Evaluation of the toxicity of a substituted 2,4-thiazolidinedione moiety to isolated rat hepatocytes : relevance to glitazone toxicity

Troglitazone (TGZ), a 2,4 thiazolidinedione (TZD) anti-diabetic agent, has been associated with hepatotoxicity in type II diabetic patients. The mechanism of toxicity has not yet been established. However, it has been reported (Kennedy et al., 2003) that the incorporation of a sulphur atom in the cyclic imide structure of N-(3,5-dichlorophenyl)succinimide (NDPS), analogous to the 2,4-TZD moiety in TGZ, resulted in hepatotoxicity. In this study we have examined the relative in vitro hepatotoxicity of 3-(3,5-dichlorophenyl)-2,4,thiazolidinedione (DCPT), which contains the 2,4-TZD moiety, and that of its structural analogue NDPS. NDPS and DCPT were synthesised using a modification of the method of Fujinami et al (1971) and characterised by NMR and mass spectrometry. Hepatocytes were prepared from male Sprague-Dawley rats (180-220g), and cell viability was measured using Trypan Blue exclusion. Preparations with initial cell viability above 80% were used in all experiments. Cells were incubated for 3 hours with NDPS and DCPT at (0μM, 100μM, 500μM and 1mM in dimethylsulphoxide (0.1% (v/v)) at 37oC in an atmosphere of 95%O2/5%CO2). Samples were taken at regular time intervals (0, 15, 30, 60 90, 120, 180 minutes) for the measurement of viability, reduced glutathione (GSH) content and lactate dehydrogenase (LDH) activity in the extracellular medium. Statistical analyses (ANOVA followed by Dunnett’s test) of the data (Table 1) obtained for hepatocytes exposed to DCPT and NDPS did not reveal significant differences in GSH content, LDH activity or cell viability over a 3h incubation period. These data indicate that the incorporation of a sulphur atom in the succinamide ring of NDPS to produce the corresponding 2,4 TZD (DCPT) does not result in an increase in hepatotoxic effects in vitro. This finding, together with our previous report on the lack of toxicity of the 2,4-TZD containing, rosiglitazone (Ball et al 2004 ), would suggest that a chemical mechanism of toxicity of TGZ (if feasible) might be a function of the whole molecule rather than the TZD moiety alone

Lithological and facies analysis of the Roseneath and Murteree shales, Cooper Basin, Australia

Unconventional shale plays have received marked attention over the last five years because of their economic potential for hydrocarbon generation, and yet they are amongst the least understood of all clastic sedimentary rock systems. The Cooper Basin is one of the largest Gondwana intracratonic basins in Australia, extending from northern South Australia into south-western Queensland and covering approximately 130,000 km2. The basin is may be prospective for shale gas, particularly within the lacustrine shales of the Permian Murteree and Roseneath formations. This study investigates lithological characteristics of these two units in relation to reservoir evaluation. Core samples representing the Dirkala-02 and Moomba-46 wells were used for petrographic analysis. A combination of wireline log analysis, thin section petrography, X-ray diffraction and pyrolysis analysis was used to define and characterize four distinct lithofacies facies within the Roseneath and Murteree shales: siliceous mudstone, organic siliceous mudstone, calcareous siliceous mudstone, and silty siliceous mudstone. The siliceous mudstone and organic siliceous mudstone are the most common. Diagenetic siderite occurs in all four lithofacies. A conceptual depositional model is developed for deposition of the Roseneath and Murteree shales. Wireline-log cross plots were interpreted and utilized in the construction of electrofacies. The study was concentrated on the northern portion of the basin between the Nappameri and Patchawarra Troughs in order to understand the nature of lithofacies and variability in reservoir architecture, which was controlled by relative lake level fluctuation. The results of this study will aid in the evaluation of shale gas potential for this portion of the basin, as well as a better understanding of shale gas opportunities in the Cooper Basin more generally

Hard-Sphere Fluids in Contact with Curved Substrates

The properties of a hard-sphere fluid in contact with hard spherical and cylindrical walls are studied. Rosenfeld's density functional theory (DFT) is applied to determine the density profile and surface tension $\gamma$ for wide ranges of radii of the curved walls and densities of the hard-sphere fluid. Particular attention is paid to investigate the curvature dependence and the possible existence of a contribution to $\gamma$ that is proportional to the logarithm of the radius of curvature. Moreover, by treating the curved wall as a second component at infinite dilution we provide an analytical expression for the surface tension of a hard-sphere fluid close to arbitrary hard convex walls. The agreement between the analytical expression and DFT is good. Our results show no signs for the existence of a logarithmic term in the curvature dependence of $\gamma$.Comment: 15 pages, 6 figure

Speleothems Reveal 500,000-year History of Siberian Permafrost

Soils in permafrost regions contain twice as much carbon as the atmosphere, and permafrost has an important influence on the natural and built environment at high northern latitudes. The response of permafrost to warming climate is uncertain and occurs on time scales longer than those assessed by direct observation. We dated periods of speleothem growth in a north-south transect of caves in Siberia to reconstruct the history of permafrost in past climate states. Speleothem growth is restricted to full interglacial conditions in all studied caves. In the northernmost cave (at 60°N), no growth has occurred since Marine Isotopic Stage (MIS) 11. Growth at that time indicates that global climates only slightly warmer than today are sufficient to thaw extensive regions of permafrost

Penultimate Deglacial Sea-Level Timing from Uranium/Thorium Dating of Tahitian Corals

The timing of sea-level change provides important constraints on the mechanisms driving Earth's climate between glacial and interglacial states. Fossil corals constrain the timing of past sea level by their suitability for dating and their growth position close to sea level. The coral-derived age for the last deglaciation is consistent with climate change forced by Northern Hemisphere summer insolation (NHI), but the timing of the penultimate deglaciation is more controversial. We found, by means of uranium/thorium dating of fossil corals, that sea level during the penultimate deglaciation had risen to similar to 85 meters below the present sea level by 137,000 years ago, and that it fluctuated on a millennial time scale during deglaciation. This indicates that the penultimate deglaciation occurred earlier with respect to NHI than the last deglacial, beginning when NHI was at a minimum

A fully integrated GIS-based model of particulate waste distribution from marine fish-cage sites

Modern Geographical Information System (GIS) offers a powerful modelling environment capable of handling large databases. It is a very suitable environment in which to develop a suite of tools designed for environmental management of aquaculture sites, including carrying capacity prediction, land–water interactions and multi-site effects. One such tool, presented here, is a fully integrated and validated particulate fish waste dispersion module which uses mass balance to estimate waste input and takes account of variable bathymetry and variable settling velocity for feed and faecal components. The model also incorporates the effect of cage movement on waste dispersion, the first such model to do so. When tidal range was low (1.67 m), the maximum movement of a 22 m diameter circular cage was 10.1 m and 7.7 m easting and northing, respectively. Highest deposition from particulate fish waste is under the cage and incorporation of cage movement increased the effective area under a cage by 72%. This reduced peak deposition measurements by up to 32% and reduced the average modelled feed and faecal settlement at the cage centre by 23% and 11%, respectively. The model was validated by comparing model predictions with observed deposition measured using sediment traps during three 2-week field trips at a fish farm on the west coast of Scotland. The mean ratio of observed to predicted waste deposition at 5–25 m from the cage centre ranged from 0.9 to 1.06, whilst under the cage the model over-predicts deposition (observed/predicted=2.21). Although far-field data was seen to be comparable the near-field discrepancies resulted in variable overall accuracy in the model. The overall accuracy based on August 2001 data was ±50.9%, on February 2002, ±72.8% and on April 2002, ±50.6%. Summarizing the data resulted in an overall average predictive accuracy of ±58.1%. © 2006 Elsevier B.V. All rights reserved

Influence of childhood growth on asthma and lung function in adolescence

Background Low birth weight and rapid infant growth in early infancy are associated with increased risk of childhood asthma, but little is known about the role of postinfancy growth in asthmatic children. Objectives We sought to examine the associations of children's growth patterns with asthma, bronchial responsiveness, and lung function until adolescence. Methods Individual growth trajectories from birth until 10 years of age were estimated by using linear spline multilevel models for 9723 children participating in a population-based prospective cohort study. Current asthma at 8, 14, and 17 years of age was based on questionnaires. Lung function and bronchial responsiveness or reversibility were measured during clinic visits at 8 and 15 years of age. Results Rapid weight growth between 0 and 3 months of age was most consistently associated with increased risks of current asthma at the ages of 8 and 17 years, bronchial responsiveness at age 8 years, and bronchial reversibility at age 15 years. Rapid weight growth was associated with lung function values, with the strongest associations for weight gain between 3 and 7 years of age and higher forced vital capacity (FVC) and FEV1 values at age 15 years (0.12 [95% CI, 0.08 to 0.17] and 0.11 [95% CI, 0.07 to 0.15], z score per SD, respectively) and weight growth between 0 and 3 months of age and lower FEV1/FVC ratios at age 8 and 15 years (-0.13 [95% CI, -0.16 to -0.10] and -0.04 [95% CI, -0.07 to -0.01], z score per SD, respectively). Rapid length growth was associated with lower FVC and FVC1 values at age 15 years. Conclusion Faster weight growth in early childhood is associated with asthma and bronchial hyperresponsiveness, and faster weight growth across childhood is associated with higher FVC and FEV1 values

Mineralogical variability of the Permian Roseneath and Murteree Shales from the Cooper Basin, Australia: Implications for shale properties and hydrocarbon extraction

Brittleness and plasticity indices in hydrocarbon reservoirs are calculated to understand how rocks behave under stress, and for assessing the fracturing performance of clay-rich shale reservoirs and assessing borehole stability. Evaluating shale plasticity/brittleness requires careful analysis of clay mineral composition in target shales and the development of fracking strategies for optimal shale stimulation. Here we report on the mineralogical variability of two Permian lacustrine shale units, the Roseneath and Murteree shales in the Cooper Basin, Australia, that are considered to have potential as unconventional hydrocarbon producers. The study involved a combination of X-ray diffraction, scanning electron microscopy and petrophysical modelling of the Roseneath and Murteree shales in order to obtain a better understanding of the compositions and microfabrics of these two units. This is part of a larger investigation of the shale gas potential of these two units in the Cooper Basin, and the results presented here may ultimately lead to improved reservoir stimulation techniques in both units. Core data has been integrated with wireline logging data to better identify brittle and plastic zones within the Roseneath and Murteree shales. Mineralogical analysis shows that both units are composed mainly of detrital quartz and clay/mica minerals with siderite cement. The clay mineral composition is dominated by illite/mica, and kaolinite in both units. However, based on the relative mineralogical differences between the two units, the Murteree Shale has more favourable brittle properties than the Roseneath Shale, and is considered to be more amenable to hydraulic fracturing for gas exploitation. However, the Roseneath Shale also has potential for gas stimulation, especially in intervals where siderite cement is prevalent

Seasonal trends and phenology shifts in sea surface temperature on the North American northeastern continental shelf

The northeastern North American continental shelf from Cape Hatteras to the Scotian Shelf is a region of globally extreme positive trends in sea surface temperature (SST). Here, a 33-year (1982–2014) time series of daily satellite SST data was used to quantify and map spatial patterns in SST trends and phenology over this shelf. Strongest trends are over the Scotian Shelf (>0.6°C decade –1 ) and Gulf of Maine (>0.4°C decade –1 ) with weaker trends over the inner Mid-Atlantic Bight (~0.3°C decade –1 ). Winter (January–April) trends are relatively weak, and even negative in some areas; early summer (May–June) trends are positive everywhere, and later summer (July–September) trends are strongest (~1.0°C decade –1 ). These seasonal differences shift the phenology of many metrics of the SST cycle. The yearday on which specific temperature thresholds (8° and 12°C) are reached in spring trends earlier, most strongly over the Scotian Shelf and Gulf of Maine (~ –0.5 days year –1 ). Three metrics defining the warmest summer period show significant trends towards earlier summer starts, later summer ends and longer summer duration over the entire study region. Trends in start and end dates are strongest (~1 day year –1 ) over the Gulf of Maine and Scotian Shelf. Trends in increased summer duration are >2.0 days year –1 in parts of the Gulf of Maine. Regression analyses show that phenology trends have regionally varying links to the North Atlantic Oscillation, to local spring and summer atmospheric pressure and air temperature and to Gulf Stream position. For effective monitoring and management of dynamically heterogeneous shelf regions, the results highlight the need to quantify spatial and seasonal differences in SST trends as well as trends in SST phenology, each of which likely has implications for the ecological functioning of the shelf