Natural defense against multi-drug resistant Pseudomonas aeruginosa: Cassia occidentalis L. in vitro and in silico antibacterial activity.

Cassia occidentalis L. is widely used in indigenous and traditional medicine, but its impact on multi-drug resistant (MDR) bacterial infections mostly remains unknown. Therefore, this study aimed to evaluate the in vitro antibacterial efficiency of methanol and ethyl acetate extracts of C. occidentalis L. leaves (MECOL and EAECOL) against multi-drug resistant Pseudomonas aeruginosa and to identify potential antibacterial agents through computational studies targeting the LasR protein. Initially, 82 compounds were identified using GC-MS analysis, and the functional groups were determined through FT-IR analysis. Both extracts of the plant exhibited dose-dependent antibacterial activity, with MICs of 104.16 ± 36.08 µg mL-1 for MECOL and 83.33 ± 36.08 µg mL-1 for EAECOL, and an MBC of 125 µg mL-1. Among the 82 compounds, 12 potential compounds were identified based on binding scores using molecular docking with the LasR protein and MM-GBSA analysis. Furthermore, screening for ADME properties, including physicochemical features, water solubility, lipophilicity, RO5 compliance, and toxicity, identified the top three compounds: methyl dihydrojasmonate, methyl benzoate, and 4a-methyl-4,4a,5,6,7,8-hexahydro-2(3H)-naphthalenone, which also demonstrated binding affinity with the active site residues of the LpxC protein of the bacteria. Additionally, molecular dynamics (MD) simulations confirmed the binding reliability of these three phytochemicals to LasR's active pocket, comparable to the protein native inhibitory ligands (C12-HSL). The study offers scientific support for the traditional use of C. occidentalis in treating bacterial infections, highlighting the potential of the three compounds as leads for developing LasR inhibitors to combat multi-drug resistant P. aeruginosa.

Green synthesis of silver nanoparticles using Cinnamomum tamala (Tejpata) leaf and their potential application to control multidrug resistant Pseudomonas aeruginosa isolated from hospital drainage water.

Green Synthesis of Metal Nanoparticles is becoming a more common method for producing nanoparticles with a diameter of 1-100 nm that may be employed in a variety of medical applications. The antibacterial efficacy of silver nanoparticles (AgNPs) derived from Cinnamomum tamala (Tejpata) leaf extract against antibiotic-resistant Pseudomonas aeruginosa is investigated in this study. Green AgNP synthesis is safe, cost-effective, and ecologically friendly. The biosynthesized AgNPs were studied using UV-Visible spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), Dynamic Light Scattering (DLS), X-ray Diffraction (XRD), and Transmission Electron Microscopy (TEM). The AgNPs were virtually spherical, with an average size of 25-30 nm, according to TEM observations. Biochemical and molecular identification were used to isolate multidrug-resistant P. aeruginosa from the hospital's drainage water. The antibacterial potential of AgNPs against P. aeruginosa is determined using the agar diffusion method. Silver nanoparticles produced from Cinnamomum tamala (Tejpata) leaf extract were shown to be effective in inhibiting four strains of P. aeruginosa. According to the agar disc diffusion method, AgNPs had the largest inhibition zone of 17.67 ± 0.577 mm, while aqueous extract had 5.67 ± 0.5777 mm, indicating that AgNPs had antibacterial activity. This study on AgNPs might assist with managing multidrug resistant pathogenic bacteria and be a possible source of medicinal application due to its potential antibacterial effect.

An autopsy case of heatstroke under the influence of psychotropic drugs.

We present here a fatal case of heatstroke, involving olanzapine and levomepromazine medications. A male in his sixties was found dead in his storage room in the middle of August, with a high rectal temperature. Autopsy revealed congestion of the lungs without any specific findings. Quantitative toxicological analysis demonstrated concentrations of olanzapine, levomepromazine, 7-aminonitrazepam, and 7-aminoflunitrazepam in a femoral blood sample of 0.433 µg/mL, 0.177 µg/mL, 0.604 µg/mL, and 0.041 µg/mL, respectively. The concentration of olanzapine exceeded toxic levels; however, levomepromazine level was within the therapeutic range. Due to the blocking mechanism of both olanzapine and levomepromazine against muscarinic receptors, they might depress sweating and impair heat dissipation. Based on autopsy findings, results of toxicological examination, and investigation by the authorities, we concluded that the cause of death was heatstroke under the influence of olanzapine and levomepromazine.

Medicolegal implication of an autopsy case of methidathion ingestion.

We present an autopsy case involving ingestion of methidathion, an organothiophosphate pesticide. A headspace gas chromatography mass spectrometry system was used for screening of volatile compounds. Subsequent toxicological analysis was performed using liquid chromatography tandem mass spectrometry. Xylene and ethylbenzene were detected in stomach contents. We also identified methidathion at concentrations of 3.07 and 2240 µg/ml in femoral venous blood and stomach contents, respectively. We concluded that the victim ingested methidathion insecticide, with an estimated dose of at least 9.2 g.

Detection of toluene, methanol and formic acid in the autopsy case of a solvent abuser.

A fatal case of abuse of solvent containing mixture of toluene and methanol is presented. Concentrations of toluene, methanol and formic acid in a femoral venous blood sample were 20.1 mg/L, 210 mg/L and 25.2 mg/L, respectively. From the autopsy findings and toxicological examination, we concluded that the cause of death was poisoning by toluene and methanol.

Ethanol metabolism in ALDH2 knockout mice--blood acetate levels.

We described here blood acetate levels in aldehyde dehydrogenase 2 knockout (ALDH2 KO) male mice based on C57BL/6J strain after ethanol (EtOH) dosing (2 g/kg). Blood samples were collected at 30, 60, 90, 120 180, and 240 min after decapitation, and then EtOH, acetaldehyde (AcH) and acetate were determined by head-space gas chromatography. We found that blood acetate levels in ALDH2 KO mice were slightly lower than those in wild type (WT), whereas EtOH and AcH levels in ALDH2 KO were significantly higher than those in WT. These observations indicate that high EtOH, AcH and low acetate in the blood of ALDH2 KO are due to the deficient effect of ALDH2 enzyme activity.

Different blood acetaldehyde concentration following ethanol administration in a newly developed high alcohol preference and low alcohol preference rat model system.

A significant difference in blood-acetaldehyde concentration was observed between high alcohol-preference (HAP) rats and low alcohol-preference (LAP) rats, newly developed different alcohol preference lines. This difference of acetaldehyde accumulation may be due to cytosolic aldehyde dehydrogenase (ALDH1) polymorphism, which has been reported previously. As the doses of ethanol we employed are higher than that of voluntary drinking, there may be little direct relationship between acetaldehyde accumulation and alcohol preference. We suggest therefore that the ALDH1 polymorphism is associated with alcohol preference in HAP/LAP lines through some other unidentified mechanism.