Search

Introduction: This study evaluates trends in drug-related death cases within both Pasco and Pinellas County, Florida, from the calendar years 2011 to 2016. Specifically, it focuses on opioids and the role of fentanyl in overdose-related mortality in rural versus suburban populations., Methods: Two sets of data from each calendar year were obtained from a Medical Examiner's Office. These data were compared by year to assess differences using the nonparametric ANOVA test with the statistical software SAS, University Edition. Binary logistic regression was performed to assess which drugs occurred most frequently in the presence or absence of fentanyl., Results: There was not a significant difference in the month of the year or the day of the week that drug-related fatalities occurred. More drug-related mortalities occurred during daylight hours (e.g., 8:00 AM-4:00 PM) and more fentanyl-related mortalities occurred in Pinellas County compared to Pasco County. Fentanyl and heroin tended to co-occur in mortalities, while ethanol, hydrocodone, morphine, oxycodone, and methadone were negatively associated with fentanyl-related overdose cases., Conclusion: The characteristics of drug-related mortalities identified here may be used to better target interventions against drug abuse and overdose., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Emergencies, Trauma, and Shock.)

Poly(ADP-ribosyl)ation is an immediate cellular repair response to DNA damage and is catalyzed primarily by poly(ADP-ribose)polymerase-1 (PARP1), which is the most abundant of the 18 different PARP isoforms and accounts for more than 90% of the catalytic activity of PARP in the cell nucleus. Upon detection of a DNA strand break, PARP1 binds to the DNA, cleaves nicotinamide adenine dinucleotide between nicotinamide and ribose and then modifies the DNA nuclear acceptor proteins by formation of a bond between the protein and the ADP-ribose residue. This generates ribosyl-ribosyl linkages that act as a signal for other DNA-repairing enzymes and DNA base repair. Extensive DNA breakage in cells results in excessive activation of PARP with resultant depletion of the cellular stores of nicotinamide adenine dinucleotide (NAD+) which slows the rate of glycolysis, mitochondrial electron transport, and ultimately ATP formation in these cells. This paper focuses on PARP in DNA repair in atherosclerosis, acute myocardial infarction/reperfusion injury, and congestive heart failure and the role of PARP inhibitors in combating the effects of excessive PARP activation in these diseases. Free oxygen radicals and nitrogen radicals in arteries contribute to disruption of the vascular endothelial glycocalyx, which increase the permeability of the endothelium to inflammatory cells and also low-density lipoproteins and the accumulation of lipid in the vascular intima. Mild inflammation and DNA damage within vascular cells promote PARP1 activation and DNA repair. Moderate DNA damage induces caspase-dependent PARP cleavage and vascular cell apoptosis. Severe DNA damage due to vascular inflammation causes excessive activation of PARP1. This causes endothelial cell depletion of NAD+ and ATP, downregulation of atheroprotective SIRT1, necrotic cell death, and ultimately atherosclerotic plaque disruption. Inhibition of PARP decreases vascular endothelial cell adhesion P-selectin and ICAM-1 molecules, inflammatory cells, pro-death caspase-3, and c-Jun N-terminal kinase (JNK) activation and upregulates prosurvival extracellular signal-regulated kinases and AKT, which decrease vascular cell apoptosis and necrosis and limit atherosclerosis and plaque disruption. In myocardial infarction with coronary occlusion then reperfusion, which occurs with coronary angioplasty or thrombolytic therapy, reperfusion injury occurs in as many as 31% of patients and is caused by inflammatory cells, free oxygen and nitrogen radicals, the rapid transcriptional activation of inflammatory cytokines, and the activation of PARP1. Inhibition of PARP attenuates neutrophil infiltration and inflammatory cytokine expression in the reperfused myocardium and preserves myocardial NAD+ and ATP. In addition, PARP inhibition increases the activation of myocyte survival enzymes protein kinase B (Akt) and protein kinase C epsilon (PKCε), and decreases the activity of myocardial ventricular remodeling enzymes PKCα/β, PKCζ/λ, and PKCδ. As a consequence, cardiomyocyte and vascular endothelial cell necrosis is decreased and myocardial contractility is preserved. In heart failure and circulatory shock in animal models, PARP inhibition significantly attenuates decreases in left ventricular systolic pressure, ventricular contractility and relaxation, stroke volume, and increases survival by limiting or preventing upregulation of adhesion molecules, proinflammatory cytokines, myocardial mononuclear cell infiltration, and PKCα/β and PKC λ/ζ. In this manner, PARP inhibition partially restores the myocardial concentrations of NAD+, limits ventricular remodeling and fibrosis, and prevents significant decreases in myocardial contractility. Based primarily on investigations in preclinical models of atherosclerosis, myocardial infarction, and heart failure, PARP inhibition appears to be beneficial in limiting or inhibiting cardiovascular dysfunction. These studies indicate that investigations of acute and chronic PARP inhibition are warranted in patients with atherosclerotic coronary artery disease.

Acrolein is a reactive electrophilic aldehyde known to cause mitochondrial dysfunction, oxidative stress, and dysregulation of signaling transduction in vitro. Most in vitro systems employ standard cell culture maintenance conditions of 95% air/5% CO 2 , translating to a culture oxygen tension of approximately 20%, far above most physiological tissues. The purpose of this investigation was to examine whether low-serum, retinoic acid differentiated H9c2 cells were less sensitive to acrolein insult when cultured under reduced oxygen tension. H9c2 cells were maintained separately in 20% and 5% oxygen, differentiated for 5 d, and then exposed to acrolein for 30 min in media containing varying concentrations of tricarboxylic acid and glycolytic substrates, followed by fresh medium replacement. Cells were then assessed for MTT reduction at 2 h and 24 h after acrolein insult. We showed that pyruvate supplementation in combination with lowered oxygen culturing significantly attenuated acrolein-induced viability loss at 24 h. Poly(ADP-ribose) polymerase inhibition and EGTA preferentially provided partial rescue to low oxygen cultures, but not for standard cultures. Collectively, these results offer evidence supporting altered toxicogenic response of H9c2 during physiologically relevant oxygen tension culturing.

Three independently conducted asbestos exposure evaluations were conducted using wire gauze pads similar to standard practice in the laboratory setting. All testing occurred in a controlled atmosphere inside an enclosed chamber simulating a laboratory setting. Separate teams consisting of a laboratory technician, or technician and assistant simulated common tasks involving wire gauze pads, including heating and direct wire gauze manipulation. Area and personal air samples were collected and evaluated for asbestos consistent with the National Institute of Occupational Safety Health method 7400 and 7402, and the Asbestos Hazard Emergency Response Act (AHERA) method. Bulk gauze pad samples were analyzed by Polarized Light Microscopy and Transmission Electron Microscopy to determine asbestos content. Among air samples, chrysotile asbestos was the only fiber found in the first and third experiments, and tremolite asbestos for the second experiment. None of the air samples contained asbestos in concentrations above the current permissible regulatory levels promulgated by OSHA. These findings indicate that the level of asbestos exposure when working with wire gauze pads in the laboratory setting is much lower than levels associated with asbestosis or asbestos-related lung cancer and mesothelioma., (Copyright © 2018. Published by Elsevier Inc.)

Acrolein is a reactive α,β-unsaturated aldehyde known for its adduction to endogenous biomolecules, resulting in initiation or exacerbation of several disease pathways. In-vitro systems are routinely used to elucidate the cytotoxic or mechanistic role(s) of acrolein in pathogenesis. Nevertheless, the half-life of acrolein in biological or in-vitro systems, e.g. blood or culture media, has not been well characterized. Since in-vitro cytotoxic and mechanistic investigations routinely expose cultures to acrolein from 1 hour to 72 hours, we aimed to characterize the half-life of acrolein in culture medium to ascertain the plausible exposure window. Half-life determinations were conducted in low-serum DMEM at room temperature and 37 °C, both with and without H9c2 cells. For quantitative assessment, acrolein was derivatized to a fluorescent 7-hydroxyquinoline method validated in-house and assessed via fluorescent spectroscopy. In closed vessel experiments at room temperature, acrolein in DMEM was reduced by more than 40% at 24 hours, irrespective of the initial concentration. Expectedly, open vessel experiments demonstrated accelerated depletion over time at room temperature, and faster still at 37 °C. The presence of cells tended to further accelerate degradation by an additional 15-30%, depending on temperature. These results undermine described experimental exposure conditions stated in most in-vitro experiments. Recognition of this discrepancy between stated and actual exposure metrics warrant examination of novel alternative objective and representative exposure characterization for in-vitro studies to facilitate translation to in-vivo and in-silico methods.

This paper focuses on three classes of commonly used anticancer drugs, which can cause cardiotoxicity: anthracyclines, monoclonal antibodies exemplified by trastuzumab and tyrosine kinase inhibitors. Anthracyclines can induce cardiomyocyte necrosis and fibrosis. Trastuzumab can cause cardiac stunning. The tyrosine kinase inhibitors can increase systemic arterial pressure and impair myocyte contractility. In addition, radiation therapy to the mediastinum or left chest can exacerbate the cardiotoxicity of these anticancer drugs and can also cause accelerated atherosclerosis, myocardial infarction, heart failure and arrhythmias. Left ventricular ejection fraction measurements are most commonly used to assess cardiac function in patients who receive chemo- or radiation-therapy. However, echocardiographic determinations of global longitudinal strain are more sensitive for detection of early left ventricular systolic dysfunction. Information on patient-risk stratification and monitoring is presented and guidelines for the medical treatment of cardiac dysfunction due to cancer therapies are summarized.

Acrolein is a highly reactive unsaturated aldehyde that is formed during the burning of gasoline and diesel fuels, cigarettes, woods and plastics. In addition, acrolein is generated during the cooking or frying of food with fats or oils. Acrolein is also used in the synthesis of many organic chemicals and as a biocide in agricultural and industrial water supply systems. The total emissions of acrolein in the United States from all sources are estimated to be 62,660 tons/year. Acrolein is classified by the Environmental Protection Agency as a high-priority air and water toxicant. Acrolein can exert toxic effects following inhalation, ingestion, and dermal exposures that are dose dependent. Cardiovascular tissues are particularly sensitive to the toxic effects of acrolein based primarily on in vitro and in vivo studies. Acrolein can generate free oxygen radical stress in the heart, decrease endothelial nitric oxide synthase phosphorylation and nitric oxide formation, form cytoplasmic and nuclear protein adducts with myocyte and vascular endothelial cell proteins and cause vasospasm. In this manner, chronic exposure to acrolein can cause myocyte dysfunction, myocyte necrosis and apoptosis and ultimately lead to cardiomyopathy and cardiac failure. Epidemiological studies of acrolein exposure and toxicity should be developed and treatment strategies devised that prevent or significantly limit acrolein cardiovascular toxicity.

Safety assessment evaluating the presence of impurities, residual materials, and contaminants in vaccines is a focus of current research. Thresholds of toxicological concern (TTCs) are mathematically modeled levels used for assessing the safety of many food and medication constituents. In this study, six algorithms are selected from the open-access ToxTree software program to derive a method for calculating TTCs for vaccine constituents: In Vivo Rodent Micronucleus assay/LD50, Benigni-Bossa/LD50, Cramer Extended/LD50, In Vivo Rodent Micronucleus assay/TDLo, Benigni-Bossa/TDLo, and the Cramer Extended/TDLo. Using an initial dataset (n = 197) taken from INCHEM, RepDose, RTECS, and TOXNET, the chemicals were divided into two families: "positive" - based on the presence of structures associated with adverse outcomes, or "negative" - no such structures or having structures that appear to be protective of health. The final validation indicated that the Benigni-Bossa/LD50 method is the most appropriate for calculating TTCs for vaccine constituents. Final TTCs were designated as 18.06 μg/person and 20.61 μg/person for the Benigni-Bossa/LD50 positive and negative structural families, respectively.

Objective: The purpose of this study was to elicit the opinions of Emergency Department (ED) physicians, currently practicing in the United States, regarding the impact of economic and regulatory factors on their management of patients exhibiting "drug seeking" behavior., Methods: A descriptive, cross-sectional study, utilizing a convenience sample of ED physicians located in Florida and Georgia was conducted for a period of 2 months. The inclusion criteria specified that any ED physician, currently practicing within the United States, could participate., Results: Of the ED physicians surveyed (n = 141), 71% reported a perceived pressure to prescribe opioid analgesics to avoid administrative and regulatory criticism and 98% related patient satisfaction scores as being too highly emphasized by reimbursement entities as a means of evaluating their patient management. Rising patient volumes and changes in the healthcare climate were cited by ED physicians as impacting their management of patients exhibiting "drug seeking" behavior., Conclusions: The ED physician faces unique challenges in changing healthcare and economic climates. Requirements to address pain as the "fifth vital sign," patient satisfaction based reimbursement metrics and an economically driven rise in ED patient volume, may have inadvertently created an environment conducive to exploitation by prescription opioid abusers. There is an identified need for the development of continuing medical education and standardized regulatory and legislative protocols to assist ED physicians in the appropriate management of patients exhibiting "drug seeking" behavior.

Calcining processes including handling and storage of raw petroleum coke may result in Particulate Matter (PM) and gaseous emissions. Concerns have been raised over the potential association between particulate and aerosol pollution and adverse respiratory health effects including decrements in lung function. This risk characterization evaluated the exposure concentrations of ambient air pollutants including PM10 and gaseous pollutants from a petroleum coke calciner facility. The ambient air pollutant levels were collected through monitors installed at multiple locations in the vicinity of the facility. The measured and modeled particulate levels in ambient air from the calciner facility were compared to standards protective of public health. The results indicated that exposure levels were, on occasions at sites farther from the facility, higher than the public health limit of 150 μg/m(3) 24-h average for PM10. However, the carbon fraction demonstrated that the contribution from the calciner facility was de minimis. Exposure levels of the modeled SO2, CO, NOx and PM10 concentrations were also below public health air quality standards. These results demonstrate that emissions from calcining processes involving petroleum coke, at facilities that are well controlled, are below regulatory standards and are not expected to produce a public health risk., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This investigation aims to assess whether the hepatocellular carcinoma cell line, HepG2, is an appropriate model to assess the role of poly (ADP-ribose) polymerase (PARP) during acute ethanol toxicosis. HepG2 cells were dosed with graded concentrations of ethanol, ranging from 100 mM to 800 mM, for 6 hours to assess PARP activity induction, while another parallel experiment examined cellular damage via medium aspartate aminotransferase activity and cellular viability via MTT reduction. Aspartate aminotransferase activity was significantly elevated at 600 mM ethanol (FOLD; P < 0.01), with further increases at the 800 mM dose (1.43 fold; P < 0.001), compared to controls. Cellular viability was not significantly decreased compared to controls among all dose groups. PARP activity measured in total cell lysates showed a significant decreasing trend with respect to ethanol dose, reaching statistical significance at the 100 mM dose group (P < 0.05). Paradoxically, exposure to 50 μM etoposide (Positive apoptosis-inducing control) did not demonstrate significant PARP activity ablation. When analyzing PARP activity observation temporally, a significant correlation (R(2) =0.5314) was observed between activity and assay sequence. Overall, a clear HepG2 insensitivity to ethanol was observed.

Emergency responders may be exposed to a variety of fumes, gases, and particulates during the course of their job that can affect pulmonary function (PF) and require the use of respiratory protection. This investigation used occupational health monitoring examination data to characterize PF in a population currently employed as emergency responders. PF tests for workers who required health examinations to ensure fitness for continued respirator use were compared to the National Health and Nutrition Examination Survey (NHANES) III Raw Spirometry database to determine if decreased PF was associated with employment as an emergency responder. The results of this research indicated that the emergency responders experienced a modest, but statistically significant, increase in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) mean values over the NHANES III population in both total and stratified analyses, including stratification by age, gender, height, and smoking history. Results are likely due to a combination of effectively controlled exposures in the workplace, and the healthy worker effect among long-term workers. PF testing required by the Occupational and Safety Health Administration (OSHA) has substantial utility for conducting occupational surveillance at the population level. In this investigation, we were able to quickly evaluate if abnormal PF existed in an industrial sector known to have exposures that, when uncontrolled, can lead to PF impairment.

Flexane® 80 is a trowelable urethane product used in combination with cleaners and primers to effect rubber conveyor belt repairs. These products are of concern due to the potential for worker exposure to isocyanates and volatile organic compounds (VOCs). Small chamber experiments were used to identify chemicals liberated to the ambient air from each of the Flexane®-related products. A new sample collection method using treated cotton sleeves as a surrogate skin surface to assess potential dermal exposure to isocyanates during mixing and application of the Flexane® product was validated. Six simulations of a worst case scenario were performed by an experienced belt repair technician in a walk-in laboratory exposure chamber. Analysis of air samples from the large chamber simulations did not detect airborne isocyanates. The average airborne VOC concentrations were below established occupational exposure levels. Dermal sleeve samples detected intermittent and low levels of isocyanates from self-application while wearing gloves having surface residues of uncured Flexane®. The data strongly suggest that the normal and intended use of Flexane® putty, and its associated products under worst case or typical working conditions is not likely to result in worker VOC or isocyanate exposure levels sufficient to produce adverse health effects., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Asbestos-containing fire sleeves have been used as a fire protection measure for aircraft fluid hoses. This investigation was conducted to determine the level of airborne asbestos fiber exposure experienced by mechanics who work with fire sleeve protected hoses. Duplicate testing was performed inside a small, enclosed workroom during the fabrication of hose assemblies. Personal air samples taken during this work showed detectable, but low airborne asbestos fiber exposures. Analysis of personal samples (n=9) using phrase contract microscopy (PCM) indicated task duration airborne fiber concentrations ranging from 0.017 to 0.063 fibers per milliliter (f/ml) for sampling durations of 167-198 min, and 0.022-0.14 f/ml for 30 min samples. Airborne chrysotile fibers were detected for four of these nine personal samples, and the resulting asbestos adjusted airborne fiber concentrations ranged from 0.014 to 0.025 f/ml. These results indicate that work with asbestos fire sleeve and fire sleeve protected hose assemblies, does not produce regulatory noncompliant levels of asbestos exposure for persons who handle, cut and fit these asbestos-containing materials., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Inhibitors of the nuclear enzyme poly (ADP-ribose) polymerase (PARP-1) have been demonstrated to attenuate pathophysiologic conditions associated with oxidative stress, specifically with carbon tetrachloride (CT)-induced hepatotoxicity., Settings and Design: In this investigation, we evaluated 3 previously untested water-soluble PARP-1 inhibitors, namely, 3-aminobenzamide (ABA), 5-aminoisoquinolinone (AIQ), and N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide HCl (PJ-34) to determine their efficacy in blocking or attenuating CT-induced hepatotoxicity in male imprinting control region (ICR) mice., Statistical Analysis: Indicators of hepatotoxicity were compared with F-tests among groups to determine statistically significant effects. Pearson's correlation coefficients were used to evaluate the correlation between PARP inhibition and the attenuation of hepatotoxicity., Results and Conclusions: CT treatment resulted in hepatic cytotoxicity, increased serum transaminase (ALT), lipid peroxidation (MDA), intracellular glutathione (GSH) depletion, increased carbonyl content, and substantially increased PARP-1 activity. CT treatment also produced profound observable hemorrhagic necrosis in the hepatic centrilobular region of ICR mice. Pretreatment with PJ-34, ABA, and AIQ before CT treatment significantly decreased PARP-1 activity in hepatocytes after CT treatment by 3.4, 2.0, and 1.9 times, respectively. Corresponding to this reduction in PARP-1 activity, a significant reduction in the ALT levels and MDA and a reduction in the GSH depletion were observed. Also, there were no visible tissue defects in the liver samples from animals pretreated with individual PARP-1 inhibitors before CT administration. These results demonstrate the efficacy of the 3 previously untested water-soluble PARP-1 inhibitors in attenuating CT-induced hepatocellular toxicity and further characterize the role of PARP-1 activation and oxidative stress among the cascade of events in hepatocellular necrosis induced by CT treatment.

Soil vapor intrusion (SVI) has recently garnered much interest as a potential exposure route for occupants of properties overlying and surrounding former Manufactured Gas Plants (MGPs). This investigation evaluates SVI at 10 commercial buildings and 26 single family and multi-family residential properties overlying and/or adjacent to three former MGPs. SVI was evaluated in three categories according to thickness of the vadose zones: no vadose zone; 0-6 feet thick, and 6-25 feet thick. Indoor and outdoor air, and soil vapor samples were analyzed for volatile organic compounds (VOCs). Comparative risks were evaluated based on maximum and mean concentrations for benzene, toluene, ethylbenzene, and xylenes relative to background levels. All calculated Hazard Indices were less than 1 or were comparable to mean and maximum background levels. Cancer risks for exposure to benzene ranged from 9.75×10(-6) to 4.52×10(-4). Comparative background cancer risk from benzene exposure not related to former MGP sites ranged from 9.9×10(-6) to 3.59×10(-3). The results did not identify evidence of MGP-related soil vapor intrusion from any of the 36 sites. No increased public health risks were associated with occupied residential or commercial properties overlying or surrounding MGPs., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Introduction: Previous findings have demonstrated that preparedness and planning within the public health system are inadequately developed to respond to an act of biological or chemical terrorism., Materials and Methods: This investigation used Internet-based surveys to assess the level of preparedness (PL) and willingness to respond (WTR) to a bioterrorism attack, and identify factors that predict PL and WTR among Florida community healthcare providers. Invitations were sent to 22,800 healthcare providers in Florida, which resulted in 2,279 respondents., Results: Respondents included physicians (n=604), nurses (n=1,152), and pharmacists (n=486). The results indicated that only 32% of Florida healthcare providers were competent and willing to respond to a bioterrorism attack, 82.7% of providers were willing to respond in their local community, and 53.6% within the State. Respondents were more competent in administrative skills than clinical knowledge (62.8% vs. 45%). Areas in which respondents had the highest competency were the initiation of treatment and recognition of their clinical and administrative roles. Areas in which respondents showed the lowest competency were the ability to identify cases and the ability to communicate risk to others. About 55% of the subjects had previous bioterrorism training and 31.5% had conducted emergency drills. Gender, race, previous training and drills, perceived threats of bioterrorism attack, perceived benefits of training and drills, and feeling prepared were all predictors of overall preparedness., Conclusions: The findings suggest that only one-third of Florida community healthcare providers were prepared for a bioterrorism attack, which is an insufficient response rate to effectively respond to a bioterrorism incident.

Airborne benzene is a ubiquitous environmental air pollutant. However, research regarding ambient environmental benzene exposures and leukemogenesis is lacking. Alternatively, occupational exposure to significantly elevated levels of benzene is associated with acute myeloid leukemia (AML). This investigation uses ambient air monitoring data from six counties in the state of Florida to characterize the extrapolated cancer risk from airborne benzene concentrations. The study uses both a regulatory and comparative risk analysis methodology to appropriately frame "risk" for the public. Between the years 2003 and 2006, 3794 air samples were collected from 23 monitoring stations distributed in Broward, Duval, Orange, Miami-Dade, Hillsborough, and Pinellas counties. The mean benzene concentrations by site ranged from 0.18 to 3.58ppb. Extrapolated cumulative lifetime exposures ranged from 0.036 to 0.702ppm-years. Regulatory risk analysis resulted in cancer risk estimates ranging from 4.37 x10(-6) to 8.56 x 10(-5), all of which exceed the Florida Department of Environmental Protection acceptable risk of 1x10(-6). Comparative analysis with the epidemiologic literature indicates the association between benzene exposure and AML is related to cumulative exposures far in excess of 1ppm-years, with the likely threshold for benzene-induced leukemogenesis of 50ppm-years cumulative exposure. Based upon the results of this investigation, it is unreasonable to anticipate AML cases in Florida residents as a result of ambient airborne benzene concentrations.

Asbestos containing materials are a component of many vehicle brake systems, including those found in some light aircraft. To characterize the asbestos exposure that results from the installation and maintenance of these components, an aircraft fitted with asbestos containing brake pads had brake changes performed while both area and personal air samples were taken. The brake changing process took place in a closed, unventilated aircraft hanger and all operations were performed according to the manufacturer's recommended procedure. Personal air samples did not detect any measurable amount of asbestos fibers during the brake changing or subsequent cleanup procedures. Analysis of personal samples (n=9) using phase contrast microscopy indicated airborne fiber concentrations at or below 0.003f/ml as 8-h time weighted averages (TWAs) and less than 0.069f/ml averaged over 28-30min sampling periods. Airborne chrysotile fibers were detected by two area air samples with fiber concentrations remaining at or below 0.0013f/ml over an 8-h TWA. These results indicate that normal brake changing work practices on aircraft with asbestos containing brake pads does not produce a harmful level of asbestos exposure for aircraft mechanics.

Inhibitors of the nuclear enzyme poly-(ADP-ribose) polymerase (PARP) have been demonstrated to attenuate pathophysiological conditions associated with toxicant-induced oxidative stress. This investigation evaluates Nicotinamide (NIC), a non-specific PARP inhibitor, and 6(5)-Phenanthridinone (Phen), a specific PARP-1 inhibitor, for their efficacy in blocking or attenuating bromobenzene (BB) induced hepatocellular toxicity. Male ICR mice were treated with an intraperitoneal injection of bromobenzene, followed by concomitant treatment with NIC or with NIC at 0.5, 1 and 2 hours after BB treatment, or with concomitant treatment of Phen at 10 mg/ml, 20 mg/ml, or 40 mg/ml solution concentration. Mice with only BB treatment displayed substantial hepatotoxicity as evidenced by a 3.5-fold increase in serum alanine transferase (ALT) compared to controls. Mice treated with 3 injections of NIC (at 0.5, 1 and 2 hours) after BB treatment demonstrated a 90% reduction in serum ALT at 24 hours after BB treatment (p < 0.05). Mice with concomitant BB and Phen treatment demonstrated a 75% reduction in ALT at 24 hours after treatment (p < 0.05). Histological evaluations of centrilobular hepatic tissue from treated animals confirm findings of reduced hepatotoxicity as indicated by the ALT results in the NIC and Phen treatment groups. Mortality after 7 days was reduced to levels near controls in the NIC and Phen treatment groups. The PARP-1 inhibitors evaluated in this investigation produce clinically significant attenuation of BB-induced liver injury in male ICR mice.

Two independent assessments were performed of airborne asbestos concentrations generated during automotive repair work on vintage vehicles . The first involved removal of asbestos-containing seam sealant, and the second involved servicing of a drive clutch. Despite the relatively high concentrations (5.6-28%) of chrysotile fibers detected within bulk samples of seam sealant, the average asbestos concentration for personal breathing zone (PBZ) samples during seam sealant removal was 0.006 f/cc (fibers/cubic centimeter of air). Many other air samples contained asbestos at or below the analytical limit of detection (LOD). Pneumatic chiseling of the sealant material during removal resulted in 69% of area air samples containing asbestos. Use of this impact tool liberated more asbestos than hand scraping. Asbestos fibers were only detected in air samples collected during the installation of a replacement clutch. The highest asbestos corrected airborne fiber concentration observed during clutch installation was 0.0028 f/cc. This value is approximately 100 times lower than Occupational Safety and Health Administration's (OSHA) permissible exposure limit (PEL) of 0.1f/cc. The airborne asbestos concentrations observed during the servicing of vintage vehicles with asbestos-containing seam sealant and clutches are comparable to levels reported for repair work involving brake components and gaskets.

Malathion is an organophosphate pesticide commonly used on field crops, fruit trees, livestock, agriculture, and for mosquito and medfly control. Aerial applications can result in solubilized malathion in swimming pools and other recreational waters that may come into contact with human skin. To evaluate the human skin absorption of malathion for the assessment of risk associated with human exposures to aqueous solutions, human volunteers were selected and exposed to aqueous solutions of malathion. Participants submerged their arms and hands in twenty liters of dilute malathion solution in either a stagnant or stirred state. The "disappearance method" was applied by measuring malathion concentrations in the water before and after human exposure for various periods of time. No measurable skin absorption was detected in 42% of the participants; the remaining 58% of participants measured minimal absorbed doses of malathion. Analyzing these results through the Hazard Index model for recreational swimmer and bather exposure levels typically measured in contaminated swimming pools and surface waters after bait application indicated that these exposures are an order of magnitude less than a minimal dose known to result in a measurable change in acetylcholinesterase activity. It is concluded that exposure to aqueous malathion in recreational waters following aerial bait applications is not appreciably absorbed, does not result in an effective dose, and therefore is not a public health hazard.

Carbon tetrachloride (CCl4) is a compound associated with free radical mediated hepatotoxicity in humans and laboratory animals. Previous research indicates that the cytotoxicity caused by CCl4 may be mediated by the rapid induction of PARP-1, a nuclear repair enzyme, which results in celluar depletion of NAD+ and ATP. Animal models indicate that the inhibition of PARP-1 after CCl4 exposure will attenuate cytotoxicity in mouse hepatocytes. In this investigation, the potential hepatoprotective effects of the PARP-1 inhibitor 6,(5H)-phenanthridinone against CCl4-induced hepatotoxicity was tested in human cells from the HepG2 primary hepatoma cell line. Cytotoxicity assay results indicate significant reductions in cell death with treatment of 20uM and 40uM solutions of 6,(5H)-phenanthridinone. PARP-1 activity assay results confirm that these protective effects correspond to the inhibition of PARP-1 by 6,(5H)-phenanthridinone. The findings in this study indicate that the effect of PARP-1 inhibition on cytotoxicity in human hepatocytes after CCl4 insult is consistent with the effect of PARP-1 inhibition on cytotoxicity found in animal models.

Five test sessions were conducted to assess asbestos exposure during the removal or installation of asbestos-containing gaskets on vehicles. All testing took place within an operative automotive repair facility involving passenger cars and a pickup truck ranging in vintage from late 1960s through 1970s. A professional mechanic performed all shop work including engine disassembly and reassembly, gasket manipulation and parts cleaning. Bulk sample analysis of removed gaskets through polarized light microscopy (PLM) revealed asbestos fiber concentrations ranging between 0 and 75%. Personal and area air samples were collected and analyzed using National Institute of Occupational Safety Health (NIOSH) methods 7400 [phase contrast microscopy (PCM)] and 7402 [transmission electron microscopy (TEM)]. Among all air samples collected, approximately 21% (n = 11) contained chrysotile fibers. The mean PCM and phase contrast microscopy equivalent (PCME) 8-h time weighted average (TWA) concentrations for these samples were 0.0031 fibers/cubic centimeters (f/cc) and 0.0017 f/cc, respectively. Based on these findings, automobile mechanics who worked with asbestos-containing gaskets may have been exposed to concentrations of airborne asbestos concentrations approximately 100 times lower than the current Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (PEL) of 0.1 f/cc.

The contribution of consumer purchases of non-essential products to environmental pollution is characterized. Purchase decisions by consumers induce a complex sequence of economy-wide production interactions that influence the production and consumption of chemicals and subsequent exposure and possible public health risks. An economic input-output life-cycle analysis (EIO-LCA) was used to link resource consumption and production by manufacturers to corresponding environmental impacts. Using the US Department of Commerce's input-output tables together with the US Environmental Protection Agency's Toxics Release Inventory and AIRData databases, the economy-wide air discharges resulting from purchases of household appliances, motor homes, and games and toys were quantified. The economic and environmental impacts generated from a hypothetical 10,000 US dollar purchase for selected consumer items were estimated. The analysis shows how purchases of seemingly benign consumer products increase the output of air pollutants along the supply chain and contribute to the potential risks associated with environmental chemical exposures to both consumers and non-consumers alike.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme involved in the detection of DNA strand termini. Extensive cellular damage can overactivate PARP-1, which rapidly depletes the cellular stores of NAD+ and ATP, resulting in necrotic cell death. The purpose of the present study was to determine whether 6(5H)-phenanthridinone, a potent inhibitor of PARP-1, could attenuate the hepatotoxicity of carbon tetrachloride (CCl4). Male ICR mice treated via the intraperitoneal route with CCl4 exhibited severe necrotic centrilobular lesions and significantly elevated serum transaminases. In contrast, the histopathology and serum biochemistry of animals treated concomitantly with CCl4 and 6(5H)-phenanthridinone were not significantly different versus controls. In conclusion, the results of this study demonstrate that the hepatotoxicity of CCl4 can be blocked independently of its metabolism and suggest the predominant role of PARP-1 overactivation in chemical-induced toxicity.

Adult male ICR mice were treated by intraperitoneal injection with 250 mg/kg of bodyweight of commercial malathion (a dose corresponding to 1/12 the LD50). After 6 h, acetylcholinesterase (AChE) activity in blood, liver, and six brain regions was determined. A statistically significant inhibition was observed in whole blood (23%), liver (21%), and, in particular, the central nervous system; the greatest degree of AChE inhibition was observed in the cerebellum (45%), followed by the hippocampus (29%). There was no significant change in AChE activity in the caudate putamen, frontal cortex, midbrain, or pons medulla. These results demonstrate that the magnitude of AChE inhibition in peripheral tissues does not accurately reflect the central-inhibitory effects of malathion on AChE activity in specific brain regions.

The use in the past, and to a lesser extent today, of chrysotile asbestos in automobile brake systems causes health concerns among professional mechanics. Therefore, we conducted four separate tests in order to evaluate an auto mechanic's exposure to airborne asbestos fibers while performing routine brake maintenance. Four nearly identical automobiles from 1960s having four wheel drum brakes were used. Each automobile was fitted with new replacement asbestos-containing brake shoes and then driven over a predetermined public road course for about 2253 km. Then, each car was separately brought into a repair facility; the brakes removed and replaced with new asbestos-containing shoes. The test conditions, methods, and tools were as commonly used during the 1960s. The mechanic was experienced in brake maintenance, having worked in the automobile repair profession beginning in the 1960s. Effects of three independent variables, e.g., filing, sanding, and arc grinding of the replacement brake shoe elements, were tested. Personal and area air samples were collected and analyzed for the presence of fibers, asbestos fibers, total dust, and respirable dust. The results indicated a presence in the air of only chrysotile asbestos and an absence of other types of asbestos. Airborne chrysotile fiber exposures for each test remained below currently applicable limit of 0.1 fiber/ml (eight-hour time-weighted average).

Male Sprague Dawley rats were administered a vitrified material obtained from the former Charleston Naval Shipyard (Charleston, SC, USA) by gavage once daily for 32 days. Group mean body weight of treated animals was within +/-5.4% of controls. No gross or histopathological changes were observed when animals were treated with 67, 174, or 370 mg/kg per day. Analysis of heavy metals revealed a statistically significant increase only in the concentration of arsenic in the livers of animals treated with 174 or 370 mg/kg per day versus controls. Although there was a statistically significant increase in liver arsenic levels, the concentrations were far below mean soil concentrations for western and eastern United States. If the standard assumption of 100% absorption is used, the concentrations observed in the present study are about 20 times less than the average background soil levels in these regions. Based on this, it is concluded that the vitrified material would not pose a public health risk for its intended use as an additive for asphalt and glass beams.

Ethylene dibromide (EDB) has been used as a model compound for eliciting hepato- and nephrotoxicity. Conjugation with glutathione (GSH) has been shown to play a role in the bioactivation of EDB. The aim of this study was to determine whether activation of alpha(1)-adrenergic receptors, which causes a decrease in cellular GSH levels, could modulate the nephrotoxicity of EDB. For this purpose, male ICR mice were treated with EDB and/or the alpha-adrenergic agonist, phenylephrine (Pe), or the alpha-adrenergic antagonist, phentolamine (Phe). Animals treated with EDB (40 mg/kg, i.p.) had a 9.3-fold increase in urinary gamma-glutamyltranspeptidase (GGTP: EC 2.3.2.2) activity and a 38% decrease in renal non-protein bound sulfhydryl (NPSH) levels; however, animals co-treated with EDB and Pe (50 mg/kg, i.p.) exhibited a 27.8-fold increase in urinary GGTP activity and a 60% decrease in NPSH levels. The enhanced presence of urinary GGTP and decrease in cellular levels of NPSH was nearly blocked by treating animals concomitantly with EDB and Phe (10 mg/kg, i.p.) or EDB, Pe, and Phe. Histopathological examination revealed the enhanced degree of tissue damage and necrosis following treatment with EDB and Pe, and the protective effect of Phe at ameliorating EDB toxicity. These results indicate that factors that can influence alpha-adrenergic receptors may be critical in assessing dose-response data used in the risk assessment process.

Overactivation of poly(ADP-ribose) polymerase-1 (PARP-1) in response to oxidative stress has been shown to contribute to necrotic cell death by consuming NAD+ and ATP. In the present study, PARP-1 overactivation was determined by identifying the distribution and accumulation of poly(ADP-ribose) following intraperitoneal administration of a hepatotoxic dose of carbon tetrachloride (572 mg/kg). Treated animals exhibited lipid peroxide levels 16.5-fold higher than controls. Serum activities of glutamic pyruvic transaminase and glutamic oxaloacetic transaminase were increased by 6.1-fold and 22.8-fold, respectively. Lactate dehydrogenase activity was significantly increased by 1.2-fold. Histopathological analyses revealed severe necrosis and increased poly(ADP-ribsyl)ation of cells in the centrilobular region of treated animals versus saline controls. These results demonstrate the role of PARP-1 overactivation in chemical-induced pathologies and suggest the potential role of PARP-1 inhibitors at preventing toxicity.

Dieldrin, an organochlorine pesticide and known neurotoxicant, is ubiquitously distributed in the environment. Dieldrin depletes brain monoamines in some animal species and is toxic for dopaminergic neurons in vitro. Dieldrin interferes with mitochondrial electron transport and increases generation of superoxide anion. Reactive oxygen species have been shown to produce oxidative lesions to DNA bases, i.e., 8-hydroxy-2'-deoxyguanosine (8-oxodGuo). Accumulation of 8-oxodGuo has been shown to be promutagenic in proliferating cells, and can lead to degeneration in fully differentiated cells. The objective of this study was to determine the effects of dieldrin exposure on the activity of the enzyme responsible for removing 8-oxodGuo, OGG1, from undifferentiated (untreated with NGF) and differentiated (NGF-treated) PC 12 cells. Proliferating PC 12 cells exhibited a mild upregulation of glycosylase activity, reaching a maximum by 1 h and returning to baseline by 6 h. Differentiated (+) NGF cells showed a time-dependent decline in activity reaching a nadir at 3 h with a return towards baseline by 6 h. Levels of the damaged base, 8-oxodGuo, in the differentiated PC12 cells appeared to be regulated by the activity of OGG1. In contrast, levels of the damaged base in actively proliferating cells were independent of the OGG1 activity. This difference between actively dividing and differentiated cells in the regulation of base-excision repair and DNA damage accumulation explains, in part, the vulnerability of postmitotic neurons to oxidative stresses and neurotoxins.

Stimulation of alpha-adrenergic receptors by cold stress or adrenergic agents has been shown to potentiate the toxicity of numerous toxicants. Several lines of evidence indicate that this interaction is dependent on glutathione depression and increased cytosolic Ca2+ concentrations produced by alpha1-adrenergic compounds. In this report, evidence is provided in support of the mechanism of adrenoreceptor-mediated potentiation of nephrotoxicity. Alpha1-adrenergic agonists are shown to potentiate the toxicity of nephrotoxicants that exert their toxic effects via glutathione conjugation or Ca2+ deregulation. This review summarizes the effects of the alpha1-adrenergic agonist, phenylephrine, at enhancing the toxicity of 2-bromohydroquinone, 1,2-dibromoethane, and cis-diammineplatinum(II) dichloride.

The lung has been shown to be a target organ for the deleterious effects of Benzo[a]pyrene (B[a]P), regardless of the route of exposure. 8-hydroxy-2'-deoxyguanosine (oxo8dG) is a mutagenic lesion formed in DNA following exposure to B[a]P. The objective of this study was to determine the capacity of different organs to repair oxo8dG following intraperitoneal (i.p.) treatment with B[a]P. Male Spraque-Dawley rats were administered 20 mg/kg B[a]P i.p., 2 times/day for 5 days. A 26% decrease in the capacity to remove oxo8dG was observed in lung tissue at 72 hours and recovered 20% above control values at 120 hours. The capacity of the liver and kidney remained at baseline for all time points analyzed. A 7-fold increase in oxo8dG was observed in the lung at 72 hours. This study demonstrates that organ-specific differences exist in the capacity to remove oxo8dG and further demonstrates the susceptibility of lung tissue to the effects of B[a]P.

In recent years there has been an increase in the use of traditional Asian medicines. It is estimated that 30% of the US population is currently using some form of homeopathic or alternative therapy at a total cost of over $13 billion annually. Herbal medications are claimed and widely believed to be beneficial; however, there have been reports of acute and chronic intoxications resulting from their use. This study characterizes a random sampling of Asian medicines as to the content of arsenic, mercury, and lead. Traditional herbal remedies were purchased in the USA, Vietnam, and China. The Asian remedies evaluated contained levels of arsenic, lead, and mercury that ranged from toxic (49%) to those exceeding public health guidelines for prevention of illness (74%) when consumed according to the directions given in or on the package. Heavy metals contained in Asian remedies may cause illness of unknown origin and result in the consumption of health care resources that are attributable to other causes. The public health hazards of traditional herbal Asian remedies should be identified and disclosed.