Sequential effects

Sequential effects arise when one chemical is absorbed first and the second chemical is absorbed at a finite, but important, time thereafter, 

The administering of ethanol or acetone prior to administering acetaminophen results in a marked increase in the hepatotoxicity of acetaminophen (because of enzyme induction by ethanol). 14  

Pretreatment with diethyl maleate increases toxicity of bromoben-zene (because of depletion of glutathione by diethyl maleate). 15  

Individuals with hepatic injury, such as alcohol-induced cirrhosis, experience greater hepatotoxic effects than those not so previously injured. 16  

The toxic mixture examples just presented are only a small fraction of those that are fully discussed and referenced in Parts 3 and 4 of this book. 

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Aureolic acid group of antibiotics We have given below an extended summary of the work done with this group of antibiotics, because we have been actively involved in understanding the mode of action of these DNA-binding antibiotics. The summary also illustrates the model example of how different biophysical and biochemical approaches were undertaken to characterize the association of these drugs with chromosomal DNA and the sequential effect of this binding upon the chromatin structure. 

As with SSRIs, TDM is not a standard of care issue with this agent. A recent study demonstrated that the sequential effects of venlafaxine on serotonin and then NE uptake pumps is dose and hence concentration dependent (137). Thus, TDM can be used with venlafaxine in the same manner as with the SSRIs. 

Sams M, Alho K, Naatanen R. 1983. Sequential effects on the ERP in discriminating two stimuli. Biol Psychol 17 41-58. 

Figure 5 The nitrogen cascade illustrates the sequential effects a single atom of N can have in various reservoirs after it has been converted from a nonreactive to a reactive form (source Galloway et al, 2003b).

Traditionally, toxicologists have addressed the effects of chemical mixtures as being additive, antagonistic, potentiated, or synergistic.M To these, sequential effects are added here. 

A comparison has been made between the reorientational behavior of a series of copolymers of DR with MMA (13, Figure 4) and that of series of blends of a DR homopolymer (12) with PMMA to elucidate the sequential effect of the DR monomer units on the orientability caused by intramolecular interactions between dye chromophore groups in polymer solids.79 The maximum birefringence induced by linearly polarized light for the blends80 increased linearly with an increase in the DR fraction. In contrast, the copolymers showed a nonlinear... 

Two groups have studied the incorporation of labeled arachidonic acid into membrane phospholipids, a reaction that depends on the sequential effects of FACE and ACLAT. Excess amounts of LyPL substrate are available in schizophrenic platelets, but in spite of that, the rate of incorporation of AA into phospholipids is impaired (Yao, 1999 Demisch, Heinz, Gerbaldo, Kirsten, 1992). 

Timing The time point(s) selected may not be optimal Sequential effects on different subsets after exposure to cyclosporine Huby et al. (1995)... 

Two possible mechanisms for acquisition of new folds have been described (1) structural drift and (2) passage from an ancestral fold to a new fold through a structurally ambiguous intermediate that can adopt both folds. Structural drift results from the sequential effects of insertions and deletions (indels). A hypothetical pathway for transformation of an all-beta protein to an all-alpha protein as a result of sequential indels is shown in Figure Each structure in the figure corresponds to an actual protein. Some of the proteins are evolutio-narily related (based upon significant pairwise sequence identity) and others are not, but simply serve as models... 

In this study, we demonstrated that the calcium mobilization induced by flubendiamide caused sequential effects on the Ca pump. The pronoimced stimulation of the Ca pump by flubendiamide was closely correlated to insecticidal activity. Further investigation suggested that luminal Ca was an important mediator for the functional co-ordination of RyR and the Ca pump. It is also suggested that this compoimd should provide a promising probe for imderstanding the functional regulations of the insect RyR. 

Rabie, A., Favre, C., Clavel, M.C., and Legrand, J., 1979a, Sequential effects of thyroxine on the developing cerebellum of rats made hypothyroid by propylthiouracil, Brain Res.. 161 469. 

Sequential effects on cleavage rate are correlated with sequential Eu " binding. Cleavage rate at the major cleavage site increases and plateaus as the major Eu " " binding site becomes occupied see Table 16a, No. 17, Fig. 4. 

Sequential effects arise when one chanical is absorbed first and the second one is absorbed at a finite, but important time, thereafter resulting in an effect not obsaved from exposure to either one of the single chanicals. Examples that d onstrate this effect are ... 

HNJ Schifferstein, JER Frijters. Contextual and sequential effects on judgments of sweetness intensity. Percept Psychophys 52 243-255, 1992. 

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