Tobacco smoking causes high rates of mortality and morbidity throughout the world. Despite the availability of smoking-cessation medications, maintenance of long-term abstinence is difficult, and most individuals who attempt to quit smoking relapse. Although tobacco smoke contains many substances, researchers and policymakers agree that nicotine is a major cause of tobacco dependence. Understanding the neural substrates of nicotine dependence is essential for the development of more effective antismoking medications than those currently available. This article focuses on the neural substrates, especially nicotinic acetylcholine receptors, that mediate the reinforcing effects of nicotine and the development of nicotine dependence. Neuroadaptations in the function of the neurotransmitters dopamine, glutamate, and gamma-aminobutyric acid (GABA), which have been shown to be critically involved in nicotine dependence, are also reviewed. Finally, the article discusses progress in the discovery and development of smoking-cessation medications.

Neuronal mechanisms underlying development of nicotine dependence: implications for novel smoking-cessation treatments.

More than 22 million Americans age 12 and older have used inhalants, and every year more than 750,000 use inhalants for the first time. Despite the substantial prevalence and serious toxicities of inhalant use, it has been termed "the forgotten epidemic." Inhalant abuse remains the least-studied form of substance abuse, although research on its epidemiology, neurobiology, treatment, and prevention has accelerated in recent years. This review examines current findings in these areas, identifies gaps in the research and clinical literatures pertaining to inhalant use, and discusses future directions for inhalant-related research and practice efforts.

Inhalant use and inhalant use disorders in the United States.

Vitreous humor (VH) is a gelatinous substance contained in the posterior chamber of the eye, playing a mechanical role in the eyeball. It has been the subject of numerous studies in various forensic applications, primarily for the assessment of postmortem interval and for postmortem chemical analysis. Since most of the xenobiotics present in the bloodstream are detected in VH after crossing the selective blood-retinal barrier, VH is an alternative matrix useful for forensic toxicology. VH analysis offers particular advantages over other biological matrices: it is less prone to postmortem redistribution, is easy to collect, has relatively few interfering compounds for the analytical process, and shows sample stability over time after death. The present study is an overview of VH physiology, drug transport and elimination. Collection, storage, analytical techniques and interpretation of results from qualitative and quantitative points of view are dealt with. The distribution of xenobiotics in VH samples is thus discussed and illustrated by a table reporting the concentrations of 106 drugs from more than 300 case reports. For this purpose, a survey was conducted of publications found in the MEDLINE database from 1969 through April 30, 2015.

/pdf/vitreous-humor-analysis-for-the-detection-of-xenobiotics-in-3xu8hgqfjx.pdf

Vitreous humor analysis for the detection of xenobiotics in forensic toxicology: a review

Ethanol is the most frequently identified compound in forensic toxicology. Although confirmation involving mass spectrometry is desirable, relatively few methods have been published to date. A novel technique utilizing a Dean's Switch to simultaneously quantitate and confirm ethyl alcohol by flame-ionization (FID) and mass spectrometric (MS) detection after headspace sampling and gas chromatographic separation is presented. Using 100 μL of sample, the limits of detection and quantitation were 0.005 and 0.010 g/dL, respectively. The zero-order linear range (r(2) > 0.990) was determined to span the concentrations of 0.010 to 1.000 g/dL. The coefficient of variation of replicate analyses was less than 3.1%. Quantitative accuracy was within ±8%, ±6%, ±3%, and ±1.5% at concentrations of 0.010, 0.025, 0.080, and 0.300 g/dL, respectively. In addition, 1,1-difluoroethane was validated for qualitative identification by this method. The validated FID-MS method provides a procedure for the quantitation of ethyl alcohol in blood by FID with simultaneous confirmation by MS and can also be utilized as an identification method for inhalants such as 1,1-difluoroethane.

/pdf/ethanol-analysis-by-headspace-gas-chromatography-with-1ii89fy3w8.pdf

Ethanol Analysis by Headspace Gas Chromatography with Simultaneous Flame-Ionization and Mass Spectrometry Detection

Sample preparation is an important step in the development of an analytical method but is often regarded as time-consuming, laborious work. Optimum sample preparation leads to enhanced selectivity and sensitivity, however, and reduces amounts of interfering matrix compounds, resulting in less signal suppression or enhancement. Recent developments in extraction techniques that could be of interest in clinical and forensic toxicology, for example liquid-liquid, solid-phase, and headspace extraction, are summarized in this review. The advantages and disadvantages of several extraction techniques are discussed, to enable the reader to choose an appropriate method of extraction for his or her application. Attention is paid to current trends in analytical toxicology, for example miniaturization, high throughput, and automation.

Recent developments in extraction procedures relevant to analytical toxicology

A 42-year-old man was found dead after repeated exposure to 1,1-difluoroethane (DFE, Freon 152a), a propellant found in CRC Duster, a product intended for the removal of dust and lint. Toxicologic analysis detected DFE in femoral blood 136.3 mg/L, brain 117.5 mg/kg, liver 87.6 mg/kg, lung 60.3 mg/kg, adipose 235.7 mg/kg, and vitreous fluid 25.1 mg/L. The cause of death was determined to be a fatal cardiac arrhythmia due to intoxication with 1,1-difluoroethane. After comparison to previously published cases involving DFE, we suggest that analysis of adipose tissue for DFE and similar compounds, along with blood and other tissues, may be useful in distinguishing between acute versus chronic exposure. Adipose may also be a valuable alternate specimen for detection in cases where loss or elimination from blood is likely to have occurred.

Fatal cardiac arrhythmia after repeated exposure to 1,1-difluoroethane (DFE).

A 24-year-old female driver with a history of substance abuse was pronounced dead following a single car motor vehicle accident. A surviving front seat passenger witnessed the decedent inhaling "Dust Off" cleaner just prior to losing control of the vehicle. The propellant compound used in this product is the halogenated hydrocarbon 1,1-difluoroethane (DFE). Sealed autopsy specimens were examined for the presence and subsequent quantitation of DFE utilizing an Agilent 6850 gas chromatograph (GC)-flame-ionization detector. The levels of DFE obtained were as follows: 29.8 mg/L in femoral blood, 40.3 mg/L in pulmonary arterial blood, 85.6 mg/L in aortic blood, 79.9 mg/L in chest cavity blood, 21.2 mg/L in vitreous, 11.7 mg/kg in brain, 27.9 mg/kg in liver, 71.0 mg/L in urine, and 51.8 mg/total gastric contents. The presence of DFE was confirmed in the decedent's urine by injection on an Agilent 6890/5973 GC-mass spectrometer in full scan mode. This case presents a uniquely witnessed observation of the apparent impairing effects and consequences of the acute inhalation of halogenated hydrocarbons such as DFE and the operation of a motor vehicle. The proximity of time of death to inhalant use may also provide insight to postmortem distribution patterns of DFE in relation to normal physiologic blood flow. With further investigations, estimating the time of final use of an inhalant prior to death may be deciphered from such patterns, although a degree of caution should be applied in deaths resulting from severe trauma in which normal tissue structure is compromised because postmortem redistribution may result.

/pdf/a-motor-vehicle-accident-fatality-involving-the-inhalation-1ded2u16qp.pdf

A motor vehicle accident fatality involving the inhalation of 1,1-difluoroethane.

1,1-Difluoroethane (DFE) is a halogenated hydrocarbon used as a propellant in products designed for dusting electronic equipment and air brush painting. When abused, inhaled DFE produces intoxication and loss of muscular coordination. To investigate DFE toxicokinetics, groups (n = 3) of Sprague-Dawley rats were exposed to 30 s of 20 L/min DFE. The experimental model was designed to mimic exposure during abuse, a protocol which has not been conducted. Tissue collection (blood, brain, heart, liver, and kidney) occurred at 0, 10, 20, 30, 45, 60, 120, 240, 480, and 900 s. Average peak DFE levels were blood 352, brain 519, heart 338, liver 187, and kidney 364 mg/L or mg/kg. The total percent uptake of the administered dose was 4.0%. Uptake into individual compartments was 2.72, 0.38, 0.15, 0.41, and 0.32% for blood, brain, heart, liver, and kidney, respectively. All animals showed signs of intoxication within 20 s manifested as lethargy, prostration and loss of righting reflex. Marked intoxication continued for about 4 min when DFE averaged 21 mg/L in blood and 17 mg/kg in brain. Between 4 and 8 min, animals continued to show signs of sedation as evidenced by reduced aggression and excitement during handling. No discernable intoxication was evident after 8 min and blood and brain levels had fallen to 10 and 6 mg/L or kg, respectively. Plots of concentration (log) versus time were consistent with a two compartment model. Initial distribution was rapid with average half life (t((1/2))) during the alpha phase of 9 s for blood, 18 s for brain and 27 s in cardiac tissue. During beta slope elimination average t((1/2)) was 86 s in blood, 110 s in brain and 168 s in heart. Late elimination half lives were longer with blood gamma = 240 s, brain gamma = 340 s, and heart gamma = 231 s. Following acute exposure the Vd = 0.06 L, beta = 0.48 min(-1), AUC = 409.8 mg.min L(-1), and CL from blood was 0.03 L min(-1). The calculated toxicokinetic data may underestimate these parameters if DFE is abused chronically due to continued uptake into lowly perfused tissues with repeated dosing.

/pdf/uptake-and-distribution-of-the-abused-inhalant-1-1-3ep2fg60u7.pdf

Uptake and distribution of the abused inhalant 1,1-difluoroethane in the rat.

A 43-year-old female was reported to inject heroin, which led to her rapid death. Because of the potential for criminal charges, laboratory results that could verify "hotshot" heroin overdose were valuable. Initial toxicological analysis detected morphine (0.78 mg/L), amitriptyline (2.91 mg/L), and nortriptyline (2.80 mg/L) in femoral blood. Because these tricyclic antidepressant levels alone might normally be associated with a fatal outcome, the ratio of free versus total morphine (88.6%) and presence of 6-monoacetylmorphine in vitreous fluid were used support a history of rapid death following intravenous (IV) administration. The distribution of amitriptyline and nortriptyline was consistent with accumulation of drug after chronic dosing. Our other results suggest that the low morphine level in vitreous humor fluid (0.16 mg/L) relative to free morphine in femoral blood (0.78 mg/L) may also be an indicator of limited survival time following exposure to morphine. Based upon comprehensive toxicologic analysis, we determined overdose due to IV abuse of heroin was likely to have precipitated the fatal outcome. This case underscores the need for complete toxicologic workup and to consider individual variation in the dose response during toxicologic interpretation of postmortem results.

/pdf/assessing-free-and-total-morphine-following-heroin-overdose-22lmzji3hr.pdf

Assessing free and total morphine following heroin overdose when complicated by the presence of toxic amitriptyline levels.

A woman was alleged to have committed suicide by consuming a gasoline additive shortly before jumping from a second floor balcony within her home. She was found dead by police with a multitude of injuries, lying nude in a partially evaporated unknown residue that was later determined to be methanol. Samples collected at autopsy were found to contain methanol in the following concentrations: femoral blood 31.2 mg/dL, pulmonary artery blood 111.0 mg/dL, aortic blood 77.8 mg/dL, vitreous fluid 196.4 mg/dL, brain 22.0 mg/100 g, liver 21.2 mg/100 g, and kidney 25.9 mg/100 g using a headspace gas chromatographic method. Significantly, no methanol was detected in samples recovered from the esophagus, stomach, duodenum, small intestine, bile, or urine. These findings are inconsistent with either recent or delayed oral ingestion of methanol. We concluded that absorption of methanol occurred dermally and through the oral mucosa as she lay dying and saturated in the fuel additive. Based upon the toxicological data and a comprehensive forensic investigation (including documentation and analysis of evidence recovered at the scene and the autopsy), the cause of death was determined to be blunt impact trauma and methanol poisoning.

Percutaneous Absorption and Distribution of Methanol in a Homicide

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Michael Lehrer

Author Tools

Chat about Author