Biomedical subjects

R Guthke

Publications and source records attributed to R Guthke.

9 recordsLinked to original sources

PubMed1988

[Changes in the pharmacokinetics of gentamycin during nephrotoxic therapy].

Nephrotoxicity secondary to aminoglycoside antibiotic therapy is a well-known complication in clinical medicine. We have analysed the influence of a 10-day gentamicin treatment with 3.40 mg/d on pharmacokinetic parameters and renal excretion of electrolyses and beta-NAG in 10 patients (9 female, 1 males) with UTJ. Using compartment-independent methods the following kinetic parameters at the first and 10th day of treatment were estimated: total body clearance from 100 to 80 ml/min (-20%), mean residence time from 2.7 to 3.5 h (+28%) and AUC from 6.7 to 9.4 mg/l.h (+41%). Similar results could be obtained using a linear two-compartment model: k13 is changed from 0.74 to 0.54 h-1 (-27%). Vdss approximately 16 1, k12 and k21 are not significantly influenced. There was no significant difference between the first and 10th day for renal excretion electrolyses, urine volume and osmolality with the exception of beta-NAG, which increased from 7.2 to 11.7 U/l (p less than 0.05). From the results it can be concluded that even a ten day gentamicin treatment with normal doses and serum concentrations in the therapeutic range less than 5 mg/l induce nephrotoxic effects at the glomerular and tubular side of the nephron. For quantification of the nephrotoxic effects we propose a nonlinear two-compartment model with a new pharmacokinetic parameter for renal damage. This new model allows to predict and to compare the nephrotoxic effects for different aminoglycoside antibiotics and different modes of treatment.

Electrolytes↗

PubMed1987

Dynamic model of the pathogenesis of Mengo virus infection in mice.

A mathematical model of the pathogenesis of experimental Mengo virus infection in mice has been developed and fitted using kinetic data of both virus multiplication in different organs and mortality. The behaviour of the model proved to be bistable. In contrast to the widely accepted hypothesis that an acutely virus-infected host dies when virus replication has attained a critical level in the main target organ, the present results showed the following: the maximum virus titre in brain, the main target organ, has been reached already 24 hr post infection (p.i.) but the animals began to die since 60 hr. Hence, it was postulated and confirmed by a good model fit to the experimental data that the so-called AUC (area under the curve) of the virus multiplication kinetics may be a critical quantity. From this finding a hypothesis was deduced assuming that in the presence of high amounts of the virus the antiviral effect of IFN wanes with time. Since this process accounts for death, it may be a potential target of antiviral therapy.

Animals↗

PubMed1985

Two-pool model analysis of data in hemodialysis by means of programmable pocket calculator TI 59.

Four parameters of a two-pool model are evaluated by an iterative method using the explicit solutions of the linear differential equations. For this it was presumed that the residual renal clearance is sufficiently small. Five data pairs of measured plasma concentrations ci for the time points ti (i = 0 to 4), as well as the dialyzer and residual renal clearances (KD and KR), must be given and put in the calculator. A sample run is shown for urea kinetics. The parameter estimation takes about 10 min. The program is suitable to assist in the individualization of dialysis therapy.

Computers↗

PubMed1984

Model aided dynamic process analysis and optimization for the nourseothricin fermentation.

The relation between product formation and growth kinetics could be characterized by two facts: the specific product formation rate depends on the ageing of the population and on the specific growth rate. These relation was formulated and quantified by a mathematical model, which was fitted to experimental data of a representative fermentation run und used to predict an optimal fermentation mode. In the result of this discussion cyclic fed batch fermentation was found to be optimal.

Anti-Bacterial Agents↗

PubMed1984

Dynamic model of discontinuous and continuous phaseolotoxin production of Pseudomonas syringae pv. phaseolicola.

From experimental data of kinetics of growth, glucose consumption and product formation of Pseudomonas syringae pv. phaseolicola the development and parameter estimation of a mathematical model is presented. The model describes the behaviour of both, batch and chemostat culture, as well as for different temperatures. The model is favoured for dynamic optimization studies. Maximal productivity is reached in the chemostat for a dilution rate which is only a little bit smaller than the wash out point.

Culture Media↗

PubMed1980

Bistability in a model of microbial product formation.

A mathematical model of continuous growth of microorganisms and product formation with growth inhibition by the product is presented and investigated. Two stable steady states occur due to the competion of growth and product formation for the same limiting substrate. One stable state is characterized by a high product concentration but low biomass concentration whereas the other state is characterized by the opposite relations. The first steady state is approached by oscillating kinetics. Both phenomena are consistent with frequently observed kinetic instabilities in industrial fermentation processes.

Anti-Bacterial Agents↗

PubMed1978

[Multiphasic growth of microorganisms: modeling and computer simulation of linear growth phases].

A phenomenological and a more causal model are developed for the multiphasic discontinuous growth. The first model distinguished between the lag-phase, the exponential phase, the transient phase from the exponential to the linear phase, the linear phase, the transient phase from the linear to the stationary phase, and the stationary phase. The parameters are rate constants, critical values of biomass, and time constants. The parameters are estimated for experimental data of growth of Candida lipolytica under limitation of thiamine (Müller et al. 1978). These data are fitted also by a more causal model. This second model is in agreement with Monod's idea that a linear growth phase may be due to an enzyme or enzyme system which has a constant activity. In the analysed case of limitation of thiamine the constancy of the dehydrogenase activity is caused by a constant level of the coenzymethiaminepyrophosphate. Thus, when such a thiamine requiring enzymatic step becomes to the "bottle-neck", bacterial culture switches over from exponential to linear growth. The end of linear phase is discussed more hypothetically by the high cooperativity of activity of dehydrogenases and the existence of a mimimal specific growth rate. The results of modeling and parameter estimation are compared with experimental data of C. lipolytica. These two models are able to interpret the growth kinetic of these multiphasic growth.

Candida↗

PubMed1977

A mathematical model of microbial growth including an intermediate. I. Growth in batch cultures.

A mathematical model of microbial growth is presented and examined which, in contrast to the well-known MONOD model, includes transitions from one cell "bottle-neck" to another. This is achieved by introducing an intermediate product in the model. Three variants of the model for different regulatory functions of the intermediate are considered. The results permit to describe a set of experimentally observable microbial growth curves. According to the model, the shape of the growth curves, the kinetics of substrate consumption and changes of intermediate concentration depend on culture prehistory and the nature of the intermediate regulatory function.

Bacteria↗

PubMedDate not supplied

Influence of steroid hormones on pS2/BCEI gene expression in xenografted colon tumors.

The biological function of the hormone inducible human pS2/BCEI gene, cloned from the breast cancer cell line MCF-7, still remains unknown. Our aim was to determine the in vivo influence of steroid hormones on pS2 expression and tumour growth in colorectal tumours. We transplanted aliquots of human colon tumours into male and female nude mice and studied tumour growth and expression of the pS2/BCEI gene by immunostaining and mRNA analysis. Our results show that the sex of the host and therefore the hormonal background does not play a dominant role in pS2 expression and growth of the xenografts.

Animals↗