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PubMed1997

Ex vivo degradation of a poly(propylene glycol-fumarate) biodegradable particulate composite bone cement.

We have developed a biodegradable particulate composite bone cement consisting of a poly(propylene glycolfumarate)-(methylmethacrylate) matrix mixed with calcium carbonate and tricalcium phosphate particulates. Previous ex vivo studies suggest that this system provides sufficient strength for a number of potential clinical applications including structural reinforcement of osseous defects, internal fixation devices for age-related fractures, and delivery of antibiotics to treat osteomyelitis. As a first step toward investigating in vivo responses to this material, we studied the influence of varied concentrations of crosslinker, accelerator, and free radical on the mechanical properties of the cement. We then developed an ex vivo degradation assay and correlated the mechanical properties of degrading cement with the temporal changes in chemical properties of both the cement and the bathing medium. The optimal cement formulation was composed of one-third poly(propylene glycolfumarate)-(methylmethacrylate), one-third calcium carbonate, and one-third tricalcium phosphate, and provided initial compressive strengths of up to 30 MPa and compressive moduli of up to 300 MPa. Degradation rates, measured by a decline in mechanical properties, dissolution of calcium from the cement, and change in pH of the bathing medium, could be controlled by changing the concentration of reactants in the matrix. Specifically, an increase in methylmeth-acrylate or increase in both methylmethacrylate and benzoyl peroxide was inversely proportional to the rate of degradation and directly proportional to the initial mechanical properties. The degradation products and environmental changes appear to be compatible with physiologic remodeling and therefore justify examination of the in vivo response to implantation of this material.

Analysis of Variance↗
PubMed1996

Synthesis and calcium antagonistic activity of 8-[N-[2-(3,4-dimethoxy- phenyl)ethyl]-beta-alanyl]-5,6,7,8-tetrahydrothieno[3,2-b][1,4]thiazepi ne fumarate.

KT-362 is an antiarrhythmic and antihypertensive agent with vasodilating activity. Since it carries a homoveratryl group in the side chain, an obvious relation exists to the verapamil-type calcium antagonists. Replacement of the fused aromatic moiety in KT-362 with thiophene provided 8-[N-[2-(3,4-dimethoxyphenyl) ethyl]-beta-alanyl]-5,6,7,8-tetrahydrothieno[3,2-b][1,4] thiazepine (1). Compound 1 shows a negative chronotropic activity in spontaneously beating right atria (IC50 = 23 microM, n = 7), and a negative inotropic effect in papillary muscles (IC50 = 2.7 microM, n = 7) and left atria (IC50 = 4 microM, n = 6) of the guinea-pig heart. The decrease of contractility in papillary muscles could be antagonized by increasing the extracellular calcium concentration. Compound 1 was found to affect high (IC50: 70 +/- 5 microM) and low (IC50: 129 +/- 34 microM) voltage-activated calcium channel currents as well as voltage-activated sodium channel currents (IC50: 80 +/- 13 microM) in chick dorsal root ganglion neurons. In addition nicotine-induced currents were potently inhibited (IC50: 6 +/- 0.7 microM) in bovine chromaffin cells.

Animals↗
PubMed2001

Asymmetric induction in the [4+2]cycloaddition of cyclopentadiene and furan to chiral derivatives of fumaric acid.

[4+2]Cycloaddition reactions of cyclopentadiene (1a) and furan (1b) to N,N'-fumaroyldi[(2R)-bornane-10,2-sultam] (2) and to N,N'-fumaroyldi[(2R)-bornane-10,2-(2'-phenyl-pyrazol-3'-one)] (3) are presented. A correlation between the solvent polarity and the logarithm of the diastereoisomer ratio (dr) was found for the uncatalyzed [4+2]cycloaddition of 1a to 3.

Journal Article↗
PubMed1992

Effects of semotiadil fumarate (SD-3211) on renal hemodynamics and function in dogs.

Studies were carried out to define the effect of semotiadil on renal hemodynamics, renal function and renin release in pentobarbital-anesthetized dogs. Intrarenal arterial infusion of semotiadil resulted in a significant increase in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow, urinary excretion of electrolytes and renin release. Semotiadil did not affect the linear relationship between osmolar clearance and the free water reabsorption rate, and increased the urinary excretion of sodium and calcium to the same extent. These results suggest that the main tubular site of action of semotiadil is the proximal tubule. Intrarenal infusion of a potent non-peptide angiotensin II antagonist, DuP753 (15 micrograms/kg per min), resulted in an increase in RBF, GFR, urine flow and UNaV. In spite of the blockade of the intrarenal renin angiotensin system(RAS) with DuP753, semotiadil caused almost the same effects as it did in the absence of DuP753. These results suggest that the renal effects of semotiadil are independent of the intrarenal RAS.

Analysis of Variance↗
PubMed1984

A comparison of the effect of tiamulin hydrogen fumarate and tylosin tartrate on mycoplasmas of ruminants and some animal ureaplasmas.

The in vitro efficacy of tiamulin was compared to that of tylosin against 7 bovine, 7 ovine and 3 caprine mycoplasma strains isolated from various organs and belonging to different species, as well as 7 ureaplasma strains cultured from cattle, sheep, swine, chickens and turkeys. The minimal mycoplasmacidal concentrations of tiamulin varied between 0.01 and 10.0 micrograms ml-1, while tylosin proved to be active in concentrations of 0.5 and 100.0 micrograms ml-1. Five of 17 mycoplasma strains showed identical sensitivities to both antibiotics while all other strains, including the ureaplasmas, were sensitive to tiamulin at concentrations 5-5000-times lower than tylosin.

Animals↗