Isolated tissues

Investigations are carried out using a variety of biological systems, including observations on exposed whole animals in vivo studies) or on appropriately treated isolated tissues and cells, homogenates of tissues, or cultured lower organisms in vitro studies). 

It is also clear that it is difficult to relate cause and effect to any specific chemical since, with the exception of point source effluents, many waterways contain a multitude of chemicals, of which the active endocrine disruptor may not be that which has been measured in the water or tissue. For such reasons, many studies have used in vitro experiments in which isolated tissue, either from a control animal or one captured in a polluted water system, is exposed to a single pollutant in the laboratory. Such experiments have shown significant disruption to testicular activity by a wide range of xenobiotics, including cadmium, lindane, DDT, cythion, hexadrin and PCBs. ... 

Previously, pharmacologists were constrained to the prewired sensitivity of isolated tissues for agonist study. As discussed in Chapter 2, different tissues possess different densities of receptor, different receptor co-proteins in the membranes, and different efficiencies of stimulus-response mechanisms. Judicious choice of tissue type could yield uniquely useful pharmacologic systems (i.e., sensitive screening tissues). However, before the availability of recombinant systems these choices were limited. With the ability to express different densities of human target proteins such as receptors has come a transformation in drug discovery. Recombinant cellular systems can now... 

Figure 6.10b shows a pattern of antagonism often observed in isolated tissue studies but not so often in cell-based assays. Saturation of uptake systems for the agonist or saturation of an adsorption site for the agonist can account for this effect. The linear portion of the regression can be used to estimate the pKB or the pA2. If there is a loss of concentration dependence of antagonism, as seen in... 

Functional assays (continued) dissimulation, 87-88 group I, 81-82 group II, 81, 83 group III, 83-84 group IV, 84 isolated tissues for, 81 membrane, 81 output from, 79... 

Level 2 Computer Simulation of Isolated Tissues and Organs... 

LEVEL 2 COMPUTER SIMULATION OF ISOLATED TISSUES AND ORGANS 519... 

These approaches to receptor identification and classification were, of course, pioneered by studies with peripheral systems and isolated tissues. They are more difficult to apply to the CNS, especially in in vivo experiments, where responses depend on a complex set of interacting systems and the actual drug concentration at the receptors of interest is rarely known. However, the development of in vitro preparations (acute brain slices, organotypic brain slice cultures, tissue-cultured neurons and acutely dissociated neuronal and glial cell preparations) has allowed more quantitative pharmacological techniques to be applied to the action of drugs at neurotransmitter receptors while the development of new recording methods such as patch-clamp... 

Pertwee RG, Fernardo SR, Griffin G, Abadji Y, Makriyannis A. Effect of phenylmethylsulphonyl fluoride on the potency of anandamide as an inhibitor of electrically evoked contractions in two isolated tissue preparations. Eur J Pharmacol 1995b 272 73-78. 

The glycocalyx and the mucus layer make up the structure of the unstirred water layer (UWL) [73]. The thickness of the UWL is estimated to be 30-100 pm in vivo, consistent with very efficient stirring effects [74]. In isolated tissue (in the absence of stirring), the mucus layer is 300-700 pm thick [73]. The pH in the unstirred water layer is 5.2-6.2, and might be regulated independently of the luminal pH (Section 2.3). The mucus layer may play a role in regulating the epithelial cell surface pH [73]. 

Also, were the underlying assumptions to be correct, the value of the intercept of the line on the abscissa (i.e., when the response is half maximal) would give an estimate of KA. A. J. Clark was the first to test this using the responses of isolated tissues, and Figure 1.2 illustrates some of his results. Figure 1.2A shows that Eq. (1.4) provides a reasonably good fit to the experimental values. 

While in vivo studies assess absorption rates as process-lumped time constants from blood level versus time data, these rate parameters encompass the kinetics of dosage-form release, GI transit, metabolism, and membrane permeation. The use of isolated tissue and cellular preparations to screen for drug absorption potential and to evaluate absorption rate limits at the tissue and cellular levels has been expanded by the pharmaceutical industry over the past several years. For more detail in this regard, the reader is referred to an article by Stewart et al. [68] for references on these preparations and for additional details on the various experimental techniques outlined below. 

The effects of D-glucose observed in vivo are not well reproduced in vitro. Madara [203] reported that cytoskeletal contraction and enhanced paracellular permeability were observed only in an in situ perfusion preparation and not in an isolated tissue preparation. Although its in vivo effect was not tested, 25 mM D-glucose, an effective concentration in the jejunum [47], failed to enhance the in vitro transport of sotalol (log PC = -0.62), atenolol (log PC = 0.16), or nadolol (log PC = 0.93) across the isolated conjunctiva [213], For a similar reason and possibly due to the absence of a Na+-glucose cotransporter in the cornea, 25 mM D-glucose was ineffective in increasing the corneal transport of these three drugs. 

The site of pheromone production is varied amongst the insects just as there are variable structures in the different orders. Several reviews are available detailing the ultrastructure of these glands [9-11]. Evidence that pheromone biosynthesis occurs in these cells and tissues requires that the isolated tissue be shown to incorporate labeled precursors into pheromone components. In the more studied model insects this criteria has been met. 

Massi M., loan P., Budriesi R., Chiarini A., Vitali B., Lammers K.M., Gionchetti P., Campieri M., Lembo A. and Brigidi P. (2006). Effects of probiotic bacteria on gastrointestinal motility in guinea-pig isolated tissue . World J Gastroenterol, 7,12(37),... 

The term cell culture refers to the growth of isolated cells in vitro, whereas tissue culture is a term used to describe the growth of not only isolated cells, but also isolated tissues or organs. Both these terms are often used to describe the growth of animal and human cells in culture. Advances in medical research have largely driven animal cell culture development. 

A survey of the ability of various marine invertebrates and their isolated tissues to accumulate prostaglandins from surrounding fluids has led to the speculation that some marine invertebrates may rely on this mechanism to obtain their physiological requirement of prostaglandins [107], It is further speculated that P. homomalla, with its wealth of prostaglandins, may be the ultimate provider of these substances in the Caribbean through release and subsequent uptake by dependent species. 

Cytokine profiling has also been measured as a function of changes in cytokine mRNA expression using either reverse transcription polymerase chain reaction (RT-PCR) [87, 91-93] or ribonuclease protection assay (RPA) [94-97], Measurement of cytokine transcripts by RT-PCR revealed that prolonged exposure to TMA induced increased levels of IL-4 mRNA expression compared with treatment with DNCB [87,92-93]. However, expression of the type 1 cytokine IFN-y by DNCB-activated LNC was variable and failed to discriminate between contact and respiratory allergens [87,91,93). A similar profile was observed for freshly isolated tissue analyzed by RPA. This somewhat less... 

McHale Isn t it true, nonetheless, that redundancy is what physiology is all about For example, we have found that using two different species of animal (cattle and sheep) the same end result can be achieved with two completely different neurotransmission systems. It is also helpful to work on isolated tissues and on isolated cells, because of the much greater control afforded by reductionist techniques. 

Isolated organisms Intact yet isolated tissue and vascular system Controlled environment and exposure conditions Donor organism still required Time-consuming and expensive No intact organismic responses Limited duration of viability... 

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