Observations of ionospheric ELF and VLF wave generation by excitation of the thermal cubic nonlinearity.

Extremely-low-frequency (ELF, 3-3000 Hz) and very-low-frequency (VLF, 3-30 kHz) waves generated by the excitation of the thermal cubic nonlinearity are observed for the first time at the High-Frequency Active Auroral Research Program high-frequency transmitter in Gakona, Alaska. The observed ELF and VLF field amplitudes are the strongest generated by any high frequency (HF, 3-30 MHz) heating facility using this mechanism to date. This manner of ELF and VLF generation is independent of naturally forming currents, such as the auroral electrojet current system. Time-of-arrival analysis applied to experimental observations shows that the thermal cubic ELF and VLF source region is located within the collisional D-region ionosphere. Observations are compared with the predictions of a theoretical HF heating model using perturbation theory. For the experiments performed, two X-mode HF waves were transmitted at frequencies ω1 and ω2, with |ω2-2ω1| being in the ELF and VLF frequency range. In contrast with previous work, we determine that the ELF and VLF source is dominantly produced by the interaction between collision frequency oscillations at frequency ω2-ω1 and the polarization current density associated with the lower frequency HF wave at frequency ω1. This specific interaction has been neglected in past cubic thermal nonlinearity work, and it plays a major role in the generation of ELF and VLF waves.

Cefoselis, a beta-lactam antibiotic, easily penetrates the blood-brain barrier and causes seizure independently by glutamate release.

Cefoselis is a widely used beta-lactam antibiotic, but occasionally induces seizures and convulsion in elder and renal failure patients. However, beta-lactams are known not to pass through the blood-brain barrier (BBB). In this study, we examined the BBB penetration of cefoselis in normal and renal failure rats by means of brain microdialysis. Cefoselis was dose-dependently appeared in brain extracellular fluid in proportion to its blood level. The elimination constant from brain extracellular fluid (apparent) was slightly lower than that from blood. These results indicated that cefoselis might penetrate the BBB or be discharged by a certain transport system. In contrast to the result of cefoselis, cefazolin, a leading drug of cephalosporins, could not be detected in the brain extracellular fluid after an intravenous injection. In renal dysfunction rats, the elimination half-lives of cefoselis from both blood and brain were extensively prolonged. This would be one of responsible factors inducing seizures seen in patients. However, the additional factor, such as decrease in brain function related to aging, would be involved in seizures in patient received cefoselis, because an extremely high dose was required to induce seizures even in renal failure rats. A local administration of cefoselis into the hippocampus through the microdialysis probe caused a striking elevation of extracellular glutamate, with a minimum increase in gamma-aminobutyric acid (GABA). However, a systematic cefoselis administration via the tail vein did not elevate extracellular glutamate and GABA concentrations in the hippocampus of renal failure rats that exhibited marked seizures. These results suggested that not the stimulation of glutamate release, but the blockade of GABA receptors might be responsible for the seizure induced by cefoselis.

Paraquat induces long-lasting dopamine overflow through the excitotoxic pathway in the striatum of freely moving rats.

The herbicide paraquat is an environmental factor that could be involved in the etiology of Parkinson's disease. We have previously shown that paraquat penetrates through the blood-brain barrier and is taken up by neural cells. In this study, we examined the in vivo toxic mechanism of paraquat to dopamine neurons. GBR-12909, a selective dopamine transporter inhibitor, reduced paraquat uptake into the striatal tissue including dopaminergic terminals. The subchronic treatment with systemic paraquat significantly decreased brain dopamine content in the striatum and slightly in the midbrain and cortex, and was accompanied by the diminished level of its acidic metabolites in rats. When paraquat was administered through a microdialysis probe, a transitory increase in the extracellular levels of glutamate, followed by long-lasting elevations of the extracellular levels of NO(x)(-) (NO(2)(-) plus NO(3)(-)) and dopamine were detected in the striatum of freely moving rats. This dopamine overflow lasted for more than 24 h after the paraquat treatment. Dopamine overflow was inhibited by N(G)-nitro-L-arginine methyl ester, dizocilpine, 6,7-dinitroquinoxaline-2,3-dione and L-deprenyl. The toxic mechanism of paraquat involves glutamate induced activation of non-NMDA receptors, resulting in activation of NMDA receptor-channels. The influx of Ca(2+) into cells stimulates nitric oxide synthase. Released NO would diffuse to dopaminergic terminals and further induce mitochondrial dysfunction by the formation of peroxynitrite, resulting in continuous and long-lasting dopamine overflow. The constant exposure to low levels of paraquat may lead to the vulnerability of dopaminergic terminals in humans, and might potentiate neurodegeneration caused by the exposure of other substances, such as endogenous dopaminergic toxins.