Human & experimental toxicology最新文献

Background: Until now, no definite standardized method has been used to promptly assess the severity and outcome of acute aluminum phosphide (ALP) poisoning. The current study aimed to evaluate the performance of the new Poisoning Mortality Score (PMS) and PGI score for predicting mortality in acute ALP-poisoned patients, highlighting the accuracy of new PMS components.

Patients and methods: A 2-year cross-sectional study was conducted on ALP-poisoned patients admitted to Tanta University Poison Control Centre from April 2021 to March 2023. Socio-demographics, poisoning data, and initial vital signs were recorded. Additionally, new PMS and PGI scores were calculated on admission. Patients were categorized according to the mortality outcome into survivors and nonsurvivors.

Results: Out of 160 included ALP poisoned patients, mortality was recorded in 112 (70%) patients. The nonsurvivors had significantly higher median PGI and new PMS values than survivors. New PMS, vital signs component of new PMS, and PGI conveyed good discriminatory power for predicting mortality (AUC = 0.883, 0.873, and 0.817, respectively). Although the new PMS outperformed PGI in all predictive metrics, no significant difference in AUCs was observed between the new PMS and its vital signs component.

Conclusion: The new PMS vital signs component is closely aligned with the new PMS. Thus, it can be used as a valid, comprehensive, and practical tool to substitute the whole score calculation for rapid ALP-poisoned patient assessment to enhance emergency clinical decision-making.

Introduction: The outbreak of acute kidney injury (AKI) due to mushroom poisoning is not a frequently encountered medical challenge. Herein, we present 13 mushroom poisoning cases associated with AKI related to Amanita Proxima (A. Proxima) causing poisoning reported in a short time period in Turkey.

Methods: A total of 13 patients with AKI due to mushroom poisoning admitted to Usak Research and Training Hospital between November and December 2020 were included. Under morphological and microscopical investigations of mushroom specimens (from three patients), the species of the mushrooms were identified.

Results: The median age of 13 patients presenting with AKI due to mushroom poisoning was 55 (ranging between 19 and 72 years), and 60.4% were males. Nausea and vomiting were the first symptoms in most patients and appeared at a mean time of 12.8 ± 7.6 h after ingesting mushrooms. Mean serum creatinine on admission was 7.2 ± 3.8 mg/dL. Kidney replacement therapy (KRT) was administered to all patients, and mortality occurred in two due to sepsis and heart failure (HF). Species of the mushroom specimens obtained from three patients were identified as A. Proxima, a rarely encountered type of mushroom. A. Proxima has a considerable similarity to a common and edible species specific to the Mediterranean Basin, known as A. Ovoidea.

Discussion: Based on our findings, we emphasize the consideration of nephrotoxic mushrooms of the genus Amanita in the evaluation of mushroom poisoning cases, as well as the efforts needed to increase public awareness regarding the risk of fatal outcomes of consuming wild mushrooms.

Introduction: Organophosphate pesticides (Ops) like diazinon (DZN) have well-known neurotoxic effects and low-level chronic exposure has been linked to detrimental neurobehavioral impairments and memory deficits. However, it's not entirely clear how DZN-induced biological changes, particularly in the prefrontal cortex (PFC) contribute to these effects. The purpose of this study is to investigate the impact of DZN exposure on inhibitory avoidance (IA) memory function, amyloid precursor expression (APP), and proinflammatory tumor necrosis factor-α (TNF-α) levels in the rat cortex.

Materials and methods: Rats were divided into 4 groups and recived 2 mg/kg DZN for 5-days or 12-weeks and two control groups recived the same volume of vehicle. IA memory was assesed using the shuttle box apparatus. Rats were sacrificed and the prefrontal cortex PFC were removed. Real-time PCR and Western blotting were used to messure TNF-α, and amyloid protein precursors gene expression and protein levels.

Results: Our findings indicated that DZN caused body weight loss and a notable decline in performance on the IA memory. Additionally, 5-days exposure increased APP and APLP2 protein levels in the PFC, while 12-weeks exposure decreased these levels. Furthermore, expression of APP and APLP2 gens were decreased in PFC. TNF-α levels increased as a result of 5-days exposure to DZN, but these levels dropped to normal after 12-weeks administration, and this observation was significant.

Conclusion: Taken together, exposure to low doses of DZN leads to disturbances in IA memory performance and also alternations in amyloid beta precursors that can be related to increased risk of Alzheimer's disease.

Thioacetamide (TAA), a widely employed hepatotoxic substance, has gained significant traction in the induction of liver failure disease models. Upon administration of TAA to experimental animals, the production of potent oxidative derivatives ensues, culminating in the activation of oxidative stress and subsequent infliction of severe damage upon multiple organs via dissemination through the bloodstream. This review summarized the various organ damages and corresponding mechanistic explanations observed in previous studies using TAA in toxicological animal experiments. The principal pathological consequences arising from TAA exposure encompass oxidative stress, inflammation, lipid peroxidation, fibrosis, apoptosis induction, DNA damage, and osteoclast formation. Recent in vivo and in vitro studies on TAA bone toxicity have confirmed that long-term high-dose use of TAA not only induces liver damage in experimental animals but also accompanies bone damage, which was neglected for a long time. By using TAA to model diseases in experimental animals and controlling TAA dosage, duration of use, and animal exposure environment, we can induce various organ injury models. It should be noted that TAA-induced injuries have a time-dependent effect. Finally, in our daily lives, especially for researchers, we should take precautions to minimize TAA exposure and reduce the probability of related organ injuries.

Background: A considerable portion of acutely intoxicated patients is presented with impaired consciousness. Early identification of those patients who require advanced medical care, such as mechanical ventilation (MV), can improve their prognosis.

Methods: This study included 330 acutely intoxicated patients who were presented with impaired consciousness and admitted to Tanta University Poison Control Center, Egypt, in the period from January 2021 to December 2023. Patients were enrolled in derivation (257 patients) and validation (73 patients) cohorts. Patients' data were analyzed to develop and validate a predictive nomogram to determine the probability of MV need in acutely intoxicated patients.

Results: Significant predictors for MV need were mean arterial blood pressure (OR = 0.96, p = .014), PaO₂ (OR = 0.96, p = .001), pH (OR = 0.00, p < . 001), and glucose/potassium ratio (OR = 1.59, p = .030). These four parameters were used to formulate a bedside nomogram. Receiver-operating characteristic (ROC) analysis for the proposed nomogram shows that area under the curve (AUC) = 95.7%, accuracy = 93.4%, sensitivity = 88.9%, and specificity = 95.1%. The internal validation for the developed nomogram was assessed using a bootstrapping method and calibration curve. Regarding external validation, AUCs for the developed nomogram probability was 96.5%, and for predicted probability using the developed nomogram was 97.8%.

Conclusion: The current study provides a validated nomogram that could be used as a reliable tool for the accurate prediction of MV need among acutely intoxicated patients with impaired consciousness. It could assist in the early identification of patients who will require MV, especially in low-income countries with limited resources.

The present study aimed to identify the possible effect of gentamicin (GEN) in Rats' Cervi. Estradiol Valerate (EV) was used to induce cervical hyperkeratosis. GEN was administered in absence of EV. Serum and cervical GEN concentration were determined. Levels of malondialdehyde (MDA), total nitrites/nitrate (NOx), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), sirtuin type 1 (Sirt1) and nuclear factor (erythroid-derived 2)-like-2 factors (Nrf2) were measured in cervix tissue. Expression of BAX and Bcl2 were determined. Cervical histopathological examination was done. EV and GEN significantly increased MDA, NOx, TNF-α and BAX/Bcl2 ratio with decrease in GSH, Nrf2 and Sirt1 levels in cervical tissue. Histopathological picture of diffuse and marked hyperkeratosis was detected in EV and GEN groups. In conclusion, GEN-induced cervical hyperkeratosis via induction of oxidative stress, inflammation and apoptosis.

Objective: To retrospectively analyze the etiology of non-diabetic retinopathy (DR) and non-traumatic vitreous haemorrhage (VH), and the effects of different anti-vascular endothelial growth factor (VEGF) drugs.

Methods: A retrospective analysis was conducted on VH patients diagnosed as non-diabetic retinopathy or trauma. Among 101 patients treated with anti-VEGF drugs, there were 48 cases in the Conbercept group and 53 cases in the Ranibizumab group. The causes of bleeding and gender distribution of the included cases were analyzed.

Results: In cases of retinal vein occlusion, the proportion of males was much higher than females (p < 0.05). After treatment, the best corrected visual acuity (BCVA), intraocular pressure, central macular thickness (CMT), aqueous humor VEGF, TNF-α, IL-10, and IL-6 of the two groups showed a decreasing trend (p < 0.05). The Conbercept group had markedly lower CMT than the Ranibizumab group (p < 0.05). In addition, there existed no significant statistical differences between the two groups in terms of BCVA, intraocular pressure, aqueous humor VEGF, TNF-α, IL-10, IL-6, incidence of adverse reactions, and recurrence rate (p > 0.05).

Conclusion: In patients with non-DR and traumatic VH, retinal vein occlusion, perivenous retinitis, retinal tears/detachment, exudative AMD, and polypoidal choroidal vasculopathy were the main etiologies. Conbercept and Ranibizumab had comparable efficacy and could effectively improve visual acuity and aqueous humor inflammation, with high safety and low recurrence rate. Conbercept had a more pronounced effect on the reduction of CMT in patients.

Methods: This single-center, retrospective observational study was conducted on 455 patients with Undergoing Treatment for Mushroom Poisoning at Affiliated Hospital of Zunyi Medical University (AHZMU), the tertiary governmental hospital of China, between January 2013 and December 2020. We investigated the impact of prognostic factors, including the mortality rate of patients who completed treatment at AHZMU versus those transferred to AHZMU, average length of hospital stay, mortality rate for a latency period of > 6-h, major damaged organs, HOPE6-TALK scoring and established a predictive model to assess the severity of acute mushroom poisoning.

Results: In 2013-2020, there are 455 patients of mushroom poisoning at AHZMU. Mushroom poisonings mainly concentrated in the summer and autumn months, resulted in 47 patients deaths. The first diagnosis cases at AHZMU resulting in a case fatality rate of 12.77% (6/47), Non-first diagnosis patients fatality accounting for 87.23% (41/47). The majority of deaths (89.36%) were attributed to liver injury. Death with incubation period >6-h accounting for 70.21% (33/47) of the total mortality rate. Logistic regression analysis revealed age and HOPE6 scores as independent risk factors, thereby establishing the logistic model equation, an examination via the ROC curve analysis indicates that a combination predictor values (Y_coalition) of 289.6 is the cut-off values for death resulting from acute mushroom poisoning.

Conclusion: The attending physician should conduct an early HOPE6-TALK scoring and calculate the Y_coalition for patients with acute mushroom poisoning, as well as promptly identify the toxic mushrooms through morphological and molecular biological identification. Identify mushroom species and further infer the clinical type and clinical characteristics. For example, amanitoxion can cause acute liver injury with high mortality. Identify mushroom species that may cause organ damage so that timely implementation of the bundled therapy for poisonous mushrooms will increase the cure rate and reduce the mortality rate (Lu et al., 2019).

Background: Cancer is a leading cause of death globally and in the US, prompting research into medicinal plants with anticancer properties. Withania somnifera, or Ashwagandha, is one such plants, known for its diverse pharmacological effects. Withaferin A and Viscosalactone B are two compounds found in Ashwagandha with known anticancer activity. The protein NQO1, overexpressed in various cancers, was the focus of this study.

Hypothesis and aim: We hypothesize that specific phytochemicals in Withania somnifera can effectively interact with and inhibit the NQO1 protein, thereby exhibiting anticancer properties. This study aims to identify these interactions using in silico approaches.

Methodology: CFDT was performed using the Gaussian 16 program package, followed by QSAR analysis of the compounds in the PASS online web server. The Schrodinger suite was used to carry out ligand and protein preparation, molecular docking, and molecular dynamic simulation to analyse the interaction of these compounds with NQO1 and ADME studies. Protox-II and SWISSADME tools were used to predict the toxicity and blood-brain barrier permeability of the phytochemicals.

Results and conclusion: CDFT and frontier molecular orbital analyses predicted the stability and reactivity of all the selected molecules. QSAR analysis predicted the biological activity and toxicity of the compounds. Withaferin A exhibited the highest glide gscore (-4.953 kcal/mol) and demonstrated 6 hydrogen bond interactions with NQO1, suggesting its potential as an anticancer agent. Conceptual density functional theory-based analysis suggested the strong electrophilicity of the ligands, further supporting their potential anticancer activities. Viscosalactone B, another phytochemical from Ashwagandha, also showed interactions involving 6 hydrogen bonds with NQO1, with a glide gscore of (-4.593 kcal/mol). Molecular dynamic simulations validated the stability of the Withaferin A-NQO1 complex. ADME-T properties predicted high oral absorption for the selected ligands, indicating that Withaferin A could be a viable orally administered drug.