Trials and tribulations in the removal of dextropropoxyphene from the Australian register of therapeutic goods

The Therapeutic Goods Administration determined in November 2011 that dextropropoxyphene should be removed from the Australian Register of Therapeutic Goods. This is consistent with this drug's removal from the market in many other developed countries. H

Pre-synaptic alpha adrenoceptors and noradrenaline in neurotransmission in the mouse-isolated vas deferens

Imperial Users onl

Mating System Biology of the Florida Native Plant: Illicium parviflorum

Self-incompatibility is thought to have played a profound role in the evolution of the angiosperms. However, there is little evidence of self-incompatibility systems in early diverging lineages of flowering plants. Illicium parviflorum, one such early-divergent angiosperm, is an evergreen perennial species endemic to central Florida, particularly within the Ocala National Forest. Although locally abundant, I. parviflorum is currently listed as endangered at the state level due to being under constant threat of habitat disturbance and over-harvesting. Notably, this species had been described as self-incompatible due to its low seed-set. However, low seed set may also be a result of strong, early inbreeding depression. Using cross-pollinations, histology, and molecular analysis, I provide conclusive evidence that I. parviflorum possesses the ability to self-fertilize, while finding no evidence of a self-incompatibility system. Furthermore, cross-pollinations of individuals within and between populations revealed heterosis, while seeds collected from self-pollinations were smaller than those collected from out-crosses, suggesting that inbreeding may be reducing fitness within populations. An analysis used to estimate parental genotypes of individuals in a population using AFLP markers identified two out of 23 plants to be the result of natural self-pollination, while the mean (+ s.e.) pollen: ovule ratio of I. parviflorum was found to be 511 + 86, a ratio consistent with a species that relies primarily, but not exclusively, on outcrossing. Pollen/ovule ratios of I. parviflorum and other small flowered Illicium are lower than their larger flowered, derived relatives, suggesting that the ancestral floral type to the Illicium lineage was self-compatible. These results support the hypothesis that early angiosperm species had the ability to self-fertilize and that self-incompatibility systems did not arise until after the origin of the bisexual flower

Stereoelectronic effects on the binding of neutral Lewis bases to CdSe nanocrystals

Using P-31 nuclear magnetic resonance (NMR) spectroscopy, we monitor the competition between tri-nbutylphosphine (Bu3P) and various amine and phosphine ligands for the surface of chloride terminated CdSe nanocrystals. Distinct P-31 NMR signals for free and bound phosphine ligands allow the surface ligand coverage to be measured in phosphine solution. Ligands with a small steric profile achieve higher surface coverages (Bu3P = 0.5 nm(-2), Me2P-n-octyl = 2.0 nm(-2), NH2Bu = >3 nm(-2)) and have greater relative binding affinity for the nanocrystal (binding affinity: Me3P > Me2P -n-octyl similar to Me2P -n-octadecyl > Et3P > Bu3P). Among phosphines, only Bu 3 P and Me2P-n-octyl support a colloidal dispersion, allowing a relative surface binding affinity (K-rel) to be estimated in that case (K-rel = 3.1). The affinity of the amine ligands is measured by the extent to which they displace Bu3P from the nanocrystals (K-rel: H2NBu similar to N-n-butylimidazole > 4-ethylpyridine > Bu3P similar to HNBu2 > Me2NBu > Bu3N). The affinity for the CdSe surface is greatest among soft, basic donors and depends on the number of each ligand that bind. Sterically unencumbered ligands such as imidazole, pyridine, and n-alkylamines can therefore outcompete stronger donors such as alkylphosphines. The influence of repulsive interactions between ligands on the binding affinity is a consequence of the high atom density of binary semiconductor surfaces. The observed behavior is distinct from the self-assembly of straight-chain surfactants on gold and silver where the ligands are commensurate with the underlying lattice and attractive interactions between aliphatic chains strengthen the binding

Effect of acetylcholinesterase (AChE) point-of-care testing in OP poisoning on knowledge, attitudes and practices of treating physicians in Sri Lanka

BACKGROUND: Toxicology and Emergency medicine textbooks recommend measurement of acetylcholinesterase (AChE) in all symptomatic cases of organophosphorus (OP) poisoning but laboratory facilities are limited in rural Asia. The accuracy of point-of-care (POC) acetylcholinesterase testing has been demonstrated but it remains to be shown whether results would be valued by clinicians. This study aims to assess the effect of seeing AChE POC test results on the knowledge, attitudes and practices of doctors who frequently manage OP poisoning. METHODS: We surveyed 23 clinicians, who had different levels of exposure to seeing AChE levels in OP poisoned patients, on a) knowledge of OP poisoning and biomarker interpretation, b) attitudes towards AChE in guiding poison management, oxime therapy and discharge decisions, and c) practices of ordering AChE in poisoning scenarios. RESULTS: An overall high proportion of doctors valued the test (68-89%). However, we paradoxically found that doctors who were more experienced in seeing AChE results valued the test less. Lower proportions valued the test in guidance of acute poisoning management (50%, p = 0.015) and guidance of oxime therapy (25%, p = 0.008), and it was apparent it would not generally be used to facilitate early discharge. The highest proportion of respondents valued it on admission (p < 0.001). A lack of correlation of test results with the clinical picture, and a perception that the test was a waste of money when compared to clinical observation alone were also comments raised by some of the respondents. Greater experience with seeing AChE test results was associated with increased knowledge (p = 0.034). However, a disproportionate lack of knowledge on interpretation of biomarkers and the pharmacology of oxime therapy (12-50%) was noted, when compared with knowledge on the mechanism of OP poisoning and management (78-90%). CONCLUSIONS: Our findings suggest an AChE POC test may not be valued by rural doctors. The practical use of AChE in OP poisoning management is complex, and a poor understanding of how to interpret test results may have affected its perceived utility. Future research should evaluate the impact of providing both AChE and training in interpretation on clinicians’ attitudes and practice.This research was funded by an international collaborative research grant from the Wellcome Trust/National Health and Medical Research Council, Australia (GR071669)

The crux of the matter: did the ABC&#039;s Catalyst program change statin use in Australia?

This article argues that the ABC’s Catalyst program criticising statins affected people’s willingness to take these drugs. Abstract Objectives: To examine the impact of a two-part special edition of the Australian Broadcasting Corporation\u27s science journalism program Catalyst (titled Heart of the matter), aired in October 2013, that was critical of HMG-CoA reductase inhibitors (“statins”). Design, setting and participants: Population-based interrupted time-series analysis of a 10% sample of Australian long-term concessional beneficiaries who were dispensed statins under the Pharmaceutical Benefits Scheme (about 51% of all people who were dispensed a statin between 1 July 2009 and 30 June 2014); dispensing of proton pump inhibitors (PPIs) was used as a comparator. Main outcome measures: Change in weekly dispensings and discontinuation of use of statins and PPIs, adjusting for seasonal and long-term trends, overall and (for statins only) stratified by the use of cardiovascular and diabetes medicines. Results: In our sample, 191&nbsp;833 people were dispensed an average of 26&nbsp;946 statins weekly. Following the Catalyst program, there was a 2.60% (95% CI, 1.40%–3.77%; P&nbsp;&lt;&nbsp;0.001) reduction in statin dispensing, equivalent to 14&nbsp;005 fewer dispensings Australia-wide every week. Dispensing decreased by 6.03% (95% CI, 3.73%–8.28%; P&nbsp;&lt;&nbsp;0.001) for people not dispensed other cardiovascular and diabetes medicines and 1.94% (0.42%–3.45%; P&nbsp;=&nbsp;0.01) for those dispensed diabetes medicines. In the week the Catalyst program aired, there was a 28.8% (95% CI, 15.4%–43.7%; P&nbsp;&lt;&nbsp;0.001) increase in discontinuation of statin use, which decayed by 9% per week. An estimated 28&nbsp;784 additional Australians ceased statin treatment. Discontinuation occurred regardless of the use of other cardiovascular and diabetes medicines. There were no significant changes in PPI use after the Catalyst program. Conclusions: Following airing of the Catalyst program, there was a temporary increase in discontinuation and a sustained decrease in overall statin dispensing. Up until 30 June 2014, there were 504&nbsp;180 fewer dispensings of statins, and we estimate this to have affected 60&nbsp;897 people

2-methyl-4-chlorophenoxyacetic acid and bromoxynil herbicide death.

CASE REPORT: We report a fatal case of a 37 year old gentleman who ingested a MCPA/bromoxynil co-formulation herbicide. Although clinically well on initial examination, our patient declined dramatically over his 18 h admission with increasing CO2 production, hyperthermia and metabolic derangement to eventually die from cardiac asystole 20 h post ingestion. Two hours after ingestion the MCPA concentration was 83.9 μg/mL and bromoxynil concentration was 137 μg/mL. DISCUSSION: The patients' mechanism of death appeared to be uncoupling of oxidative phosphorylation, excess CO2 production and hyperthermia. There is limited knowledge on the acute toxicity of these herbicides, in particular bromoxynil, and this case highlights the relentless progression of severe toxicity in humans.The collaboration was supported by an NHMRC Program Grant (1055176). Geoff Isbister is supported by an NHMRC Senior Research Fellowship ID 1061041 and Mike Roberts is supported by an NHMRC Senior Principal Research Fellowship ID 1002611

Predicting food-web structure with metacommunity models

Synthesis Metacommunity theory aims to elucidate the relative influence of local and regional-scale processes in generating diversity patterns across the landscape. Metacommunity research has focused largely on assemblages of competing organisms within a single trophic level. Here, we test the ability of metacommunity models to predict the network structure of the aquatic food web found in the leaves of the northern pitcher plant Sarracenia purpurea. The species-sorting and patch-dynamics models most accurately reproduced nine food web properties, suggesting that local-scale interactions play an important role in structuring Sarracenia food webs. Our approach can be applied to any well-resolved food web for which data are available from multiple locations. The metacommunity framework explores the relative influence of local and regional-scale processes in generating diversity patterns across the landscape. Metacommunity models and empirical studies have focused mostly on assemblages of competing organisms within a single trophic level. Studies of multi-trophic metacommunities are predominantly restricted to simplified trophic motifs and rarely consider entire food webs. We tested the ability of the patch-dynamics, species-sorting, mass-effects, and neutral metacommunity models, as well as three hybrid models, to reproduce empirical patterns of food web structure and composition in the complex aquatic food web found in the northern pitcher plant Sarracenia purpurea. We used empirical data to determine regional species pools and estimate dispersal probabilities, simulated local food-web dynamics, dispersed species from regional pools into local food webs at rates based on the assumptions of each metacommunity model, and tested their relative fits to empirical data on food-web structure. The species-sorting and patch-dynamics models most accurately reproduced nine food web properties, suggesting that local-scale interactions were important in structuring Sarracenia food webs. However, differences in dispersal abilities were also important in models that accurately reproduced empirical food web properties. Although the models were tested using pitcher-plant food webs, the approach we have developed can be applied to any well-resolved food web for which data are available from multiple locations. © 2012 The Authors. Oikos © 2012 Nordic Society Oikos