Towards the physiological function of uric acid

A drug and drug delivery system may be utilized in the treatment of vascular disease. A local delivery system is coated with rapamycin or other suitable drug, agent or compound and delivered intraluminally for the treatment and prevention of neointimal hyperplasia following percutaneous transluminal coronary angiography. The local delivery of the drugs or agents provides for increased effectiveness and lower systemic toxicity.

Drug/Drug Delivery Systems For The Prevention And Treatment Of Vascular Disease

The present invention relates generally to the control of body weight of animals including mammals and humans, and more particularly to materials identified herein as modulators of weight, and to the diagnostic and therapeutic uses to which such modulators may be put. In its broadest aspect, the present invention relates to the elucidation and discovery of nucleotide sequences, and proteins putatively expressed by such nucleotides or degenerate variations thereof, that demonstrate the ability to participate in the control of mammalian body weight. The nucleotide sequences in object represent the genes corresponding to the murine and human OB gene, that have been postulated to play a critical role in the regulation of body weight and adiposity. Preliminary data, presented herein, suggests that the polypeptide product of the gene in question functions as a hormone. The present invention further provides nucleic acid molecules for use as molecular probes, or as primers for polymerase chain reaction (PCR) amplification, i.e., synthetic or natural oligonucleotides. In further aspects, the present invention provides a cloning vector, which comprises the nucleic acids of the invention; and a bacterial, insect, or a mammalian expression vector, which comprises the nucleic acid molecules of the invention, operatively associated with an expression control sequence. Accordingly, the invention further relates to a bacterial or a mammalian cell transfected or transformed with an appropriate expression vector, and correspondingly, to the use of the above-mentioned constructs in the preparation of the modulators of the invention. Also provided are antibodies to the OB polypeptide. Moreover, a method for modulating body weight of a mammal is provided. In specific examples, genes encoding two isoforms of both the murine and human OB polypeptides are provided.

Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof

An implantable medical device carries on at least part of its external surface a coating. The coating consists essentially of aterpolymer of vinyl pyrrolidone, acrylic acid and activated acrylic acid, and optionally a colouring agent.

Coated medical devices

Objectives:The purpose of this study was to determine the ability of dynamic 64 slice multidetector computed tomography (d-MDCT) to provide an accurate measurement of myocardial blood flow (MBF) during first-pass d-MDCT using semiquantitative and quantitative analysis methods.Materials and Methods:S

Quantification of myocardial perfusion using dynamic 64-detector computed tomography.

Much of the adenosine formed in the heart is degraded by endothelial enzymes to uric acid, which is exported across the coronary capillary endothelial cell membrane before renal excretion. Because previous experiments suggested that cell permeability for uric acid is either very high (similar to water) or very low, multiple indicator-dilution experiments were carried out to distinguish between the two possibilities. An intravascular reference tracer, 131I-labeled albumin, and an extracellular reference tracer, L-[3H]glucose, were injected together with [14C]uric acid as a bolus into the coronary inflow, while fractionating the venous outflow for 90 s. Recovery of injected uric acid averaged 99.0 +/- 2.9% (mean +/- SD, n = 12) that of L-glucose. Peak capillary extraction of L-glucose and uric acid averaged 0.38 +/- 0.032 and 0.42 +/- 0.035 (P less than 0.005) compared with albumin. Except at the peaks, the dilution curves for [14C]uric acid and L-[3H]glucose coincided closely, indicating that little uric acid was transported into cells. The dilution curves were analyzed using an axially distributed, multipathway, four region mathematical model, to estimate membrane permeability-surface area (PS) products. Since the endothelial cell PS for uric acid was low (0.12 +/- 0.09 ml.g-1.min-1), approximately 3% of the PS reported for adenosine, the possibility of flow-limited exchange for uric acid is ruled out. To estimate steady-state endothelial concentrations of uric acid in vivo, equations were developed describing electrochemical potential gradients for dissociated and undissociated forms of a weak acid. Despite endothelial production, intracellular concentrations that are lower than outside are expected because the negative membrane potential and lower cellular pH assist uric acid efflux.

/pdf/capillary-endothelial-transport-of-uric-acid-in-guinea-pig-5avrp2z2w2.pdf

Capillary endothelial transport of uric acid in guinea pig heart.

Appetite suppression factor and related methods appetite suppression factor and related methods

Endothelial cells lining myocardial capillaries not only impede transport of blood solutes to the contractile cells, but also take up and release substrates, competing with myocytes. Solutes permeating this barrier exhibit concentration gradients along the capillary. This paper introduces a generic model, GENTEX, to characterize blood–tissue exchanges. GENTEX is a whole organ model of the vascular network providing intraorgan flow heterogeneity and accounts for substrate transmembrane transport, binding and metabolism in erythrocytes, plasma, endothelial cells, interstitial space and cardiomyocytes. The model is tested here for the analysis of multiple tracer indicator dilution data on purine nucleoside metabolism in the isolated Krebs–Henseleit-perfused non-working hearts. It has been also used for analysing NMR contrast data for regional myocardial flows and for positron emission tomographic studies of cardiac receptor kinetics. The facilitating transporters, binding sites and enzymatic reactions are nonlinear elements and allow competition between substrates and a reaction sequence of up to five substrate–product reactions in a metabolic network. Strategies for application start with experiment designs incorporating inert reference tracers. For the estimation of endothelial and sarcolemmal permeability-surface area products and metabolism of the substrates and products, model solutions were optimized to fit the data from pairs of tracer injections (of either inosine or adenosine, plus the reference tracers) injected under the same circumstances a few minutes later. The results provide a self-consistent description of nucleoside metabolism in a beating well-perfused rabbit heart, and illustrate the power of the model to fit multiple datasets simultaneously.

/pdf/gentex-a-general-multiscale-model-for-in-vivo-tissue-4sqk7ssgt7.pdf

GENTEX, a general multiscale model for in vivo tissue exchanges and intraorgan metabolism.

The influence of transmembrane flux limitations on cellular metabolism of purine nucleosides was assessed in whole organ studies. Transcapillary transport of the purine nucleosides adenosine (Ado) ...

/pdf/cardiac-endothelial-transport-and-metabolism-of-adenosine-499yiy1gsj.pdf

Cardiac endothelial transport and metabolism of adenosine and inosine

Methods for identifying factors that regulate appetite are disclosed. N-terminally-modified ob protein useful as an appetite suppression factor is also disclosed. Further, methods for purifying ob protein from yeast cells transformed with recombinant ob protein are described.

Thomas R. Bukowski

Papers

Capillary endothelial transport of uric acid in guinea pig heart.

Appetite suppression factor and related methods appetite suppression factor and related methods

GENTEX, a general multiscale model for in vivo tissue exchanges and intraorgan metabolism.

Cardiac endothelial transport and metabolism of adenosine and inosine

Appetite suppression factor and related methods