LY293558 prevents soman-induced pathophysiological alterations in the basolateral amygdala and the development of anxiety.

Exposure to nerve agents can cause brain damage due to prolonged seizure activity, producing long-term behavioral deficits. We have previously shown that LY293558, a GluK1/AMPA receptor antagonist, is a very effective anticonvulsant and neuroprotectant against nerve agent exposure. In the present study, we examined whether the protection against nerve agent-induced seizures and neuropathology conferred by LY293558 translates into protection against pathophysiological alterations in the basolateral amygdala (BLA) and the development of anxiety, which is the most prevalent behavioral deficit resulting from exposure. LY293558 (15 mg/kg) was administered to rats, along with atropine and HI-6, at 20 min after exposure to soman (1.2 × LD50). At 24 h, 7 days, and 30 days after exposure, soman-exposed rats who did not receive LY293558 had reduced but prolonged evoked field potentials in the BLA, as well as increased paired-pulse ratio, suggesting neuronal damage and impaired synaptic inhibition; rats who received LY293558 did not differ from controls in these parameters. Long-term potentiation of synaptic transmission was impaired at 7 days after exposure in the soman-exposed rats who did not receive anticonvulsant treatment, but not in the LY293558-treated rats. Anxiety-like behavior assessed by the open field and acoustic startle response tests was increased in the soman-exposed rats at 30 and 90 days after exposure, while rats treated with LY293558 did not differ from controls. Along with our previous findings, the present data demonstrate the remarkable efficacy of LY293558 in counteracting nerve agent-induced seizures, neuropathology, pathophysiological alterations in the BLA, and anxiety-related behavioral deficits.

Possible gabapentin and ketamine interaction causing prolonged central nervous system depression during post-operative recovery following cervical laminoplasty: a case report.

INTRODUCTION: The drugs gabapentin and ketamine are used frequently in the peri-operative setting. There is poor documentation whether or not gabapentin and ketamine interact to cause prolonged depression of the central nervous system. CASE PRESENTATION: The following is a case report in which a patient, a 58-year-old African-American man, with a history of post-traumatic stress disorder and chronic pain underwent a cervical laminoplasty procedure. The patient presented post-operatively in a dissociative state with paralysis, anarthria and preservation of consciousness. All organic causes were excluded, with the exception of prolonged central nervous system depression from a gabapentin/ketamine drug interaction. A new onset conversion disorder could also not be excluded. CONCLUSION: Although this case by itself is not enough evidence to substantiate a true adverse reaction between gabapentin and ketamine, it is enough to warrant further investigation.

Association of Phytophthora cinnamomi with White Oak Decline in Southern Ohio.

A decline syndrome and widespread mortality of mature white oak tree (Quercus alba) associated with wet and low-lying areas has been recently observed in southern Ohio forests. Previous studies have isolated Phytophthora cinnamomi from white oak rhizospheres. In 2008 and 2009, P. cinnamomi population densities in two healthy and two declining white oak stands at Scioto Trail State Forest were quantified and potential roles of three environmental drivers of Phytophthora spp.-induced decline were assessed: soil texture, soil moisture, and topography. Significantly higher P. cinnamomi propagule densities were found in declining stands in both years but propagule densities were not associated with soil moisture content. Trends in population densities were not correlated with soil moisture or topographic position within field sites. There was a positive, exponential relationship between overall P. cinnamomi population levels and soil moisture on a seasonal scale in 2008 but not 2009. Sites with greater soil clay content were associated with greater decline. Effects of P. cinnamomi inoculum and periodic flooding on root health of 1-year-old potted white oak trees grown in native soil mixes in the greenhouse were examined. Root systems of potted oak were significantly damaged by soil inoculation with P. cinnamomi, especially under flooding conditions. Results of these studies support the hypothesis that P. cinnamomi is a contributing agent to white oak decline in southern Ohio.

Sugar maple growth in relation to nutrition and stress in the northeastern United States.

Sugar maple, Acer saccharum, decline disease is incited by multiple disturbance factors when imbalanced calcium (Ca), magnesium (Mg), and manganese (Mn) act as predisposing stressors. Our objective in this study was to determine whether factors affecting sugar maple health also affect growth as estimated by basal area increment (BAI). We used 76 northern hardwood stands in northern Pennsylvania, New York, Vermont, and New Hampshire, USA, and found that sugar maple growth was positively related to foliar concentrations of Ca and Mg and stand level estimates of sugar maple crown health during a high stress period from 1987 to 1996. Foliar nutrient threshold values for Ca, Mg, and Mn were used to analyze long-term BAI trends from 1937 to 1996. Significant (P < or = 0.05) nutrient threshold-by-time interactions indicate changing growth in relation to nutrition during this period. Healthy sugar maples sampled in the 1990s had decreased growth in the 1970s, 10-20 years in advance of the 1980s and 1990s decline episode in Pennsylvania. Even apparently healthy stands that had no defoliation, but had below-threshold amounts of Ca or Mg and above-threshold Mn (from foliage samples taken in the mid 1990s), had decreasing growth by the 1970s. Co-occurring black cherry, Prunus serotina, in a subset of the Pennsylvania and New York stands, showed opposite growth responses with greater growth in stands with below-threshold Ca and Mg compared with above-threshold stands. Sugar maple growing on sites with the highest concentrations of foliar Ca and Mg show a general increase in growth from 1937 to 1996 while other stands with lower Ca and Mg concentrations show a stable or decreasing growth trend. We conclude that acid deposition induced changes in soil nutrient status that crossed a threshold necessary to sustain sugar maple growth during the 1970s on some sites. While nutrition of these elements has not been considered in forest management decisions, our research shows species specific responses to Ca and Mg that may reduce health and growth of sugar maple or change species composition, if not addressed.

Tristetraprolin regulates IL-8 mRNA stability in cystic fibrosis lung epithelial cells.

Cystic fibrosis (CF) is due to mutations in the CFTR gene and is characterized by hypersecretion of the proinflammatory chemokine IL-8 into the airway lumen. Consequently, this induces the highly inflammatory cellular phenotype typical of CF. Our initial studies revealed that IL-8 mRNA is relatively stable in CF cells compared with those that had been repaired with [WT]CFTR (wild-type CFTR). Relevantly, the 3'-UTR of IL-8 mRNA contains AU-rich sequences (AREs) that have been shown to mediate posttranscriptional regulation of proinflammatory genes upon binding to ARE-binding proteins including Tristetraprolin (TTP). We therefore hypothesized that very low endogenous levels of TTP in CF cells might be responsible for the relative stability of IL-8 mRNA. As predicted, increased expression of TTP in CF cells resulted in reduced stability of IL-8 mRNA. An in vitro analysis of IL-8 mRNA stability in CF cells also revealed a TTP-induced enhancement of deadenylation causing reduction of IL-8 mRNA stability. We conclude that enhanced stability of IL-8 mRNA in TTP-deficient CF lung epithelial cells serve to drive the proinflammatory cellular phenotype in the CF lung.