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O Friedrich

Publications and source records attributed to O Friedrich.

At least 19 recordsLinked to original sources
PubMed2006

Elementary Ca2+ release events in mammalian skeletal muscle: effects of the anaesthetic drug thiopental.

We examined the effect of clinically relevant doses of thiopental (10-100 microM) on Ca2+ release from the sarcoplasmic reticulum of chemically skinned skeletal muscle fibres of the mouse. Elementary Ca2+ release events (ECRE) were recorded with confocal microscopy and were detected and analysed by an automated algorithm. Thiopental at 25 microM evoked a marked increase in ECRE frequency (events/100 microm/s) from 0.64 +/- 0.32 to 1.56 +/- 0.38 (P < 0.001). Incubation with 5 microM ryanodine significantly reduced spontaneous and evoked ECRE frequencies to 0.08 +/- 0.08 (P < 0.001) and 0.39 +/- 0.25 (25 microM thiopental, P < 0.001) respectively. Thiopental-evoked ECRE show different morphological characteristics compared to spontaneous events. Maximum relative amplitudes (DeltaF/F0)max and spatial width (full width at half maximum) of the events were substantially increased. Full duration at half maximum was increased and some very long events (200 ms compared to approximately 30 ms standard) were produced. The rise times as an indicator of the channel open time were slightly increased. Furthermore, the occurrence of repetitive ECRE was observed. These events, in contrast to previous observations in amphibian skeletal muscle fibres, displayed a multitude of different release patterns. In particular, a repetitive ECRE mode with successively decaying amplitudes was identified and the inter-event intervals were analysed. Estimation of the underlying Ca2+ release current suggests that during repetitive events with a decaying amplitude a decreasing amount of Ca2+ was released within the individual release event. Possible underlying mechanisms are discussed. In summary, thiopental seems to be a potent RyR1 agonist and substantially alters the gating mechanisms of RyR Ca2+ release channel clusters already in clinically relevant doses, i.e. doses administered during general anaesthesia.

Algorithms↗
PubMed2006

[Critical illness myopathy in intensive care patients. Pathogenetic concepts and clinical management].

Intensive care patients are at increased risk of developing sepsis with multi-organ failure during treatment (severe sepsis) possibly leading to complications of the central and peripheral nervous system. Among these, septic encephalopathy, critical illness polyneuropathy (CIP) and critical illness myopathy (CIM) are the most important. Neuromuscular complications in particular are difficult to diagnose as they mostly become apparent only when sedation has ceased and the awakening patient experiences difficulties in weaning from the respirator and reduced voluntary strength. CIP and CIM are generally self-limiting, however, they greatly prolong ICU stay and rehabilitation, thus nowadays also imposing a real budget threat. The diagnostics, especially the differentiation between CIM and CIP is difficult and a multi-disciplinary approach involving ICU physicians, anesthetists and neurologists is needed. Our knowledge of the causes of the primary ICU myopathy, although rapidly evolving during recent years, is still in its infancy and specific treatment of CIM is not yet available. The present overview summarizes insights into clinical and new diagnostic strategies for early detection of neuromuscular dysfunction in ICU patients. This article focuses on current concepts and results revealing the pathomechanism(s) of CIM and some simple therapeutic or preventive measures have been deduced which are summarized and discussed.

Anti-Inflammatory Agents↗
PubMed2006

GABAmimetic intravenous anaesthetics inhibit spontaneous Ca2+ -oscillations in cultured hippocampal neurons.

BACKGROUND: Spontaneous Ca2+ -oscillations are a possible mechanism of Ca2+ -mediated signal transduction in neurons. They develop by a periodical interplay of Ca2+, which enters the neuron from the extracellular medium and triggers Ca2+ release from the endoplasmic reticulum (ER). Ca2+ -oscillations are terminated by reuptake into the ER or plasmalemmal extrusion. Spontaneous Ca2+ -oscillations are glutamate dependent and appear to be responsible for neuronal plasticity and integration of information. Here, we examined the role of the gamma-aminobutyric acid (GABAA) receptor on spontaneous Ca2+ -oscillations and studied the effects of the anaesthetics midazolam, thiopental and the non-anesthetic barbituric acid on spontaneous Ca2+ -oscillations. METHODS: Hippocampal neuronal cell cultures of 19-day-old embryonic Wistar rats 17-18 days in culture were loaded with the Ca2+ -sensitive dye Fura-2AM. Experiments were performed using dual wave-length excitation fluorescence microscopy and calibration constants were obtained from in situ calibration. RESULTS: Spontaneous Ca2+ -oscillations are influenced by the GABAA receptor. The intravenous anaesthetics midazolam and thiopental suppressed the amplitude and frequency reversibly in a dose-dependent manner with EC50 in clinically relevant concentrations. This effect was mediated via the GABAA receptor as it could be reversed by the GABAA receptor antagonist bicuculline. In contrast, the application of barbituric acid had no effects on the spontaneous Ca2+ -oscillations. CONCLUSION: Spontaneous Ca2+ -oscillations are influenced by the GABAA receptor. Spontaneous Ca2+ -oscillations might represent an interesting model system to study anaesthetic mechanisms on neuronal information processing.

Anesthetics, Intravenous↗
PubMed2006

Prolonged high-pressure treatments in mammalian skeletal muscle result in loss of functional sodium channels and altered calcium channel kinetics.

Activation and inactivation of ion channels involve volume changes from conformational rearrangements of channel proteins. These volume changes are highly susceptible to changes in ambient pressure. Depending on the pressure level, channel function may be irreversibly altered by pressure. The corresponding structural changes persist through the post-decompression phase. High-pressure applications are a useful tool to evaluate the pressure dependence as well as pressure limits for reversibility of such alterations. Mammalian cells are only able to tolerate much lower pressures than microorganisms. Although some limits for pressure tolerance in mammalian cells have been evaluated, the mechanisms of pressure-induced alteration of membrane physiology, in particular of channel function, are unknown. To address this question, we recorded fast inward sodium (I(Na)) and slowly activating L-type calcium (I(Ca)) currents in single mammalian muscle fibers in the post-decompression phase after a prolonged 3-h, high-pressure treatment of up to 20 MPa. I(Na) and I(Ca) peak amplitudes were markedly reduced after pressure treatment at 20 MPa. This was not from a general breakdown of membrane integrity as judged from in situ high-pressure fluorescence microscopy. Membrane integrity was preserved even for pressures as high as 35 MPa at least for pressure applications of shorter durations. Therefore, the underlying mechanisms for the observed amplitude reductions have to be determined from the activation (time-to-peak [TTP]) and inactivation (tau(dec)) kinetics of I(Na) and I(Ca). No major changes in I(Na) kinetics, but marked increases, both in TTP and tau(dec) for I(Ca), were detected after 20 MPa. The apparent molecular volume changes (activation volumes) deltaV(double dagger) for the pressure-dependent irreversible alteration of channel gating approached zero for Na+ channels. For Ca2+ channels, deltaV(double dagger) was very large, with approx 2.5-fold greater values for channel activation than inactivation (approx 210 A3). We conclude, that in skeletal muscle, high pressure differentially and irreversibly affects the gating properties and the density of functional Na+ and Ca2+ channels. Based on these results, a model of high pressure-induced alterations to the channel conformation is proposed.

Animals↗
PubMed2003

Mini-dystrophin restores L-type calcium currents in skeletal muscle of transgenic mdx mice.

L-type calcium currents (iCa) were recorded using the two-microelectrode voltage-clamp technique in single short toe muscle fibres of three different mouse strains: (i) C57/SV129 wild-type mice (wt); (ii) mdx mice (an animal model for Duchenne muscular dystrophy; and (iii) transgenically engineered mini-dystrophin (MinD)-expressing mdx mice. The activation and inactivation properties of iCa were examined in 2- to 18-month-old animals. Ca2+ current densities at 0 mV in mdx fibres increased with age, but were always significantly smaller compared to age-matched wild-type fibres. Time-to-peak (TTP) of iCa was prolonged in mdx fibres compared to wt fibres. MinD fibres always showed similar TTP and current amplitudes compared to age-matched wt fibres. In all three genotypes, the voltage-dependent inactivation and deactivation of iCa were similar. Intracellular resting calcium concentration ([Ca2+]i) and the distribution of dihydropyridine binding sites were also not different in young animals of all three genotypes, whereas iCa was markedly reduced in mdx fibres. We conclude, that dystrophin influences L-type Ca2+ channels via a direct or indirect linkage which may be disrupted in mdx mice and may be crucial for proper excitation-contraction coupling initiating Ca2+ release from the sarcoplasmic reticulum. This linkage seems to be fully restored in the presence of mini-dystrophin.

Animals↗
PubMed2002

Membrane ion conductances of mammalian skeletal muscle in the post-decompression state after high-pressure treatment.

Exposure of excitable tissues to hyperbaric environments has been shown to alter membrane ion conductances, but only little is known about the state of the membranes of intact cells in the post-decompression phase following a prolonged high-pressure treatment. Furthermore, almost nothing is known about high-pressure effects on skeletal muscle membranes. Therefore, we investigated changes to the input resistances, membrane potentials and voltage-gated membrane currents for sodium (INa), potassium (IK) and calcium (ICa) ions under voltage-clamp conditions in enzymatically isolated intact mammalian single fibers following a 3-hr high-pressure treatment up to 25 MPa at +4 degrees C. After a 3-hr 20 MPa treatment, the input resistance was increased but declined again for treatments with higher pressures. The resting membrane potentials were depolarized in the post-decompression phase following a 20-MPa high-pressure treatment; this could be explained by an increase in the Na+- over K+-permeability ratio and in intracellular [Na+]i. Following a 10-MPa high-pressure treatment, INa, IK and ICa amplitudes were similar compared to controls but were significantly reduced by 25 to 35% after a 3-hr 20-MPa high-pressure treatment. Interestingly, the voltage-dependent inactivation of INa and ICa seemed to be more stable at high pressures compared to the activation parameters, as no significant changes were found up to a 20-MPa treatment. For higher pressure applications (e.g., 25 MPa), there seemed to be a marked loss of membrane integrity and INa, IK and ICa almost disappeared.

Animals↗
PubMed2001

Bound ro-vibronic states of triplet H3(+).

On the basis of a new, highly accurate potential energy hypersurface for the lowest triplet state of H+3, (3)Sigma(+)(u), the bound ro-vibronic states are calculated for J</=5. Since the potential has very shallow minima, those states exist only up to single vibrational excitation. The symmetry properties of the ro-vibrational states are investigated. Further, it is demonstrated that the first excited triplet state, which intersects conically with the (3)Sigma(+)(u) state, has no effect on the reported ro-vibrational energies.

Journal Article↗
PubMed2001

Numerical analysis of Ca2+ depletion in the transverse tubular system of mammalian muscle.

Calcium currents were recorded in contracting and actively shortening mammalian muscle fibers. In order to characterize the influence of extracellular calcium concentration changes in the small unstirred lumina of the transverse tubular system (TTS) on the time course of the slow L-type calcium current (I(Ca)), we have combined experimental measurements of I(Ca) with quantitative numerical simulations of Ca2+ depletion. I(Ca) was recorded both in calcium-buffered and unbuffered external solutions using the two-microelectrode voltage clamp technique (2-MVC) on short murine toe muscle fibers. A simulation program based on a distributed TTS model was used to calculate the effect of ion depletion in the TTS. The experimental data obtained in a solution where ion depletion is suppressed by a high amount of a calcium buffering agent were used as input data for the simulation. The simulation output was then compared with experimental data from the same fiber obtained in unbuffered solution. Taking this approach, we could quantitatively show that the calculated Ca2+ depletion in the transverse tubular system of contracting mammalian muscle fibers significantly affects the time-dependent decline of Ca2+ currents. From our findings, we conclude that ion depletion in the tubular system may be one of the major effects for the I(Ca) decline measured in isotonic physiological solution under voltage clamp conditions.

Animals↗
PubMed2001

Reversibility of high pressure effects on the contractility of skeletal muscle.

High pressure application has been extensively used to thermodynamically influence complex physiological processes such as membrane ion conductances and the mechanism of muscle contraction. However, little is known about the reversibility of high pressure effects on intact cells. Therefore, we studied the reversibility of 3 h pressure applications up to 25 MPa at +4 degrees C to intact murine skeletal muscle. Functional mechanical properties were tested in extensor digitorum muscle fibres skinned following a high pressure exposure. Calcium activated force and stiffness were nearly unchanged following pressure applications up to 20 MPa, whereas for higher pressures we found a marked reduction of peak force, a decline of activation kinetics, an increase of relaxation stiffness but still unchanged peak stiffness. The rigor kinetics showed a similar behaviour as the activation kinetics. pCa-force relations remained unchanged up to 20 MPa but were shifted towards smaller pCa values for higher pressures. In conclusion there is a rather sharp high pressure limit of 20 MPa above of which pressure application results in a substantial irreversible loss of contractile functionality in differentiated muscle which may at least partly be explained by changes in the Ca2+ regulatory process. This is supported by a degradation of the 37 kDa band, i.e. Troponin T, shown by SDS gel electrophoresis. However, the general stability of the other bands does not indicate a substantial increase of unspecific protease activity following a high pressure treatment up to 25 MPa.

Animals↗
PubMed1999

Calcium currents during contraction and shortening in enzymatically isolated murine skeletal muscle fibres.

1. Calcium currents (ICa) were monitored in enzymatically isolated murine toe muscle fibres using the two-microelectrode voltage-clamp technique. ICa was recorded (i) in hypertonic solution to suppress contraction, and (ii) in actively shortening fibres in isotonic solution. 2. In hypertonic solution the threshold potential for ICa was about -30 mV for both 2 and 10 mM external Ca2+ solution. Maximum peak currents measured -12.6 +/- 2.3 nA (mean +/- s.d.; n = 4) in 2 mM Ca2+ and -65 +/- 15 nA (n = 7) in 10 mM Ca2+. The time to peak (TTP) ICa was 96 +/- 22 ms (n = 4) in 2 mM Ca2+ and 132 +/- 13 ms (n = 7) in 10 mM Ca2+. The exponential decay of ICa was similar in 2 and 10 mM Ca2+ with rate constants (tau-1(V)) of 3.7 s-1 (2 mM) and 3.8 s-1 (10 mM) at +10 mV. 3. ICa in isotonic 10 mM Ca2+ solution was recorded by inserting the micropipettes exactly opposite to each other close to the centre of mass of the fibre where negligible contraction-induced movement occurs. 4. In isotonic 10 mM Ca2+ solution ICa had a smaller peak amplitude (-45 +/- 5 nA; n = 7) and faster TTP (82.8 +/- 22.1 ms; n = 7) than in hypertonic solution. The exponential decay of ICa showed a significantly larger tau-1(V) of 6.4 s-1 at +10 mV (P < 0.03). 5. To test for calcium depletion, extracellular Ca2+ was buffered by malic acid in isotonic solution to 9 mM. The decay of ICa had a time constant of 348 +/- 175 ms (n = 14) vs. 107 +/- 24 ms (n = 12; P < 0.001) at 0 mV in unbuffered 10 mM Ca2+ solution. 6. We conclude that calcium depletion from the transverse tubular system contributes significantly to the decay of calcium currents in murine toe muscle fibres under hypertonic as well as isotonic conditions. In the latter, depletion is even more prominent.

Animals↗
PubMed1988

[Determination of phenolic compounds in alcoholic beverages by HPLC with an electrochemical detector].

A method has been developed for the quantitative determination of phenolic lignin degradation products in alcoholic distillates. After diluting the samples with the eluent (1:5-1:10, v/v) the phenolic compounds are separated by high-pressure liquid chromatography and detected by an electrochemical detector at +1.3 V. To identify the compounds the k'-values and the hydrodynamic voltammograms of the samples are compared with those of the standard solution. Several distilled alcoholic beverages were analysed. The content of phenolic compounds was found to vary between 0.15 and 7.7 mg/l. The detection limits were 0.3-0.9 ng.

Alcoholic Beverages↗
PubMed1981

[Bacteriocin typing of Enterobacter cloacae strains (author's transl)].

By means of bacteriocin typing epidemic studies were carried out with regard to 65 strains of Enterobacter cloacae, isolated from various specimens of 59 patients. Based on detailed preliminary investigations the presentation with bacteriocins in liquid cultures induced by Mitomycin C was found most preferable. Since constant and reproducible results are essential, standardization of culture media, incubation temperature, incubation time and inoculum size is required. By means of 13 bacteriocin-producing strains the isolates could be typed and categorized into 24 types according to their sensitivity to bacteriocins. A rather varied picture emanated from the distribution of the individual types with regard to the different medical fields so that cross-infection with a certain strain was negligible. Seeing that one bacteriocin type was found predominantly in the intensive care unit, it can be maintained that this strain originated from the ward itself. The importance of bacteriocin typing for the interpretation of certain up-to-date epidemic situations is obvious which typing has also been successfully employed with regard to investigations of Enterobacter cloacae infections. However, it is doubtful whether bacteriocin production and bacteriocin sensitivity sufficiently constant in order to obtain comparable results over a more extended period of time and in different areas.

Bacteriocins↗
PubMedDate not supplied

Aging of liver: morphological and biochemical changes.

Light-microscopically there are no significant age-dependent changes in the liver, due to the slight increase in biochemically determined connective tissue components. Electron-microscopical comparison of young and old animals show a larger size and decreased numbers of liver cell mitochondria in older animals. Collagen synthesis in liver is accelerated during growth, as demonstrated by assay of the [3H] proline incorporation rates and of the specific activity of hydroxyproline, corresponding to a decrease in the prolyl hydroxylase activity with age. The neutral salt-soluble collagen fraction may be regarded as a parameter for collagen synthesis, which is activated during the growth period and then remains constant without age and sex differences. Not much is known about the significance of these changes with increasing age or about their initiating factors, although there are parallel findings for liver intoxication and inflammation.

Adolescent↗
PubMedDate not supplied

'In situ' high pressure confocal Ca(2+)-fluorescence microscopy in skeletal muscle: a new method to study pressure limits in mammalian cells.

We combined 'in situ' high pressure microscopy with confocal laser scanning microscopy to directly study Ca2+ homeostasis in intact mammalian (murine) skeletal muscle fibres during high pressure exposure up to 35 MPa. Cytosolic Fluo-4 and mitochondrial Rhod-2 Ca2+ fluorescence were simultaneously monitored. To separate changes in Ca2+ and direct/indirect effects of pressure on the dye, experiments in permeabilized ('skinned') muscle fibres were performed at a fixed Ca2+ concentration. Normalized Fluo-4 fluorescence sharply declined up to 10 MPa but showed a plateau between 10 MPa and -35 MPa. In the intact fibre, Fluo-4 fluorescence exponentially decreased during pressurization to 35 MPa with a pressure constant of pi-5 MPa whereas mitochondrial Rhod-2 fluorescence exponentially increased with a four-fold larger pi. Holding the pressure at 35 MPa almost did not change Fluo-4 fluorescence. However, Rhod-2 fluorescence started to decrease after -40 min. Upon decompression, Rhod-2 and Fluo-4 fluorescence increased exponentially with similar pi. However, initial Fluo-4 fluorescence values were not restored. Our results are in agreement with pressure induced Ca2+ leakage from the sarcoplasmic reticulum. Ca2+ might then be taken up in large amounts by mitochondria preventing cytosolic increase in Ca2+. Prolonged pressure applications (-40 min at 35 MPa) seem to destabilize mitochondrial function with release of Ca2+ from mitochondria back into the cytosol and eventually mechanical activation resulting in irreversible contractures. The pressure induced disturbance of Ca2+ homeostasis might have important implications for the pressure exposure limits and/or dive profiles of deep sea mammals.

Aniline Compounds↗