Marked elevation in cortical urate and xanthine oxidoreductase activity in experimental bacterial meningitis

Experimental bacterial meningitis due to Streptococcus pneumoniae in infant rats was associated with a time-dependent increase in CSF and cortical urate that was approximately 30-fold elevated at 22 h after infection compared to baseline. This increase was mirrored by a 20-fold rise in cortical xanthine oxidoreductase activity. The relative proportion of the oxidant-producing xanthine oxidase to total activity did not increase, however. Blood plasma levels of urate also increased during infection, but part of this was as a consequence of dehydration, as reflected by elevated ascorbate concentrations in the plasma. Administration of the radical scavenger alpha-phenyl-tert-butyl nitrone, previously shown to be neuroprotective in the present model, did not significantly affect either xanthine dehydrogenase or xanthine oxidase activity, and increased even further cortical accumulation of urate. Treatment with the xanthine oxidoreductase inhibitor allopurinol inhibited CSF urate levels earlier than those in blood plasma, supporting the notion that urate was produced within the brain. However, this treatment did not prevent the loss of ascorbate and reduced glutathione in the cortex and CSF. Together with data from the literature, the results strongly suggest that xanthine oxidase is not a major cause of oxidative stress in bacterial meningitis and that urate formation due to induction of xanthine oxidoreductase in the brain may in fact represent a protective response

An efficient and accurate representation of complex oceanic and biospheric models of anthropogenic carbon uptake

Establishing the link between atmospheric CO2 concentration and anthropogenic carbon emissions requires the development of complex carbon cycle models of the primary sinks, the ocean and terrestrial biosphere. Once such models have been developed, the potential exists to use pulse response functions to characterize their behaviour. However, the application of response functions based on a pulse increase in atmospheric CO2 to characterize oceanic uptake, the conventional technique, does not yield a very accurate result due to nonlinearities in the aquatic carbon chemistry. Here, we propose the use of an ocean mixed-layer pulse response function that characterizes the surface to deep ocean mixing in combination with a separate equation describing air-sea exchange. The use of a mixed-layer pulse response function avoids the problem arising from the nonlinearities of the carbon chemistry and gives therefore more accurate results. The response function is also valid for tracers other than carbon. We found that tracer uptake of the HILDA and Box-Diffusion model can be represented exactly by the new method. For the Princeton 3-D model, we find that the agreement between the complete model and its pulse substitute is better than 4% for the cumulative uptake of anthropogenic carbon for the period 1765–2300 applying the IPCC stabilization scenarios S450 and S750 and better than 2% for the simulated inventory and surface concentration of bomb-produced radiocarbon. By contrast, the use of atmospheric response functions gives deviations up to 73% for the cumulative CO2uptake as calculated with the Princeton 3-D model. We introduce the use of a decay response function for calculating the potential carbon storage on land as a substitute for terrestrial biosphere models that describe the overturning of assimilated carbon. This, in combination with an equation describing the net primary productivity permits us to exactly characterize simple biosphere models. As the time scales of biospheric overturning are one key aspect to determine the amount of anthropogenic carbon which might be sequestered by the biosphere, we suggest that decay response functions should be used as a simple and standardized measure to compare different models and to improve understanding of their behaviour. We provide analytical formulations for mixed-layer and terrestrial biosphere decay pulse response functions which permit us to easily build a substitute for the ‘Bern’ carbon cycle model (HILDA). Furthermore, mixed-layer response functions for the Box-Diffusion, a 2-D model, and the Princeton 3-D model are given

Oxidative stress in brain during experimental bacterial meningitis: differential effects of alpha-phenyl-tert-butyl nitrone and N-acetylcysteine treatment

Antioxidant treatment has previously been shown to be neuroprotective in experimental bacterial meningitis. To obtain quantitative evidence for oxidative stress in this disease, we measured the major brain antioxidants ascorbate and reduced glutathione, and the lipid peroxidation endproduct malondialdehyde in the cortex of infant rats infected with Streptococcus pneumoniae. Cortical levels of the two antioxidants were markedly decreased 22 h after infection, when animals were severely ill. Total pyridine nucleotide levels in the cortex were unaltered, suggesting that the loss of the two antioxidants was not due to cell necrosis. Bacterial meningitis was accompanied by a moderate, significant increase in cortical malondialdehyde. While treatment with either of the antioxidants alpha-phenyl-tert-butyl nitrone or N-acetylcysteine significantly inhibited this increase, only the former attenuated the loss of endogenous antioxidants. Cerebrospinal fluid bacterial titer, nitrite and nitrate levels, and myeloperoxidase activity at 18 h after infection were unaffected by antioxidant treatment, suggesting that they acted by mechanisms other than modulation of inflammation. The results demonstrate that bacterial meningitis is accompanied by oxidative stress in the brain parenchyma. Furthermore, increased cortical lipid peroxidation does not appear to be the result of parenchymal oxidative stress, because it was prevented by NAC, which had no effect on the loss of brain antioxidants

Estimates of anthropogenic carbon uptake from four three-dimensional global ocean models

We have compared simulations of anthropogenic CO$_2$ in the four threedimensional ocean models that participated in the first phase of the Ocean Carbon-Cycle Model Intercomparison Project (OCMIP), as a means to identify their major differences.Simulated global uptake agrees to within $\pm$19%, giving a range of 1.85$\pm$0.35 PgC yr$^{-1}$ for the 1980-1989 average. Regionally, the Southern Ocean dominates the present-day air-sea flux of anthropogenic CO$_2$ in all models, with one third to one half of the global uptake occurring south of 30°S. The highest simulated total uptake in the Southern Ocean was 70% larger than the lowest. Comparison with recent data-based estimates of anthropogenic CO$_2$ suggesthat most of the models substantially overestimate storage in the Southern Ocean; elsewhere they generally underestimate storage by less than 20%. Globally, the OCMIP models appear to bracket the real ocean's present uptake, based on comparison of regional data-basedstimates of anthropogenic CO$_2$ and bomb $^{14}$C. Column inventories of bomb $^{14}$C have become more similar to those for anthropogenic CO$_2$ with the time that has elapsed between the Geochemical Ocean Sections Study (1970s) and Word Ocean Circulation Experiment (1990s) global sampling campaigns. Our ability to evaluate simulated anthropogenic CO$_2$ would improve if systematic errors associated with the data-based estimates could be provided regionally

Interannual variability of the oceanic sink of CO₂ from 1979 through 1997

International audienceWe have estimated the interannual variability in the oceanic sink of CO2 with a three-dimensional global-scale model which includes ocean circulation and simple biogeochemistry. The model was forced from 1979 to 1997 by a combination of daily to weekly data from the European Center for Medium-Range Weather Forecast and the National Centers for Environmental Prediction/National Center for Atmospheric Research reanalysis as well as European Remote Sensing satellite observations. For this period, the ocean sink of CO2 is estimated to vary between 1.4 and 2.2 Pg C yr-1, as a result of annually averaged interannual variability of +/-0.4 Pg C yr-1 that fluctuates about a mean of 1.8 Pg C yr-1. Our interannual variability roughly agrees in amplitude with previous ocean-based estimates but is 2 to 4 times less than estimates based on atmospheric observations. About 70% of the global variance in our modeled flux of CO2 originated in the equatorial Pacific. In that region, our modeled variability in the flux of CO2 generally agreed with that observed to +/-0.1 Pg C yr-1. The predominance of the equatorial Pacific for interannual variability is caused by three factors: (1) interannual variability associated with El Niño events occurs in phase over the entire basin, whereas elsewhere positive and negative anomalies partly cancel each other out (e.g., for events such as Antarctic Circumpolar Wave and the North Atlantic Oscillation); (2) dynamic processes dominate in the equatorial Pacific, whereas dynamic, thermodynamic, and biological processes partly cancel one another at higher latitudes; and (3) our model underestimates the variability in ocean dynamics and biology at high latitudes

Glutathione peroxidase overexpression causes aberrant ERK activation in neonatal mouse cortex after hypoxic preconditioning

Preconditioning of neonatal mice with nonlethal hypoxia (HPC) protects the brain from hypoxic-ischemic (HI) injury. Overexpression of human glutathione peroxidase 1 (GPx1), which normally protects the developing murine brain from HI injury, reverses HPC protection, suggesting that a certain threshold of hydrogen peroxide concentration is required for activation of HPC signaling

Dust impact on marine biota and atmospheric CO2 during glacial periods

We assess the impact of high dust deposition rates on marine biota and atmospheric CO2 using a state-of-the-art ocean biogeochemistry model and observations. Our model includes an explicit representation of two groups of phytoplankton and colimitation by iron, silicate, and phosphate. When high dust deposition rates from the Last Glacial Maximum (LGM) are used as input, our model shows an increase in the relative abundance of diatoms in today's iron-limited regions, causing a global increase in export production by 6% and an atmospheric CO2 drawdown of 15 ppm. When the combined effects of changes in dust, temperature, ice cover, and circulation are included, the model reproduces roughly our reconstruction of regional changes in export production during the LGM based on several paleoceanographic indicators. In particular, the model reproduces the latitudinal dipole in the Southern Ocean, driven in our simulations by the conjunction of dust, sea ice, and circulation changes. In the North Pacific the limited open ocean data suggest that we correctly simulate the eastwest gradient in the open ocean, but more data are needed to confirm this result. From our model-data comparison and from the timing of the dust record at Vostok, we argue that our model estimate of the role of dust is realistic and that the maximum impact of high dust deposition on atmospheric CO2 must b