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Biomedical subjects

A H Scaf

Publications and source records attributed to A H Scaf.

45 records · Page 3Linked to original sources
PubMed1975

Cooperativity in classical receptor theory.

Classical receptor-theory presents models of the relation between drug concentration and biological effect, also in the case where more than one binding site on a receptor must be occupied by the agonist to evoke a response. These models have considered only the possibility that none or all of these sites on the receptor are occupied by drug molecules; the possibility that receptors might by only partly occupied was disregarded. The present paper considers the consequences of this last possibility. It is concluded that the relation between concentration and effect, represented in different types of plots, is not determined only by the order of the reaction between the drugs and their receptors, but also by the ratios of the dissociation constants for the different steps of dissociation of the drug-receptor complex. This may make it almost impossible to make statements about the order of the reaction between drugs and receptors based on experimental data, and to discriminate between allosteric and classical receptor-theories.

Binding Sites↗
PubMedDate not supplied

Pharmacokinetic analyses with RUGFIT: an interactive pharmacokinetic computer program.

RUGFIT is an interactive computer program to fit polyexponential equations to experimental points without the need of assumptions about the number of exponential terms and without the need of initial parameter estimates. The fitting is performed by iterative stripping minimizing the sum of squared residuals. This procedure leads to multiple model equations describing the profile of the y-value in time, that are compared with the test of Boxenbaum et al. The examples analysed in this paper are: a plasma decay curve after an intravenous bolus injection and one after an oral gift, a dA/dt versus time curve with a lag time and a curve possibly reflecting an entero-hepatic recirculation. The outcomes are, where possible, compared with the outcomes obtained with the computer programs CFT3, NONLIN, and NONLINEAR (SPSS). The latter three programs sometimes run into a local minimum, as the outcomes obtained with RUGFIT were close to the best ones obtained with the other programs. The analyses with RUGFIT show that a choice of an inadequate model equation can lead to a marked error in the value of the area under the curve that may result in a marked error of, for instance, the bioavailability. The procedures of RUGFIT are illustrated in the Appendix. RUGFIT also contains options to calculate microparameters, to simulate dosage regimes, to calculate exponents and intercepts from rate constants and to analyse time effect relationships.

Animals↗
PubMedDate not supplied

Strand break repair, DNA polymerase activity and heat radiosensitization in thermotolerant cells.

HeLa S3 cells were made thermotolerant by 'chronic' (5 h at 42 degrees C) or 'acute' (15 min at 44 degrees C followed by 5 h at 37 degrees C) heat treatments. Cell survival, repair of radiation-induced DNA strand breaks, alpha and beta DNA polymerase activity and radiation sensitivity following hyperthermia were all measured in both control and thermotolerant cells. The ability to repair DNA strand breaks correlated well with cell survival following hyperthermia. Hyperthermic inhibition of strand break repair was reduced in thermotolerant relative to control cells, although the thermal tolerance ratios for repair were less than for hyperthermic cell killing. Both radiosensitization and DNA polymerase inactivation by hyperthermia were only slightly reduced in thermotolerant relative to control cells. Hence a poor correlation was found between these two parameters and hyperthermic cell survival. For all heat treatments applied, alpha and beta DNA polymerase activity correlated well with the extent of hyperthermic radiosensitization.

Cell Survival↗