Bubble Technology Industries Inc. (BTI), with the support of the Canadian Space Agency, has finished the construction of the Canadian High-Energy Neutron Spectrometry System (CHENSS). This spectrometer is intended to measure the high energy neutron spectrum (approximately 1-100 MeV) encountered in spacecraft in low earth orbit. CHENSS is designed to fly aboard a US space shuttle and its scientific results should facilitate the prediction of neutron dose to astronauts in space from readings of different types of radiation dosimeters that are being used in various missions.

Astronauts↗

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Radiobiological principles in intravascular irradiation.

BACKGROUND: There is wide interest in the use of intravascular irradiation to control restenosis following balloon angioplasty. Part of the mechanism of restenosis appears to be the proliferation of smooth muscle cells (SMCs), triggered to divide by the damage caused by the angioplasty, and this proliferation can be inhibited by irradiation with y-rays or beta-rays. METHODS: In vitro data for the survival of smooth muscle cells exposed to radiation was used to model the likely control of restenosis by radiation. Physical and biological data were used to estimate differences in biological effectiveness of gamma-rays and beta3-rays, as well as the effect on cell killing of extending the exposure time. RESULTS: Based on the radiosensitivity of SMCs, measured in vitro, and the limited proliferative potential of these normal somatic cells, it is possible to understand and to model quantitatively how a single acute gamma-ray dose in the range of 15-20 Gy can inhibit restenosis. The few successful trials carried out to date where radiation has been shown to inhibit restenosis have all involved the gamma-emitter Iridium-192. The use of this radionuclide involves radiation safety problems and an inconveniently long treatment time. Consequently, there is much interest in developing a beta-emitting source that would solve both problems, and a number of different possibilities are being pursued. This development introduces two new problems discussed in this paper. First, beta-rays in the megavoltage range are less effective biologically than gamma-rays in the kilovoltage range, but the magnitude of the difference is not well known. Second, in the case of a single large dose, such as that proposed to inhibit restenosis, the biological effect will vary substantially as the exposure time varies from 1 to 20 min. If the clinical data are to be compared between centers using a variety of beta and y-emitting radionuclides, these factors will need to be taken into account. CONCLUSIONS: Doses of > 15 Gy are unlikely to result in elimination of the restenosis problem but should delay onset of restenosis for a significant period; the larger the dose, the longer the delay. Successful trials of endovascular radiation completed to date involve y-rays, while many systems being developed are based on beta-emitting radionuclides. Experimental data are urgently needed so that allowances can be made for the difference in dose-rate and radiation quality between gamma and beta-emitting radionuclides.

Angioplasty, Balloon↗

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Processing of fusion proteins with immobilized factor Xa.

Factor Xa, with a cellulose-binding domain (CBD) fused to the C-terminus of the heavy chain (FXa-CBD), is active in solution and when immobilized on cellulose. A second derivative of factor Xa in which a hexahistidine tail is fused to the C-terminus of the heavy chain (FXa-H6) also retains activity when immobilized, in this case on Ni(2+)-NTA agarose. The stabilities and activities of of FXa-CBD and FXa-H6 immobilized on cellulose and Ni(2+)-NTA agarose, respectively, are similar. Immobilized factor Xa derivatives can be used to remove affinity tags from appropriate fusion proteins without contaminating the desired product with factor Xa.

Affinity Labels↗

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Calcium channel activation does not increase release of endothelial-derived relaxant factors (EDRF) in rat aorta although tonic release of EDRF may modulate calcium channel activity in smooth muscle.

We investigated whether Ca2+ channel activation by K+ or Bay K 8644 could cause release of endothelium-derived relaxant factor (EDRF) from rat aorta. Bay K 8644 (0.1-100 nM) did not relax rat aorta preparations partially contracted with phenylephrine, although acetylcholine caused large relaxations. Following partial K+-depolarization (12 or 15 mM), Bay K 8644 (10 nM-1 microM) contracted rat aorta preparations directly. Preparations were more sensitive to Bay K 8644 when stripped of the endothelium in 12 mM K+; concentration-effect curves were displaced to the left, and maximum responses were enhanced. In 15 mM K+, there was a leftward shift of the curves without change of maximal responses. However, Bay K 8644 (1 microM), did not increase the guanosine 3',5' cyclic-monophosphate (cGMP) content of rat aorta in the presence of endothelium, which is a function of EDRF release. Representatives (nifedipine, verapamil, cinnarizine) from different calcium antagonist subgroups had differential effects on contractions induced by Bay K 8644, and the effects of verapamil (1 and 10 microM) and lower concentrations of cinnarizine (1 microM) were reduced in the presence of endothelium. We propose that there is a tonic liberation of EDRF in rat aorta, which is unaffected by Ca2+ channel activation and which gives effects similar to a weak hyperpolarization of the smooth muscle cells. Consequently, Ca2+ channel activation and sensitivity to certain calcium-antagonists may be modified.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

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Effects of changes in external calcium concentration and frequency of stimulation on inotropic responses to isoprenaline and tolbutamide in rabbit atria.

1. Driven left atrial preparations were used to study inotropic responses to isoprenaline and tolbutamide. 2. Decreasing the external calcium concentration from 2.2 to 1.1 and 0.55 mM decreased resting force of contraction but increased the maximal inotropic responses to isoprenaline. There was an associated increase in EC50 values. 3. Decreasing the external calcium concentration from 2.2 to 1.1 mM also increased the maximal inotropic responses to tolbutamide. These responses were 23- and 44-fold less than those to isoprenaline at equivalent calcium concentrations. 4. Preparations maintained in 1.1 mM calcium were used to compare inotropic responses to isoprenaline and tolbutamide at different frequencies of stimulation. 5. Decreasing the frequency of stimulation from 4 to 2 or 1 Hz decreased the resting force of contraction and increased the maximal inotropic responses to isoprenaline. There was an associated increase in EC50 values. 6. No significant inotropic responses to tolbutamide were observed at 4 Hz. Positive inotropic responses of similar magnitude occurred at 2 and 1 Hz. The maximal inotropic responses at these frequencies were 43- and 127-fold less than those to isoprenaline. 7. It is concluded that tolbutamide is a very weak inotropic agent.

Animals↗

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Effect of indomethacin on responses of sheep isolated coronary artery to arachidonic acid.

Indomethacin (2.8 mumol/l) did not consistently affect basal tone of sheep coronary artery strips, while a ten-fold higher concentration increased tension in 50% of the preparations tested. When acetylcholine was used as a spasmogen, oscillations in induced tone and relaxations produced by arachidonic acid (6.6 mumol/l) were abolished by indomethacin, 2.8 mumol/l and 7 mumol/l, respectively. Prostacyclin (PGI2) and prostaglandin E1 decreased and PGE2 increased arterial tension while PGF2 alpha was inactive. Responses to PGI2 were reduced by indomethacin (28 mumol/l) but not by indomethacin (2.8 mumol/l). It is suggested that sheep isolated coronary arteries synthesize and release prostacyclin in the presence of acetylcholine and arachidonic acid and that such synthesis can be inhibited by indomethacin.

Acetylcholine↗

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Interaction of heat with X-rays and cis-platinum; cell lethality and oncogenic transformation.

There is increasing concern for the oncogenic potential of agents used to treat cancer. Hyperthermia is one of the few modalities that does not, of itself, produce transformed foci in vitro. The adjuvant use of heat with X-rays or chemotherapy agents is an interesting approach to increasing the cell-killing potential while decreasing the oncogenicity of combined-modality therapy. Following a priming heat dose in C3H 10T1/2 cells, resistance to cell killing by a second heat dose develops and is maximal by 10 h. This is known as thermotolerance, and can be monitored by the appearance of proteins of specific molecular weight known as heat-shock proteins. By contrast, a priming heat dose does not confer resistance to killing by cis-platinum (cis-DDP). Indeed, heat potentiates the cytotoxicity due to cis-DDP. The interaction is greatest if heat and drug are applied simultaneously, but is still substantial if the drug is applied many hours after heating. The loss of interaction between heat and cis-DDP occurs slowly, but by 48 h, heat and drug act independently. Thermotolerant cells are less sensitive to the induction of transformation by X-rays than previously unheated cells. On the other hand, 48 h after a heat exposure, when cells have regained their normal sensitivity to killing by cis-DDP, their sensitivity to the induction of transformation by cis-DDP has also returned to normal.

Animals↗

PubMedDate not supplied

Interaction of hyperthermia and chemotherapy agents; cell lethality and oncogenic potential.

Hyperthermia was combined with bleomycin, melphalan and cis-platinum in order to examine cell lethality and oncogenic transformation in C3H10T1/2 cells from the adjuvant use of heat with chemotherapy agents. When cells were exposed concurrently to 42.5 degrees C and each of the three chemotherapy agents, heat enhanced both the cytotoxic and oncogenic potential of the drugs. Hyperthermia-enhanced ratios were largest for bleomycin-treated cells. Examination of transformation incidences expressed as a function of surviving fraction, i.e. the cytotoxicity of treatment and therefore drug-heat efficacy, showed that for a given level of cell killing the combination of heat and cis-platinum resulted in fewer transformants per surviving cell than for cis-platinum alone. Hyperthermia appears to reduce the oncogenic potential of low concentrations of melphalan but has no effect on bleomycin-induced oncogenic transformation.

Animals↗