Poisoning Research Articles

Electron-donating and -withdrawing groups discriminate the fluorometric sensing of phosgene.

Phosgene, diphosgene, and chlorine are called choking agents due to their acute toxicity to the respiratory system by directly attacking through inhalation and causing acute hypoxia, asphyxia and death. For these reasons, small-molecule fluorescent probes have been developed for their detection to ensure public safety. In this regard, two thiophene-based chemodosimetric fluorescent probes TCAO ((Z)-3-(4-(dimethylamino)phenyl)thiophene-2-carbaldehyde oxime) and HMBT ((Z)-4-(2-((hydroxyimino)methyl)thiophen-3-yl)benzonitrile) were designed, synthesized and characterized using 1H-NMR, 13C NMR, FT-IR spectroscopy and HRMS methods. Probe TCAO exhibited higher selectivity and sensitivity for detecting phosgene than probe HMBT. The electron-donating group (EDG) and electron-withdrawing group (EWG) play a crucial role in detecting phosgene. TCAO, bearing EDG, exhibited a fluorescence 'turn-on' response by the NGP-assisted conversion of aldoxime to the cyano group in the presence of phosgene; whereas HMBT, bearing EWG, did not show any fluorometric response. Therefore, further studies were conducted on TCAO, and the quantum yield changed from Φ = 0.043 to Φ = 0.155 in the presence of phosgene. The limit of detection for TCAO was estimated to be as low as 51 nm. In addition, onsite monitoring for visual detection was performed using the easy-to-handle paper-strip method.

Effects of Chlorich®EnergyBoost on Enhancing Physical Performance and Anti-Fatigue Properties in Mice

Chlorich®EnergyBoost, a water extract obtained from Chlorella sorokiniana, has been proposed to enhance physical performance and provide anti-fatigue effects. This study assessed the impact of Chlorich®EnergyBoost supplementation on physical performance and its anti-fatigue properties. Twenty-four mice were allocated into four groups: (1) the control group receiving only water,;(2) the 1X group (49.2 mg/kg/day); (3) the 2X group (98.4 g/kg/day); and (4) the 5X group (246 g/kg/day). All groups were orally administered the supplements for four consecutive weeks. The evaluation included grip strength, swimming endurance, an exhaustion test, and serum biochemistry analysis. Additionally, the study examined the bioactive peptides through matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) and conducted bacterial reverse mutation and acute oral toxicity tests for safety assessment. The findings indicated that Chlorich®EnergyBoost supplementation led to a significant reduction in serum lactate levels by 14.08% to 22.54% and blood urea nitrogen levels by 12.23% to 16.76%, an increase in the lactate clearance rate by 0.28 to 0.35, an enhancement of muscle glycogen storage by 1.10 to 1.44-fold, and hepatic glycogen storage by 1.41 to 1.47-fold. These results demonstrated dose-dependent effects. MALDI-TOF analysis revealed the expression of dihydrolipoamide dehydrogenase and superoxide dismutase. Both the bacterial reverse mutation and acute oral toxicity tests showed no adverse effects.

Preliminary phytochemical and biological activity screening of Sargassum lapazeanum

Algae are exposed to substantial stress. In response, these organisms have developed efficient defense systems, such as protective secondary metabolite synthesis, making algae a primary source of bioactive compounds with a wide spectrum of biological activities. Thus, algae show potential for use in treatments of thrombotic, infectious, and chronic degenerative diseases. Therefore, the objective of this study was to evaluate the phytochemical compounds and pharmacological activity of an extract obtained from Sargassum lapazeanum. Algae were collected in the intertidal zone of Tarabillas beach (Bahía de La Paz, BCS). The biological activities of an ethanolic extract and its fractions were evaluated using chromatographic techniques. In addition, a bioautographic assay of hemolytic activity was conducted, and phytochemical profiles and acute toxicity in Artemia franciscana were evaluated. The relationships among the main extract components were also determined. The ethanolic extract exhibited significant antioxidant and hemolytic activity, which was mainly attributed to its content of anthrones, anthraquinones, and unsaturated triterpenes. Its toxicological activity reached an LC50 value of 225.1 μg mL-1, which was mainly attributed to alkaloids, flavonoids, anthrones, and saponins. The results suggest that Sargassum lapazeanum, which is endemic to the Gulf of California, has great pharmacological potential with biomedical applications.

Study on Clinical Profile and Treatment Outcome of Acute Paraquat Poisoning in an Intensive Care Unit in Bangladesh

Background: Paraquat, one of the most widely used herbicides, is a major cause of self-harm related death in Bangladesh resulting from multiple organ failure. The primary objective aimed to identify the demographic & clinical characteristics of paraquat poisoning and the outcome of different treatment modalities. Materials and Methods: A prospective observational study was conducted over twenty-four months at the Intensive Care Unit of Dhaka Medical College Hospital, a tertiary care referral hospital.Between March 2022 and March 2024, patients presenting with acute paraquat toxicity who fulfilled inclusion and exclusion criteriawere selected by purposive sampling. A total of 42 patients were enrolled in the study.Demographic, clinical, and treatment particulars were collected. The study evaluated the outcomes, including length of stay in the intensive care unit (ICU), the need for mechanical ventilation&hemodialysisandin-hospital mortality. SPSS version 25.0 was used for statistical analysis and reporting. Results: Among the patients, 54.8% were men with a median age of 23.31 years residing in rural areas (85.7%). All cases were suicidal, primarily due to family disputes (40.5%) and personal relationship issues (21.4%). Symptoms included shortness of breath (40.5%), disorientation (28.6%), difficulty in swallowing (14.3%), vomiting (9.5%), and low urine output (7.1%). Most ICU admissions occurred after 24 hours postingestion (59.5%). Organ involvement included acute kidney injury (57.14%), acute respiratory distress syndrome (50%), hepatic impairment (14.3%), pulmonary fibrosis (14.3%), and septic shock (2.4%). Methylprednisolone was administered to 21 patients (50%), with an equal number also receiving methylprednisolone plus cyclophosphamide (50%). Only 10 (23.80%) patients received gastric lavage.The median ICU stay was 6 days (IQR 4-9), while the Median hospital stay was 8 days (IQR 1-12). In-hospital mortality was high, and 41 out of 42 patients (97.8%) died. Conclusion: The rural population is mostly affected by paraquat poisoning for its easy availability,and clinical presentations, particularly pulmonary, renal and multi-systeminvolvement, are significantly associated with high mortality with the limited role of different treatment approaches. J MEDICINE 2024; 25: 129-135

Antibacterial potential of Propolis: molecular docking, simulation and toxicity analysis

The issue of antibiotic resistance in pathogenic microbes is a global concern. This study was aimed to explore in silico and in vitro analysis of the antibacterial efficacy of different natural ligands against bacterial activity. The ligands included in the study were Propolis Neoflavanoide 1, Carvacrol, Cinnamaldehyde, Thymol, p-benzoquinone, and Ciprofloxacin (standard drug S*). The outcomes of molecular docking revealed that Propolis Neoflavaniode-1 showed a highly significant binding energy of − 7.1 and − 7.2 kcal/mol for the two gram-positive bacteria, as compared to the gram-negative bacteria. All ligands demonstrated acute toxicity (oral, dermal), except for Propolis Neoflavanoide 1 and S* drugs, with a confidence score range of 50–60%. Using a molecular dynamic simulation approach, we investigated Propolis Neoflavaniode-1’s potential for therapeutic use in more detail. An MD simulation lasting 100 ns was performed using the Desmond Simulation software to examine the conformational stability and steady state of Propolis Neoflavaniode-1 in protein molecule complexes. Additionally, in vitro studies confirmed the antimicrobial activity of Propolis Neoflavaniode 1 by increasing the zone of inhibition against Gram-positive bacteria, p < 0.005 as compared to gram-negative bacteria. This study revealed the promising antibacterial efficacy of Propolis Neoflavaniode 1, demonstrated through robust in silico analyses, minimal toxicity, and confirmed in vitro antimicrobial activity, suggesting its potential as a viable alternative to combat antibiotic resistance.

Acute toxicity of chemotherapy in central nervous system germ cell tumour patients according to age

BackgroundSIOP-CNS-GCT-II European trial was opened for the treatment of patients of any age with central nervous system germ cell tumour (CNS-GCT). Four courses of pre-irradiation chemotherapy were delivered. The influence of patient age on chemotherapy related acute toxicity (CRAT) was assessed.MethodsCRAT was analysed according to age-groups: children (aged ≤11 years), adolescents (aged 12-17 years), adults (aged ≥18 years) and to chemotherapy type: CarboPEI (alternating etoposide-carboplatin/etoposide-ifosfamide) for non-metastatic germinoma; PEI (cisplatin-etoposide-ifosfamide) for standard-risk non-germinomatous GCT (NGGCT); PEI and high-dose PEI (HD-PEI), for high-risk or poorly responsive NGGCTs.Results296 patients were assessable for CRAT: 105 children, 121 adolescents, 70 adults (max age: 41 years). Median cumulative doses/m² of chemotherapy were similar among age-groups. The proportion of germinoma over NGGCT (and accordingly use of CarboPEI chemotherapy) was higher in the adult groups (79%) versus the other two groups (62%). Delay in chemotherapy ≥7 days was noticed in 27%, 38%, and 19% of children, adolescents, and adults, respectively. Grade ≥3 haematological and non-haematological adverse events (AEs) were observed in 94%/31%, 97%/36%, and 77%/21% of children, adolescents, and adults, respectively. No toxic death was reported. Grade ≥3 AEs and delayed chemotherapies were significantly rarer in adults when compared with adolescents, even when adjusted on chemotherapy type: odds ratio: 0.1 [95%CI 0.02-0.4], and 0.2 [95%CI 0.1-0.4] in the group treated with CarboPEI.ConclusionAdult patients can be treated safely with a chemotherapy intensive protocol, with even less toxicity than that observed in adolescents. Further work is required to understand age-related differences regarding toxicity.

JWH-182: a safe and effective synthetic cannabinoid for chemotherapy-induced neuropathic pain in preclinical models

Chemotherapy-induced neuropathic pain (CINP), a condition with unmet treatment needs, affects over half of cancer patients treated with chemotherapeutics. Researchers have recently focused on the endocannabinoid system because of its critical role in regulating our bodies' most important functions, including pain. We used in vitro and in vivo methods to determine the toxicity profile of a synthetic cannabinoid, JWH-182, and whether it could be potentially effective for CINP alleviation. In vitro, we evaluated JWH-182 general toxicity, measuring fibroblast viability treated with various concentrations of compound, and its neuroprotection on dorsal root ganglion neurons treated with paclitaxel. In vivo, we performed an evaluation of acute and 28-day repeated dose toxicity in mice, with monitoring of health status and a complete histopathological examination. Finally, we evaluated the efficacy of JWH-182 on a CINP model in mice using specific pain assessment tests. JWH-182 has an acceptable toxicity profile, in both, in vitro and in vivo studies and it was able to significantly reduce pain perception in a CINP model in mice. However, the translation of these results to the clinic needs further investigation.

Unveiling the Subtle Threats: The Neurobehavioral Impact of Chlorpyrifos on Girardia tigrina

Chlorpyrifos, an organophosphate insecticide widely used to control agricultural pests, poses a significant environmental threat due to its toxicity and persistence in soil and water. Our work aimed to evaluate the acute (survival) and chronic (regeneration, locomotion, and reproduction) toxicity of chlorpyrifos to the non-target freshwater planarian Girardia tigrina. The 48 h lethal concentration (LC50) of the commercial formulation, containing 480 g L−1 of chlorpyrifos, the active ingredient, was determined to be 622.8 µg a.i. L−1 for planarians. Sublethal effects were translated into a significant reduction in locomotion and delayed head regeneration (lowest observed effect concentration—LOEC = 3.88 µg a.i. L−1). Additionally, chlorpyrifos exposure did not affect planarian fecundity or fertility. Overall, this study demonstrates the potential of chlorpyrifos-based insecticides to harm natural populations of freshwater planarians at environmentally relevant concentrations. The observed toxicity emphasizes the need for stricter regulations and careful management of chlorpyrifos usage to mitigate its deleterious effects on aquatic ecosystems. By understanding the specific impacts on non-target organisms like G. tigrina, we can make more informed suggestions regarding the usage and regulation of organophosphate insecticides, ultimately promoting sustainable agricultural practices and environmental conservation.

Efficacy and safety of proton therapy versus intensity-modulated radiation therapy in the treatment of head and neck tumors: A systematic review and meta-analysis.

To comprehensively evaluate the therapeutic efficacy and safety when utilizing proton therapy (PT) versus intensity-modulated radiation therapy (IMRT) in head and neck cancer patients. Pubmed, ScienceDirect, Embase, Scopus, and Web of Science were systematically searched for studies on comparative PT and IMRT outcomes. We performed a random effect model meta-analysis to estimate the hazard ratio (HR) and odds ratio (OR) for efficacy and safety outcome variables between PT and IMRT. From 641 identified articles, 11 studies met the inclusion criteria, comprising 3087 patients (606 treated with PT and 2481 with IMRT). On toxicity analysis, PT is associated with decreased acute grade 1 nausea (OR = 0.34, 95% CI: 0.13-0.84, p = 0.02) compared to IMRT. In grade 2 toxicity, PT showed significant advantages over IMRT in mucositis (OR = 0.44, p < 0.0001), dysgeusia (OR = 0.35, p = 0.02), dysphagia (OR = 0.36, p < 0.0001), fatigue (OR = 0.29, p = 0.001), pain (OR = 0.34, p = 0.01), and weight loss (OR = 0.54, p = 0.02). Proton therapy also exhibited increased safety in grade 3 dysphagia incidence (OR = 0.44, p < 0.0001) compared to IMRT. PT demonstrated improved overall survival (OS) compared to IMRT across multiple time points: 1-year OS (HR = 0.43, p = 0.02), 2-year OS (HR = 0.44, p < 0.0001), and 5-year OS (HR = 0.78, p = 0.004). In terms of disease-free survival (DFS), PT also showed improved outcomes at 2-year DFS (HR = 0.65, p = 0.03) and 5-year DFS (HR = 0.81, p = 0.03). Proton therapy demonstrated superior overall survival (OS), disease-free survival (DFS), and better local control rate (LCR) compared to IMRT. The data also showed better safety outcomes in PT patients, particularly when involving grade 2 acute toxicity events.

Carbon-ion radiotherapy alone vs. standard dose photon radiation with carbon-ion radiotherapy boost for high-grade gliomas: a retrospective study

BackgroundThis study aimed to compare the survival outcome and side effects in patients with primary high-grade glioma (HGG) who received carbon ion radiotherapy (CIRT) alone or as a boost strategy after photon radiation (photon + CIRTboost).Patients and methodsThirty-four (34) patients with histologically confirmed HGG and received CIRT alone or Photon + CIRTboost, with concurrent temozolomide between 2020.03–2023.08 in Wuwei Cancer Hospital & Institute, China were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), and acute and late toxicities were analyzed and compared.ResultsEight WHO grade 3 and 26 grade 4 patients were included in the analysis. The median PFS in the CIRT alone and Photon + CIRTboost groups were 15 and 19 months respectively for all HGG cases, and 15 and 17.5 months respectively for grade 4 cases. The median OS in the CIRT alone and Photon + CIRTboost groups were 28 and 31 months respectively for all HGG cases, and 21 and 19 months respectively for grade 4 cases. No significant difference in these survival outcomes was observed between the CIRT alone and Photon + CIRTboost groups. Only grade 1 acute toxicities were observed in CIRT alone and Photon + CIRTboost groups. CIRT alone group had a significantly lower ratio of acute toxicities compared to Photon + CIRTboost (3/18 vs. 9/16, p = 0.03). No significant difference in late toxicities was observed.ConclusionBoth CIRT alone and Photon + CIRTboost with concurrent temozolomide are safe, without significant differences in PFS and OS in HGG patients. It is meaningful to explore whether dose escalation of CIRTboost might improve survival outcomes of HGG patients in future randomized trials.

A review on the enantioselective distribution and toxicity of chiral pesticides in aquatic environment.

Chiral pesticides account for about 40% of the total pesticides. In the process of using pesticides, it will inevitably flow into the surface water and even penetrate into the groundwater through surface runoff and other means, as a consequence, it affects the water environment. Although the enantiomers of chiral pesticides have the same physical and chemical properties, their distribution, ratio, metabolism, toxicity, etc. in the organism are often different, and sometimes even show completely opposite biological activities. In this article, the selective fate of different types of chiral pesticides such as organochlorine, organophosphorus, triazole, pyrethroid and other chiral pesticides in natural water bodies and sediments, acute toxicity to aquatic organisms, chronic toxicity and other aspects are summarized to further reflect the risks between the enantiomers of chiral pesticides to non-target organisms in the water environment. In this review, we hope to further explore its harm to human society through the study of the toxicity of chiral pesticide enantiomers, so as to provide data support and theoretical basis for the development and production of biochemical pesticides.

Airways Relaxant and Antiasthmatic Activity of Aconitum heterophyllum Wall ex Royle. Roots: A Mechanistic Insight.

Aconitum heterophyllum Wall ex Royle. (Ranunculaceae) is a traditional medicinal herb that has shown extensive pharmacological potential to treat cough, diarrhea, and infectious diseases but no scientific evidence is available to validate its antiasthmatic potential. In this study, we have investigated the tracheal relaxation and antiasthmatic activity of the selected bioactive fraction of A. heterophyllum. Chemical profiling of the most effective fraction obtained via bioassay-guided fractionation was done using LC-MS (Liquid chromatography-mass spectrometry, a technique utilized in the identification, separation, and quantification of known and unknown compounds). Molecular docking analysis of characterized constituents was performed to recognize the binding receptors, followed by an evaluation of the tracheal relaxation ability of active fraction. An acute oral toxicity study of the most effective fraction was done using OECD guidelines 423. Further, the therapeutic efficacy of the fraction was validated in asthma using a guinea pig model of ovalbumin (OVA) induced allergic asthma. The bio-guided activity revealed that hydro-methanolic extract of A. heterophyllum roots (F-1) was the most active fraction. LC-MS analysis of F-1 showed the presence of six major bioactive compounds in F-1. Molecular docking studies revealed strong binding affinities of identified constituents with histaminic receptor (H1) and muscarinic receptor (M3). The ex vivo study demonstrated smooth muscle relaxant activity of F-1 via dysregulating diverse signal transduction pathways viz. histaminic and muscarinic receptors antagonism (non-competitive), stimulation of β2-adrenergic receptor pathway, and soluble guanylyl cyclase activation. The findings of acute oral toxicity studies revealed that F-1 had no toxicity up to the dose of 2000 mg/Kg. The anti-asthmatic therapeutic efficacy of F-1 was further confirmed by the amelioration of respiratory hyperresponsiveness in asthmatic guinea pigs. This is the first evidence-based study showing the antiasthmatic therapeutic potential of the traditionally used herb A. heterophyllum through, computational and animal studies.

STRILL: Phase I Trial Evaluating Stereotactic Body Radiotherapy (SBRT) Dose Escalation for Re-Irradiation of Inoperable Peripheral Lung Lesions

Few data are available on the role of SBRT re-irradiation for isolated recurrences. We designed a prospective phase I study to evaluate the maximum tolerated dose (MTD) of SBRT for thoracic re-irradiation, for peripheral lung lesions. RT was delivered with a dose escalation design from 30 Gy in five fractions up to 50 Gy in five fractions. The primary end point was the definition of the maximum tolerated dose (MTD) of SBRT for thoracic re-irradiation. The dose-limiting toxicity was pneumonia ≥G3. Fifteen patients were enrolled. No cases of pneumonia ≥G3 occurred in any of our cohorts. Only one patient developed pneumonia G1 during treatment. Three patients developed acute toxicities that included dyspnea G1, cardiac failure G3, and chest wall pain. One patient developed G3 late toxicity with acute coronary syndrome. After a median follow-up of 21 months (range 3.6–29.1 months), six patients (40%) had a local relapse. Distant relapse occurred in five patients (33.3%). At the last follow-up, six patients died, all but two due to progressive disease. SBRT dose escalation for thoracic re-irradiation is an effective and well-tolerated option for patients with inoperable lung lesions after a first thoracic RT with acceptable acute and late toxicities.

“Mid-P strategy” versus “internal target volume strategy in locally advanced non small cell lung cancer: Clinical results from the randomized non-comparative phase II study Mid-P

BackgroundLocally advanced non-small cell lung cancer (LA-NSCLC) reported poor 5-year survival rates with frequent local or regional recurrences. Personalized RT may contribute to improve control and clinical outcome. We investigated efficacy and tolerance of “Mid-position” (Mid-P) strategy versus the conventional Internal Target Volume (ITV) strategy in LA-NSCLC patients treated by definitive conformal radiotherapy. MethodsThis prospective non-comparative randomized monocentric phase II trial included adult patients with non-resected, non-metastatic, non-previously irradiated proven LA-NSCLC treated with definitive normo-fractionated conformal radiotherapy (+/- chemotherapy). Allocated patients (randomisation 2:1) were treated using Mid-P or ITV strategy. A Fleming single-stage design (1-sided α = 0.1, 80 % power, P0 = 30 %, P1 = 50 %) planned enrolment of 36 patients in the Mid-P group. The ITV group ensured the absence of selection bias. The primary outcome was 1-year progression-free- survival (1y-PFS) rate. Results. Among 54 eligible patients included from September 2012 to May 2018, 51 patients were analyzed (Mid-P: N = 34; ITV: 17). The 1y-PFS was 38 % (1-sided 95 %CI 25 %-not reached) with Mid-P strategy, and 47 % (95 %CI [27 %-not reached[) with ITV. Loco-regional failure as first event mainly occurred within radiation-field regardless the strategy. Acute and middle-term radiation toxicities were observed with both strategies. ConclusionLocal control and survival remain poor using the Mid-P strategy in this prospective randomized non-comparative monocentric study investigating Mid-P strategy versus ITV strategy in LA-NSCLC. Since the Mid-P strategy is not integrated into routine software, and perceived as a time-consuming method, Mid-P strategy cannot be recommended in LA-NSCLCC treated by definitive normo-fractionated conformal radiotherapy outside clinical trials.

Interpretable machine learning for the prediction of death risk in patients with acute diquat poisoning

The aim of this study was to develop and validate predictive models for assessing the risk of death in patients with acute diquat (DQ) poisoning using innovative machine learning techniques. Additionally, predictive models were evaluated through the application of SHapley Additive ExPlanations (SHAP). A total of 201 consecutive patients from the emergency departments of the First Hospital and Shengjing Hospital of China Medical University admitted for deliberate oral intake of DQ from February 2018 to August 2023 were analysed. The initial clinical data of the patients with acute DQ poisoning were collected. Machine learning methods such as logistic regression, random forest, support vector machine (SVM), and gradient boosting were applied to build the prediction models. The whole sample was split into a training set and a test set at a ratio of 8:2. The performances of these models were assessed in terms of discrimination, calibration, and clinical decision curve analysis (DCA). We also used the SHAP interpretation tool to provide an intuitive explanation of the risk of death in patients with DQ poisoning. Logistic regression, random forest, SVM, and gradient boosting models were established, and the areas under the receiver operating characteristic curves (AUCs) were 0.91, 0.98, 0.96 and 0.94, respectively. The net benefits were similar across all four models. The four machine learning models can be reliable tools for predicting death risk in patients with acute DQ poisoning. Their combination with SHAP provides explanations for individualized risk prediction, increasing the model transparency.

The use of insect cell line Sf21 for ecotoxicity testing.

Insect cell lines are finding utility in many areas of biology, but their application as an in vitro tool for ecotoxicity testing has been given less attention. Our study aimed to demonstrate the utility and sensitivity of Sf21 cells to commonly used fungicides: Propiconazole and CuSO4, as well as dimethyl sulphoxide (DMSO) an industrial solvent. Sf21 cells were readily cultured from frozen stocks in 3-4 days and showed utility as an invertebrate in vitro acute toxicity test. The data showed the threshold levels of cell survivability against propiconazole and CuSO4. The EC50 values were 135.1 μM and 3.31 mM respectively. The LOAEL (lowest observed adverse effect level) was ≈ 1 μM for propiconazole and ≈ 10 μM for CuSO4. Culturing of Sf21 cells in media containing the solvent DMSO showed that 0.5% DMSO concentration did not effect cell viability. Sf21 cells are sensitive and useful as a robust ecologically relevant screening tool for acute toxicity testing.

Antimalarial efficacy test of the aqueous crude leaf extract of Coriandrum sativum Linn.: an in vivo multiple model experimental study in mice infected with Plasmodium berghei

BackgroundMalaria continues to wreak havoc on the well-being of the community. Resistant parasites are jeopardizing the treatment. This is a wake-up call for better medications. Folk plants are the key starting point for antimalarial drug discovery. After crushing and mixing the leaves of Coriandrum sativum with water, one cup of tea is drunk daily for a duration of three to five days as a remedy for malaria by local folks in Ethiopia. Additionally, in vitro experiments conducted on the plant leaf extract elsewhere have also demonstrated the plant’s malaria parasite inhibitory effect. There has been no pharmacologic research to assert this endowment in animals, though. This experiment was aimed at evaluating the antimalarial efficacy of C. sativum in Plasmodium berghei infected mice.MethodsThe plant's leaf was extracted using maceration with distilled water. The extract was examined for potential acute toxicity. An evaluation of secondary phytoconstituents was done. Standard antimalarial screening models (prophylactic, chemosuppressive, curative tests) were utilized to assess the antiplasmodial effect. In each test, thirty mice were organized into groups of five. To the three categories, the test substance was given at doses of 100, 200 and 400 mg/kg/day before or after the commencement of P. berghei infection. Positive and negative control mice were provided Chloroquine and distilled water, respectively. Rectal temperature, parasitemia, body weight, survival time and packed cell volume were ultimately assessed. Analysis of the data was performed using Statistical Package for Social Sciences.ResultsNo toxicity was manifested in mice. The extract demonstrated a significant inhibition of parasitemia (p < 0.05) in all the models. The inhibition of parasite load was highest with the upper dose in the suppressive test (82.74%) followed by the curative procedure (78.49%). Likewise, inhibition of hypothermia, weight loss hampering, improved survival and protection against hemolysis were elicited by the extract.ConclusionsThe results of our experimental study revealed that the aqueous crude leaf extract of C. sativum exhibits significant antimalarial efficacy in multiple in vivo models involving mice infected with P. berghei. Given this promising therapeutic attribute, in depth investigation on the plant is recommended.

Feasibility of weekly cisplatin and radiotherapy for localized anal cancer – A Danish anal cancer group report

BackgroundChemoradiotherapy (CRT) with flourouracil and mitomycin is the standard treatment for squamous cell carcinoma of the anus (SCCA), however the associated acute toxicity often hinders compliance. Although weekly cisplatin is a well-established treatment for other squamous cell carcinomas, it has not been explored in SCCA. PurposeTo investigate if radiotherapy (RT) with weekly cisplatin is a feasible option for SCCA and to report the acute toxicity. Material/methodsPatients were treated with RT and weekly cisplatin 40 mg/m2 between 1998–2020. Retrospective data from medical records (n = 65) and prospectively collected data from an observational study (n = 51) comprising physicianassessed toxicity (NCI-CTCAE 4.0), patient-reported outcomes (EORTC-QlQC30 + CR29) baseline, mid-therapy, end of treatment and 2–4 weeks post-treatment were included. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. ResultsWe included 116 patients. T-stages were T1:4 %, T2: 71 %, T3: 17 %, T4: 8 % and 47 % has N + disease. RT doses were 53.75–64 Gy/45–51.2 Gy and the mean cumulative dose of cisplatin was 307.5 mg. The median overall treatment time was 43 days. Within 6 months after CRT 88.9 % had complete response. The median follow-up time was 4.5 years and 5-year DFS and OS were 77 % (95 %CI 68.7–84.5 %) and 86.4 % (95 %CI 78.3–91.7 %), respectively. Hospitalization occured in 20 % with 2.6 % being admitted due to febrile neutropenia. Hematological toxicty was low with 13.7 % grade 3 and 3.9 % grade 4. Anal pain, skin, gastrointestinal and urogenital toxicity were mild. ConclusionRT and weekly cisplatin for SCCA showed good outcome results and an acceptable acute toxicity profile.

Acute toxicity and early PSA response after two-fraction stereotactic radiotherapy for localized prostate cancer using peri-rectal spacing – Initial report of the SABR-Dual trial

Purpose: SABR-Dual is a phase III trial with an initial phase-I safety cohort, of two-fraction stereotactic radiotherapy (SABR) with optional MRI-based focal boost, using peri-rectal spacing, for localized prostate cancer. This represents the initial report from the phase-I non-randomized cohort. Materials and methods: Subjects had favorable intermediate risk (FIR) or low risk (LR) prostate adenocarcinoma, and gland volume <80cc. All underwent radiopaque hydrogel spacer and fiducial marker placement prior to simulation (CT and 3-tesla T2 MRI). The clinical target volume included the entire prostate, and in FIR patients, 1-2cm of seminal vesicle (SV). A 2mm expansion was applied for planning target volume (PTV), and a dose of 27 Gy was prescribed to the PTV-prostate, 23 Gy to the PTV-SV, with an optional 30 Gy simultaneous boost (SIB) to an MRI-defined dominant lesion. Primary endpoint was 3-month patient-reported changes in quality of life based on the EPIC-26, IPSS, and SHIM questionnaires. Secondary endpoints were 6-month quality of life, acute toxicity (using CTCAEv5) and early PSA response. Results: Among the 20 patients in the phase-I cohort, 95% had FIR disease, and 50% received an SIB. At median follow-up of 8 months, a 3-month minimally clinically important change occurred in 1/20 (5%), 6/20 (30%), 2/20 (10%), 4/20 (20%), and 5/20 (25%) in urinary incontinence, urinary obstructive, bowel, sexual, and hormonal domains. There was a mean increase of 1±5.4 in IPSS and decrease of 1.8±6.5 in SHIM scores. Rates of grade 2 urinary and bowel toxicity 10% and 0%, respectively, with no grade ≥3 toxicities. Mean PSA decrease at last follow-up was 70.4%±17.7%. Conclusion: This generalizable protocol of two-fraction prostate SABR using peri-rectal spacing is a safe approach for ultra-hypofractionated dose-escalation, with minimal acute toxicity. Longer-term outcomes and direct comparison with standard 5-fraction SABR are being studied in the phase-III randomized portion of SABR-Dual.

Synergistic toxic effects and mechanistic insights of beta-cypermethrin and pyraclostrobin exposure on hook snout carp (Opsariichthys bidens): A biochemical, transcriptional, and molecular approach

The extensive utilization of pesticides results in their frequent detection in aquatic environments, often as complex mixtures, posing risks to aquatic organisms. The hook snout carp (Opsariichthys bidens) serves as a valuable bioindicator for evaluating the impacts of environmental pollutants in aquatic ecosystems. However, few studies examined the toxic effects of pesticides on O.bidens, let alone the characterization of the combined effects resulting from their mixtures. This study aims to elucidate the toxic effects of beta-cypermethrin and pyraclostrobin on O.bidens, individually and in combination, focusing on biochemical, transcriptional, and molecular responses. By organizing and analyzing the toxicogenomic databases, both pesticides were identified as a contributor to processes such as apoptosis, oxidative stress, and inflammatory responses. The acute toxicity test revealed comparable acute toxicity of beta-cypermethrin and pyraclostrobin on O.bidens, with LC50 being 0.019 and 0.027 mg/L, respectively, whereas the LC50 decreased to 0.0057 and 0.0079 mg/L under the combined exposure, indicating potential synergistic effects. The activities of enzymes involved in oxidative stress and detoxification were significantly altered after exposure, with superoxide dismutase (SOD) and catalase (CAT) increasing, while malondialdehyde (MDA) levels decreased. The activity of CYP450s was significantly changed. Likewise, the expression levels of genes (mn-sod, p53, esr, il-8) associated with oxidative stress, apoptosis, endocrine and immune systems were significantly increased. Combined exposure to the pesticides significantly exacerbated the aforementioned biological processes in O.bidens. Furthermore, both pesticides can modify protein activity by binding to the surface of SOD molecules and altering protein conformation, contributing to the elevated enzyme activity. Through the investigation of the synergistic toxic effects of pesticides and molecular mechanisms in O.bidens, our findings highlight the importance of assessing the combined effects of pesticide mixtures in aquatic environments.