Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude

Amphiphilic chitosan-based polymers (M-w < 20 kDa) self-assemble in aqueous media at low micromolar concentrations to give previously unknown micellar clusters of 100-300 nm in size. Micellar clusters comprise smaller 10-30 nm aggregates, and the nanopolarity/drug incorporation efficiency of their hydrophobic domains can be tailored by varying the degree of lipidic derivatization and molecular weight of the carbohydrate. The extent of drug incorporation by these novel micellar clusters is 1 order of magnitude higher than is seen with triblock copolymers, with molar polymer/drug ratios of 1:48 to 1:67. On intravenous injection, the pharmacodynamic activity of a carbohydrate propofol formulation is increased by 1 order of magnitude when compared to a commercial emulsion formulation, and on topical ocular application of a carbohydrate prednisolone formulation, initial drug aqueous humor levels are similar to those found with a 10-fold dose of prednisolone suspension.

NOx and O3 above a tropical rainforest: an analysis with a global and box model

A cross-platform field campaign, OP3, was conducted in the state of Sabah in Malaysian Borneo between April and July of 2008. Among the suite of observations recorded, the campaign included measurements of NOx and O3 – crucial outputs of any model chemistry mechanism. We describe the measurements of these species made from both the ground site and aircraft. We then use the output from two resolutions of the chemistry transport model p-TOMCAT to illustrate the ability of a global model chemical mechanism to capture the chemistry at the rainforest site. The basic model performance is good for NOx and poor for ozone. A box model containing the same chemical mechanism is used to explore the results of the global model in more depth and make comparisons between the two. Without some parameterization of the nighttime boundary layer – free troposphere mixing (i.e. the use of a dilution parameter), the box model does not reproduce the observations, pointing to the importance of adequately representing physical processes for comparisons with surface measurements. We conclude with a discussion of box model budget calculations of chemical reaction fluxes, deposition and mixing, and compare these results to output from p-TOMCAT. These show the same chemical mechanism behaves similarly in both models, but that emissions and advection play particularly strong roles in influencing the comparison to surface measurements.

Free amino acids and sugars in rye grain: implications for acrylamide formation

Acrylamide forms from free asparagine and sugars during cooking, and products derived from the grain of cereals, including rye, contribute a large proportion of total dietary intake. In this study, free amino acid and sugar concentrations were measured in the grain of a range of rye varieties grown at locations in Hungary, France, Poland, and the United Kingdom and harvested in 2005, 2006, and 2007. Genetic and environmental (location and harvest year) effects on the levels of acrylamide precursors were assessed. The data showed free asparagine concentration to be the main determinant of acrylamide formation in heated rye flour, as it is in wheat. However, in contrast to wheat, sugar, particularly sucrose, concentration also correlated both with asparagine concentration and with acrylamide formed. Free asparagine concentration was shown to be under genetic (G), environmental (E), and integrated (G × E) control. The same was true for glucose, whereas maltose and fructose were affected mainly by environmental factors and sucrose was largely under genetic control. The ratio of variation due to varieties (genotype) to the total variation (a measure of heritability) for free asparagine concentration in the grain was 23%. Free asparagine concentration was closely associated with bran yield, whereas sugar concentration was associated with low Hagberg falling number. Rye grain was found to contain much higher concentrations of free proline than wheat grain, and less acrylamide formed per unit of asparagine in rye than in wheat flour.

Aroma compounds in French fries from three potato varieties

Sugars and free amino acids were measured in three potato varieties widely available in the United Kingdom. French fries were cooked for 6, 9 and 12 min at 180°C, and the effects of cooking time and variety on volatile composition were examined. Maillard reaction-derived aroma compounds increased as cooking time increased. Varieties Desiree and Maris Piper were relatively high in sugars and aroma compounds derived from sugars, e.g. 5-methylfurfural and dihydro-2-methyl- 3[2H]-furanone, whereas variety King Edward was relatively high in free amino acids and their associated aroma compounds, such as pyrazines and Strecker aldehydes.

Variation in acrylamide producing potential in potato: Segregation of the trait in a breeding population

Acrylamide is a neurotoxin and possible carcinogen, and concern has been voiced over human exposure to acrylamide in cooked foods. Processed potato products such as crisps and French fries are often cited as being particularly high in acrylamide. In this manuscript a sub-set of clonal progeny from a specific tetraploid potato breeding population has been assessed for acrylamide forming potential in stored tubers processed into crisps. The clone with the lowest acrylamide content in crisps had both low reducing sugars and asparagine contents. Our data show that, in the segregating breeding population used, both asparagine and reducing sugars levels needed to be taken into account to explain most of the variation in acrylamide and that selection for low levels of both metabolites should be targeted for crop improvement.

The sea-level conundrum: case studies from palaeo-archives

Uncertainties in sea-level projections for the 21st century have focused ice sheet modelling efforts to include the processes that are thought to be contributing to the recently observed rapid changes at ice sheet margins. This effort is still in its infancy, however, leaving us unable to make reliable predictions of ice sheet responses to a warming climate if such glacier accelerations were to increase in size and frequency. The geological record, however, has long identified examples of nonlinear ice sheet response to climate forcing (Shackleton NJ, Opdyke ND. 1973. Oxygen isotope and paleomagnetic stratigraphy of equatorial Pacific core V28–239, late Pliocene to latest Pleistocene. Geological Society of America Memoirs145: 449–464; Fairbanks RG. 1989. A 17,000 year glacio-eustatic sea level record: influence of glacial melting rates on the Younger Dryas event and deep ocean circulation. Nature342: 637–642; Bard E, Hamelin B, Arnold M, Montaggioni L, Cabioch G, Faure G, Rougerie F. 1996. Sea level record from Tahiti corals and the timing of deglacial meltwater discharge. Nature382: 241–244), thus suggesting an alternative strategy for constraining the rate and magnitude of sea-level change that we might expect by the end of this century. Copyright © 2009 John Wiley & Sons, Ltd.

Rapid topographic change measured by high-resolution satellite radar at Soufriere Hills Volcano, Montserrat, 2008-2010

High-resolution satellite radar observations of erupting volcanoes can yield valuable information on rapidly changing deposits and geomorphology. Using the TerraSAR-X (TSX) radar with a spatial resolution of about 2 m and a repeat interval of 11-days, we show how a variety of techniques were used to record some of the eruptive history of the Soufriere Hills Volcano, Montserrat between July 2008 and February 2010. After a 15-month pause in lava dome growth, a vulcanian explosion occurred on 28 July 2008 whose vent was hidden by dense cloud. We were able to show the civil authorities using TSX change difference images that this explosion had not disrupted the dome sufficient to warrant continued evacuation. Change difference images also proved to be valuable in mapping new pyroclastic flow deposits: the valley-occupying block-and-ash component tending to increase backscatter and the marginal surge deposits reducing it, with the pattern reversing after the event. By comparing east- and west-looking images acquired 12 hours apart, the deposition of some individual pyroclastic flows can be inferred from change differences. Some of the narrow upper sections of valleys draining the volcano received many tens of metres of rockfall and pyroclastic flow deposits over periods of a few weeks. By measuring the changing shadows cast by these valleys in TSX images the changing depth of infill by deposits could be estimated. In addition to using the amplitude data from the radar images we also used their phase information within the InSAR technique to calculate the topography during a period of no surface activity. This enabled areas of transient topography, crucial for directing future flows, to be captured.

Contribution of apolipoprotein E genotype and docosahexaenoic acid to the LDL-cholesterol response to fish oil

Objectives: To investigate the impact of apolipoprotein E (apoE) genotype on the response of the plasma lipoprotein profile to eicosapentaenoic acid (EPA) versus docosahexaenoic acid (DHA) intervention in humans. Methods and results: 38 healthy normolipidaemic males, prospectively recruited on the basis of apoE genotype (n = 20 E3/E3 and n = 18 E3/E4), completed a double-blind placebo-controlled cross-over trial, consisting of 3 × 4 week intervention arms of either control oil, EPA-rich oil (ERO, 3.3 g EPA/day) or DHA-rich oil (DRO, 3.7 g DHA/day) in random order, separated by 10 week wash-out periods. A significant genotype-independent 28% and 19% reduction in plasma triglycerides in response to ERO and DRO was observed. For total cholesterol (TC), no significant treatment effects were evident; however a significant genotype by treatment interaction emerged (P = 0.045), with a differential response to ERO and DRO in E4 carriers. Although the genotype × treatment interaction for LDL-cholesterol (P = 0.089) did not reach significance, within DRO treatment analysis indicated a 10% increase in LDL (P = 0.029) in E4 carriers with a non-significant 4% reduction in E3/E3 individuals. A genotype-independent increase in LDL mass was observed following DRO intervention (P = 0.018). Competitive uptake studies in HepG2 cells using plasma very low density lipoproteins (VLDL) from the human trial, indicated that following DRO treatment, VLDL2 fractions obtained from E3/E4 individuals resulted in a significant 32% (P = 0.002) reduction in LDL uptake relative to the control. Conclusions: High dose DHA supplementation is associated with increases in total cholesterol in E4 carriers, which appears to be due to an increase in LDL-C and may in part negate the cardioprotective action of DHA in this population subgroup.