Role of calcium in inflammation: Relevance to Alzheimer's disease

Alzheimer’s disease (AD) is neuropathologically characterized by excessive beta -amyloid (Aβ) plaques and neurofibrillary tangles composed of hyperphosphorylated tau in the brain. Although the etiology of genetic cases of AD has been attributed to mutations in presenilin and amyloid precursor protein (APP) genes, in most sporadic cases of AD, the etiology is still unknown and various predisposing factors could contribute to the pathology of AD. Predominant among these possible predisposing factors that have been implicated in AD are age, hypertension, traumatic brain injury, diabetes, chronic neuroinflammation, alteration in calcium levels and oxidative stress. Since both inflammation and altered calcium levels are implicated in the pathogenesis of AD, we wanted to study the effect of altered levels of calcium on inflammation and the subsequent effect of selective calcium channel blockers on the production of pro-inflammatory cytokines and chemokines. Our hypothesis is that Aβ, depending on it conformation, may contribute to altered levels of intracellular calcium in neurons and glial cells. We wanted to determine which conformation of Aβ was most pathogenic in terms of increasing inflammation and calcium influx and further elucidate the possibility of a link between altered calcium levels and inflammation. In addition, we wanted to test whether calcium channel blockers could inhibit the inflammation mediated by the most pathogenic form of Aβ, by antagonizing the calcium influx triggered by Aβ. Our results in human glial and neuronal cells demonstrate that the high molecular weight oligomers are the most potent at stimulating the release of pro-inflammatory cytokines IL-6 and IL-8 as well as increasing intracellular levels of calcium compared to other conformations of Aβ. Further, L-type calcium channel blockers and calmodulin kinase inhibitors are able to significantly reduce the levels of IL-6 and IL-8. These results suggest that Aβ-induced alteration of intracellular calcium levels contributes to its pro-inflammatory effect.

The role of recharge and evapotranspiration as hydraulic drivers of ion concentrations in shallow groundwater on Everglades tree islands, Florida (USA)

Recently, evapotranspiration has been hypothesized to promote the secondary formation of calcium carbonate year-round on tree islands in the Everglades by influencing groundwater ions concentrations. However, the role of recharge and evapotranspiration as drivers of shallow groundwater ion accumulation has not been investigated. The goal of this study is to develop a hydrologic model that predicts the chloride concentrations of shallow tree island groundwater and to determine the influence of overlying biomass and underlying geologic material on these concentrations. Groundwater and surface water levels and chloride concentrations were monitored on eight constructed tree islands at the Loxahatchee Impoundment Landscape Assessment (LILA) from 2007 to 2010. The tree islands at LILA were constructed predominately of peat, or of peat and limestone, and were planted with saplings of native tree species in 2006 and 2007. The model predicted low shallow groundwater chloride concentrations when inputs of regional groundwater and evapotranspiration-to-recharge rates were elevated, while low evapotranspiration-to-recharge rates resulted in a substantial increase of the chloride concentrations of the shallow groundwater. Modeling results indicated that evapotranspiration typically exceeded recharge on the older tree islands and those with a limestone lithology, which resulted in greater inputs of regional groundwater. A sensitivity analysis indicated the shallow groundwater chloride concentrations were most sensitive to alterations in specific yield during the wet season and hydraulic conductivity in the dry season. In conclusion, the inputs of rainfall, underlying hydrologic properties of tree islands sediments and forest structure may explain the variation in ion concentration seen across Everglades tree islands.

The Role of Recharge and Evapotranspiration as Hydraulic Drivers of Ion Concentrations in Shallow Groundwater on Everglades Tree Islands, Florida (USA)

Recently, evapotranspiration has been hypothesized to promote the secondary formation of calcium carbonate year-round on tree islands in the Everglades by influencing groundwater ions concentrations. However, the role of recharge and evapotranspiration as drivers of shallow groundwater ion accumulation has not been investigated. The goal of this study is to develop a hydrologic model that predicts the chloride concentrations of shallow tree island groundwater and to determine the influence of overlying biomass and underlying geologic material on these concentrations. Groundwater and surface water levels and chloride concentrations were monitored on eight constructed tree islands at the Loxahatchee Impoundment Landscape Assessment (LILA) from 2007 to 2010. The tree islands at LILA were constructed predominately of peat, or of peat and limestone, and were planted with saplings of native tree species in 2006 and 2007. The model predicted low shallow groundwater chloride concentrations when inputs of regional groundwater and evapotranspiration-to-recharge rates were elevated, while low evapotranspiration-to-recharge rates resulted in a substantial increase of the chloride concentrations of the shallow groundwater. Modeling results indicated that evapotranspiration typically exceeded recharge on the older tree islands and those with a limestone lithology, which resulted in greater inputs of regional groundwater. A sensitivity analysis indicated the shallow groundwater chloride concentrations were most sensitive to alterations in specific yield during the wet season and hydraulic conductivity in the dry season. In conclusion, the inputs of rainfall, underlying hydrologic properties of tree islands sediments and forest structure may explain the variation in ion concentration seen across Everglades tree islands.

Effect of pH and temperature on the carbonate promoted dissolution of sodium meta-autunite

Release of uranium from Na-autunite, an artificial mineral created as a result of polyphosphate injection in the subsurface at the DOE Hanford Site, takes place during slow dissolution of the mineral structure. Stability information of the uranyl-phosphate phases is limited to conditions involving pH, temperature, and a few aqueous organic materials. The carbonate ion, which creates very strong complexes with uranium, is the predominant ion in the groundwater composition. The polyphosphate technology with the formation of autunite was identified as the most feasible remediation strategy to sequester uranium in contaminated groundwater and soil in situ. The objectives of the experimental work were (i) to quantify the effect of bicarbonate on the stability of synthetic sodium meta-autunite created as a result of uranium stabilization through polyphosphate injection, (ii) calculate the kinetic rate law parameters of the uranium release from Na-autunite during dissolution, and (iii) to compare the process parameters with those obtained for natural calcium meta-autunite. Experiments were conducted using SPTF apparatus, which consists of syringe pumps for controlling flow rate, Teflon reactors and a heating/cooling system. 0.25 grams of synthetic Na-autunite was placed in the reactor and buffer solutions with varying bicarbonate concentrations (0.0005 to 0.003 M) at different pH (6 - 11) were pumped through the reactors. Experiments were conducted at four different temperatures in the range of 5 - 60oC. It was concluded that the rate of release of uranium from synthetic Na-autunite is directly correlated to the bicarbonate concentration. The rate of release of uranium increased from 1.90 x 10-12 at pH 6 to 2.64 x 10-10 (mol m-2 s-1) at pH 11 at 23oC over the bicarbonate concentration range tested. The activation energy values were invariant with the change in the bicarbonate concentration; however, pH is shown to influence the activation energy values. Uranyl hydroxides and uranyl carbonates complexes helped accelerate the dissolution of autunite mineral.