2, 4-Diamino-6- hydroxy pyrimidine inhibits NSAIDs induced nitrosyl-complex EPR signals and ulcer in rat jejunum

BACKGROUND: It has been suggested that one aspect of non-steroidal anti-inflammatory drugs induced intestinal damage is due to either uncoupling of mitochondrial oxidative phosphorylation or inhibition of electron transport. We investigated the latter possibility using electron paramagnetic resonance spectroscopy. RESULTS: Electron paramagnetic studies of NSAIDS on sub-mitochondrial particles revealed that indomethacin, but not with nabumetone, bound to a site near to Complex I and ubiquinone to generate a radical species. Normal rats exhibited prominent [3Fe-4S]ox signals (g ~ 2.01) at 20 K. One hour after indomethacin there was a prominent, intense and broad absorption pattern at (g ~2.07) suggesting, appearance of radical species overlapping [3Fe-4S]ox and was unaffected by pretreatment with 2,4 diamino -6-hydroxy pyrimidine. At 24 hrs, when macroscopic ulcers were seen, there was a new signal due to a nitric oxide radical (NO•). In contrast, nabumetone and 2,4 diamino-6-hydroxy pyrimidine pre-treated animals receiving indomethacin exhibited electron paramagnetic resonance spectra identical to those of controls at 24 hrs and neither was associated with small intestinal ulcers. Indomethacin and 2,4 diamino hydroxy pyrimidine pre-treated rats, but not nabumetone, had increased intestinal permeability. CONCLUSION: The results suggest that the in vivo effects of indomethacin modulate the mitochondrial respiratory chain directly at 1 h and 24 h through formation of nitric oxide. NO• appears to play an important role in the late pathogenic stages of NSAID enteropathy and may be the site for targeted treatment to reduce their toxicity

Determinants of mortality for adults with cystic fibrosis admitted in Intensive Care Unit: a multicenter study

BACKGROUND: Intensive care unit (ICU) admission of adults with cystic fibrosis (CF) is controversial because of poor outcome. This appraisal needs re-evaluation following recent changes in both CF management and ICU daily practice. Objectives were to determine long-term outcome of adults with CF admitted in ICU and to identify prognostic factors. METHODS: Retrospective multicenter study of 60 ICU hospitalizations for 42 adult CF patients admitted between 2000 and 2003. Reason for ICU admission, ventilatory support provided and one-year survival were recorded. Multiple logistic analysis was used to determine predictors of mortality. RESULTS: Prior to ICU admission, all patients (mean age 28.1 ± 8 yr) had a severe lung disease (mean FEV(1 )28 ± 12% predicted; mean PaCO(2 )47 ± 9 mmHg). Main reason for ICU hospitalization was pulmonary infective exacerbation (40/60). At admission, noninvasive ventilation was used in 57% of cases and was successful in 67% of patients. Endotracheal intubation was implemented in 19 episodes. Overall ICU mortality rate was 14%. One year after ICU discharge, 10 of the 28 survivors have been lung transplanted. Among recognized markers of CF disease severity, only the annual FEV(1 )loss was associated with a poor outcome (HR = 1.47 [1.18–1.85], p = 0.001). SAPSII (HR = 1.08 [1.03–1.12], p < 0.001) and endotracheal intubation (HR = 16.60 [4.35–63.34], p < 0.001) were identified as strong independent predictors of mortality. CONCLUSION: Despite advanced lung disease, adult patients with CF admitted in ICU have high survival rate. Endotracheal intubation is associated with a poor prognosis and should be used as the last alternative. Although efforts have to be made in selecting patients with CF likely to benefit from ICU resources, ICU admission of these patients should be considered

Urban tourist precincts as sites of play

This chapter examines the urban tourism precinct as an organised space for playful forms of leisure in the city. We argue that these spaces create an environment for leisured interaction where both visitor and host engage as mutual actors in urban playgrounds. The chapter commences with a conceptual overview of the urban tourism precinct. It then considers the notion of play through an analysis of selected seminal discourses. These discourses are linked to the precinct in the context of a play space within the city using data gathered from two studies conducted in The Rocks and Darling Harbour precincts in Sydney, Australia (Hayllar and Griffin 2005, 2006). The chapter concludes with a discussion on the implications for the design and management of urban tourism precincts

Personal Transport Emissions Within London: Exploring Policy Scenarios and Carbon Reductions up to 2050

This research explored the possibility of achieving significant carbon reductions from personal land-based transport using London as a case study. A profile of carbon emissions from personal land-based transport modes was derived using Great Britain National Travel Survey (NTS) data and a range of carbon emissions factors. A carbon calculator provided carbon consumption per trip. NTS survey data were grossed up to national level using Census of Population data. A baseline of carbon emissions, based on equal per capita consumption, was projected to 2050 using estimates of future population. Four future scenarios were developed and tested using this data. These were: (a) based on the London Mayor's Climate Change Action Plan; (b) a technology focussed scenario; (c) a personal carbon trading scenario; and (d) a radical walking and cycling scenario. Results suggest that the latter two scenarios have the potential to achieve emissions reductions in excess of 80%, whilst scenarios (a) and (b) are somewhat weaker, though still achieve substantial reductions in carbon emissions compared to business as usual

Outdoor and Experiential Learning: Views from the Top

This is a collection of pieces that reflect with intimacy, the integrity of the culture that founded this industry in Australia and New Zealand. Many of the pieces are in the academic conversational language of research and discussion, however clear multi-dimensional images, come thick and fast. The book entices, informs, and debates. The payoffs are fundamental insights into the connection between place, relationship and understanding. Outdoor and experiential learning discusses the gifts that can be gained from a special sort of learning with the outdoors; learning that often escapes, or is overlooked, due to our intent to control and harvest all we can. The discussions are holistic and practical, and represent a well-rounded set of perspectives. Not a quick read often due to the language, but give your self the gift of time, for the colours, sounds and magic of a great classroom