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Biomedical subjects

R Friedel

Publications and source records attributed to R Friedel.

At least 37 records · Page 2Linked to original sources
PubMed1987

Tolerance and pharmacokinetics of oral fendiline.

Two studies with healthy volunteers were carried out to correlate safety with pharmacokinetics of the calcium antagonistic drug N-(3,3-diphenylpropyl)-(1-phenylethyl)-amine (fendiline, Sensit) after single and multiple oral doses. In the first study single doses of 200, 400, 600, 800, 1000, and 1200 mg of fendiline hydrochloride were administered to 6 subjects per dose level. 3 additional subjects per dose level received placebo. No significant objective or subjective effects were noted in the dose range studied. The pharmacokinetic analysis revealed that doses higher than 800 mg were absorbed incompletely. In the second study initially 400 mg twice daily was given to 9 subjects. 3 additional subjects received placebo. Due to subjective intolerability (trembling, dizziness) after 5 days, the dose was reduced stepwise to 2 X 200 mg and was then continued for another 19 days. The pharmacokinetic evaluation revealed manifold interindividual differences in plasma levels for maximal concentrations (9-170 ng/ml) as well as for minimal concentrations (4-96 ng/ml). The absorption profile in both studies has linear and nonlinear components. Maximal plasma levels were reached after about 4 h. Terminal elimination half-lives were about 20 h.

Adolescent↗
PubMed1984

Structural and functional alterations of lipid-depleted ascites tumor cells in culture.

Ascites tumor cells growth-arrested in lipid-depleted medium were modified with respect to their lipid composition, i.e. mainly cholesterol and the phospholipid fraction. These so-called lipid-depleted cells were generally smaller, had a surface area reduced by 55% compared to the control cells and had an altered cell surface architecture with large parts being smooth, interrupted by isolated bundles of microvilli and blebs as revealed by scanning electron microscopy. This deorganization process of the cells. Lectin-induced agglutination and receptor binding capacity was reduced, and also the receptor distribution was changed resulting in a cap-like formation on the surface as shown with FITC-labelled concanavalin A. The reduction in lipid content yielding a lower C/P ratio profoundly decreased the plasma membrane fluidity which was determined by fluorescence polarization measurements. Studies on fatty acid and cholesterol de novo synthesis revealed only small increases under lipid-free conditions not sufficient to meet the requirements of the lipid-depleted cells for these substances. It is therefore concluded that ascites tumor cells need exogenous preformed lipids for adequate functioning of the cell.

Animals↗
PubMed1980

Capillary radioimmunoassay of insulin.

Capillary radioimmunoassay -- a modification of the coated tube technique -- is described. The assay is equivalent (accuracy, sensitivity, precision) to conventional methods for insulin determination; it overcomes, however, the necessity of centrifugation or filtration and offers the added bonus of being automation compatible.

Evaluation Studies as Topic↗
PubMed1979

Lymphatic transport of cellular enzymes from muscle into the intravascular compartment.

In an experimental study, employing anaesthetized dogs, it was investigated whether cellular enzymes from peripheral skeletal muscle get into the circulating blood by diffusion across capillary membranes or by lymphatic transport. In the experimental group 1, the animals were anaesthetized only. The plasma activities of the four enzymes measured--lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, creatine kinase--did not show any mentionable change during a time period of 6 h. In group 2 one hind limb of each animal was moved passively for 1 h. Alanine aminotransferase remained unchanged in plasma, the activities of the three other enzymes increased significantly. In group 3 one hind limb was made hypoxic by clamping the femoral blood vessels for 1 h. No activity changes were observed. When the period of hypoxia was followed by a 1-hour period of passive movement in group 4, the alterations in plasma activities were almost identical to those observed in group 2. In group 5 the experimental procedure was as in group 4, in addition the lymph from the thoracic duct was quantitatively withdrawn. The enzyme activities in plasma revealed a tendency to decrease rather than increase. Lymph flow increased significantly as well as the lymphatic activities of those enzymes which have high intracellular activities in muscle. The results prove, that enzymes from muscle are transported from the interstitial into the intravascular compartment mainly by lymphatic transport. Indications were found that the interruption of blood flow in one hind limb did not result in an enzyme release from muscle cells. It is discussed how changes in lymph flow, occurring during physical exercise for example, affect enzyme activities in plasma.

Alanine Transaminase↗
PubMed1979

On the mechanism of lactate dehydrogenase release from skeletal muscle in relation to the control of cell volume.

The mechanism of enzyme release from isolated skeletal muscle was illustrated by the study of the release of lactate dehydrogenase (LDH). In hypotonic media of different composition but of same tonicity the increase of LDH permeability was triggered at the same range of relative osmolality R (0.45 less than R less than 0.55), although the swelling in the respective media showed appreciable differences. The kinetics of muscle swelling showed that a deviation from the theoretically computed swelling curve to lower values of swelling was connected with an increased LDH permeability. The reduction of swelling was ATP- and Ca2+ and/or Mg2-dependent. It is concluded that swelling of cells generally precedes the leakage of soluble enzymes, and the cross-linking of filaments at the sarcoplasmic side of the sarcolemma under appropriate conditions can counteract swelling, thereby blebbing off the cell membrane from the filament meshwork. In the course of this process, sufficiently large membrane lesions are produced through which macromolecules may escape into the extracellular space.

Adenosine Triphosphate↗
PubMed1978

[A system for the mechanized radioimmunological determination of digoxin].

Because of the increased number of samples to be processed in digoxin radioimmunoassay for clinical diagnosis and pharmacokinetic studies these analyses require mechanization to a certain extent. A newly developed modular analyzer system is described which is capable of mechanizing radioimmunoassays for digoxin, for example, independent on the kind of reagent kits as well as the separation technique. In dependence on the number of replicates from 60 to 240 samples per hour can be processed. The reaction vessels are placed in belts during the whole assay including centrifugation. The final separation of the liquid and the solid phase after centrifugation can be performed in two different ways: 1. If a conventional automatic gamma counter is used an aliquot of the supernatant is automatically dispensed into the counting vials which are to be closed manually and transferred into the counting device. 2. Further reduction of manual working steps can be achieved by employment of a newly developed discontinuous flow-through gamma counter which is part of the modular analyzer system. An aliquot of the supernatants is automatically flushed into a measuring cuvette installed into a conventional crystal detector. After measurement of the radioactivity and data output the cuvette is rinsed thoroughly. Thereafter the following sample is delivered.

Autoanalysis↗
PubMed1978

Combined batchwise and continuous flow mechanization of solid-phase radioimmunoassays.

A new modification of the "coated-tube"-technique for the radioimmunoassay of human placental lactogen is described. Polyvinylchloride capillaries are used as reaction-vessels. Most working steps of the test procedure are mechanized. The possibilities and limitations of the new technique are discussed. The reliability of the method was shown by a recovery test, dilution tests, reproducibility and a comparison of the results for 71 sera, ranging from the 6th to the 42nd week of pregnancy, with those obtained by a conventional assay procedure.

Autoanalysis↗
PubMed1976

[The feigned release of cell enzymes. Distribution and transport of cell enzymes within the extracellular space. I (author's transl)].

A sudden increase of enzyme activities in plasma is not necessarily due to a release of enzymes from damaged cells. Three experimental models were used to demonstrate that acute alterations of enzyme activities, as much as +/- 15%, can be caused by fluid-shifts between the intra- and extravascular compartments. Venous occlusion of the forearm by tourniquet produces an increase of the intravascular hydrostatic pressure and subsequently results in a decrease of the plasma volume distal to the tourniquet. Because enzyme molecules are not freely diffusible across the capillary membrane the enzymatic activity increases proportionally to the decrease of plasma volume. Changes in the body posture are accompanied by changes in plasma volume and similarly by alterations in the concentration of plasma-proteins and by alterations in intravascular enzyme activities. Increased enzyme activities in plasma during strenuous physical effort are due chiefly to a concentration of macromolecules within the intravascular space because of a decrease in plasma volume and not to a release of enzymes from hypoxic muscle cells. During recovery after termination of the exercise there is a second and longer lasting increase in enzyme activities in plasma which could be related to a release of enzymes from injured cells. It is suggested that some of these changes could be due to an increase in lymph flow and thereby an increasing transport of enzymes from the interstitial to the intravascular compartment.

Biological Transport↗
PubMed1976

[Cell enzymes in lymph. Distribution and transport of cell enzymes within the extracellular space. II (author's transl)].

Enzyme patterns were measured in the lymph of the thoracic duct of the dog and in the intestinal lymph of the rat. Those patterns were compared to the corresponding activities in blood plasma. From the results it is concluded that under physiological conditions cell enzymes are released into the interstitial space and from there are transported via the lymph into the intravascular space. Only enzymes with a low molecular weight such as myokinase are able to penetrate the capillary membrane, thereby reaching the plasma without being transported exclusively by the lymph. There is a close relationship between the molecular weight of enzymes and their plasma/lymph ratios. In the rat the enzyme patterns in mesenteric lymph nodes and in intestinal mucosa and muscularis (duodenum as well as ileum) were also determined. No direct correlation between those intracellular patterns and the enzyme patterns in the intestinal lymph could be established. The significance of lymph and lymph flow for clinical enzymology is discussed with respect to physiological and pathological conditions. High sensitivity of diagnosis by means of enzyme measurements in plasma can be achieved only if the capillary permeability in the injured organ is high and/or the lymph flow from the organ is not restricted by the injury.

Animals↗
PubMed1976

[Distribution of intravenously injected enzymes of heterologous, homologous and autologous origin. Distribution and transport of cell enzymes within the extracellular space. III (author's transl)].

The disappearance rates of intravenously injected enzymes of heterologous, homologous and autologous origin were determined in rats. Within four hours after administration, the activities show an exponential decline, that is either mono- or biphasic. The constant of the exponential function is a measure of the capillary permeability. In the case of biphasic disappearance this holds true only for the first slope, whereas the second one represents the elimination of active enzyme molecules from the extracellular space. If the decline in enzyme activity is monophasic the elimination of those enzymes from the interstitial space is limited by the permeability of the capillary membrane. Enzymes of homologous and autologous origin (extracts of liver or muscle) show a close correlation between their molecular weights and their rates of distribution within the extracellular compartment. For heterologous enzymes (crystallized) such a correlation could not be found. Possible causes for these differences in distribution are discussed. Heterologous and/or crystallized enzymes seem not to be suited for studies on the distribution of cell enzymes within the extracellular space. After enzymes are released from injured cells they undergo the processes of distribution, transport and elimination which are superimposed. The effects of the distribution and transport of enzymes on the results of clinical studies on enzyme elimination are discussed. It seems questionable at this point to assume that from the elimination rate of enzymes and their actual plasma activity one can account for the amount of enzymes originally released from injured cells.

Animals↗
PubMed1976

[Plasmapheresis as an experimental model for studies on the extracellular distribution of enzymes. Distribution and transport of cell enzymes within the extracellular space. IV (author's transl)].

The rate of distribution of cell enzymes between the intravascular and extravascular space was studied, following a sudden decrease of enzyme activities in plasma. This rapid decrease of enzyme activities was achieved in rats by a rapid exchange of the blood with a twofold volume of a suspension of homologous erythrocytes in isoosmolar bovine serum albumin solution. After this plasmapheresis, the activities of seven cell enzymes in the plasma were decreased to 14 to 22% of their original values. The subsequent increase in activities showed different kinetics, depending on the enzyme. After 120 min, creatine kinase had reached the starting activity; malate dehydrogenase and aldolase reached their original activities after 180 min. Aspartate aminotransferase, glutamate dehydrogenase, alanine aminotransferase and pyruvate kinase increased more slowly and they had still not reached their starting values after 240 min. Repetition of the plasmapheresis after 90 min had no obvious effect on the kinetics of the subsequent activity increase. During the first minutes after plasmapheresis the adjustment of the activity equilibrium between the interstitial and the intravascular compartments depends mainly on the capillary permeability. It is therefore possible to determine half-life constants for the distribution of enzymes within the extracellular space. The constants for malate dehydrogenase and aldolase are almost identical with those determined by intravenous injection, whereas there are discrepancies in the constants for the remaining enzymes. The constants for pyruvate kinase and glutamate dehydrogenase are significantly lower, while those for aspartate aminotransferase, alanine aminotransferase and creatine kinase are significantly higher, than those determined after intravenous injection. Possible reasons for these differences are disucssed.

Animals↗
PubMed1975

[Effects of blood sampling on enzyme activities in the serum of small laboratory animals (author's transl)].

Because of the difficulties in drawing blood for clinical chemistry in small laboratory animals there exist many methods for sampling blood and the preparation of serum, none of which is generally accepted or well standardised. It was the aim of this study to investigate the effects of sampling techniques on normal values of enzyme activities in the serum of rat and mouse. The activities of the following enzymes were determined: sorbitol dehydrogenase, lactate dehydrogenase, malate dehydrogenase, glutamate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, pyruvate kinase, creatine kinase, myokinase, alkaline phosphatase and leucine aminopeptidase. In addition plasmaproteins, urea and inorganic phosphorus were measured. In rats blood was obtained from the following sites: retroorbital venous plexus, jugular vein, heart and ventral aorta. In mice blood was sampled from the jugular vein and the ventral aorta. Shifts of water from the interstitial to the intravascular space due to hypovolemia occurring during the experimental procedure were followed up by measuring the hematocrit and the distribution of radioiodide labelled albumin. In rats the activities of lactate dehydrogenase, malate dehydrogenase, aspartate aminotransferase, pyruvate kinase, creatine kinase and myokinase found in blood serum obtained from the retroorbital venous plexus and the ventral aorta were too high compared to the other sampling sites. Activities of alkaline phosphatase and alanine aminotransferase were slightly elevated when blood was sampled from the punctured retroorbital venous plexus. Small differences in plasmaproteins and hematocrit values were found to be due to acute shifts of water within the extracellular space. In mice the activities of lactate dehydrogenase, malate dehydrogenase, aspartate aminotransferase and myokinase were found to be too high in blood serum obtained from the ventral aorta. Efflux of enzymes from damaged cells and the interstitial space ive caused erroneous results too, but only to a minor extent. The most reliable method for blood sampling in rat and mouse is the cannulation of the jugular vein. The heart puncture can be recommended too. Attention should be paid, however, to the possibility of aspirating disrupted muscle cells through the inserted needle.

Adenylate Kinase↗