Biomedical subjects

L G Stern

Publications and source records attributed to L G Stern.

3 recordsLinked to original sources

PubMed2000

Fractional step methods applied to a chemotaxis model.

A fractional step numerical method is developed for the nonlinear partial differential equations arising in chemotaxis models, which include density-dependent diffusion terms for chemotaxis, as well as reaction and Fickian diffusion terms. We take the novel approach of viewing the chemotaxis term as an advection term which is possible in the context of fractional steps. This method is applied to pattern formation problems in bacterial growth and shown to give good results. High-resolution methods capable of capturing steep gradients (from CLAWPACK) are used for the advection step, while the A-stable and L-stable TR-BDF2 method is used for the diffusion step. A numerical instability that is seen with other diffusion methods is analyzed and eliminated.

Chemotaxis↗

PubMed1993

A nonlinear dosimetric model for hemoglobin adduct formation by the neurotoxic agent acrylamide and its genotoxic metabolite glycidamide.

Hemoglobin (Hb) adducts, formed by the neurotoxic agent acrylamide (AA) and its genotoxic metabolite glycidamide (GA), were measured in the rat by means of a method for simultaneous determination of the adducts formed to cysteine. A novel, nonlinear dosimetric model was developed to describe Hb adduct formation. This model incorporates the saturable kinetics of the metabolic conversion in vivo of AA to GA. The pharmacokinetic parameters Vmax and Km and the first-order rates of elimination, k1 and k2, for AA and GA from all processes except conversion of AA to GA, were estimated directly from Hb adduct data to 19 M hr-1, 66 microM, 0.21 hr-1, and 0.48 hr-1, respectively. At low concentrations, approximately 60% of AA was metabolized to GA. The nonlinear dosimetric model for adduct formation has potential general applicability in high-to-low-dose extrapolation of genotoxic effects.

Acrylamide↗

PubMedDate not supplied

Linear versus nonlinear models for hemoglobin adduct formation by acrylamide and its metabolite glycidamide: implications for risk estimation.

Hemoglobin cysteine adduct levels formed by acrylamide (AA) and its epoxide metabolite glycidamide (GA) as previously determined (Bergmark et al., Toxicol. Appl. Pharmacol., 111: 352-363, 1991) in rats given single injections of AA were used to estimate tissue doses, D = integral of Cdt (area under the concentration curve in the blood compartment), of the two compounds. The data were adapted to linear or nonlinear kinetic models, where the latter model accounted for the Michaelis-Menten kinetics of the metabolic conversion of AA to GA. In the linear model, the first-order rates, k*, of elimination from all processes were estimated to be 0.50 and 0.48 h-1 for AA and GA, respectively. In the nonlinear model, the parametrical values Vmax = 19.1 h-1 and Km = 66 microM for the in vivo metabolic conversion of AA to GA, and k1 = 0.21 h-1 and k2 = 0.48 h-1 for the first-order rates of elimination from all other processes of AA and GA, respectively, were found to give the best fit to the exact dosimetric expressions [formula: see text] Using Equation B, it was estimated that the percentage of AA converted to GA approaches 58% when [AA]o, the initial concentration of AA, approaches zero. The implications for high-to-low-dose extrapolation of toxic effects of the derived mathematical relationships between administered dose and tissue dose are discussed.

Acrylamide↗