Search Results (71)

Background/Objectives: Cocaine is a widely used illicit stimulant with significant toxicity. Despite its clinical relevance, the broader metabolic alterations associated with cocaine use remain incompletely characterized. This study aims to identify novel biomarkers for cocaine exposure by applying untargeted metabolomics to retrospective urine drug screening data. Methods: We conducted a retrospective analysis of a raw mass spectrometry (MS) dataset from urine comprehensive drug screening (UCDS) from 363 patients at the University of Pittsburgh Medical Center Clinical Toxicology Laboratory. The liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-qToF-MS) data were preprocessed with MS-DIAL and subjected to multiple statistical analyses to identify features significantly associated with cocaine-enzyme immunoassay (EIA) results. Significant features were further evaluated using MS-FINDER for feature annotation. Results: Among 14,883 features, 262 were significantly associated with cocaine-EIA results. A subset of 37 more significant features, including known cocaine metabolites and impurities, nicotine metabolites, norfentanyl, and a tryptophan-related metabolite (3-hydroxy-tryptophan), was annotated. Cluster analysis revealed co-varying features, including parent compounds, metabolites, and related ion species. Conclusions: Features associated with cocaine exposure, including previously underrecognized cocaine metabolites and impurities, co-exposure markers, and alterations in an endogenous metabolic pathway, were identified. Notably, norfentanyl was found to be significantly associated with cocaine -EIA, reflecting current trends in illicit drug use. This study highlights the potential of repurposing real-world clinical toxicology data for biomarker discovery, providing a valuable approach to identifying exposure biomarkers and expanding our understanding of drug-induced metabolic disturbances in clinical toxicology. Further validation and exploration using complementary analytical platforms are warranted. Full article

Background/Objectives: The emergence of cathinone-based psychostimulants necessitates ongoing research and analysis of the characteristics and properties of novel derivatives. The metabolic fate of five novel cathinone-derived substances (ASProp, MASProp, MASPent, PySProp, and PySPent) containing a selenophene moiety was investigated in vitro and in vivo. Methods: All compounds were incubated individually with pooled human liver S9 fraction. A monooxygenase activity screening investigating the metabolic contribution of eleven recombinant phase I isoenzymes was conducted. Rat urine after oral administration was prepared by urine precipitation. Liquid chromatography–high-resolution tandem mass spectrometry was used for the analysis of all samples. Reversed-phase liquid chromatography (RPLC) and zwitterionic hydrophilic interaction liquid chromatography (HILIC) were used to evaluate and compare the metabolites’ chromatographic resolution. Results: Phase I reactions of ASProp, MASProp, MASPent, PySProp, and PySPent included N-dealkylation, hydroxylation, reduction, and combinations thereof. The monooxygenase activity screening revealed the contribution of various isozymes. Phase II reactions detected in vivo included N-acetylation and glucuronidation. Both chromatographic columns complemented each other. Conclusions: All substances revealed metabolic reactions comparable to those observed for other synthetic cathinones. Contributions from isozymes to their metabolism minimized the risk of drug–drug interactions. The identified metabolites should be considered as targets in human biosamples, especially in urine screening procedures. RPLC and HILIC can both be recommended for this purpose. Full article

Opioid use disorder (OUD) and posttraumatic stress disorder (PTSD) frequently co-occur. However, there are no psychotherapy treatments intentionally designed for this comorbidity, nor designed to be augmented with medications for OUD. In this open-label pilot trial, we tested Helping Opioid Use Disorder and PTSD with Exposure (HOPE), a novel integrated, trauma-focused treatment for individuals (N = 6) with OUD/PTSD who were stabilized on medications for OUD. HOPE was delivered weekly for 10–12 sessions, and one follow-up visit was conducted ~1-month post-treatment. Primary outcomes included urine drug screens, the Timeline Followback, Desire for Drugs Questionnaire, Clinician-Administered PTSD Scale-5 (CAPS-5), and PTSD Checklist-5 (PCL-5). Boot-strapped linear mixed effect models and generalized estimating equations showed that PTSD symptoms (CAPS-5: B = −7.16, SE = 1.24, p < 0.01; PCL-5: B = −2.04, SE = 0.26, p < 0.01), desire for opioids (B = −0.56, SE = 0.15, p < 0.01), depression symptoms (B = −0.43, SE = 0.09, p < 0.01), and anxiety symptoms (B = −0.50, SE = 0.08, p < 0.01) decreased significantly over time. Client satisfaction increased throughout the study (B = 0.18, SE = 0.08, p = 0.02), and 83.3% of participants completed the therapy and follow-up visit. There were no significant changes in opioid or other substance use from baseline to follow-up. Although preliminary, results show high acceptability and feasibility of the HOPE therapy and demonstrate significant improvements in PTSD and associated symptoms with an integrated, trauma-focused treatment. Full article

Promethazine hydrochloride (PMH) is a first-generation antipsychotic drug created from phenothiazine derivatives that is widely employed to treat psychiatric disorders in human healthcare systems. However, an overdose or long-term intake of PMH can lead to severe health issues in humans. Hence, establishing a sensitive, accurate, and efficient detection approach to detect PMH in human samples is imperative. In this study, we designed orthorhombic copper molybdate microspheres decorated on reduced graphene oxide (Cu₃Mo₂O₉/RGO) composite via the effective one-pot hydrothermal method. The structural and morphological features of the designed hybrid were studied using various spectroscopic methods. Subsequently, the electrochemical activity of the composite-modified screen-printed carbon electrode (Cu₃Mo₂O₉/RGO/SPCE) was assessed by employing voltammetric methods for PMH sensing. Owing to the uniform composition and structural benefits, the combination of Cu₃Mo₂O₉ and RGO has not only improved electrochemical properties but also enhanced the electron transport between PMH and Cu₃Mo₂O₉/RGO. As a result, the Cu₃Mo₂O₉/RGO/SPCE exhibited a broad linear range of 0.4–420.8 µM with a low limit of detection (LoD) of 0.015 µM, highlighting excellent electrocatalytic performance to PMH. It also demonstrated good cyclic stability, reproducibility, and selectivity in the presence of chlorpromazine and biological and metal compounds. Furthermore, the Cu₃Mo₂O₉/RGO/SPCE sensor displayed satisfactory recoveries for real-time monitoring of PMH in human urine and serum samples. This study delivers a promising electrochemical sensor for the efficient analysis of antipsychotic drug molecules. Full article

Plasmodione is a potent early antiplasmodial compound. A metabolic study on mice treated with plasmodione revealed that 6-hydroxy–plasmodione was the main metabolite eliminated in the urine of treated mice. To block the metabolic pathway in the host, the introduction of fluorine at C-6 of the 3-benzylmenadione core was applied and showed potent antiplasmodial activity similar to that of the plasmodione analogue in vitro. In this work, a library of 38 6-fluoro-3-benzylmenadione analogues (a series) was constructed by incorporating structurally diverse groups in place of the 4-(trifluoromethyl) substituent present in the antiplasmodial plasmodione, via three synthetic routes. All new compounds were tested against the P. falciparum NF54 strain and for cytotoxicity with the rat L6 line. With a fluorine atom at C-6, A-a-21 was revealed to be the only compound from the a series, superior to the 6-H- analogue from the b series, with an IC₅₀ value of 70 nM versus 200 nM. Then, five other fluorine-based 3-benzylmenadiones, in which the fluorine was introduced in various positions of the 3-benzylmenadione core, were synthetized to assist our understanding of the impact of fluorine on antiplasmodial potencies in vitro; in particular, the aim here was to compare the effects of human serum and P. berghei species in these drug screens. This was also conducted in vivo with the P. berghei-infected mouse model. In the P. berghei species assay, PD and the 4′-fluoro-3′-trifluoromethyl-benzylmenadione A-b-9 exhibited a similar antiplasmodial behavior toward P. falciparum versus P. berghei. In the human serum versus Albumax assays, only the 6-fluoro–plasmodione showed a lower shift factor between Albumax assays and human serum conditions, suggesting a lower protein binding for the 6-F-PD compared to plasmodione or A-b-9. In vivo, 6-fluoro–plasmodione proved to be the most potent 3-benzylmenadione, reducing parasitemia by 50% after oral administration at 50 mg/kg. Full article

Schistosomiasis is a parasitic disease that is considered a major threat to public health in Madagascar. The condition is endemic in more than 90% of the country’s districts. It is estimated that as much as 52% of the country’s general population is infected with Schistosoma spp. trematodes. The aim of the present study was to assess the prevalence values of Schistosoma haematobium infections in a population of children living in northern Madagascar and to determine the impact of trematode infections on the hematological profiles of the children included in the study. This screening study was conducted in 2024, and it involved a group of 170 children aged 0–17 years. The participants were required to provide urine samples for microscopic and molecular examination. The urine samples were preserved on Whatman 903 protein sever cards using the dried urine spot (DUS) sampling technique and then were transported from Madagascar to a molecular laboratory in Poland, where the samples were tested for the presence of S. haematobium. The present study found that the incidence of S. haematobium infections in the study group consisting of 170 children was as high as 67.6%. The authors observed a reduction in mean hemoglobin (Hb) and mean corpuscular hemoglobin concentration (MCHC) values in the infected children. In spite of continuous efforts to prevent the transmission of schistosomiasis in endemic countries (WHO-recommended mass drug administration campaigns), the incidence of S. haematobium infections was found to be exceptionally high among the study participants. S. haematobium infections present with a characteristic hematological picture showing signs of increased immune response and anemia. The DUS technique has been successfully used for the molecular diagnosis of S. haematobium. This method opens up possibilities for more effective and less expensive sample collection. Full article

Background: Cocaine has been shown to cause cytotoxic neuronal damage, which has been implicated in cases of leukoencephalopathy. We present a case of cocaine-induced toxic encephalopathy resulting in predominant lesions to the gray matter on magnetic resonance imaging (MRI). Case Presentation: A 70-year-old female presented acutely with confusion, agitation, and disorientation. She was markedly hypertensive with other vital signs within normal range. On presentation to the emergency department, she was uncooperative and had an unsteady gait but showed no focal neurological deficits. Her lab work was positive for elevated cardiac troponins, elevated D-dimer, and a urine drug screen positive only for cocaine. Head computed tomography (CT) showed no hemorrhage and head CT angiogram showed no abnormalities and no significant vascular stenosis. Chest X-ray and CT showed diffuse ground glass opacities compatible with atypical pneumonia. Antibiotics were initiated to treat the pneumonia and antihypertensives were administered to manage her blood pressure. She was also given IV thiamine. Brain MRI showed restricted diffusion involving bilateral hippocampi, thalami, putamen, caudate, and right occipital lobe, findings suspicious for cytotoxic edema. After acute stabilization, the patient demonstrated profound anterograde and retrograde amnesia, which improved gradually over days to weeks. She was eventually discharged to a skilled nursing facility. Conclusion: To our knowledge, this is the first reported case of profound amnesia secondary to cocaine-induced toxic encephalopathy with bilateral hippocampal involvement. These symptoms correlate with the implicated neuroanatomical structures. This case demonstrates that cocaine may be implicated in toxic encephalopathy affecting the brain’s gray matter and highlights a unique presentation of these findings. Full article

Hypertension is a multifactorial and complex disease influenced by genetic and environmental factors, and it has become one of the most serious public health challenges. This study aimed to investigate the changes in hypertension based on urinary proteome. The stroke-prone spontaneously hypertensive rats (SHRSPs) model was used to examined urinary proteome changes during the development of hypertension. Urine proteome profiling was conducted at months 1, 4, 8, 10, 12, and 14 using liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). Given that the progression of hypertension may vary among individuals, each rat was compared before and after hypertension developed to screen for differential proteins. Differential proteins in each rat can be enriched into some important biological processes and pathways associated with hypertension, such as the regulation of systemic arterial blood pressure by renin-angiotensin, renin-angiotensin signaling, response to glucocorticoid and glucocorticoid receptor signaling, calcium transport I, aldosterone adipocyte signaling pathway, apelin adipocyte signaling pathway, and oxidative stress response. The biological processes and pathways enriched at the same time point in the progression of hypertension differed significantly among different rat individuals. This study demonstrated that the changes in hypertension can be reflected in urine proteins. Urinary proteomics has potential in researching the mechanisms underlying hypertension, discovering new drug targets, and developing personalized strategies for antihypertensive treatment. Full article

Background/Objectives: This study evaluates the applicability of a comprehensive two-dimensional gas chromatography−flame ionisation detection (GC×GC−FID) approach for the simultaneous determination of 12 underivatised psychoactive drugs, including new psychoactive substances, that comprised of amphetamine, methamphetamine, mephedrone, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, α-pyrrolidinovalerophenone, n-ethylpentylone (ephylone), norketamine, ketamine, 3,4-methylenedioxypyrovalerone, methadone, and cocaine. Methods: Separation was effected using a non-polar first dimension (¹D) and a polar second dimension (²D) column, demonstrating an improved separation of drug compounds compared to a polar/non-polar column configuration. Interference-free baseline separation of all psychoactive compounds in a urine matrix was achieved within 8 min. The GC×GC−FID method was validated according to the guidelines defined by Standard Practices for Method Validation in Forensic Toxicology. Results: The calibration curves for the 12 psychoactive drugs were well correlated (r² > 0.99) within the concentration ranges of 50–1500 ng mL⁻¹. Detection limits of 10–20 ng mL⁻¹ were obtained, and good repeatability and reproducibility (CV < 11.4%) were attained for retention times and peak areas. Method recoveries for the small-scale solvent extraction procedure ranged from 96.9 to 114.5%, and bias was between −3.1% and 14.5%. Conclusions: The validated approach was successfully applied for the determination of these illicit compounds in spiked urine samples of different concentrations, highlighting its potential for rapid forensic drug screening. Full article

Numerous weight loss preparations emerge without medical or pharmaceutical supervision, thereby accentuating the risk to public health. Recent data shed light on the extent of the problem, with an increase in cases of nephrotoxicity associated with the use of plant-based dietary supplements (DSs). A 22-year-old patient, a smoker with no significant medical history, was admitted to the nephrology department of EHU Oran for the management of impure nephrotic syndrome complicated by acute renal failure, edema, and proteinuria. During interrogation, the patient admitted to incorporating the following products into his weight loss and muscle gain program: a plant-based DS named “Animal cuts^®”, composed of 38 plant extracts, supplementation with “Whey protein” at a dosage of 300 g/day, and creatine. Two samples, blood and urine, were sent to the toxicology department of EHU Oran. Since we did not receive the DS sample, a screening for various drugs was negative. An in-depth literature search on the toxic potential of the various components of “Animal cuts^®” allowed us to identify five components posing a risk to renal function, namely dandelion root extract (Taraxacum sp.), juniper berries (Juniperus sp.), green tea leaf extract (Camelia sinensis), and ginger (Zingiber officinale). Cases of renal dysfunction related to creatine supplementation have been reported in the literature. However, numerous studies indicate that “Whey protein” may not pose any nephrotoxic risk in individuals with normal renal function. This case adds to the growing number of reports of nephrotoxicity following the use of plant-based DSs and underscores the importance of strengthening regulations governing their production. Full article

We reported the gold/silver core-shell nanoparticles (Au_core@Ag_shell NPs) functionalized with β-cyclodextrin (β-CD) as versatile nano-agents demonstrated for human urine-based biosensing of cysteamine and catalytic conversion from nitrobenzene (NB) to aniline. First, the hybrid bimetallic nanoparticles, i.e., β-CD-Au_core@Ag_shell NPs, constituted a colorimetric sensing platform based on localized surface plasmons, enabling cysteamine (Cyst) to be detected in a remarkably rapid manner, i.e., within 2 min, which was greatly shortened in comparison with that of our previous report. This was due largely to use of β-CD being effectively replaceable by Cyst. The detection of Cyst was demonstrated using human urine specimens in the linear range of 25–750 nM with a limit of detection of 1.83 nM. Excellent specificity in detecting Cyst was also demonstrated against potential interfering molecules. Meanwhile, the β-CD-Au_core@Ag_shell NPs were demonstrated as nanocatalysts for converting NB to aniline with efficiency enhanced by more than three-fold over the pure gold nanoparticles previously reported, due to the dual functions of the structural core-shell. The demonstrated versatile features of the hybrid nanoparticles can find applications in human urine-based biosensors for Cyst detection, and in the screening of Cyst-containing drugs, while detoxicating NB for ecological protection in aqueous media. Full article

Infantile occult exposure to cocaine in domestic environments represents a complex clinical and medico-legal problem, which can be associated with abuse and neglect and with potential short- and long-term health risks for children. The authors present a retrospective study on 764 children under 14 years old who accessed the Emergency Department of IRCCS Meyer from 2016 to 2023 and were included in the GAIA (Child and Adolescent Abuse Group) protocol for suspected maltreatment and abuse, and for which a urine toxicology analysis was performed. The aim is to discuss the medico-legal implications and highlight the need for a thorough evaluation and management of such situations. Urine screening tests for substances of abuse (e.g., cocaine, opiates, etc.) were performed with an EMIT^® Siemens VIVA-E drug testing system (Siemens, Newark DE) in 124 cases for which the child’s clinical condition raised suspicion of intoxication, or the family context indicated distress or substance abuse dependency. The screening results revealed the presence of cocaine and its main metabolite, benzoylecgonine, in the urine of 11 children. In one case, a single girl was brought to the Emergency Department by staff from the facility where she and her mother were staying. In most of the cases, children were brought to the Emergency Department by their parents who accessed the Emergency Department due to various clinical manifestations (drowsiness, agitation, seizures, hypotonia, diarrhea, vomiting, etc.), except for one case of eye trauma suspected to be caused by abuse or neglect by one of the parents. Three of the children did not have signs or symptoms attributable to substance exposure, whilst eight of the cases presented some of the symptoms associated with occult infant exposure to cocaine, such as neurological manifestations, seizures, gastrointestinal symptoms, and respiratory depression. The probable mode of intake was mostly through breastfeeding and continuous environmental exposure due to domestic contamination or inhalation of “crack”. In the case of a 12-hour-old infant, there was probable prenatal in utero exposure. All the children were hospitalized, some for medical reasons and others solely as a precautionary measure for proper care. In all cases, a report was made to the Prosecutors as required by the Italian Penal Code, as well as to the Court of Minor. The study highlighted the importance of a multidisciplinary approach involving pediatricians, social workers, and forensics, as well as close collaboration with the relevant authorities, as the Gaia service at IRCCS Meyer offers. The occasional detection of cocaine in cases that showed no suspicion of intoxication led to a modification of the procedure and the development of a standardized protocol at IRCCS Meyer both in terms of prevention and in the detection and interception of hidden cases, in order to intervene early and initiate the necessary care pathways (secondary prevention). This protocol includes routine toxicological urine testing in all suspected or confirmed cases of child abuse, not just in those where symptoms might suggest a suspicion of intoxication. Full article

17β-estradiol (E2), a vital female sex hormone, plays a crucial role in female reproductive cycles and secondary sexual characteristics. The quantification of E2 concentration in human blood and urine samples is essential because a deviation from physiological levels of E2 indicates the development of diseases and abnormalities such as precocious puberty, breast cancer, weight gain, abnormal menstruation, osteoporosis, and infertility. In addition, the detection of E2 in food and the environment has gained widespread interest because of its role as an endocrine disruptor (environmental hormone) that can perturb physiological processes. E2 is used as a drug for hormone therapy. Various E2 detection technologies for diagnosing relevant human diseases, drug screening, and environmental monitoring have been demonstrated in studies. In this article, we have reviewed technological strategies developed for E2 detection with ultrahigh sensitivity, with a limit of detection comparable to several pg/mL or lower. We observed that gold nanoparticles (AuNPs) were used as nanoplatforms for signal amplification, which enabled ultrahigh sensitivity in most studies. Signal amplification was facilitated by AuNP characteristics such as the versatility of surface biochemistry, exceedingly large surface-to-volume ratio, surface plasmonic activity, luminescence quenching ability, and biocompatibility. These techniques have been used to detect E2 in food, water, human serum, and urine with ultrahigh sensitivity. We summarize the working principles of E2 detection strategies that allow ultrahigh sensitivity and provide an approach for future work required for the elucidation of practical applications of these technologies. Full article

Individuals with mental illness have a high incidence of comorbid substance use, with one of the most prevalent being alcohol use disorder (AUD). Naltrexone, FDA-approved for AUD, decreases reward associated with alcohol-related social cues. This study aimed to determine if a pharmacist-driven screening tool would increase the use of extended-release naltrexone (XR-NTX) in patients with AUD and a comorbid psychiatric condition. Pharmacists screened and recommended XR-NTX for adults admitted to the inpatient psychiatric unit, who had a DSM-5 diagnosis of AUD, a negative urine drug screen for opioids, and were hospitalized for at least 1 day. Endpoints evaluated included the number of XR-NTX doses administered during the screening period to the prescreening period, 30-day readmission rates, recommendation acceptance rates, and reasons for not administering XR-NTX. Pharmacists identified 66 of 641 screened patients who met the inclusion criteria and were candidates for XR-NTX. Compared to the preintervention period, more patients received XR-NTX for AUD (2 vs. 8). Readmission rates were similar between those with AUD who received XR-NTX and those who did not. Pharmacist-driven screening for AUD led to greater administration of XR-NTX when compared to the same 4-month period the year prior to initiating the study. Full article

Schistosomiasis and soil-transmitted helminthiasis remain a public health concern in Tanzania. This study investigated the prevalence and intensities of Schistosoma haematobium, S. mansoni, and soil-transmitted helminths and associated factors in Itilima district, north-western Tanzania. A cross-sectional survey was conducted between August and September 2020 among 3779 primary schoolchildren in 62 primary schools and 1122 adults in 19 villages. Urine samples were obtained from each participant and examined visually for the presence of macrohaematuria, microhaematuria, and S. haematobium eggs using a urine dipstick and urine filtration test. A single stool sample was obtained from each participant and screened for S. mansoni and soil-transmitted helminths using the Kato Katz and formalin-ether concentration techniques. A questionnaire was administered to schoolchildren to elucidate the risk factors for schistosomiasis. The overall prevalence of S. haematobium in adults was 8.1% (95% confidence interval (CI), 6.6–9.8%). In total, 3779 schoolchildren had complete results from urine testing, and the overall prevalence of S. haematobium was 10.1% (95% CI, 9.1–11.1%). The prevalence of S. mansoni and soil-transmitted helminths was relatively low among both children and adults compared to S. haematobium. Factors associated with S. haematobium infection among schoolchildren were the mother’s occupation, children aged 11–15 years, and water contact behaviour. The odds of having schistosomiasis infection among children aged 11–15 are 40% higher than those aged 5–10 (95% confidence interval (CI), 10–80%, p = 0.04). Children of parents who are livestock keepers have 12.3 times higher odds of having infection compared to those who have small-scale businesses (95% CI, 1.0–5.4, p = 0.03). Children who are in contact with infested water more than three times a week have 2.1 times higher odds of having an infection compared to those who do not (95% CI, 2.1; 1.6–2.8, p < 0.001). The findings provide updated geographical information on prevalence, yielding insights into the planning and implementation of mass drug administration in rural Tanzania. Full article