Ex vivo systems

Epidemiological studies and intervention trials with food and beverages rich in flavonoids are not conclusive although flavonoids were recognized to display numerous antioxidant, anti-inflammatory, anti-tumoral, and anti-microbial activities. The antioxidant capacity of flavonoids has been largely reported in numerous in vitro and ex vivo systems. Numerous reviews "" have been published on the antioxidant properties of flavonoids. Degenerative diseases are largely associated with oxidative mechanisms that may be counteracted by flavonoids. 

Ex vivo systems derived from animals and from human organs can be used to investigate the in vitro metabolism of xenobiotics. Cell lines, which are transfected to express species-specific metabolic enzymes, can also be used to identify the enzymes involved in the metabolism of a specific substance. Blocking the metabolism by an enzyme specific substrate or by antibodies is also helpful for the identification of the enzymes involved in the metabolism of a substance. 

Nasal tissue from animals can be mounted in Ussing chambers, permitting experiments similar to those performed in cell cultures to be performed in intact tissues. The nasal tissues of rabbits, dog, sheep, and cattle have been used and such experiments provide the reassurance that the ex vivo system is representative of the nasal mucosa in vivo. The limitations of this technique are the requirement for the use of fresh tissue, the limited duration of tissue viability, and interspecies variation in tissue permeability and metabolic capacity. 

The Canine Model. While ex vivo models often are considered to be an improvement over in vitro biocompatibility test systems, the problem of describing extremely complex blood—polymer interactions still remains. In this study, we used radioisotope-labeled proteins and platelets and scanning electron microscopy. In other studies, we applied immunolabeling techniques and transmission electron microscopy. The application of these tools to an in vivo or ex vivo system provides more pertinent data than that often obtained in an in vitro system. Through this approach we hope to gain some insights into the complicated interactions of blood with biomaterials. 

The oxygen-binding reaction of the liposome-embedded heme was examined by using poly-lipid liposome/lipid-heme in a pseudo vivo and ex vivo system. 

Anandamide (AEA) is the most studied member of a new class of lipid mediators, collectively called endocannabinoids. The biological activity of AEA at cannabinoid and noncannabinoid receptors depends on its Hfe span in the extracellular space, which is regulated by a rapid cellular uptake, followed by intracellular degradation by the enzyme AEA hydrolase (fatty acid amide hydrolase). Here, we present the methodological details of the procedures that we have developed to assay fatty acid amide hydrolase activity and to characterize AEA transport through cell membranes in a new ideal ex vivo system like brain synaptosomes. 

To obtain an increased intrinsic capacity to transgress biological membranes, a number of different modifications have been introduced to PNA. These modifications include conjugation of PNA to Hpophilic moieties [51, 97, 98], conjugation of PNA to certain so-caUed ceU-penetrating peptides [49, 55, 56, 66, 99-102] and conjugation to different moieties, which are supposed to be internahzed by specific cellular receptors [48, 103-105]. The work on cellular dehvery of PNA is, like the related work on ex vivo and in vivo effects of PNA, very difficult to summarize conclusively. First of all, the pronounced diversity of the reporter systems employed makes it impossible to directly compare the studies. Secondly, the widespread use of fluorescence studies in spite of the many inherent pitfalls of this technique makes it sometimes difficult to judge even qualitatively whether a presented result actually indicates cellular uptake. We have recently published a comprehensive review on cellular dehvery of PNA [82], with a more detailed assessment of the PNA dehvery hterature. 

Three different types of white wines and four red wines were compared after PCL testing in an ex vivo model system of the influence of oxidation resistance on LDL. 

In biological systems, therefore, the behavior of Li+ is predicted to be similar to that of Na+ and K+ in some cases, and to that of Mg2+ and Ca2+ in others [12]. Indeed, research has demonstrated numerous systems in which one or more of these cations is normally intrinsically involved, including ion transport pathways and enzyme activities, in which Li+ has mimicked the actions of these cations, sometimes producing inhibitory or stimulatory effects. For example, Li+ can replace Na+ in the ATP-dependent system which controls the transport of Na+ through the endoplasmic reticulum Li+ inhibits the activity of some Mg2+-dependent enzymes in vitro, such as pyruvate kinase and inositol monophosphate phosphatase Li+ affects the activity of some Ca2+-dependent enzymes— it increases the levels of activated Ca2+-ATPase in human erythrocyte membranes ex vivo and inhibits tryptophan hydroxylase. 

With the exception of whole-animal host resistance assays, the actual testing approach can be described as ex vivo-in vitro in that exposure of the immune system to potential immunotoxicants takes place in vivo, with subsequent immunological evaluation taking place in vitro. Although this approach obviates many uncertainties (effect of xenobiotics on primary or secondary lymphoid tissue, potential requirements for metabolism/bio-transformation, etc.), the use of whole animals presents many secondary issues, such... 

In the future, it is likely that many labor-intensive functional immunological assays performed in vivo or ex vivo will be replaced by high throughput multiparameter cytometric-based assays. The challenges faced both today and in the future have been recently described.56 For example, translational aspects of the nonclinical data to the clinical setting are difficult because despite much similarity, there are still species differences in some of the very basic aspects of the immune system. Additionally, reagents... 

Effects of TCDD on macrophages have also been examined. When assessed ex vivo, macrophage functions such as tumor cell lysis, phagocytosis and oxidative burst were not suppressed by exposure to TCDD.9396 101 In other experimental systems, exposure to TCDD increases IL-1 and TNF production by macrophages.99 102 103 However, the ability of TCDD to alter IL-1 and TNF production is likely organ- or stimulus-specific, because in the context of respiratory viral infection, exposure to TCDD had no effect on IL-1 or TNF-a levels.80... 

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