Analysis of skeletal muscle has potential value in the assessment of cocaine-related deaths

Rees, Kelly A.; Seulin, Saskia Carolina; Yonamine, Maurı́cio; Leyton, Vilma; Muñoz, Daniel Romero; Gianvecchio, Victor Alexandre Percínio; Pounder, Derrick J.; Osselton, M. David

doi:10.1016/j.forsciint.2012.12.005

Cited by 14 publications

(13 citation statements)

References 29 publications

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“…Interest is currently focused on the quantification of drugs in PM materials other than blood, including bile, brain, liver, muscle, and vitreous humor . However, while these alternative materials show promising results with individual drugs or in specific circumstances, femoral venous blood still represents the most viable material for interpretative purposes in PM toxicology, with a more extensive range of reference concentrations published in the literature.…”

Section: Resultsmentioning

confidence: 99%

Summary statistics for drug concentrations in post‐mortem femoral blood representing all causes of death

Ketola

Ojanperä

2019

Drug Testing and Analysis

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Concentration distributions for 183 drugs and metabolites frequently found in post‐mortem (PM) femoral venous blood were statistically characterized based on an extensive database of 122 234 autopsy cases investigated during an 18‐year period in a centralized laboratory. The cases represented all causes of death, with fatal drug poisonings accounting for 8%. The proportion of males was 74% with a median age of 58 years compared with 26% females with a median age of 64 years. In 36% of these cases, blood alcohol concentration was higher than or equal to 0.2‰, the median being 1.6‰. The mean, median, and upper percentile (90th, 95th, 97.5th) drug concentrations were established, as the median PM concentrations give an idea of the “normal” PM concentration level, and the upper percentile concentrations indicate possible overdose levels. A correspondence was found between subsets of the present and the previously published PM drug concentrations from another laboratory that grouped cases according to the cause of death. Our results add to the knowledge for evidence‐based interpretation of drug‐related deaths.

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Section: Resultsmentioning

confidence: 99%

Summary statistics for drug concentrations in post‐mortem femoral blood representing all causes of death

Ketola

Ojanperä

2019

Drug Testing and Analysis

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“…VH also appears useful, in the absence of blood, for revealing use of cocaine [ 104 , 268 ]. Moreover, the detection window is wider than in blood, as seen from the cases where cocaine is detected in VH but not in blood [ 91 ]. Jenkins and Oblock [ 269 ] showed that phencyclidine (PCP) was systematically detected in VH when detected in blood and/or urine.…”

Section: Interpretation Of Vitreous Humor Analysis Resultsmentioning

confidence: 99%

“…Bévalot et al [ 88 ], in a series of 92 human autopsies, found the left/right VH differential to be non-significant for meprobamate. Findings were similar for 3,4-methylenedioxymethamphetamine (MDMA) [ 89 ], phenytoin [ 90 ], barbiturates [ 90 ] and cocaine [ 91 ]. However, for compounds such as digitalis-glycoside, which accumulates dramatically in the retina [ 92 ], sampling problems such as choroid and retinal cell aspiration may affect observed concentrations, and we recommend separate sampling of the two VH specimens, without pooling.…”

Section: Analysis Of Vitreous Humourmentioning

confidence: 99%

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

et al. 2015

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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.

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“…Our lower signal-to-noise and relatively small current at 0 mV may have precluded detection of a subtle fast flicker block. It is also important to note that the cocaine concentration in cardiac cells (in patients) very likely never exceeds 1 mM (Rees et al, 2013 Bystrowska et al, 2012; Giroud et al, 2004; Patel, 1996; Peretti et al, 1990). In addition, the SR membrane potential is not likely to stray far from 0 mV (Somlyo et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

Potential role of cardiac calsequestrin in the lethal arrhythmic effects of cocaine

Sanchez

Hayes

Barr

et al. 2013

Drug and Alcohol Dependence

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Background Cocaine-related deaths are continuously rising and its overdose is often associated with lethal cardiotoxic effects. Methods and Results Our approach, employing isothermal titration calorimetry (ITC) and light scattering in parallel, has confirmed the significant affinity of human cardiac calsequestrin (CASQ2) for cocaine. Calsequestrin (CASQ) is a major Ca2+-storage protein within the sarcoplasmic reticulum (SR) of both cardiac and skeletal muscles. CASQ acts as a Ca2+ buffer and Ca2+-channel regulator through its unique Ca2+-dependent oligomerization. Equilibrium dialysis and atomic absorption spectroscopy experiments illustrated the perturbational effect of cocaine on CASQ2 polymerization, resulting in substantial reduction of its Ca2+-binding capacity. We also confirmed the accumulation of cocaine in rat heart tissue and the substantial effects cocaine has on cultured C2C12 cells. The same experiments were performed with methamphetamine as a control, which displayed neither affinity for CASQ2 nor any significant effects on its function. Since cocaine did not have any direct effect on the Ca2+-release channel judging from our single channel recordings, these studies provide new insights into how cocaine may interfere with the normal E-C coupling mechanism with lethal arrhythmogenic consequences. Conclusion We propose that cocaine accumulates in SR through its affinity for CASQ2 and affects both SR Ca2+ storage and release by altering the normal CASQ2 Ca2+-dependent polymerization. By this mechanism, cocaine use could produce serious cardiac problems, especially in people who have genetically-impaired CASQ2, defects in other E-C coupling components, or compromised cocaine metabolism and clearance.

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Analysis of skeletal muscle has potential value in the assessment of cocaine-related deaths

Cited by 14 publications

References 29 publications

Summary statistics for drug concentrations in post‐mortem femoral blood representing all causes of death

Summary statistics for drug concentrations in post‐mortem femoral blood representing all causes of death

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

Potential role of cardiac calsequestrin in the lethal arrhythmic effects of cocaine

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