Although they are known to be effective antidiabetic agents, little is published about the toxic effects of carnitine palmitoyltransferase-1 (CPT-1) inhibitors, such as etomoxir (ET). These compounds inhibit mitochondrial fatty acid beta-oxidation by irreversibly binding to CPT-1 and preventing entry of long chain fatty acids into the mitochondrial matrix. Treatment of HepG2 cells with 1 mM etomoxir for 6 h caused significant modulations in the expression of several redox-related and cell cycle mRNAs as measured by microarray analysis. Upregulated mRNAs included heme oxygenase 1 (HO1), 8-oxoguanine DNA glycosylase 1 (OGG1), glutathione reductase (GSR), cyclin-dependent kinase inhibitor 1A (CDKN1 [p21(waf1)]) and Mn+ superoxide dismutase precursor (SOD2); while cytochrome P450 1A1 (CYP1A1) and heat shock 70kD protein 1 (HSPA1A) were downregulated. Real time quantitative PCR (RT-PCR) confirmed the significant changes in 4 of 4 mRNAs assayed (CYP1A1, HO1, GSR, CDKN1), and identified 3 additional mRNA changes; 2 redox-related genes, gamma-glutamate-cysteine ligase modifier subunit (GCLM) and thioredoxin reductase (TXNRD1) and 1 DNA replication gene, topoisomerase IIalpha (TOP2A). Temporal changes in selected mRNA levels were examined by RT-PCR over 11 time points from 15 min to 24 h postdosing. CYP1A1 exhibited a 38-fold decrease by 4 h, which rebounded to a 39-fold increase by 20 h. GCLM and TXNRD1 exhibited 13- and 9-fold increases, respectively at 24 h. Etomoxir-induced oxidative stress and impaired mitochondrial energy metabolism were confirmed by a significant decrease in reduced glutathione (GSH), reduced/oxidized glutathione ratio (GSH/GSSG), mitochondrial membrane potential (MMP), and ATP levels, and by concurrent increase in oxidized glutathione (GSSG) and superoxide generation. This is the first report of oxidative stress caused by etomoxir.

Seasonal changes in numbers and body condition of honeyeaters were examined over 2 years in the New England National Park, New South Wales, Australia. Nectar availability measured as inflorescence density and nectar production were also recorded. In the main study site, the abundance of six of the seven most common species ofhoneyeater was significantly correlated with inflorescence density. However, honeyeater numbers were not significantly correlated with daily energy productivity. Unlike most honeyeater communities, the New England community was dominated numerically by the Eastern Spinebill, the smallest of the most common species present. Among the most common species, the duration of time a species was recorded in the area was negatively, but not signifcantly, correlated with its size. All species examined showed similar seasonal changes in body condition, with the highest bodyweights and fat deposits recorded in winter.

The honeyeater community of an open-layered forest was studied in the New England National Park over a 2.5 year period. Various aspects of honeyeater behaviour (aggression, social and foraging) were examined during transects and by use of time-budgets. Time-budgets were used to estimate the daily energy requirements for each species. Since nectar availability in the study area was variable, the energy produced per day by the nectar sources was occasionally insufficient to meet the daily energy demands of the honeyeater community. No strong spatial partitioning ofthe nectar resources by the birds was found. Use ofthe resources appeared to be based primarily on dominance interactions (interspecific aggression), with the larger species tending to dominate the smaller ones. Smaller species survive in the area because of their behavioural attributes and greater foraging efficiency which enables them to use the sparse supply of nectar on poor days. Temporal gradients in nectar richness may be just as important as spatial gradients in permitting the coexistence of species which use the same resource in the same habitat. Most ofthe results from this study fail to support the predictions made elsewhere concerning the organization of communities in unpredictable environments.