scholarly journals Femoral blood concentrations of flualprazolam in 33 postmortem cases

2020 ◽  
Vol 307 ◽  
pp. 110101 ◽  
Author(s):  
Pirkko Kriikku ◽  
Ilpo Rasanen ◽  
Ilkka Ojanperä ◽  
Gunilla Thelander ◽  
Robert Kronstrand ◽  
...  
Keyword(s):  
Blood Concentrations ◽  
Femoral Blood

Femoral blood concentrations of the designer benzodiazepine etizolam in post-mortem cases

2020 ◽  
pp. 002580242097381
Author(s):  
Laura J Hikin ◽  
Paul R Smith ◽  
Peter D Maskell ◽  
Hassan Kurimbokus ◽  
Emily Ashong ◽  
...  
Keyword(s):  
Drug Abusers ◽  
Post Mortem ◽  
Limited Data ◽  
Spectrometry Method ◽  
Blood Concentrations ◽  
Blunt Force Trauma ◽  
The World ◽  
Femoral Blood ◽  
The Mean ◽  
Multiple Drugs

Etizolam is a thienodiazepine that although licensed for clinical usage in Japan, India and South Korea is commonly abused and detected in post-mortem cases around the world. To date, there are limited data in the literature to allow for the interpretation of blood concentrations of etizolam in post-mortem cases. A liquid chromatography with tandem mass spectrometry method was used to quantitate etizolam concentrations in 28 post-mortem cases where etizolam was detected. The median concentration of etizolam in femoral blood was 8.5 ng/mL (range 1.0–172.0 ng/mL; n = 24); in antemortem plasma, the etizolam concentration range was 4–44 ng/mL ( n = 4). The mean age of the individuals abusing etizolam was 38.5 ± 8.4 years (median 39 years), with the majority being male (86%). In all of the cases, multiple drugs were detected, with the most common being pregabalin (61%) followed by morphine/heroin (54%), diazepam (54%) and benzoylecgonine (21%), illustrating the increasing problem of poly-substance use in drug abusers. The cause of death in the cases in which etizolam was detected was multi-drug toxicity in 87.5% of the cases, with 12.5% unrelated to drug use (hangings and blunt-force trauma). These data will further help forensic practitioners with the interpretation of post-mortem etizolam concentrations.

scholarly journals Emerging Synthetic Fentanyl Analogs

2017 ◽  
Vol 7 (1) ◽  
pp. 36-40 ◽  
Author(s):  
Harold E. Schueler
Keyword(s):  
Illicit Drug ◽  
Forensic Toxicology ◽  
Drug Market ◽  
Medical Examiner ◽  
The Internet ◽  
Blood Concentrations ◽  
Fentanyl Analogs ◽  
Femoral Blood ◽  
Drug Traffickers ◽  
Death Investigation

Hundreds of synthetic substances have been introduced into the illicit drug market over the last ten years, but none of these drugs has had as poisonous a consequence as the emergence of the synthetic fentanyl analogs. Initially, pharmaceutical grade or illicit fentanyl was mixed with heroin, allegedly to boost the potency of the heroin. Then, the amounts of fentanyl spiked gradually increased until the proportion of fentanyl was greater than the proportion of heroin. Ultimately, many overdose cases began consisting of only fentanyl. The emergence of numerous synthetic fentanyl analogs, including acetylfentanyl, butyrylfentanyl, acrylfentanyl, furanylfentanyl and β-hydroxythiofentanyl, which are manufactured in China, were made available to the illicit drug traffickers over the Internet. In July of 2016, the most potent commercially available opioid, carfentanil, started appearing in illicit drug submissions and medical examiner death investigation cases in Northeast Ohio. Postmortem femoral blood carfentanil concentrations are in the picogram per milliliter (pg/mL) range, which is extremely low, and tests the limits of detection for most analytical forensic toxicology laboratories. The interpretation of these low carfentanil blood concentrations in antemortem and postmortem specimens is made difficult due to the overlap in the concentrations between these specimen types. The presence of these powerful synthetic fentanyl analogs presents a challenge to forensic toxicology laboratories preparing to analyze for these substances.

scholarly journals Postmortem Femoral Blood Concentrations of Risperidone

2013 ◽  
Vol 38 (1) ◽  
pp. 57-60 ◽  
Author(s):  
Kristian Linnet ◽  
Sys Stybe Johansen
Keyword(s):  
Blood Concentrations ◽  
Femoral Blood

scholarly journals Postmortem Femoral Blood Concentrations of Amlodipine

2011 ◽  
Vol 35 (4) ◽  
pp. 227-231 ◽  
Author(s):  
K. Linnet ◽  
L. M. Lang ◽  
S. S. Johansen
Keyword(s):  
Blood Concentrations ◽  
Femoral Blood

The role of aromatic microbial metabolites

2018 ◽  
pp. 97-108
Author(s):  
Н.В. Белобородова ◽  
В.В. Мороз ◽  
А.Ю. Бедова
Keyword(s):  
Process Integration ◽  
Biological Effects ◽  
Clinical Findings ◽  
Multiple Organ ◽  
Critical Conditions ◽  
Clear Understanding ◽  
Microbial Metabolites ◽  
Blood Concentrations

Интеграция метаболизма макроорганизма и его микробиоты, обеспечивающая в норме симбиоз и саногенез, нарушается при заболеваниях, травме, критическом состоянии, и вектор взаимодействия может изменяться в пользу прокариотов по принципу «метаболиты бактерий - против хозяина». Анализ литературы показал, что, с одной стороны, имеется живой интерес к ароматическим микробным метаболитам, с другой - отсутствует четкое представление об их роли в организме человека. Публикации, касающиеся ряда ароматических микробных метаболитов (фенилкарбоновых кислот, ФКК), как правило, не связаны между собой по тематике и направлены на решение тех или иных прикладных задач в разных областях биологии и медицины. Цель обзора - анализ информации о происхождении, биологических эффектах ФКК в экспериментах in vitro и in vivo , и клинических наблюдениях. Обобщая результаты приведенных в обзоре исследований на клеточном, субклеточном и молекулярном уровнях, логично предположить участие ароматических микробных метаболитов в патогенезе полиорганной недостаточности при сепсисе. Наиболее перспективным для раскрытия роли ароматических микробных метаболитов представляется изучение механизмов вторичной почечной недостаточности и септической энцефалопатии. Важным направлением для будущих исследований является изучение влияния продуктов микробной биодеградации ароматических соединений на развитие диссеминированного внутрисосудистого свертывания крови, артериальной гипотензии и септического шока. Результаты дальнейших исследований будут иметь не только фундаментальное значение, но и обогатят практическую медицину новыми диагностическими и лечебными технологиями. Significant increases in blood concentrations of some aromatic metabolites (phenylcarboxylic acids, PhCAs) in patients with sepsis have been previously shown. Enhanced bacterial biodegradation of aromatic compounds has been demonstrated to considerably contribute to this process. Integration of macroorganism metabolism and its microbiota, which provides normal symbiosis and sanogenesis, is disturbed in diseases, trauma, and critical conditions. Direction of this interaction may change in favor of prokaryotes according to the principle, “bacterial metabolites are against the host”. Analysis of literature showed a particular interest of many investigators to aromatic microbial metabolites. However, there is no clear understanding of their role in the human body. Publications on PhCAs are generally not thematically interrelated and usually focus on solving applied tasks in different fields of biology and medicine. The aim of this work was to consolidate existing information about origin and biological effects of PhCAs in in vitro / in vivo experiments and some clinical findings. The presented summary of reported data from studies performed at cellular, sub-cellular, and molecular levels suggests participation of aromatic microbial metabolites in the pathogenesis of multiple organ failure in sepsis. Studying mechanisms of secondary renal failure and septic encephalopathy is most promising for discovering the function of aromatic microbial metabolites. Effects of microbial biodegradation products of aromatic substances on development of disseminated intravascular coagulation, hypotension, and septic shock are an important challenge for future studies. Results of further investigations will be not only fundamental, but will also enrich medical practice with new diagnostic and therapeutic technologies.

Interrelation between ofsystemic inflammation factors and cardiovascular calcification factors in patients of chronic kidney disease 5D stage

2020 ◽  
Vol 24 (5) ◽  
pp. 58-63
Author(s):  
A. M. Mambetova ◽  
M. H. Hutueva ◽  
I. K. Thabisimova ◽  
A. S. Kegaduyev
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Systemic Inflammation ◽  
Heart Valves ◽  
Prognostic Score ◽  
Risk Index ◽  
Glasgow Prognostic Score ◽  
Probability Of Detection ◽  
Blood Concentrations ◽  
The Glasgow Prognostic Score

BACKGROUND. The role of inflammation and uremic intoxication in the development and progression of bone mineral dis­orders, including cardiovascular calcification, has been actively studied over the past decades. PATIENTS AND METHODS. A single-stage, cohort study of 85 patients with stage 5D CKD treated with programmatic hemodialysis was conducted. The blood concentrations of interleukin-3 (IL-3) and interleukin-6 (IL-6) were determined using the enzyme immunoassay, the level of fibrinogen - using the Rutberg method, and the level of p2-microglobulins - using the nephelometric method. The blood leu­kocyte shift index (ISLC) and the Glasgow Prognostic Score (GPS) risk index for systemic inflammation were also calculated, taking into account the level of C-reactive protein (CRP) and blood albumin. The presence of valvular calcification, its severity, and calcification of the abdominal aortic wall was recorded. Statistical analysis was performed using the program STATISTICA 12.6 ("StatSoft", USA). THE AIM: to evaluate the relationship between factors of systemic inflammation and cardiovascular cal­cification in patients with stage 5D chronic kidney disease. RESULTS. The risk of detecting calcification of the aorta and heart valves was influenced by the pro-inflammatory cytokines IL-3 and IL-6, as well as ISLK and GPS. However, inflammatory fac­tors such as fibrinogen, p2-microglobulin, and CRP levels in the blood did not show a statistically significant effect. In the case when the predicted parameter was chosen not friendly calcification, but the presence of any of its components, the predictive significance of IL-3 decreased, but IL-6 remained. The 20% risk threshold was exceeded at IL-6 values of more than 33 pg/ml. The effect of ISLC on the probability of detection of calcification was shown both about friendly calcification and concerning isolated calcification of the aorta or valves. CONCLUSION. It was found that among the studied factors of inflammation, IL-6, ILK, and IL-3 demonstrate a relationship with the processes of cardiovascular calcification, GPS-only in relation to friendly calcification. Nomograms have been developed that allow predicting the detection of cardiovascular calcification in dialysis patients, depending on the state of the inflammatory circuit.

CLINICAL AND FORENSIC ASPECTS OF PHARMACOBEZOARS

2020 ◽  
Vol 12 ◽  
Author(s):  
Francisco Basílio ◽  
Ricardo Jorge Dinis-Oliveira
Keyword(s):  
State Of The Art ◽  
Signs And Symptoms ◽  
Immediate Release ◽  
Diagnosis And Treatment ◽  
Blood Concentrations ◽  
Forensic Practice ◽  
Wide Range ◽  
Therapeutic Doses ◽  
Complete History ◽  
Lethal Blood

Background: Pharmacobezoars are specific types of bezoars formed when medicines, such as tablets, suspensions, and/or drug delivery systems, aggregate and may cause death by occluding airways with tenacious material or by eluting drugs resulting in toxic or lethal blood concentrations. Objective: This work aims to fully review the state-of-the-art regarding pathophysiology, diagnosis, treatment and other relevant clinical and forensic features of pharmacobezoars. Results: patients of a wide range of ages and in both sexes present with signs and symptoms of intoxications or more commonly gastrointestinal obstructions. The exact mechanisms of pharmacobezoar formation are unknown but is likely multifactorial. The diagnosis and treatment depend on the gastrointestinal segment affected and should be personalized to the medication and the underlying factor. A good and complete history, physical examination, image tests, upper endoscopy and surgery through laparotomy of the lower tract are useful for diagnosis and treatment. Conclusion: Pharmacobezoars are rarely seen in clinical and forensic practice. They are related to controlled or immediate-release formulations, liquid or non-digestible substances, in normal or altered digestive motility/anatomy tract, and in overdoses or therapeutic doses, and should be suspected in the presence of risk factors or patients taking drugs which may form pharmacobezoars.

Cytotoxicity Evaluation of the First Ten MEIC Chemicals: Acute Lethal Toxicity in Man Predicted by Cytotoxicity in Five Cellular Assays and by Oral LD50 Tests in Rodents

1989 ◽  
Vol 17 (2) ◽  
pp. 83-100
Author(s):  
Björn Ekwall ◽  
Inger Bondesson ◽  
José V. Castell ◽  
Maria José Gómez-Lechón ◽  
Sven Hellberg ◽  
...  
Keyword(s):  
In Vitro Cytotoxicity ◽  
In Vitro Tests ◽  
Human Toxicity ◽  
Blood Concentrations ◽  
Cell Systems ◽  
Cellular Assays ◽  
Preliminary Validation ◽  
Partial Least Squares Model ◽  
Lethal Dosage

The MEIC (multicentre evaluation of in vitro cytotoxicity) programme is a five-year programme to validate in vitro tests for general toxicity, and is organised by the Scandinavian Society for Cell Toxicology. Interested laboratories are invited, on an international basis, to test 50 published reference chemicals in their respective assays. Submitted results will then be evaluated yearly by the MEIC Committee for their relevance to various types of human toxicity, including an evaluation for the same chemicals of the prediction by animal tests of human toxicity. To establish the validation methods, a preliminary validation cycle is being performed in 1989/90 with submitted results for the first ten MEIC chemicals. The present paper is the very first step of this preliminary validation process. The prediction of human toxicity by five cytotoxicity assays (altogether 14 different cell systems/endpoints) has been evaluated, and also compared with the predictive value of rodent LD50 tests. Mouse LD50 prediction of human lethal dosage for these substances was good, while rat LD50 prediction was less satisfactory. The collective predictions by all 14 cell systems/endpoints of human toxicity in the form of a multivariate PLS (partial least squares) model of human acute lethal blood concentrations, as well as the corresponding prediction by a HeLa cell assay, were comparable to the efficiency of mouse LD50 prediction of human lethal dosage. When combined with simple toxicokinetic data (absorption of chemicals in the intestine and distribution volumes), the PLS model and the HeLa assay were able to predict human lethal dosage of the ten chemicals as accurately as the mouse LD50 value. The small number of chemicals studied to date means that general conclusions cannot be drawn from these results. Further validation of more chemicals with the in vitro methods is essential and promises to be worthwhile.

scholarly journals Anti-Rheumatic Effect of Antisense Oligonucleotide Cytos-11 Targeting TNF-α Expression

2021 ◽  
Vol 22 (3) ◽  
pp. 1022
Author(s):  
Tatyana P. Makalish ◽  
Ilya O. Golovkin ◽  
Volodymyr V. Oberemok ◽  
Kateryna V. Laikova ◽  
Zenure Z. Temirova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Rat Model ◽  
Peripheral Blood ◽  
Antisense Oligonucleotide ◽  
Joint Inflammation ◽  
Blood Concentrations ◽  
Tnf Α ◽  
Effective Drugs ◽  
First Time

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund’s adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.

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