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Biomedical subjects

R Bauer

Publications and source records attributed to R Bauer.

At least 235 records · Page 13Linked to original sources

Deterministic--chaotic and periodic properties of heart rate and arterial pressure fluctuations and their mediation in piglets.

OBJECTIVE: Only the simultaneous analysis of periodic and nonlinear properties of heart rate fluctuations (HRF) can describe completely this complex physiological process. Up to now there is, apart from a study of our own, no systematic and correlative investigation using both parameter groups, also not in early development. Thus, we tried to describe in this manner these properties of HRF, the corresponding mean arterial pressure fluctuations (MAPF) and respiratory movements (RM) and their mutual relations in neonatal pig. METHODS: In 6 term newborn piglets, periodic properties of HRF, RM, and MAPF were analyzed by spectral and coherence analysis, and deterministic-chaotic properties by calculation of correlation dimension (CD), Lyapunov exponent (LE), and construction of phase space plots. The assumption of deterministic chaotic components was supported by Theiler's test for nonlinearity, by always positive leading LEs, and by the results of a nonlinear deterministic model. These analyses were done in sleep states, general anaesthesia, hypoxic hypoxia, in ventilated state, and during cholinergic and additional beta-adrenergic blockade. RESULTS: In all experimental states, HRF and MAPF have periodic and nonlinear, very probably deterministic-chaotic properties, but in different relations. In anaesthetized piglets, periodic properties of HRF and MAPF dominate. In hypoxia the decreasing LE and CD of HRF and CD of MAPF were connected with increasing MAPF power density. Cholinergic blockade caused a decreased overall HRF and MAPF power and a decreasing LE and CD, but beta-adrenergic blockade decreased a small part of power density of both in 0.02-0.08 Hz only. The results of CD, LE, Theiler's test and the low dimensional deterministic model data suggested mainly deterministic-chaotic properties in the nonlinear part of HRF and MAPF. CONCLUSIONS: Already in neonatal piglets, both periodic and nonlinear, very probably deterministic chaotic properties of HRF and MAPF exist which change both during hypoxia and cholinergic blockade. They are partly cholinergically and--to a small extent--also beta-adrenergically mediated. The decrease of nonlinear complexity of HRF and MAPF during hypoxia suggests characteristic pathological change even in early development.

Anesthesia, General↗

[Echinacea drugs--effects and active ingredients].

Echinacea-containing drugs have to be classified according to the used plant species (Echinacea purpurea, E. pallida or E. angustifolia), the processed part of the plant (root, upper parts or whole plant), and the mode of processing. Significant pharmacological effects have been found in vitro and in vivo for the expressed juice of the upper parts of E. purpurea and for alcoholic extracts of the roots of E. pallida, E. angustifolia and E. purpurea. The activity is mainly directed towards the nonspecific cellular immune system. Several active constituents are discussed: polysaccharides, glycoproteins, caffeic acid derivatives (cichoric acid) and alkamides.

Adjuvants, Immunologic↗

Effect of inhibitors on the coordination geometries of cadmium at the metal sites in angiotensin-I-converting enzyme.

Perturbed angular correlation of gamma-rays (PAC) spectroscopy has been used to investigate the angiotensin-I-converting enzyme (ACE) of rabbit lung. By substituting the zinc ions in ACE with excited 111mCd2+ ions, analysis of PAC spectra gave directly the percentage of cadmium ions bound to ACE. The result of the analysis was a dissociation constant of about 1 microM for the cadmium-ACE complex, and a stoichiometry of two moles cadmium/mole enzyme. Cadmium binding is thus about two orders of magnitude weaker than zinc binding to ACE but two orders of magnitude stronger than cobalt binding. PAC spectra monitor the nuclear quadrupole interaction (NQI) for 111mCd. The NQI for ACE exhibits very low frequencies in the PAC spectra with a rather large spectral broadening. In the presence of the inhibitor ramiprilat, the frequencies increase but the spectral broadening is about the same as for ACE without inhibitor. When the inhibitor captopril is added, very high frequencies are obtained consistent with sulfur binding, but now with a narrower distribution of NQI's. A simple molecular orbital analysis of the obtained NQI's has been performed, using a coordination sphere of two His, one Glu residue and a solvent ligand, equivalent to the zinc ligands in thermolysin and carboxypeptidase. The calculated spectral parameters could be modelled with the measured parameters if the solvent ligand is H2O in free ACE, carboxylate from ramiprilat in the ACE-ramiprilat complex and a mercapto group in the ACE-captopril complex. The coordination geometry for cadmium carboxypeptidase obtained by X-ray diffraction gives a calculated set of NQI parameters consistent with the measured parameters for cadmium in the captopril-ACE complex using a mercapto group as the solvent ligand. However, for ACE and its complex with ramiprilat, a significant distortion of the cadmium geometry for carboxypeptidase A had to be adopted in order to calculate NQI's close to the experimental values.

Angiotensin-Converting Enzyme Inhibitors↗

Structure of metal site in Cd-substituted His117Gly mutant of azurin with and without addition of imidazole derivatives.

The present work uses 111mCd-perturbed angular correlations of gamma-rays (PAC) to investigate the structure of the metal site of the His117Gly mutant of Pseudomonas aeruginosa azurin in aqueous solution and the effect on the structure upon addition of the following exogenous ligands: imidazole, 4-methyl imidazole, 1-methyl imidazole, 2-methyl imidazole and histidine. The nuclear quadrupole interaction of cadmium bound to the mutant without addition of exogenous ligands shows a strong pH dependence with three different nuclear quadrupole interactions consistent with two pKa values at about 7.2 and 8.6 at 2 degrees C. Addition of the imidazole derivatives resulted in a significant change in the PAC spectrum showing that they coordinate. This is in accordance with observations by EPR for the same mutant with copper at the metal site [den Blaauwen, T. & Canters, G. W. (1993) J. Am. Chem. Soc. 115, 1121-1129]. However, whereas EPR and ultraviolet/visual absorption show that the characteristics of the wild-type copper protein are regained by addition of the imidazole derivatives with the exception of the possible bidentates (histidine and histamine), the comparison of the PAC results to model calculations shows that the cadmium ion must be fourfold coordinated in most cases, probably binding an additional water or hydroxide ligand. A fourfold coordination is in contrast to cadmium-substituted wild-type azurin where PAC data inferred a threefold coordination by a Cys and two His residues [Danielsen, E. Bauer, R., Hemmingsen, L., Andersen. M., Bjerrum, M. J., Butz, T., Tröger, W., Canters, G. W., Hoitink, C. W. G., Karlsson, G., Hansson, O. & Messerschmidt, A. (1995) J. Biol. Chem. 270, 573-580]

Azurin↗

Cd-substituted horse liver alcohol dehydrogenase: catalytic site metal coordination geometry and protein conformation.

The coordination geometry of the catalytic site in Cd-substituted horse liver alcohol dehydrogenase (LADH) has been investigated as a function of pH using the method of perturbed angular correlation of gamma-rays (PAC). LADH in solution fully loaded with cadmium, including radioactive 111mCd in the catalytic site [Cd2(111mCd)Cd2LADH], was studied over the pH range 7.9-11.5. Analysis of the PAC spectra showed the ionization of a group with pKa of 11. This pKa value is about 2 pH units higher than that of native zinc-containing LADH. A pKa of 9.6 was found for the binary complex of Cd2(111mCd)Cd2LADH with NAD+. This value is also about 2 pH units higher than that of the binary complex of native zinc-containing enzyme and NAD+. No pH dependency was detected for the binary complex of Cd2(111mCd)Cd2LADH with NADH within the pH range measured (pH 8.3-11.5). Assuming that metal-coordinated water is the ionizing group [Kvassman, J., & Pettersson, G. (1979) Eur. J. Biochem. 100, 115-123], we conclude that the larger ionic radius of Cd(II) relative to Zn(II) in the catalytic site causes the elevated pKa values of metal-bound water. Interpretation of nuclear quadrupole interaction (NQI) parameters derived from PAC spectra is based on the use of the angular overlap model, using the coordinates for the catalytic zinc site from the 1.8 A resolution crystal structure of the ternary complex between LADH, NADH, and dimethyl sulfoxide as a model.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Dehydrogenase↗

Different rules of spatial summation from beyond the receptive field for spike rates and oscillation amplitudes in cat visual cortex.

We measured spike rates in parallel with visually induced oscillations of multi-unit activity (MUA) and local field potentials (LFP) from cortical areas 17 and 18 of anesthetized cats. Variations in the three response types were systematically correlated with stimulus size and placement. Oscillation amplitudes of both MUA and LFP were on average low with stimuli covering just the receptive field and they increased progressively with larger stimuli, whereas average spike rates rather decreased monotonically with stimulus sizes beyond the receptive field (area 18) or reached a plateau with stimuli in the far surround (area 17). Thus, spike rates and oscillation amplitudes follow different rules of spatial summation. Since the spatial spread of the synchronized components of oscillations roughly matches the horizontal divergence zone of the pyramidal cells' axonal collaterals in area 17 and 18, the interconnected system of neighbouring columns seems to constitute a functional unit, within which the oscillations could exert their functional role.

Animals↗

Structure of metal site in azurin, Met121 mutants of azurin, and stellacyanin investigated by 111mCd perturbed angular correlation (PAC).

The geometries of the metal sites in cadmium-substituted azurins have been investigated by 111mCd perturbed angular correlation (PAC). The study includes wild type azurin as well as Met121 mutants of azurin, where methionine has been substituted by Ala, Asn, Asp, Gln, Glu, and Leu. The nuclear quadrupole interaction of wild type azurin analyzed in the angular overlap model is well described as coordination of His46, His117, and Cys112 and cannot be described by coordination of Met121 and/or Gly45. For most of the mutants, there exist two coordination geometries of the cadmium ion. With the exception of the Glu and Asp mutants, one of the conformations is similar to the wild type conformation. The other coordination geometries are either best described by a coordinating water molecule close to the original methionine position or by coordination by the substituting amino acid. These experiments show that even though the methionine does not coordinate it plays an important role for the geometry of the metal site. The nuclear quadrupole interaction of stellacyanin was also measured. The value resembles the most prominent nuclear quadrupole interaction of the Met121-->Gln mutant of Alcaligenes denitrificans azurin, indicating that the structures of the two metal sites are similar.

Azurin↗

Synchronous high-frequency oscillations in cat area 18.

The present study extends knowledge of the basic properties of correlated oscillatory activity patterns in the visual cortex of anaesthetized cats. Recordings with multiple electrodes were performed in area 18 and the correlations of multi-unit activity in the frequency range 35-80 Hz were determined using the coherence function. Statistical analysis revealed that the multi-unit correlations depended on the cortical distance between the recording sites, the orientation selectivity of the neurons and their cortical layer. On average, correlations dropped to chance level within several millimetres and were higher in lower than in upper cortical layers. Similar results were found by analysing the correlations of oscillatory patterns in local field potentials recorded from the same electrodes. Correlations of neurons with similar orientation preferences were higher than those of neurons with different orientation preferences. Comparison to a matched sample from area 17 showed that the correlations in areas 18 and 17 depended on similar properties of the neurons. The dependences of correlated oscillations resembled the known pattern and specificity of intra-areal fibre connections, suggesting that the correlations were intracortically established. Since correlations were specifically and not randomly related to the response properties of cortical neurons and were prominent in a visual area other than area 17, the findings suggest that correlated oscillatory activity provides a potential neural code supporting sensory information processing.

Animals↗

Heart rate fluctuations of lower frequencies than the respiratoryrhythm but caused by it.

In conscious adult rabbits, "classical" respiratory sinus arrhythmia does not occur because the respiratory frequency (RF) always exceeds half the heart rate (HR). However, slow HR fluctuations, not synchronous with the respiratory rhythm but affected by it, occur systematically. We have shown that these can be calculated by using aliasing rules. During general anaesthesia, when the RF decreases so that respiratory frequency is less than half the heart rate, classical respiratory sinus arrhythmia occurs and can be greatly reduced by vagal blockade. The slow HR fluctuations which are not synchronous with the respiratory rhythms, but are affected by it are mainly vagally mediated, because vagal blockade virtually eliminates them.

Animals↗

EBRA: a method to measure migration of acetabular components.

In orthopedics there is a demand for determining migration of hip sockets by evaluation of standard radiographs. In this case problems are caused mainly by changing pelvis positions on the X-ray table at successive exposures. A method (EBRA) is described that evaluates standard AP radiographs without requiring additional means at exposure (e.g. ball markers). Simulating the spatial situation it computes parameters of longitudinal and transverse migration of prosthetic cup and femoral head. A comparability algorithm using a grid of transverse and longitudinal tangents of the pelvis contour divides serial radiographs into sets of comparable ones. Comparability of serial radiographs takes place if the distances of corresponding grid lines do not transcend a given limit L. Migration is measured only between comparable radiographs. Different studies are described concerning the interdependence of pelvis rotations and changes of the grid lines, the degree of pelvis rotations appearing in practice, the choice of the limit L, the properties of the comparability algorithm and the accuracy of EBRA. The 95% confidence limits for EBRA results are 1.0 mm for longitudinal and 0.8 mm for transverse migration.

Arthrography↗

Brain peroxidative and glutathione status after moderate hypoxia in normal weight and intra-uterine growth-restricted newborn piglets.

In order to investigate the pathogenetic factors causing the relatively frequent occurrence of brain injury in intrauterine growth-restricted newborns, lipid peroxidation products (TBAR), glutathione (GSH, GSSG) and in vitro production of reactive oxygen species (chemiluminescence, stimulated lipid peroxidation, H2O2 formation) were studied in the brain of normal weight (NW) and intra-uterine growth-restricted newborn piglets (IUGR) after 1 hour of hypoxia (FiO2 11%) and 90 min reoxygenation. Cardiocirculatory parameters and catecholamine release into the blood were also measured. In the cerebellum, higher GSH content, but also higher in vitro production of lucigenin amplified chemiluminescence were found in comparison to other brain regions, independent of growth restriction and hypoxia. Moderate hypoxia without acidosis and hypercapnia resulted in GSH depletion especially in the brain of IUGR, but no changes in GSSG concentrations were measured. Though TBAR decreased after hypoxia/reoxygenation, in some brain areas of IUGR higher TBAR values were found in comparison to NW. H2O2 formation, stimulated lipid peroxidation and lucigenin and luminol amplified chemiluminescence in the 9000 x/g supernatant of brain tissue did not reveal special response of IUGR to hypoxia/reoxygenation. Hypoxia-induced circulatory centralisation due to increased release of catecholamines into the plasma prevented oxygen deficiency also in the brain of IUGR. The role of brain monoamine metabolism in the production of reactive oxygen species, followed by greater GSH depletion and higher in vivo formation of lipid peroxides in IUGR is discussed.

Animals↗