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Biomedical subjects

H Pelzer

Publications and source records attributed to H Pelzer.

At least 37 records · Page 2Linked to original sources
PubMed1991

Determination of thrombin-hirudin complex in plasma with an enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) was developed for the determination of the thrombin-hirudin complex (TH) in plasma. The test is based on the sandwich principle and uses appropriate antibodies which selectively bind the corresponding moieties of the complex. The assay was calibrated by adding performed TH to normal human citrated plasma. The detection limit of the assay was 1.2 ng/ml. Mean coefficients of variation of 6.0% (intra-assay) and 6.4% (inter-assay) were found. The presence of TH was demonstrated in normal human plasma that was spiked with hirudin and subsequently activated in vitro by calcium-thromboplastin to generate thrombin. This complex was also found in plasma samples from pigs which had been treated with hirudin during experimentally induced septicaemia.

Animals↗
PubMed1991

Prothrombin fragment 1 + 2, thrombin-antithrombin III complexes and D-dimers in acute deep vein thrombosis: effects of heparin treatment.

Plasma levels of prothrombin fragment 1 + 2 (F 1 + 2), of thrombin-antithrombin III complexes (TAT) and of D-dimers were evaluated at several time intervals in 15 patients affected by acute proximal deep vein thrombosis, complicated or not by pulmonary embolism, and treated by conventional heparin therapy for 9 d. The mean levels of the three markers remained significantly increased throughout the period of observation, except for F 1 + 2 on day 9, when compared to normal values established in a population of normal healthy blood donors. However, whereas heparin significantly decreased the plasma levels of F 1 + 2 and of TAT complexes in less than 3 d. D-dimer levels were not significantly altered. Significant correlations were observed between the plasma levels of the three markers but they were not correlated to the actual intensity of heparin treatment evaluated as the activated partial thromboplastin time prolongation. These results indicate that heparin improves the hypercoagulable state associated with a deep vein thrombosis within the first days of treatment as indicated by TAT and F 1 + 2. They also account for the performances of D-dimer assay for the diagnosis of deep vein thrombosis in patients already receiving heparin, a common situation in routine hospital practice.

Acute Disease↗
PubMed1991

Influence of cytostatic treatment on the coagulation system and fibrinolysis in patients with non-Hodgkin's lymphomas and acute leukemias.

Cytostatic therapy is known to aggravate tumor-induced coagulopathy. Therefore, we have studied the effect of different chemotherapeutic regimens on the activation of coagulation and fibrinolysis in patients with non-Hodgkin's lymphomas or acute leukemias. In non-Hodgkin's lymphoma patients treated with an aggressive protocol (COL-BLAM) and in leukemia patients (TAD-9) fibrinopeptide A, prothrombin fragment (F1 + 2) and thrombin antithrombin III complexes (TAT) increased (Tables 4 and 6), while D-dimer did not deviate significantly. The ratio D-dimer/TAT consequently showed a significant decrease, indicating increased formation of thrombin after release of procoagulant factors, which is not paralleled by an activation of fibrinolysis. Both these groups were also characterized by an increase in uric acid and in C-reactive protein and plasminogen-activator inhibitor, two acute-phase reactants. In contrast, patients with non-Hodgkin's lymphomas treated with a less aggressive protocol (COP) showed no significant changes in hemostatic variables, uric acid, or acute-phase reactants. The release of procoagulant factors relates to the cytostatic sensitivity of the tumor and to a high tumor-cell destruction. Our results further emphasize the need for large-scale studies on antithrombotic prophylaxis in patients undergoing cytostatic treatment.

Acute Disease↗
PubMed1990

Intraoperative radiation of canine carotid artery, internal jugular vein, and vagus nerve. Therapeutic applications in the management of advanced head and neck cancers.

As a step in the application of intraoperative radiotherapy (IORT) for treating advanced head and neck cancers, preliminary information was obtained on the radiation tolerance of the canine common carotid artery, internal jugular vein, and vagus nerve to a single, high-dose electron beam. Both sides of the neck of eight mongrel dogs were operated on to expose an 8-cm segment of common carotid artery, internal jugular vein, and vagus nerve. One side of the neck was irradiated, using escalating doses of 2500, 3500, 4500, and 5500 cGy. The contralateral side of the neck served as the unirradiated control. At 3 and 6 months after IORT, one dog at each dose level was killed. None of the dogs developed carotid bleeding at any time after IORT. Light microscopic investigations using hematoxylin-eosin staining on the common carotid artery and internal jugular vein showed no consistent changes that suggested radiation damage; however, the Masson trichrome stain and hydroxyproline concentration of irradiated common carotid artery indicated an increase in the collagen content of the tunica media. Marked changes in the irradiated vagus nerve were seen, indicating severe demyelination and loss of nerve fibers, which appeared to be radiation-dose dependent. Four patients with advanced recurrent head and neck cancer were treated with surgical resection and IORT without any acute or subacute complications. The role of IORT as a supplement to surgery, external beam irradiation, and chemotherapy in selected patients with advanced head and neck cancer needs further exploration.

Animals↗
PubMed1990

Beta-adrenoceptor-binding studies of the cardioselective beta blockers bisoprolol, H-I 42 BS, and HX-CH 44 BS to heart membranes and intact ventricular myocytes of adult rats: two beta 1-binding sites for bisoprolol.

beta-Adrenoceptor binding of cardioselective drugs to intact ventricular myocytes was performed using [3H]CGP-12177, a hydrophilic non-beta 1/beta 2-selective antagonist radioligand. The beta-adrenoceptor density on the intact cardiomyocytes was about 2 x 10(5) molecules/cell. The beta 1-selective antagonists H-I 42 BS and HX-CH 44 BS competed for [3H]CGP-12177 binding sites on the ventricular myocytes in an essentially monophasic manner with Ki = 72.6 nM and Ki = 76.7 nM, respectively. This is in contrast to the results of binding data from heart membranes, where these beta 1-antagonists bind in a biphasic manner with about 30% of an additional low affinity site, presumably corresponding to the beta 2-adrenoceptor. The beta 1-selective antagonist bisoprolol revealed two binding sites at the heart membranes and at the myocytes as well with Ki(1) = 34.2 and 20.0 nM and Ki(2) = 3,014 and 918 nM, respectively. Our results suggest that viable adult rat ventricular myocytes may contain two beta 1-adrenoceptor binding sites exhibiting different affinities for bisoprolol, whereas beta 2-adrenergic receptors are completely absent.

Adrenergic beta-Antagonists↗
PubMed1989

Biocompatibility and safety of cytapheresis.

Cytaphereses are safe and can be used routinely like whole blood donations on the premise that standard techniques based on appropriate guidelines and regulations are performed. Before the introduction of a new cell or plasma separator, a thorough clinical investigation is always recommended in order to demonstrate biocompatibility and safety features. In this context cell loss and damage as well as activation of coagulation and complement should be tested primarily. The examination should consist of a direct comparison with an approved system. In addition, it is necessary to repeat periodically on multicenter studies adverse donor reactions such as those already described so that it is possible to recognize even rare side effects. Of special importance are long-term studies of donors undergoing frequent cytaphereses for many years in order to detect relevant immunological changes. On the other hand, harm caused by the plasticizer or cancer due to cancerogenicity of the plastics are only speculative at the moment.

Biocompatible Materials↗
PubMed1989

New trends in the field of coagulation diagnosis--new possibilities to improve monitoring of antithrombotic therapy.

Two specific and sensitive enzyme immunoassays have been developed for the measurement of TAT and PTF, respectively. The TAT-ELISA uses two different antibodies binding selectively to the corresponding antigen moieties of TAT; anti-PTF antibodies were obtained from rabbits using a synthetic peptide from the COOH-terminus of PTF. Concentration in plasma samples of healthy individuals was found to be 1.45 +/- 0.4 micrograms/l for TAT, and 0.65 +/- 0.2 nMol/l for PTF. Patients with coagulation disorders showed markedly increased concentrations of both TAT and PTF. It can be assumed that these parameters might be suitable indicators for monitoring of both anticoagulant and thrombolytic therapy.

Amino Acid Sequence↗
PubMed1988

Determination of human thrombin-antithrombin III complex in plasma with an enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) was developed for the determination of thrombin-antithrombin III complex (TAT) in human plasma. The test system follows the sandwich principle and uses two different antibodies directed against human thrombin and human antithrombin III, respectively. The antibodies bind selectively to the corresponding antigen moieties of TAT. The assay was calibrated with definite concentrations of preformed purified TAT added to TAT-poor plasma. The lower limit of sensitivity of the assay was 0.5 microgram/l. Mean coefficients of variation of 4.2% (intraassay) and 3.5% (interassay) were found for TAT concentrations between 2 and 60 micrograms/l. A reference range from 0.85 to 3.2 micrograms/l was calculated from TAT concentration in plasma samples from 88 healthy donors (mean value +/- SD: 1.45 +/- 0.4 micrograms/l). In plasma samples from patients with pulmonary embolism (n = 17), TAT concentrations between 3 and 25 micrograms/l were measured. In 15 patients with deep vein thrombosis, TAT was found up to 3 to 25 micrograms/l. From these data we conclude that measurement of TAT can be a sensitive parameter for specific detection of a latent activation of the clotting pathway.

Antithrombin III↗
PubMed1988

Determination of human thrombin-antithrombin III complex by enzyme immunoassay.

We have developed a specific and sensitive ELISA for the measurement of the TAT in human plasma. The assay follows the sandwich principle and uses two different antibodies directed against human thrombin and human antithrombin III, respectively. The anti-thrombin antibody population used for coating was purified by immunoadsorption on immobilized prothrombin and thrombin, respectively. Antithrombin III antibodies were conjugated with peroxidase. Plasma samples containing TAT were incubated in polystyrene tubes coated with anti-thrombin antibodies; after washing, peroxidase-conjugated antithrombin III antibodies were added and bound enzyme activity was subsequently measured using o-phenylenediamine. The assay was calibrated with definite concentrations (2.0 to 60 micrograms/l) of preformed purified TAT added to TAT-poor plasma. Plots of absorbance at 492 nm against TAT concentrations revealed a linear correlation (r = 0.98). A reference range from 0.85 to 3.0 micrograms/l was calculated from TAT concentration in plasma samples from 88 healthy donors (mean value +/- SD: 1.45 +/- 0.4 micrograms/l). In patients with deep vein thrombosis confirmed by phlebography (n = 15), TAT was found up to 7-13 micrograms/l. Patients with septicemia associated with a consumption coagulopathy (n = 10) showed markedly increased TAT values (greater than or equal to 10 micrograms/l). From these data it can be concluded that measurement of TAT might be a parameter for detection of a latent clotting pathway activation.

Antithrombin III↗
PubMed1987

Tricyclic compounds as selective antimuscarinics. 1. Structural requirements for selectivity toward the muscarinic acetylcholine receptor in a series of pirenzepine and imipramine analogues.

The M1-selective antiulcer drug pirenzepine (1) is a tricyclic compound with close resemblance to tricyclic psychotropic agents such as imipramine (2). Despite this fact, pirenzepine is devoid of any psychotropic effects, exhibiting measurable antagonistic effects in biochemical assays and receptor binding studies only toward the muscarinic receptor system. To understand how different groups in these tricyclic molecules affect binding affinities, a set of nine compounds structurally related to pirenzepine (1) and imipramine (2) has been selected for analysis, comprising three different tricycles and three different side chains. The compounds were tested for their affinity to the imipramine and muscarinic receptors in homogenized rat cortex tissue. The result of these studies suggests that it is the nature and placement of accessory groups that determine the differences in receptor recognition and the binding process. In the case of pirenzepine (1), preferential binding toward the muscarinic receptor is brought about by the endocyclic amide group, by the positioning of the protonated N atom of the side chain, and to a minor extent by the exocyclic amide group. From these findings a putative model for the explanation of selective binding of pirenzepine (1) to the muscarinic receptor has been derived.

Animals↗
PubMed1987

Separation of muscarinic acetylcholine receptor entities from rat cerebral cortex by ion exchange chromatography.

Digitonin solubilized muscarinic acetylcholine receptor (mAChR) of rat cerebral cortex membranes were chromatographed on the FPLC anion exchanger Mono Q. [3H]QNB (quinuclidinyl benzilate) and [3H]PZ (pirenzepine) binding activity was retarded from a NaCl free elution buffer and thereby separated from a part of the accompanying proteins. Elution of the column with a continuously increasing NaCl concentration desorbed the radioligand binding activities forming several peaks, two of which were nearly completely separated. Our data show that the mAChR in rat cerebral cortex consists of several entities with different electrical charges.

Animals↗
PubMed1986

Performance and biocompatibility of a new hemodialysis membrane.

Performance studies and investigations of the biocompatibility of a new hemodialysis membrane were conducted in patients being chronically hemodialyzed. The investigated polycarbonate membrane revealed a very satisfying performance with regard to clearance values and the ultrafiltration rate. The biocompatibility studies showed a significant leukopenia and an increase of C5a, platelet factor 4 and granulocyte elastase. Thrombocytes and C3d remained unchanged. Long-term studies have to confirm whether or not the new membrane is more biocompatible, a suggestion which could be advanced, as no febrile episodes were observed during any treatment, a finding which is not typical for Cuprophan hemodialysis.

Biocompatible Materials↗
PubMed1986

New approaches for the detection of early activation products in thrombotic states.

The occurrence of a consumption coagulopathy as well as prethrombotic and thrombotic states are connected with the formation of thrombin. The proteinase acts upon physiological substrates leading to activation products, e.g. fibrinopeptides, platelet factors or thrombin-antithrombin III-complex. For the determination of such products we have developed immunochemical assays, which detect parameters of a direct or indirect action of thrombin in a specific and sensitive manner: 1. ELISA for determination of platelet factor 4; 2. Latex-test for determination of D-Dimer; 3. ELISA for determination of thrombin-antithrombin III complex. Preliminary results from clinical investigations indicate that the determination of these parameters can be valuable for the diagnosis of activation processes of the clotting system.

Blood Coagulation Disorders↗
PubMed1986

Biochemical pharmacology of pirenzepine. Similarities with tricyclic antidepressants in antimuscarinic effects only.

5,11-Dihydro-11-[(4-methyl-1-piperazinyl) acetyl]-6H-pyrido[2,3-b][-1,4]-benzodiazepin-6-one dihydrochloride (pirenzepine, Gastrozepin) and some tricyclic antidepressant drugs which show a very close relationship concerning the chemical structure were investigated in numerous binding, uptake and enzymatic studies in vitro. With pirenzepine a high affinity binding could be demonstrated only to muscarinic receptors (Ki = 58 nmol/l). In all other studies pirenzepine had a very weak or no effect at all. In contrast, tricyclic antidepressants bound with high but different affinities to various receptors as known from numerous publications. The highest affinities were found with imipramine at the specific imipramine binding sites (Ki = 9.8 nmol/l) and at the alpha 1-receptor (Ki = 39 nmol/l), with desipramine at the muscarinic receptors (Ki = 88 nmol/l), with mianserin at the H1-(Ki = 3.4 nmol/l) and 5HT2-receptors (Ki = 7.3 nmol/l). Moreover, imipramine and desipramine showed their known substantial inhibition of noradrenaline and/or 5-hydroxytryptamine uptake. Thus, a homogeneous affinity or activity profile of the antidepressants studied does not exist. The only common property of pirenzepine and the tricyclic antidepressants was found to be the high affinity binding to the muscarinic receptors which might explain the common antisecretory action of these agents. Because of the unique specificity of pirenzepine lacking all other effects of the tricyclic antidepressants as demonstrated in this study, it is very unlikely that this drug exerts any antidepressant-like central action.

Animals↗