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B Vojnovic

Publications and source records attributed to B Vojnovic.

43 records · Page 3Linked to original sources

Radiofrequency diathermy for uniform heating of mouse tumours.

A system has been developed for uniformly heating mouse tumours by using a combination of 27.12 MHz radiofrequency electric fields (RF) and immersion in heated liquid. Continuous tumour thermometry with implanted thermocouples is necessary in order to modulate the RF power to maintain a constant temperature over 1 h. Tumours implanted intramuscularly in the hind limbs of mice were heated between a pair of 1.9 cm diameter parallel copper plates. The optimum temperature profile was achieved if the RF heating was combined with immersion of the limb in circulating saline, preheated to the desired temperature. This method of electrical coupling between the plates and tissues has been shown to be significantly better than using ECG jelly or unheated liquid, and it is better than simple immersion in heated liquid without RF. A temperature monitoring system has been developed, using fine thermocouples implanted into the tumour, to regulate the applied RF power. Each complete thermocouple probe is less than 0.5mm in diameter and consists of 6 separate monitoring junctions spaced at 1.5mm intervals along its length. Using this monitoring system the temperature within tumours has been maintained constant (+/- 0.1 degrees C) for a period of 1 h.

Animals↗

Changes in nerve conduction velocity in the mouse after acute and chronic administration of nitroimidazoles.

The effect of the nitroimidazoles misonidazole, Ro-05-9963, RGW-608 and metronidazole on nerve conduction velocity (NCV) were measured in the anaesthetized mouse. The compounds were administered by i.p. injection either as a single dose of 1 mg/g (only 0.5 mg/g for RGW-608) or in 36 fractions of 0.15 mg/g over 18 days (only 4 fractions in 2 days for RGW-608). After single doses a reduction in nerve conduction velocity was seen with all the compounds except metronidazole, which had no significant effect. During chronic exposure, a reduction in NCV occurred towards the end of the course of injections. All compounds produced an effect, although RGW-608 was the most neurotoxic, giving the largest reduction in NCV after only 4 injections. After the end of chronic exposure to misonidazole, Ro-05-9963 and metronidazole, recovery to normal took 2-3 weeks.

Animals↗

The effect of the radiosensitizer misonidazole on motor nerve conduction velocity in the mouse.

The clinical use of misonidazole as a hypoxic cell radiosensitizer is at present limited by its neurotoxicity at high doses (Urtasun et al., 1977; Dische et al., 1977). An in vivo neurological end point, viz. measurement of nerve conduction velocity, has been developed to examine sensitizer action. Conduction velocity in mice was measured as a function of time after a single dose of misonidazole and as a function of drug dose. Doses greater than 0.33 mg/g produced significant transient reductions in velocity. The time course of the reduction in velocity closely followed the uptake/excretion profile of misonidazole from blood serum.

Action Potentials↗

A multiple RF heating system for experimental hyperthermia in small animals.

A versatile system is described for locally heating a number of mouse tumours simultaneously using RF capacitive coupling. The system is designed around a single RF power amplifier supplying a number of heating jigs via an efficient isolated power splitter. It is primarily intended for use at 13.56 and 27.12 MHz, but can operate from 2-30 MHz and could be modified for use at other frequencies. Microthermocouples are used for monitoring the intra-tissue temperature quasi-continuously, by making temperature measurements every 220 ms within 20 ms periods during which the RF power is turned off to all the jigs. This method avoids any artefacts in the temperature measurement which are associated with electromagnetic interference. Thermostatic regulation of tissue temperature is provided by on-off control of the average power supplied independently to each heating jig.

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Effects of combretastatin A4 phosphate on endothelial cell morphology in vitro and relationship to tumour vascular targeting activity in vivo.

BACKGROUND: Combretastatin A4 Phosphate (CA4P) is a tubulin binding agent which causes rapid tumour vascular shutdown. It has anti-proliferative and apoptotic effects on dividing endothelial cells after prolonged exposure, but these effects occur on a much longer time scale than the reduction in tumour blood flow. This study compared the time course of CA4P effects on endothelial cell shape and reduction in red cell velocity. METHODS: Endothelial cell area and form factor (1-4 pi x area x perimeter-2) were measured for proliferating and confluent HUVECs after CA4P treatment. Recovery of shape after CA4P and colchicine was compared. Window chamber studies of tumours were used to measure red cell velocity. Results 70% reduction in red cell velocity and 44% reduction in HUVEC form factor occurred by 10 minutes. Proliferating HUVECs underwent greater cell shape change after CA4P, which occurred at lower doses than for confluent cells. Cell shape recovered 24 hours after 30 minutes exposure to CA4P, but not after colchicine. CONCLUSIONS: The similar time course of cell shape change and red cell velocity reduction suggests endothelial cell shape change may be involved early in the in vivo events leading to vascular shutdown. Differences in the recovery from the shape changes induced by CA4P and colchicine could underlie the different toxicity profiles of these drugs.

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