EFFECTS OF SOLVENT POLARITY ON SOLVATION FREE ENERGY, DIPOLE MOMENT, POLARIZABILITY, HYPERPOLARIZABILITY AND MOLECULAR REACTIVITY OF ASPIRIN

Objective: The aim of the study is to explore the effects of solvent polarity on solvation free energy, dipole moment, polarizability, first order hyperpolarizability and different molecular properties like chemical hardness and softness, chemical potential, electronegativity, electrophilicity index of aspirin which may lead to better understand the reactivity and stability of aspirin in different solvent systems.Methods: Becke, 3-parameter, Lee-Yang-Parr (B3LYP) level of theory with 6-31G(d,p) basis set was employed to conduct all type of calculations for both in the gas phase and in solution. The solvation free energy, dipole moment and molecular properties were calculated by applying the Solvation Model on Density (SMD) in four solvent systems namely water, methanol, ethanol and n-octanol.Results: The solvation energies steadily increased as the dielectric constant was decreased i.e. free energy increases with decreasing polarity of the solvent. The dipole moment of aspirin was found to be increased when going from non-polar to polar solvents. The dipole moment of aspirin was higher in different solvents than that of the gas phase. The polarizability and first order hyperpolarizability were also increased with the increasing dielectric constant of the solvent. Moreover, ongoing from non-polar to polar solvent the chemical potential, electronegativity and electrophilicity index were increased except in n-octanol. The chemical potential, electronegativity and electrophilicity index of aspirin in n-octanol was higher than that of ethanol. On the other hand, chemical hardness was increased with decreasing polarity of the solvent and the inverse relation was found in the case of softness.Conclusion: The calculated solvation free energy, dipole moment, polarizability, first order hyperpolarizability and molecular properties found in this study may lead to the understanding of stability and reactivity of aspirin in different solvent systems

World Journal of Pharmaceutical Sciences Cytotoxic, thrombolytic, antioxidant and antimicrobial activities of Cocos nucifera linn. endocarp extracts

ABSTRACT Different partitionates of methanol extract of Cocos nucifera Linn. were subjected to screening for cytotoxic, thrombolytic, antioxidant and antimicrobial activities. Cytotoxicity was determined using brine shrimp nauplii in which vincristine sulfate was used as positive control and gave LC50 of 0.45±0.08 g/ml. Among the partitionates, carbon tetrachloride soluble fraction demonstrated the highest cytotoxic activity (LC50 value of 0.82±0.19 g/ml). While assaying for thrombolytic activity, the petroleum ether soluble fraction demonstrated highest thrombolytic activity (37.44±0.33%) compared to the standard streptokinase (66.76±0.03%). In total phenolic content assay, the highest amount of phenolic compounds was found in the crude methanol extract (113.94±2.01 mg of GAE/g of sample). In antioxidant assay, crude methanol extract (IC50 value of 4.39±0.69 μg/ml) showed maximum free radical scavenging activity whereas reference standards tert-butyl-1-hydroxytoluene and ascorbic acid gave IC50 values of 27.50±0.95 μg/ml and 5.80±1.03 μg/ml, respectively. In antimicrobial screening, the crude methanol extract and its carbon tetrachloride and chloroform soluble fractions exhibited mild zone of inhibition against the test organisms

IFN-λ Diminishes the Severity of Viral Bronchiolitis in Neonatal Mice by Limiting NADPH Oxidase-Induced PAD4-Independent NETosis

Infants with attenuated type III IFN (IFN-λ) responses are at increased risk of severe lower respiratory tract infection (sLRI). The IL-28Rα–chain and IL-10Rβ–chain form a heterodimeric receptor complex, necessary for IFN-λ signaling. Therefore, to better understand the immunopathogenic mechanisms through which an IFN-λlo microenvironment predisposes to a sLRI, we inoculated neonatal wild-type and IL-28R–deficient (IL-28R−/−) mice with pneumonia virus of mice, a rodent-specific pneumovirus. Infected IL-28R−/− neonates displayed an early, pronounced, and persistent neutrophilia that was associated with enhanced reactive oxygen species (ROS) production, NETosis, and mucus hypersecretion. Targeted deletion of the IL-28R in neutrophils was sufficient to increase neutrophil activation, ROS production, NET formation, and mucus production in the airways. Inhibition of protein-arginine deiminase type 4 (PAD4), a regulator of NETosis, had no effect on myeloperoxidase expression, citrullinated histones, and the magnitude of the inflammatory response in the lungs of infected IL-28R−/− mice. In contrast, inhibition of ROS production decreased NET formation, cellular inflammation, and mucus hypersecretion. These data suggest that IFN-λ signaling in neutrophils dampens ROS-induced NETosis, limiting the magnitude of the inflammatory response and mucus production. Therapeutics that promote IFN-λ signaling may confer protection against sLRI.</p

Drinking Water Sources along the Banks of Buriganga River of Bangladesh are Polluted and Possess Serious Health Risks: A Comprehensive In Vivo Analysis

Background. The river Buriganga, one of the major dumping zones of industrial wastes in Bangladesh, is responsible for contaminating the drinking water sources along its length. This study aimed to assess the water quality from these sources by monitoring the changes in hematological, biochemical, and histological parameters caused in healthy rats due to their consumption. Methods. Using ethylenediaminetetraacetic acid (EDTA) as an anticoagulant agent, hematological and biochemical analyses of Sprague–Dawley rat models were executed in this study. Following blood sampling, the rats were sacrificed, and the heart, lungs, kidneys, liver, and spleen were separated to carry out the histological analysis. Later, to perform the statistical analysis, SPSS, V.25.0 was utilized. Results. A significant rise (p<0.02) in body weight was recorded due to increased protein synthesis, inflammations; increased lymphocyte, white blood cell (WBC), and neutrophil count but hemoglobin (20.0 ± 1.39 g/dL vs. 15.25 ± 0.36 g/dL; p) and red blood cell (RBC) count ((6.24 ± 0.45) × 106/µL vs. (5.47 ± 0.34) × 106/µL)) decreased due to infections and hematopoietic stem cell poisoning by pathogens in water samples. Elevated (p<0.01) serum urea, creatinine, alanine, and aspartate aminotransferase levels indicated kidney malfunction and hepatic tissue necrosis. Histological analysis revealed gross lesions, internal hemorrhages in the brain; inflammations, granulomas, migrating macrophages in the spleen; fibrosis (resulting in hypo-perfusion), and collagen formation in cardiac muscles. Conclusions. The findings in this study provide comprehensive evidence, based on in vivo analysis, that the water bodies around the Buriganga river are likely to be contaminated with toxic chemicals and microbial entities making them unfit for human consumption

Targeting the P2Y13 Receptor Suppresses IL-33 and HMGB1 Release and Ameliorates Experimental Asthma

Rationale: The alarmins IL-33 and HMGB1 (high mobility group box 1) contribute to type 2 inflammation and asthma pathogenesis. Objectives: To determine whether P2Y13-R (P2Y13 receptor), a purinergic GPCR (G protein–coupled receptor) and risk allele for asthma, regulates the release of IL-33 and HMGB1. Methods: Bronchial biopsy specimens were obtained from healthy subjects and subjects with asthma. Primary human airway epithelial cells (AECs), primary mouse AECs, or C57Bl/6 mice were inoculated with various aeroallergens or respiratory viruses, and the nuclear-to-cytoplasmic translocation and release of alarmins was measured by using immunohistochemistry and an ELISA. The role of P2Y13-R in AEC function and in the onset, progression, and exacerbation of experimental asthma was assessed by using pharmacological antagonists and mice with P2Y13-R gene deletion. Measurements and Main Results: Aeroallergen exposure induced the extracellular release of ADP and ATP, nucleotides that activate P2Y13-R. ATP, ADP, and aeroallergen (house dust mite, cockroach, or Alternaria antigen) or virus exposure induced the nuclear-to-cytoplasmic translocation and subsequent release of IL-33 and HMGB1, and this response was ablated by genetic deletion or pharmacological antagonism of P2Y13. In mice, prophylactic or therapeutic P2Y13-R blockade attenuated asthma onset and, critically, ablated the severity of a rhinovirusassociated exacerbation in a high-fidelity experimental model of chronic asthma. Moreover, P2Y13-R antagonism derepressed antiviral immunity, increasing IFN-l production and decreasing viral copies in the lung. Conclusions: We identify P2Y13-R as a novel gatekeeper of the nuclear alarmins IL-33 and HMGB1 and demonstrate that the targeting of this GPCR via genetic deletion or treatment with a small-molecule antagonist protects against the onset and exacerbations of experimental asthma.</p