11 research outputs found
Expression and Function of Serotonin 2A and 2B Receptors in the Mammalian Respiratory Network
Neurons of the respiratory network in the lower brainstem express a variety of serotonin receptors (5-HTRs) that act primarily through adenylyl cyclase. However, there is one receptor family including 5-HT2A, 5-HT2B, and 5-HT2C receptors that are directed towards protein kinase C (PKC). In contrast to 5-HT2ARs, expression and function of 5-HT2BRs within the respiratory network are still unclear. 5-HT2BR utilizes a Gq-mediated signaling cascade involving calcium and leading to activation of phospholipase C and IP3/DAG pathways. Based on previous studies, this signal pathway appears to mediate excitatory actions on respiration. In the present study, we analyzed receptor expression in pontine and medullary regions of the respiratory network both at the transcriptional and translational level using quantitative RT-PCR and self-made as well as commercially available antibodies, respectively. In addition we measured effects of selective agonists and antagonists for 5-HT2ARs and 5-HT2BRs given intra-arterially on phrenic nerve discharges in juvenile rats using the perfused brainstem preparation. The drugs caused significant changes in discharge activity. Co-administration of both agonists revealed a dominance of the 5-HT2BR. Given the nature of the signaling pathways, we investigated whether intracellular calcium may explain effects observed in the respiratory network. Taken together, the results of this study suggest a significant role of both receptors in respiratory network modulation
The role of inflammation in epilepsy.
Epilepsy is the third most common chronic brain disorder, and is characterized by an enduring predisposition to generate seizures. Despite progress in pharmacological and surgical treatments of epilepsy, relatively little is known about the processes leading to the generation of individual seizures, and about the mechanisms whereby a healthy brain is rendered epileptic. These gaps in our knowledge hamper the development of better preventive treatments and cures for the approximately 30% of epilepsy cases that prove resistant to current therapies. Here, we focus on the rapidly growing body of evidence that supports the involvement of inflammatory mediators-released by brain cells and peripheral immune cells-in both the origin of individual seizures and the epileptogenic process. We first describe aspects of brain inflammation and immunity, before exploring the evidence from clinical and experimental studies for a relationship between inflammation and epilepsy. Subsequently, we discuss how seizures cause inflammation, and whether such inflammation, in turn, influences the occurrence and severity of seizures, and seizure-related neuronal death. Further insight into the complex role of inflammation in the generation and exacerbation of epilepsy should yield new molecular targets for the design of antiepileptic drugs, which might not only inhibit the symptoms of this disorder, but also prevent or abrogate disease pathogenesis
ĐĐŸĐŽ Đ·ĐœĐ°ĐŒĐ”ĐœĐ”ĐŒ ĐĐ”ĐœĐžĐœĐ°. 1989. â 155
Robert Nozick initiated one of the most inspired and inspiring discussions in political philosophy with his 1974 response in Anarchy, State, and Utopia to John Rawlsâs 1971 account of distributive justice in A Theory of Justice. These two works have informed an enormous amount of subsequent, especially liberal, discussions of economic justice, where Nozickâs work typically functions as a resource for those defending more right-wing (libertarian) positions, whereas Rawlsâs has been used to defend various left-wing stances. Common to these discussions, as found in politics generally (where similar kinds of arguments frequently are used to defend right and the left-wing policies and conclusions) is that they end in rather stubborn stalemates: the right defending minimal states while the left defends more extensive states. Interesting, too, is that both Nozick and Rawls take themselves to be consistent with, inspired by, and furthering Kantâs freedom project in the development of their own theories of justice. In this paper, I start by outlining the structures of these debates with an emphasis on the original disagreements between Nozick and Rawls. I then show how neither theory actually employed Kantâs own theory of justice, but rather drew on or out (presumed) implications of his ethical theory. In the final sections, I argue that if Nozick and Rawls had instead used Kantâs theory of justice and not his ethics, not only would their individual theories have been stronger, but they could have found ways of overcoming the unproductive stalemates that characterize their own as well as subsequent related discussions of economic justice as we currently find them in much scholarly and contemporary political debate
Distributed applications monitoring at system and network level
Most distributed applications are based on architectural models that do not involve real-time knowledge of network status and of their network usage. Moreover the new "network aware" architectures are still under development and their design is not yet complete. We considered, as a use case, an application using ODBMS (Objectivity/DB) for the distributed analysis of experimental data. The dynamic usage of system and network resources at host and application levels has been measured in different client/server configurations, and on several LAN and WAN layouts. The aim was to study the application efficiency and behavior versus the network characteristics and conditions.
The most interesting results of the LAN and WAN tests are described. System bottlenecks and limitations have been identified, and efficient working conditions in the different scenarios have been defined. The behavior observed when moving away from the optimal working conditions is also described. (C) 2001 Elsevier Science B.V. All rights reserved