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Biomedical subjects

P Bauer

Publications and source records attributed to P Bauer.

At least 253 records · Page 14Linked to original sources
PubMedDate not supplied

Selenium, oxygen-derived free radicals, and ischemia-reperfusion injury. An experimental study in the rat.

Circulatory shock and its treatment have been compared to a whole-body ischemia and reperfusion with activation of oxygen-derived free radicals. A pilot study had suggested a selenium redistribution in this context. To verify this hypothesis, an experimental study was designed. Temporary occlusion of the superior mesenteric artery was performed in 18 male adult Wistar rats using clamping for 0, 10, and 20 min. Hemodynamic and biochemical data were assessed before clamping and 20 min after release of the mesenteric blood flow. After release, mean arterial pressure decreased, plasma lactate increased, and erythrocyte glutathione peroxidase decreased. Plasma and erythrocyte selenium did not change; however, a slight decrease in plasma selenium was observed when related to hematocrit (to take into account the fluid balance). Erythrocyte-reduced glutathione did not change. In contrast, liver and kidney selenium increased, whereas reduced glutathione decreased in kidney, but not in liver after 20 min of clamping as compared to the sham-operated group. These results suggest that, after temporary intestinal ischemia, the changes in selenium and reduced glutathione observed in blood and tissues, like liver or kidney, could be related to a redistribution pattern in selenium metabolism during shock injury.

Animals↗
PubMedDate not supplied

Characterization of the highly variable bioavailability of tiludronate in normal volunteers using population pharmacokinetic methodologies.

Currently, the use of classical bioequivalence criteria is being called into question for certain classes of drugs such as bisphosphonates. These compounds typically possess a wide therapeutic index but may be characterized by low and variable absorption. The purpose of this communication was to characterize the highly variable bioavailability of tiludronate using a population pharmacokinetic method (NONMEM program) and compare the results to a standard 2 way cross-over bioequivalence trial in healthy subjects. Over 3500 plasma samples from 153 healthy subjects, representing 12 different clinical trials were pooled for mixed effect modeling purposes (complete data set). These studies, conducted under single and multiple dose conditions, contained all the directly comparable data available in healthy subjects administered a 400 mg dose of tiludronate. A two compartment model with first order absorption was fit to the plasma concentration-time data and a term for relative bioavailability (BA) was included. Intersubject and residual variability were modeled using a constant coefficient of variation (CCV) model. A pilot model development data set was obtained from a 24 subject cross-over bioequivalence study. Population estimates of BA and its associated 90% confidence interval of 1.12 and 0.89-1.35 compared favorably to standard bioequivalence methodology (1.15 and 0.93-1.42, respectively). Since a good fit of predicted and observed plasma concentrations as well as estimates of BA were obtained, a two compartment model with a term for BA was then applied to the complete data set. Under these conditions, BA and its 90% confidence interval were found to be 1.17 and 0.98-1.36. Intersubject variability of 31%, compared with 38% in the pilot model development data set and residual variability of 38% were seen. No differences in absorption characteristics as measured by Ka were found. Good agreement between the population pharmacokinetic parameters were observed when the pilot data set was compared with the full data set. The proposed model was confirmed by creating 10 additional smaller data sets that were matched for the number of subjects given both formulations under single and multiple dose conditions. No change in the estimate of BA was observed under these study conditions. This study demonstrated that population pharmacokinetic methodology can be applied successfully to problematical bioequivalence issues that may occur during the development process. Increasing the number of subjects in the overall analysis did not alter the estimate of BA or its 90% confidence interval, when compared to the original cross-over bioequivalence study. Bayesian approaches can be of value in large clinical trials where typically relatively few plasma samples are obtained from individual subjects.

Biological Availability↗
PubMedDate not supplied

Cell-microcarrier adhesion to gas-liquid interfaces and foam.

The interaction of microcarriers, both with and without cells attached, with gas bubbles was studied. These studies consisted of qualitative microscopic observations of microcarriers with bubbles, quantitative measurements of microcarrier entrapment in foam, and quantitative measurements of the effect of bubble rupture at gas-medium interfaces. Ten different "protective additives" were evaluated for their ability to change the dynamic surface tension of the culture media and to prevent microcarrier adhesion to air bubbles during gas sparging and to prevent entrapment in the foam layer. These studies indicate that microcarriers, with and without cells, readily attach to gas-medium interfaces; yet unlike suspended cells, cells attached to microcarriers are not damaged by bubble ruptures at gas-medium interfaces. Only one surfactant was found to substantially prevent microcarrier entrapment in the foam layer; however, this surfactant was toxic to cells. No correlation was observed between surface tension and the prevention of microcarrier adhesion to gas-liquid interfaces. It is suggested that cell damage as a result of sparging in microcarrier cultures is the result of cells, attached to microcarriers, attaching to rising bubbles and then detaching from the microcarrier as this combination rises through the medium. It is further suggested that the hydrodynamic drag force of the rising microcarrier is sufficiently high to remove the bubble-attached cell from the microcarrier.

Animals↗
PubMedDate not supplied

CO2 removal with hemodialysis and control of plasma oncotic pressure.

CO2 removal by hemodialysis, associated with systemic alkalinization, is the simplest method of metabolic CO2 elimination. In this experimental work, the authors investigated the efficacy of this protocol in modifying an alkaline perfusate by addition of dextran 40. The results, unlike those of preceding experimental series without dextran, disclosed no significant change in weight, hemodynamic variables, electrolyte concentrations or osmotic or oncotic pressures after 12 hours. Sixty-five percent of metabolic CO2 was eliminated with a bypassed blood flow rate of only 8% of cardiac output.

Acid-Base Equilibrium↗