Intravenous haloperidol and cocaine alter the distribution of T CD3+ CD4+ , non-T/NK and NKT cells in rats.

The modulation of dopamine transmission evokes strong behavioural effects that can be achieved by commonly used psychoactive drugs such as haloperidol or cocaine. Cocaine non-specifically increases dopamine transmission by blocking dopamine active transporter (DAT) and evokes behavioural arousal, whereas haloperidol is a non-specific D2-like dopamine receptor antagonist with sedative effects. Interestingly, dopamine has been found to affect immune cells in addition to its action in the central nervous system. Here, we address the possible interactions between haloperidol and cocaine and their effects on both immune cells and behaviour in freely moving rats. We use an intravenous model of haloperidol and binge cocaine administration to evaluate the drugs' impact on the distribution of lymphocyte subsets in both the peripheral blood and the spleen. We assess the drugs' behavioural effects by measuring locomotor activity. Cocaine evoked a pronounced locomotor response and stereotypic behaviours, both of which were completely blocked after pretreatment with haloperidol. The results suggest that blood lymphopenia, which was induced by haloperidol and cocaine (except for natural killer T cells), is independent of D2-like dopaminergic activity and most likely results from the massive secretion of corticosterone. Haloperidol pretreatment prevented the cocaine-induced decrease in NKT cell numbers. Moreover, the increased systemic D2-like dopaminergic activity after cocaine administration is a significant factor in retaining T CD3+ CD4+ lymphocytes and non-T/NK CD45RA+ cells in the spleen.

Development and validation of a method for the simultaneous analysis of fatty acid ethyl esters, ethyl sulfate and ethyl glucuronide in neonatal meconium: application in two cases of alcohol consumption during pregnancy.

Alcohol consumption during pregnancy constitutes one of the leading preventable causes of birth defects and neurodevelopmental disorders in the exposed children. Fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG) and ethyl sulfate (EtS) have been studied as potential biomarkers of alcohol consumption. However, most analytical approaches proposed for their analysis in meconium samples consist of separated extraction procedures requiring the use of two meconium aliquots, which is costly in terms of both time and materials. Therefore, the aim of this study was to develop and validate a method for the simultaneous extraction of 9 FAEEs, EtG and EtS from one meconium aliquot. The sample was homogenized using methanol, and then FAEEs were extracted with hexane while EtG and EtS were isolated using acetonitrile. Then, extracts were applied to solid-phase extraction columns and analysed by gas chromatography mass spectrometry (FAEEs) and liquid chromatography tandem mass spectrometry (EtG and EtS). Calibration curves were linear with r values greater than 0.99. The LODs ranged from 0.8 to 7.5 ng/g for FAEEs and were 0.2 ng/g and 0.8 ng/g for EtS and EtG, respectively. LOQs ranged from 5 to 25 ng/g for FAEEs and were 1 ng/g and 2.5 ng/g for EtS and EtG, respectively. Accuracies and precisions were between 93.8 and 107% and between 3.5 and 9.7%, respectively. The recovery values ranged from 89.1 to 109%. The method proved to be sensitive, specific, simple and fast and allowed for the reduction of the amount of organic solvent used for extraction compared to other published data while higher recoveries were obtained. The method was used for analysis of meconium samples in two cases of mothers who were consuming alcohol during pregnancy.

Reduced ribosomal DNA transcription in the prefrontal cortex of suicide victims: consistence of new molecular RT-qPCR findings with previous morphometric data from AgNOR-stained pyramidal neurons.

Prefrontal cortical regions play a key role in behavioural regulation, which is profoundly disturbed in suicide. The study was carried out on frozen cortical samples from the anterior cingulate cortex (dorsal and ventral parts, ACd and ACv), the orbitofrontal cortex (OFC), and the dorsolateral cortex (DLC) obtained from 20 suicide completers (predominantly violent) with unknown psychiatric diagnosis and 21 non-suicidal controls. The relative level of ribosomal RNA (rRNA) as a marker of the transcriptional activity of ribosomal DNA (rDNA) was evaluated bilaterally in prefrontal regions mentioned above (i.e. in eight regions of interest, ROIs) by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). The overall statistical analysis revealed a decrease in rDNA activity in suicide victims versus controls, particularly in male subjects. Further ROI-specific post hoc analyses revealed a significant decrease in this activity in suicides compared to non-suicides in five ROIs. This effect was accentuated in the ACv, where it was observed bilaterally. Our findings suggest that decreased rDNA transcription in the prefrontal cortex plays an important role in suicide pathogenesis and corresponds with our previous morphometric analyses of AgNOR-stained neurons.

Ribosomal DNA transcription in prefrontal pyramidal neurons is decreased in suicide.

Prefrontal cortical regions, which are crucial for the regulation of emotionally influenced behaviour, play most probably a dominant role in the pathogenesis of suicide. The study was carried out on paraffin-embedded brain tissue blocks containing specimens from the anterior cingulate cortex (dorsal and ventral parts), the orbitofrontal cortex, and the dorsolateral cortex obtained from 23 suicide completers (predominantly violent) with unknown psychiatric diagnosis and 25 non-suicidal controls. The transcriptional activity of ribosomal DNA (rDNA) as a surrogate marker of protein biosynthesis was evaluated separately in layers III and V pyramidal neurons in regions of interest (ROIs) mentioned above by the AgNOR silver staining method bilaterally. The overall statistical analysis revealed a decrease of AgNOR area suggestive of attenuated rDNA activity in suicide victims versus controls, particularly in male subjects. Further ROI-specific post-hoc analyses revealed decreases of the median AgNOR area in suicides compared to non-suicides in all 16 ROIs. However, this effect was only significant in the layer V pyramidal neurons of the right ventral anterior cingulate cortex. Our findings suggest that decreased rDNA transcription in prefrontal pyramidal neurons plays possibly an important role in suicide pathogenesis.

Decreased ribosomal DNA transcription in dorsal raphe nucleus neurons differentiates between suicidal and non-suicidal death.

An involvement of the central serotonergic system has been implicated in the pathogenesis of suicide. The dorsal raphe nucleus (DRN) is the main source of serotonergic innervation of forebrain limbic structures disturbed in suicidal behaviour. The study was carried out on paraffin-embedded brainstem blocks containing the DRN obtained from 27 suicide completers (predominantly violent) with unknown psychiatric diagnosis and 30 non-suicidal controls. The transcriptional activity of ribosomal DNA (rDNA) in DRN neurons as a surrogate marker of protein biosynthesis was evaluated by the AgNOR silver staining method. Significant decreases in AgNOR parameters suggestive of attenuated rDNA activity were found in the cumulative analysis of all DRN subnuclei in suicide victims versus controls (U test P values < 0.00001). Our findings suggest that the decreased activity of rDNA transcription in DRN neurons plays an important role in suicide pathogenesis. The method accuracy represented by the area under receiver operating characteristic curve (>80 %) suggests a diagnostic value of the observed effect. However, the possible application of the method in forensic differentiation diagnostics between suicidal and non-suicidal death needs further research.

[Chemical analysis of wastewater as a new way of monitoring drugs and medicines consumption at workplace]. / Analiza chemiczna scieków jako nowy sposób monitorowania stosowania narkotyków i leków w miejscu pracy.

The available information on the quality and frequency of illegal psychoactive substances used or medicines misused by workers, are often out of date at the time of its publication. This is due to the dynamic introduction of new synthetic drugs on the black market, changes in trends in the recreational use of medicines and the lack of readily available and reliable tests for fast identification. Strategy for detection of narcotic and non-medical psychoactive drugs use at workplace should embrace all possible sources of information. Classical sources of information on the use of psychoactive substances at the workplace include: statistical data (general information on trends and magnitude of drug and medicine addiction collected by the Polish National Police, the National Bureau for Drug Prevention and emergency medical services), surveys, psychomotor tests and qualitative and quantitative analyses of biological material. Of the new and promising methods, used throughout the world in recent years, chemical-toxicological analysis of surface water and wastewater deserve special mention. An increasing interest in the study of urban waste water can significantly complement the source of knowledge about drug and medicine addiction using obtainable conventional methods. In recent years, a municipal wastewater analysis has become a new and very promising way of collecting updated information on the use of psychoactive substances and medicines. It seems that this kind of study may play an important role in the ongoing monitoring of drug and/or medicines use by selected groups of population (e.g., students, military, firemen, policemen, etc.).

[Intoxication of female patient with generalised cancer in hospital--a case report]. / Zatrucie pacjentki z uogólniona choroba nowotworowa w szpitalu--opis przypadku.

Medical errors are crucial factors influencing hospital mortality. We present a case of 79-year-old female, who was admitted to the hospital due to complications associated with advanced cancer disease. After several days of hospitalization, the woman died as a result of cancer as well as severe drugs intoxication. The investigation showed extremely high concentrations of chlorprothixen and tramadol in the. blood of the patient. This paper describes a number of medical errors made by hospital staff, of which the most significant was an inappropriate drugs policy.

Measurement uncertainty of ethyl alcohol concentration in the exhaled breath of drivers and determination of sobriety at the time of incident. / Niepewnosc pomiaru stezenia alkoholu etylowego w powietrzu wydychanym kierowców oraz ustalenia stanu trzezwosci w chwili zdarzenia.

The aim of the study was to determine the components of measurement uncertainty in the concentration of alcohol in exhaled breath and to determine the state of sobriety at the time of incident. Based on the literature review and the authors' experience in providing opinions for law enforcement and the judiciary, the influence of various factors on the final interpretation of sobriety state is described on the basis of measurement uncertainty of breath analyzers, uncertainty of retrospective and prospective calculations, and uncertainty related to the conversion of alcohol concentrations detected during breath and blood tests. The paper pays particular attention to interpreting the concentrations of ethanol in exhaled breath close to the legal limits of the state of sobriety and the state after alcohol use, or the state after alcohol use and the state of insobriety. Analyzing the results of an exhaled breath test concerning concentrations close to the values of 0.1 mg/dm3 and 0.25 mg/dm3, it is necessary to take into account the factors affecting the measurements obtained, including the measurement uncertainty of the determination of alcohol in exhaled breath, the processes of absorption, distribution and metabolism of ethyl alcohol, and the possibility of the presence of alcohol lingering in the oral cavity. The incorrect execution of measurements of the tested person's alcohol concentration is also a problematic issue. When determining sobriety state by means of retrospective and prospective calculations, it is important to remember that the uncertainty of the result is affected by a number of factors and depends, among other things, on the information provided by the suspect. Hence, the expert should draw conclusions particularly cautiously and any overestimation or underestimation of the components of uncertainty can lead to erroneous conclusions. Awareness of the uncertainties inherent in the results of a sobriety test or alcohol calculation allows for meaningful interpretation of test results and determination of the sobriety state of the person tested.

[Accidental poisoning with peach seeds used as anticancer therapy--report of two cases]. / Przypadkowe zatrucie pestkami brzoskwini stosowanymi w celach przeciwnowotworowych--opis dwóch przypadków.

UNLABELLED: We described two cases of poisoning with amygdalin. Clinical signs presented by two females were mild and lasted up to 5 hours. CONCLUSIONS: The usage of amygdalin may be connected with serious side effects. The cyanide and prussic acid which are deliberated in digestive system are responsible for toxicity in such cases. The rarity of poisoning with amygdalin as well as high cost of analysis are responsible for the reason that most labs are not prepare for such procedure.

Reports analysis of psychotropic drugs related adverse reactions in Australia and Poland during the COVID 19 pandemic.

BACKGROUND: The COVID-19 pandemic has caused significant changes to the global health care system AIMS: It is unknown whether the COVID-19 pandemic influenced the occurrence of adverse drug reactions (ADR) of antidepressive agents, benzodiazepines, and antipsychotics plus mood stabilizers (AaMS). The study was designed in order to compare the incidence of ADR during the COVID-19 pandemic with the period preceding the pandemic in Poland and Australia, different in terms of their COVID-19 prevention strategy. METHOD: We analysed ADR from the three surveyed pharmacological groups of drugs observed in Poland and Australia in the period prior to, and during the COVID-19 pandemic RESULTS: In Poland, a noticeable increase in the reported ADR of the assessed drug groups was observed during the COVID-19 pandemic. The highest was for antidepressive agents, but the reporting of ADR for benzodiazepines and AaMS drugs also increased significantly. In the case of ADR in Australian patients, the increase in the number of reported ADR for antidepressive agents was modest compared to that seen in Poland, but still noticeable, and there was a significant increase in ADR for benzodiazepines CONCLUSIONS: This study showed that the COVID-19 pandemic has had an impact on the incidence of ADR reported among both Polish and Australian patients but the modality of this was different.

Contributors to Preterm Birth: Data from a Single Polish Perinatal Center.

Preterm birth may result from overlapping causes including maternal age, health, previous obstetric history and a variety of social factors. We aimed to identify factors contributing to preterm birth in respect to new social and environmental changes in the reproductive patterns. Our cross-sectional study included 495 mother-infant pairs and was based on maternal self-reporting in an originally developed questionnaire. Neonates were divided into two groups: 72 premature babies (study group) and 423 full-term babies (control group). We analyzed maternal, sociodemographic and economic characteristics, habits, chronic diseases, previous obstetric history and pregnancy complications. For statistical analysis, Pearson's Chi-squared independence test was used with a statistical significance level of 0.05. Preterm births were more common among mothers living in villages (p < 0.001) and with lower education level (p = 0.01). Premature births were also positively associated with mothers who were running their own businesses (p = 0.031). Mothers with a history of previous miscarriages gave birth at a significantly older age (p < 0.001). The most frequent pregnancy complications were hypothyroidism (41.4%), pregestational and gestational diabetes mellitus (DM; 17.8%) and hypertension (8.1%). Pregestational DM significantly influenced the occurrence of prematurity (p < 0.05). Pregestational DM, being professionally active, a lower education level and living outside cities are important risk factors of prematurity.

[Atypical poisoning with mixture of toxic alcohols--a case report]. / Nietypowe zatrucie mieszanina alkoholi niespozywczych--opis przypadku.

UNLABELLED: We presented the male who was addicted to ethanol, and who drank the mixture of different toxic alcohols. Toxicological screening of ingested fluid found 42% vol propan-1-OL, and 17% vol propan-2-OL (isopropanol). After regaining consciousness, the patient stated that substance is becoming more and more popular as a new type of cheap alcohol, and because of its "low price and high power". CONCLUSIONS: 1. It is advisable to consult all cases of poisoning with inedible alcohols with Regional Centers of Toxicology. 2. There is an urgent need to create a reference toxicological laboratories, which would have the ability to diagnose poisoning with different xenobiotics. 3. Further training for students and doctors, about diagnosis and therapy of acute poisonings, should be done. 4. The endemic foci of intoxication with inedible alcohols should be checked and discovered.

Accidental intoxication with high dose of methoxetamine (MXE)--a case report.

UNLABELLED: Methoxetamine (MXE) is an analogue of ketamine. CASE REPORT: We present a 25-year-old male who, after getting an information from the Internet, started to use MXE to avoid the excitement connected with recreational codeine abuse. For about 8 - 10 months he injected about 100 mg of MXE intramuscularly. On the day of admission the patient decided to take much higher dose of 750 mg of MXE. For the first 3-4 hours of hospitalization the profound agitation, which demanded the usage of high doses of benzodiazepines, was observed every several minutes. After 6-7 hours of supportive treatment the patient returned to his baseline mental status. CONCLUSION: MXE presents the new healthcare threat because of easy accessibility via Internet, and lack of legal restrictions in many countries. The low dose of MXE can cause "peace and serenity", however, higher dose may act opposite.

[Estimation of the usage of psychoactive substances in academic campus based on analysis of municipal waste water]. / Oszacowanie stosowania srodków odurzajacych w kampusie akademickim na podstawie wyników analizy chemicznej scieków komunalnych.

Important source of objective information about the nature and the scale of the usage of psychoactive substances becomes test of municipal waste water or surface water. From the analytical chemistry point of view municipal waste water are a complex mixture of substances therefore the authoritative analysis requires careful planning of both the place of sampling and the use of effective methods of research. The aim of this work was the attempt to estimate the scale of the usage of narcotic drugs in the academic campus Kortowo in Olsztyn during the students May holidays "Kortowiady". The positive results of the concentration of 11 -nor-9-carboxy-delta9-tetrahydrocannabinol (THC-COOH) and amphetamines in the samples of effluent shall indicate the need to continue research in this field and improvement methods for the determination of narcotic drugs.

[Suicidal intoxication with sodium azide--a case report]. / Smiertelne samobójcze zatrucie azydkiem sodu--opis przypadku.

Sodium azide (NaN3) is an inorganic matrix compound with a very high toxicity. Mechanism of action is not clarified, and it is assumed to interfere with the processes of oxidative phosphorylation. The acute intoxications with sodium azide are extremely rare. We described a case of 19-year-old man who was found dead. In the course of prosecution the empty container, with label "NaN3, 20 g", was found near the body. There were traces of white powder detected in the container. Azide ions were determined by derivatization, i.e. they were transformed to pentafluorobenzaldehyde azide compound. Analysis of the final extract after derivatization was performed by gas chromatography coupled with mass spectrometry GC/MS. The largest concentration of azide ions were determined in the stomach content and vitreous humour, and much less one in whole blood, urine and kidney fluid.

[Proposal of interpreting analytical results indicating borderline-legal alcohol concentration values in individuals after alcohol consumption or being alcohol-intoxicated]. / Propozycja interpretacji wyników analitycznych uzyskanych w poblizu prawnej granicy stezen dla stanu po uzyciu alkoholu lub stanu nietrzezwosci.

Interpretation of analytical results indicating borderline-legal alcohol concentration values after the substance intake or intoxication requires consideration of many factors, such as: road safety, measurement uncertainty, determination of ethanol in breath, alcohol metabolism in the body, the possibility of residual alcohol in the mouth. Decree No 738 of the Chief of Police issued on 21 June 2011, introduces the obligation to verify the results ranging close to the borderline concentration of 0.1 mg/l by executing the third measurement, but the interpretation of these results is questionable. The paper proposes a new manner of taking measurements and their interpretation. Upon arriving at the scene the police should record the starting time of testing the driver and wait 15 minutes (the time required to eliminate residual alcohol). If, after that time, the first result falls within the borderline values legally described as the condition after alcohol consumption or alcohol intoxication, the second and third measurements should be taken immediately. Thus, three measurements taken quickly in a few minutes should not be affected by the alcohol metabolism in the body. If two of the three determined values are less than or equal to 0.09 mg/l, the driver should be pronounced sober. If two of the three results are within the range of 0.10-0.25 mg/l, the result indicates condition after alcohol intake. If two of the three results are equal to or more than 0.26 mg/l, the status of the driver may be described as alcohol intoxication.

[Dextromethorphan (DXM): new methods of intoxications among teenagers--a case description]. / Dekstrometorfan (DXM): nowe metody odurzania sie nastolatków--opis przypadku.

The study highlighted the problem of intoxication using substances and/or preparations, to which nowadays young people have unrestricted access. Based on the case developed in the Department of Forensic Medicine of the Medical University of Gdansk, our team members were able to gather information showing "ingenuity" of today's teenagers, which was reflected in the types of preparations used to induce a state of euphoria and intoxication. The study was based on the case of a 17-year-old woman, who took Acodin in combination with compressed air used to clean computer keyboards in order to induce psychoactive effects. The study used qualitative and quantitative methods: GC-FID and GC-MS. The results were compared with data from the literature.

[Proposal of psychomotor skill assessment tests for drivers and a protocol for sampling and testing of saliva, blood and urine when there is reason to suspect involvement of substances with alcohol-like effect]. / Propozycja testów oceniajacych zdolnosci psychomotoryczne kierowcy oraz protokolu do zastosowania w trakcie pobrania i badania sliny, krwi oraz moczu w przypadku podejrzenia przyjecia srodków dzialajacych podobnie do alkoholu.

The paper proposes tests to assess psychomotor impairment in drivers suspected of using substances acting similarly to alcohol. The authors also present a proposal for the protocol to be used in sampling and testing of saliva, blood and urine when psychoactive substance abuse has been suspected. A detailed procedure is based on the joined experience of German, U.S. and Polish police from Gdansk. The purpose of the appendix is to help police officers to perform and document tests confirming psychomotor impairment, as well as to provide the basis for saliva, urine and blood analysis.

Fatal Suicidal Intoxication with Pentoxifylline Complicated by Cardiovascular Disorders.

Pentoxifylline is a xanthine derivative used in vascular disorders that is recognized as a safe drug for patients. The paper describes a rare case of fatal and suicidal pentoxifylline poisoning in an 82-year-old man with multiple preexisting diseases (arterial hypertension, coronary artery disease, type 2 diabetes, and intermittent claudication). The patient was admitted to the clinical toxicology unit approximately 2 h after the overdose and died 36 h after the admission despite intensive care. Multiple arterial blood gas analyses and other laboratory tests were performed during the hospitalization and are reported in the paper. Postmortem examination of the biological material was carried out with the use of histopathological techniques. The toxicological studies using chromatographic techniques coupled with mass spectrometry showed that postmortem blood levels of pentoxifylline have been found in the range which is described in the available literature to be toxic and lethal. The analysis of test results and clinical data showed that the patient died as a result of increasing circulatory and respiratory failure, complicated by disorders of the acid-base and electrolyte balance (respiratory alkalosis, concomitant lactic acidosis, and hypokalemia), hyperglycemia, and coagulation disorders.

Selected Political Criminal Poisonings in the Years 1978-2020: Detection and Treatment.

Criminal poisonings are among the least frequently detected crimes in the world. Lack of suspicion of this type of event by police officers and prosecutors, clinical symptoms imitating many somatic diseases and technical difficulties in diagnostics, as well as high research costs make the actual frequency of these events difficult to estimate. The substance used for criminal poisoning is often characterized by: lack of taste, color and smell, delayed action, easy availability and difficulty to detect. The aim of the study was to analyze selected cases of political poisoning that took place in the years 1978-2020, to describe the mechanisms of action of the substances used and to evaluate the diagnosis and treatment. The analyzed cases of criminal poisoning concerned: Georgi Markov (ricin), Khalid Maszal (fentanyl), Wiktor Yushchenko (TCDD dioxin), Jasir Arafat (polonium 210Po isotope), Alexander Litvinenko (polonium 210Po isotope), Kim Jong-Nam (VX), Sergei Skripal (Novichok) and Alexei Navalny (Novichok). Contemporary poisons, to a greater extent than in the past, are based on the use of synthetic substances from the group of organophosphorus compounds and radioactive substances. The possibility of taking appropriate and effective treatment in such cases is the result of many factors, including the possibility of quick and competent rescue intervention, quick and reliable detection of the toxic substance and the possibility of using an antidote.