Excitation functions of the analyzing power in pp--> scattering from 0.45 to 2.5 GeV

Excitation functions A(N)(p(p),Theta(c.m.)) of the analyzing power in pp--> elastic scattering have been measured with a polarized atomic hydrogen target for projectile momenta p(p) between 1000 and 3300 MeV/ c. The experiment was performed for scattering angles 30 degrees

[Blood level oriented ambulatory cyclosporin A therapy following kidney transplantation]. / Blutspiegelorientierte ambulante Cyclosporin-A-Therapie nach Nierentransplantation.

It is reported on the blood level-oriented oral long-term therapy with cyclosporin-A (Sandimmun) in 20 patients after kidney transplantation. The Cy-A-concentrations were measured in the whole blood by means of a radioimmunoassay (Sandoz) under steady state conditions. The mathematical analysis of the steady state daily minimum concentrations in the whole blood depending upon the dosage rate allows individual calculations of the dosage for the stabilisation of the therapeutic concentration desirable for the individual patient in each case. In the majority of the patients a non-linear relation between the steady state blood concentration and the dosage rate was present. The observation of a defined therapeutic area under the conditions of the ambulatory treatment could be achieved without any problems. The control intervals were 4-6 weeks. The long-term stability of the individual pharmacokinetic parameters can at present not be judged reliably, since the average observation time is still too short. In 6 patients who are controlled on the way demonstrated already for several months no systemic changes in the behaviour of the blood level were to be seen.

Comparative bioavailability of two carbamazepine tablets.

The comparative bioavailability of two commercial carbamazepine tablets (Finlepsin and Tegretol) was investigated. In a single-dose study in eight healthy volunteers and in a multiple-dose study in five epileptic patients carbamazepine absorption from both drug products was shown to have the same extent and reliability. Despite a somewhat increased rate of absorption in Finlepsin, as regards the fit of the drug level in the therapeutic range under chronic treatment conditions, there was no difference between the two preparations. On the basis of these results we conclude that Finlepsin and Tegretol are bioequivalent drug products.

[Effect of portasystemic anastomoses in childhood on propranolol pharmacokinetics]. / Auswirkungen porto-systemischer Anastomosen im Kindesalter auf die Propranolol-Pharmakokinetik.

Kinetics of propranolol after oral administration were investigated in 9 children aged 5--11 years with intact liver function who had undergone porto-systemic anastomosis surgery for pylethrombosis and in a 16-year-old boy with a Warren shunt. Bioavailability of the drug had increased by twice the values measured in physiologic liver blood flow; elimination half-life had doubled. These alterations must be taken into consideration in medication, e.g. extreme care must be exercised in the oral administration of "first pass" drugs in porto-systemic shunt patients and it is recommended that the initial dose should be at the level of intravenous administration. The reduced rate of elimination should be taken into account in the case of drugs whose elimination depends on liver blood flow.

[Theoretical studies on the influence of binding constants of hemoglobin for ATP and 2,3-diphosphoglycerate on erythrocyte glycolysis]. / Theoretische Untersuchung über den Einfluss der Bindungskonstanten von Hämoglobin für ATP und 2,3-Diphosphoglyzerat auf die Erythrozytenglykolyse.

In the red blood cell exist a binding equilibrium of ATP and 2,3-DPG with hemoglobin. For the metabolism only the free active levels of organic phosphates are relevant. The binding constants of hemoglobin increase with decreasing temperature and pH. Using a stoichometric model of glycolysis, the change of free concentrations by altered binding constants and its import on the energy metabolism of the erythrocyte was theoretically studied. The results are: 1. Total ATP-content (bound plus free ATP) does not depend on the binding properties of hemoglobin. 2. Total 2,3-DPG-content is changed by altered binding constants of hemoglobin. The direction of change depends on the ratio energy-consumption/substrate-uptake. 3. In the case of strong binding of organic phosphates to hemoglobin the experimentally measurable total ATP-content does not reflect the free ATP-concentration in the cell water. As a result of binding, free ATP may be low even if total ATP is unchanged. 4. The free concentration of 2,3-DPG always parallels the total content.

[Importance of binding of 2,3-diphosphoglycerate and ATP to hemoglobin for erythrocyte glycolysis: activation by 2,3-diphosphoglycerate of hexokinase at intracellular conditions]. / Bedeutung der Bindung von 2,3-Diphosphoglyzerat und ATP an Hämoglobin für die Glykolyse in Erythrozyten: Aktivierung der Hexokinase durch 2,3-Diphosphoglyzerat unter intrazellulären Bedingungen.

In a theoretical study the influence of hemoglobin and Mg-ions as binding partners of red cell 2,3-diphosphoglycerate and ATP was investigated. Free hemoglobin may be an efficient competitor of Mg2+ for the ligand ATP. At conditions which favour hemoglobin as binding partner (i.e. desoxygenation, low medium pH and incubation temperature, as in blood preservation) up to 95% of the whole cellular ATP (ca. 2mM in cell water) may be bound to hemoglobin (ca. 7 mM). This binding is largely prevented in the presence of physiological amounts of diphosphoglycerate (ca. 7 mM) which is in excess and has a higher binding affinity to hemoglobin. Therefore, diphosphoglycerate keeps ATP (MgATP) in cell water solution at conditions in which Hb would trop it in the presence of Mg2+ (ca. 3mM). It can be calculated that, by lack of free MgATP, the activity of hexokinase within the cell drops by a factor of greater than 10 when diphosphoglycerate is metabolized. This indirect activation by diphosphoglycerate of hexokinase is operative at free concentrations of DPG far below those which exert the well known excess inhibitory effect on hexokinase and phosphofructokinase. In a model study, the activation by diphosphoglycerate of the initial two-kinase stage was introduced into a simplified kinetic model of glycolysis. A pronounced hysteresis loop of the stationary concentrations of ATP and diphosphoglycerate was produced indicating the existence of several stationary states, one with high ATP and high diphosphoglycerate, the other one with low values. It is demonstrated that diphosphoglycerate, being a protector of glycolysis at physiological concentrations, triggers an autocatalytic breakdown of the energy state when permitted to drop to low values.

[Effect of rapid changes of the oxygenation state and other external parameters on the long-term behavior of the energy metabolism in the erythrocyte]. / Einfluss schneller Bewegungen des Oxygenierungszustandes und anderer äusserer Parameter auf das Langzeitverhalten des Energiestoffwechsels der roten Blutzelle.

The red blood cell when transported through the circulatory system is exposed to a steady (approximately periodical) change of environmental conditions causing a permanent fluctuation of its important metabolic parameters. In a simple theoretical model it is demonstrated that a rapid oscillation of such parameters may stabilize a metabolic state which will collapse when this oscillation breaks off. The hypothesis is advanced that parameter oscillations caused by the physiological function of the red blood cell may be of importance for the maintenance of its energy metabolism and that the break-off of these oscillations may be a potential cause for the metabolic collapse, e.g. in stored blood.