DESIGN AND CHARACTERIZATION OF SEVELAMER HYDROCHLORIDE: A NOVEL PHOSPHATE-BINDING PHARMACEUTICAL

ABSTRACT

Sevelamer hydrochloride (polyallylamine crosslinked with epichlorohydrin) is a polymeric hydrogel that has been developed as an oral pharmaceutical to prevent the absorption of dietary phosphate by kidney dialysis patients. It has been found to bind to phosphate in vitro, and to do so more effectively than a wide range of other cationic polymers. It shows a preference for phosphate over other intestinal anions, such as chloride and bicarbonate. The preference for phosphate is believed to be due to its dianion character, and may also involve hydrogen bonding. The absorption of phosphate in vitro is rapid (less than a minute) relative to the time of passage of such a drug through the small intestine (hours). It has also been found to prevent the absorption of dietary phosphate in vivo and in humans, and is presently awaiting FDA approval.     

A new non-conforming Petrov-Galerkin finite-element method with triangular elements for a singularly perturbed advection-diffusion problem

A new non-conforming exponentially fitted Petrov-Galerkin finite-elementmethod based on Delaunay triangulation and its Dirichlet tessellationis constructed for the numerical solution of singularly perturbedstationary advectiondiffusion problems with a singular perturbationparameter . The method is analyzed mathematically and its stabilityis shown to be independent of . The error estimate in an -independentdiscrete energy norm for the approximate solution is shown todepend on first-order seminorms of the flux and the zero-orderterm of the equation, the sup norm of the exact solution, thefirst-order seminorm of the coefficient of the advection term,and the approximation error of the inhomogeneous term. Sincethe first two seminorms are not bounded uniformly in , the -uniformconvergence of the method still remains an open question. Noassumption is required that the angles in the triangulationare all acute. Since the system matrix for this method is identicalto that for the exponentially fitted box method, the theoreticalresults also provide an analysis of that box method. The newmethod also contains the central-difference and upwind methodsas two limiting cases. It can be regarded as a weighted finite-differencemethod on a triangular mesh. Numerical results are presentedto show the superior performance of the method in comparisonwith the upwind and central-difference methods for a small increasein the computation cost. Present address: School of Mathematics, The University of NewSouth Wales, Kensington, NSW 2033, Australia.     

DISTRIBUTIONS OF FREE RADICALS AMONG AMINO ACIDS FROM LYOPHILIZED ULTRAVIOLET-IRRADIATED PROTEINS

Abstract— The effects of u.v.-irradiation at 254 nm upon lyophilized ribonuclease, lysozyme, insulin, and chymotrypsinogen have been investigated by electron spin resonance (ESR). enzymatic assay, and labeling of free radical sites with tritiated hydrogen sulfide (HST). The ESR signal of the irradiated protein diminishes on exposure to HST, and tritium becomes covalently bound to carbon. The distribution of tritium among the amino acids of each protein. studied as an indicator of the carbon free radical distribution, differs markedly from those observed previously to result from exposure to gamma radiation, electrical discharge. or hydrogen atoms. However, the earlier observation that the tritium distribution is influenced by protein conformation holds true as well for u.v.-irradiation. Moreover, the distributions of tritium among the amino acids of u.v.-irradiated proteins indicate a broad scattering of free radicals. Tyrosine and phenylalanine, residues that absorb light energy in the region of the wavelength employed, are not particularly important as radical carriers. Thus, for ribonuclease, these residues incorporated 3.8 and 1.5 per cent of the total tritium, but they absorb 51 and 12 per cent of the light, respectively. These results, together with the observed low recoveries of methionine, an amino acid that does not absorb at 254 nm, add weight to the concept that a migration of energy ensues after the initial absorption of light energy and that photolytic damage may thus be due to destruction of amino acids other than those initially absorbing the u.v.-radiation.