LCM produced a significant and profound dose-dependent inhibition of many electrophysiological and behavioural measures of nociception after spinal or systemic administration in MIA animals.
If mass effect is profound, doses as high as 20 mg every 4 hours may be considered [ 45].
In acetic acid induced abdominal writhing test the test groups treated with 100, 200 and 300 mg/kg of AETS exhibited profound and dose dependent inhibition of the abdominal writhes.
This could in part be explained by the profound differences in dose rate; dose rate effects on the transcriptional response have previously been described in vivo following radionuclide administration [22, 25, 29].
Small cell lung cancer xenografts treated continuously with 5 IU ADI-PEG20 study demonstrated a sustained response to ADI-PEG20 for the 90-day period of the study, suggesting that at least at this dose, profound resistance to the anti-proliferative effect of ADI-PEG20 had not been induced.
Consistent with cisplatin treatment, ATM-depleted A549 cells manifested profound sensitivity to low dose of doxorubicin and etoposide while being resistant to high doses of the drugs, suggesting that, apart from apoptotic functions at high dose of genotoxic stress, ATM might have a significant role in chemoresistance at low dose of the stress.
While shielding was observed to have the most profound impact on surface dose, the radiotherapy technique proved to be most important in determining internal dose.
The mean drop in serum calcium concentration for the Zn-dosed lactating cows was more profound after the first ZnO dose than after the following doses, and the time required to reach the pre-dosing serum calcium level was longer following the first dose than following the succeeding ones (Figs. 1 and 2).
The effects were less profound when a lower dose was examined (30 mg/kg/day), although significant neuroprotection still occurred.
However, at 8 and 12 hours, this dose demonstrated profound inhibition of phosphorylation of all PI3K downstream substrates, including Akt, S6RP, 4EBP1 and eIF4E,.
The approach taken when extrapolating dose response relationships to low doses has profound impact on risk-management decision making.
