Endothelial layer

In another approach, Parnigotto and coworkers reconstructed corneal structures in vitro by using corneal stroma containing keratocytes to which corneal epithelial cells from bovine primary cultures were overlaid [73], However, this particular corneal model did not contain an endothelial layer. This model was histochemically characterized and the toxicity of different surfactants was tested using MTT methods. This stroma-epithelium model has been reported to show a cornea-like morphology, where a multilayered epithelial barrier composed of basal cells (of a cuboidal shape) and superficial cells (of a flattened shape) is noted. Furthermore, the formation of a basement membrane equivalent and expression of the 64-kDa keratin were reported, indicating the presence of differentiated epithelial cells. The toxicity data for various surfactants obtained with this model correlate well with those seen by the Draize test [73], However, this corneal equivalent was not further validated or used as a model for permeation studies. 

TNF-a and IL-1 are current targets of antiinflammatory drug therapy. A homotrimer of 17-kDa protein subunits whose effects include the activation of neutrophils and eosinophils, induction of COX-2, induction of proinflammatory cytokines (e.g., IL-1, IL-6), enhancement of endothelial layer permeabihty, induction of adhesion molecules by endothelial cells and leukocytes, stimulation of fibroblast proliferation, degradation of cartilage, and stimulation of bone reabsorption. Two receptors mediate these effects a 55-kDa receptor (p55) and a 75-kDa receptor (p75). Each of these receptors is found in both cell surface and soluble forms. The binding of two or three cell surface receptors to TNF-a initiates an inflammatory response. Soluble p55 also acts as a signaling receptor for inflammatory responses, whereas soluble p75 acts as an antagonist. 

Melkonian, P. Talbot, K. E. Pinkerton, and J. C. Rutledge. Reactive carbonyls from tobacco smoke increase arterial endothelial layer injury. Am J Physiol Heart Circ Physiol 2002 283(2) H591-H597. 

Prominent changes in the cells have been revealed after 30 min of irradiation. Besides the oedema of the cytoplasm and nuclei swelUng, crater-like erosions appeared on the luminal surface of the endotheUocytes (Fig. 30.1b). Intercellular spaces became wider, and fibrin thread and single erythrocytes were found in these spaces. In some zones the longitudinal folds of the intima were smoothed, but the endothelial layer remained intact. Such zones may correspond to the sub-endothelial oedema. These changes remained for 6 h after kradiation. One day later the microrelief of the aorta s intima returned to normal. 

In the ventricular myocardium Cx40, Cx43 and Cx45 have been detected [Kanter et al., 1994 Verheule et al., 1997] but only Cx43 and Cx45 have been found in the human heart in considerable amounts, whereas only a very low expression of Cx40 was observed which was located at the subendocardium and at endothelial layers [Davis et al., 1995]. 

A biologic surface that develops an endothelial cell surface is referred to as a neointima. If it is covered with blood components such as fibrin, it is called a pseudointima. In both cases, the surfaces are passive with respect to the blood to which they come into contact. A pseudointima, however, is typically unstable and subject to further ihrombic response. If the surface is damaged, as during surgical implantation, a catastrophic failure can result. This coupled with the difficulty of developing a complete endothelial layer caused one researcher to describe a device as physiologically tolerable rather than biocompatible or hemocompatible. 

The factor that differentiates natural and synthetic surfaces is the endothelial layer. The layer is truly nonthrombogenic and is capable of repairing itself. While it can develop on synthetic material, its growth in humans is slow. One way of accelerating growth is to seed the synthetic material. 

A passive flux of water continually flows across the endothelial layer toward the stroma, which has a tendency to swell. An active pump mechanism pulls an aqueous flux in the opposite direction which controls corneal turgescence [13]. Corneal deturgescence is an ATP-dependent process of the endothelial cells and as such any disruption of the endothelium may result in corneal oedema, thereby affecting corneal transparency. The specific distribution of different proteoglycans across the cornea has recently been implicated in water gradients across the cornea. This water gradient serves to diminish dehydration of the front of the cornea, which is exposed to the atmosphere. 

Lubricity. Outer-wall lubricity is particularly important for intravascular catheters, otherwise the endothelial layer of blood vessels is easily damaged by interventional insertion. Lubricity is usually acquired by coating with hydrogels or biopolymers. 

Based on the morphology and continuity of the endothelial layer, capillary endothelium can be divided into three categories continuous, fenestrated, and discontinuous endothelium (see Section 5.1.3). 

In the aorta of an adult man the tunica intima consists of an endothelial layer backed by a layer containing longitudinally oriented branching elastic fibers. Between these fibers are collagenous fibers, fibroblasts, and... 

Recent research has demonstrated that adult human corneal endothelial cells can be grown in culture and transplanted into recipient corneas. Because human endothelial cells retain the capacity to proliferate, growth factors and inhibitors are under study as a potential method for regenerating damaged endothelial cells and increasing cell density to restore endothelial layer function. 

Atherosclerosis is accepted as a common mechanism underlying all CVDs [2], Atherosclerosis is a disease of large and medium-sized arteries. It affects all three coats of the arterial wall in its more advanced stages. The arterial wall consists of three layers intima, media, and adventitia. The most inner luminal part of the intima is a monolayer of endothelial cells lining the whole wall. The intact endothelial layer is a selective barrier for plasma lipids and also has antitrombotic properties [3,7]. The pathogenesis of atherosclerosis can be divided into three main stages. 

LDL Enter the Endothelial Cell Layer, and Become Oxidized. As LDLs circulate through the blood stream, they pass in between the cells of the endothelial layer of the arteries, where they are exposed to toxic oxygen released by the endothelial cells and bv white blood cells. I hese white blood cells make their home... 

The inflammatory response is initiated by stimuli released from sites of tissue injury that results in the expression of selectins on the endothelial layer. These selectins (E(endothelial)-selectin and P(platelet)-selectin) function through recognition of oligosaccharides on the opposing leukocyte cell surface [194]. This interaction eventually weakly tethers the leukocyte to the endothelial layer, at which point integrin binding events lead to firm adhesion and extravasation of the leukocyte into the tissue. In certain disease processes, excessive leukoc)4e infiltration becomes deleterious to the body, and inhibitors of this process are desirable. Rheumatoid arthritis, asthma, organ transplant rejection, and reperfusion injury are just a few of the cases in which these events occur [27]. 

The BBB of the brain has two major components. An endothelial layer lies between the arterial blood in the brain capillaries and the interstitial fluid of the brain. In humans, the surface area of the endothelial layer in the brain is approximately 21 square meters [51]. An epithehal layer lies between venous blood and the cerebrospinal fluid (CSF) in the choroid plexus, and has a surface area of only 0.021 square meters in humans [52]. At the spinal cord, the BBB... 

Figure 3.95. Fundamental principles of the LSCM (a) and the TPEM (b). In the LSCM, OP excitation laser light is condensed in a focal plane (endothelial layer) by an objective lens the light also excites upper (smooth muscle layer) and lower planes of the focal plane. However, fluorescence emission exclusively from the focal plane is detected through the pinhole. (From Ref. [105] with permission of The Japanese Pharmacological Society.)...

Figure 1 Diagrammatic representation of the ultrastructure of the respiratory membrane. Arrows indicate the passage of drugs (horizontal heavy lines) through the respiratory membrane after alveolar or capillary exposure, or of metabolites (horizontal broken lines) generated in the epithelial or endothelial layers. Key (1) monomolecular surfactant layers, (2) thin fluid film, (3) interstitial space, (4) endothelial capillary basement membrane, (5) drug transport from the alveoli, (6) absorption of drug into endothelial cells from the circulation, (7) transport of drug from the circulation to alveolar epithelium, (8) transport of drug from the circulation to the alveoli. (From Ref. 102. Reproduced by permission, CRC Press, Inc.)...

The large size of plasmid DNA greatly limits its distribution after in vivo administration. The distribution processes have some limitations as far as size is concerned, such as the passage through capillaries (about 5 pm in diameter) and fenestrae (50-300 nm) in the endothelial layers. Tissue distribution of intravascularly administered plasmid DNA is highly restricted by the endothelial wall, which is composed of vascular endothelial cells and basement membrane. Discontinuous endothelium, which is present only in the liver, spleen, bone marrow, and some solid tumors, allows plasmid DNA to come into contact with tissue cells. 

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