Biological response, influencing

Altered enzyme levels and activities may thus render some individuals more susceptible to exposure to chemicals than the general population. It could therefore be hypothesized that even a very low exposure to a chemical may be associated with various biological responses in such susceptible individuals as altered enzyme levels and activities may influence the individual s ability to detoxify a chemical or increase the conversion of a chemical to a toxic metabolite. Whether and to what extent an altered enzyme level or activity will increase an individual s risk of experience adverse effects from exposure to chemicals is generally not known. 

Thiazolidinediones are the newer agents that favourably influence insulin sensitivity and possibly also pancreatic fS-cell function. The biological response of thiazolidinediones is mediated by binding to the nuclear peroxisome proliferator-activated receptor-y (PPAR)... 

Throughout the text we will relate polymer structure to the properties of the polymer. Polymer properties are related not only to the chemical nature of the polymer, but also to such factors as extent and distribution of crystallinity, distribution of polymer chain lengths, and nature and amount of additives, such as fillers, reinforcing agents, and plasticizers, to mention a few. These factors influence essentially all the polymeric properties to some extent including hardness, flammability, weatherability, chemical stability, biological response, comfort, flex life, moisture retention, appearance, dyeability, softening point, and electrical properties. 

H)2D3 exerts its influence within target tissues through high-affinity sterol-specific intracellular receptor proteins. The D3 receptor, similar to steroid receptor systems, translocates the hormone from the cell cytoplasm to the nucleus, where biological response is initiated via transcription and translation (Fig. 66.3). 

Most of the proteins that are used clinically provide pharmaceutical properties that lead to safe and effective therapy for approved therapeutic indications. Some proteins, however, may influence multiple pharmacologic pathways and elicit unwanted effects. An understanding of the specific domains that mediate biologic response permits the engineering of macromolecules that are more specific and less likely to interact with receptors other than the target (see Boxes 4.4 and 4.5). 

However, it was immediately recognized by peptide chemists that, even in the cases where a direct (backbone)peptide -protein(backbone) interaction is not operative, the backbone conformation may dramatically influence the biological response. It is evident that the introduction of new, promising peptidomimetics is based primarily on the combined knowledge of the complementary conformational, topochemical, and electronic properties of the native peptide and of its address (in other words, of the receptor or the active site of the enzyme with which it interacts). Then, the design of peptidomimetics as potential bioactive compounds must take into particular account two structural factors (i) a favorable fit (tertiary structure) with respect to the corresponding complementary spatial situation at the active site (ii) the placement of structural elements (e.g., functional groups, polar and... 

It was with the action of phenothiazine that the importance of particle size was first recognised, in 1939, in relation to its toxicity to codling moth larvae, and in 1940 in relation to its anthelmintic effect, in both of which it was shown that reduction in particle size increased activity. The improvement in biological response to griseofulvin on microni-sation is well known similar blood levels of the dmg were obtained with half the dose of micronised dmg compared to those of non-micronised griseofulvin. The influence of... 

Table 2-8 illustrates several items that must be kept in mind when selecting. substituents to be evaluated in terms nf the type of factors that influence a biological response. Fur electronic parameters such as aromatic ring is important because of resonance versus inductive effects. Notice the twofold differences seen between and fur the three aliphatic substituents and iodo. and scvcralfold difference for methuxy, amino. Huoru, and phenolic hydroxyl. 

Reliability. This can be considered under two headings (1) environmental influences that modulate the organism s response to a chemical, and (2) inherent variation in the biological response to a given exposure. It is important to know the extent of all variations in order to have a reliable biomarker. 

With regard to estrogen-associated toxicity, the primary mechanism appears to be via association with the estrogen receptor and subsequent alteration in the signal transduction pathway. Many studies of toxicokinetics suggest the difficulty in extrapolating structure-activity relationships of particular compounds with their influence on biological responses (e.g., reproduction, neuroendocrine behavior). 

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