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Biomedical subjects

H Pusch

Publications and source records attributed to H Pusch.

At least 19 recordsLinked to original sources
PubMed1998

Na+/K+ pump inhibition and positive inotropic effect of digitoxigenin and some C-22-substituted derivatives in sheep cardiac preparations.

Affinity labeling might be used to localize the binding site(s) of the lactone ring of cardioactive steroids on the Na+/K+-ATPase. The aim of the experiments described below was to identify C-22-substituted derivatives of digitoxigenin suitable for this purpose. The positive inotropic effect of digitoxigenin, 22-benzoyloxy-digitoxigenin, 22-acetoxy-digitoxigenin, 22-allyl-digitoxigenin, and 22-hydroxy-digitoxigenin was studied in sheep cardiac Purkinje fibres. In addition, the inhibition of the Na+/K+ pump by these drugs was investigated by means of simultaneous measurements of membrane current and intracellular Na+ concentration in voltage-clamped Purkinje fibres and by means of whole-cell recording in isolated sheep Purkinje cells. The experiments were performed at 5.4 mM K+ and 30 to 33 degrees C. All compounds exerted a reversible positive inotropic effect. The concentrations required for the half maximal effect (EC50 value) amounted to approximately 5 x 10(-7) M digitoxigenin, 22-acetoxy-digitoxigenin or 22-hydroxy-digitoxigenin. The EC50 values for 22-benzoyloxy-digitoxigenin and 22-allyl-digitoxigenin were estimated to be 1.3 x 10(-6) M and 1.1 x 10(-5) M, respectively. From measurements on voltage-clamped Purkinje fibres the concentrations required for half maximal Na+/K+ pump inhibition (K'D value) were calculated to be approximately 10(-6) M for digitoxigenin, 22-acetoxy-digitoxigenin or 22-hydroxy-digitoxigenin. The K'D value for 22-benzoyloxy-digitoxigenin was 10 times larger. The K'D value for 22-allyl-digitoxigenin was even larger and amounted to approximately 4 x 10(-5) M. The K'D values of the drugs derived from whole-cell recording on single Purkinje cells tended to be smaller by a factor 2 to 8. Measurements of drug binding and unbinding revealed that the apparent association rate constant of 22-benzoyloxy-digitoxigenin (approximately 9 x 10(2) s(-1) M[-1]) was smaller than the association rate constant of digitoxigenin (approximately 2 x 10(4) s(-1) M[-1]), whereas the apparent dissociation rate constants of both compounds were similar (approximately 4 x 10(-3) s[-1]). Compared to digitoxigenin 22-allyl-digitoxigenin displayed a lower association rate constant (approximately 3 x 10(3) s(-1) M[-1]) and a larger dissociation rate constant (approximately 8 x 10(-2) M[-1]). The structure-activity relationships of the drugs are discussed. We conclude that esters derived from 22-hydroxy-digitoxigenin might be suitable to localize the binding site(s) of the lactone moiety on the Na+/K+ pump by affinity labeling.

Affinity Labels↗
PubMed1996

[Environmental factors on male fertility].

The fact that the incidence of infertile marriages is on the increase throughout the world has stimulated a greater interest in identifying possible effects of the environment on the fertility of both man and woman. Over the last 50 years, the average number of spermatozoa in the ejaculate has decreased by about a half. The present review takes a look at recognized noxae and their effect on fertility, with the aim of providing clinically active physicians with up-to-date information about the major noxious substances, thus enabling them to be avoided.

Environmental Exposure↗
PubMed1996

Tibolone versus conjugated estrogens and sequential progestogen in the treatment of climacteric complaints.

OBJECTIVE: Tibolone has been shown to alleviate climacteric symptoms. This study was designed to compare the effect of tibolone (Livial, 2.5 mg daily) on different climacteric complaints and its impact on the endometrium, determined by vaginal ultrasound, with that of conjugated estrogens (Premarin, 0.625 mg daily) continuously for 6 months in combination with the progestogen medrogestone (Colpron, 2 x 5 mg daily for 12 days each month). METHODS: One hundred and twenty-nine postmenopausal women were recruited and the severity of climacteric symptoms as well as endometrial thickness were recorded at the pre-trial examination and after 1, 3, and 6 months. RESULTS: With the exception of vertigo, mood depression, mood disorder, loss of libido, and dryness of skin, where tibolone was found to be more effective than conjugated estrogens/medrogestone, climacteric symptoms improved significantly in both groups over the 6-month study period. Endometrial thickness did not increase significantly in the tibolone group, whereas in the conjugated estrogens/medrogestone group there was a highly significant increase after 1 month and still a trend towards significance after 6 months. Recurrence of vaginal bleeding occurred significantly less frequently in the tibolone group than in the comparison group. CONCLUSION: Tibolone seems to offer a complete treatment of the climacteric complaints whilst avoiding some of the problems associated with classical hormone replacement therapy.

Climacteric↗
PubMed1996

Carbohydrate-deficient transferrin as a screening marker for drinking in a general hospital population.

We investigated the usefulness of the laboratory marker of alcohol consumption carbohydrate-deficient transferrin (CDT) in 101 consecutively admitted patients in a surgical and internal medical ward of a hospital in a rural wine-growing area. Four major aspects were considered: the influence of liver disease, the method of expression of CDT values (relative % vs absolute units/1), level and pattern of alcohol consumption and comparison with y-glutamyl transferase (GGT). The results show that %CDT is a more valuable discriminating marker of high alcohol consumption than absolute CDT values and its usefulness in this respect is independent of changes in serum total transferrin levels, as in liver disease. Sensitivity and specificity of % CDT were 70 and 98% respectively, compared with 65 and 83% respectively for GGT.

Adult↗
PubMed1990

The action of 22,23-dihydrobufalin and other cardioactive steroids on contraction and active sodium/potassium transport of sheep cardiac Purkinje fibres.

The recent synthesis of bufenolides permits the introduction into the lactone moiety of a latently reactive group suitable to localize exactly the binding site of the lactone ring of cardioactive steroids on the sodium potassium pump. For this purpose it is essential to demonstrate that the bufenolides are cardioactive. In the present paper the effect of the bufenolide 22,23-dihydrobufalin on contraction and active sodium/potassium transport is studied by means of electrophysiological methods in sheep cardiac Purkinje fibres. The results are compared to the corresponding actions of some other cardioactive steroids. 22,23-dihydrobufalin exerts a reversible positive inotropic effect. Simultaneous measurements of intracellular sodium activity and membrane current in voltage clamped fibres reveal an inhibition of the sodium potassium pump by 22,23-dihydrobufalin in the concentration range tested (10(-7) to 5 x 10(-5) mol/l). An apparent equilibrium dissociation constant K'D of about 10(-6) mol/l is derived for the drug--sodium/potassium pump interaction. The K'D value for bufalin is smaller, whereas the value for ouabain is comparable. The K'D value estimated for dihydroouabain is slightly larger. It is concluded that 22,23-dihydrobufalin shares important characteristics with cardioactive steroids. Thus, bufenolides are probably useful tools for an exact localization of the lactone binding site on the cardiac sodium/potassium pump.

Animals↗
PubMed1990

Evaluation of metabolic control in type 1 (insulin-dependent) diabetic patients by estimation of serum fructosamine.

The method of Johnson et al. (1982) for the estimation of non-enzymatically glycated serum proteins (fructosamine test) was critically evaluated and modified with respect to photometric readings, incubation conditions, and standardization of the procedure. With this modified method, serum fructosamine concentrations were estimated in type 1 (insulin-dependent) diabetic patients whose glycemic control ranged from strictly to poorly controlled and in normoglycemic healthy control subjects. The mean fructosamine concentrations were for the control group (n = 52) 2.17 mmol/l (range 1.73-2.61 mmol/l) and for the diabetic patients (n = 432) 2.87 +/- 0.60 mmol/l (range 2.27-3.25 mmol/l). There were significant differences in fructosamine concentrations among the diabetic patients, corresponding to the degree of metabolic control. Serum fructosamine levels were closely correlated to the HbA1 levels. Compared with HbA1, fructosamine reflects short-term metabolic changes and appears to be an useful index of short-term glycemia.

Diabetes Mellitus, Type 1↗
PubMed1990

[The fructosamine test for the determination of nonenzymatic glycosylated serum proteins. A critical inspection of the method].

A modification of the original method of R.A. Johnson et al. for nonenzymatically glycated serum proteins (fructosamine test) is described. Problems of performance and optimization of the method as well as of calibration and the influence of protein composition on the results are discussed. Measuring is manually performed after a 8 min preincubation interval over a 1 min's period using the spectrophotometer "Spekol 220". Interserial precision was 3.2%. First clinical results demonstrate the possibility to assess glycemic control in type 1 diabetic patients over a integrated time interval.

Blood Proteins↗
PubMed1989

Effect of isoprenaline on active Na transport in sheep cardiac Purkinje fibres.

The effect of isoprenaline (ISO; 5.10(-8) to 10(-6) M) on active Na transport was studied in depolarized sheep cardiac Purkinje fibres. Membrane current (I) and intracellular Na activity were measured simultaneously during enhanced Na pumping in voltage clamped preparations. ISO stimulated enhanced active Na transport but did not affect membrane current or intracellular Na concentration (ciNa) in the steady state under the chosen experimental conditions. The stimulatory effect of ISO was mediated by beta 1-adrenoceptors via a cAMP dependent pathway. The effect depended on the extracellular K concentration (coK) and was inhibited by external Ba ions. Complementary experiments on isolated sheep Purkinje cells revealed no ISO induced alteration of the Na pump current. The mechanism of the ISO induced stimulation of enhanced Na pumping in sheep Purkinje fibres probably involves an augmented K efflux. A direct effect on the pump molecule seems unlikely.

Animals↗
PubMed1989

The dependence of sodium pump current on internal Na concentration and membrane potential in cardioballs from sheep Purkinje fibres.

The effect of various intracellular Na concentrations (CiNa) and membrane potentials on the Na pump current (Ip) was studied in isolated, cultured sheep cardiac Purkinje cells ('cardioballs'). Ip was identified as cardiac steroid sensitive current. The dependence of Ip on CiNa was investigated at a membrane potential of -40 mV by means of whole-cell recording from cardioballs internally perfused with media containing various Na concentrations. Internal perfusion with a Na free solution abolished Ip. The amplitude of Ip as a function of CiNa displayed saturation kinetics. Half maximal activation of Ip occurred at a CiNa of about 9 mM. The maximal Ip density was estimated to be 1.1 microA/cm2. The potential dependence of Ip was studied by conventional whole-cell recording under various ionic conditions. Generally Ip displayed little voltage dependence at membrane potentials positive to -20 mV. Ip declined at more negative potentials. The pump cycle probably includes only one voltage sensitive step. The potential dependence of Ip was more pronounced at lower CiNa or lower concentrations of the external pump activator Cs+. The findings are in line with the idea that increasingly steeper ionic gradients against which the cations are pumped strengthen the voltage dependence of Ip in the potential range studied. Other factors probably affecting the pump current-voltage (Ip-V) relation are discussed. The results suggest that Ip varies during electrical activity.

Animals↗
PubMed1988

Lack of HLA class I and class II antigens on human preimplantation embryos.

The expression of HLA Ag on polyploid early human embryonic stages, obtained in an in vitro fertilization and embryo transfer program, was investigated by indirect immunofluorescence tests using a panel of mAb. Neither HLA class I Ag, beta 2-microglobulin, nor HLA class II molecules could be detected on blastomers. The zona pellucida also lacked these Ag, but granulosa cells expressed HLA class I Ag, beta 2-microglobulin, and HLA class II Ag. These results make it likely that the absence of HLA Ag is one of the mechanisms involved in protecting the implanting embryo from rejection by the immunocompetent mother.

Antibodies, Monoclonal↗
PubMed1986

The contribution of Na and K ions to the pacemaker current in sheep cardiac Purkinje fibres.

The ionic components of the pacemaker current are quantitatively analysed in sheep cardiac Purkinje fibres by simultaneous measurements of the intracellular Na activity (alpha iNa) and the membrane current under voltage clamp. The pacemaker current is operationally defined as the Cs inhibited membrane current (ICs) in Ba containing media at clamp potentials negative to -60 mV. At these potentials solutions containing CsCl (0.2-5 mM) shift the holding membrane current into the outward direction and simultaneously decrease alpha iNa. The Cs effects on membrane current and alpha iNa display a similar voltage dependence. A Cs inhibited Na influx contributes to ICs. The ratio ICs/(Cs inhibited Na influx in electrical units) is less than 1 at membrane potentials positive to the potassium equilibrium potential EK and greater than 1 at potentials negative to EK. The ratio is close to 1 at EK suggesting Na ions to be the only carriers of the current at EK whereas K ions contribute to ICs at potentials different from EK. The effects of Cs on the Cs inhibited Na influx and ICs show a very similar dose dependence. The effect is half maximum at approximately 0.2 mM CsCl (in 21.6 mM K; clamp potential: -85 mV). An increase of the external K concentration augments ICs and the Cs inhibited Ca influx. Na and K ions carrying ICs probably cross the membrane via an identical channel. The permeability of the channel for K+ is about 10-20 times larger than for Na+. The ICs reversal potential of a fibre bathed in a medium containing 5.4 mM K is estimated to be -50 to -60 mV.

Animals↗