A Tissue Distribution Study of Propafenone in an Intentional Fatal Poisoning Case.

Propafenone (PPF) belongs to the class 1C antiarrhythmics and can cause electrocardiogram-associated adverse/toxic effects. Cases of PPF intoxication are rarely investigated. We developed a novel and selective GC-MS/MS method for the determination of PPF and its tissue distribution in an intentional fatal poisoning case, which is applicable to PPF quantification in the range of therapeutic to lethal concentrations in complex post-mortem samples. A simple and effective sample pretreatment was applied to all analyzed samples. PPF was determined without the need for dilution, even in highly complex samples containing a wide range of analyte concentrations. Quantification was performed using the standard addition method, developed and validated according to the ICH M10 guidelines. The obtained results indicated that the PPF concentration in the serum from blood taken while alive, before therapy, was the highest ever reported in the literature. Despite the intensive therapy after the patients' admission, the PPF concentrations in the lungs, spleen, femoral blood and cardiac blood were fatal or abnormally high. On the other hand, the concentrations in the liver and skeletal muscle were lower or approximately the same as observed in cases with therapeutic doses. To the best of our knowledge, the distribution of PPF has not been investigated in fatal intoxication cases and can be helpful in clinical or forensic toxicology.

Unusual concentration of tramadol detected in cadaver in the last stage of decomposition and in fly larvae in the immediate vicinity: case report and literature review.

Determination of the manner and cause of death from skeletal remains is almost always very difficult and can be a challenge for medical examiners. At the end also on skeletal remains, it is possible to assess mechanical, chemical, and thermal injuries, although it can be usually impossible. Possibilities to analyze biological material for the presence of drugs are also limited. The present study describes a case of a homeless man's skeletal remains on which a large number of fly larvae were found. Unusually high concentration of tramadol (TML) in the bone marrow (BM) = 4530 ng/g, muscle (M) = 4020 ng/g, and fly larvae (FL) = 280 ng/g was detected using a validated GC/MS method. In all analyzed samples, caffeine and N-desmethyltramadol (except BM) were qualitatively determined. Autopsy findings and toxicological analyses of the BM suggested that the cause of death could probably be intoxication by TML. It is apparent from the reviewed literature that analysis of TML in the late stages of decomposition of human body is rarely performed. Literature is predominantly focused on animal studies. Thus, TML concentrations analyzed in BM, M, or FL could be found helpful in relation to evaluation of intoxication by this substance. However, the significance of the results obtained in the presented study should be confirmed by further analyses of BM, M, or FL, where TML would be proved in lethal concentration in the blood.

Modern suicide trend from internet.

INTRODUCTION: The most common suicide methods vary slightly from country to country, partly related to the availability of effective means. Societal development over the years and especially the advent of the Internet has enabled the sudden spread of new suicide methods. Recently, especially since 2019, intentional sodium nitrite poisoning has appeared on many social networks as an increasingly popular method of suicide. MATERIAL AND METHODS: There was performed a retrospective-prospective study of the autopsy protocols of the Medico-Legal Departments of the Healthcare Surveillance Authority in Slovakia, in a period of 15 years (2008-2022). We performed the analysis of cases of death due to nitrite poisoning, focusing on cases of intentional self-harm. In all selected cases, we present complete information, including photo documentation from the place of death, as well as the results of the performed autopsy and the results of additional laboratory examinations. RESULTS: We did not record any fatal cases of unintentional, accidental consumption of sodium nitrite in Slovakia, nor any fatal cases of homicidal poisoning by this substance. However, there were three cases of intentional self-harm (completed suicide) by sodium nitrite poisoning (in 2019, 2020 and 2022). CONCLUSIONS: The correct diagnosis of the cases of sodium nitrite poisoning deaths is possible only based on evaluating all the information obtained, a thorough examination of the body and the crime scene, and the correct interpretation of the findings found during a subsequent autopsy and the results of the toxicological analysis.

Natural Taxanes: From Plant Composition to Human Pharmacology and Toxicity.

Biologically active taxanes, present in small- to medium-sized evergreen conifers of various Taxus species, are widely used for their antioxidant, antimicrobial and anti-inflammatory effects, but mostly for their antitumour effects used in the treatment of solid tumours of the breast, ovary, lung, bladder, prostate, oesophagus and melanoma. More of the substances found in Taxus plant extracts have medical potential. Therefore, at the beginning of this review, we describe the methods of isolation, identification and determination of taxanes in different plant parts. One of the most important taxanes is paclitaxel, for which we summarize the pharmacokinetic parameters of its different formulations. We also describe toxicological risks during clinical therapy such as hypersensitivity, neurotoxicity, gastrointestinal, cardiovascular, haematological, skin and renal toxicity and toxicity to the respiratory system. Since the effect of the drug-form PTX is enhanced by various Taxus spp. extracts, we summarize published clinical intoxications and all fatal poisonings for the Taxus baccata plant. This showed that, despite their significant use in anticancer treatment, attention should also be focused on the risk of fatal intoxication due to ingestion of extracts from these plants, which are commonly found in our surroundings.

Ayahuasca as a Decoction Applied to Human: Analytical Methods, Pharmacology and Potential Toxic Effects.

Ahyahuasca is a term commonly used to describe a decoction prepared by cooking the bark or crushed stems of the liana Banisteriopsis caapi (contains ß-carbolines) alone or in combination with other plants, most commonly leaves of the shrub Psychotria viridis (contains N,N-dimethyltryptamine-DMT). More than 100 different plants can serve as sources of ß-carbolines and DMT, which are the active alkaloids of this decoction, and therefore it is important to know the most accurate composition of the decoction, especially when studying the pharmacology of this plant. The aim was to summarize the latest sensitive methods used in the analysis of the composition of the beverage itself and the analysis of various biological matrices. We compared pharmacokinetic parameters in all of the studies where decoction of ayahuasca was administered and where its composition was known, whereby minimal adverse effects were observed. The therapeutic benefit of this plant is still unclear in the scientific literature, and side effects occur probably on the basis of pre-existing psychiatric disorder. We also described toxicological risks and clinical benefits of ayahuasca intake, which meant that the concentrations of active alkaloids in the decoction or in the organism, often not determined in publications, were required for sufficient evaluation of its effect on the organism. We did not find any post-mortem study, in which the toxicological examination of biological materials together with the autopsy findings would suggest potential lethality of this plant.

Synthetic cathinones - From natural plant stimulant to new drug of abuse.

As recreational substances, synthetic cathinones started to be used at the beginning of the 21st century. There is still limited data on these compounds, introduced to the illicit drug market for the most part after 2009. Considering that synthetic cathinones are currently the second largest group of new psychoactive and dangerous substances among over 670 new psychoactive substances identified in Europe and monitored by the EMCDDA, research on them should be regarded as extremely important. This review focuses on the availability of synthetic cathinones on the illicit drug market, presentation of current trends in the use of these substances, and their mechanisms of action and toxicity. The authors discuss cases of intoxication with synthetic cathinones and post-mortem diagnostics as well as the problem of combined used of synthetic cathinones with other psychoactive substances. Literature as well as clinical and forensic data indicate the need for further research on the metabolism, toxicokinetics, toxicodynamics, clinical effects, and addictive potential of synthetic cathinones, especially in the context of potential threats caused by increased consumption of this group of drugs in future.

Suicides by ingestion of pure caffeine powder. New challenge for public health?

OBJECTIVES: Intentional or unintentional caffeine abuse due to excessive intake of energy beverages is frequent. Fatalities due to caffeine intoxication are presented rarely. Over the last years, cases of caffeine ingestion for purposes of committing suicide have been reported in scientific literature. DESIGN: The aim of this case study is to report a fatal case of a 26-year-old man who intentionally ingested pure caffeine powder. METHODS: Standard autopsy, microscopic examination and toxicological examination using screening method, TLC, GC, and GC/MS were performed. RESULTS AND CONCLUSIONS: The presence of caffeine only at the concentration of 362 ug/mL in blood and 187 ug/mL in urine was revealed. The cause of death was cardiac arrest most likely due to ventricular dysrhythmia. The concentration of caffeine determined in the femoral blood of the decedent was three times higher than the lethal concentrations reported in other published case studies. Based on the investigated circumstances, the manner of death was evaluated as a suicide.

[Addictive substances in fatal cases of fall/jump from height]. / Návykové látky vo fatálnych prípadoch pádov/skokov z výsky.

The aim of the study is to analyse causes of fatal cases of falls from height focusing on the occurrence of addictive substances. The authors performed a retrospective analysis of cases dealing with falls/jumps autopsied at the Institutes of Forensic Medicine in Bratislava in the years 2005-2014 accounting for a catchment area with approximately 1.2 m population. Selection criteria were met in 360 cases, i.e. approximately 4 % of all cases autopsied. There were 68 % of men and 32 % of women involved. The age interval ranged from 10 up to 93 years (mean age 50 years). Addictive substances were found in a total of 32 % of cases, ethanol alone in 22 % of cases. The cases were divided into groups according to the cause as follows: accidental falls (24%) also involving occupational accidents (11 %), jumps in suicidal ideation (63 %) and cases with the unspecified cause of falling (13 %). Most of the cases with detected addictive substances were in the group of suicidal jumps (35 %). In this group, 32 % of patients were treated for psychiatric disorders. The most common diagnosis was a depressive disorder and schizophrenia. In the group of occupational accidents, ethanol was found in 25 % of cases. The results of the study show that it is essential to pay more attention to psychiatric patients as not even regular psychiatric care and treatment can always prevent suicide. Accordingly, there is a need to strictly monitor the ban on alcohol consumption at work and the observance of safety regulations for working at heights, and thus to minimise the occurrence of falls with fatal outcomes.

Glutamic acid decarboxylase gene disruption reveals signalling pathway(s) governing complex morphogenic and metabolic events in Trichoderma atroviride.

Glutamate decarboxylase (GAD) catalyses decarboxylation of glutamate to gamma-aminobutyrate (GABA) in a metabolic pathway connected to citrate cycle and known as GABA shunt. The gene (gad) was disrupted in Trichoderma atroviride CCM F-534 and viable mutants were characterized. Two of them were found to arise by homologous recombination and were devoid of both GAD activity and GABA. Mutants grew slower as compared to the wild type (F534). In the submerged culture, mutants developed less CO2 and consumed less O2 than the F534 without changing their respiratory quotients. Hyphae of mutants were more ramified than those of F534. Their ramification, in contrast to F534, was not increased by cyclosporin A, a drug causing hyphae ramification of several fungi and which is a calcineurin/cyclophilin inhibitor, or by FK506. Rapamycin, which is a cyclophilin but not calcineurin inhibitor, had a different effect on hyphae ramification in F534 and mutants. To examine the presence of GABA receptors in the fungus the effect of mammalian GABA-receptor modulators, such as bicuculline, gabapentin or carbamazepine on fungal morphology were investigated. Conidia of mutants germinated in a multipolar manner more frequently (up to 80 %) than those of F534. This trait was modified with cyclosporine A, FK506 and GABA receptor modulators in a different manner. Transport of chlorides, an intimate feature of GABA-regulated receptors/channels in animal cells, was measured in vegetative mycelia by means (36)Cl(-) uptake. It was significantly reduced in gad mutants. The results suggest that T. atroviride possesses a signalling pathway that involves GABA, putative GABA receptor(s), calcineurin, target of rapamycin and chloride transporter(s) to regulate physiological functions.