LY 294002 inhibits adenosine receptor activation by a mechanism independent of effects on PI-3 kinase or casein kinase II

Adenosine reduces both evoked and spontaneous calcium-dependent acetylcholine (ACh) release through a mechanism downstream of calcium entry at amphibian motor nerve endings (Silinsky EM. J Physiol 1984; 346: 243-6). LY 294002 (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one), an inhibitor of both phosphoinositide-3 kinase (PI-3 kinase) and casein kinase II, has been reported to increase spontaneous ACh release reflected in miniature endplate potential (MEPP) frequencies independently of intraterminal calcium at the frog neuromuscular junction (Rizzoli SO, Betz WJ. J Neurosci 2002; 22: 10680-). It has been suggested that the increase in MEPP frequency caused by LY 294002, is mediated through an action on synaptotagmins, vesicle associated calcium sensors believed to trigger synaptic vesicle exocytosis. We thus examined the effects of adenosine on MEPP frequencies and evoked ACh release reflected as endplate potentials (EPPs) in order to determine if the presumed calcium-independent ACh release is affected by adenosine. We also wanted to determine if PI-3 kinase or casein kinase II is involved in mediating or modulating the inhibitory effects of adenosine. To these ends, we examined the effects of adenosine in the presence of LY 294002, wortmannin (a highly selective the PI-3 kinase inhibitor), or DRB (5,6-dichlorobenzimidazole riboside, an inhibitor of casein kinase II). LY 294002 reduced the sensitivity of both MEPP frequencies and the nerve-evoked calcium dependent EPPs to adenosine. The occlusive effects of LY 294002 on the actions of adenosine on MEPPs and EPPs were overcome by increasing adenosine concentration. Neither wortmannin nor DRB had any effect on the sensitivity of the EPPs to adenosine indicating that neither PI-3 kinase nor casein kinase II inhibition mediates the reduction in motor-nerve terminal sensitivity to adenosine produced by LY 294002. The results indicate a competitive relationship between LY 294002 and adenosine at A1 receptors at the frog neuromuscular junction. This effect is independent of the previously described effects of LY 294002 on the exocytotic process, and is also independent of PI-3 kinase or casein kinase II

Snapshots of Simulation: Innovative Strategies Used by International Educators to Enhance Simulation Learning Experiences for Health Care Students

Innovations in simulation in nursing and health care continue to be developed as creative and committed educators respond to challenges of providing pedagogically sound, engaging and effective learning experiences for large student cohorts. Time-pressed educators may find it difficult to network with others working in simulation-based learning, and thus, it is useful to provide summaries or snapshots to provide a brief overview of activities in various countries using simulation in a variety of ways. The purpose of this paper is to profile a diverse range of innovative, cost-effective, and tested simulation approaches that have been implemented in healthcare programs by nursing educators from a range of countries to spark creativity. Each strategy was designed to address contemporary and critical practice issues. They facilitate immersion in authentic clinical scenarios, increase students’ awareness of cues in the environent that may compromise health and safety, and prepare students for cultural or clinical realities that they may not routinely encounter because of the inherent restrictions associated with clinical placements

An open system transportation security sensor network: field trial experiences

Abstract Cargo shipments are subject to hijack, theft, or tampering. Furthermore, cargo shipments are at risk of being used to transport contraband, potentially resulting in fines to shippers. The Transportation Security Sensor Network (TSSN), which is based on open software systems and Service Oriented Architecture (SOA) principles, has been developed to mitigate these risks. Using commercial off-the-shelf (COTS) hardware, the TSSN is able to detect events and report those relevant to appropriate decision makers. However, field testing is required to validate the system architecture as well as to determine if the system can provide timely event notification. Field experiments were conducted to assess the TSSN's suitability for monitoring rail-borne cargo. Log files were collected from these experiments and postprocessed. We present the TSSN architecture and results of field experiments, including the time taken to report events using the TSSN as well as on the interaction between various components of the TSSN. These results show that the TSSN architecture can be used to monitor rail-borne cargo. i

The Liberal Playground: Susan Isaacs, Psychoanalysis and Progressive Education in the Interwar Era

The Cambridge Malting House, an experimental school, serves here as a case study for investigating the tensions within 1920s liberal elites between their desire to abandon some Victorian and Edwardian sets of values in favour of more democratic ones, and at the same time their insistence on preserving themselves as an integral part of the English upper class. Susan Isaacs, the manager of the Malting House, provided the parents – some of whom were the most famous scientists and intellectuals of their age – with an opportunity to fulfil their ‘fantasy’ of bringing up children in total freedom. In retrospect, however, she deeply criticized those from their milieu for not fully understanding the real socio-cultural implications of their ideological decision to make independence and freedom the core values in their children’s education. Thus, 1920s progressive education is a paradigmatic case study of the cultural and ideological inner contradictions within liberal thought in the interwar era. The article also shows how psychoanalysis – which attracted many progressive educators – played a crucial role in providing liberals of all sorts with a new language to articulate their political visions, but, at the same time, explored the limits of the liberal discourse as a whole

Thermal conductivity of refractory glass fibres

In the present study, the current international standards and corresponding apparatus for measuring the thermal conductivity of refractory glass fibre products have been reviewed. Refractory glass fibres are normally produced in the form of low-density needled mats. A major issue with thermal conductivity measurements of these materials is lack of reproducibility in the test results due to transformation of the test material during the test. Also needled mats are inherently inhomogeneous, and this poses additional problems. To be able to compare the various methods of thermal conductivity measurement, a refractory reference material was designed which is capable of withstanding maximum test temperatures (1673 K) with minimum transformation. The thermal conductivity of this reference material was then measured using various methods according to the different standards surveyed. In order to compare different materials, samples have been acquired from major refractory glass fibre manufacturers and the results have been compared against the newly introduced reference material. Materials manufactured by melt spinning, melt blowing and sol–gel have been studied, and results compared with literature values

It is time to talk about people: a human-centered healthcare system

Examining vulnerabilities within our current healthcare system we propose borrowing two tools from the fields of engineering and design: a) Reason's system approach [1] and b) User-centered design [2,3]. Both approaches are human-centered in that they consider common patterns of human behavior when analyzing systems to identify problems and generate solutions. This paper examines these two human-centered approaches in the context of healthcare. We argue that maintaining a human-centered orientation in clinical care, research, training, and governance is critical to the evolution of an effective and sustainable healthcare system

Excitatory effect of ATP on rat area postrema neurons

ATP-induced inward currents and increases in the cytosolic Ca2+ concentration ([Ca]in) were investigated in neurons acutely dissociated from rat area postrema using whole-cell patch-clamp recordings and fura-2 microfluorometry, respectively. The ATP-induced current (IATP) and [Ca]in increases were mimicked by 2-methylthio-ATP and ATP-γS, and were inhibited by P2X receptor (P2XR) antagonists. The current–voltage relationship of the IATP exhibited a strong inward rectification, and the amplitude of the IATP was concentration-dependent. The IATP was markedly reduced in the absence of external Na+, and the addition of Ca2+ to Na+-free saline increased the IATP. ATP did not increase [Ca]in in the absence of external Ca2+, and Ca2+ channel antagonists partially inhibited the ATP-induced [Ca]in increase, indicating that ATP increases [Ca]in by Ca2+ influx through both P2XR channels and voltage-dependent Ca2+ channels. There was a negative interaction between P2XR- and nicotinic ACh receptor (nAChR)-channels, which depended on the amplitude and direction of current flow through either channel. Current occlusion was observed at Vhs between −70 and −10 mV when the IATP and ACh-induced current (IACh) were inward, but no occlusion was observed when these currents were outward at a Vh of +40 mV. The IATP was not inhibited by co-application of ACh when the IACh was markedly decreased either by removal of permeant cations, by setting Vh close to the equilibrium potential of IACh, or by the addition of d-tubocurarine or serotonin. These results suggest that the inhibitory interaction is attributable to inward current flow of cations through the activated P2XR- and nAChR-channels