Synthetic studies of the HIV-1 protease inhibitive didemnaketals: Stereocontrolled synthetic approach to the key mother spiroketals

[GRAPHICS] The stereocontrolled synthesis of (2S,4R,6R,8S,10S,1'R,1"R)-2(acetylhydroxymethyl)-4, 10-dimethyl-8(isopropenylhydroxymethyl)-1, 7-dioxaspiro[5,5]-undecane (4a) and its C1"-epimer (4b), the key mother spiroketals of the HIV-1 protease inhibitive didemnaketals from the ascidian Didemnum sp., has been carried out through multisteps from the natural (R)-(+)-pulegone, which involved the diastereoselective construction of four chiral carbon centers(C-2, C-6, C-8, and C-1') by intramolecular chiral induce.

ReoPro rules: results from the 'DoTirofiban and ReoPro give similar efficacy trial' (TARGET) - A Key Paper Evaluation (Topol, Ej et al)

In the treatment of atherosclerotic disease, stenting in the presence of a glycoprotein (GP) IIb/IIIa antagonist is becoming an increasingly common procedure. The ‘Do Tirofiban and ReoPro Give Similar Efficacy Trial’ (TARGET) was designed to determine whether the cheaper tirofiban was as effective and safe as abciximab in the prevention of ischaemic events with stenting. Unexpectedly, abciximab was shown to be superior to tirofiban. Tirofiban is a selective GP IIb/IIIa antagonist whereas abciximab has additional anti-inflammatory actions, which may contribute to its superiority.

Is bucindolol BEST? (A Key Paper Evaluation)

Carvedilol, a non-selective β-adrenoceptor blocker with ancillary properties, and metoprolol and bisoprolol, selective β1-blockers without ancillary properties, have been shown to reduce mortality and morbidity in heart failure. In the Beta-blocker Evaluation of Survival Trial (BEST), bucindolol, a non-selective β-adrenoceptor blocker with different ancillary properties to carvedilol, did not reduce overall survival in heart failure. Possible explanations for this include: more Blacks being included in the trial, bucindolol being more ‘sympatholytic’ than the other β-blockers and more advanced heart failure in BEST. Another possible explanation is that bucindolol is stimulating cardiac β2-adrenoceptors to counter the effects of inhibiting cardiac β1-adrenoceptors. Bucindolol is not the best treatment and carvedilol, metoprolol and bisoprolol should be preferred in heart failure.

Clopidogrel: A CURE in acute coronary syndromes? (A Key Paper Evaluation)

The standard approach to preventing acute coronary syndromes (ACSs)has been to inhibit platelet aggregation with aspirin and to inhibit blood coagulation with low molecular-weight heparin (LMWH). Even with this combination there is still a substantial short and long-term cardiovascular risk. The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial [1] compared clopidogrel plus aspirin against aspirin alone in patients with ACSs. The clopidogrel regimen was a loading dose of 300 mg p.o. followed by 75 mg/day and the recommended dose of aspirin was 75 - 325 mg/day. The first primary outcome was a composite of death from cardiovascular causes, non-fatal myocardial infarction (MI) or stroke and this occurred significantly less often in the clopidogrel than the placebo group (9.3 vs. 11.4%). Although there were more clopidogrel patients with life-threatening bleeding (clopidogrel 2.2%, placebo 1.8%), this represented GI haemorrhages and bleeding at sites of arterial puncture rather than fatal bleeding. This trial suggests a role for clopidogrel in the long-term treatment of ACSs

A molecular phylogeny of rainbow skinks (Scincidae : Carlia): taxonomic and biogeographic implications

The phylogenetic relationships amongst 29 species of Carlia and Lygisaurus were estimated using a 726-base-pair segment of the protein-coding mitochondrial ND4 gene. Results do not support the recent resurrection of the genus Lygisaurus. Although most Lygisaurus species formed a single clade, this clade is nested within Carlia and includes Carlia parrhasius. Due to this new molecular evidence, and the paucity of diagnostic morphological characters separating the genera, Lygisaurus de Vis 1884 is re-synonymised with Carlia Gray 1845. Our analysis is also inconsistent with a previous suggestion that Lygisaurus timlowi should be removed to Menetia, a genus that is distantly related relative to outgroups used here. Intraspecific variation in Carlia is, in several instances, greater than interspecific distance. The most strikingly divergent lineages are found within C. rubrigularis, which appears to be paraphyletic, with southern populations more closely related to C. rhomboidalis than to northern populations of C. rubrigularis. The two C. rubrigularis-C. rhomboidalis lineages form part of a major polytomy at an intermediate level of divergence. Lack of resolution at this level, however, does not appear to be due to saturation or loss of phylogenetic signal. Rather, the polytomy probably reflects a period of relatively rapid diversification that occurred sometime during the Miocene.

Taxonomic theory and the ICF: Foundations for a unified disability athletics classification

Development of a unified classification system to replace four of the systems currently used in disability athletics (i.e., track and field) has been widely advocated. The definition and purpose of classification, underpinned by taxonomic principles and collectively endorsed by relevant disability sport organizations, have not been developed but are required for successful implementation of a unified system. It is posited that the International classification of functioning. disability, and health (ICF), published by the World Health Organization (2001), and current disability athletics systems are, fundamentally, classifications of the functioning and disability associated with health conditions and are highly interrelated. A rationale for basing a unified disability athletics system on ICF is established. Following taxonomic analysis of the current systems, the definition and purpose of a unified disability athletics classification are proposed and discussed. The proposed taxonomic framework and definitions have implications for other disability sport classification systems.

Electrospray liquid chromatography/mass spectrometry fingerprinting of Acanthophis (death adder) venoms: taxonomic and toxinological implications

Death adders (genus Acanthophis) are unique among elapid snakes in both morphology and venom composition. Despite this genus being among the most divergent of all elapids, the venom has been historically regarded as relatively quite simple. In this study, liquid chromatography/mass spectrometry (LC/MS) analysis has revealed a. much greater diversity in venom composition, including the presence of molecules of novel molecular weights that may represent a new class of venom component. Furthermore, significant variation exists between species and populations,, which allow for the LC/MS fingerprinting of each species. Mass profiling of Acanthophis venoms clearly demonstrates the effectiveness of this technique which underpins fundamental studies ranging from chemotaxonomy to drug design. Copyright (C) 2002 John Wiley Sons, Ltd.

Roof gutters: A key container for Aedes aegypti and Ochlerotatus notoscriptus (Diptera : Culicidae) in Australia

The contribution of roof gutters to Aedes aegypti (L.) and Ochlerotatus notoscriptus (Skuse) pupal populations was quantified for the first time in Cairns, Australia. Concurrent yard and roof surveys yielded ill estimated 6,934 mosquito pupae, comprising four species. Roof gutters were all uncommon but productive source of Ae. aegypti in both wet season (n = 11) and dry season (n = 2) surveys, producing 52.6% and 39.5% of the respective populations. First story gutters accounted for 92.3% of the positive gutters. Therefore, treatment of roof gutters is a critical element in Ae. aegypti control campaigns during dengue outbreaks. In wet season yards, the largest standing, crops of Ae. aegypti occurred in garden accoutrements, discarded household items, and rubbish (36.4%, 28.0%, and 20.6%, respectively). In dry season yards, rubbish produced 79.6% of the Ae. aegypti pupae. The number of Ae. aegypti pupae/person was 2.36 and 0.59 for the wet and dry season surveys, respectively.

Towards a taxonomic revision of the genus Echinococcus

Echinococcus remains a significant public health problem worldwide and, in several regions, the aetiological agents of cystic hydatid disease/echinococcosis are extending their range. The taxonomy of Echinococcus has been a controversial issue for decades, but the outcome of recent molecular epidemiological studies has served to reinforce proposals made ten years ago to revise the taxonomy of Echinococcus. A formal nomenclature is essential for effective communication, and provides the stability that underpins epidemiological investigations. It will also serve to recognize the contribution of early taxonomists.

A new species of Phyllurus (Lacertilia : Gekkonidae) and a revised phylogeny and key for the Australian leaf-tailed geckos

Phyllurus gulbaru, sp. nov., is a highly distinct species of leaf-tailed gecko restricted to rocky rainforest of Pattersons Gorge, north-west of Townsville. The possession of a cylindrical, non-depressed, tapering original and regenerated tail separates P. gulbaru from all congeners except P. caudiannulatus. From this species P. gulbaru is separated by having a partially divided, as opposed to fully divided, rostral scale. Furthermore, the very small spinose body tubercles of P. gulbaru are in marked contrast to the large spinose body scales of P. caudiannulatus. An analysis of 729 bp of mitochondrial 12S rRNA and cytochrome b genes reveals P. gulbaru to be a deeply divergent lineage with closer affinities to mid-east Queensland congeners than the geographically neighbouring P. amnicola on Mt Elliot. In conservation terms, P. gulbaru is clearly at risk. Field surveys of Pattersons Gorge and the adjacent ranges indicate that this species is restricted to a very small area of highly fragmented habitat, of which only a small proportion receives a degree of protection in State forest. Further, there is ongoing, unchecked destruction of dry rainforest habitat by fire. Under current IUCN criteria, P. gulbaru warrants an Endangered ( B1, 2) listing.