Hyperthermia and Serotonin: The Quest for a “Better Cyproheptadine”

Fine temperature control is essential in homeothermic animals. Both hyper- and hypothermia can have deleterious effects. Multiple, efficient and partly redundant mechanisms of adjusting the body temperature to the value set by the internal thermostat exist. The neural circuitry of temperature control and the neurotransmitters involved are reviewed. The GABAergic inhibitory output from the brain thermostat in the preoptic area POA to subaltern neural circuitry of temperature control (Nucleus Raphe Dorsalis and Nucleus Raphe Pallidus) is a function of the balance between the (opposite) effects mediated by the transient receptor potential receptor TRPM2 and EP3 prostaglandin receptors. Activation of TRPM2-expressing neurons in POA favors hypothermia, while inhibition has the opposite effect. Conversely, EP3 receptors induce elevation in body temperature. Activation of EP3-expressing neurons in POA results in hyperthermia, while inhibition has the opposite effect. Agonists at TRPM2 and/or antagonists at EP3 could be beneficial in hyperthermia control. Activity of the neural circuitry of temperature control is modulated by a variety of 5-HT receptors. Based on the theoretical model presented the “ideal” antidote against serotonin syndrome hyperthermia appears to be an antagonist at the 5-HT receptor subtypes 2, 4 and 6 and an agonist at the receptor subtypes 1, 3 and 7. Very broadly speaking, such a profile translates in a sympatholytic effect. While a compound with such an ideal profile is presently not available, better matches than the conventional antidote cyproheptadine (used off-label in severe serotonin syndrome cases) appear to be possible and need to be identified.     

A preamble-based approach for providing quality of service support in wireless sensor networks

Medium Access Control (MAC) protocols for Wireless Sensor Networks (WSN) are usually designed as random access protocols that apply different kinds of backoff strategies since Time Division Multiple Access (TDMA) based protocols with admission control are very complex and require additional mechanisms for synchronization. Without such mechanisms, fair or priority based medium access with Quality of Service (QoS) guarantees can hardly be achieved by existing protocols. Therefore, we developed a random access protocol which uses a new preamble-based medium access strategy that enables collision-free priority based access without the need of synchronization. In this paper we introduce different QoS strategies and their use cases. All strategies can be easily integrated in our protocol to meet the requirements of different target applications. Furthermore, we compare the performance of the strategies with a typical carrier-sense based protocol.     

Fluorous Iminoalditols: A New Family of Glycosidase Inhibitors and Pharmacological Chaperones

A collection of new reversible glycosidase inhibitors of the iminoalditol type featuring N‐substituents containing perfluorinated regions has been prepared for evaluation of physicochemical, biochemical and diagnostic properties. The vast variety of feasible oligofluoro moieties allows for modular approaches to customised structures according to the intended applications, which are influenced by the fluorine content as well as the distance of the fluorous moiety from the ring nitrogen. The first examples, in particular in the D ‐galacto series, exhibited excellent inhibitory activities. A preliminary screen with two human cell lines showed that, at subinhibitory concentrations, they are powerful pharmacological chaperones enhancing the activities of the catalytically handicapped lysosomal D ‐galactosidase mutants associated with GM1 gangliosidosis and Morquio B disease.     

Combating moisture in timber flat roofs

Soft rot which occurred in timber-based flat roofs of houses in Albertslund, a Copenhagen suburb, provoked a major on-site research and testing programme. The main findings are presented here by Knud Prebensen, of consulting engineers, COWI consult, who worked on this collaborative project and co-authored the original reports and this article with Georg Christensen, of the Danish Building Research Institute, and Prof. Vagn Korsgaard, of the Danish Technical Institute.