Diffusion of Oxygen Through Saturated Porous Media

The purpose of this investigation are to develop apparatus for the measurement of diffusion through water saturated media, and to compare the effect of porosity on diffusion through water saturated media with that on diffusion through media saturated with gases

Universities and primary care organisations working together to recruit GPs: a qualitative evaluation of the Enfield clinical teaching fellow programme

Background General practice recruitment is in difficulty in the UK as many experienced GPs retire or reduce their commitment. The numbers of junior doctors choosing to specialise in the discipline is also falling, leading to primary care workforce issues particularly in 'hard to serve' areas. Aim To evaluate an academic service collaboration on GP recruitment between a primary care organisation (PCO), Enfield CCG, and a university, University College London (UCL). Design & setting Evaluation of an academic service collaboration in the Enfield CCG area of north east London. Method An action research method utilising qualitative methodology was used to evaluate a local service intervention, undertaken by the participants themselves. The qualitative data were analysed by one researcher but themes were agreed by the whole team. Enfield CCG, an NHS PCO, funded a collaboration with UCL to employ five GPs as clinical teaching fellows to work in Enfield, to increase patients' access, to provide input to CCG development projects, and to provide undergraduate medical student teaching in practice. Results Five teaching fellows were employed for ≤2 years and provided 18 266 extra appointments, engaged with development projects, and delivered local undergraduate teaching. The themes identified by stakeholders were the challenges of these organisations working together, recruiting GPs to an underserved area, and perceptions of the model’s value for money. Conclusion The evaluation showed that the collaboration of an NHS PCO and a higher education institution can work, and the prestige of being associated with a universty and clinical variety ensured GP recruitment in an area that had previously struggled. However, the project’s costs were high, which affected perceptions of its value

Differentiated Human NT2-N Neurons Possess a High Intracellular Content of myo -Inositol

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65665/1/j.1471-4159.1999.721431.x.pd

Selective inhibitors of cardiac ADPR cyclase as novel anti-arrhythmic compounds

ADP-ribosyl cyclases (ADPRCs) catalyse the conversion of nicotinamide adenine dinucleotide to cyclic adenosine diphosphoribose (cADPR) which is a second messenger involved in Ca2+ mobilisation from intracellular stores. Via its interaction with the ryanodine receptor Ca2+ channel in the heart, cADPR may exert arrhythmogenic activity. To test this hypothesis, we have studied the effect of novel cardiac ADPRC inhibitors in vitro and in vivo in models of ventricular arrhythmias. Using a high-throughput screening approach on cardiac sarcoplasmic reticulum membranes isolated from pig and rat and nicotinamide hypoxanthine dinuleotide as a surrogate substrate, we have identified potent and selective inhibitors of an intracellular, membrane-bound cardiac ADPRC that are different from the two known mammalian ADPRCs, CD38 and CD157/Bst1. We show that two structurally distinct cardiac ADPRC inhibitors, SAN2589 and SAN4825, prevent the formation of spontaneous action potentials in guinea pig papillary muscle in vitro and that compound SAN4825 is active in vivo in delaying ventricular fibrillation and cardiac arrest in a guinea pig model of Ca2+ overload-induced arrhythmia. Inhibition of cardiac ADPRC prevents Ca2+ overload-induced spontaneous depolarizations and ventricular fibrillation and may thus provide a novel therapeutic principle for the treatment of cardiac arrhythmias

Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance

Inositol phospholipids and inositol phosphates mediate well-established functions in signal transduction and in Ca 2+ homeostasis in the CNS and non-neural tissues. More recently, there has been renewed interest in other roles that both myo -inositol and its highly phosphorylated forms may play in neural function. We review evidence that myo -inositol serves as a clinically relevant osmolyte in the CNS, and that its hexakisphosphate and pyrophosphorylated derivatives may play roles in such diverse cellular functions as DNA repair, nuclear RNA export and synaptic membrane trafficking.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65201/1/j.1471-4159.2002.01041.x.pd

Identification of Intracellular and Plasma Membrane Calcium Channel Homologues in Pathogenic Parasites

Ca2+ channels regulate many crucial processes within cells and their abnormal activity can be damaging to cell survival, suggesting that they might represent attractive therapeutic targets in pathogenic organisms. Parasitic diseases such as malaria, leishmaniasis, trypanosomiasis and schistosomiasis are responsible for millions of deaths each year worldwide. The genomes of many pathogenic parasites have recently been sequenced, opening the way for rational design of targeted therapies. We analyzed genomes of pathogenic protozoan parasites as well as the genome of Schistosoma mansoni, and show the existence within them of genes encoding homologues of mammalian intracellular Ca2+ release channels: inositol 1,4,5-trisphosphate receptors (IP3Rs), ryanodine receptors (RyRs), two-pore Ca2+ channels (TPCs) and intracellular transient receptor potential (Trp) channels. The genomes of Trypanosoma, Leishmania and S. mansoni parasites encode IP3R/RyR and Trp channel homologues, and that of S. mansoni additionally encodes a TPC homologue. In contrast, apicomplexan parasites lack genes encoding IP3R/RyR homologues and possess only genes encoding TPC and Trp channel homologues (Toxoplasma gondii) or Trp channel homologues alone. The genomes of parasites also encode homologues of mammalian Ca2+ influx channels, including voltage-gated Ca2+ channels and plasma membrane Trp channels. The genome of S. mansoni also encodes Orai Ca2+ channel and STIM Ca2+ sensor homologues, suggesting that store-operated Ca2+ entry may occur in this parasite. Many anti-parasitic agents alter parasite Ca2+ homeostasis and some are known modulators of mammalian Ca2+ channels, suggesting that parasite Ca2+ channel homologues might be the targets of some current anti-parasitic drugs. Differences between human and parasite Ca2+ channels suggest that pathogen-specific targeting of these channels may be an attractive therapeutic prospect