Unprecedented oxidation of a biologically active aroylhydrazone chelator catalysed by iron(III): serendipitous identification of diacylhydrazine ligands with high iron chelation efficacy

Ligands of the 2-pyridylcarbaldehyde isonicotinoylhydrazone class show high iron (Fe) sequestering efficacy and have potential as agents for the treatment of Fe overload disease. We have investigated the mechanisms responsible for their high activity. X-ray crystallography studies show that the tridentate chelate 2-pyridylcarbaldehyde isonicotinoylhydrazone undergoes an unexpected oxidation to isonicotinoyl(picolinoyl)hydrazine when complexed with Fe-III. In contrast, in the absence of Fel the parent hydrazone is not oxidized in aerobic aqueous solution. To examine whether the diacylhydrazine could be responsible for the biological effects of 2-pyridylcarbaldehyde isonicotinoylhydrazone, their Fe chelation efficacy was compared. In contrast to its parent hydrazone, the diacylhydrazine showed little Fe chelation activity. Potentiometric titrations suggested that this might be because the diacylhydrazine was charged at physiological pH, hindering its access across membranes to intracellular Fe pools. In contrast, the Fe complex of this diacylhydrazine was charge neutral, which may allow facile movement through membranes. These data allow a model of Fe chelation for this compound to be proposed: the parent aroylhydrazone diffuses through cell membranes to bind Fe and is subsequently oxidized to the diacylhydrazine complex which then diffuses from the cell. Other diacylhydrazine analogues that were charge neutral at physiological pH demonstrated high Fe chelation efficacy. Thus, for this class of ligands, the charge of the chelator appears to be an important factor for determining their ability to access intracellular Fe. The results of this study are significant for understanding the biological activity of 2-pyridylcarbaldehyde isonicotinoylhydrazone and for the design of novel diacylhydrazine chelators for clinical use.

A study of the oxidation of two aromatic polyimide fluoropolymers containing phenylphosphine oxide by a water plasma and gamma-radiolysis in air

The oxidation of two fluorinated polyimides containing phenylphosphine oxide units, TOR-RC and TOR-RC ODPA, have been studied at 300 K for treatment by a water plasma and gamma -radiolysis in air. The changes in the O 1s/C 1s ratios obtained from x-ray photoelectron spectroscopy (XPS) analysis showed that for exposure to the water plasma the ratio increases at short exposure times and then levels to a constant value. Evidence for the formation of phosphate species was also obtained from the XPS analyses. Similar observations were made for gamma -radiolysis of the polymers in air. The polymers containing phenylphosphine oxide were found to be more resistant to oxidation in the water plasma than Kapton(R). Radiolysis of the polymers in air to high doses were also accompanied by a red shift in the visible absorption spectra.

PCDDs in the water/sediment-seagrass-dugong (Dugong dugon) food chain on the Great Barrier Reef (Australia)

Polychlorinated dibenzo-p-dioxin (PCDD) and dibenzofuran (PCDF) concentrations were measured in sediment and seagrass from five locations in or adjacent to the Great Barrier Reef Marine Park. A full spectrum of Cl(5-8)DDs were present in all samples and, in particular, elevated levels of Cl8DD were found. PCDFs could not be quantified in any samples. The PCDD concentrations ranged over two orders of magnitude between sites, and there was a good correlation between sediment and seagrass levels. There were large quantities of sediment present on the seagrass (20-62% on a dry wt. basis), and it was concluded that this was a primary source of the PCDDs in the seagrass samples. The PCDD levels in the seagrass samples were compared with the levels in the tissue of three dugongs stranded in the same region. The relative accumulation of the 2,3,7,8-substituted PCDD congeners in the dugongs decreased by over two orders of magnitude with increasing degree of chlorination. This was attributed to the reduced absorption of the higher chlorinated congeners in the digestive tract, a behaviour that has been observed in other mammals such as domestic cows. (C) 2001 Elsevier Science Ltd. All rights reserved.

In situ electron paramagnetic resonance (EPR) study of surface oxygen species on Au/ZnO catalyst for low-temperature carbon monoxide oxidation

Some paramagnetic superoxide ions detectable by electron paramagnetic resonance (EPR) can be generated on Au/ZnO catalyst by oxygen adsorption at room temperature as well as at 553 K. In both the cases, the O-2(-) ions are present on the catalyst surface. The disappearance of the O-2(-) signal by the introduction of carbon monoxide over the catalyst surface implies that the O-2(-) ions are either the active oxygen species or the precursors of the active oxygen species. The CO3- species produced are also detected by EPR. (C) 2001 Elsevier Science B.V. All rights reserved.

Begging and food distribution in crimson rosella (Platycercus elegans) broods: why don't hungry chicks beg more?

Altricial nestlings solicit food by begging and engaging in scramble competition. Solicitation displays can thus signal both hunger and competitive ability. I examined nestling solicitation and parental responses in crimson rosellas (Platycercus elegans), a species in which parents engage in complex patterns of food allocation and appear to control the distribution of food. By manipulating the hunger of individual chicks and entire broods, I assessed how chick behaviours and parental food allocation varied with hatching rank, level of hunger, and intensity of nestling competition. Last-hatched chicks begged more than first-hatched chicks irrespective of individual hunger levels. The two parents combined fed individually hungry chicks more, but mothers and fathers varied in their responses to begging chicks: fathers fed last-hatched chicks in proportion to their begging intensity, whereas mothers fed chicks equally. Since fathers generally allocate more food to first-hatched chicks, fathers appear to use begging rates to adjust food allocation to non-preferred chicks within the brood. When I manipulated brood hunger levels, begging rates increased for first- and last-hatched chicks suggesting that chick begging rates are sensitive to the level of competition. This study shows that begging by rosella chicks does not correlate with hunger in a straightforward way and that the primary patterns of food allocation by parents art: not influenced by chick begging. Thus the benefits of increased begging may be limited for nestlings in this species.

Specificity of 17 beta-oestradiol and benzo[a] pyrene oxidation by polymorphic human cytochrome P4501B1 variants substituted at residues 48, 119 and 432

1. Eight human cytochrome P4501B1 (CYP1B1) allelic variants, namely Arg(48)Ala(119)Leu(432), Arg(48)Ala(119)Val(432), Gly(48)Ala(119)Leu(432), Gly(48)Ala(119)Val(432), Arg(48)Ser(119)Leu(432), Arg(48)Ser(119)Val(432), Gly(48)Ser(119)Leu(432) and Gly(48)Ser(119)Val(432) (all with Asn(453)), were expressed in Escherichia coli together with human NADPH-P450 reductase and their catalytic specificities towards oxidation of 17 beta -oestradiol and benzo[a]pyrene were determined. 2. All of the CYP1B1 variants expressed in bacterial membranes showed Fe2+. CO versus Fe2+ difference spectra with wavelength maxima at 446 nm and they reacted with antibodies raised against recombinant human CYP1B1 in immunoblots. The ratio of expression of the reductase to CYP1B1 in these eight preparations ranged from 0.2 to 0.5. 3. CYP1B1 Arg(48) variants tended to have higher activities for 17 beta -oestradiol 4-hydroxylation than Gly(48) variants, although there were no significant variations in 17 beta -oestradiol 2-hydroxylation activity in these eight CYP1B1 variants. Interestingly, ratios of formation of 17 beta -oestradiol 4-hydroxylation to 2-hydroxylation by these CYP1B1 variants were higher in all of the Val(432) forms than the corresponding Leu(432) forms. 4. In contrast, Leu(432) forms of CYP1B1 showed higher rates of oxidation of benzo[a]pyrene (to the 7, 8-dihydoxy-7,8-dihydrodiol in the presence of epoxide hydrolase) than did the Val(432) forms. 5. These results suggest that polymorphic human CYP1B1 variants may cause some altered catalytic specificity with 17 beta -oestradiol and benzo[a]pyrene and may influence susceptibilities of individuals towards endogenous and exogenous carcinogens.

Relationship of high energy expenditure and variation in dietary intake with reporting accuracy on 7 day food records and diet histories in a group of healthy adult volunteers

Objectives: To assess the accuracy of reporting from both a diet history and food record and identify some of the characteristics of more accurate reporters in a group of healthy adult volunteers for an energy balance study. Design: Prospective measurements in free-living people. Setting: Wollongong, Australia. Subjects: Fifteen healthy volunteers (seven male, eight female; aged 22 -59 y; body mass index (BMI) 19 - 33 kg/m(2)) from the local community in the city of Wollongong, Australia. Interventions: Measurement of energy intake via diet history interview and 7 day food records, total energy expenditure by the doubly labelled water technique over 14 days, physical activity by questionnaire, and body fat by dual-energy X-ray absorptiometry. Results: Increased misreporting of energy intake was associated with increased energy expenditure (r = 0.90, P < 0.0001, diet history; r(s)=0.79, P=0.0005, food records) but was not associated with age, sex, BMI or body fat. Range in number of recorded dinner foods correlated positively with energy expenditure (r(s)=0.63, P=0.01) and degree of misreporting (r(s)=0.71, P=0.003, diet history; r(s)=0.63, P=0.01, food records). Variation in energy intake at dinner and over the whole day identified by the food records correlated positively with energy expenditure (r=0.58, P = 0.02) and misreporting on the diet history (r=0.62, P=0.01). Conclusions: Subjects who are highly active or who have variable dietary and exercise behaviour may be less accurate in reporting dietary intake. Our findings indicate that it may be necessary to screen for these characteristics in studies where accuracy of reporting at an individual level is critical. Sponsorship: The study was supported in part by Australian Research Council funds made available through the University of Wollongong.

Eating 'Green': Motivations behind organic food consumption in Australia

Central to the development of green lifestyles is the consumption of foods that by dint of their status as chemical-free, locally produced and/or free of genetically modified ingredients, reduce the environmental impact of food provision. Yet there are many other factors, such as health concerns, that may also encourage the consumption of 'green' foods. This paper explores the ways in which Australian consumers construct organic food-a sector of the food industry that is currently growing at between 20 and 50 percent per annum but is struggling to keep up with rising consumer demand. In order to examine the significance of 'green' signifiers in the consumption practices of Australian consumers a series of focus group interviews and a national consumer survey were conducted. These examined both those characteristics of food that were valued in general, and those meanings that were associated with organic food in particular. In very general terms, analysis reveals that while consumers believed organic foods to be healthy and environmentally sound-both of which were considered desirable-these characteristics were subsumed by an overarching concern with convenience. This does not mean that consumers did not hold genuinely positive environmental attitudes. Rather, it reflects a range of contradictory beliefs and practices that appeared to derive from the discursive conflict between conventional and organic food industries over environmental, health and safety claims. The paper concludes by identifying the barriers and opportunities for expanding the organic industry in Australia in the context of the ways organics is constructed by consumers.

The measurement of actual acidity in acid sulfate soils and the determination of sulfidic acidity in suspension after peroxide oxidation

Improvements to the routine methods for the determination of actual acidity in suspension for acid sulfate soils (ASS) are introduced. The titratable sulfidic acidity (TSA) results using an improved peroxide-based method were compared with the theoretical acidity predicted by the chromium reducible sulfur method for 9 acid sulfate soils. The regression between these 2 measures of sulfidic acidity was highly significant, the slope of the regression line not significantly different from unity (P = 0.05) and the intercept not significantly different from zero. This contrasts with results of other workers using earlier peroxide oxidation methods, where TSA substantially underestimated the theoretical acidity predicted by reduced inorganic sulfur analysis. Comparison was made between the 2 principal measurements from the improved peroxide method (TSA and S-POS), with S-POS converted to theoretical sulfidic acidity to allow comparison. The relationship between these 2 measurements was highly significant. The effects of titration in suspension, as well as raising titration end points to pH 6.5, were investigated, principally with respect to the titratable actual acidity (TAA) result. TAA results obtained by KCl extraction were compared with those obtained using BaCl2, MgCl2, and water extraction. TAA in 1 M KCl suspensions titrated to pH 6.5 agreed well with titratable actual acidity measured using the 25-h extraction approach of the Lin et al. (2000a) BaCl2 method. Both BaCl2 and KCl solutions were ineffective at fully recovering acidity from synthetic jarosite without repeated extraction and titration. The application of correction factors for the estimation of total actual acidity in ASS is not supported by the results of this investigation. Acid sulfate soils that contain substantial quantities of jarosite or other acid-producing but relatively insoluble sulfate minerals continue to prove problematic to chemically analyse; however, an approach for estimating this component is discussed.