Further studies have been initiated in order to obtain a wider distribution of peak levels which will enable the establishment of dose-response relationships.
Establishment of dose-response relationships was not considered relevant due to the small number of areas studied and the similarity in exposure levels (around 85 dB(A) FAST expressed as peak levels).
Therefore, the goal of this mini-review is to discuss how quantitative morphometric analyses and the establishment of dose-dependent relationships helped distinguish primary, mechanistically relevant toxicant effects from non-specific consequences.
Following the establishment of dose-response curves (Fig. 2A and B) and based on others' and our previous studies [25], [39] [42], we chose to use DP at a concentration of 100 µM and IBMX at a concentration of 300 µM in all further assays.
Each drug was tested over a 1000-fold concentrangen rallowinglowing the establishment of dose-response curves and the identification of half-maximal effective concentration responses.
After the establishment of MTD, dose expansion was undertaken to better estimate the tolerability of this dose and provide a preliminary assessment of efficacy.
After establishment of the dose range and optimal (IC50) sorafenib concentration (4 μM, 48 h of treatment), cells were plated in 6 well dishes at the appropriated cell density for proliferation (BrdU), apoptosis (TUNEL) and protein (Western blot) analysis.
Testing this hypothesis, however, requires first, establishment of the dose of hookworm required to generate the necessary intensity of infection; and second, confirmation that infection is sufficiently safe and well tolerated to make clinical trials feasible.
Often, the establishment of "safe" doses is approached rather pragmatically with dose-response experiments in laboratory animals or even humans.
