In vivo physiology

We used outdated human CPD (citrate-phosphate-dextrose) blood from the Dayton Community Blood Center. At 21 days, CPD blood still retains 78% survival of the red blood cells and would fairly well simulate in vivo physiological conditions. During these tests, many enzymes and proteins may denature and/or precipitate. Even after suffering that trauma, the resulting fluid is more suitable for material testing than other pseudo-physiological fluids, since it still contains most of the salts, lipids, hormones, oligomers, nucleotides, saccharides, etc., found in whole blood in vivo. 

PET and SPECT are both functional imaging methods that use externally administered radionuclide-labeled substances to image in vivo physiological processes in 3-D space 944... 

V3. Van Petten, G. R., Feng, H., Withey, R. J., and Lettan, H. F., The physiological availability of solid dosage forms of phenylbutazone. Part I. In vivo physiologic... 

Only a few of the Oatps/OATPs identified so far have been characterized in detail on the functional, structural, and genomic levels. Despite the fact that a larger number of endogenous compounds are known to be transported by the Oatps/ OATPs, little is known about the in vivo physiological importance of these transporters. The exact transport mechanism(s) of the OATPs has not yet been worked out. However, studies with rat Oatps suggest that they act as organic anion exchangers [1]. 

Marcus CS. 1972. Use of 87mSr and semiconductor radiation detectors for in vivo physiological studies. 

In contrast to the CLB assay format, cell-based bioassays are more complex, time, consuming, costly, and often are less sensitive. However, it is important to note that this methodology is a functional assay and, thus, demonstrates neutralization of a biological response. It is argued by some that a functional end point more closely mimics in vivo physiological responses [15]. 

The data coming from in vitro incubation studies must be interpreted with caution before being extrapolated to in vivo physiological mechanisms, as they involve a closed system, with limited enzymatic activities, with the absence of turnover - in the presence of a limited size of distribution volume for the tracer. 

Also, when working with flavonoids, dose is always a concern. Ideally, doses should reflect in vivo physiologic situations, but most of the times, the detection and quantification tools available are not sensible enough for these doses. This leads to the use of higher doses which could compel a particular effect that would not happen or could be less pronounced if lower doses were used. Furthermore, in vitro studies often use the aglycones or native glycosides that, as discussed before, could be biologically irrelevant to the tissue or cell line used in the study subsequently, the relevance of the conclusions as to their nutritive effects remains speculative. 

There are many variables that pertain to the usefulness of any particular test system for retinoids. These include its sensitivity, specificity, precision, ease of performance and expense, accuracy (false positives or false negatives), relevance to the in vivo physiology of retinoids, and relevance to therapeutic purposes. Each of these considerations is discussed briefly with respect to the test systems that have been reviewed above. 

---