Current Perspective on the Location and Function of Gamma- Aminobutyric Acid (GABA) and its Metabolic Partners in the Kidney.

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter located in the mammalian central nervous system, which binds to GABAA and GABAB receptors to mediate its neurological effects. In addition to its role in the CNS, an increasing number of publications have suggested that GABA might also play a role in the regulation of renal function. All three enzymes associated with GABA metabolism; glutamic acid decarboxylase, GABA ?-oxoglutarate transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH) have been localised to the kidney providing the necessary machinery for localised GABA synthesis and metabolism. Moreover GABA receptors have been localised to both tubular and vascular structures in the kidney, and GABA is excreted in urine (~3 ?M) in humans. Despite the collective evidence describing the presence of a GABA system in the kidney, the precise function of such a system requires further clarification. Here we provide an overview of the current renal GABA literature and provide novel data that indicates GABA can act at contractile pericyte cells located along vasa recta capillaries in the renal medulla to potentially regulate medullary blood flow

P2X receptors: epithelial ion channels and regulators of salt and water transport.

When the results from electrophysiological studies of renal epithelial cells are combined with data from in vivo tubule microperfusion experiments and immunohistochemical surveys of the nephron, the accumulated evidence suggests that ATP-gated ion channels, P2X receptors, play a specialized role in the regulation of ion and water movement across the renal tubule and are integral to electrolyte and fluid homeostasis. In this short review, we discuss the concept of P2X receptors as regulators of salt and water salvage pathways, as well as acknowledging their accepted role as ATP-gated ion channels

Impact Absorbent Rapid Manufactured Structures (IARMS)

Rapid Manufacturing (RM) is increasingly becoming a viable manufacturing process due to dramatic advantages that it facilitates in the area of design complexity. Through the exploration of the design freedom afforded by RM, this paper introduces the concept and initial research surrounding Impact Absorbent Rapid Manufactured Structures (IARMS), with an application in sports personal protective equipment (PPE). Designs are based on the cellular structure of foams; the inherent advantages of the cellular structure are used as a basis to create IARMS that have the potential to be optimised for a specific impact absorbent response. The paper provides some initial results from compression testingMechanical Engineerin

Urinary ATP and visualization of intracellular bacteria: a superior diagnostic marker for recurrent UTI in renal transplant recipients?

Renal transplant recipients (RTR) are highly susceptible to urinary tract infections (UTIs) with over 50% of patients having at least one UTI within the first year. Yet it is generally acknowledged that there is considerable insensitivity and inaccuracy in routine urinalysis when screening for UTIs. Thus a large number of transplant patients with genuine urine infections may go undiagnosed and develop chronic recalcitrant infections, which can be associated with graft loss and morbidity. Given a recent study demonstrating ATP is released by urothelial cells in response to bacteria exposure, possibly acting at metabotropic P2Y receptors mediating a proinflammatory response, we have investigated alternative, and possibly more appropriate, urinalysis techniques in a cohort of RTRs.Mid-stream urine (MSU) samples were collected from 53 outpatient RTRs. Conventional leukocyte esterase and nitrite dipstick tests, and microscopic pyuria counts (in 1 ?l), ATP concentration measurements, and identification of intracellular bacteria in shed urothelial cells, were performed on fresh unspun samples and compared to ‘gold-standard’ bacterial culture results.Of the 53 RTRs, 22% were deemed to have a UTI by ‘gold-standard’ conventional bacteria culture, whereas 87%, 8% and 4% showed evidence of UTIs according to leukocyte esterase dipstick, nitrite dipstick, and a combination of both dipsticks, respectively. Intracellular bacteria were visualized in shed urothelial cells of 44% of RTRs, however only 1 of the 23 RTRs (44%) was deemed to have a UTI by conventional bacteria culture. A significant association of the ‘gold-standard’ test with urinary ATP concentration combined with visualization of intracellular bacteria in shed urothelial cells was determined using the Fisher’s exact test.It is apparent that standard bedside tests for UTIs give variable results and that seemingly quiescent bacteria in urothelial cells are very common in RTRs and may represent a focus of subclinical infection. Furthermore, our results suggest urinary ATP concentration combined with detection of intracellular bacteria in shed urinary epithelial cells may be a sensitive means by which to detect ‘occult’ infection in RTRs

Studies of Mass and Size Effects in Three-Dimensional Vibrofluidized Granular Mixtures

We examine the steady state properties of binary systems of driven inelastic hard spheres. The spheres, which move under the influence of gravity, are contained in a vertical cylinder with a vibrating base. We computed the trajectories of the spheres using an event-driven molecular dynamics algorithm. In the first part of the study, we chose simulation parameters that match those of experiments performed by Wildman and Parker. Various properties computed from the simulation including the density profile, granular temperature and circulation pattern are in good qualitative agreement with the experiments. We then studied the effect of varying the mass ratio and the size ratio independently while holding the other parameters constant. The mass and size ratio are shown to affect the distribution of the energy. The changes in the energy distributions affect the packing fraction and temperature of each component. The temperature of the heavier component has a non-linear dependence on the mass of the lighter component, while the temperature of the lighter component is approximately proportional to its mass. The temperature of both components is inversely dependent on the size of the smaller component.Comment: 14 Pages, 12 Figures, RevTeX

Exact solution of a one-dimensional Boltzmann equation for a granular tracer particle

We consider a one-dimensional system consisting of a granular tracer particle of mass $M$ in a bath of thermalized particles each of mass $m$. When the mass ratio, $M/m$, is equal to the coefficient of restitution, $\alpha$, the system maps to a a one-dimensional elastic gas. In this case, Boltzmann equation can be solved exactly. We also obtain expressions for the velocity autocorrelation function and the diffusion coefficient. Numerical simulations of the Boltzmann equation are performed for $M/m\neq \alpha$ where no analytical solution is available. It appears that the dynamical features remain qualitatively similar to those found in the exactly solvable case.Comment: 17 pages, 3 figures, Accepted in Physica

Economic evaluation of integrated new technologies for health and social care: Suggestions for policy makers, users and evaluators

With an ageing population there is a move towards the use of assisted living technologies (ALTs) to provide social care and health care services, and to improve service processes. These technologies are at the forefront of the integration of health and social care. However, economic evaluations of ALTs, and indeed economic evaluations of any interventions providing both health benefits and benefits beyond health are complex. This paper considers the challenges faced by evaluators and presents a method of economic evaluation for use with interventions where traditional methods may not be suitable for informing funders and decision makers. We propose a method, combining economic evaluation techniques, that can accommodate health outcomes and outcomes beyond health through the use of a common numeraire. Such economic evaluations can benefit both the public and private sector, firstly by ensuring the efficient allocation of resources. And secondly, by providing information for individuals who, in the market for ALTs, face consumption decisions that are infrequent and for which there may be no other sources of information. We consider these issues in the welfarist, extra-welfarist and capabilities framework, which we link to attributes in an individual production model. This approach allows for the valuation of the health component of any such intervention and the valuation of key social care attributes and processes. Finally, we present a set of considerations for evaluators highlighting the key issues that need to be considered in this type of economic evaluation

Close-packed floating clusters: granular hydrodynamics beyond the freezing point?

Monodisperse granular flows often develop regions with hexagonal close packing of particles. We investigate this effect in a system of inelastic hard spheres driven from below by a "thermal" plate. Molecular dynamics simulations show, in a wide range of parameters, a close-packed cluster supported by a low-density region. Surprisingly, the steady-state density profile, including the close-packed cluster part, is well described by a variant of Navier-Stokes granular hydrodynamics (NSGH). We suggest a simple explanation for the success of NSGH beyond the freezing point.Comment: 4 pages, 5 figures. To appear in Phys. Rev. Let