A drug based model to predict enhanced transdermal and blood brain barrier drug deliverability using ultrasonic methods

Abstract A previously described equation using the free energy of water desolvation (ΔG desolv,CDS), the lipophilicity free energy (ΔG lipo,CDS), dipole moment and molecular volume that describes the ability of drugs to cross the blood brain barrier and other cell membranes has been shown to apply to transdermal permeation when combined with ultrasound treatment. The dipole moment is particularly important when seeking to predict how drugs will interact with the transient pores in the cell membrane or blood brain barrier under ultrasound treatment. A quantum mechanical DFT analysis of the molecular interaction of mannitol and BCNU interacting with a surrogate membrane based on DPhPC has shown that the unexpected greater US induced permeability of mannitol compared to BCNU is due to differences in how the dipoles of mannitol and BCNU interact with the electric dipole potential of the lipid bilayers of the blood brain barrier, specifically by interacting with the phosphatidylcholine headgroup not the ester group. This result indicates that the design of therapeutic drugs to cross dermal and BBB membranes should consider whether such drugs can interact with the phosphatidylcholine headgroup of the membranes thereby possibly lowering the dipole potential of the lipid bilayer and hence enhancing drug permeation. The observed increase in electrical conductivity of the stratium corneum of the skin and blood brain barrier upon ultrasound treatment is an important factor which determines the transient permeabilization enhancement of drugs. It is likely that the dipole moment of permeating drugs may be a critically important factor that interacts with the membrane dipole potential of the stratium corneum of the skin and blood brain barrier upon ultrasound treatment. Transient pores are known to be involved when electrical fields are exerted on biological membranes, with conductance spikes occurring during the opening and closing of these transient pores. The opening and closing of lipidic pores also involve electrically invisible (silent) pre-pores

Social and economic data for regional and natural resource management in Western Australia\u27s south west catchment : results of the 2006 landholder survey

This report presents a summary of the key findings from a mailed survey to 2,000 landholders in the South West Region of Western Australia in 2006. The survey gathered information on the key social and economic factors affecting landholder decision-making about the adoption of practices expected to improve the management of natural resources in the region. The response rate for the survey was 69.4%. The South West Catchment Council, Western Australian Department of Agriculture and Food and the Bureau of Rural Sciences were key project partners. Funding was from a mix of national, state and regional programmes, including the Natural Heritage Trust Extension (NHT). The South West Catchment is geographically, socially and economically diverse and is made up of six sub-regions (Blackwood, Cape to Cape, Geographe, Leschenault, Peel-Harvey, and Warren). These sub-regions were used to report on differences across the catchment

Requirements: ULSA demerits

Details requirements for a demerit point system in the Voyager Integrated Library System, as defined by the 3 university libraries in South Australia

Splenomegaly and Tumor Marker Response Following Selective Internal Radiation Therapy for Non-Resectable Liver Metastases from Neuroendocrine Tumor

PURPOSE:The aim of this study was to investigate changes in spleen size, the level of chromogranin Aas a tumor marker, and the relationship between these two parameters before and 3 months after selectiveinternal radiation therapy (SIRT) for non-resectable liver metastases from neuroendocrine tumor (NET).Our first serious adverse event with this relatively new treatment is also discussed.METHODS:A retrospective review of a prospective database identified patients with non-resectable livermetastases from NET who underwent SIRT between 2003 and 2007. Patients who underwent CT scansbefore and 3 months after treatment were included. The patients were divided into two groups:those withand without a 20 % or more increase in splenic volume on the CT scans. The percentages of patients showinga tumor marker response in the two groups were then comparedRESULTS:Fourteen patients were included in the present analysis. A tumor marker response was seenin 6 of 7 patients( 85.7%) who showed an increase in splenic volume of>20%, and in 3 of 7 patients( 42.9%) without an increase in splenic volume (p=0.266). There was one death as a result of oesophageal varicealbleeding due to portal hypertension at 9 months after treatment.CONCLUSION:Splenic enlargement after SIRT may be associated with tumor marker response, althoughthis could not be confirmed statistically in this study due to the small number of patients. Long-termsplenomegaly and portal hypertension may be important complications of SIRT. This issue needs to be investigatedfurther using a larger number of patients and longer follow-up