Vascular surface

Human bodies are constantly exposed to a plethora of bacteria, viruses, and other inflammatory substances. To combat these infections and toxic agents, the body has developed a carefully regulated inflammatory response system. Part of that response is the orderly migration of leukocytes to sites of inflammation. Leukocytes literally roll along the vascular wall and into the tissue site of inflammation. This rolling movement is mediated by reversible adhesive interactions between the leukocytes and the vascular surface. 

The highly vascular surface of the gastrointestinal mucosa ensures rapid absorption and onset of action, as well as the maintenance of sink conditions. 

The highly vascular surface of the oral mucosa ensures rapid absorption and onset of action, as well as the maintenance of sink conditions. In particular, the sublingual route is characterized by a rapid onset of action. The buccal cavity offers the combined advantages of a relatively rapid onset of action, with the potential for sustained delivery over several hours. 

The kidneys are more sensitive than many other organs to drug toxicity. Immune-mediated, drug-induced nephrotoxicities include glomerulonephritis and allergic interstitial nephritis, either with or without nephrotic syndrome. The kidney is highly susceptible in part because of its large vascular surface area for exposure to circu-... 

Implicit in this equation is the assumption that because of a large vascular surface area, the blood temperature equilibrates with the tissue temperature. The concept of effective thermal conductivity has been used by several investigators in thermal physiology (Shitzer and Eberhart, 1985). Jain and Wei (1977) also used this concept to describe the drug distribution in tumors. 

Cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet endothelial cell adhesion molecule (PECAM) and E-selectin have been associated with atherogenesis and progression of disease. These are molecules which are expressed in endothelial cells, platelets and white blood cells. Their increased expression has been associated with the adhesion, recruitment and migration of white blood cells in vascular surfaces, essential processes in atherosclerosis (Vaccari et al. 2007a,b). 

Another notion to be emphasized is that polymeric drugs should not be cationic but either neutral or anionic because the luminal sinface of blood vessels is highly negatively charged, and thus cationic polymer drugs are adsorbed on the vascular surface and are expected to have a short in vivo half-life. In addition, it is obvious that these molecules should not exhibit antigenic or immunogenic characteristics . 

The second focus area explores the recruitment and attachment of immune monocytes to the TGRL-activated endothelial cell surface. In order to establish the biomechanical properties of the adhesive phenotype and the membrane-interaction between the endothelial cells and monocytes, a novel MEMS-based microfluidic platform has been developed to mimic the vascular surface. This platform is amenable to confocal and other advanced microscopic techniques and has been used to demonstrate the upregulation of VCAM-1 (a cell adhesion molecule expressed on the... 

The expression of selectins is normally tightly regulated to ensure that leukocytes tether to and roll on the vascular surface only at appropriate locations [53]. However, dysregulated expression of selectins has been implicated in several forms of leukocyte-mediated tissue injury [54]. 

Yuan F, Leunig M, Berk DA, Jain RK. Microvascular permeability of albumin, vascular surface area, and vascular volume measured in human adenocarcinoma LS174T using dorsal chamber in SCID... 

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