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Medical Science Monitor : International... Jun 2024The 'recreational use' of selected over-the-counter (OTC) medicines is an unofficial activity. The traditional surveys assessing the use of drugs are affected by the... (Review)
Review
The 'recreational use' of selected over-the-counter (OTC) medicines is an unofficial activity. The traditional surveys assessing the use of drugs are affected by the bias of underreporting and are thus unreliable. The development of analytical techniques helps to monitor the substances at trace levels, such as in wastewater, and might be applied to estimate the consumption of an analyte of interest and ensure additional, evidence-based information complementary to population surveys. We reviewed studies focused on evaluating the estimated consumption of drugs as a reliable and unbiased source of evidence-based information (called wastewater-based epidemiology, WBE) to monitor the scale of this phenomenon. We found there is a need to test not only narcotics in the environment but also medicines that may be abused or recreationally used. The reviewed studies show methods that might provide reliable information about consumption of drugs, narcotics, and OTC medications for proposing targeted, preventive actions. Moreover, as all the selected studies were based on mass spectrometry, there is a potential to include the dextromethorphan and/or related compounds as part of the screening for narcotics and OTC drugs that can be socially harmful, overused, or misused. This article reviews the analytical methods for detecting dextromethorphan and/or its transformation products in environmental water samples.
Topics: Dextromethorphan; Nonprescription Drugs; Wastewater; Humans; Illicit Drugs; Recreational Drug Use; Substance Abuse Detection; Wastewater-Based Epidemiological Monitoring; Water Pollutants, Chemical
PubMed: 38902914
DOI: 10.12659/MSM.944120 -
Scientific Reports Jun 2024Butorphanol is widely used as an anesthetic drug, whether butorphanol could reduce organ injury and protecting lung tissue is unknown. This study explored the effects of...
Butorphanol is widely used as an anesthetic drug, whether butorphanol could reduce organ injury and protecting lung tissue is unknown. This study explored the effects of butorphanol on ALI and investigated its underlying mechanisms. We established a "two-hit" rat model and "two-hit" cell model to prove our hypothesis. Rats were divided into four groups [control, "two-hit" (OA + LPS), "two-hit" + butorphanol (4 mg/kg and 8 mg/kg) (OA + LPS + B1 and OA + LPS + B2)]. RPMVE cells were divided into four groups [control, "two-hit" (OA + LPS), "two-hit" + butorphanol (4 μM and 8 μM) (OA + LPS + 4 μM and OA + LPS + 8 μM)]. Inflammatory injury was assessed by the histopathology and W/D ratio, inflammatory cytokines, and arterial blood gas analysis. Apoptosis was assessed by Western blotting and flow cytometry. The effect of NF-κB p65 was detected by ELISA. Butorphanol could relieve the "two-hit" induced lung injury, the expression of TNF, IL-1β, IL-6, and improve lung ventilation. In addition, butorphanol decreased Bax and cleaved caspase-3, increased an antiapoptotic protein (Bcl-2), and inhibited the "two-hit" cell apoptosis ratio. Moreover, butorphanol suppressed NF-κB p65 activity in rat lung injury. Our research showed that butorphanol may attenuate "two-hit"-induced lung injury by regulating the activity of NF-κB p65, which may supply more evidence for ALI treatment.
Topics: Animals; Butorphanol; Apoptosis; Rats; Male; Acute Lung Injury; Inflammation; Transcription Factor RelA; Lipopolysaccharides; Rats, Sprague-Dawley; Lung Injury; Disease Models, Animal; Cytokines; Lung
PubMed: 38902260
DOI: 10.1038/s41598-024-53483-5 -
Redox Biology Jun 2024Morphine, a typical opiate, is widely used for controlling pain but can lead to various side effects with long-term use, including addiction, analgesic tolerance, and...
Morphine, a typical opiate, is widely used for controlling pain but can lead to various side effects with long-term use, including addiction, analgesic tolerance, and hyperalgesia. At present, however, the mechanisms underlying the development of morphine analgesic tolerance are not fully understood. This tolerance is influenced by various opioid receptor and kinase protein modifications, such as phosphorylation and ubiquitination. Here, we established a murine morphine tolerance model to investigate whether and how S-nitrosoglutathione reductase (GSNOR) is involved in morphine tolerance. Repeated administration of morphine resulted in the down-regulation of GSNOR, which increased excessive total protein S-nitrosation in the prefrontal cortex. Knockout or chemical inhibition of GSNOR promoted the development of morphine analgesic tolerance and neuron-specific overexpression of GSNOR alleviated morphine analgesic tolerance. Mechanistically, GSNOR deficiency enhanced S-nitrosation of cellular protein kinase alpha (PKCα) at the Cys78 and Cys132 sites, leading to inhibition of PKCα kinase activity, which ultimately promoted the development of morphine analgesic tolerance. Our study highlighted the significant role of GSNOR as a key regulator of PKCα S-nitrosation and its involvement in morphine analgesic tolerance, thus providing a potential therapeutic target for morphine tolerance.
PubMed: 38901102
DOI: 10.1016/j.redox.2024.103239 -
Journal of Forensic Sciences Jun 2024When faced with increasing drug-related deaths and decline in practicing forensic pathologists, the need to quickly identify toxicology-related deaths is evident in...
When faced with increasing drug-related deaths and decline in practicing forensic pathologists, the need to quickly identify toxicology-related deaths is evident in order to appropriately triage cases and expedite turnaround times. Lateral flow immunoassays conducted pre-autopsy offer quick urine drug screen (UDS) results in minutes and are used to inform the need for autopsy. Over 1000 medicolegal cases were reviewed to compare UDS results to laboratory enzyme-linked immunosorbent assay (ELISA) blood results to evaluate how well autopsy UDS predicted laboratory findings. Mass spectral analysis was performed on ELISA-positive specimens and these data were used to investigate UDS false-negative (FN) results when possible. Five different UDS devices (STAT One Step Drug of Abuse dip card and cassette, Premiere Biotech multi-drug and fentanyl dip cards and ATTEST 6-acetylmorphine (6-AM) dip card) were tested encompassing 11 drug classes: 6-AM, amphetamine/methamphetamine, benzodiazepines, benzoylecgonine, fentanyl, methadone, opioids, phencyclidine, and delta-9-tetrahydrocannabinol. Sensitivity, specificity, efficiency, and positive and negative predictive values >80% indicated that UDS was useful for predicting cases involving benzoylecgonine, methadone, methamphetamine, and phencyclidine. UDS was unreliable in predicting amphetamine, benzodiazepines, fentanyl, and opiates-related cases due to a high percentage of FN (up to 11.2%, 8.0%, 12.4%, and 5.5%, respectively) when compared to ELISA blood results. For the later analytes, sensitivities were as low as 57.5%, 60.0%, 72.2%, and 66.7%, respectively. Overall results support that UDS cannot replace laboratory testing. Because UDS is subject to false-positive and FN results users must understand the limitations of using UDS for triage or decision-making purposes.
PubMed: 38898613
DOI: 10.1111/1556-4029.15561 -
Immunity, Inflammation and Disease Jun 2024Ischemia-reperfusion (I/R) injury, resulting from blood flow interruption and its subsequent restoration, is a prevalent complication in liver surgery. The liver, as a...
INTRODUCTION
Ischemia-reperfusion (I/R) injury, resulting from blood flow interruption and its subsequent restoration, is a prevalent complication in liver surgery. The liver, as a crucial organ for carbohydrate and lipid metabolism, exhibits decreased tolerance to hepatic I/R in patients with diabetes mellitus (DM), resulting in a significant increase in hepatic dysfunction following surgery. This may be attributed to elevated oxidative stress and inflammation. Our prior research established sinomenine's (SIN) protective role against hepatic I/R injury. Nevertheless, the impact of SIN on hepatic I/R injury in DM rats remains unexplored.
OBJECTIVE AND METHODS
This study aimed to investigate the therapeutic potential of SIN in hepatic I/R injury in DM rats and elucidate its mechanism. Diabetic and hepatic I/R injury models were established in rats through high-fat/sugar diet, streptozotocin injection, and hepatic blood flow occlusion. Liver function, oxidative stress, inflammatory reaction, histopathology, and Nrf-2/HO-1 signaling pathway were evaluated by using UV spectrophotometry, biochemical assays, enzyme-linked immunosorbent assay, hematoxylin-eosin staining, and Western blot analysis.
RESULTS
High-dose SIN (300 mg/kg) significantly attenuated hepatic I/R injury in DM rats, reducing serum activities of ALT and AST, decreasing the AST/ALT ratio, enhancing tissue contents of SOD and GSH-Px, suppressing the levels of TNF-α and IL-6, improving the liver histopathology, and activating Nrf-2/HO-1 signaling by promoting Nrf-2 trans-location from cytoplasm to nucleus. Low-dose SIN (100 mg/kg) was ineffective.
CONCLUSIONS
This study demonstrates that high-dose sinomenine's mitigates hepatic I/R-induced inflammation and oxidative stress in diabetes mellitus (DM) rats via Nrf-2/HO-1 activation, suggesting its potential as a preventive strategy for hepatic I/R injury in DM patients.
Topics: Animals; Oxidative Stress; Morphinans; Rats; Diabetes Mellitus, Experimental; Reperfusion Injury; Male; Liver; Rats, Sprague-Dawley; Inflammation; NF-E2-Related Factor 2; Signal Transduction
PubMed: 38888355
DOI: 10.1002/iid3.1271 -
Swiss Medical Weekly Jun 2024In Switzerland, a cantonal authorisation is required to introduce opioid agonist treatments (OAT). We investigated and compared the terms of these cantonal OAT...
BACKGROUND AND AIM
In Switzerland, a cantonal authorisation is required to introduce opioid agonist treatments (OAT). We investigated and compared the terms of these cantonal OAT authorisations throughout Switzerland. The primary objective was to determine how the overseeing cantonal officials implemented and perceived the legal requirements.
METHOD
We started with a cross-sectional analysis of legal texts and cantonal OAT guidelines. Based on the document analysis, we conducted 26 semi-structured interviews with the cantonal officials who grant OAT authorisations.
FINDINGS
In most cantons (21 of 25), the OAT authorisation is specific to the person treated and must be renewed every year. Today, 21 cantons either have implemented or are implementing the same web-based software to process and manage OAT authorisation requests. Cantons have implemented diverging requirements regarding, amongst others, the involvement of third parties in OAT and the training required of prescribing physicians. Lastly, the OAT process does not seem to be a high priority for the overseeing officials.
CONCLUSIONS
From a legal standpoint, OAT authorisations should be straightforward, yet we found significant divergences among cantonal systems. We could not find scientific evidence that supports a given framework. We recommend harmonizing the 26 cantonal systems while reviewing the need for OAT authorisation.
Topics: Humans; Switzerland; Cross-Sectional Studies; Analgesics, Opioid; Qualitative Research; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 38885521
DOI: 10.57187/s.3629 -
PloS One 2024The objective of this study was to estimate the associations of jail-initiated medication for opioid use disorder (MOUD) and patient navigation (PN) with opioid use... (Randomized Controlled Trial)
Randomized Controlled Trial
The objective of this study was to estimate the associations of jail-initiated medication for opioid use disorder (MOUD) and patient navigation (PN) with opioid use disorder (OUD) at 6 months post-release. Three randomized trials (combined N = 330) were combined to assess whether MOUD (extended-release naltrexone or interim methadone) initiated prior to release from jail with or without PN would reduce the likelihood of a DSM-5 diagnosis of OUD 6 months post-release relative to enhanced treatment-as-usual (ETAU). Across the three studies, assignment to MOUD compared to ETAU was not associated with an OUD diagnosis at 6 months post-release (69% vs. 75%, respectively, OR = 0.67, 95% CI: 0.42 to 1.20). Similarly, PN compared to MOUD without PN was not associated with an OUD diagnosis (63% vs 77%, respectively, OR = 0.61, 95% CI: 0.27 to 1.53). Results underscore the need to further optimize the effectiveness of MOUD for patients initiating treatment in jail, beginning with an emphasis on post-release treatment adherence.
Topics: Humans; Opioid-Related Disorders; Male; Naltrexone; Female; Adult; Methadone; Jails; Opiate Substitution Treatment; Middle Aged; Narcotic Antagonists; Prisoners
PubMed: 38885220
DOI: 10.1371/journal.pone.0305165 -
The International Journal on Drug Policy Jun 2024In this essay we want to foreground a question: what happens to 'addiction' when we take seriously cultural scripts informing its trajectories? Can this bring us to...
In this essay we want to foreground a question: what happens to 'addiction' when we take seriously cultural scripts informing its trajectories? Can this bring us to unthink addiction as problematic notion and move it onto new paradigms that fit better the now acknowledged fluidity and pluralistic episteme of 'addiction' and more broadly of chronic life conditions? Indeed, 'addiction' has become a pivotal concept in the contemporary world. A powerful diagnostic framework in interpreting human behaviour, for some 'addiction' has become the 'new normal' with chronic relations with different things such as food, sex, gambling, and mind-altering substances touching upon the lifestyle of a majority of individuals, making everyone 'addicts in practice'. Perhaps this has something to do with the constituent force that 'habit' - as in 'addiction' - has in defining our present and future. Though 'addiction' goes beyond the question of mind-altering drugs, the politics of 'addiction' is intimately tied to substances such as opioids and opiates, cocaine, cannabis, and psychedelics that have been the object of durable systemic political control and security repression. Contextually the line between licit/illicit substances is softening and blurring, the 'dual' purpose that drugs serve is now recognised in scientific and popular analysis moving the question of 'addiction' beyond the medicine/drug dichotomy. Yet, culture is generally absent in understanding 'addiction.' When it is referred to, this happens in diminutive terms limited to Anglo-American modern culture. Culture matters and it matters with different weights and measures as it moves across the world. There are cultural environments of health informed by practices and epistemologies of well-being that have evolved in lines opposites from or only intersecting with the Anglo-American, and generally Western, world. Exploring these spaces and cultural scripts enables our scholarship on drugs and 'addiction' to move the barycentre of discussion towards novel considerations around the historical trajectories and potential futures of our diagnostic terms and policy interventions.
PubMed: 38875879
DOI: 10.1016/j.drugpo.2024.104473 -
Journal of Neuroimmune Pharmacology :... Jun 2024The opioid epidemic has received considerable attention, but the impact on perinatal opioid-exposed (POE) offspring remains underexplored. This study addresses the...
The opioid epidemic has received considerable attention, but the impact on perinatal opioid-exposed (POE) offspring remains underexplored. This study addresses the emerging public health challenge of understanding and treating POE children. We examined two scenarios using preclinical models: offspring exposed to oxycodone (OXY) in utero (IUO) and acute postnatal OXY (PNO). We hypothesized exposure to OXY during pregnancy primes offspring for neurodevelopmental deficits and severity of deficits is dependent on timing of exposure. Notable findings include reduced head size and brain weight in offspring. Molecular analyses revealed significantly lower levels of inflammasome-specific genes in the prefrontal cortex (PFC). Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) highlighted the enrichment of genes associated with mitochondrial and synapse dysfunction in POE offspring. Western blot analysis validated IPA predictions of mitochondrial dysfunction in PFC-derived synaptosomes. Behavioral studies identified significant social deficits in POE offspring. This study presents the first comparative analysis of acute PNO- and IUO-offspring during early adolescence finding acute PNO-offspring have considerably greater deficits. The striking difference in deficit severity in acute PNO-offspring suggests that exposure to opioids in late pregnancy pose the greatest risk for offspring well-being.
Topics: Animals; Oxycodone; Pregnancy; Female; Prenatal Exposure Delayed Effects; Male; Analgesics, Opioid; Behavior, Animal; Rats; Rats, Sprague-Dawley; Neurodevelopmental Disorders; Prefrontal Cortex
PubMed: 38874861
DOI: 10.1007/s11481-024-10129-7 -
Addiction Science & Clinical Practice Jun 2024The 15-method is a targeted screening and treatment approach for alcohol problems in primary care. The 15-method used in primary care has proven as effective as... (Randomized Controlled Trial)
Randomized Controlled Trial
The identification and treatment of alcohol problems in primary care (iTAPP) study: protocol for a stepped wedge cluster randomized control trial testing the 15-method in a primary care setting.
BACKGROUND
The 15-method is a targeted screening and treatment approach for alcohol problems in primary care. The 15-method used in primary care has proven as effective as specialized treatment for mild to moderate alcohol dependence in Sweden. A feasibility study of the 15-method in Danish primary care found the method acceptable and feasible.
AIMS
To evaluate the effectiveness of the 15-method in a Danish primary care setting in (1) lowering the proportion of patients exceeding the Danish low-risk alcohol consumption limit of ten standard units per week and a maximum of four standard units on a single day for men and women, and (2) increasing the likelihood of alcohol use being addressed during a consultation in general practice. Further, the rate of prescribed pharmacological treatment for alcohol problems (Disulfiram, Naltrexone, Acamprosate, and Nalmefene) will be measured along with the use of the biomarkers Alanine Transaminase and Gamma-Glutamyl Transferase.
METHODS
Stepped wedge cluster randomized controlled trial in sixteen general practices in the Region of Southern Denmark. Following a three-month baseline, the practices are randomly assigned to launch dates in one of four clusters. General practitioners and nurses receive three hours of training in the 15-method before launch. Patient questionnaires will collect data on alcohol consumption levels among patients affiliated with the practices. The healthcare professionals will register consultations in which alcohol is addressed in their patient filing system. Pharmacological treatment rates and the use of biomarkers will be collected through Danish national registries. The study follows the Medical Research Council's guidelines for developing and evaluating complex interventions.
DISCUSSION
From the patient's perspective, the 15-method may help identify alcohol-related problems at an earlier stage with flexible treatment offers in a familiar setting. For healthcare professionals, it addresses a traditionally challenging topic by equipping them with concrete tools, communication training, and clear treatment directives. From a societal perspective, primary care holds a unique position to identify hazardous and harmful alcohol use across different age groups, with potential public health and economic benefits through early identification and intervention.
TRIAL REGISTRATION
Clinicaltrials.gov NCT05916027. Retrospectively registered 22 June 2023.
Topics: Humans; Primary Health Care; Denmark; Naltrexone; Alcoholism; Male; Female; Alcohol Deterrents; Disulfiram; Acamprosate; Adult; Taurine; Alanine Transaminase; gamma-Glutamyltransferase; Middle Aged; Mass Screening; Randomized Controlled Trials as Topic
PubMed: 38872214
DOI: 10.1186/s13722-024-00474-6