In July 2001, a 140 m long ice core was recovered from the Belukha glacier (49°48′26″N, 86°34′43″E, 4062 m a.s.l.) in the Siberian Altai. The ion chemistry of the upper 86 m, covering the last two centuries, is characterized by biogenic emissions (ammonium and formate), aeolian dust (calcium, magnesium, chloride, and sodium) and anthropogenic species (sulfate, nitrate, and ammonium). Particularly high ammonium and formate concentrations indicate pronounced emissions from Siberian forests. The inferred fire frequency does not show a long‐term trend but distinct periods of enhanced activity. Sulfate has the highest industrial to preindustrial ratio and an anthropogenic contribution of more than 80%. Variations in this record reflect sulfur dioxide emissions in Siberia and Kazakhstan. Sulfate concentrations remained low until 1950, then sharply increased and peaked in the 1970s. The decrease in the 1980s is attributed to the economic, political, and social crises and to the replacement of coal with gas. Rising nitrate concentrations since 1960 reflect traffic growth and enhanced fertilizer application. Increasing ammonium concentrations since the 1950s are attributable to population inflow in southern Siberia with the associated enhancement of agricultural activity. A nitrate peak of short duration in 1908 is thought to be the atmospheric signature from the Tunguska event on 30 June 1908.
Streptococcus pneumoniae is the most common pathogen causing non-epidemic bacterial meningitis worldwide. The immune response and inflammatory processes contribute to the pathophysiology. Hence, the anti-inflammatory dexamethasone is advocated as adjuvant treatment although its clinical efficacy remains a question at issue. In experimental models of pneumococcal meningitis, dexamethasone increased neuronal damage in the dentate gyrus. Here, we investigated expressional changes in the hippocampus and cortex at 72 h after infection when dexamethasone was given to infant rats with pneumococcal meningitis. Nursing Wistar rats were intracisternally infected with Streptococcus pneumoniae to induce experimental meningitis or were sham-infected with pyrogen-free saline. Besides antibiotics, animals were either treated with dexamethasone or saline. Expressional changes were assessed by the use of GeneChip® Rat Exon 1.0 ST Arrays and quantitative real-time PCR. Protein levels of brain-derived neurotrophic factor, cytokines and chemokines were evaluated in immunoassays using Luminex xMAP® technology. In infected animals, 213 and 264 genes were significantly regulated by dexamethasone in the hippocampus and cortex respectively. Separately for the cortex and the hippocampus, Gene Ontology analysis identified clusters of biological processes which were assigned to the predefined categories “inflammation”, “growth”, “apoptosis” and others. Dexamethasone affected the expression of genes and protein levels of chemokines reflecting diminished activation of microglia. Dexamethasone-induced changes of genes related to apoptosis suggest the downregulation of the Akt-survival pathway and the induction of caspase-independent apoptosis. Signalling of pro-neurogenic pathways such as transforming growth factor pathway was reduced by dexamethasone resulting in a lack of pro-survival triggers. The anti-inflammatory properties of dexamethasone were observed on gene and protein level in experimental pneumococcal meningitis. Further dexamethasone-induced expressional changes reflect an increase of pro-apoptotic signals and a decrease of pro-neurogenic processes. The findings may help to identify potential mechanisms leading to apoptosis by dexamethasone in experimental pneumococcal meningitis.
BackgroundBacterial meningitis in children causes high rates of mortality and morbidity. In a recent clinical trial, oral glycerol significantly reduced severe neurological sequelae in paediatric meningitis caused by Haemophilus influenzae type b, and a tendency towards a benefit of adjunctive glycerol was seen in pneumococcal meningitis.MethodsHere we examined the effects of glycerol in pneumococcal meningitis of infant rats and adult mice. All animals received ceftriaxone, and glycerol or placebo. Brain damage, hearing loss, and inflammatory parameters were assessed.ResultsClinically and by histopathology, animals treated with glycerol or placebo did not differ. While both groups showed equally high levels of matrix metalloproteinase-9 at 24 h after infection, a significant difference in favour of glycerol was observed at 40 h after infection. However, this difference in matrix metalloproteinase-9 in late disease did not result in an improvement of histopathologic parameters.ConclusionNo benefit of adjunctive glycerol was found in these models of pneumococcal meningitis.
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