Evaluation and modeling of the impact of coexposures to VOC mixtures on urinary biomarkers

2016 ◽  
Vol 28 (6) ◽  
pp. 260-273 ◽  
Author(s):  
Axelle Marchand ◽  
Rocio Aranda-Rodriguez ◽  
Robert Tardif ◽  
Andy Nong ◽  
Sami Haddad
Keyword(s):  
Urinary Biomarkers ◽  
Voc Mixtures ◽  
The Impact

scholarly journals Grill Workers Exposure to Polycyclic Aromatic Hydrocarbons: Levels and Excretion Profiles of the Urinary Biomarkers

2020 ◽  
Vol 18 (1) ◽  
pp. 230
Author(s):  
Marta Oliveira ◽  
Sílvia Capelas ◽  
Cristina Delerue-Matos ◽  
Simone Morais
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Aromatic Hydrocarbons ◽  
High Performance ◽  
Principal Component ◽  
Fold Increase ◽  
Urinary Biomarkers ◽  
Analysis Model ◽  
Exposed Workers ◽  
Polycyclic Aromatic ◽  
The Impact

Grilling activities release large amounts of hazardous pollutants, but information on restaurant grill workers’ exposure to polycyclic aromatic hydrocarbons (PAHs) is almost inexistent. This study assessed the impact of grilling emissions on total workers’ exposure to PAHs by evaluating the concentrations of six urinary biomarkers of exposure (OHPAHs): naphthalene, acenaphthene, fluorene, phenanthrene, pyrene, and benzo(a)pyrene. Individual levels and excretion profiles of urinary OHPAHs were determined during working and nonworking periods. Urinary OHPAHs were quantified by high-performance liquid-chromatography with fluorescence detection. Levels of total OHPAHs (∑OHPAHs) were significantly increased (about nine times; p ≤ 0.001) during working comparatively with nonworking days. Urinary 1-hydroxynaphthalene + 1-hydroxyacenapthene and 2-hydroxyfluorene presented the highest increments (ca. 23- and 6-fold increase, respectively), followed by 1-hydroxyphenanthrene (ca. 2.3 times) and 1-hydroxypyrene (ca. 1.8 times). Additionally, 1-hydroxypyrene levels were higher than the benchmark, 0.5 µmol/mol creatinine, in 5% of exposed workers. Moreover, 3-hydroxybenzo(a)pyrene, biomarker of exposure to carcinogenic PAHs, was detected in 13% of exposed workers. Individual excretion profiles showed a cumulative increase in ∑OHPAHs during consecutive working days. A principal component analysis model partially discriminated workers’ exposure during working and nonworking periods showing the impact of grilling activities. Urinary OHPAHs were increased in grill workers during working days.

scholarly journals 1569. A Translational Model to Assess the Impact of Polymyxin B Dose Fractionation on Kidney Injury

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S573-S574
Author(s):  
Jiajun Liu ◽  
Gwendolyn M Pais ◽  
Sean N Avedissian ◽  
Andrew Lee ◽  
Nathaniel J Rhodes ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Kidney Injury ◽  
Polymyxin B ◽  
Urinary Biomarkers ◽  
Dose Fractionation ◽  
Total Daily Dose ◽  
Translational Model ◽  
Urine Biomarkers ◽  
Daily Dose ◽  
The Impact

Abstract Background Progression of antimicrobial resistance has revived Polymyxin B (PB) use in clinical practice. Dose-dependent acute kidney injury (AKI) limits its clinical use. It is unclear whether dose fractionation of total daily dose can lessen kidney injury. We assessed the role of PB fractionation on AKI in a translational model that employs sensitive urine biomarkers qualified by the FDA. Methods Male Sprague–Dawley rats received 12 mg/kg/day PB subcutaneously for 3 days or equal-volume normal saline (NS). PB was administered in 3 separate fractionated daily doses: 12 mg/kg daily (QD), 6 mg/kg twice daily (BID), and 4 mg/kg thrice daily (TID). Staggered blood sampling was done on days 1 to 4 and 24 hour urine was collected at baseline, on days 1, 2, and 3. Plasma creatinine (Cr) was quantified using LCMS/MS, and 24 hour urinary biomarkers (KIM1, OPN, CLN, calbindin, GSTα, IP-10, TIMP-1, and VEGF) were assayed with MILLIPLEX Rat Kidney Toxicity Magnetic Bead Panel. Mixed-effects models were used. Results A total of 32 rats contributed to the study data. Mean Cr were constant across groups over time (Figure 1, P = 0.18). For NS group, all biomarkers remained at baseline throughout study. Significant differences were seen for fractionation schemes for KIM1 (P = 0.02), CLN (P = 0.03), IP-10 (0.007) and TIMP-1 (P = 0.04). The differences for KIM1, IP-10, and TIMP-1 were driven by higher observed values in TID than those of BID as early as day 1 (P < 0.04). Furthermore, CLN was elevated for TID when compared with BID at baseline (P = 0.048). Similarly, TID group had the highest (but non-significant) elevations for IP-10 and TIMP-1 compared with QD on study days. Amongst all urine biomarkers, KIM1 in TID exhibited the most rapid rise from baseline to day 2 (Figure2, P < 0.0001). Conclusion In this translational model in which a single total daily dose was fractionated, sensitive urinary biomarkers indicated that TID dosing was worse than BID or QD dosing; dose fractionation of PB may lead to increased AKI. In addition, KIM1 rose rapidly as an early marker for AKI. Further efforts are needed to investigate the PK-TD relationship of PB in order to decrease AKI. Disclosures All authors: No reported disclosures.

scholarly journals 64. Novel Biomarkers Improve Estimation of Vancomycin Clearance in Critically Ill Children

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S43-S44
Author(s):  
Kevin J Downes ◽  
Athena F Zuppa ◽  
Anna Sharova ◽  
Lauren Gianchetti ◽  
Emily Duffey ◽  
...  
Keyword(s):  
Renal Function ◽  
Critically Ill ◽  
Urinary Biomarkers ◽  
Critically Ill Children ◽  
Research Support ◽  
Final Model ◽  
Plasma Ngal ◽  
Population Pk ◽  
Novel Biomarkers ◽  
The Impact

Abstract Background There are a paucity of robust population PK (popPK) models to inform vancomycin (VAN) dosing in critically ill children. The majority of published models incorporate peak/trough data and rely on flawed estimates of renal function. We sought to develop a popPK model for IV VAN in critically ill children utilizing novel plasma and urinary biomarkers. Methods We conducted a prospective observational study of critically ill children prescribed VAN for a suspected infection in the CHOP pediatric ICU. Children &lt; 1 year of age and those receiving ECMO or CRRT were excluded. Five VAN samples were collected from a single dosing interval for each subject. Plasma biomarkers (creatinine [Cr], cystatin C [CysC], NGAL) and urinary biomarkers (CysC, NGAL, KIM-1, osteopontin) were collected the morning of PK sampling; urinary biomarkers were corrected for urine creatinine. Nonparametric popPK modeling was performed using Pmetrics. The impact of renal function (GFR) on VAN clearance (CL) was estimated first, comparing model performance with each biomarker (Cr and plasma CysC). The influence of age, sex, additional biomarkers, PIM3 score, and receipt of vasopressors as covariates was then assessed for relevant PK parameters. Results 30 subjects completed the study. Median age was 10 years (range 1-17); 76% were male. The majority (90%) of children received VAN for suspected sepsis. PK sampling occurred at a median of 37.7 hours (range 24.6-94.8) into VAN treatment; 136 VAN samples were included. A 2-compartment model with fixed allometric scaling of 0.75 on clearances and 1 on volumes best described the data. CysC-based GFR as a covariate on VAN CL using the HOEK formula (GFR = -4.32 + (80.35/CysC)) resulted in the best model fit. Age and plasma NGAL were also informative on VAN CL in the final model (Figure 1). During model building, urinary NGAL was also associated with VAN CL (comparable to plasma NGAL) and outperformed Cr, although it was not retained in the final model. Figure 1. Final population PK model and parameter estimates. Conclusion Plasma CysC is a better renal function estimate than Cr to inform VAN clearance in critically ill children. Urinary and plasma NGAL also improved estimation of VAN CL during popPK modeling. Novel biomarkers can better describe VAN exposures in critically ill children than reliance on Cr alone. Disclosures Kevin J. Downes, MD, Merck (Individual(s) Involved: Self): Grant/Research Support Stuart L. Goldstein, MD, Bioporto (Consultant, Grant/Research Support)

scholarly journals Utility of Urinary Biomarkers in Predicting Loss of Residual Renal Function: The BAL Anz Trial

2015 ◽  
Vol 35 (2) ◽  
pp. 159-171 ◽  
Author(s):  
Yeoungjee Cho ◽  
David W. Johnson ◽  
David A. Vesey ◽  
Carmel M. Hawley ◽  
Margaret Clarke ◽  
...  
Keyword(s):  
Renal Function ◽  
Degradation Products ◽  
Kidney Injury ◽  
Residual Renal Function ◽  
Interferon Γ ◽  
Urinary Biomarkers ◽  
Rapid Decline ◽  
Solution Type ◽  
Kidney Injury Molecule 1 ◽  
The Impact

Background The ability of urinary biomarkers to predict residual renal function (RRF) decline in peritoneal dialysis (PD) patients has not been defined. The present study aimed to explore the utility of established biomarkers from kidney injury models for predicting loss of RRF in incident PD patients, and to evaluate the impact on RRF of using neutral-pH PD solution low in glucose degradation products. Methods The study included 50 randomly selected participants from the balANZ trial who had completed 24 months of follow-up. A change in glomerular filtration rate (GFR) was used as the primary clinical outcome measure. In a mixed-effects general linear model, baseline measurements of 18 novel urinary biomarkers and albumin were used to predict GFR change. The model was further used to evaluate the impact of biocompatible PD solution on RRF, adjusted for each biomarker. Results Baseline albuminuria was not a useful predictor of change in RRF in PD patients ( p = 0.84). Only clusterin was a significant predictor of GFR decline in the whole population ( p = 0.04, adjusted for baseline GFR and albuminuria). However, the relationship was no longer apparent when albuminuria was removed from the model ( p = 0.31). When the effect of the administered PD solutions was examined using a model adjusted for PD solution type, baseline albuminuria, and GFR, higher baseline urinary concentrations of trefoil factor 3 (TFF3, p = 0.02), kidney injury molecule 1 (KIM-1, p = 0.04), and interferon γ–induced protein 10 (IP-10, p = 0.03) were associated with more rapid decline of RRF in patients receiving conventional PD solution compared with biocompatible PD solution. Conclusions Higher urinary levels of kidney injury biomarkers (TFF3, KIM-1, IP-10) at baseline predicted significantly slower RRF decline in patients receiving bio-compatible PD solutions. Findings from the present investigation should help to guide future studies to validate the utility of urinary biomarkers as tools to predict RRF decline in PD patients.

Formation of Lunar Craters and Bright Rays as a Result of Meteorite Impacts

1962 ◽  
Vol 14 ◽  
pp. 415-418
Author(s):  
K. P. Stanyukovich ◽  
V. A. Bronshten
Keyword(s):  
Explosive Charge ◽  
The Moon ◽  
Meteorite Impacts ◽  
The Earth ◽  
Lunar Craters ◽  
The Impact

The phenomena accompanying the impact of large meteorites on the surface of the Moon or of the Earth can be examined on the basis of the theory of explosive phenomena if we assume that, instead of an exploding meteorite moving inside the rock, we have an explosive charge (equivalent in energy), situated at a certain distance under the surface.

The Geosciences Applied to Lunar Exploration

1962 ◽  
Vol 14 ◽  
pp. 169-257 ◽  
Author(s):  
J. Green
Keyword(s):  
Lunar Surface ◽  
Probable Mechanism ◽  
Point Of View ◽  
Lunar Exploration ◽  
Geological Model ◽  
Apply Geophysics ◽  
Surface Features ◽  
The Impact

The term geo-sciences has been used here to include the disciplines geology, geophysics and geochemistry. However, in order to apply geophysics and geochemistry effectively one must begin with a geological model. Therefore, the science of geology should be used as the basis for lunar exploration. From an astronomical point of view, a lunar terrain heavily impacted with meteors appears the more reasonable; although from a geological standpoint, volcanism seems the more probable mechanism. A surface liberally marked with volcanic features has been advocated by such geologists as Bülow, Dana, Suess, von Wolff, Shaler, Spurr, and Kuno. In this paper, both the impact and volcanic hypotheses are considered in the application of the geo-sciences to manned lunar exploration. However, more emphasis is placed on the volcanic, or more correctly the defluidization, hypothesis to account for lunar surface features.

Asteroid and Comet Impact Speeds upon Mars: Significance for Panspermia and the Supply of Organics

1997 ◽  
Vol 161 ◽  
pp. 197-201 ◽  
Author(s):  
Duncan Steel
Keyword(s):  
Probability Distributions ◽  
Regions Of Interest ◽  
Significant Fraction ◽  
Organic Chemicals ◽  
Impact Speed ◽  
The Mean ◽  
The Impact

AbstractWhilst lithopanspermia depends upon massive impacts occurring at a speed above some limit, the intact delivery of organic chemicals or other volatiles to a planet requires the impact speed to be below some other limit such that a significant fraction of that material escapes destruction. Thus the two opposite ends of the impact speed distributions are the regions of interest in the bioastronomical context, whereas much modelling work on impacts delivers, or makes use of, only the mean speed. Here the probability distributions of impact speeds upon Mars are calculated for (i) the orbital distribution of known asteroids; and (ii) the expected distribution of near-parabolic cometary orbits. It is found that cometary impacts are far more likely to eject rocks from Mars (over 99 percent of the cometary impacts are at speeds above 20 km/sec, but at most 5 percent of the asteroidal impacts); paradoxically, the objects impacting at speeds low enough to make organic/volatile survival possible (the asteroids) are those which are depleted in such species.

Organic Syntheses During the Impact of a Comet with a Gaseous Planet

1997 ◽  
Vol 161 ◽  
pp. 189-195
Author(s):  
Cesare Guaita ◽  
Roberto Crippa ◽  
Federico Manzini
Keyword(s):  
Polymeric Material ◽  
Molecular Form ◽  
Parent Compound ◽  
Blue Filter ◽  
Organic Syntheses ◽  
The Impact

AbstractA large amount of CO has been detected above many SL9/Jupiter impacts. This gas was never detected before the collision. So, in our opinion, CO was released from a parent compound during the collision. We identify this compound as POM (polyoxymethylene), a formaldehyde (HCHO) polymer that, when suddenly heated, reformes monomeric HCHO. At temperatures higher than 1200°K HCHO cannot exist in molecular form and the most probable result of its decomposition is the formation of CO. At lower temperatures, HCHO can react with NH3 and/or HCN to form high UV-absorbing polymeric material. In our opinion, this kind of material has also to be taken in to account to explain the complex evolution of some SL9 impacts that we observed in CCD images taken with a blue filter.

Hydrogen Cyanide Polymers from the Impact of Comet P/Shoemaker-Levy 9 on Jupiter

1997 ◽  
Vol 161 ◽  
pp. 179-187
Author(s):  
Clifford N. Matthews ◽  
Rose A. Pesce-Rodriguez ◽  
Shirley A. Liebman
Keyword(s):  
Amino Acids ◽  
Solar System ◽  
Hydrogen Cyanide ◽  
Nitrogen Heterocycles ◽  
Laboratory Studies ◽  
Heterogeneous Solids ◽  
The Many ◽  
Comet Halley ◽  
The Impact ◽  
By Products

AbstractHydrogen cyanide polymers – heterogeneous solids ranging in color from yellow to orange to brown to black – may be among the organic macromolecules most readily formed within the Solar System. The non-volatile black crust of comet Halley, for example, as well as the extensive orangebrown streaks in the atmosphere of Jupiter, might consist largely of such polymers synthesized from HCN formed by photolysis of methane and ammonia, the color observed depending on the concentration of HCN involved. Laboratory studies of these ubiquitous compounds point to the presence of polyamidine structures synthesized directly from hydrogen cyanide. These would be converted by water to polypeptides which can be further hydrolyzed to α-amino acids. Black polymers and multimers with conjugated ladder structures derived from HCN could also be formed and might well be the source of the many nitrogen heterocycles, adenine included, observed after pyrolysis. The dark brown color arising from the impacts of comet P/Shoemaker-Levy 9 on Jupiter might therefore be mainly caused by the presence of HCN polymers, whether originally present, deposited by the impactor or synthesized directly from HCN. Spectroscopic detection of these predicted macromolecules and their hydrolytic and pyrolytic by-products would strengthen significantly the hypothesis that cyanide polymerization is a preferred pathway for prebiotic and extraterrestrial chemistry.

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