Biological response assays

It is important to note that both the quality and quantity of biological response obtained with a given drug depends very much on the assay system used to make the measurement. If the assay does not have the means to detect a given efficacy, then none will be observed this should not be taken to mean that the drug does not have that particular efficacy. A common case in point... 

A biomarker is here defined as a biological response to an environmental chemical at the individual level or below, which demonstrates a departure from normality. Responses at higher levels of biological organization are not, according to this definition, termed biomarkers. Where such biological responses can be readily measnred, they may provide the basis for biomarker assays, which can be nsed to stndy the effects of chemicals in the laboratory or, most importantly, in the field. There is also interest in their employment as tools for the environmental risk assessment of chemicals. 

The LDH+ALT reactor provided a linear response from 0.1 to 50 pmol/L lactate, thereby increasing lactate conversion by 117-183% relative to LDH alone. The intra- and inter-assay CV were both less than 5%, and recoveries ranged from 93 to 106%. Even though roughly 100% of the LDH and ALT added bound to the support under the immobilization conditions used, the activities of the immobilized enzymes were ca. 3% of those of the free enzymes, which is consistent with previous results obtained by the same [67] and other authors [69,70]. Jointly immobilized LDH and ALT preserved ca. 50% of their original activity after 60-90 days of intermittent use. On the other hand, immobilized luciferase was less markedly inhibited than that in the free solution by substances present in the biological samples assayed [71]. 

Interestingly, the conformational changes observed in these biophysical assays were correlated with biological responses in functional assays. Dopamine, which induces only a rapid conformational change, is efficient at activating Gs but not receptor internalization. In contrast, norepinephrine... 

Assay A technique that measures a specific biological response. 

Bucher and Portier have suggested that it is important for toxicologists to reevaluate our collective understanding of adverse biological responses in short-term in vivo and in vitro assays. That in spite of the recognized limitations, our understanding of carcinogenicity has advanced to the point that data from these assays could support decisions that are as protective of the public... 

Some of the examples and discussion in this chapter draw on the two-class classification problem, which here is hit versus inactive . The word active refers to a validated hit, that is, a molecule that truly does exhibit some level of the desired biological response. A key point is that an assay is itself an estimator. With this in mind, definitions and a discussion of error rates are given in the context of predictive models. Borrowing from the terminology of signal detection, the sensitivity of a model refers to the fraction of observed hits that are classified as (or predicted to be) hits by the model, and specificity refers to the fraction of observed inactives classified as inactives by the model. An observed hit is not necessarily an active molecule, but simply a molecule for which the primary screening result exceeded a decision threshold. Whether such a molecule turns out to be an active is a problem that involves the sensitivity of the assay, but the task at hand is for... 

Biological data should pertain to an aspect of biological/biochemical function that can be measured. The events could be occurring in enzymes, isolated or bound receptors, in cellular systems, or whole animals. Because there is considerable variation in biological responses, test samples should be run in duplicate or preferably triplicate, except in whole animal studies where assay conditions (e.g., plasma concentrations of a drug) preclude such measurements. 

Some species of lichens are very sensitive to air pollutants. Consequently, urban environments are often highly impoverished in lichen species. Some ecologists have developed schemes by which the intensity of air pollution can be reliably assayed or monitored using the biological responses of lichens in their communities. Monitoring of air quality using lichens can be based on the health and productivity of these organisms in places variously stressed by toxic pollution. Alternatively, the chemical composition of lichens may be assayed, because their tissues can effectively take up and retain sulfur and metals from the atmosphere. 

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