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M Weber-Frisch

Publications and source records attributed to M Weber-Frisch.

5 recordsLinked to original sources

Short-term immobilization of mice by methohexitone.

The feasibility of short-term immobilization for <5 min of female mice by methohexitone sodium was studied. In C3H/Neu mice, methohexitone at a dose <40 mg/kg did not result in chemical restraint, doses >50 mg/kg caused considerable lethality. A dose of 44 mg/kg, applied intraperitoneally at a concentration of 6.46 mg/ml, is suitable for immobilization without complications. This concentration was chosen in order to achieve an injection volume of about 0.15 ml for a mouse with an average body weight of 22 g, corresponding to about 1 mg/mouse. Complete immobilization, defined as absence of the righting reflex, was observed within 3.3 +/- 0.8 min (mean +/- SD, n = 10) after the injection and lasted for 1.5 +/- 0.7 min. Recovery of the animals was complete after a total period of 10 to 15 min post-injection. No gross pathomorphological changes were induced when intraperitoneal injections of methohexitone were repeated 10 times within 10 days. In the present study, complete immobilization of the mice was safely achieved after 87 out of 90 injections. In conclusion, immobilization by intraperitoneal injection of methohexitone is a feasible and reliable method in the experimental studies of female mice.

Anesthesia Recovery Period↗

Tissue kinetics in mouse tongue mucosa during daily fractionated radiotherapy.

The purpose of the present investigation was to quantify cell flux between the distinct layers of the epithelial lining of the ventral surface of mouse tongue during daily fractionated radiotherapy. A fraction of DNA-synthesizing cells in control epithelium, or at various days through a course of daily fractionated radiotherapy with 3 or 4 Gy per day, was labelled with [3H]dT or BrdUrd, respectively. The labelling indices (LI) in the different epithelial layers were defined histologically after autoradiography, or immunohistochemistry, at intervals between 1 and 10 days after label administration. In tongue epithelium of untreated mice, the minimum residence time of cells in the germinal layer is 2-3 days. Migration through the functional layers requires an additional 2-3 days before labelled cells are observed in the most superficial layer of nucleated cells. A plateau in LI is observed for several days post-labelling in control epithelium, indicating an equilibrium between loss and proliferation of labelled cells. During fractionated radiotherapy, the minimum time from division to occurrence of labelled cells in the stratum lucidum is less than 2 days, and hence significantly shorter than in control epithelium. In contrast to untreated epithelium, no plateau in the germinal layer LI is seen, indicating that frequently both labelled daughters from dividing labelled cells are being lost from this compartment. In conclusion, the present data support a recently described model of radiation-induced accelerated repopulation in squamous epithelia, which postulates that the majority of damaged cells undergoes abortive' divisions resulting in two differentiating daughters.

Animals↗

Repopulation response of mouse oral mucosa during unconventional radiotherapy protocols.

Repopulation in mouse tongue epithelium was determined during unconventional fractionation schedules, i.e., hyperfractionation (2 x 1.5 and 2 x 1.75 Gy/day) and accelerated treatment (2 x 3 Gy/day). The residual tolerance of the epithelium at defined days of the fractionated treatment was tested by graded single test doses (top-up design). The dose required to induce complete epithelial denudation in 50% of the animals (ED50) was used to calculate the number of fractions repopulated during the preceding treatment. After the first week of hyperfractionation, tolerance was reduced compared to untreated epithelium. However, subsequently no further change was observed, indicating complete compensation of the weekly dose with all doses per fraction used. Epithelial cell density, defined by histological examination in additional experiments, in all fractionation arms decreased similarly by approximately 40% during the first week and remained constant at 60-80% in the subsequent 2 weeks. During accelerated fractionation, the residual mucosal tolerance decreased continuously with treatment time and resulted in epithelial denudation after 12 fractions. However, a substantial repopulation effect was observed, compensating 1.5 fractions by day 2, and 5 fractions by day 5, respectively. After cessation of the therapy the repopulation rate clearly decelerated to compensate a dose equivalent to about 0.5 fractions per day. Cell density decreased linearly during the treatment with 5, 10 or 12 fractions at a rate close to normal cell loss. Marked cell production, dependent on the total fractionated dose, was seen from one day after the last fraction in each experimental arm. These results indicate that maximum stem cell repopulation occurs predominantly during treatment, while major production of differentiating cells take place in treatment splits.

Animals↗

Effect of changing weekly dose on accelerated repopulation during fractionated irradiation of mouse tongue mucosa.

The effect on accelerated repopulation of fractionated radiotherapy with changing weekly dose was studied in mouse oral mucosa. The basic conventional treatment protocol comprised five daily fractions per week, 3 Gy per fraction, given over 3 weeks. In dynamic treatment schedules the same total dose was delivered by giving 5 x 2, 5 x 3 and 5 x 4 Gy, or the reverse sequence. In concomitant boost experiments five additional daily doses of 1 or 2 Gy respectively were applied either during the first or last week of the conventional treatment. Graded terminating test doses were given in order to establish dose-effect curves for complete mucosal denudation. Higher initial doses consistently resulted in longer latent times between top-up irradiation and complete epithelial denudation, corresponding to significantly higher cell densities at the time of test irradiation. The top-up ED50's served as a measure of repopulation efficacy. The difference in repopulated dose between schedules with initial or terminal dose concentration was 10% for dynamic fractionation (p = 0.02) and about 7% in the 2-Gy boost protocol (p = 0.13), and no difference was observed with boost doses of 5 x 1 Gy. In conclusion, a clear though moderate increase in both cell density and residual tissue tolerance can be achieved by protocols with substantially higher doses in the first treatment week.

Animals↗