Induction of cyclooxygenase-2 (COX-2) has been described in a wide range of neurological diseases including animal models of epilepsy. The present study was undertaken to assess COX-2 expression in hippocampal biopsies from patients with therapy-refractive temporal lobe epilepsy (TLE). For this purpose, hippocampal CA1 subfield was dissected from epileptic patients with (n=5) or without (n=2) hippocampal sclerosis (HS). COX-2 expression was investigated using immunohistochemistry and semi-quantitative RT-PCR. COX-2 immunoreactivity in TLE patient material in the absence of HS was restricted to a few neurons of the hippocampus. In the presence of HS, on the other hand, a significant induction of astrocytic COX-2 immunoreactivity associated with a concomitant increase in the steady-state level of COX-2 mRNA was observed in the CA1 subfield. These findings suggest that induction of astrocytic COX-2 is implicated in the pathogenesis of HS in TLE and is consistent with the previous findings of increased concentrations of prostaglandins in the cerebrospinal fluid of these patients.
The application of orthodontic forces significantly increased MMP-1 transcript levels. The use of anti-inflammatory drugs may have an inhibitory effect on MMP-1 expression.
Thiamine deficiency provides an effective model of selective neuronal cell death.1 H and 13 C-NMR was used to investigate the effects of thiamine deficiency on the synthesis of amino acids derived from [1-13 C]glucose in vulnerable (medial thalamus; MT) compared to non-vulnerable (frontal cortex; FC) brain regions. Following 11 days of thiamine deficiency, a time-point associated with the absence of significant neuronal cell death, regional concentrations of glutamate, glutamine and GABA remained unaffected in FC and MT; however, decreased levels of aspartate in MT at this time-point were a predictor of regional vulnerability. De novo synthesis of glutamate and GABA were unaffected at 11 days of thiamine deficiency, while synthesis of [2-13 C]aspartate was significantly impaired. Glucose loading, which has been shown to exacerbate symptoms in patients with thiamine deficiency, resulted in further decreases of TCA cycle flux and reduced de novo synthesis of glutamate, aspartate and GABA in thiaminedeficient (TD) rats. Isotopomer analysis revealed that impaired TCA cycle flux and decreased aspartate synthesis due to thiamine deficiency occurred principally in neurons. Glucose loading deteriorated TD-related decreases in TCA cycle flux, and concomitantly reduced synthesis of aspartate and glutamate in MT.
Gradients of ion channels across the left ventricular (LV) wall have been well characterized and it has been shown that disruption of such gradients leads to altered rates of repolarization across the wall, which is associated with the generation of arrhythmias.
We have hypothesized that a transmural gradient of INa is present and have directly measured this current in adult rat myocytes isolated from both the epicardial and endocardial layers of the left ventricle. Currents were also recorded in right ventricular (RV) myocytes for comparison.
Peak inward INa currents, at −30 mV, were −49.7 ± 2.5 pA pF−1 (n= 22), −32.9 ± 3.2 pA pF−1 (n= 16) and −49.7 ± 3.7 pA pF−1 (n= 24) for RV, LV epicardial and LV endocardial myocytes, respectively. No differences in the voltage dependence of inactivation, the voltage dependence of steady‐state inactivation, or reactivation were reported.
Our results demonstrate that a gradient of sodium current density is present across the LV wall of adult rat hearts.
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