- Email: [email protected]
Applications of alternative matrices (hair, saliva, sweat …) in forensic toxicology
Symp osium 4. New Trends in Forensic Tox icology
6
pleiotropic responses by peroxisome proliferators, and ii) downstream events that are responsible for the development of liver tumors in species that are sensitive to the induction of peroxisome proliferation. Tissue and species responses to peroxisome proliferators may depend on pharmacokinetics, relative abundance of PPAR isoforms, nature of PPRE in upstream regions of target genes, the extent of competition or cross-talk among the nuclear transcription factors for the PPAR heterodimerization partner RXR, and the modulating role of coactivators and corepressors on the ligand dependent transcription of PPARs. SRC·I and PBP act as coactivators of PPARs. The binding of SRC-I to PPAR is ligand independent and coexpression of SRC-l with PPAR increases the transcriptional activity of PPAR. PBP also binds to PPAR and this binding is increased in the presence of specific ligands. Since coactivators and corepressors may influence the expression of PPARs, an understanding of the expression patterns of PPARs and other components of transcriptional machinery becomes necessary. Support for a mechanistic relationship between peroxisome proliferation and hepatocarcinogenicity is provided, in part, by a close concordance with the magnitude of hepatic peroxisome proliferation and liver tumor development in rats and mice. Mice deficient in peroxisomal fatty acyl-CoA oxidase, display profound generalized spontaneous peroxisome proliferation and increased mRNA levels of genes that are regulated by PPARa . Hepatic adenomas and carcinomas develop in AOX-I- mice by 15 months of age due to sustained activation of PPARu. These observations implicate acyl-CoA and other putative substrates of AOX as possible ligands for PPARu, thus a normal AOX gene is indispensable for the physiological regulation of PPARu .
84. New Trends in Forensic Toxicology
IS41L 1 I
FORENSIC TOXICOLOGY IN THE RAPIDLY MODERNIZING SOCIETIES OF LATIN AMERICA
A. Wong. Brazil Abstract not received at time of publication.
concentrations and time of onset of drug effects as the intravenous route. In addition, arterial boli drug concentrations reaching the brain are likely to be higher following the smoked route compared to the intravenous route. Overall, these studies demonstrated that the smoked and intranasal routes are highly efficacious for the delivery of illicit drugs and produce a similar profile of drug action to the intravenous route of administration.
IS41L31
RECENT DEVELOPMENTS IN ANALYTICAL TOXICOLOGY, FOR BETTER OF WORSE
Rokus A. de Zeeuw. Dept. ofAnalytical Chemistry and Toxicology, University Centre fo r Pharma cy, NL-9 713 AV Groningen, The Netherlands When considering the state of the art in forensic toxicology from an analytical perspective, the key developments can be subdivided into 3 major areas: (I ) Basic analytical. Here we see the need to be able to deal with more drugs (and metabolites) at ever decreasing levels in a large variety of matrices. As a result, there are constant changes in approaches and instrumentation. (2) Forensic horizon, Gone are the days that forensic toxicology was a rather obscure discipline, mainly limited to digging into dead bodies and affecting only a few people in society. Today. forensic analysis has widened its scope dramatically, in areas such as workplace toxicology, drug abuse testing, drugs and driving, doping, environmental and veterinary toxicology, etc. Hence, it now affects a considerable percentage of our society and focuses much more on living individuals and systems. (3) Validation and interpretation. Because forensic analyses may have severe criminal, civil or punitive consequences, the validation of our methods and approaches is of utmost importance. Also, the interpretation of the analytical results must be done with prudence, taking into account the chemical and biological diversity of our society. The pro' s and con's in these developments will be discussed.
IS4/L41
APPLICATIONS OF ALTERNATIVE MATRICES (HAIR, SALIVA , SWEAT ...) IN FORENSIC TOXICOLOGY
P. Kintz *, B. Lud es. lnstitut de Medecine Legale, Strasbo urg, France
Is4/l2 1RECENT DISCOVERIES IN PHARMACOKINETICS OF DRUGS OF ABUSE
E.J. Cone. Addiction Research Center, NIDA, PO Box 5180, Baltimore, MD, USA Controlled human dosing studies with drugs of abuse have revealed the importance of the chosen route of administration on the delivery of drugs to the bloodstream and to their site of action. Recently, the intranasal and smoked routes have become favored by some populations for the administration of illicit drugs. Research studies with experienced heroin and cocaine users indicated that intranasally administered drug generally provided lower blood concentrations of drug and a slower onset of action compared to the intravenous route; however, intranasal doses are easily manipulated by the user and adequate bioavailability and desired drug effects can be achieved. In addition, the trauma of needle use is avoided and disease exposure is reduced by this route. For marijuana, the smoked route of administration has always been the preferred route. In recent studies with smoked marijuana, it was revealed that single puffs of marijuana smoke produced detectable blood concentrations of tetrahdyrocannabinol, the active ingredient of marijuana. Continued smoking produced rapid increases in blood concentrations with peak concentrations and effects occurring before or near the end of smoking, demonstrating the rapidity and efficacy of the smoking route for marijuan a. The smoked route has also become popular with cocaine and heroin users. This route provided equivalent peak blood
It is generally accepted that chemical testing of biological fluids is the most objective means of diagnosis of drug use. The presence of a drug analyte in a biological specimen can be used to document exposure. The standard in drug testing is the immunoassay screen, followed by the gas chromatographic-mass spectrometric confirmation conducted on a urine sample. In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional biological specimens such as saliva, sweat, meconium or hair. The advantages of these samples over traditional media, like urine and blood, are obvious: collection is almost noninvasive, relatively easy to perform, and in forensic situations it may be achieved under close supervision of law enforcement officiers to prevent adulteration or substitution. Moreover, the window of drug detection is dramatically extended to weeks, months or even years. The aim of this review is to document usefullness of these alternative matrices in forensic situations.
6
pleiotropic responses by peroxisome proliferators, and ii) downstream events that are responsible for the development of liver tumors in species that are sensitive to the induction of peroxisome proliferation. Tissue and species responses to peroxisome proliferators may depend on pharmacokinetics, relative abundance of PPAR isoforms, nature of PPRE in upstream regions of target genes, the extent of competition or cross-talk among the nuclear transcription factors for the PPAR heterodimerization partner RXR, and the modulating role of coactivators and corepressors on the ligand dependent transcription of PPARs. SRC·I and PBP act as coactivators of PPARs. The binding of SRC-I to PPAR is ligand independent and coexpression of SRC-l with PPAR increases the transcriptional activity of PPAR. PBP also binds to PPAR and this binding is increased in the presence of specific ligands. Since coactivators and corepressors may influence the expression of PPARs, an understanding of the expression patterns of PPARs and other components of transcriptional machinery becomes necessary. Support for a mechanistic relationship between peroxisome proliferation and hepatocarcinogenicity is provided, in part, by a close concordance with the magnitude of hepatic peroxisome proliferation and liver tumor development in rats and mice. Mice deficient in peroxisomal fatty acyl-CoA oxidase, display profound generalized spontaneous peroxisome proliferation and increased mRNA levels of genes that are regulated by PPARa . Hepatic adenomas and carcinomas develop in AOX-I- mice by 15 months of age due to sustained activation of PPARu. These observations implicate acyl-CoA and other putative substrates of AOX as possible ligands for PPARu, thus a normal AOX gene is indispensable for the physiological regulation of PPARu .
84. New Trends in Forensic Toxicology
IS41L 1 I
FORENSIC TOXICOLOGY IN THE RAPIDLY MODERNIZING SOCIETIES OF LATIN AMERICA
A. Wong. Brazil Abstract not received at time of publication.
concentrations and time of onset of drug effects as the intravenous route. In addition, arterial boli drug concentrations reaching the brain are likely to be higher following the smoked route compared to the intravenous route. Overall, these studies demonstrated that the smoked and intranasal routes are highly efficacious for the delivery of illicit drugs and produce a similar profile of drug action to the intravenous route of administration.
IS41L31
RECENT DEVELOPMENTS IN ANALYTICAL TOXICOLOGY, FOR BETTER OF WORSE
Rokus A. de Zeeuw. Dept. ofAnalytical Chemistry and Toxicology, University Centre fo r Pharma cy, NL-9 713 AV Groningen, The Netherlands When considering the state of the art in forensic toxicology from an analytical perspective, the key developments can be subdivided into 3 major areas: (I ) Basic analytical. Here we see the need to be able to deal with more drugs (and metabolites) at ever decreasing levels in a large variety of matrices. As a result, there are constant changes in approaches and instrumentation. (2) Forensic horizon, Gone are the days that forensic toxicology was a rather obscure discipline, mainly limited to digging into dead bodies and affecting only a few people in society. Today. forensic analysis has widened its scope dramatically, in areas such as workplace toxicology, drug abuse testing, drugs and driving, doping, environmental and veterinary toxicology, etc. Hence, it now affects a considerable percentage of our society and focuses much more on living individuals and systems. (3) Validation and interpretation. Because forensic analyses may have severe criminal, civil or punitive consequences, the validation of our methods and approaches is of utmost importance. Also, the interpretation of the analytical results must be done with prudence, taking into account the chemical and biological diversity of our society. The pro' s and con's in these developments will be discussed.
IS4/L41
APPLICATIONS OF ALTERNATIVE MATRICES (HAIR, SALIVA , SWEAT ...) IN FORENSIC TOXICOLOGY
P. Kintz *, B. Lud es. lnstitut de Medecine Legale, Strasbo urg, France
Is4/l2 1RECENT DISCOVERIES IN PHARMACOKINETICS OF DRUGS OF ABUSE
E.J. Cone. Addiction Research Center, NIDA, PO Box 5180, Baltimore, MD, USA Controlled human dosing studies with drugs of abuse have revealed the importance of the chosen route of administration on the delivery of drugs to the bloodstream and to their site of action. Recently, the intranasal and smoked routes have become favored by some populations for the administration of illicit drugs. Research studies with experienced heroin and cocaine users indicated that intranasally administered drug generally provided lower blood concentrations of drug and a slower onset of action compared to the intravenous route; however, intranasal doses are easily manipulated by the user and adequate bioavailability and desired drug effects can be achieved. In addition, the trauma of needle use is avoided and disease exposure is reduced by this route. For marijuana, the smoked route of administration has always been the preferred route. In recent studies with smoked marijuana, it was revealed that single puffs of marijuana smoke produced detectable blood concentrations of tetrahdyrocannabinol, the active ingredient of marijuana. Continued smoking produced rapid increases in blood concentrations with peak concentrations and effects occurring before or near the end of smoking, demonstrating the rapidity and efficacy of the smoking route for marijuan a. The smoked route has also become popular with cocaine and heroin users. This route provided equivalent peak blood
It is generally accepted that chemical testing of biological fluids is the most objective means of diagnosis of drug use. The presence of a drug analyte in a biological specimen can be used to document exposure. The standard in drug testing is the immunoassay screen, followed by the gas chromatographic-mass spectrometric confirmation conducted on a urine sample. In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional biological specimens such as saliva, sweat, meconium or hair. The advantages of these samples over traditional media, like urine and blood, are obvious: collection is almost noninvasive, relatively easy to perform, and in forensic situations it may be achieved under close supervision of law enforcement officiers to prevent adulteration or substitution. Moreover, the window of drug detection is dramatically extended to weeks, months or even years. The aim of this review is to document usefullness of these alternative matrices in forensic situations.