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O Messerschmidt

Publications and source records attributed to O Messerschmidt.

At least 19 recordsLinked to original sources
PubMed1990

Prolonged radioprotective activity of WR-2721 linked to dextran.

The radioprotective agent WR-2721 was linked to dextran and poly(glutamic acid) respectively, to obtain a prolonged radioprotective ability. Male mice were administered these water soluble polymer conjugates one to 72 hours prior to a whole body irradiation with X-rays. A prolongation of radioprotective efficiency was achieved with two dextran-(WR-2721)-conjugates. For a period of 24 hours between administration, and irradiation dose reduction factors of 1.14 +/- 0.04 and 1.10 +/- 0.03 respectively were found. After 72 hours, no protective effect was observed. Histopathological investigations of the liver for formation of tumors 200 to 600 days after irradiation seems to indicate that a protective effect is not produced by the dextran-(WR-2721)-conjugates.

Amifostine↗
PubMed1989

Combined effects of radiation and trauma.

Injuries, caused by both whole-body irradiation and wounds or burns, have been relatively little studied. Possibly because many investigators think that these injuries are just modified radiation-induced diseases for which the same treatment principles are valid. Other authors had the impression that, for instance, the radiation burn trauma is a new kind of disease which differs significantly from either radiation syndrome alone or from burn disease. There are many experimental data on animals which suggest that the pathology of combined injuries differs significantly from that of radiation-induced disease or of thermal or mechanical traumas. Wounds or burns which, in general, do not cause septicaemia could become entrance ports for bacteria when animals are exposed to whole-body irradiation. Thrombocytopenia is the reason for hemorrhages in wounds. The susceptibility to shock is increased considerably in combined injuries and the formation of callus in the bone fractures is significantly delayed. The healing of wounds and burns in the initial phase of the radiation syndrome does not always differ from healing in the non-irradiated organism. However, a few days or weeks later very serious wound infections and hemorrhages can occur. The additional injuries almost always worsen the development and prognosis of radiation-induced disease. The recommended treatment for combined injuries will differ in many respects from the treatment of wounds and burns or the radiation syndrome.

Animals↗
PubMed1989

A norfloxacin dose finding study for selective decontamination of the digestive tract in pigs.

Five pigs were treated orally with norfloxacin for 5 consecutive days in two well-separated periods. This was done to determine the lowest dose required to free the pigs of Enterobacteriaceae. In the first period of the study, the animals were treated with 400 mg per day while in the second treatment 800 mg norfloxacin was given. Daily faecal culturing indicated that the faeces became free of Enterobacteriaceae in 3-5 days when treated with 400 mg/day, while all animals were found negative on culturing after 3 days of treatment with 800 mg/day. Investigation of the concentration of norfloxacin in the faeces revealed that a substantial fraction of the dose was either absorbed or inactivated by faecal substances. An in vitro study in faeces confirmed that a substantial part, some 75% of the dose, may have been inactivated by intestinal contents. This finding helps to explain the much lower concentration of 120 mg norfloxacin per kg of faeces in the pig in comparison with the almost tenfold higher concentration reported to develop in man during treatment with an identical dose.

Animals↗
PubMed1986

The influence of the solvent on the toxicity and radioprotective effect of thiophosphate WR2721 in mice.

The influence of various solvents on the toxicity as well as the protective efficiency of thiophosphate WR2721 in X-irradiated male mice is described. The use of Sörensen buffer as solvent with a pH-value of 7.4 leads to a statistically significant lower lethality in animals than aqua bidest. However, the radiation efficacy of thiophosphate with respect to the acute lethality within 30 days after irradiation is not influenced by the choice of the solvent used. A dose reduction factor of 2.49 +/- 0.03 is gained for the LD50/30 d at 500mg WR2721 per kg animal weight.

Amifostine↗
PubMed1984

Acute radiation injury of mice and the influence of sudden time shift.

The daily light-dark regimen for two groups of mice was advanced by 8 hr. A third group remained in unchanged lighting conditions. At seven different times within the following day subgroups of the time-shifted mice as well as of the group with unchanged time schedule were exposed to whole-body X irradiation. Mortality, body weight, and temperature of each animal were registered for 30 days following exposure and were regarded as indicators of radiation response. Radioresistance was found to be highest after two-thirds of the daily light span, confirming earlier reports by other authors. Well-defined effects of time shift and a corresponding shift of the maximum of radioresistance could be demonstrated. With the individual body weight as an independent variable, mathematical formulas for survival prognosis could be established.

Animals↗
PubMed1983

Experimental chemotherapy of radiation injury with synthetic lysophospholipid analogs in mice.

Synthetic lysophospholipids represent a variety of analogs of the naturally occurring 2-lysophosphatidylcholine. Some of these compounds showed significant therapeutic effects on the survival of mice following radiation injury when administered after various doses of whole-body X irradiation. Such therapeutic effects were discernible even when the treatment was given 6 hr after irradiation, and both intravenous and oral application were effective. Intravenous application of 2 X 25 mg/kg lysophospholipid after whole-body X irradiation around the LD50 resulted in significantly higher numbers of surviving animals. The mode of action remains speculative.

Animals↗
PubMed1983

[Therapeutic effect of fetal mesenchyma in acute radiation disease of mice].

The effects of an intramuscular application of fetal mesenchym (Resistocell) in mice with acute radiation injury was investigated. A single dose of 80 mg/kg body weight one day after radiation exposure (LD70/30, 635 cGy) showed significant therapeutic effects. Further experiments are recommended in order to improve and explain the reported results.

Animals↗
PubMed1982

Amount of peripheral reticulocytes as biologic dosimetry of ionizing radiation. Experiments in the rabbit.

The amount of reticulocytes in peripheral blood generally reflect the bone-marrow status of erythropoiesis and may therefore be useful in evaluating radiation injury. The blood reticulocytes in rabbits exposed to various doses of ionizing radiation were examined using an apparatus capable of microfluorometric quantification of reticulocytes as well as the conventional technique of reticulocyte count. A dose-dependent decrease of reticulocytes was observed. The possibilities of further improvements of the technique using flow cytometry and its application for screening human population are discussed.

Accidents↗
PubMed1982

[Studies about combined lesions - 30th communication. Activation and inhibition of blood-coagulation after whole-body irradiation combined with trauma (author's transl)].

45 rabbits of both sexes were divided into five groups. Animals were sham irradiated, inflicted with an autologous haematoma as a trauma, whole-body irradiated with 500 RX-rays, and inflicted with a combination of irradiation and autologous haematoma or skin-wound. Already 24 hr after irradiation a highly significant prolongation of the activated partial thromboplastin-time was observed. The concentrations of factor X and fibrinogen increased in all irradiated animals 24 hr after irradiation. Following the combination injury of irradiation and skin-wound such increases were significantly higher than those after irradiation alone. The activities of antithrombin III and antiplasmin, measure with chromogen substrates, rose after irradiation as well as after combined injuries. In spite of the increased level of fibrinogen we could register hypocoagulability with significant increase of activation as well as of inhibition of the plasmatic coagulation system 24 hr after combined injuries.

Animals↗
PubMed1981

Aging in vitro and D-glucose uptake kinetics of diploid human fibroblasts.

By use of a rapid technique, initial rates of D-glucose transport were obtained during the lifespan in vitro of a commercially available strain of human embryo lung fibroblasts (Flow 2000). The apparent Km of the D-glucose carrier did not change during senescence in vitro: x = 1.8 mM (range 1.3-2.3) in phase II, x = 1.8 mM (range 1.5-2.2) in phase III. Transport rates remained constant in stationary phase II cultures, which had completed between 30% and 80% of their replicative lifespan. A wide variation, however, was observed in terminally differentiated cells (phase III), which showed a two- to threefold increase in average cell size and protein content. In some senescent cultures, glucose transport calculated on a per cell basis was also two- to threefold increased, while it was strongly decreased (-75%) in others. When calculated per unit of cell water, protein, and surface area, respectively, transport rates in phase III cultures ranged from values established for stationary phase II cultures down to very low values. Detaching cells flushed off from senescent cultures did not show measurable rates of glucose transport into the inulin impermeable cell space. Present evidence argues against the idea that an impairment of D-glucose transport might precede loss of replicative potential in aging human fibroblasts. Instead our data indicate that the transport capacity of cell membrane finally decreases during postreplicative senescence in terminally differentiated cells.

Biological Transport↗
PubMed1980

D-Glucose transport into suspended human fibroblasts. Rapid measurement of uptake by silicone oil filtration centrifugation, and comparison of different cell detachment procedures.

The uptake of 14C-labeled D-glucose into the cellular space of human diploid fibroblasts (Flow 2000)--grown to confluency and detached with trypsin-EDTA--was studied using silicone-oil-layerfiltering centrifugation. This method is rapid enough to enable the determination of initial transport rates, which are not complicated by subsequent metabolism of the hexose taken up into the cells. D-Glucose uptake shows saturation kinetics with a Km of 1.8mM and maximal transport capacity of 4--8 nmol/(10(6) cells x min) at 20 degrees C. This saturable transport system is responsible for at least 80% of the total glucose taken up into the cells in the concentration range tested (0.1--10mM D-glucose in incubation medium). The glucose carrier is stereo-specific, is independent of sodium and potassium ions, and is inhibited by cytochalasin B. Its temperature dependence reveals an activation energy of 3 1 kJ/mol (7.5 kcal/mol; Q10 approximately equal to 1.5). As detachment of the cells from the culture flasks is necessary for applying silicone-layer-filtering centrifugation, various detachment procedures were tested. In the enzymatic procedure cells were treated with either trypsin or pronase. In the chelating method, Ca2+ and Mg2+ ions were chelated by EDTA and K+ ions with sodium tetraphenylborate. For mechanical detachment, cells were grown initially on plastic foil. After each of these detachment procedures the transport of D-glucose was the same. It is therefore concluded that this method of rapid measurement of D-glucose uptake in suspended human fibroblasts may serve as an alternative to the uptake measurement with glucose analogues in attached cells when studying the hexose transport system in human diploid fibroblasts.

Biological Transport, Active↗
PubMed1980

[Investigations on combined injuries, 29th communication. Protective effect of aminopropylamino-ethylthiophosphate (WR 2721) in mice with radiation and combined injuries (irradiation and skin wound or burn) (author's transl)].

Because of the crucial practical importance of combined injuries, investigations of the efficacy of the radioprotective agent aminopropylamino-ethylthiophosphate (WR 2721) were performed on mice which were whole-body X-irradiated and stressed with a second trauma either as an open wound or as burn wounds on the skin. In cases of sole whole-body irradiation, probit analyses of our data yielded the dose reduction factors (DRF) of 2.42 (NMRI-Hannover) and 2.12 (NMRI-Kisslegg). In case of a combination of an open skin wound (SW) with irradiation in mice of the Hannover breed the following dose reduction factors have been obtained: for irradiation+SDW 10 min p. r. the DRF 2.22, for irradiation+SW 2 d p. r. the DRF 2.30, and for irradiation+SW 8 d p. R.. the DRF 2.29. In cases of combined injuries with two burn wounds (BW) as second trauma in mice of the Kissblegg breed yielded: the DRF 2.01 for irradiation+BW 10 min p. r., and the DRF 1.91 for irradiation+BW 2 d p. r. The protective effect of WR 2721 is apparently similar in the various groups with combined injuries as compared to the animals exposed to whole-body irradiation only. The mechanisms of action of the sulphur-containing radioprotective agents are discussed.

Amifostine↗
PubMed1980

[Investigations with beagles about toxicity and radioprotective effect of the clinical radioprotection substance WR 2721. Part I. Toxicity of WR 2721 (author's transl)].

The toxicity of the chemical radioprotection substance WR 2721 (S-2-(3-aminopropylamino)ethyl-thiophosphate) was examined in 25 beagles. The study showed that the toxicity of the substance increases as the dose gets higher. Between the doses 200 and 250 mg/kg of body weight, the increase of toxicity was significantly greater than could be expected on the basis of the dose difference. Until a dose of 200 mg/kg, the authors found no side effects which would have disturbed vital functions, but higher doses led to marked symptoms of intoxication.

Amifostine↗