Behavioral, biochemical and histopathological toxic profiles induced by sub-chronic cannabimimetic WIN55, 212-2 administration in mice.

WIN55, 212-2 mesylate is a synthetic cannabinoid (SC) agonist of CB1 and CB2 receptors with much higher affinity to CB1 receptor than tetrahydrocannabinol and many potential therapeutic effects. Few studies have evaluated SCs effects on more complex animal behavior and sex differences in cannabinoids toxicology. The current study was undertaken for determination of behavioral (Open Field test), biochemical (liver and kidney function test plus GABA & Glutamate levels), histopathological and CB1 immunohistochemistry risks of sub-chronic administration of SC WIN55, 212-2 mesylate in male and female mice. A total of 40 healthy adult mice were randomly divided into four groups (5 mice each): a negative control group, a vehicle group, a low dose (0.05 mg/kg) group and a high dose group (0.1 mg/kg) for each gender.Open Field Test revealed dose and gender-dependent anxiogenic effect with reduced locomotor activity in both sexes especially the higher doses with female mice being less compromised. GABA and glutamate levels increased significantly in both dose groups compared to controls alongside female mice versus males. No significant biochemical alterations were found in all groups with minimal histopathological changes. The CB1 receptors immunohistochemistry revealed a significant increase in the number of CB1 positive neurons in both low and high dose groups against controls with higher expression in female brains.ConclusionsThere were sexual dimorphism effects induced by sub-chronic exposure to WIN55, 212-2 with lesser female mice affection and dose-dependent influences.

Accuracy of Rapid Emergency Medicine Score and Sequential Organ Failure Assessment Score in predicting acute paraphenylenediamine poisoning adverse outcomes.

Paraphenylenediamine (PPD) is a commonly used xenobiotic in hair dying, causing deleterious outcomes in acute poisoning. Although many epidemiological studies and case reports explained their clinical presentations and fatal consequences, no studies have evaluated the early determinants of adverse outcomes. Therefore, the present study aimed to assess the initial predictors of acute PPD poisoning adverse outcomes, focusing on the discriminatory accuracy of the Rapid Emergency Medicine Score (REMS) and Sequential Organ Failure Assessment (SOFA) score. A retrospective cohort study included all acute PPD-poisoned patients admitted to three Egyptian emergency hospitals from January 2020 to January 2022. Data was gathered on admission, including demographics, toxicological, clinical, scoring systems, and laboratory investigations. Patients were categorized according to their outcomes (mortality and complications). Ninety-seven patients with acute PPD poisoning were included, with a median age of 23 years, female predominance (60.8%), and suicidal intention (95.9%). Out of all patients, 25.77% died, and 43.29% had complicated outcomes. Respiratory failure was the primary cause of fatalities (10.30%), while acute renal failure (38.14%) was a chief cause of complications. The delay time till hospitalization, abnormal electrocardiogram, initial creatine phosphokinase, bicarbonate level, REMS, and SOFA scores were the significant determinants for adverse outcomes. The REMS exhibited the highest odds ratio (OR = 1.91 [95% confidence interval (CI): 1.41-2.60], p < 0.001) and had the best discriminatory power with the area under the curve (AUC) = 0.918 and overall accuracy of 91.8% in predicting mortality. However, the SOFA score had the highest odds ratio (OR = 4.97 [95% CI: 1.16-21.21], p = 0.001) and only yielded a significant prediction for complicated sequels with AUC = 0.913 and overall accuracy of 84.7%. The REMS is a simple clinical score that accurately predicts mortality, whereas the SOFA score is more practicable for anticipating complications in acute PPD-poisoned patients.

Trimetazedine with hyperinsulinimea-euoglycemia, N-acetyl cysteine, and vitamin C: A new approach concept for management of aluminum phosphide poisoning.

Aluminum phosphide (AlP) is commonly used as a powerful suicidal tool. The exact mechanism of acute toxicity has not been well defined despite high mortality rates as well as its supportive treatment including rapid decontamination and institution of resuscitative measures. The current study aimed to investigate a new combination therapy using trimetazidine, N-acetyl cysteine, vitamin C, and hyperinsulinemia-euglycemia to manage acute AlP poisoning. Acute AlP-induced cardiotoxicity, hemodynamic changes, and hepatotoxicity were evaluated using electrocardiogram, creatinine kinase MB iso-enzyme, troponin-1, blood pressure, random blood glucose level, liver function tests, and histopathological changes in both the heart and liver in a rabbit model of AlP poisoning. The results showed that the new regimen therapy ameliorates the toxic effect of AlP with significant improvement in survival, cardiovascular and hemodynamic parameters in addition to histopathological changes. These results highlight the strong cardioprotective, antioxidant, hepatoprotective effects of the new combined therapy along with correction of hemodynamic changes and hyperglycemia as a potential target in the management of acute AlP poisoning.

Neurobehavioral, testicular and erectile impairments of chronic ketamine administration: Pathogenesis and ameliorating effect of N-acetyl cysteine.

Ketamine, a dissociative anesthetic, recently has spread as a recreational drug. Its abuse lead to neurobehavioral disturbance in addition to toxic effects on other body organs. To evaluate the toxic effects of chronic administration of low ketamine doses on the memory, testicles, and erection, explore its pathophysiology through oxidative stress mechanism and examine the ameliorating effect of N-acetyl cysteine (NAC). A total of 40 male albino rats were assigned to control, vehicle, ketamine only I.P. (10 mg/kg), and ketamine (10 mg/kg) + NAC (150 mg/kg) groups. Assessment of memory affection and erectile function by Passive Avoidance, Novel Object Recognition, and copulatory tests were performed. Estimation of malondialdehyde (MDA), catalase (CAT), and total antioxidant capacity (TAC) in serum and prefrontal & hippocampal homogenate, and luteinizing hormone (LH), testosterone in serum were done. Prefrontal cortex, hippocampus, and testes were collected for histopathology. Chronic ketamine administration induced significant memory deficits (P < 0.05), reduced erectile function (P < 0.05), severe hypospermatogenesis, increased MDA, reduced CAT, TAC levels in serum, and tissue homogenate (P < 0.05) and reduction of LH, and testosterone (P < 0.05). Treatment with NAC resulted in significant improvement of memory function, improved erectile function, and decrease in oxidative injury in both serum and tissue homogenates. Testosterone and LH levels exhibited significant difference between treatment groups and controls (P < 0.05). NAC reduced the deleterious histopathological changes. These data suggest that long-term ketamine affects short and long memory, induces erectile and testicular dysfunction through oxidative stress. Co-administration with NAC ameliorates these toxic effects.

Toxicological and epidemiological studies of scorpion sting cases and morphological characterization of scorpions (Leiurusquin questriatus and Androctonus crassicauda) in Luxor, Egypt.

BACKGROUND AND AIM: Scorpion envenomation is a common acute life threatening health problem in developing countries as Egypt. Scorpion venom is a complex structure composed of neurotoxic proteins, salts, acidic proteins, and organic compounds, thereby having of neurologic, cardiovascular, hematologic, and renal side effects, in addition to local effects such as redness, pain, burning, and swelling. AIMS: The study consisted of two parts to describe demographic characteristics, toxicological manifestations of scorpion sting cases in Luxor, Egypt and morphological characterization of the commonest scorpion species in the studied community for easy rapid identification of scorpion species by doctors from the patient history to provide better choices of management. MATERIALS & METHODS: First part of the study include all cases of scorpion envenomation attending General Hospital of Esna, Luxor, Egypt during the period of scorpion activity 2017, demographic data was collected then cases were assessed for clinical manifestations, ECG, complications and deaths related to scorpion species. Second part: scorpions were collected from areas around patient housing for morphological description of their sense organs and venom apparatus by Scanning Electron Microscopy. RESULTS: A total of 110 cases of scorpion stings were reviewed, males 81 (72.9%) and females 30 (27.1%), with a mean age of 31.9 ± 17.9 years. Localized pain was the most frequent presenting complaint (89 80.2%), vomiting was the commonest clinical symptom (90.9%). All scorpion stings were due to the most endemic species in North Africa, Leiurusquinquestriatus & Androctonuscrassicauda. Death rate among cases was (5.5%) all were Abroug's Grade III. Cardiac dysrhythmia and subsequent pulmonary edema were the commonest cause of death. Clinical manifestations were more sever in Leiurus quinquestriatus stings while death rate was more in Androctonus crassicauda stings. The morphological characterization of the sense organs (eyes, pedipalps, pectines& sensory setae) and venom apparatus of the scorpions L. quinquestriatus & A. crassicauda were described by Scanning Electron Microscopy. CONCLUSION: Scorpion sting is an acute heath threating in Southern Egypt, Leiurus quinquestriatus & Androctonus crassicauda are most endemic scorpion species in Southern Egypt. More attention for scorpion envenomation in such subtropical hyper desert localities is required to eradicate toxic scorpion species and prevent possible causes of deaths.