Population Pharmacokinetics of Fixed Dose Combination of Ceftriaxone and Sulbactam in Healthy and Infected Subjects

Increased antibacterial resistance (ABR) and limited drug discovery warrant optimized use of available antibiotics. One option is to rationally combine two antibiotics (fixed dose combination (FDC)) that may delay or prevent emergence of ABR in notorious pathogen. Major concern with FDC is the mutual interaction of its components that might influence their pharmacokinetic (PK) profile, requiring reassessing of whole formulation (adding cost and time). The interaction can be identified by comparing PK profile of a drug present in FDC with its independent entity. An open-label, crossover, single-dose comparative PK study of FDC (ceftriaxone and sulbactam) with their individual reference formulations was performed in 24 healthy adult subjects. No mutual PK interactions between ceftriaxone and sulbactam were observed. Pharmacokinetic data was used to develop a population-PK model to understand between-subject variability (BSV). Pharmacokinetics of ceftriaxone/sulbactam was explained by one and two compartment models, respectively. The subject’s “weight” was identified as a covariate explaining BSV. Both internal and external validations (healthy/infected subjects) were done. The model-derived population-PK parameters of FDC’s active components in infected subjects were similar to literature reported values of individual components. Efficacies of various FDC dosage regimens over a range of minimum inhibitory concentrations (MICs) were assessed by Monte Carlo simulations using population-PK parameters of infected/healthy subjects. In infected subjects, 3 g FDC/24 h can treat bacteria with MIC ≤8 μg/mL, while for MIC 8–32 μg/mL, 3 g FDC/12 h is recommended. Lastly, the developed population-PK model was successfully used to predict drug exposure in pediatric population.     

Sardine oil loaded vanillic acid grafted chitosan microparticles,a new functional food ingredient: attenuates myocardial oxidative stress and apoptosis in cardiomyoblast cell lines (H9c2)

Fish oil has been widely recognized as an excellent dietary source of polyunsaturated n-3 fatty acids such as EPA and DHA. However, it can undergo oxidation easily resulting in the formation of toxic off flavor compounds such as hydroperoxides. These compounds adversely affect the nutritional quality and may induce several stress reactions in body. To solve this problem, a new antioxidant bio-material, vanillic acid-grafted chitosan (Va-g-Ch), was synthesized and used as a wall material for microencapsulation of fish oil. The sardine oil loaded Va-g-Ch microparticles could be a potential functional food ingredient considering the numerous health benefits of fish oil, chitosan, and vanillic acid. The current study aimed to investigate the possible protective effect of sardine oil-loaded Va-g-Ch microparticles against doxorubicin-induced cardiotoxicity and the underlying mechanisms. In vitro cytotoxicity evaluation was conducted using H9c2 cardiomyocytes. MTT assay revealed that effective cytoprotective effect was induced by a sample concentration of 12.5 μg/mL. Results of apoptosis by double fluorescent staining with acridine orange/ethidium bromide and caspase-3 evaluation by ELISA substantiated the above findings. Further, flow cytometric determination of membrane potential, relative expression of NF-κB by PCR, and ROS determination using DCFH-DA also confirmed the protective effect of encapsulated sardine oil against doxorubicin-induced cardiotoxicity. NF-κB expression was down-regulated nearly by 50% on cells treated with encapsulated sardine oil. Altogether, the results revealed that sardine oil-loaded Va-g-Ch microparticles demonstrated potential cell protection against doxorubicin-induced oxidative stress     

The influence of cumin seed exudates on fungal spore germination

Summary Effect of cumin seed exudates on spore germination of Curvularia lunata, Alternaria solani and Colletotrichum capsici was studied in the laboratory. Three-hour exudate obtained for first 3-hour favoured initial protrusion but inhibited subsequent growth of the germ tubes. Two-hour exudate obtained between 5 and 7 hours after soaking was suggested to have no effect on initial protrusion but was found to have promotive effect on subsequent growth of germ tube. Short treatment with inhibitor for 45 minutes followed by a treatment with promotor ensured high germination and uniform germ tube growth. Modifying effects on the spermatosphere and adaptive significance of sequential exudation are discussed. re]19730125     

Rapid eco-friendly synthesis,characterization, and cytotoxic study of trimetallic stable nanomedicine: A potential material for biomedical applications

In the current scenario of the fight against cancer Integration of potential elements seems to be the best alternative since it overcomes the weaknesses of individuals and the combination of elements makes them formidable in the fight against the cancer war. Inspired by this objective and trusting our knowledge of paddy straw grown oyster mushroom, Pleurotus florida (Pf) mediated synthesis; a first-of-kind approach has been developed for the rapid synthesis of Au–Pt–Ag trimetallic nanoparticles (TMNPs). The developed method was successful, which was confirmed by Ultraviolet–Visible, X-ray diffraction, Transmission Electron Microscopy, Energy Dispersive Spectroscopy. Specifically, prepared TMNPs have been studied for their stability and size as a primary prerequisite for nanomedicine. Finally, the stable nanomedicine developed has been assessed for its performance against the highly metastatic breast cancer cell line (mda-mb-231). The performance was assessed using MTT assay and morphological readings, which were integrated with the cell viability data. We also determined the IC50 value, which was far superior to individual components and motivated us to postulate the possible breast cancer cell killing mechanism of TMNPs. The present study unlocks the new paths for the mushroom-mediated environmentally friendly, economic synthesis of trimetallic nanoparticles, which can be effectively used in cancer nanomedicine.     

The Ess1 prolyl isomerase is required for growth and morphogenetic switching in Candida albicans.

Prolyl-isomerases (PPIases) are found in all organisms and are important for the folding and activity of many proteins. Of the 13 PPIases in Saccharomyces cerevisiae only Ess1, a parvulin-class PPIase, is essential for growth. Ess1 is required to complete mitosis, and Ess1 and its mammalian homolog, Pin1, interact directly with RNA polymerase II. Here, we isolate the ESS1 gene from the pathogenic fungus Candida albicans and show that it is functionally homologous to the S. cerevisiae ESS1. We generate conditional-lethal (ts) alleles of C. albicans ESS1 and use these mutations to demonstrate that ESS1 is essential for growth in C. albicans. We also show that reducing the dosage or activity of ESS1 blocks morphogenetic switching from the yeast to the hyphal and pseudohyphal forms under certain conditions. Analysis of double mutants of ESS1 and TUP1 or CPH1, two genes known to be involved in morphogenetic switching, suggests that ESS1 functions in the same pathway as CPH1 and upstream of or in parallel to TUP1. Given that switching is important for virulence of C. albicans, inhibitors of Ess1 might be useful as antifungal agents.