BACKGROUND: There is a lack of studies on methamphetamine (MA) exposure and morbidity in children beyond the perinatal period. OBJECTIVES: We compared morbidity in children (0-3 years) with prenatal MA exposure to opioid-exposed and to non-exposed children. METHODS: We used data from a Czech nationwide, registry-based cohort study (2000-2014). Children, who reached 3 years of age, of mothers hospitalized with (i) MA use disorder during pregnancy (MA; n = 194), (ii) opioid use disorder during pregnancy (opioids; n = 166), and (iii) general population (GP; n = 1,294,349) with no recorded history of substance use disorder (SUD). Information on inpatient contacts, length of stay, and diagnoses (International Statistical Classification of Diseases and Related Health Problems 10th Revision [ICD-10]) were assessed. Crude and adjusted odds ratios (aOR), 95% confidence interval (CI) for the risk of hospitalization, and for getting diagnosis from the ICD-10 diagnosis chapters were calculated using binary logistic regression. A stratified analysis on hospitalizations with SUD of mothers was performed. RESULTS: No significant differences were found in the measures of hospitalization between the MA and opioid groups. Children prenatally exposed to MA and opioids had higher numbers of hospitalizations and diagnoses and longer stays in hospital than children in the GP. Increased risks of certain infectious and parasitic diseases were found in both MA (aOR = 1.6; CI: 1.1-2.3) and opioid (aOR = 1.9; 1.3-2.8) groups as compared to the GP group. The most pronounced difference in stratified analysis on maternal hospitalizations related to SUD after birth was observed for injury, poisoning, and certain other consequences of external causes in the strata of the MA group who had hospitalized mothers (aOR 6.3, 1.6-24.6) compared to the strata without maternal hospitalizations (aOR 1.4, 0.9-2.3). CONCLUSION: This study suggests that children born to mothers using MA during pregnancy have similar morbidity during the first 3 years of life but higher than the GP. The excess of risk was primarily due to infections and injuries in the MA group.
- MeSH
- dítě MeSH
- kohortové studie MeSH
- lidé MeSH
- methamfetamin * škodlivé účinky MeSH
- morbidita MeSH
- opioidní analgetika terapeutické užití MeSH
- poruchy spojené s užíváním opiátů * epidemiologie farmakoterapie MeSH
- registrace MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice * epidemiologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Tacrine was withdrawn from clinical use as a drug against Alzheimer's disease in 2013, mainly due to drug-induced liver injury. The culprit of tacrine-associated hepatotoxicity is believed to be the 7-OH-tacrine metabolite, a possible precursor of quinone methide (Qmeth), which binds to intracellular -SH proteins. In our study, several different animal and human models (liver microsomes, primary hepatocytes, and liver slices) were used to investigate the biotransformation and hepatotoxicity of tacrine and its 7-substituted analogues (7-methoxy-, 7-phenoxy-, and 7-OH-tacrine). Our goal was to find the most appropriate in vitro model for studying tacrine hepatotoxicity and, through rational structure modifications, to develop derivatives of tacrine that are less prone to Qmeth formation. Our results show that none of animal models tested accurately mimic human tacrine biotransformation; however, the murine model seems to be more suitable than the rat model. Tacrine metabolism was overall most accurately mimicked in three-dimensional (3D) spheroid cultures of primary human hepatocytes (PHHs). In this system, tacrine and 7-methoxytacrine were hydroxylated to 7-OH-tacrine, whereas 7-phenoxytacrine formed, as expected, only trace amounts. Surprisingly, however, our study showed that 7-OH-tacrine was the least hepatotoxic (7-OH-tacrine < tacrine < 7-methoxytacrine < 7-phenoxytacrine) even after doses had been adjusted to achieve the same intracellular concentrations. The formation of Qmeth-cysteine and Qmeth-glutathione adducts after human liver microsome incubation was confirmed by all of the studied tacrine derivatives, but these findings were not confirmed after incubation with 3D PHH spheroids. Therefore, the presented data call into question the suggested previously hypothesized mechanism of toxicity, and the results open new avenues for chemical modifications to improve the safety of novel tacrine derivatives.
- MeSH
- biotransformace MeSH
- indolochinony * MeSH
- krysa rodu rattus MeSH
- lékové postižení jater * MeSH
- lidé MeSH
- methamfetamin * MeSH
- myši MeSH
- takrin toxicita MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
INTRODUCTION: Amphetamine-type stimulants (ATSs) are the second most commonly consumed class of illicit drugs globally, but there is limited understanding of the precise factors associated with problematic versus controlled ATS consumption. This exploratory study aimed to identify which individual, social, and environmental factors are associated with different patterns of ATS use over time. METHODS: Cross-sectional surveys were conducted in Germany, England, The Netherlands, Poland, and the Czech Republic via face-to-face computer-assisted personal interviews to collect data on different user groups. 1,458 adults (18+) reported exposure to but no ATS use (n = 339); former rare/moderate ATS use (n = 242); current rare/moderate ATS use (n = 273); former frequent/dependent ATS use (n = 201); current frequent/dependent ATS use (n = 403). Extent of ATS/other substance use was assessed by number of consumption days (lifetime, past year, past month) and Severity of Dependence Scale. To identify factors associated with group membership, data were also collected on previous injecting drug use (IDU) and consumption setting/rules. Psychological distress was measured using the Brief Symptom Inventory, with additional data collected on self-reported adverse life events and physical/mental health. RESULTS: Currently, using frequent/dependent ATS users experienced more frequent unstable living conditions (27.5%) and psychological distress (59.8%) compared to other groups. A multinomial logistic regression showed that currently abstinent rare/moderate users were more likely to abstain from methamphetamine use {odds ratio (OR) = 2.48 (confidence interval [CI] = 1.32-4.68)} and from IDU (OR = 6.33 [CI = 2.21-18.14]), to avoid ATS use during working hours (OR = 6.67 [CI = 3.85-11.11]), and not to use ATS for coping reasons (OR = 4.55 [CI = 2.50-6.67]) compared to the reference group of currently using frequent/dependent users. CONCLUSIONS: People who use ATS frequently and/or at dependent levels are more likely to have experienced social and economic adversity compared to infrequent ATS users. On the other hand, there is a substantial share of users, which show a controlled use pattern and are able to integrate ATS use into their lives without severe consequences.
Central ghrelin signaling seems to play important role in addiction as well as memory processing. Antagonism of the growth hormone secretagogue receptor (GHS-R1A) has been recently proposed as a promising tool for the unsatisfactory drug addiction therapy. However, molecular aspects of GHS-R1A involvement in specific brain regions remain unclear. The present study demonstrated for the first time that acute as well as subchronic (4 days) administration of the experimental GHS-R1A antagonist JMV2959 in usual intraperitoneal doses including 3 mg/kg, had no influence on memory functions tested in the Morris Water Maze in rats as well as no significant effects on the molecular markers linked with memory processing in selected brain areas in rats, specifically on the β-actin, c-Fos, two forms of the calcium/calmodulin-dependent protein kinase II (CaMKII, p-CaMKII) and the cAMP-response element binding protein (CREB, p-CREB), within the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), dorsal striatum, and hippocampus (HIPP). Furthermore, following the methamphetamine intravenous self-administration in rats, the 3 mg/kg JMV2959 pretreatment significantly reduced or prevented the methamphetamine-induced significant decrease of hippocampal β-actin and c-Fos as well as it prevented the significant decrease of CREB in the NAC and mPFC. These results imply, that the GHS-R1A antagonist/JMV2959 might reduce/prevent some of the memory-linked molecular changes elicited by methamphetamine addiction within brain structures associated with memory (HIPP), reward (NAc), and motivation (mPFC), which may contribute to the previously observed significant JMV2959-induced reduction of the methamphetamine self-administration and drug-seeking behavior in the same animals. Further research is necessary to corroborate these results.
- MeSH
- aktiny MeSH
- ghrelin farmakologie MeSH
- krysa rodu rattus MeSH
- methamfetamin * farmakologie MeSH
- proteinkinasa závislá na vápníku a kalmodulinu typ 2 MeSH
- receptory ghrelinu * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: This study aims to identify predictors of the lifetime prevalence of methamphetamine use in the population of Czech disadvantaged neighbourhoods. METHODS: Using data from a face-to-face representative survey, two types of analysis were performed. A bivariate analysis (unadjusted odds ratios estimated with logistic regression) was conducted to determine the relationship with a dependent variable (lifetime prevalence of methamphetamine use). Subsequently, three multivariate binomial logistic regression models (socio-demographic and socioeconomic status, incarceration and victimization, mobility and space) were conducted to control for the influence of other variables. RESULTS: In a series of multinomial logit models, we have found the following predictors to be significantly associated with lifetime prevalence of methamphetamine use: age, gender, Roma ethnicity, net monthly household income, unstable housing, lifetime experience with incarceration, lifetime experience with discrimination, urban-rural divide, and index of rural peripheralization. CONCLUSIONS: The results suggest that methamphetamine users are multidimensionally disadvantaged and therefore constitute a vulnerable group with specific needs. This should be considered when designing services and policies targeting methamphetamine use in disadvantaged neighbourhoods.
- MeSH
- bydlení MeSH
- lidé MeSH
- logistické modely MeSH
- methamfetamin * MeSH
- průzkumy a dotazníky MeSH
- socioekonomické faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Naphyrone, also known as NRG-1, is a novel psychoactive substance (NPS), a cathinone with stimulatory properties available on the grey/illicit drug market for almost a decade. It is structurally related to infamously known powerful stimulants with the pyrovalerone structure, such as alpha-pyrrolidinovalerophenone (α-PVP) or methylenedioxypyrovalerone (MDPV) that are labeled as a cheap replacement for cocaine and other stimulants. Despite the known addictive potential of α-PVP and MDPV, there are no studies directly evaluating naphyrone's addictive potential e.g., in conditioned place preference (CPP) test or using self-administration. Therefore, our study was designed to evaluate the addictive potential in a CPP test in male Wistar rats and compare its effect to another powerful stimulant with a high addictive potential - methamphetamine. Naphyrone increased time spent in the drug-paired compartment with 5 and 20 mg/kg s.c. being significant and 10 mg/kg s.c. reaching the threshold (p = 0.07); the effect was comparable to that of methamphetamine 1.5 mg/kg s.c. The lowest dose, naphyrone 1 mg/kg s.c., had no effect on CPP. Interestingly, no dose response effect was detected. Based on these data, we are able to conclude that naphyrone has an addictive potential and may possess a significant risk to users.
- MeSH
- alkaloidy farmakologie MeSH
- chování zvířat účinky léků MeSH
- klasické podmiňování účinky léků MeSH
- krysa rodu rattus MeSH
- methamfetamin aplikace a dávkování farmakologie MeSH
- modely nemocí na zvířatech MeSH
- pentanony aplikace a dávkování farmakologie MeSH
- poruchy spojené s užíváním psychoaktivních látek * MeSH
- potkani Wistar MeSH
- pyrrolidiny aplikace a dávkování farmakologie MeSH
- stimulanty centrálního nervového systému aplikace a dávkování farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Patients intoxicated with methamphetamine-like substances may present with myoglobinuria but rarely require admission. An 18-year-old female was admitted due to intoxication with pervitin, a methamphetamine derivative. She presented with an altered mental status, fever, and increased heart and respiratory rates. Biomarkers showed leukocytosis and markedly increased procalcitonin levels, suggestive of sepsis. However, blood cultures and infectious disease workup were unrevealing. Clinical course was heralded by rhabdomyolysis and myoglobinuria resulting in multi-organ failure including respiratory failure necessitating mechanical ventilation, hemodynamic compromise with need for inotropic support, and an acute renal failure requiring renal replacement therapy. Surprisingly, after a transient improvement, an unexpected second peak of myoglobin was observed on hospital day 5, controlled by intensifying the elimination methods, and administration of dantrolene. Acute kidney injury resolved by hospital day 15, and the patient could be discharged on day 22. While most patients with intoxications are discharged within 24 hours from emergency departments without being admitted, our case report highlights that the organ injury may evolve beyond the usual observation period, traditional renal-replacement therapies may not be sufficient to mitigate myoglobinemia with resulting acute kidney injury, and that procalcitonin may not be a reliable biomarker of infection in the setting of drug-induced rhabdomyolysis.
- MeSH
- akutní poškození ledvin * chemicky indukované diagnóza terapie MeSH
- biologické markery MeSH
- lidé MeSH
- methamfetamin * MeSH
- mladiství MeSH
- myoglobinurie * komplikace MeSH
- prokalcitonin MeSH
- rhabdomyolýza * chemicky indukované diagnóza komplikace MeSH
- sepse * diagnóza MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Předkládaná kazuistika popisuje nález Trichomonas vaginalis u pacientky (34 let) s předčasným odtokem plodové vody a následnou sekcí v 25. týdnu těhotenství, kde přítomnost T. vaginalis nebyla jediným rizikovým faktorem předčasného porodu. I když se jedná o vzácný nález u gravidní ženy, je nutné na přítomnost tohoto mikroorganismu při obdobných situacích pomýšlet.
x
- MeSH
- antibakteriální látky terapeutické užití MeSH
- dospělí MeSH
- hypertenze MeSH
- lidé MeSH
- methamfetamin škodlivé účinky MeSH
- perinatální smrt etiologie MeSH
- předčasný odtok plodové vody etiologie MeSH
- předčasný porod etiologie MeSH
- rizikové faktory MeSH
- růstová retardace plodu etiologie farmakoterapie MeSH
- těhotenství MeSH
- Trichomonas vaginalis * patogenita MeSH
- trichomoniáza diagnóza farmakoterapie komplikace MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
There is growing evidence that methamphetamine use during pregnancy may produce detrimental cardiovascular effects in the adult offspring. Prior work demonstrated that chronic methamphetamine exposure throughout the gestational period causes adult female offspring to become hypersensitive to myocardial ischemic injury. The goal of the present study was to determine whether this methamphetamine-induced effect occurs early or late in the gestational period. Pregnant female rats were divided into 4 experimental groups. Groups 1 and 2 received subcutaneous injections of saline (group 1) or methamphetamine (5 mg/kg) (group 2) throughout the gestational period. Group 3 received methamphetamine injections on days 1-11 and saline on days 12-22, and group 4 received saline on days 1-11 and methamphetamine on days 12-22. Hearts were isolated from adult (8 weeks) female offspring and subjected to 30 min ischemia and 2 hours reperfusion on a Langendorff isolated heart apparatus. Contractile function was measured via an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Infarcts were significantly larger in methamphetamine exposed offspring regardless of whether they had been exposed to methamphetamine during the first half or the second half of the gestational period. Prenatal exposure to methamphetamine had no effect on preischemic contractile function or postischemic recovery of contractile function. These data indicate that methamphetamine use during either the first half or second half of pregnancy increases susceptibility to myocardial infarction in adult female offspring. These data provide further evidence that prenatal exposure to methamphetamine may increase the risk of developing cardiovascular diseases during adulthood.
- MeSH
- infarkt myokardu * MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- methamfetamin * toxicita MeSH
- poranění srdce * MeSH
- potkani Sprague-Dawley MeSH
- srdce MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice * chemicky indukované MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: The aim of the study is to analyse drug-related infectious diseases (DRID) rates for people who inject drugs (PWID) in the Pilsen Region in order to identify the main determiners of infection risk and also to provide a foundation for comparison between this region and the others in the Czech Republic. METHODS: In a descriptive cross-sectional study, we analysed the Pilsen Region's data on PWID. The data was transcribed from the 2003 to 2018 internal database of the Ulice Outreach Programme. In addition to the data regarding the testing of DRID, we analysed commercial sex work (CSW) and the PWID's duration of drug use, age and current address. The statistical analysis was performed using SPSS, primarily employing logistic regression (i.e., backward elimination method) to explore predictors of seropositivity. Moreover, we calculated its prevalence from an epidemiological perspective. RESULTS: In total, 384 PWID were tested, from which 54.7% were males, and 84.1% were from Pilsen. The average age for initiation of using drug was 19.37 years. The most used drug was methamphetamine (64.8%), 77 women (20.1%) were reported to be CSW. The prevalence of DRID was as follows: hepatitis C virus (HCV) 37.24%, syphilis 1.82%, hepatitis B virus (HBV) 0.78%, and HIV infection 0.26%. The analysis showed that men had a lower risk of syphilis than women. Individuals who started their drug use via injection had a 1.365-times higher risk of DRID in comparison to those who initiated intravenous drug use later in their drug-using lives. We identified a significant association between the drug type and the risk of HCV infection: the main predictor of seropositivity was the use of fentanyl, which posed a 1.930-times higher risk than in the case of methamphetamine. CONCLUSIONS: This study is the first descriptive cross-sectional study implemented in the Pilsen Region in the Czech Republic with a focus on the subpopulation of PWID with individual data. A high prevalence of HCV infection still persists but the prevalence of HBV and HIV infections in this study (and generally in the Czech Republic) is relatively low compared to foreign studies. Syphilis is not closely associated with injecting-drug use, but rather with the sexual behaviour of the people who use drugs intravenously. The most important predictor of seropositivity for syphilis was CSW. We also found the duration of being a CSW to be significant influence. The women who had been CSWs for less than 5 years had a significantly lower risk of syphilis than those who had prostituted for more than 5 years.
- MeSH
- dospělí MeSH
- Hepacivirus MeSH
- hepatitida C * epidemiologie MeSH
- HIV infekce * epidemiologie MeSH
- intravenózní abúzus drog * epidemiologie MeSH
- lidé MeSH
- methamfetamin * MeSH
- mladý dospělý MeSH
- prevalence MeSH
- prostituce MeSH
- průřezové studie MeSH
- riskování MeSH
- syfilis * epidemiologie MeSH
- uživatelé drog * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
