Phase synchronization between cardiac and respiratory oscillations is investigated during anesthesia in rats. Synchrograms and time evolution of synchronization indices are used to show that the system passes reversibly through a sequence of different phase-synchronized states as the anesthesia level changes, indicating that it can undergo phase transitionlike phenomena. It appears that the synchronization state may be used to characterize the depth of anesthesia.

Intracellular proteolysis is critical to maintain timely degradation of altered proteins including oxidized proteins. This review attempts to summarize the most relevant findings about oxidant protein modification, as well as the impact of reactive oxygen species on the proteolytic systems that regulate cell response to an oxidant environment: the ubiquitin-proteasome system (UPS), autophagy and the unfolded protein response (UPR). In the presence of an oxidant environment, these systems are critical to ensure proteostasis and cell survival. An example of altered degradation of oxidized proteins in pathology is provided for neurodegenerative diseases. Future work will determine if protein oxidation is a valid target to combat proteinopathies.

We hypothesized that, associated with the state of anaesthesia, characteristic changes exist in both cardio-respiratory and cerebral oscillator parameters and couplings, perhaps varying with depth of anaesthesia. Electrocardiograms (ECGs), respiration and electroencephalograms (EEGs) were recorded from two groups of 10 rats during the entire course of anaesthesia following the administration of a single bolus of ketamine-xylazine (KX group) or pentobarbital (PB group). The phase dynamics approach was then used to extract the instantaneous frequencies of heart beat, respiration and slow δ-waves (within 0.5-3.5 Hz). The amplitudes of δ-and θ-waves were analysed by use of a time-frequency representation of the EEG signal within 0.5-7.5 Hz obtained by wavelet transformation, using the Morlet mother wavelet. For the KX group, where slow δ-waves constituted the dominant spectral component, the Hilbert transform was applied to obtain the instantaneous δ-frequency. The θ-activity was spread over too wide a spectral range for its phase to be meaningfully defined. For both agents, we observed two distinct phases of anaesthesia, with a marked increase in θ-wave activity occurring on passage from a deeper phase of anaesthesia to a shallower one. In other respects, the effects of the two anaesthetics were very different. For KX anaesthesia, the two phases were separated by a marked change in all three instantaneous frequencies: stable, deep, anaesthesia with small frequency variability was followed by a sharp transition to shallow anaesthesia with large frequency variability, lasting until the animal awoke. The transition occurred 16-76 min after injection of the anaesthetic, with simultaneous reduction in the δ-wave amplitude. For PB anaesthesia, the two epochs were separated by the return of a positive response to the pinch test at 53-94 min, following which it took a further period of 45-70 min for the animal to awaken. δ-Waves were not apparent at any stage of PB anaesthesia. We applied non-linear dynamics and information theory to seek evidence of causal relationships between the cardiac, respiratory and slow δ-oscillations. We demonstrate that, for both groups, respiration drives the cardiac oscillator during deep anaesthesia. During shallow KX anaesthesia the direction either reverses, or the cardio-respiratory interaction becomes insignificant; in the deep phase, there is a unidirectional deterministic interaction of respiration with slow δ-oscillations. For PB anaesthesia, the cardio-respiratory interaction weakens during the second phase but, otherwise, there is no observable change in the interactions. We conclude that non-linear dynamics and information theory can be used to identify different stages of anaesthesia and the effects of different anaesthetics.

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Apomorphine (APO) is an aporphine derivative used in human and veterinary medicine. APO activates D 1 , D 2S , D 2L , D 3 , D 4 , and D 5 receptors (and is thus classified as a non-selective dopamine agonist), serotonin receptors (5HT 1A , 5HT 2A , 5HT 2B , and 5HT 2C ), and α-adrenergic receptors (α 1B , α 1D , α 2A , α 2B , and α 2C ). In veterinary medicine, APO is used to induce vomiting in dogs, an important early treatment for some common orally ingested poisons (e.g., anti-freeze or insecticides). In human medicine, it has been used in a variety of treatments ranging from the treatment of addiction (i.e., to heroin, alcohol or cigarettes), for treatment of erectile dysfunction in males and hypoactive sexual desire disorder in females to the treatment of patients with Parkinson's disease (PD). Currently, APO is used in patients with advanced PD, for the treatment of persistent and disabling motor fluctuations which do not respond to levodopa or other dopamine agonists, either on its own or in combination with deep brain stimulation. Recently, a new and potentially important therapeutic role for APO in the treatment of Alzheimer's disease has been suggested; APO seems to stimulate A catabolism in an animal model and cell culture, thus reducing the rate of A oligomerisation and consequent neural cell death.