Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

Facilitating local stories in post-disaster regional communities : evaluation in narrative-driven oral history projects

Cyclone Yasi struck the Cassowary Coast of Northern Queensland, Australia, in the early hours of February 3, 2011, destroying many homes and property, including the destruction of the Cardwell and district historical society’s premises. With their own homes flattened, many residents were forced to live in mobile accommodation, with extended family, or leave the area altogether. The historical society members seemed, however, particularly devastated by their flattened foreshore museum and loss of their precious collection of material. A call for assistance was made through the Oral History Association of Australia’s Queensland branch (OHAA Qld), which along with a Queensland University of Technology (QUT) research team sponsored a trip to best plan how they could start to pick up the pieces to rebuild the museum. This chapter highlights the need for communities to gather, preserve and present their own stories, in a way that is sustainable and meaningful to them – whether that be because of a disaster, or as they go about life in their contemporary communities – the key being that good advice, professional support and embedded evaluation practices at crucial moments along the way can be critically important.

Author response: "NPO practices and preoperative oral carbohydrate intake"

"We thank Dr Marsh for his thoughtful comments and acknowledge the limitations of our study, which we clearly outlined in the article. We also thank Dr Marsh for supporting our call for larger, independent trials to test the effectiveness of preoperative consumption of highcarbohydrate fluids to improve patient outcomes..."

Oral immunization with a novel lipid-based adjuvant protects against genital Chlamydia infection

Oral immunization is attractive as a delivery route because it is needle-free and useful for rapid mass vaccination programs to target pandemics or bioterrorism. This potential has not been realized for human vaccination, due to the requirement of large antigen doses and toxic (to humans) adjuvants to overcome the induction of oral tolerance and potential degradation of antigens in the stomach. To date, only oral vaccines based on live attenuated organisms have been approved for human use. In this study we describe the use of a lipid-based delivery system/adjuvant, Lipid C, for oral immunization to protect mice against genital tract chlamydial infection. Lipid C is formulated from food-grade purified and fractionated triglycerides. Bacterial shedding following vaginal challenge with Chlamydia muridarum was reduced by 50% in female mice orally immunized with the chlamydial major outer membrane protein (MOMP) formulated in Lipid C, protection equivalent to that seen in animals immunized with MOMP admixed with both cholera toxin (CT) and CpG oligodeoxynucleotides (CpG-ODN). Protection was further enhanced when MOMP, CT and CpG were all combined in the Lipid C matrix. Protection correlated with production of gamma interferon (IFN) by splenic T cells, a serum MOMP-specific IgG response and low but detectable levels of MOMP-specific IgA in vaginal lavage.

Return journey : Professor Efron flies in - interview in Optometry Today

Before returning from Australia for the BCLA's Pioneers Day, Professor Nathan Efron spoke to OT. Professor Efron, you’re back in the UK for a short while – What tempted you away from Australia’s summer and back to Britain in November...

The Deleuze Spray, New York 1977 : an Interview with Sanford Kwinter, Professor of Architectural Theory and Criticism at the Harvard Graduate School of Design, on the Architectural Reception of Gilles Deleuze in America

So what do you want to know? I was in Paris between ‘75 and ‘78. But about half way through, Sylvère published the Anti-Oedipus issue of Semiotext(e) and, actually, that was for me one of the deciding events that made me decide to come to the United States, to come study at Columbia University. There appeared to be this little group working at Columbia working around these issues. In 1970, in Paris even, Deleuze was a cult – there was an incredibly small number of people following Deleuze... A transcript of my Interview with Kwinter about the Architectural Reception of Deleuze in America, which took place at Jerry’s,' Soho, New York, 15 January 2003. The transcript appeared as an Appendix at the back of my Masters Thesis undertaken at Yale School of Architecture, printed May 2003.

An Interview with Sylvère Lotringer, Jean Baudrillard Chair at the European Graduate School and Professor Emeritus of French Literature and Philosophy at Columbia University, on the Architectural Contribution to Semiotext(e), Schizoculture, and the Early Deleuze and Guattari Scene at Columbia University

An Interview with Sylvère Lotringer, Jean Baudrillard Chair at the European Graduate School and Professor Emeritus of French Literature and Philosophy at Columbia University, on the Architectural Contribution to Semiotext(e), Schizoculture, and the Early Deleuze and Guattari Scene at Columbia University, which took place at the Department of French, Columbia University, New York City, July 2003. This interview exists as an audio cassette tape recording.

Practical Advice to Entrepreneurs Series by ACE Adjunct Professor Dean Shepherd: Practical advice on whether to act entrepreneurially

The author, Dean Shepherd, is interested in the psychology of entrepreneurship — how entrepreneurs think, decide to act, and feel. He recently realized that while his publications in academic journals have implications for entrepreneurs, those implications have remained relatively hidden in the text of the articles and hidden in articles published in journals largely inaccessible to those involved in the entrepreneurial process. This series is designed to bring the practical implications of his research to the forefront.

Comparative susceptibility of mosquito populations in North Queensland, Australia to oral infection with dengue virus

Dengue is the most prevalent arthropod-borne virus, with at least 40% of the world’s population at risk of infection each year. In Australia, dengue is not endemic, but viremic travelers trigger outbreaks involving hundreds of cases. We compared the susceptibility of Aedes aegypti mosquitoes from two geographically isolated populations with two strains of dengue virus serotype 2. We found, interestingly, that mosquitoes from a city with no history of dengue were more susceptible to virus than mosquitoes from an outbreak-prone region, particularly with respect to one dengue strain. These findings suggest recent evolution of population-based differences in vector competence or different historical origins. Future genomic comparisons of these populations could reveal the genetic basis of vector competence and the relative role of selection and stochastic processes in shaping their differences. Lastly, we show the novel finding of a correlation between midgut dengue titer and titer in tissues colonized after dissemination.

Practical Advice to Entrepreneurs Series by ACE Adjunct Professor Dean Shepherd: Practical advice for thinking about entrepreneurial decisions

The author, Dean Shepherd, is of entrepreneurship—how entrepreneurs think, decide to act, and feel. He recently realized that while his publications in academic journals have implications for entrepreneurs, those implications have remained relatively hidden in the text of the articles and hidden in articles published in journals largely inaccessible to those involved in the entrepreneurial process. This series is designed to bring the practical implications of his research to the forefront.

Practical Advice to Entrepreneurs Series by ACE Adjunct Professor Dean Shepherd: Practical advice on engaging values to avoid causing harm

The author, Dean Shepherd, is of entrepreneurship—how entrepreneurs think, decide to act, and feel. He recently realized that while his publications in academic journals have implications for entrepreneurs, those implications have remained relatively hidden in the text of the articles and hidden in articles published in journals largely inaccessible to those involved in the entrepreneurial process. This series is designed to bring the practical implications of his research to the forefront.

Practical Advice to Entrepreneurs Series by ACE Adjunct Professor Dean Shepherd: Practical advice on transitioning from trauma to entrepreneurship

The author, Dean Shepherd, is of entrepreneurship—how entrepreneurs think, decide to act, and feel. He recently realized that while his publications in academic journals have implications for entrepreneurs, those implications have remained relatively hidden in the text of the articles and hidden in articles published in journals largely inaccessible to those involved in the entrepreneurial process. This series is designed to bring the practical implications of his research to the forefront.

Practical Advice to Entrepreneurs Series by ACE Adjunct Professor Dean Shepherd: Practical advice for prisoners on developing an entrepreneurial career

The author, Dean Shepherd, is of entrepreneurship—how entrepreneurs think, decide to act, and feel. He recently realized that while his publications in academic journals have implications for entrepreneurs, those implications have remained relatively hidden in the text of the articles and hidden in articles published in journals largely inaccessible to those involved in the entrepreneurial process. This series is designed to bring the practical implications of his research to the forefront.

Practical Advice to Entrepreneurs Series by ACE Adjunct Professor Dean Shepherd: Practical advice on making the business more entrepreneurial

The author, Dean Shepherd, is of entrepreneurship—how entrepreneurs think, decide to act, and feel. He recently realized that while his publications in academic journals have implications for entrepreneurs, those implications have remained relatively hidden in the text of the articles and hidden in articles published in journals largely inaccessible to those involved in the entrepreneurial process. This series is designed to bring the practical implications of his research to the forefront.