Development of a comprehensive set of P2 receptor pharmacological research compounds.

Pharmacological manipulation of P2X and P2Y receptors has been critical to the elucidation of the biological roles of these receptors within a multitude of physiological and pathological processes. Initial purinergic signalling research made use of compounds based on pyridoxal phosphate, suramin and nucleotide analogues; recently developed compounds are often derivatives of these early tools. Tocris Bioscience first entered the field of purinergic signalling reagents with the commercial release of the pyridoxal phosphate derivative, iso-PPADS. During the past two decades, Tocris has assembled a collection of over 50 compounds for P2 receptor modulation, including research tools commercialised from both academic and industrial laboratories. Recently, a number of P2X subtype-selective compounds have been generated by pharmaceutical company medicinal chemistry programmes, supplementing our range of P2Y-selective compounds. Here, we detail the current, commercially available agonists and antagonists of P2X(1,2/3,3,4,7) and P2Y(1,6,11,12) receptors; considered together, they form the foundations of a comprehensive P2 receptor pharmacological 'toolkit'.

Effects of ketamine on response properties of neurons in the superior paraolivary nucleus of the mouse.

The superior paraolivary nucleus (SPON; alternative abbreviation: SPN for the same nucleus in certain species) is a prominent brainstem structure that provides strong inhibitory input to the auditory midbrain. Previous studies established that SPON neurons encode temporal sound features with high precision. These earlier characterizations of SPON responses were recorded under the influence of ketamine, a dissociative anesthetic agent and known antagonist of N-methyl-d-aspartate glutamate (NMDA) receptors. Because NMDA alters neural responses from the auditory brainstem, single unit extracellular recordings of SPON neurons were performed in the presence and absence of ketamine. In doing so, this study represents the first in vivo examination of the SPON of the mouse. Herein, independent data sets of SPON neurons are characterized that did or did not receive ketamine, as well as neurons that were recorded both prior to and following ketamine administration. In all conditions, SPON neurons exhibited contralaterally driven spikes triggered by the offset of pure tone stimuli. Ketamine lowered both evoked and spontaneous spiking, decreased the sharpness of frequency tuning, and increased auditory thresholds and first-spike latencies. In addition, ketamine limited the range of modulation frequencies to which neurons phase-locked to sinusoidally amplitude-modulated tones.

Penetrating neck trauma and the aberrant subclavian artery.

Vascular injuries from penetrating trauma to the base of the neck are accompanied by significant morbidity and potential mortality. These injuries require several diagnostic adjuncts in order to facilitate early diagnosis and appropriate treatment. Herein reported is the case of a patient who sustained penetrating injury to the thoracic inlet but had a fortuitous anomaly that prevented vascular injury and its attendant complications.

Penetrating neck trauma and the aberrant subclavian artery

Vascular injuries from penetrating trauma to the base of the neck are accompanied by significant morbidity and potential mortality. These injuries require several diagnostic adjuncts in order to facilitate early diagnosis and appropriate treatment. Herein reported is the case of a patient who sustained penetrating injury to the thoracic inlet but had a fortuitous anomaly that prevented vascular injury and its attendant complications.

Spectral integration in the inferior colliculus of the CBA/CaJ mouse.

The inferior colliculus receives a massive convergence of inputs and in the mustached bat, this convergence leads to the creation of neurons in the inferior colliculus that integrate information across multiple frequency bands. These neurons are tuned to multiple frequency bands or are combination-sensitive; responding best to the combination of two signals of different frequency composition. The importance of combination-sensitive neurons in processing echolocation signals is well described, and it has been thought that combination sensitivity is a neural specialization for echolocation behaviors. Combination sensitivity and other response properties indicative of spectral integration have not been thoroughly examined in the inferior colliculus of non-echolocating mammals. In this study we tested the hypothesis that integration across frequencies occurs in the inferior colliculus of mice. We tested excitatory frequency response areas in the inferior colliculus of unanesthetized mice by varying the frequency of a single tone between 6 and 100 kHz. We then tested combination-sensitive responses by holding one tone at the unit's best frequency, and varying the frequency and intensity of a second tone. Thirty-two percent of the neurons were tuned to multiple frequency bands, 16% showed combination-sensitive facilitation and another 12% showed combination-sensitive inhibition. These findings suggests that the neural mechanisms underlying processing of complex sounds in the inferior colliculus share some common features among mammals as different as the bat and the mouse.

A comparison of the induction of immortalized endothelial cell impermeability by astrocytes.

The suitability of various commercially available endothelial cell lines in studies of astrocytic/endothelial cell interactions was assessed. The endothelial-like cell line ECV304 was compared with T24/83, Eahy929, and b.End5 and rat cerebral endothelial cells in their ability, when co-cultured with rat (C6) glioma cells, to form a transendothelial electrical resistance (TEER), an indicator of tight junction formation which is an important property of the blood-brain barrier. As reported previously, the basal TEER of ECV304 cell monolayers was significantly enhanced upon co-culture, an effect reproduced by human 1321N1 astrocytes and primary rat astrocytes. T24/83 cells formed a patchy, gapped monolayer, which produced a poor basal TEER with little in the way of an increase upon co-culture. Similarly, all the other cell monolayers analysed demonstrated poor TEERs that were only moderately increased upon co-culture. These data confirm that while no endothelial cell line with ideal features is available, ECV304 cells remain an appropriate choice especially for studies of astrocyte/endothelial cell interactions.

Beyond the physician's office--the medical mall.

Medical groups are often judged, whether we realize it or not, by the patient's satisfaction and not necessarily by the "quality of care" the patient receives. This paper examines the process in which a clinic determines how to best serve its market through the "medical mall" concept, offering a mix of services which accommodate the ambulatory patient's needs.