Poisoning Research Articles

Evaluation of the in vivo acute toxicity and in vitro genotoxicity and mutagenicity of synthetic β-carboline alkaloids with selective cytotoxic activity against ovarian and breast cancer cell lines

The aim of this study was to evaluate the in vitro cytotoxic, genotoxic, and mutagenic potential and to determine the in silico ADME parameters of two synthetic β-carboline alkaloids developed as prototypes of antitumor agents (NQBio-06 and NQBio-21). Additionally, acute toxicity of the compounds was evaluated in mice. The results from the MTT assay showed that NQBio-06 presented higher cytotoxicity in the ovarian cancer cell line TOV-21G (IC50 = 2.5 µM, selectivity index = 23.7). NQBio-21 presented an IC50 of 6.9 µM and a selectivity index of 14.5 against MDA-MB-231 breast cancer cells. Comet assay results showed that NQBio-06 did not induce chromosomal breaks in vitro, but NQBio-21 was genotoxic with and without metabolic activation (S9 fraction). Micronucleus assay showed that both compounds were mutagenic. In addition, metabolic activation enhanced this effect in vitro. The in silico predictions showed that the compounds met the criteria set by Lipinski's rules, had strong prediction for intestinal absorption, and were possible substrates for P-glycoprotein. The in vivo results demonstrated that both the compounds exhibited low acute toxicity. These results suggest that the mechanisms underlying the cytotoxicity of NQBio-06 and NQBio-21 are related to DNA damage induction and that the use of S9 enhanced these effects. In vivo analysis showed signs of toxicity after a single administration of the compounds in mice. These findings highlight the potential of β-carboline compounds as sources for the development of new anticancer chemotherapeutic agents.

Protective Effects of Hydroalcoholic Leaf Extract of Origanum Vulgare against Paraquat-induced Lung Toxicity in Rats: The Role of the Inflammation-related Markers and Oxidative Stress

Background:: The pesticide paraquat is hazardous to both humans and animals. Lung damage is a common complication of paraquat poisoning. Objective:: This research analyzes the preventive properties of Origanum vulgare leaf extract against paraquat-induced acute pulmonary toxicity and oxidative stress. Methods:: In this experiment, the rats were assigned to five distinct groups. Group 1 served as the control, group 2 got only 25 mg/kg bw paraquat, and groups 3, 4, and 5 received paraquat and Origanum vulgare leaf extract at dosages of 200, 400, and 800 mg/kg bw, respectively. In rats, inflammation- related indicators and oxidative stress were analyzed after therapy. Results:: Compared with the control group, the levels of the serum PC, MDA, and inflammatory markers such as TNF-α, IL-6, and IL-1β remarkably rose (p < 0.05) and the pulmonary contents of the SOD, CAT, and vitamin C greatly decreased (p < 0.05) in the paraquat-only group. Origanum vulgare leaf extract administration after paraquat exposure resulted in a substantial increase in lung SOD, CAT, and vitamin C levels as well as a significant reduction in MDA, PC, and lung inflammatory markers (TNF-α, IL-6, and IL-1β) gene expression relative to the paraquat-only group. Conclusion:: Origanum vulgare leaf extract might be supplied to lessen the toxicity of paraquat, based on the findings of this research, which indicated that Origanum vulgare leaf extract has antioxidant- enhancing properties and can improve the antioxidant defense system. other: Ethic number: IR. SKUMS. REC. 1395. 151.

Methylphenidate and the risk of acute central nervous system oxygen toxicity: a rodent model and observational data in human divers.

The effects of methylphenidate, a stimulant often prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD), on the development of central nervous system oxygen toxicity (COT) have not been experimentally evaluated. The records of all pure-oxygen-rebreather divers evaluated at our institution from 1975-2022 were assessed. Cases of COT were defined as a new onset of tinnitus, tunnel vision, myoclonus, headache, nausea, loss of consciousness, or seizures resolving within 15 minutes from breathing normobaric air, and matched 4:1 with similar controls. Any medications issued to the diver in the preceding three months, including methylphenidate, were recorded. In the animal arm of this study, male mice were exposed to increasing doses of methylphenidate orally, with subsequent exposure to hyperbaric O₂ until clinically evident seizures were recorded. Seventy-five cases of COT were identified in divers, occurring at a median of 80 (range 2-240) minutes after dive initiation at a median depth of 5 m (2-13). Hypercarbia was documented in 11 (14.7%) cases. Prescription of methylphenidate in the preceding three months was not associated with increased risk (OR 0.72, 95% CI 0.16-3.32) of COT. In mice, increasing methylphenidate exposure dose was associated with significantly longer mean COT latency time being 877 s (95% CI 711-1,043) with doses of 0 mg·kg⁻¹; 1,312 s (95% CI 850-1,773) when given 0.75 mg·kg⁻¹; and 1,500 s (95% CI 988-2,012) with 5 mg·kg⁻¹ (F = 4.635, P = 0.014). Observational human data did not demonstrate an association between methylphenidate and an increased risk of COT. Methylphenidate exposure in mice prolongs COT latency and may have protective effects against COT.

Comparative Studies of Some Biochemical and Toxicological Investigations of Chromolaena odorata and Ipomoea involucrata from Lagos Suburb in Nigeria

The search for plants and plants products of medicinal potentials cannot be underestimated. Hence this study sought to investigate some parameters of medicinal importance.The phytochemical constituents, proximate and mineral composition, anti-nutrient contents, and acute toxicity of Chromolaena odorata and Ipomoea involucrata were analyzed using standard analytical methods. Phytochemical screening revealed the presence of reducing sugars, flavonoids, saponins, and alkaloids in both plants. Notably, Ipomoea involucrate exhibited higher saponin levels, suggesting potential unique medicinal properties. Proximate and mineral composition analysis indicated that both plants have low moisture content, which helps in preserving the active compounds by minimizing chemical degradation. Additionally, the plants were found to be rich in crude fiber, protein, and nutritionally valuable elements. Anti-nutrient assessments showed that Chromolaena odorata had the lowest cyanide (5.45mg/100 g) and phytate (0.23mg/100 g) levels, while Ipomoea involucrate had the lowest oxalate content (0.40 mg/100 g). Furthermore, no mortality was observed in tested animals following oral treatment with 2000 mg/kg body weight, indicating a high margin of safety. This study highlights that both Chromolaena odorata and Ipomoea involucrate possess beneficial phytochemical and nutritional profiles. The low moisture content in these plants contributes to the stability of their active compounds, enhancing their potential medicinal value. Ipomoea involucrata stands out for its higher saponin content, which may offer distinctive therapeutic benefits. The minimal presence of anti-nutrients andless lethal effectsfurther support their safety and efficacy as medicinal plants. The findings in this study however underscore the therapeutic potential of these plants and their suitability for use in drug development and their application in therapeutic products.

Determination of tetramethylammonium hydroxide in air using ion chromatography or ultra-performance liquid chromatography - high-resolution mass spectrometry

Tetramethylammonium hydroxide (TMAH) is extensively utilized in the semiconductor and optoelectronic industries, serving as either a developer or an etchant. TMAH possesses acute toxicity and alkaline corrosiveness, having caused several fatal and injurious accidents in Taiwan. However, there is currently a lack of methods available for assessing TMAH exposure. This study developed a method involving sampling with quartz fiber filters followed by ultrasonic agitation in 10 mL mobile phase, filtering, and analysis using either ion chromatography (IC) or ultra-performance liquid chromatography - high-resolution mass spectrometry (UPLC-HRMS). Utilizing the characteristics of HRMS, the compound analyzed was identified as tetramethylammonium ion (TMA+) through mass spectrometry analysis. The method exhibits excellent trapping capacity and recovery rate. The linear range of TMA+ for IC is 0.3 to 100 μg/mL, with a correlation coefficient of R = 0.9998. The linear range of TMA+ for UPLC-HRMS is 0.002 to 1 μg/mL, with a correlation coefficient of R = 0.996. The recovery rates for IC and HRMS were 116.6% and 90.6%, with corresponding coefficient of variation (CV) of 2.25% and 3.53%, respectively. Samples can be stored at room temperature for 28 days. Verification of this method was conducted at the TMAH factory, and the air concentrations measured in the TMAH filling area were 3.29 and 4.75 μg/m3 from IC and UPLC-HRMS, respectively. This method will be applied in the on-site analysis of occupational hazards for operators in chemical plants, technology factories, and recycling plants, aiming to evaluate risk values to protect the safety and health of workers and prevent occupational diseases.

Performance of a novel Built-in Static Magnetic Field – Biological Aerated Filter (BSMF–BAF) for treating high-salt textile dyeing wastewater

High-salt textile dyeing wastewater is difficult to treat. Magnetic fields can enhance the biodegradation capacity and extreme environmental adaptabilities of microorganisms. Thus, magnetically enhanced bioreactors are expected to improve the treatment efficiency and stability of high-salt textile dyeing wastewater. Accordingly, a novel Built-in Static Magnetic Field – Biological Aerated Filter (BSMF–BAF) was constructed and investigated for treating actual high-salt textile dyeing wastewater in this study. Two other BAFs packed with traditional and magnetic ceramsite carriers, respectively, were simultaneously operated for comparison. The removal of color, chemical oxygen demand (COD), suspended solid (SS) and acute toxicity were monitored. The activities of key enzymes and microbial community structure were analyzed to reveal possible mechanisms for improving the treatment efficiency of traditional BAF using the BSMF. The results showed that the BSMF–BAF possessed the highest removal efficiencies of color, COD, SS and acute toxicity among the three BAFs. The BSMF induced significant increases in the activities of azoreductase and lignin peroxidase, which were responsible for the degradation of azo compounds in the wastewater and the detoxification of toxic intermediates, respectively. Additionally, the BSMF induced the relative enrichment of potentially effective bacteria and fungi, and it maintained a relatively high abundance of fungi in the microbial community, resulting in a high treatment efficiency.

Solar-activated tin oxide photocatalysis for efficient naphthenic acids removal and toxicity reduction in oil sands process water

This research studied, for the first time, the effect of activating tin oxide (SnO2) under simulated solar light for treating real oil sands process water (OSPW). The solar/SnO2 system effectively eliminated fluorophore organic contaminants, classical naphthenic acids (O2-NAs), and oxidized NAs (Oxy-NAs) from OSPW. The best experimental conditions to remove over 90 % of O2-NAs were found to be 0.5 g/L SnO2 under 8 h of irradiation. HO• and O2•– species identified by electron paramagnetic resonance (EPR) analysis played an important role in the degradation of NAs and other contaminants in real OSPW. The initial toxic effects of untreated OSPW were noticeably reduced after treatment, with a reduction of approximately 50 % in acute toxicity using Microtox® bioassay and over 80 % in the level of bioavailable hydrocarbons. In addition, the process also demonstrated a significant reduction in immunotoxicity as measured using an immune cell bioassay and reduced the toxic effects on Staphylococcus warneri using an adapted bacterial minimal inhibitory concentration (MIC) viability assay. These results suggest that treated OSPW by SnO2 under solar light has high environmental compatibility, indicating it is safe for reuse in further applications.

Assessment of the Safety of Anti-Salmonella Disinfectant for Veterinary Use Based on a Cocktail of Bacteriophages.

The toxicity and safety of a veterinary anti-salmonella disinfectant based on three highly virulent bacteriophage strains (titers 1010 PFU/ml) were studied. Acute, chronic, and inhalation toxicity, as well as local irritancy of the disinfectant were evaluated on outbred white mice CD1 (n=65), Soviet chinchilla rabbits (n=20), and rats (n=20). No toxic effects of the disinfectant was observed after its intraperitoneal or intragastric administration to mice and intragastric administration to rats; in rabbits, application on the skin and eyes produced no local irritation effect. Inhalation of 10% of the disinfectant did not cause any pathologies in mice. Thus, the tests confirmed the high level of safety of the disinfectant based on a mixture of bacteriophages for use as an additional specific disinfection agent against Salmonella in veterinary and livestock facilities.

HI-6-Loaded Vehicle of Liposomes Mediated by an Amphiphilic Pillar[5]arene against Paraoxon Poisoning.

Organophosphate (OP) intoxication has become a severe common health matter all over the world. For the treatment of acute OP poisoning, the effective intracerebral delivery of acetylcholinesterase reactivators is crucial. Here, an amphiphilic hydrazide-pillar[5]arene (HP5A-6C), which could be readily integrated into liposomal bilayers' zwitterionic disaturated phosphatidylcholine (DSPC), was synthesized. A T7 peptide-containing guest (G) was attached on the surface via a noncovalent interaction to make mixed liposomes a particularly appealing candidate for brain-targeting delivery. Such coassembly could remain stable at room temperature for up to 6 weeks, and safety evaluations initially verified its fine biological compatibility. The hydrophilic interiors of T7/HP5A-6C@DSPC could further load HI-6 with 89.70% encapsulation efficiency. Support for brain-targeting potency came from imaging results. Notably, intravenous injection of HI-6-loaded vesicles exhibited a remarkable therapeutic effect on paraoxon (POX)-poisoned mice, effectively alleviating seizures and brain damage and significantly increasing the improving survival rate to 60% over the course of 7 days.

The effect of vibroacoustic therapy on the structural integrity of erythrocytes and platelets in patients with acute exogenous poisoning

Background. Vibroacoustic therapy is used as a non-drug method of correcting respiratory disorders in various diseases, including acute poisoning. The effect of vibroacoustic therapy on blood cells currently remains unexplored.Objective. To evaluate the impact of vibroacoustic therapy on the morphofunctional rate of erythrocytes and platelets in patients with acute poisoning in patients with acute poisoning.Material and methods. Thirty eight patients with complicated acute poisoning transferred to the Toxicology Department of the N.V. Sklifosovsky Research Institute for Emergency Medicine were examined. In 19 patients, along with the standard therapy, a vibroacoustic therapy was performed using a VibroLUNG device (the main study group); the other 19 patients received only standard therapy (the comparison group). Vibroacoustic therapy began on the 2nd day after the patient admission to the Toxicology Department. The course of vibroacoustic therapy consisted of 2–9 procedures. Morphofunctional analysis of erythrocytes and platelets in all cases was performed before the start of the vibroacoustic therapy (before treatment) and before discharge from the hospital (1–2 days after completing the vibroacoustic therapy course).Results. In both groups, before treatment, we noted normal morphofunctional rate of erythrocytes and normal level of platelets with granules in the circulating blood. The level of severely damaged or altered platelets was only slightly higher than normal and did not differ between the groups. Meanwhile, in 50% of patients, platelets had a tendency to spontaneous activation and hyperactivation. Before discharge, the morph functional parameters of erythrocytes and platelets did not significantly change in both groups, while treatment with vibroacoustic therapy allowed to eliminate or reduce spontaneous platelet activation in 7 of 9 patients in the main study group. In the comparison group spontaneous platelet activation was absent in only 3 of 10 patients. In parallel, the time till pneumonia resolution turned statistically significantly reduced, by 1.5 times.Conclusions. In acute exogenous poisoning with complicated course, the risk of spontaneous platelet activation and hyperactivation increases. Vibroacoustic therapy does not violate the structural integrity of circulating erythrocytes and platelets. Vibroacoustic therapy, using the VibroLUNG device, reduces the tendency of platelets to spontaneous activation and hyperactivation, reduces the time for resolving pneumonia.

Chemical Characterization, Evaluation of Acute Oral Toxicity, and Anti-Diabetic Activity of Aloe sabaea Flowers Extract on Alloxan-Induced Diabetic Rats.

The study aimed to conduct chemical profiling, acute in-vivo toxicity evaluation, and the potential anti-diabetic effect of standardized Aloe sabaea flowers ethanolic extracts (ASFEE) on alloxan-induced diabetic rats. The chemical composition was analyzed using GC-MS and TLC techniques. The oral acute toxicity study was performed according to the WHO 2000 and the OECD 420 guidelines. Furthermore, anti-diabetic activity was investigated using two doses of ASFEE (0.2 and 0.5 g/kg/day BW, p.o.) compared with glibenclamide (5 mg/kg/day, p.o.). A molecular docking investigation of the identified components with the PTPN9 enzyme was performed to figure out the proposed anti-diabetic mechanism. GC-MS analysis displayed the existence of 18 compounds; mostof the compoundswere fatty acids and theiresters, and phytosterols. Total phenolic and flavonoid contents were 42.00±1.26 mg GAE/g DW and 22.21±1.55 mg QE/g DW, respectively. The results of the in-vivo toxicity study revealed the absence of noticeable signs of toxicity or mortality at various doses establishing the safety of the tested extract. The estimated LD50 value was higher than 10 g/kg. Antidiabetic action exhibited a noticeable decline in fasting blood glucose (FBG) levels comparable to glibenclamide with no inducing intense hypoglycemia and considerable excess weight.

Safety and efficacy evaluation of plain OTC-HCL in acute and subacute toxicity tests and infected mice

The study aimed to evaluate the safety and efficacy of plain Oxytetracycline hydrochloride (OTC-HCL) in mice experimentally infected with 544 strain. The safety of plain OTC-HCL was assessed through acute and subacute toxicity testing. The LD value was determined, and hematologic, biochemical, and histopathological analyses were performed. For efficacy evaluation, mice were intraperitoneally injected with 3 × 10^6 CFU of 544 in 0.5 ml. Following infection, the mice received 25 mg/kg of plain OTC-HCL intravenously either daily or on alternate days for 21 days, starting from day 14 post-infection. Efficacy was assessed by measuring the logarithmic decrease in counts in the liver, lymph nodes, and spleen on days 1, 7, and 14 after treatment. Plain OTC-HCL has an LD of greater than 250 mg/kg. In both acute and subacute toxicity evaluations, the hematologic and biochemical data of the drug were within the normal range. Histopathology studies revealed no significant changes in the safety studies. In the subacute toxicity study, the drug was administered to mice received plain OTC-HCl @ 25 mg/kg intravenously for 21 days. Efficacy was measured by the decrease of counts in the liver, lymph nodes, and spleen. Plain OTC-HCL was found to be safe in both acute and subacute toxicity tests and effectively reduced the infection load of in mice. Our findings and novelties are 1) LDis more than 250 mg/kg for plain OTC-HCL by intravenously as a single dose. 2) Histopathology indicates that there is no organ toxicity for plain OTC-HCL in safety studies. 3) Plain OTC-HCL was found to be effective in reducing the infection load in -infected mice.

Acute toxicity assessment of bioactive constituents from Salvia algeriensis (Desf.) extracts: a promising natural agent against clinical bacterial isolates and pathogenic fungi

Salvia species are emerging as promising therapeutic agents due to their diverse bioactivity against various pathologies. This study was conducted to investigate the phytochemical profile, antimicrobial activity, and acute Toxicity of hydromethanolic extracts from Salvia algeriensis (Desf.) leaves, flowers, and roots. Chemical reaction tests and chromatographic analysis were employed to determine the chemical composition, while microdilution was used to determine the tested microorganisms' minimum inhibitory concentration (MIC). The acute Toxicity of the leaf extract was carried out following the rules and guidelines of OECD 425. Toxicity parameters in Swiss albino mice were evaluated after a single dose of 500 mg/kg and 2000 mg/kg. According to the preliminary phytochemical screening results, terpenoids and polyphenols (flavonoids and tannins) were found in all plant parts, but coumarins were only found in the root extract. The HPLC-DAD analysis revealed the presence of 16 phenolic compounds in varying amounts across the three extracts, of which rosmarinic acid, quercetin, caffeic acid, and 3-hydroxybenzoic acid were the most abundant. Selective antimicrobial activity was noticed, with the root extract demonstrating the most substantial effect against the two fungal strains tested. MIC values ranged from 0.3 to 10 mg/mL, and Gram-positive bacteria generally showedgreater susceptibility compared to Gram-negative bacteria. The LD50 was found to be greater than 2000 mg/kg. There were no overt clinical symptoms of Toxicity. Body weights, organ weights, and temperatures were not significantly altered, and hematological analysis showed no significant differences. Salvia algeriensis (Desf.) extracts emerge as potential candidates for natural, non-toxic antimicrobial agents. Keywords: Acute Toxicity; antimicrobial; HPLC-DAD; polyphenols; Salvia

Acute and chronic effects of methanolic extract of Teucrium polium on blood parameters and histopathology of liver and kidney in Female Rats

Teucrium polium L. is commonly used as a medicinal plant in Algeria to fight various human diseases. In this study, extracting aerial parts of T. polium with methanol gave a dry matter yield of 8.24 %. The effects of methanolic extract of T. polium "TPME" were examined per os on female rats Albino Wistar for six weeks. Biochemical and hematological serum parameters and morphology and histopathology of organs of treated rats were studied. Acute toxicity showed low toxicity with a lethal dose of 50% LD50 > 2400 mg / Kg of body weight. These data can be used to classify these plants as slightly toxic. However, sub-acute treatment for six weeks of rats with 75, 150, and 300 mg of methanolic extract / Kg of body weight significantly increased the most studied hematological parameters. Biochemical analysis revealed a significant increase of renal parameters (urea, creatinine, uric acid, Na, and K), accompanied by an increase in the relative weight of kidney, lipidic (cholesterol), and hepatic glutamate oxaloacetate transaminase (GOT) values in all treated rats. Histopathological examination confirmed the biochemical tests by the observation of perilobular necrosis areas, bile duct and inflammatory infiltration of the liver, and the presence of marked intracytoplasmic vacuoles in the kidney with the dose 300 mg of TPME Kg of animal body weight. Use of Teucrium polium L. may cause hepatotoxicity and nephrotoxicity after prolonged herb administration. Keywords: Teucrium polium L, TPME, LD50, biochemical parameters, toxicity

Merkel cells and corpuscles of Stannius as putative targets for polyethylene terephthalate microfibers in sheepshead minnow larvae

Polyethylene terephthalate (PET) fibers are contaminated in wastewater from various primary sources, such as washing textile waters. PET fibers in the environment can be degraded into microfibers because of weathering processes such as sunlight, physical wear, and heat. Although recent studies reported adverse effects of PET microfibers on aquatic organisms, the lack of information on their toxicity and mode of action hampers the risk assessment of PET microfibers. Therefore, this study aimed to investigate the biological effects of PET microfibers and their underlying mechanisms in early-staged sheepshead minnows (Cyprinodon variegatus). PET microfibers (about 13 μm diameter × 106 μm length) were prepared by cutting PET threads and treated to sheepshead minnow larvae at 10 and 100 mg/L for 10 days. No acute toxicity was found in the minnow, but PET microfibers significantly produced reactive oxygen species and reduced behavioral responses of traveled distance and maximum velocity. The transcriptomic data suggested that Merkel cells (flow sensors) and corpuscles of Stannius (calcium regulator) are putative targets, which were derived from oxidative stress, sensory neuropathy, cognitive impairment, and movement disorders. These findings underscore that although PET microfibers are not directly lethal to sheepshead minnows, they could impact their survival by damaging swimming-related key genes. This study provides new insights into how PET microfibers are toxic to aquatic organisms and disrupt ecosystems beyond survival and pathological changes.

Acute toxicity of chlorpyrifos to some non-target freshwater organisms: which one is more toxic-technical grade or commercial formulation?

Chlorpyrifos is among the most widely sold organophosphates in the agriculture sector worldwide. Static bioassays were performed in the laboratory to compare the acute toxicity between the technical grade (94% a.i.) and commercial formulation (20% EC) of chlorpyrifos to four freshwater organisms: the crustacean zooplankton Cyclops viridis, the oligochaete worm Branchiura sowerbyi, the gastropod Pila globosa, and tadpole larvae of Duttaphrynus melanostictus. The recovery of actual chlorpyrifos concentrations in water after 2 h of exposure to the nominal concentrations ranged from 82.98% to 88.56%. The commercial formulation (F) of chlorpyrifos was found to be 1.94 to 2.76 times more toxic than the technical grade (T). Based on 96 h LC50 values of T and F chlorpyrifos, C. viridis was found to be most sensitive (0.56 and 0.25 μg/L) and P. globosa as most tolerant (1482 and 536 μg/L) to chlorpyrifos. Changes in LC50 values of both T and F chlorpyrifos were noted in respect of exposure hours for the three aquatic invertebrates and the tadpole larvae of the toad. In conclusion, the acute toxicity of chlorpyrifos to some non-target freshwater organisms differs between technical grade and commercial formulations.

Comparing long-term efficacy and safety of GP versus TPF sequential chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a propensity score-matched analysis

PurposeTo evaluate the long-term efficacy and safety of GP and TPF sequential chemotherapy regimens in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC).MethodsFrom 2005 to 2016, a total of 408 LA-NPC patients treated with GP or TPF sequential chemoradiotherapy were retrospectively included. Propensity Score Matching (PSM) was employed to balance the baseline variables. Survival outcomes and acute toxicities were compared between both groups.ResultsA total of 230 patients were selected by 1:1 PSM. At a median follow-up of 91 months, no significant differences were observed between the matched GP and TPF groups regarding 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregionally relapse-free survival (83.4% vs. 83.4%, P = 0.796; 75.6% vs. 68.6%, P = 0.301; 86.7% vs. 81.1%, P = 0.096; and 87.4% vs. 87.2%, P = 0.721). Notable disparities in adverse effects were identified, with higher incidences of grade 3/4 thrombocytopenia in the GP group while grade 3/4 leukopenia and neutropenia in the TPF group. Though not recorded in our cohort, combined with the FAERS database, thrombotic adverse reactions are a concern for the GP regimen, while the TPF regimen requires vigilance for life-threatening adverse reactions such as septic shock, acute respiratory distress syndrome, and laryngeal edema.ConclusionNo significant difference in long-term outcomes was observed between the GP and TPF sequential chemotherapy regimens for LA-NPC. Differences in adverse effects should be noted when choosing the regimen.

Assessment of acute poisoning in children using poisoning severity scores: A cross-sectional study at Damietta General Hospital Egypt

Acute poisoning is a prevalent health issue, particularly among children, due to their natural curiosity and tendency to explore. This cross-sectional study aimed to evaluate the characteristics, causes, clinical presentation, and outcomes of acute intoxication in children at Damietta General Hospital, Egypt. We included 106 pediatric patients (aged under 18 years) with a clear history or clinical signs of acute poisoning. Data collection encompassed sociodemographic information, type of poison, mode of poisoning, and clinical outcomes. Poison Severity Score (PSS) was employed to assess the severity. The most affected age group was preschool children (3–6 years), accounting for 41.5 % of cases, with males representing 52.8 %. Accidental poisoning constituted 83 % of cases, with household cleaning products (34 %) and petroleum products (18.9 %) being the most common toxic agents. Clinical outcomes revealed that 33 % of patients experienced morbidity, with electrolyte imbalances being the most prevalent complication. The overall cure rate was 94.3 %, while the mortality rate was 5.7 %. This study highlights the significance of parental education and preventive measures, especially in rural areas, to reduce the risk of pediatric poisoning. The PSS proved useful in guiding clinical care, supporting its further use in pediatric toxicology settings.

Rapid analysis of amatoxins in human urine by means of affinity column chromatography and liquid chromatography-high-resolution tandem mass spectrometry

Analysis of amatoxins is of great importance as these cyclic peptides contribute to a high number of fatalities each year. Development of analytical approaches needs to focus on rapid, sensitive, and reliable methods. By establishing an affinity column chromatography-based assay using the monoclonal amanitin antibody AMA9G3 and liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS) for the trace detection of α-, β-, and γ-amanitin in human urine samples to confirm ingestion, we report the first approach that extents the current status of amatoxin analysis. The presented procedure allows detection of amatoxins in human urine down to 1 ng/mL. The method was successfully validated qualitatively for α- and γ-amanitin according to international recommendations. A proof of concept was performed by analyzing 37 urine samples after suspected amatoxin consumption submitted for regular clinical toxicological analysis. Using this antibody-based enrichment strategy, acute amatoxin intoxications can be determined within 90 min and due to the high sensitivity and selectivity, a comparable approach using target specific antibodies may also be used for other toxicological relevant peptides.

Engineered PLGA Core-Lipid Shell Hybrid Nanocarriers Improve the Efficacy and Safety of Irinotecan to Combat Colon Cancer.

Poly(lactide-co-glycolide) (PLGA) is a biocompatible and biodegradable copolymer that has gained high acceptance in biomedical applications. In the present study, PLGA (Mw = 13,900) was synthesized by ring-opening polymerization in the presence of a biocompatible zinc-proline initiator through a green route. Irinotecan (Ir) loaded with efficient PLGA core-lipid shell hybrid nanocarriers (lipomers, LPs) were formulated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)-2000] (DSPE-PEG-2000), using soya lecithin, by a nanoprecipitation method, and the fabricated LPs were designated as P-DSPE-Ir and P-DSPE-PEG-Ir, respectively. The formulated LPs were further validated for their physicochemical properties and biological potential for colon cancer application. The potential delivery of a poorly water-soluble chemotherapeutic drug (Ir) was studied for the treatment of colon cancer. LPs were successfully prepared, providing controlled size (80-120 nm) and surface charge (∼ -35 mV), and the sustained release properties and cytotoxicity against CT-26 colon cancer cells were studied. The in vivo biodistribution and tumor site retention in CT-26 xenograft tumor-bearing Balb/C mice showed promising results for tumor uptake and retention for a prolonged time period. Unlike P-DSPE-Ir, the P-DSPE-PEG-Ir LP exhibited significant tumor growth delay as compared to untreated and blank formulation-treated groups in CT-26 (subcutaneous tumor model) after 4 treatments of 10 mg irinotecan/kg dose. The biocompatibility and safety of the LPs were confirmed by an acute toxicity study of the optimized formulation. Overall, this proof-of-concept study demonstrates that the PLGA-based LPs improve the efficacy and bioavailability and decrease neutropenia of Ir to combat colon cancer.