4 resultados para low drug dose

em Brock University, Canada


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Low levels of ionizing radiation induce two translocation responses in soybean: a reduction in photoassimilate export from leaves and a change in the distribution pattern of exported photoassimilate within the plant. In this investigation these responses have been further studied specifically to ascertain the site of radiation damage and to better understand the physiological responses observed. Experimentally the primary data was obtained from studies in which a mature trifoliate leaf of a young soybean plant (Glycine ~ L. cultivar Harosoy '63) is isolated in a closed transparent chamber and allowed to photoassimilate 14C02 for 15 minutes. This is followed by an additional 45 ~_il'1;ute period before the plant is sectl.o ne d an d 14 C-ra dl' oactl.v.l ty d eterml. ne d'l n a 11 parts. Such 14c data provides one with the magnitude and distribution pattern of translocation. Further analyses were conducted to determine the relative levels of the major photosynthetic products using the techniques of paper chromatography and autoradiography. Since differences between control and irradiated P 1 ants were not 0 b serve d l' n t h e par tl't"lo nlng 0 f 14 C between the 80% ethanol-soluble and -insoluble fractions 14 or in the relative amounts of C-products of photosynthesis, the reduction in export in irradiated plants is not likely due to reduced availability of translocatable materials. Data presented in this thesis shows that photoassimilate export was not affected by gamma radiation until a threshold dose between 2.0 and 3.0 krads was reached. It was also observed that radiation-induced damage to the export process was capable of recovery in a period of 1 to 2 hours provided high light intensity was supplied. In contrast, the distribution pattern was shown to be extremely radiosensitive with a low threshold dose between .25 and .49 krads. Although this process was also capable of recovery,lt" occurred much earlier and was followed by a secondary effect which lasted at least for the duration of the experiments. The data presented in this thesis is interpreted to suggest that the sites of radiation action for the two translocation responses are different. In regards to photoassimilate export, the site of action of ionizing radiation is the leaf, quite possibly the process of photophosphorylation which may provide energy directly for phloem loading and for membrane integrity of the phloem tissue* In regards to the pattern of distribution of exported photoassimilate, the site is likely the apical sink, possibly the result of changes of levels of endogenous hormones. By the selection of radiation exposure dose and time post-irradiation, it is possible to affect independently these two processes suggesting that each may be regulated independent of the other and involves a distinct site.

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The influence of peak-dose drug-induced dyskinesia (DID) on manual tracking (MT) was examined in 10 dyskinetic patients (OPO), and compared to 10 age/gendermatched non-dyskinetic patients (NDPD) and 10 healthy controls. Whole body movement (WBM) and MT were recorded with a 6-degrees of freedom magnetic motion tracker and forearm rotation sensors, respectively. Subjects were asked to match the length of a computer-generated line with a line controlled via wrist rotation. Results show that OPO patients had greater WBM displacement and velocity than other groups. All groups displayed increased WBM from rest to MT, but only DPD and NDPO patients demonstrated a significant increase in WBM displacement and velocity. In addition, OPO patients exhibited excessive increase in WBM suggesting overflow DID. When two distinct target pace segments were examined (FAST/SLOW), all groups had slight increases in WBM displacement and velocity from SLOW to FAST, but only OPO patients showed significantly increased WBM displacement and velocity from SLOW to FAST. Therefore, it can be suggested that overflow DID was further increased with increased task speed. OPO patients also showed significantly greater ERROR matching target velocity, but no significant difference in ERROR in displacement, indicating that significantly greater WBM displacement in the OPO group did not have a direct influence on tracking performance. Individual target and performance traces demonstrated this relatively good tracking performance with the exception of distinct deviations from the target trace that occurred suddenly, followed by quick returns to the target coherent in time with increased performance velocity. In addition, performance hand velocity was not correlated with WBM velocity in DPO patients, suggesting that increased ERROR in velocity was not a direct result of WBM velocity. In conclusion, we propose that over-excitation of motor cortical areas, reported to be present in DPO patients, resulted in overflow DID during voluntary movement. Furthermore, we propose that the increased ERROR in velocity was the result of hypermetric voluntary movements also originating from the over-excitation of motor cortical areas.

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Rats emit two distinct types of ultrasonic vocalizations in adulthood: 22 kHz (aversive situation), and 50 kHz calls (appetitive situation). The present project is focussed on pharmacological studies of 50 kHz vocalizations. The 50 kHz calls are elicited from dopaminergic activation in the meso limbic pathway and are emitted in such appetitive situations as social contact(s), sexual encounters, food reward, etc. Eighty-five male rats were stereotaxically implanted with bilateral guide cannulae in the nucleus accumbens shell (A= 9.7, L= 1.2, V= 6.7). Quinpirole, a D2/D3 dopaminergic agonist, was injected in low doses to the nucleus accumbens shell in an attempt to elicit 50 kHz vocalizations. A dose response was obtained for the low dose range of quinpirole for six doses: 0.025 Jlg, 0.06 Jlg, 0.12 Jlg, 0.25 Jlg, 0.5 Jlg, and 1.0 Jlg. It was found that only application of the 0.25 Jlg dose of quinpirole and the 7 Jlg dose of amphetamine (positive control) significantly increased the total number of 50 kHz calls (p < 0.006 and p < 0.004 respectively); and particularly significantly increased the frequency modulated type of these calls (p < 0.01, and p < 0.006 respectively). In a double injection procedure, the dose of 0.25 Jlg quinpirole was antagonized with raclopride (D2 antagonist) or U99194A maleate (D3 antagonist) in an attempt to antagonize the response. The 0.25 Jlg dose of quinpirole was successfully antagonized by pre-treatment with an equimolar dose of U99194A maleate (p < 0.008) but not with raclopride. The 7Jlg amphetamine response was also antagonized with an equimolar dose of raclopride. Based on these results, it seems that low doses of quinpirole, particularly the 0.25 Jlg dose, are capable of increasing 50 kHz vocalizations in rats and do so by activation of the D3 dopamine receptor. This is not a biphasic response as seen with locomotor studies. Also noteworthy is the increase in frequency modulated 50 kHz calls elicited by the 0.25 Jlg dose of quinpirole indicating a possible increase in positive affect.

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The Madagascar periwinkle (Catharanthus roseus) is the sole source of the anticancer drug vinblastine, which is formed via the coupling of monoterpenoid indole alkaloids (MIAs) catharanthine and vindoline. A mutant line of C. roseus (M2-1865) with an altered MIA profile was identified in a screen of 4000 M2 lines generated by ethylmethanesulfonate (EMS) chemical mutagenesis. While this line did not accumulate vinblastine due to reduced levels of vindoline within the leaves, significant levels of 2,3-epoxide derivatives of tabersonine accumulated on the leaf surface. Detailed nucleotide, amino acid, and enzyme activity analyses of tabersonine 3-reductase in the M2-1865 line showed that a single amino acid substitution (H189Y) diminished the biochemical activity of T3R by 95%. Genetic crosses showed the phenotype to be recessive, exhibiting standard Mendelian single-gene inheritance. The usefulness of EMS mutagenesis in elucidating MIA biosynthesis is highlighted by the results of this study.