Detection of Acetaminophen-Protein Adducts in Decedents with Suspected Opioid-Acetaminophen Combination Product Overdose.

Acetaminophen overdose is a leading cause of drug-induced liver failure in the United States. Acetaminophen-protein adducts have been suggested as a biomarker of hepatotoxicity. The purpose of this study was to determine whether protein-derived acetaminophen-protein adducts are quantifiable in postmortem samples.

A comparative evaluation of self-report and biological measures of cigarette use in nondaily smokers.

A large subset of individuals who smoke cigarettes do not smoke regularly, but the assessments used to collect data on cigarette consumption in nondaily smokers have not been rigorously evaluated. The current study examined several self-report and biomarker approaches to the assessment of cigarette use in a sample of nondaily smokers (n = 176). Participants were randomly assigned to a daily monitoring condition (n = 89), requiring a daily report of the number of cigarettes smoked in the previous 24 hours, or a no monitoring condition (n = 87).

A Population Pharmacokinetic Analysis of Dextroamphetamine in the Plasma and Hair of Healthy Adults.

Background And Objective: Hair is an attractive matrix for amphetamine drug testing; however, little is known about the rate at which amphetamines are deposited into hair. Therefore, the purpose of this study was to determine the pharmacokinetics of oral dextroamphetamine in plasma and quantify the rate of deposition into hair in healthy adults using a linked population pharmacokinetic model.

Methods: Healthy adults >18 years of age received dextroamphetamine 10 mg orally for 7 days.

Time course of acetaminophen-protein adducts and acetaminophen metabolites in circulation of overdose patients and in HepaRG cells.

1. It has been suggested that acetaminophen (APAP)-protein adducts can be measured in circulation to diagnose APAP-induced liver injury. However, the full-time course of plasma adducts has not been studied specifically in early-presenting overdose patients.

Quantification of a biomarker of acetaminophen protein adducts in human serum by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry: clinical and animal model applications.

The aims of this study were to develop, validate, and apply a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method for quantification of protein-derived 3-(cystein-S-yl)-acetaminophen (APAP-Cys) in human serum. Formation of acetaminophen (APAP) protein adducts is thought to be a critical, early event in the development of APAP-induced hepatotoxicity, and quantification of these protein adducts in human serum represents a valuable tool for assessment of APAP exposure, metabolism, and toxicity. In the reported procedure, serum samples were first dialyzed or passed through gel filtration columns to remove APAP-Cys not covalently bound to proteins.

Prolonged Acetaminophen-Protein Adduct Elimination During Renal Failure, Lack of Adduct Removal by Hemodiafiltration, and Urinary Adduct Concentrations After Acetaminophen Overdose.

Elevated concentrations of serum acetaminophen-protein adducts, measured as protein-derived acetaminophen-cysteine (APAP-CYS), have been used to support a diagnosis of APAP-induced liver injury when histories and APAP levels are unhelpful. Adducts have been reported to undergo first-order elimination, with a terminal half-life of about 1.6 days.

Establishment and characterization of a primary calcifying epithelial odontogenic tumor cell population.

Unlabelled: Calcifying epithelial odontogenic tumors (CEOTs) are rare neoplasms derived from dental tissue with the unique characteristic of calcifying amyloid-like material.

Objectives: To establish primary CEOT epithelial-derived cell populations, investigate the expression of enamel matrix proteins (EMPs), and identify potential ameloblastin (AMBN) and patched 1 (PTCH1) gene alterations.

Materials And Methods: A 28-year-old patient with a lesion of the posterior maxilla, radiographically characterized by a radiolucency with well-defined borders containing mixed radiopacities, agreed to participate with informed consent.

Plasma and liver acetaminophen-protein adduct levels in mice after acetaminophen treatment: dose-response, mechanisms, and clinical implications.

At therapeutic doses, acetaminophen (APAP) is a safe and effective analgesic. However, overdose of APAP is the principal cause of acute liver failure in the West. Binding of the reactive metabolite of APAP (NAPQI) to proteins is thought to be the initiating event in the mechanism of hepatotoxicity.

Recommendations of the national football league physician society task force on the use of toradol(®) ketorolac in the national football league.

Ketorolac tromethamine (Toradol(®)) is a non-steroidal anti-inflammatory drug that has potent analgesic and anti-inflammatory properties. It can be administered orally, intravenously, intramuscularly, or via a nasal route. Ketorolac injections have been used for several years in the National Football League (NFL), in both the oral and injectable forms, to treat musculoskeletal injuries and to prevent post-game soreness.

The androgen receptor and its use in biological assays: looking toward effect-based testing and its applications.

Steroid abuse is a growing problem among amateur and professional athletes. Because of an inundation of newly and illegally synthesized steroids with minor structural modifications and other designer steroid receptor modulators, there is a need to develop new methods of detection which do not require prior knowledge of the abused steroid structure. The number of designer steroids currently being abused is unknown because detection methods in general are only identifying substances with a known structure.

Validation of a liquid chromatography-tandem mass spectrometry method for the detection of nicotine biomarkers in hair and an evaluation of wash procedures for removal of environmental nicotine.

The aim of this exploratory study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for the quantification of nicotine, eight nicotine metabolites, and two minor tobacco alkaloids in fortified analyte-free hair and subsequently apply this method to hair samples collected from active smokers. An additional aim of the study was to include an evaluation of different wash procedures for the effective removal of environmentally deposited nicotine from tobacco smoke. An apparatus was designed for the purpose of exposing analyte-free hair to environmental tobacco smoke in order to deposit nicotine onto the hair surface.

HepaRG cells: a human model to study mechanisms of acetaminophen hepatotoxicity.

Unlabelled: Acetaminophen (APAP) overdose is the leading cause of acute liver failure in Western countries. In the last four decades much progress has been made in our understanding of APAP-induced liver injury through rodent studies. However, some differences exist in the time course of injury between rodents and humans.

Identification and quantification of nicotine biomarkers in human oral fluid from individuals receiving low-dose transdermal nicotine: a preliminary study.

The objective of this preliminary study was to identify and quantify potential nicotine (NIC) biomarkers in post-exposure oral fluid samples collected from 10 NIC-abstinent human participants administered 7 mg transdermal NIC using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Oral fluid samples were collected prior to NIC patch application and at 0.5 and 0.

Effect of anabolic-androgenic steroids and glucocorticoids on the kinetics of hAR and hGR nucleocytoplasmic translocation.

Although the qualitative nucleocytoplasmic transport of nuclear hormone receptors (NHRs) has been studied, there is little documentation of the cellular kinetics of this transport. Here, translocation studies using the human androgen receptor (hAR) and the human glucocorticoid receptor (hGR) were performed to aid in identifying the mechanism by which anabolic-androgenic steroids (AAS) were activating hAR and potentially interacting with hGR and how glucocorticoid ligands were interacting with the hGR and hAR. The real-time analysis of EGFP-labeled hAR and hGR ligand-induced cytoplasm-to-nucleus translocation was performed using fluorescence microscopy to better understand the action of these NHRs in a physiologically relevant cell-based model.

A novel validated procedure for the determination of nicotine, eight nicotine metabolites and two minor tobacco alkaloids in human plasma or urine by solid-phase extraction coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry.

A novel validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) procedure was developed and fully validated for the simultaneous determination of nicotine-N-beta-D-glucuronide, cotinine-N-oxide, trans-3-hydroxycotinine, norcotinine, trans-nicotine-1'-oxide, cotinine, nornicotine, nicotine, anatabine, anabasine and cotinine-N-beta-D-glucuronide in human plasma or urine. Target analytes and corresponding deuterated internal standards were extracted by solid-phase extraction and analyzed by LC-MS/MS with electrospray ionization (ESI) using multiple reaction monitoring (MRM) data acquisition. Calibration curves were linear over the selected concentration ranges for each analyte, with calculated coefficients of determination (R(2)) of greater than 0.

Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations.

Aims: Our goal was to determine if clinically relevant concentrations of aqueous extract of cigarette smoke (CSE) have direct deleterious effects on ventricular myocytes during simulated ischemia, and to investigate the mechanisms involved.

Methods: CSE was prepared with a smoking chamber. Ischemia was simulated by metabolic inhibition (MI) with cyanide (CN) and 0 glucose.

Ketoconazole, a cytochrome P450 3A4 inhibitor, markedly increases concentrations of levo-acetyl-alpha-methadol in opioid-naive individuals.

Background: Levo-acetyl-alpha-methadol (LAAM) exerts most of it mu-agonist activity through the action of its 2 N-demethylation metabolites, norLAAM and dinorLAAM. The N-demethylation of LAAM to norLAAM and norLAAM to dinorLAAM is primarily performed by cytochrome P450s (CYP) in the 3A family. No previous studies have been conducted to determine the effect of in vivo inhibition of CYP3A on the pharmacokinetics and pharmacodynamics of LAAM.

The effect of hair color on the incorporation of codeine into human hair.

The influence of melanin on the binding of xenobiotics in hair will impact the interpretation of drug concentrations determined by hair testing. The purpose of this study was to determine if codeine, as a model compound of abused drugs, would be incorporated into black, brown, blond, or red hair as a function of melanin concentration. Such data would assist in the interpretation of codeine concentrations in hair and help elucidate the potential influence of hair color on incorporation of drugs.

Ofloxacin as a reference marker in hair of various colors.

It has been proposed that administration of a reliable marker substance to human subjects may enhance the ability to identify drug use and treatment compliance in drug treatment programs. The goal of this study was to determine if an oral dose of the antibiotic ofloxacin (OFLX) could be used as a "marker" substance to establish reference points with respect to time in hair of various colors. Male and female subjects (n = 32) between 18 and 40 years of age received 800 mg of OFLX as a divided oral dose on a single day.

Cocaine, benzoylecgonine, amphetamine, and N-acetylamphetamine binding to melanin subtypes.

Experiments have been performed to document the in vitro binding of cocaine, benzoylecgonine (BE), amphetamine, and N-acetylamphetamine (N-AcAp) to synthetic melanin subtypes. The two predominant melanin types in hair are the black eumelanins and the reddish-brown pheomelanins. The melanins included in this study are two black eumelanin subtypes [5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) derived melanins], a reddish-brown pheomelanin [from 5-cysteinyl-S-Dopa (5-CysDOPA)], and two mixed eu-/pheomelanin copolymers.

Influx and efflux of amphetamine and N-acetylamphetamine in keratinocytes, pigmented melanocytes, and nonpigmented melanocytes.

To establish an in vitro model of drug incorporation into hair and to elucidate the potential roles of hair cell selectivity and hair color in the incorporation of certain drugs into hair, the basic drug amphetamine and its nonbasic analog N-acetylamphetamine (N-AcAp) were analyzed for influx and efflux into and out of keratinocytes, pigmented melanocytes (PM), and nonpigmented melanocytes (NPM) as a model for incorporation and efflux of these drugs from hair cells. NPM were of the same melan-a cell line as PM, but cultured in the presence of the tyrosinase inhibitor phenylthiocarbamide. Results show that PM take up large amounts of the basic drug amphetamine (levels of uptake dependent on melanin content), whereas keratinocytes and NPM take up only small amounts of amphetamine.

Indicators of cocaine exposure and preterm birth.

Objective: To identify predictors of cocaine exposure during pregnancy, using hair and urine assays and self-report, and the association with preterm birth.

Methods: A nested case-control study was conducted in a cohort of 2611 black and white women enrolled in prenatal care in central North Carolina. Cocaine exposure was ascertained by self-report (263 cases, 612 controls), urine assays at 24-29 weeks' gestation (226 cases, 564 controls) and postpartum (160 cases, 408 controls), and postpartum hair assays (169 cases, 435 controls).