Hasil untuk "Toxicology. Poisons"

Pramod Chandru, Ian Ngo, Helene Benedicte Fabrin Brasted et al.

Background Prescription drug misuse is a growing contributor to morbidity and mortality in Australia. Off-label use of sedating psychotropics is common, but their role in overdose presentations is poorly characterised.Objectives To describe the characteristics, intent and outcomes of prescription and off-label drug overdoses presenting to two toxicology referral centres in Western Sydney.Methods A retrospective cohort study included all toxicology consultations from January to August 2025 across two toxicology referral centers. Data were extracted from electronic records and classified as prescription or non-prescription. Off-label status was defined using the Australian Medicines Handbook and Therapeutic Guidelines. Primary outcomes were admission rates, length of stay (LOS) and mortality.Results We analysed 597 presentations (median age 32 years, IQR 25–47; 27% female). Hospital admission was more frequently observed in the prescription overdose group compared to the non-prescription group (33.9% vs 27.9%). While the median length of hospital stay was 0 days in both groups, admissions involving prescription agents demonstrated greater variability (IQR 0–3 vs 0–1). Deliberate self-poisoning was significantly more common in prescription overdoses (64% vs 25%, p < 0.0001), whereas recreational intent was more frequently observed in non-prescription cases, particularly among males. A total of 38 presentations (13%) involved off-label prescribing, most commonly quetiapine, diazepam, clonidine, and pregabalin. Compared to both on-label prescription and non-prescription overdoses, off-label cases had significantly higher hospital admission rates (26.5% vs 14.5% vs 13.1%, p = 0.032) and longer hospital stays (median 2.5 days, IQR 0–7, p < 0.001). ICU admission was most common following overdoses involving anticonvulsants (45%) and antipsychotics (34%), with lithium-associated overdoses showing the longest ICU stays (median 14.4 days, IQR 13.9–14.9).Conclusions Prescription overdoses, particularly those involving off-label psychotropic agents, were observed to have higher rates of healthcare utilisation and longer hospital stays.

Ziwei LIANG, Chao FENG, Jiawen YOU et al.

BackgroundPer- and polyfluoroalkyl substances (PFASs) are a class of persistent organic pollutants that pose potential health risks to humans. Infants and young children have higher requirements for food safety due to the underdeveloped detoxification and immune systems. Therefore, developing a comprehensive method for determination of PFASs and their novel alternatives in infant complementary food is of great significance. ObjectiveTo develop an analytical method using liquid chromatography high-resolution mass spectrometry technology for determination of 55 PFASs in plant- and animal-derived infant complementary fruit purees.MethodsOasis WAX (200 mg, 6 CC) solid-phase extraction columns were used for sample enrichment and purification. The pH of the acetonitrile extract was adjusted using 0%, 1%, 1.5%, and 2% formic acid aqueous solutions to evaluate its impact on the recovery rate of target compounds. Additionally, the impact of a 2 mL methanol wash during the purification process on the recovery of target compounds was assessed to determine the optimal pretreatment conditions. Three types of chromatographic columns—Agilent Poroshell 120 EC-C18, Thermo InfinityLab Poroshell 120 Aq-C18, Acquity Waters BEH-C18, and changes in mobile phase, were compared for their effects on retention time, peak shape, and response of target compounds. The method was validated in terms of selectivity, linear range, detection limit, and precision. The established method was applied to 49 commercial samples of infant complementary fruit purees. ResultsAdjusting the sample pH using 1.5% formic acid water and incorporating a 2 mL methanol wash during purification achieved satisfactory recovery rates. The target compounds were chromatographically separated using an Agilent Poroshell 120 EC-C18 column with a gradient elution system. The mobile phase consisted of methanol-water (methanol/water: 2/98, v/v) containing 5 mmol·L−1 ammonium formate as mobile phase A, and methanol as mobile phase B. Good separation was achieved within 15 min, resulting in optimal chromatographic peak shapes. The 55 target compounds exhibited good linearity across the standard curve range, with correlation coefficients (R²) greater than 0.99. The method detection limits ranged from 0.02 to 0.05 µg·L−1. In the plant- and animal-based fruit puree samples, the spiked recovery rates ranged from 60% to 112% and 57% to 119%, respectively, with relative standard deviations (RSD) ≤ 30%. A total of 9 traditional PFASs and 5 novel PFASs were positive in 49 samples of infant complementary fruit purees. ConclusionThis method enables comprehensive detection of 55 traditional and emerging PFASs, offering wide coverage, high accuracy, and excellent sensitivity. It provides technical support for characterizing contamination by traditional and emerging PFASs in food matrices.

Jitu Halder, Shuvam Mishra, Ivy Saha et al.

Abstract Background Azithromycin (ATM) has limitations, such as poor oral bioavailability and gastrointestinal (GI) side effects that restrict its widespread application. Objective To develop a localized hydroxy propyl β-cyclodextrin (HP-βCD) inclusion complex-based in situ pH-responsive mucoadhesive gel of azithromycin (ATM) and evaluate its performance for the treatment of upper respiratory tract infections (URTIs). Methods According to the phase solubility diagram, the ATM HP-βCD complex was prepared and analyzed by FT-IR, DSC, and SEM. Then, using a quality-by-design approach, pH-responsive in-situ gel was prepared. It was characterized in terms of their gelling capacity, pH, spreadability, swelling index, rheological properties and antimicrobial potential. Results ATM HP- βCD complex 20-fold increased solubility of ATM, i.e., 49.84 ± 1.39 µg/mL with improved dissolution profile compared to pure ATM. Optimized formulation characterized by its gelation pH (6.7), time (1.59 min), and viscosity (1607.9 Pa.s). The developed gel showed a good spreadability index (322.6 ± 0.5%), swelling index (98.26 ± 1.54% after 10 h) and mucoadhesive strength (589 g/cm2). Also, it exhibits a sustained drug release profile for 12 h(94 ± 1.37%) and a broader zone of Staphylococcus aureus growth inhibition (31 ± 3.54 mm). Conclusion The developed mucoadhesive in situ gels demonstrated promising in vivo performance, primarily due to their effective antimicrobial activity. In vivo, local retention studies confirmed that the formulations adhered to the throat mucosa and remained in place for up to 24 h after application. The findings presented here suggested that this localized delivery system could serve as a useful strategy for improving the therapeutic effects of ATM against URTIs. Graphical Abstract

Karolina Kopańska, Adrian Cabrera, Manuel Pastor

In the search for alternatives to replace in vivo studies, the application of assessment frameworks involving New Approach Methodologies (NAMs) often leads to the simultaneous availability of multiple pieces of evidence of different quality. When integrated into defined data structures, combinations of NAMs can generate answers to complex toxicological questions. However, if they are not integrated correctly, a collection of NAM results may produce misleading results that complicate the assessment process or lead to wrong conclusions.To support transparent decision-making in situations in which multiple NAMs are applied to generate results for the same toxicological question, we developed TOXTRUST (www.github.com/phi-grib/TOXTRUST) — an open-source computational tool integrating the mathematical framework of the Dempster-Shafer Theory (DST).In this article, we briefly describe the DST framework for the integration of NAM results to define the scope of its application and data requirements. This is followed by a description of the functionalities and infrastructure of TOXTRUST. Lastly, we illustrate how TOXTRUST can be applied to any endpoint with binary end-results, with a focus on the generation and interpretation of results expressed through probability bounds.

Sumi Wijaya, Henry Kurnia Setiawan

Background: Throughout many decades, researchers all around the world still extensively search for treatment strategies for Alzheimer's disease. Dispute the small number of medicines that can be used for the treatment, the side effects, and the only symptomatic treatments of the drug, which makes the necessity of finding new sources of drugs from plant sources a critical movement. Objective: In this research, we investigate the potential of 33 traditional medicines plants from Indonesia for their acetylcholinesterase inhibitor and antioxidant properties. Methods: The inhibitory potential of acetylcholinesterase was carried out using spectrophotometry using acetylcholine as a substrate and antioxidant activity was measured using the FRAP method. Results: The results indicate that among the 33 plants, only seven plants with an acetylcholinesterase inhibitor (AChEI). Those plants are Chromolaena odorata, Mikania scandes, Piper cubeba, Peperomia pellucida, Persea americana, Lycium barbarum and Phyllanthus niruri.  All the plant samples showed remarkable antioxidant potency with the range of value 4.11 – 52.65 mg/mL. Conclusions: Persea americana (Lauraceae) had the greatest AChEI with a value of 4.11 mg/mL, meanwhile Piper cubeba (Piperaceae) has the highest potency in scavenging free radicals with an FRAP Value of 10.89 mg/mL. There was no correlation between AChEI and Antioxidant potency.

V. Sravani, Saira Zia, Shaiesta Amreen et al.

Introduction: First trimester bleeding is troublesome problem in pregnant women. It occurs due to various causes, some not related to pregnancy. It leads to various maternal & fetal adverse outcomes as well. Aim: To study pregnancy outcome in women with first trimester bleeding. Materials and Methods: This prospective observational study was done among 150 women with first trimester bleeding in Department of obstetrics & Gynecology, Shifaa hospital, Bangalore. Various adverse outcomes in pregnant women & neonates were observed as variables and their incidences were calculated. Results: Among 150 pregnant women, maximum adverse outcomes were seen in age group 23-26yrs, multigravidas and those with previous term pregnancies. Antepartum complications in decreasing order of frequency were PROM, Pre- Eclampsia, Abruption, Low-Lying placenta, Eclampsia. Majority of pregnant women had normal vaginal deliveries followed by cesarean and instrumental delivery. 20.7% of neonates had low birth weight who needed close monitoring in NICU. Conclusion: First trimester bleeding is considered as one of the indicator for determining fetal & maternal outcome. Knowledge regarding this aspect will help obstetricians to anticipate complications and manage them effectively.

Fiona Chapman, Luuk de Haan, Linda Gijzen et al.

BackgroundSmoking cigarettes is a cause of serious diseases in smokers, including cardiovascular disease. Through a pathway of endothelial dysfunction, lipid infiltration, macrophage recruitment and vascular remodeling, atherosclerosis is fundamental in the development of most cardiovascular diseases. There is an increasing number of next-generation products (NGP) which provide potentially reduced harm forms of nicotine delivery to adult smokers. This study aimed to optimise an in vitro cardiovascular model to assess such products. Human Coronary Artery Endothelial Cells (HCAECs) were cultured on an OrganoPlate®2-lane chip (Mimetas BV) combined with THP-1 monocytes under flow conditions.MethodsAn aqueous aerosol extract from the 1R6F reference cigarette was compared with two categories of NGP, (a heated tobacco product (HTP) and an electronic nicotine delivery system (ENDS)), to assess relative effects on select atherogenic endpoints (oxidative stress, monocyte adhesion, ICAM-1 expression, and inflammatory markers). Following exposure of THP-1 monocytes with the aqueous extracts, the resulting conditioned medium was then added to the HCAEC vessels.Results1R6F was consistently the most potent test article, eliciting observed responses at 4x lower concentrations than applied for both the HTP and ENDS. The HTP was more potent than the ENDS product across all endpoints, however, all test articles increased monocyte adhesion. ICAM-1 did not appear to be a main driver for monocyte adhesion, however, this could be due to replicate variability. Upon comparison to an extract-only control exposure, THP-1-medium pre-conditioning was an important mediator of the responses observed.ConclusionIn conclusion, the data suggests that the NGP extracts, containing primary aerosol chemical constituents exhibit a marked reduction in biological activity in the early key events associated with atherogenesis when compared to a cigarette, adding to the weight of evidence for the tobacco harm reduction potential of such products.

Valery Gunas, Oleksandr Maievskyi, Nataliia Raksha et al.

Problem of scorpion envenomation becomes more alarming each year. Main effects of scorpion venom are commonly believed to be related to its neurotoxic properties, yet severe symptoms may also be developed due to the uncontrolled enzymatic activity and formation of various bioactive molecules, including middle-mass molecules (MMMs). MMMs are considered as endogenous intoxication markers, their presence may indicate multiple organ failure. Scorpions, belong to the Leiurus macroctenus species, are very dangerous, nevertheless, effects of their venom on protein and peptide composition within the tissues remains unclear. In this work we have focused the attention on changes in protein and MMM levels and peptide composition in various organs during Leiurus macroctenus envenomation. The results revealed a decrease in protein level during envenomation as well as a significant increment of MMM210 and MMM254 levels in all assessed organs. Quantitative and qualitative compositions of various protein and peptide factions were continually changing. All of this may suggest that Leiurus macroctenus sting causes considerable destruction of cell microenvironment across all essential organs, providing systemic envenomation. In addition, MMM level increment may indicate endogenous intoxication development. Peptides, formed during envenomation, may possess various bioactive properties, analysis of which constitutes an area of further studies.

Azza Naija, Huseyin Cagatay Yalcin

Chemicals are at the top of public health concerns and metals have received much attention in terms of toxicological studies. Cadmium (Cd) and mercury (Hg) are among the most toxic heavy metals and are widely distributed in the environment. They are considered important factors involved in several organ disturbances. Heart and brain tissues are not among the first exposure sites to Cd and Hg but they are directly affected and may manifest intoxication reactions leading to death. Many cases of human intoxication with Cd and Hg showed that these metals have potential cardiotoxic and neurotoxic effects. Human exposure to heavy metals is through fish consumption which is considered as an excellent source of human nutrients. In the current review, we will summarize the most known cases of human intoxication with Cd and Hg, highlight their toxic effects on fish, and investigate the common signal pathways of both Cd and Hg to affect heart and brain tissues. Also, we will present the most common biomarkers used in the assessment of cardiotoxicity and neurotoxicity using Zebrafish model.

Grace Patlewicz, Andrew Worth, Chihae Yang et al.

Maryam Tanveer, Shaghef Ejaz, Syed Muhammad Zaka et al.

Tribolium castaneum (Herbst), one of the invasive stored pest, is resistant to the most of synthetic insecticides used against this it. Moreover, synthetic insecticides are a major threat to human health, the environment, and the ecosystem. The development of some smart tools is needed to minimize the use of hazardous chemicals. As an alternative, nano-insecticides are on the horizon. Emulsions are expressed as sustain release of insecticidal components to achieve maximum efficacy and low residual toxicity. In this study, some essential oils (Cymbopogon citratus (DC.) Stapf, Ocimum basilicum L., Curcuma longa L., and Trachyspermum ammi L.), diatomaceous earth (DE), and their nano-emulsions are evaluated against T. castaneum. Essential oils and DE were tested at four (60 ppm, 30 ppm, 15 ppm, 7.5 ppm) different concentrations with and without emulsions, and data was recorded after 6, 12, 24, 48, and 72 h of exposure respectively. The mortality observed in essential oils of C. citratus, O. basilicum, and C. longa without emulsion after 72 h of treatment at the highest concentration was 98%, 95%, and 85%, respectively. While, at the highest concentration the lowest mortalities were observed with DE and T. ammi i.e. 65%. Insecticidal activity of emulsion essential oils increased to 100%, 98%, 90%, and 68.3% for C. longa, C. citratus, O. basilicum, and T. ammi, respectively. The results support that these admixed emulsions could be used as an alternative to synthetic insecticides in conventional formulations.

Shobha V. Huilgol

There is increasing realization and demand for health professional education to link curriculum to healthcare needs. Health professional educators have now professional and ethical obligation to meet the above demands and they need to be accountable. Accreditation bodies attach importance and weightage to curricula, that state the process of curriculum development also the educational and evaluation strategies [1]. These bodies look for outcome measurements in the curricula [2].

Gurudatt Chandorkar, Qiao Zhan, Julie Donovan et al.

Abstract Background Surotomycin, a novel, orally administered, cyclic, lipopeptide antibacterial in development for the treatment of Clostridium difficile-associated diarrhea, has demonstrated minimal intestinal absorption in animal models. Methods Safety, tolerability, and plasma pharmacokinetics of single and multiple ascending oral doses (SAD/MAD) of surotomycin in healthy volunteers were characterized in two randomized, double-blind, placebo-controlled, phase 1 studies. Results Participants were sequentially enrolled into one of four SAD (500, 1000, 2000, 4000 mg surotomycin) or three MAD (250, 500, 1000 mg surotomycin twice/day for 14 days) cohorts. Ten subjects were randomized 4:1 into each cohort to receive surotomycin or placebo. Surotomycin plasma concentrations rose as dose increased (maximum plasma concentration [Cmax]: 10.5, 21.5, 66.6, and 86.7 ng/mL). Systemic levels were generally low, with peak median surotomycin plasma concentrations observed 6–12 h after the first dose. In the MAD study, surotomycin plasma concentrations were higher on day 14 (Cmax: 25.5, 37.6, and 93.5 ng/mL) than on day 1 (Cmax: 6.8, 11.0, and 21.1 ng/mL for increasing doses), indicating accumulation. In the SAD study, <0.01% of the administered dose was recovered in urine. Mean surotomycin stool concentration from the 1000 mg MAD cohort was 6394 μg/g on day 5. Both cohorts were well tolerated with all adverse events reported as mild to moderate. Conclusion Both SAD and MAD studies of surotomycin demonstrated minimal systemic exposure, with feces the primary route of elimination following oral administration; consistent with observations with similar compounds, such as fidaxomicin. Results of these phase 1 studies support the continued clinical development of surotomycin for the treatment of Clostridium difficile-associated diarrhea. Trial registration NCT02835118 and NCT02835105 . Retrospectively registered, July 13 2016.

Chizuko Sasaki, Takeshi Saito, T. Shinozuka et al.

Jing Yang, Wen-lin Bai, Yu-jiao Chen et al.

Benzene, a known occupational and environmental contaminant, is associated with increased risk of leukemia. The objectives of this study were to elucidate the regulatory mechanism of the hypomethylated STAT3 involved in benzene toxicity in vitro. As 1,4-benzoquinone (1,4-BQ) is one of benzene’s major toxic metabolites, AHH-1 cells were treated by 1,4-BQ for 24 h with or without pretreatment of the antioxidant a-LA or the methyltransferase inhibitor, 5-aza-2′ deoxycytidine (5-aza). The cell viability was investigated using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. ROS was determined via 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) flow cytometric assays. The level of oxidative stress marker 8-OHdG was measured by enzyme-linked immunosorbent assay. Methylation-specific PCR was used to detect the methylation status of STAT3. Results indicated the significantly increasing expression of ROS and 8-OHdG which accompanied with STAT3 hypomethylation in 1,4-BQ-treated AHH-1 cells. α-LA suppressed the expression of both ROS and 8-OHdG, simultaneously reversed 1,4-BQ-induced STAT3 hypomethylation. However, although the methylation inhibitor, 5-aza reduced the expression level of ROS and 8-OHdG, but had no obvious inhibiting effect on STAT3 methylation level. Taken together, oxidative stress are involved 1,4-BQ-induced STAT3 methylation expression.

Yahya Kemal Günaydın, Nazire Belgin Akıllı, Zerrin Defne Dündar et al.

Introduction: Antiepileptic drugs, which are also called anticonvulsants, are used in the therapy and prophylaxis of epileptic seizures. The purpose of this paper was to investigate the relevant epidemiological data and to determine which of these drugs was the most frequent cause of intoxication. Another purpose of this study was to determine the neurological, cardiac, and biochemical problems caused by antiepileptics. Material and method: This retrospective study included 95 consecutive patients under 18 years of age with antiepileptic intoxication, presenting to and being followed-up in, the Toxicology Unit between January 2010 and February 2013. The data were obtained by screening the patient files. Results: Of the cases, 67 (70.5%) were self-poisoned by first generation antiepileptics (FGAEs) and 28 (29.5%) by second generation antiepileptics (SGAEs). The Glasgow Coma Scale (GCS) scores and the serum lactate levels of the patients poisoned by FGAEs and SGAEs on admission to emergency department were 15 (25th: 12; 75th: 15; 95th: 15; IQR: 3) and 1.9 (25th: 1.4; 75th: 3.1; 95th: 5.6; IQR: 1.7), and 15 (25th: 14.3; 75th: 15; 95th: 15; IQR: 0.75) and 1.07 (25th: 0.9; 75th: 1.6; 95th: 5.5; IQR: 0.71), respectively. The serum lactate levels of patients poisoned by FGAEs were significantly higher (p < 0.001). Among the cases poisoned by carbamazepine, the most frequent cause of intoxication, the GCS score was significantly lower and serum lactate level was significantly higher in the group with high serum levels of carbamazepine (p = 0.004 and p < 0.001, respectively). In cases poisoned by valproic acid (VPA), the second frequent cause of intoxication, there was neither a significant association between the serum VPA level and the GCS score, nor between the serum lactate level and the systolic blood pressure (p = 0.470, p = 0.897, and p = 0.088, respectively). However, there was a positive correlation between the serum VPA level and the serum ammonia level (kk = 0.742, p < 0.001). Conclusion: First generation antiepileptics are more toxic than SGAEs. In patients with serum carbamazepine level, particularly those over 30 mg/L, serious disorders of consciousness, cardiovascular toxicity, and metabolic disorders may occur. In VPA intoxication, there is a positive correlation between the serum VPA levels and ammonia levels. On account of this finding, one should be more careful about hyperammonemic hepatic encephalopathy as the serum VPA level rises.

Subhasish Dan, Jnankumar Chaudhuri, Maitreya Samanta et al.

Introduction: Osteodystrophy is more common among hemodialysis patients than normal population. Earlier the higher incidence of osteodystrophy among maintenance hemodialysis (MHD) patients was attributed to high Intact Parathyroid Hormone (iPTH) level (150-300 pg/ml). Osteodystrophy due to high iPTH level is called High Turnover Bone Disease (HTBD). It was later found that another type of osteodystrophy, which can be attributed to low iPTH level and called Low Turnover Bone Disease (LTBD), also afflicts a subset of hemodialysis population, the diabetic End Stage Renal Disease (ESRD) patients. In our study, we propose to ascertain if diabetic ESRD patients on MHD have lower iPTH level than their non-diabetic counterparts. Methods: Total 193 patients were enrolled into the study. Of them, 98 had diabetic nephropathy as primary cause of ESRD, 69 had Chronic Glomerulonephritis, 13 had Hypertensive Nephropathy, 8 had Polycystic Kidney Disease, 3 had Urolithiasis and 2 had Drug Induced Nephrotoxicity as primary cause of ESRD. All of them had been on MHD for more than 6 months. We measured the iPTH level of all the patients enrolled in the study. Result. Serum iPTH level was significantly lower in diabetic group than in non-diabetic group (P < 0.001). Conclusion: Type 2 Diabetes Mellitus contributes towards relatively low iPTH level in diabetic ESRD patients on MHD.

Robert G. Hendrickson, K. Osterhoudt

K. McMartin

J. Domingo