Repurposing of Meropenem and Nadifloxacin for Treatment of Burn Patients?

The escalating number of multidrug resistant pathogens has demanded the swift development of new and potent antibiotics (ref. 2). Metallo-[beta]-lactamases (MBLs) continue to evolve, rendering the latest generation of carbapenem antibiotics useless (ref. 8). SPM-1, a recently discovered MBL, was isolated from a juvenile leukemia patient residing in a hospital in San Palo, Brazil just prior to the patient succumbing to septicemia brought on by Pseudomonas aeruginosa expressing SPM-1 (ref. 8). Screening of the Johns Hopkins Compound library of 1,514 FDA or FAD approved drugs (ref. 1) identified a novel SPM-1 inhibitor that is synergistically compatible with meropenem. Using clinically achievable concentrations, meropenem coupled with nadifloxacin inhibits Pseudomonas aeruginosa expressing SPM-1. This shotgun approach to new drug discovery provided a prompt solution to the grave problem of antibiotic resistant pathogens that are thriving in hospitals today

Oleic acid and peanut oil high in oleic acid reverse the inhibitory effect of insulin production of the inflammatory cytokine TNF-α both in vitro and in vivo systems

<p>Abstract</p> <p>Background</p> <p>Chronic inflammation is a key player in pathogenesis. The inflammatory cytokine, tumor necrosis factor-alpha is a well known inflammatory protein, and has been a therapeutic target for the treatment of diseases such as Rheumatoid Arthritis and Crohn's Disease. Obesity is a well known risk factor for developing non-insulin dependent diabetes melitus. Adipose tissue has been shown to produce tumor necrosis factor-alpha, which has the ability to reduce insulin secretion and induce insulin resistance. Based on these observations, we sought to investigate the impact of unsaturated fatty acids such as oleic acid in the presence of TNF-α in terms of insulin production, the molecular mechanisms involved and the in vivo effect of a diet high in oleic acid on a mouse model of type II diabetes, KKA^y.</p> <p>Methods</p> <p>The rat pancreatic beta cell line INS-1 was used as a cell biological model since it exhibits glucose dependent insulin secretion. Insulin production assessment was carried out using enzyme linked immunosorbent assay and cAMP quantification with competitive ELISA. Viability of TNF-α and oleic acid treated cells was evaluated using flow cytometry. PPAR-γ translocation was assessed using a PPRE based ELISA system. In vivo studies were carried out on adult male KKA^ymice and glucose levels were measured with a glucometer.</p> <p>Results</p> <p>Oleic acid and peanut oil high in oleic acid were able to enhance insulin production in INS-1. TNF-α inhibited insulin production but pre-treatment with oleic acid reversed this inhibitory effect. The viability status of INS-1 cells treated with TNF-α and oleic acid was not affected. Translocation of the peroxisome proliferator- activated receptor transcription factor to the nucleus was elevated in oleic acid treated cells. Finally, type II diabetic mice that were administered a high oleic acid diet derived from peanut oil, had decreased glucose levels compared to animals administered a high fat diet with no oleic acid.</p> <p>Conclusion</p> <p>Oleic acid was found to be effective in reversing the inhibitory effect in insulin production of the inflammatory cytokine TNF-α. This finding is consistent with the reported therapeutic characteristics of other monounsaturated and polyunsaturated fatty acids. Furthermore, a diet high in oleic acid, which can be easily achieved through consumption of peanuts and olive oil, can have a beneficial effect in type II diabetes and ultimately reverse the negative effects of inflammatory cytokines observed in obesity and non insulin dependent diabetes mellitus.</p

Tuning the bandgap of Cs2AgBiBr6 through dilute tin alloying.

The promise of lead halide hybrid perovskites for optoelectronic applications makes finding less-toxic alternatives a priority. The double perovskite Cs2AgBiBr6 (1) represents one such alternative, offering long carrier lifetimes and greater stability under ambient conditions. However, the large and indirect 1.95 eV bandgap hinders its potential as a solar absorber. Here we report that alloying crystals of 1 with up to 1 atom% Sn results in a bandgap reduction of up to ca. 0.5 eV while maintaining low toxicity. Crystals can be alloyed with up to 1 atom% Sn and the predominant substitution pathway appears to be a ∼2 : 1 substitution of Sn2+ and Sn4+ for Ag+ and Bi3+, respectively, with Ag+ vacancies providing charge compensation. Spincoated films of 1 accommodate a higher Sn loading, up to 4 atom% Sn, where we see mostly Sn2+ substitution for both Ag+ and Bi3+. Density functional theory (DFT) calculations ascribe the bandgap redshift to the introduction of Sn impurity bands below the conduction band minimum of the host lattice. Using optical absorption spectroscopy, photothermal deflection spectroscopy, X-ray absorption spectroscopy, 119Sn NMR, redox titration, single-crystal and powder X-ray diffraction, multiple elemental analysis and imaging techniques, and DFT calculations, we provide a detailed analysis of the Sn content and oxidation state, dominant substitution sites, and charge-compensating defects in Sn-alloyed Cs2AgBiBr6 (1:Sn) crystals and films. An understanding of heterovalent alloying in halide double perovskites opens the door to a wider breadth of potential alloying agents for manipulating their band structures in a predictable manner

The evolution of research and development in the pharmaceutical industryToward the open innovation model - Can pharma reinvent itself?

The global pharmaceutical industry is facing diminishing returns from its massive investment in research and development. This is particularly troublesome because the industry has long enjoyed monopoly rents that come from innovative new drugs. The purpose of this paper is to examine the extant R&D practices in the industry and make a strong case for a shift to the open innovation model. Potential roadblocks to adopting the open innovation model are identified as well as ways to overcome these roadblocks. This conceptual paper makes use of archival R&D and sales data to support its contentions

The Evolution of Research and Development in the Pharmaceutical Industry: Toward the Open Innovation Model - Can Pharma Reinvent Itself?

The global pharmaceutical industry is facing diminishing returns from its massive investment in research and development. This is particularly troublesome because the industry has long enjoyed monopoly rents that come from innovative new drugs. The purpose of this paper is to examine the extant R&D practices in the industry and make a strong case for a shift to the open innovation model. Potential roadblocks to adopting the open innovation model are identified as well as ways to overcome these roadblocks. This conceptual paper makes use of archival R&D and sales data to support its contentions