metal in humans, have not previously been reported in the semen of environmentally metal-exposed populations. We report here uranium seminal fluid results and the high correlation of uranium concentrations across several body fluid matrices in a cohort of military veterans exposed to depleted uranium in combat events during the Iraqi Gulf War. These results inform the risk communication conversation for exposed populations and broaden the public health assessments from various exposure scenarios.
A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly-fire incidents have been monitored for health changes in a clinical surveillance program at the Veterans Affairs Medical ...Center, Baltimore since 1994.
During the spring of 2015, an in-patient clinical surveillance protocol was performed on 36 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes.
On-going mobilization of U from embedded fragments is evidenced by elevated urine U concentrations. The DU isotopic signature is observed principally in participants possessing embedded fragments. Those with only an inhalation exposure have lower urine U concentration and a natural isotopic signature.
At 25 years since first exposure to DU, an aging cohort of military veterans continues to show no U-related health effects in known target organs of U toxicity. As U body burden continues to accrue from in-situ mobilization from metal fragment depots, and increases with exposure duration, critical tissue-specific U concentration thresholds may be reached, thus recommending on-going surveillance of this veteran cohort.
•Gulf War I veterans wounded with depleted uranium are monitored for health changes.•In 2015 in-patient clinical surveillance was performed on 36 members of the cohort.•Mobilization of U from embedded fragments is evidenced by elevated U in urine.•This cohort of continues to show no U-related health effects.
A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly fire incidents have been monitored in a clinical surveillance program at the Veterans Affairs Medical Center, Baltimore ...since 1994.
An in-patient clinical surveillance protocol was performed on 35 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes.
Although urine U concentrations continue to be elevated in this group, illustrating on-going in situ mobilization of U from embedded fragments, no consistent U-related health effects have been observed.
Now more than 20 years since first exposure to DU, an aging cohort of military veterans continues to show no U-related health effects in known target organs of U toxicity. As tissue concentrations continue to accrue with exposure duration, critical tissue-specific U concentration thresholds may be reached, thus recommending on-going surveillance of this veteran cohort.
Health effects stemming from depleted uranium (DU) exposure in a cohort of Gulf War veterans who were in or on US Army vehicles hit by friendly fire involving DU munitions are being carefully ...monitored through the Baltimore Veterans Affairs (VA) DU Follow-Up Program initiated in 1993. DU exposure in this cohort has been directly measured using inductively coupled plasma-mass spectrometer (ICP-MS) isotopic analysis for DU in urine specimens. Soldiers with embedded DU fragments continue to excrete elevated concentrations of U in their urine, documenting ongoing systemic exposure to U released from their fragments. Biennial surveillance visits provide a detailed health assessment that includes basic clinical measures and surveillance for early changes in kidney function, an expected target organ for U. Tests also include measurements of genotoxicity and neuroendocrine, neurocognitive and reproductive function. With the exception of the elevated urine U excretion, no clinically significant expected U-related health effects have been identified to date. Subtle changes in renal function and genotoxicity markers in veterans with urine U concentrations greater than 0.1 μg−1 creatinine, however, indicate the need for continued surveillance of these DU-exposed veterans.
A frequent comorbidity of traumatic injury due to a blast or explosion, commonly reported in Iraq and Afghanistan veterans, is that of retained embedded fragments typically of unknown content. ...Because of concerns over both local and systemic health effects related to both the physical presence of and mobilization of materials from embedded fragments, the Department of Veterans Affairs established a surveillance program for this group of veterans. We present here the case of a surveillance-enrolled veteran who submitted: (1) three surgically removed fragments for content analyses, (2) tissue adhered to the fragments for histology and metal concentration evaluation, and (3) pre- and postfragment removal urine samples to assess concentrations of various metals often found in fragments. Results indicate that removed fragments were aluminum-copper alloys. Surrounding tissue analyses revealed elevated concentrations of these metals and evidence of chronic inflammation, but no neoplastic changes. Urine aluminum concentrations, initially elevated compared to normal population values, decreased significantly after fragment removal, illustrating the utility of urine biomonitoring to provide insight into fragment composition. A medical surveillance program integrating fragment composition data, tissue analyses, and repeat urine biomonitoring can help inform the patient-specific medical management of both the local and systemic effects of retained metal fragments.
A total of 70 military Veterans have been monitored for HPRT T-cell mutations in five separate studies at 2-year intervals over an 8-year period. Systemic depleted uranium (DU) levels were measured ...at the time of each study by determining urinary uranium (uU) excretion. Each HPRT study included 30-40 Veterans, several with retained DU-containing shrapnel. Forty-nine Veterans were evaluated in multiple studies, including 14 who were in all five studies. This permitted a characterization of the HPRT mutation assay over time to assess the effects of age, smoking and non-selected cloning efficiencies, as well as the inter- and intra-individual variability across time points. Molecular analyses identified the HPRT mutation and T-cell receptor (TCR) gene rearrangement in 1,377 mutant isolates. An unexpected finding was that in vivo clones of HPRT mutant T-cells were present in some Veterans, and could persist over several years of the study. The calculated HPRT mutant frequencies (MFs) were repeatedly elevated in replicate studies in three outlier Veterans with elevated urinary uranium excretion levels. However, these three outlier Veterans also harbored large and persistent in vivo HPRT mutant T-cell clones, each of which was represented by a single founder mutation. Correction for in vivo clonality allowed calculation of HPRT T-cell mutation frequencies (MutFs). Despite earlier reports of DU associated increases in HPRT MFs in some Veterans, the results presented here demonstrate that HPRT mutations are not increased by systemic DU exposure. Additional battlefield exposures were also evaluated for associations with HPRT mutations and none were found.
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