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Biomedical subjects

R Heinrich

Publications and source records attributed to R Heinrich.

At least 73 records · Page 4Linked to original sources

[Prosthetic status, conditions of the oral mucosa and temporomandibular joint, as well as treatment needs in the elderly population of a Hungarian city (Györ) II].

In a Hungarian city a special oral health survey concerning prosthetic status, oral mucosa and temporo-mandibular joint condition of the elderly population has been performed by standardized methods. The most frequent prosthetic finding was the removable prosthetic appliance (denture). It is suggested, that the number of dentures should be decreased with higher priority for the preservation of natural dentition and it should be achieved to change the dentures at proper intervals among denture-wearing patients. The prevalence of temporo-mandibular joint function-disturbances was low. In order to diagnose earlier the praecancerous lesions and conditions a regular oral health survey at least once a year among the people above 55 years of age should be organized.

Aged↗

Evolutionary optimization of enzyme kinetic parameters; effect of constraints.

The distribution of the kinetic parameters of enzymic reactions is theoretically studied, on the assumption that, during evolution, the increase of reaction rates was an important target of natural selection. In extension of previous work on the optimization of enzyme kinetic parameters, the influence of constraints concerning upper limits of the individual rate constants is analyzed. The concept of "evolutionary effort" is applied to derive an expression for the cost function, leading to an overall upper limit for the values of the rate constants. The resulting optimization problem is solved for ordered mechanisms involving different numbers of elementary steps. It is shown that the optimum for the enzyme kinetic parameters strongly depends on the concentrations of the reactants. Low reactant concentrations lead generally to a tight binding of the reactants, while high concentrations result in a weak binding, favouring the rate constants of the other steps. In particular, states of maximum activity are not always characterized by maximal values of second-order rate constants. The results support the hypothesis that there is a mutual adaptation of Michaelis constants and reactant concentrations in an evolutionary timescale. In the limit of infinite values of the exponent of the cost function the results of the present "overall limit model" turn into the results of a model which takes into account individual upper limits for rate constants ("separate limit model"). The distributions of optimal rate constants are discussed in terms of free-energy profiles. The model is applied to the interpretation of the kinetic data of triosephosphate isomerase and inorganic pyrophosphatase.

Animals↗

The kinetic basis of threshold effects observed in mitochondrial diseases: a systemic approach.

Threshold effects in the expression of metabolic diseases have often been observed in mitochondrial pathologies, i.e. the clinical demonstration of the disease appears only when the activity of a step has been reduced to a rather low level. We show experimentally that an inhibition of cytochrome c oxidase activity by cyanide, simulating a defect in this step, leads to a decrease in mitochondrial respiration which then exhibits a threshold behaviour similar to that observed in mitochondrial diseases. We discuss this behaviour in terms of metabolic control theory and construct a mathematical model simulating this behaviour.

Animals↗

A second-order approach to metabolic control analysis.

In the mathematical formalism of metabolic control analysis the changes in metabolite concentrations and fluxes have been related to the underlying parameter perturbations by a linear approximation, thus restricting the analysis to very small parameter perturbations. Obviously, the response of the system variables to larger parameter perturbations can be described more accurately if, in addition to the linear terms, the second-order terms are considered. The basic equations of this approach are derived. The second-order effects can be expressed (i) by the second-order elasticity coefficients of the reaction rates with respect to the kinetic parameters and/or metabolite concentrations, and (ii) by the control coefficients and pi-elasticities of the linear theory. Parameter-independent second-order control coefficients can be defined if the reaction rates depend linearly on the perturbation parameters. These coefficients satisfy summation theorems similar to those of the linear theory. The formalism is applied to an unbranched chain of monomolecular reactions and to a skeleton model of glycolysis. The second-order approximation turns out to be more accurate for a relatively wide range of rate perturbations. However, the use of the second- and higher-order expansions for tackling practical problems seems limited since the required higher-order elasticity coefficients may be hard, if not impossible, to obtain experimentally. These difficulties, as well as the general limitations of the local approach of metabolic control analysis, may be compensated for by a combination with kinetic modelling.

Animals↗

Mathematical modelling of lipid transbilayer movement in the human erythrocyte plasma membrane.

A model is presented to simulate transverse lipid movement in the human erythrocyte membrane. The model is based on a system of differential equations describing the time-dependence of phospholipid redistribution and the steady state distribution between the inner and outer membrane monolayer. It takes into account several mechanisms of translocation: (i) ATP-dependent transport via the aminophospholipid translocase; (ii) protein-mediated facilitated and (iii) carrier independent transbilayer diffusion. A reasonable modelling of the known lipid asymmetry could only be achieved by introducing mechanism (iii). We have called this pathway the compensatory flux, which is proportional to the gradient of phospholipids between both membrane leaflets. Using realistic model parameters, the model allows the calculation of the transbilayer motion and distribution of endogenous phospholipids of the human erythrocyte membrane for several biologically relevant conditions. Moreover, the model can also be applied to experiments usually performed to assess phospholipid redistribution in biological membranes. Thus, it is possible to simulate transbilayer motion of exogenously added phospholipid analogues in erythrocyte membranes. Those experiments have been carried out here in parallel using spin labeled lipid analogues. The general application of this model to other membrane systems is outlined.

Adenosine Triphosphate↗

Carrier-mediated residual K+ and Na+ transport of human red blood cells.

Residual, i.e., (ouabain, bumetanide, and EGTA)-insensitive K+ and Na+ influxes as well as effluxes of human red blood cells are enhanced in isotonic solutions of low (NaCl + KCl) concentration using sucrose to maintain constant osmolarity. Various carrier models were tested to fit the experimental data of these fluxes simultaneously. The residual K+ and Na+ fluxes can be described on the basis of a carrier mechanism of competing substrates with modifier sites.

Biological Transport↗

The definitions of metabolic control analysis revisited.

Various definitions of coefficients in metabolic control analysis are examined with respect to their theoretical consistency and practical applicability. We suggest agreement upon a definition for control coefficients which is clearly distinct from that for response coefficients, in such a way that the former describe inherent properties of the metabolic system while the latter refer to the influence of special parameters. Advantages and drawbacks of using normalized or non-normalized control coefficients are studied. It is shown that normalized control coefficients have the advantage of being invariant to a different rescaling of the particular fluxes. We demonstrate that some problems are easier to tackle if the consistency of time-independent control coefficients with their time-dependent counterparts is taken into account. It is shown that the matrix of flux control coefficients is an indempotent matrix. This allows an interpretation in terms of the transduction of the effect of parameter perturbations. Several aspects of the experimental measurement of control coefficients are discussed, with special reference to the different definitions.

Enzymes↗

[Long-term results with dental treatment concepts for disabled children].

More than 10 years ago 400 mentally and physically handicapped children aged 3 to 18 years were included in a dental care program to improve their oral health status. Besides dental treatment a comprehensive preventive program (tooth brushing, application of fluorides, dietetic recommendations) was carried out. The results prove a significant caries reduction and an increase in caries free children. A reduction of dental plaque and marginal inflammations were also observed. To prevent the carious destruction of the dentition of the handicapped, these patients should receive regular prevention-oriented dental care from the age of 3 years.

Adolescent↗

Kinetic parameters of enzymatic reactions in states of maximal activity; an evolutionary approach.

A theoretical investigation is presented which allows the calculation of states of maximal reaction rates for single enzymes and for unbranched enzymatic chains. As an extension to previous papers (Heinrich & Holzhütter, 1985, Biomed. biochim. Acta 44, 959-969; Heinrich et al., 1987, Bull. math. Biol. 49, 539-595) a detailed enzymatic mechanism was taken into consideration. Conclusions are drawn for the optimal values of the microscopic rate constants as well as of the maximal activities and Michaelis constants. Ten solutions are found which depend on the equilibrium constant as well as on the concentrations of substrates and products. It is shown that for high equilibrium constants one of the solutions applies to a very large range of the concentrations of the outer reactants. This solution is characterized by maximal values of the rate constants of all forward reactions and by non-maximal values of the rate constants of all backward reactions. In contrast to previous assumptions (Albery & Knowles, 1976b, Biochemistry 15, 5631-5640; Burbaum et al., 1989, Biochemistry 28, 9293-9305) states of maximal reaction rate are not always characterized by the highest possible values of the second-order rate constants which are related to the diffusion of the substrate and the product to the active site of the enzyme. Predictions are made concerning the ratios of maximal activities in optimal states as well as for the adaptation of the Michaelis constants to the concentrations of the outer reactants. Using metabolic control analysis it is shown that the solutions obtained for single enzymes may also be applied in multi-enzyme systems.

Animals↗

Minimization of intermediate concentrations as a suggested optimality principle for biochemical networks. II. Time hierarchy, enzymatic rate laws, and erythrocyte metabolism.

The multiobjective problem of minimizing all intermediate concentrations is solved for a model of glycolysis, the pentose monophosphate shunt and the glutathione system in human erythrocytes. It turns out that one solution out of four obtained corresponds qualitatively to the real system. Furthermore, it is shown that for any reaction system, the mentioned optimality principle implies distinct time hierarchy in that some reactions are infinitely fast and subsist in quasi-equilibrium. Finally, the relationships to the standard method of deriving enzymatic rate laws are discussed.

Energy Metabolism↗

[The diagnosis of approximal caries--a comparison of clinical, fiber optic and x-ray diagnostic procedures (the diagnosis of approximal caries)].

A comparison of the efficiency of fibre-optic transillumination with clinical and radiographic diagnosis of proximal caries in posterior teeth was carried out on 186 subjects aged 12 to 17 years. The proportion of diagnosed proximal lesions detected by fibre-optic transillumination was two times more often than by clinical examination while the increase in lesion detection by bitewing radiography was more than threefold. Taking radiographic diagnosis as the validating criteria, the sensitivity of clinical examination was 0.30 and of fibre-optic transillumination 0.68 resp. The specificity was 0.99 for both examinations. In patients with low prevalence of proximal caries and good preventive dental care fibre-optic transillumination should be used as an additional method before using of regular radiographic diagnosing of proximal caries.

Adolescent↗

[Clinical controlled study on the treatment of deep carious lesions in deciduous molars].

Compared with a step-by-step procedure, the one-step excavation of deep carious lesions in primary molars proved to be the treatment of choice in a clinically, microbiologically and histologically controlled trial. The stepwise method failed to produce any significant reduction in pulp exposure. Sensitivity assessment and percussion findings did not result in a reliable and unambiguous evaluation of treatment success. Histology showed inflammation-free pulps in 67% of the deciduous molars irrespective of the treatment method used. Microbiological examination revealed slightly softened dentin to be significantly more infected than clinically acceptable, hard dentin; although only 59.3% of the cavity floors were free of microorganisms. Chronic pulp inflammations were correlated with the presence of streptococci and lactobacilli, whereas actinomycetes were associated with inflammation-free pulps.

Case-Control Studies↗

[Tooth health and periodontal condition in adults with and without root caries].

In a population sample of 2261 men and women aged between 35 and 74 years the prevalence of root caries increased for both sexes consistently with age and ranged between 49 and 73%. In the mean 1.8 to 2.9 teeth were affected. Subjects with root caries had fewer teeth, more teeth with untreated coronal caries, and more teeth which needed conservative treatments. The number of extractions required was the same in subjects affected by root caries. In the age older than 65 years subjects affected by root caries had more teeth in the average of 2 teeth and significantly more fillings in their teeth. If a DMF/T-index of 15 to 19 was recorded nearly half of all subjects were affected by root caries. In individuals with root caries lesions aged between 35 and 54 years significant severe periodontal disease were seen.

Adult↗

[Will root caries become a treatment problem of the future?].

Based upon the present prevalence of root caries an attempt is taken to evaluate the future importance of this carious type. A population sample of 2,261 men and women aged 35 to 74 years were examined. The participation rate was 81%. Root caries was recorded when the lesion was obviously soft and located on cementum. The prevalence of root caries increased for both sexes almost consistently with age and ranged between 49 and 73%. In the mean 1.8 to 2.9 teeth were affected. Root caries was found more often among men than women. Over the sixth decades the reduction of the relative frequency of root caries was stated. Up to this age the rates of tooth extraction were higher than the rates of incidence. If it succeeded that in the future aged people will retain more teeth than nowadays a increase of root caries can be expected.

Adult↗