Effects on ontogenesis of Carausius morosus hit by cosmic heavy ions.

Among the biological problems that arise in long duration spaceflights, the effects of weightlessness and ionizing radiation appear to be the two main risk factors. Eggs of the stick insect Carausius morosus were exposed to spaceflight conditions during the 12.56 day Biosatellite mission Cosmos 1887. Five different ages were used, representing different sensitivities to radiation and different capacities for regeneration. During spaceflight the eggs continued their development. Already, in the Spacelab D1 mission in 1985, it has been shown that microgravity leads to a reduced hatching rate of eggs exposed during the early steps of development. When the eggs were hit by a heavy ion, a further but not significant reduction of the hatching rate was observed. Hatching was normal for eggs which were exposed on a 1 g reference centrifuge in space. Heavy ion hits caused body anomalies. The combined action of heavy ions and microgravity resulted in an unexpectedly high rate of anomalies. In the experiment on Cosmos 1887 these results were confirmed. Studies on the embryonic development before hatching showed no major difference between flight and ground control specimen, neither in speed of development nor in morphological anomalies. Hatching therefore seems to be the critical point in insect ontogenesis.

Influence of cosmic radiation and/or microgravity on development of Carausius morosus.

Eggs of Carausius morosus were exposed to spaceflight conditions in two spaceflight missions, the German 7 day Spacelab Mission D1 and the Soviet 12.56 day Biosatellite Mission "COSMOS 1887". During spaceflight the eggs continued their development. Eggs of five different ages representing different sensitivity to radiation and different capacity to regeneration were used to investigate the influence of cosmic radiation and/or microgravity on insect development. Using the Biostack concept--eggs in monolayers sandwiched between nuclear track detectors--and the 1 g reference centrifuge of BIORACK in D1 we were able to separate effects of heavy ions of the cosmic radiation from microgravity effects and also from combined effects of these two factors in space. After retrieval, hatching rates, embryonic and larval growth kinetics and anomaly frequencies were determined. Microgravity leads to a reduced hatching rate of eggs exposed in the early stages of development. Hatching was normal in eggs which were exposed on the 1 g reference centrifuge. Hits by heavy ions caused body anomalies. The combined action of heavy ions and microgravity resulted in an unexpectedly high frequency of anomalies. These results obtained from the Spacelab Mission D1, were confirmed in an experiment onboard of COSMOS 1887. In addition to the previous analysis, embryonic development before hatching was followed which showed no major difference between flight and the ground control specimens. Since a reconfirmation of reduced hatching rates was observed in COSMOS 1887, too, the above results suggest some microgravity induced functional impairment of the hatching activity, rather than blockage in embryonic development.

[Distribution of 4-14C-mofebutazone in the rat]. / Zur Verteilung von 4-14C-Mofebutazon bei der Ratte.

To further elucidate the distribution and differentiation of mofebutazone in comparison to phenylbutazone, 6 rats received 200 mg/kg 4-14C-mofebutazone corresponding to approx. 27 microCi/animal. 2 animals were sacrificed each time after 45 min, 6 h and 24 h. The 4-14C-plasma level was determined at the corresponding test periods and the radioactivity eliminated within 24 h in the urine was also determined. In addition autoradiograms of the whole animal were prepared for each animal. According to this study 4-14C-mofebutazone is distributed mainly in the metabolisation and elimination organs, a moderate activity was to be found under the skin and muscle tissue, but none, however, in the central nervous system and the bone marrow. Nearly 81% of the substance was eliminated after 24 h and with exception the colon the corresponding autoradiograms were practically free of activity. Because of the short half-life time and the rapid elimination mofebutazone does not lead to any accumulation.

Measurement of theophylline absorption from different regions of the gastro-intestinal tract using a remote controlled drug delivery device.

The absorption of a theophylline solution containing 80-120 mg doses delivered to different sites in the gastro-intestinal tract has been determined in 3 male volunteers using a remote controlled drug release system (HF-capsule). There was no difference between the stomach, ileum and the colon in the amount of theophylline absorbed (AUC). The T 1/2abs of theophylline absorbed via the colon was prolonged when compared with that entering via the upper gastro-intestinal tract. The results provide a rational basis for the further development of theophylline formulations and are indispensable for planned development and to account for variation in the bioavailability of retarded release drug preparations.

Embryogenesis and organogenesis of Carausius morosus under spaceflight conditions.

The influence of cosmic radiation and/or microgravity on insect development was studied during the 7 day German Spacelab Mission D1. Eggs of Carausius morosus of five stages differing in sensitivity to radiation and in capacity to regeneration were allowed to continue their development in the BIORACK 22 degrees C incubator, either at microgravity conditions or on the 1 g reference centrifuge. Using the Biostack concept--eggs in monolayers were sandwiched between visual track detectors--and the 1 g reference centrifuge, we were able to separate radiation effects from microgravity effects and also from combined effects of these two factors in space. After retrieval, hatching rates, growth kinetics and anomaly frequencies were determined in the different test samples. The early stages of development turned out to be highly sensitive to single hits of cosmic ray particles as well as to the temporary exposure to microgravity during their development. In some cases, the combined action of radiation and microgravity even amplified the effects exerted by the single parameters of space. Hits by single HZE particles caused early effects, such as body anomalies, as well as late effects, such as retarded growth after hatching. Microgravity exposure lead to a reduced hatching rate. A synergistic action of HZE particle hits and microgravity was established in the unexpectedly high frequency of anomal larvae. However, it cannot be excluded, that cosmic background radiation or low LET HZE particles are also causally involved in damage observed in the microgravity samples.

Dose-dependent pharmacokinetics of dexamethasone.

The dose dependency of the pharmacokinetics of dexamethasone and its influence on the endogenous secretion of cortisol has been studied in healthy females. The maximum plasma level occurred between 1.6 and 2.0 h after doses of 0.5-3.0 mg independent of the type of administration. AUC, distribution volume, plasma clearance and cmax did not increase in proportion to the dose but only by the factor of about 0.6-0.7 after the oral administration of 0.5-1.5 mg. Comparatively high values were reached after 3.0 mg i.m. This may be due to reduced bioavailability of the oral doses. Within the first 12 h after the administration of 0.5-3.0 mg, endogenous cortisol secretion was influenced independent of dose. However, the suppressive effect after 24 h was dose dependent and amounted to approximately 24% for 0.5 mg p.o., 62% for 1.5 mg p.o. and 90% for 3.0 mg i.m. In the case of administration every second day, the integral reduction within 24 h after the administration of 0.5 mg dexamethasone was 44 to 65% and for 1.5 mg between 59 and 62%.

[Pharmacology, toxicology and pharmacokinetics of mofebutazone]. / Zur Pharmakologie, Toxikologie und Pharmakokinetik von Mofebutazon.

The difference between mofebutazone and phenylbutazone is shown by means of toxicological, pharmacological and pharmacokinetic studies as well as by the protein binding. In spite of a certain chemical similarity both substances differ distinctly. Mofebutazone is approx. 5-6 times less toxic than phenylbutazone but its analgesic and antiphlogistic effects are weaker than those of phenylbutazone. The half life time of mofebutazone of 1.9 h is considerably shorter than that of phenylbutazone (54-99 h). Mofebutazone, in contrast to phenylbutazone, is mainly glucuronidised and to 94% eliminated within 24 h, phenylbutazone on the other hand to only 88% within 21 days. In spite of a high plasma protein binding quota of 99%, mofebutazone is classed among those substances with a medium binding potential. Conclusions may only be drawn with great reservation with regard to a category of substances from the effect and side effects of one substance on the basis of the present studies.

[Therapy of heart failure with combined furosemide retard/triamterene]. / Therapie der Herzinsuffizienz mit der Kombination Furosemid retard/Triamteren.

20 patients with an average age of 73.3 years suffering from left cardiac insufficiency in stage II to III of the NYHA, who could not be recompensated alone by means of digitalisation, received additionally the diuretic combination furosemide-retard (30 mg)/triamterene (50 mg) for 2 to 3 weeks. Subjective side effects were not observed. The laboratory parameters did not show any substantial changes. A short increase of uric acid and serum creatinine in the older patients returned to normal spontaneously. A decreased potassium level returned to normal; a hyperkaliemia was not observed. The repeated administration of the combination did not lead to any accumulation; only a balanced concentration at a low level appeared. The urine elimination, the decrease in body weight, the regression of the lung congestion and the size of the heart were statistically significant.

Life sciences: radiobiological advanced biostack experiment.

The radiobiological properties of the heavy ions of cosmic radiation were investigated on Spacelab 1 by use of biostacks, monolayers of biological test organisms sandwiched between thin foils of different types of nuclear track detectors. Biostacks were exposed to cosmic radiation at several locations with different shielding environments in the module and on the pallet. Evaluations of the physical and biological components of the experiment to date indicate that in general they survived the spaceflight in good condition. Dosimetric data are presented for the different shielding environments.

A radiopharmacological study without human radiation exposure.

The development, study and control of new drugs today is hardly conceivable without nuclear medicine studies. Nuclear physicians on ethical commissions bear great responsibility in the planning and execution of such studies. In order to protect subjects and patients those nuclear techniques are therefore to be welcome which do not include exposure to radiation. Nuclear techniques used in in-vitro diagnostics (RIA) and the determination of naturally occurring nuclides incorporated in the human body belong to this category. With the aid of a clinico-pharmacological study of a new combination of diuretics it is shown that both methods supply valuable pharmacodynamic evidence.

Advanced biostack: experiment 1 ES 027 on Spacelab-1.

The radiobiological properties of the heavy ions of cosmic radiation were investigated on Spacelab 1 by use of biostacks, monolayers of biological test organisms sandwiched between thin foils of different types of nuclear track detectors. Biostacks were exposed to cosmic radiation at several locations with different shielding environments in the module and on the pallet. Evaluations of the physical and biological components of the experiment to date indicate that in general they survived the spaceflight in good condition. Dosimetric data are presented for the different shielding environments.

[Nuclearmedical tumor diagnosis]. / Nuklearmedizinische Tumorsuche.

Nuclear medicine diagnosis is an important discipline in cancer searching. By using reliable radiopharmaceuticals practically all organs can be investigated, especially bone cancer.

[Varying standard concentrations as a cause of divergent serum digoxin estimations using radioimmune-essays (author's transl)]. / Unterschiedliche Standardkonzentrationen als Ursache für divergierende Serumdigoxinbestimmungen mit Radioimmunoassays

1. The results of various commercial radio-immune essays for digoxin differ and cannot readily be compared. 2. For each RIA it is therefore necessary to determine one's own therapeutic and toxic levels in relation to the clinical requirements. 3. When quoting data, it is necessary to define the method of RIA with its therapeutic and toxic levels. 4. A cause for the high digoxin estimations of 2 RIA's carried out by the same firm has been identified as being due to the low concentration of the standard preparation. 5. The introduction of a defined and obligatory digoxin standard is recommended.

[Serum dixogin determination. Clinical significance, results and error consideration based on comparative studies with different radioimmunoassays]. / Digoxinbestimmung im Serum. Klinische Bedeutung, Ergebnisse und Fehlerdiskussion an Hand vergleichender Untersuchungen mit verschiedenen Radioimmunoassays

In order to compare 5 different radioimmunoassays (RIA's) and their results we determined the digoxin concentration in the serum of 186 patients and point out some sources of error. We consider the following points important: 1. There were found varying results in the determination of digoxin concentration in patient's sera using different RIA's. 2. One of the essential reasons for these differences are discrepancies of the RIA standards which belong to each kit. 3. It should be required that the control standard is equal to all RIA's. 4. Each laboratory which carries out digoxin determinations should, in collaboration with the clinic, work out and announce its own guide-line values for the RIA used in regard to the optimal therapeutic range and also to overdoses.

[Sources of error in the radioimmunochemical determination of digoxin in serum]. / Fehlerquellen bei der radioimmunochemischen Digoxinbestimmung im Serum

In a study with numerous samples of serum we compared 5 Digoxin RIA and evaluated the reliability of tests by simultaneous determinations. There were found considerable differences in the determinations with the various RIA for the same serum; evident differences also were recorded in the recovery and in the reproducibility of the assays. Among some other sources of error the dependence of temperature and of the duration of the dextran-charcoal separation were observed; therefore, the charcoal incubation is recommendable at 4 degrees C. Each laboratory which is able to perform the determinations of digoxin concentrations in the serum should declare its own range for the therapeutic and toxic levels for the used RIA in collaboration with the clinicians.