The effect of Galleria mellonella hemolymph polypeptides on Legionella gormanii

Among Legionella species, which are recognized to be pathogenic for humans, L. gormanii is the second prevalent causative agent of community-acquired pneumonia after L. pneumophila. Anti-L. gormanii activity of Galleria mellonella hemolymph extract and apolipophorin III (apoLp-III) was examined. The extract and apoLp-III at the concentration 0.025 mg/ml caused 75% and 10% decrease of the bacteria survival rate, respectively. The apoLp-III-induced changes of the bacteria cell surface were analyzed for the first time by atomic force microscopy. Our studies demonstrated the powerful anti-Legionella effects of the insect defence polypeptides, which could be exploited in drugs design against these pathogens

Synthesis and Characterization of Electro-Explosive Magnetic Nanoparticles for Biomedical Applications

Nowadays there are new magnetic nanostructures based on bioactive metals with low toxicity and high efficiency for a wide range of biomedical applications including drugs delivery, antimicrobial drugs design, cells' separation and contrasting. For such applications it is necessary to develop highly magnetic particles with less than100 nm in size. In the present study magnetic nanoparticles Fe, Fe[3]O[4] and bimetallic Cu/Fe with the average size of 60- 90 nm have been synthesized by electrical explosion of wire in an oxygen or argon atmosphere. The produced nanoparticles have been characterized with transmission electron microscopy, X-ray phase analysis, and nitrogen thermal desorption. The synthesized particles have shown antibacterial activity to gram-positive (S. aureus, MRSA) and gramnegative (E. coli, P. aeruginosa) bacteria. According to the cytological data Fe, Fe[3]O[4]and Cu/Fe nanoparticles have effectively inhibited viability of cancer cell lines Neuro-2a and J774. The obtained nanoparticles are promising for new antimicrobial drugs and antitumor agents' developmen

Is the Food and Drug Administration Safe and Effective?

In the United States, drug safety and efficacy are primarily regulated by the Food and Drug Administration (FDA) and the legal system, which gives manufacturers large incentives to produce safe drugs and provide proper warnings for side effects, since patients can sue manufacturers that provide unsafe drugs and/or insufficient warnings. In this paper, we begin by examining the efficiency implications of this joint regulation of drug safety. We find that joint regulation of drug safety can be inefficient when the regulatory authority mandates a binding and well enforced level of safety investment. In this case, product liability has no effect on a firm's safety investment, but affects welfare by raising a firm's costs and therefore prices. Using these results, we calibrate a model of the pharmaceutical market and find that, depending on the share of liability costs in marginal costs, a product liability exemption for activities that are well regulated by the FDA could increase consumer welfare by $47.8-$754.7 billion annually (4-66 percent of sales) and producer welfare by $11.9-$173.9 billion annually (1-15 percent of sales). In addition, we summarize the welfare effects of recent legislation, the Prescription Drug User Fee Acts (PDUFA), which mandated faster FDA review times in exchange for user fees levied on the pharmaceutical industry. Overall, we find that the faster review times mandated by PDUFA raised social surplus by $18-31 billion, and that at most, the concomitant cost of reduced drug safety was$5.6-$16.6 billion.

Provenance-based trust for grid computing: Position Paper

Current evolutions of Internet technology such as Web Services, ebXML, peer-to-peer and Grid computing all point to the development of large-scale open networks of diverse computing systems interacting with one another to perform tasks. Grid systems (and Web Services) are exemplary in this respect and are perhaps some of the first large-scale open computing systems to see widespread use - making them an important testing ground for problems in trust management which are likely to arise. From this perspective, today's grid architectures suffer from limitations, such as lack of a mechanism to trace results and lack of infrastructure to build up trust networks. These are important concerns in open grids, in which "community resources" are owned and managed by multiple stakeholders, and are dynamically organised in virtual organisations. Provenance enables users to trace how a particular result has been arrived at by identifying the individual services and the aggregation of services that produced such a particular output. Against this background, we present a research agenda to design, conceive and implement an industrial-strength open provenance architecture for grid systems. We motivate its use with three complex grid applications, namely aerospace engineering, organ transplant management and bioinformatics. Industrial-strength provenance support includes a scalable and secure architecture, an open proposal for standardising the protocols and data structures, a set of tools for configuring and using the provenance architecture, an open source reference implementation, and a deployment and validation in industrial context. The provision of such facilities will enrich grid capabilities by including new functionalities required for solving complex problems such as provenance data to provide complete audit trails of process execution and third-party analysis and auditing. As a result, we anticipate that a larger uptake of grid technology is likely to occur, since unprecedented possibilities will be offered to users and will give them a competitive edge

Antiemetic research: future directions

PURPOSE AND METHODS: As a part of reviewing the Multinational Association of Supportive Care in Cancer (MASCC) antiemetic guidelines in Perugia in 2009, an expert group identified directions for future antiemetic research. RESULTS AND CONCLUSIONS: In future trials, the prediction of nausea and vomiting may combine algorithms based on observed prognostic factors relating to the patient and the anticancer therapy, the identification of the genes that code for receptors, and pharmacogenetic studies of the metabolism of drugs. Design issues for future trials include standardising the emetic stimulus across studies and finding the minimum tolerated effective dose and schedule of an antiemetic. Also control of delayed emesis is not independent of the control of acute emesis. The full range of side effects and the impact on global quality of life scores should be part of the routine assessment of an antiemetic. With current high rates of control of acute vomiting, future trials will need to consider new primary endpoints such as nausea, a complex symptom, where improvement is needed. Economic endpoints should be incorporated to ascertain the cost benefit of antiemetic prophylaxis, taking into account the impact of nausea on work capacity. New antiemetic drugs may be targeted at different receptors, such as opioid, cannabinoid and peptide YY receptors. New research is needed into determining the extent of corticosteroid use. The emetic potential of a range of newer cytotoxics particularly when used in combinations and different scheduling, such as prolonged oral dosing of cytotoxics and use of targeted therapies, are all areas in need of research. More antiemetic studies are needed in niche areas such as in patients receiving high dose chemotherapy, radiation therapy or combined modality therapy. Further evidence of the efficacy of newer antiemetic agents is required in children

Synthesis and Characterization of Electro-Explosive Magnetic Nanoparticles for Biomedical Applications

Nowadays there are new magnetic nanostructures based on bioactive metals with low toxicity and high efficiency for a wide range of biomedical applications including drugs delivery, antimicrobial drugs design, cells' separation and contrasting. For such applications it is necessary to develop highly magnetic particles with less than100 nm in size. In the present study magnetic nanoparticles Fe, Fe[3]O[4] and bimetallic Cu/Fe with the average size of 60- 90 nm have been synthesized by electrical explosion of wire in an oxygen or argon atmosphere. The produced nanoparticles have been characterized with transmission electron microscopy, X-ray phase analysis, and nitrogen thermal desorption. The synthesized particles have shown antibacterial activity to gram-positive (S. aureus, MRSA) and gramnegative (E. coli, P. aeruginosa) bacteria. According to the cytological data Fe, Fe[3]O[4]and Cu/Fe nanoparticles have effectively inhibited viability of cancer cell lines Neuro-2a and J774. The obtained nanoparticles are promising for new antimicrobial drugs and antitumor agents' developmen