Fenestrated capillaries

Polymeric micelles. When water-soluble polymers are conjugated with lipophilic, poorly water-soluble polymers, the resulting copolymers are amphiphilic and can be used to constitute spherical micelles.54 The sizes of the polymeric micelles range between 10 and 100 nm, which is ideal for preferential extravasation at the fenestrated capillary blood vessels. The polymeric micelles have a hydrophobic core consisting of the... 

Fenestrated capillaries are present in all exocrine and endocrine glands, gastric and intestinal mucosa, choroid plexuses of brain, renal tubules and glomeruli, and ciliary body of the eye. The passage of macromolecules through these capillary walls is restricted by size (the fenestrae are 40-60 nm in diameter), and by the presence of the basement membrane. 

M. SimioficscuL N, Simitnescu, and G. E Palade. Preferential distribution of anionic sites oa the basement membrane and the abhiminal aspect of the endothelium in fenestrated capillaries. L Ceil BioL 55 425-434 (Ivsz). 

Figure 5.1 Schematic illustration of the structure of the wall of different classes of blood capillaries. (1) Continuous capillary (as found in the general circulation). The endothelium is continuous with tight junctions between adjacent endothelial cells. The subendothehal basement membrane is also continuous. (2) Fenestrated capillary (as found in exocrine glands and the pancreas). The endothelium exhibits a series of fenestrae which are sealed by a membranous diaphragm. The subendothehal basement membrane is continuous. (3) Discontinuous (sinusoidal) capillary (as found in the liver, spleen and bone marrow). The overlying endothelium contains numerous gaps of varying size. The subendothehal basement is either absent (hver) or present as a fragmented interrupted structure (spleen, bone marrow)...

Due to their large molecular weight (> 1,000 kDa) and hydrodynamic diameter in aqueous suspension of 100 nm, plasmids extravasate poorly via continuous capillaries because of tight junctions between the cells. However, plasmids can easily extravasate to sinusoidal capillaries of liver and spleen. Formulating plasmids into unimeric particles of 20-40 nm in diameter may enhance extravasation of plasmids across continuous and fenestrated capillaries. 

The deposition of plasmids after systemic administration is restricted to the intravascular space due to its low microvascular permeability in most organs with continuous capillary bed. Some organs with fenestrated capillaries, such as liver, spleen, and bone marrow, provide some opportunities for extravasation of plasmids. Intravenously injected plasmids initially perfuse the pulmonary vascular beds, maximizing the... 

The TIDA neurosecretory neurons terminating in the median eminence lack true synapses and the DA released from these neurons into the extracellular fluid diffuses through fenestrated capillaries of the hypophysial portal system where it is transported to the anterior pituitary (Fig. 3 Bottom Panel). Considering this unique cytoarchitecture, it is not surprising that the TIDA neurons are reported to lack inhibitory autoreceptors (Demarest and Moore, 1979b Timmerman et al., 1995a), have lower levels of DA transporter mRNA (Meister and Elde, 1993) and protein (Ciliax et al., 1995 Revay et al.,... 

The effectiveness of cisplatin depends on its ability to penetrate target tissue. Therefore, we need to estimate its penetration depth from a distributed model such as that represented by Equation 9.1. However, this is difficult to do with ovarian tumors because the permeabilities and reaction rates are not available. Hence, a first estimate is made for penetration of normal peritoneal cavity tissues by ethylenediamine-tetraacetic acid (EDTA), a molecule of molecular weight similar to that of cisplatin. The steady-state concentration profiles of EDTA should resemble those of cisplatin in normal peritoneal tissues because both compounds are cleared primarily by permeation through the fenestrated capillaries in these tissues, and the small molecular weight-related differences in P s and D should cancel out in Equations 9.5 and 9.5T By first focusing on EDTA, experimental data also become available for assessing the ability of the distributed model to account for the observed spatial dependent of concentration. 

Neighboring RPE cells are connected by tight]unctions that help to create the blood/retinal barrier separating the neuro-sensory retina from fenestrated capillaries in the choroid. The basement membrane of RPE, together with the adjacent basement membrane of the choroid, forms a structure known as Bruch s membrane. RPE cells possess a number of organic and ion transporters to help move polar molecules across the blood retinal barrier. These include transporters for amino acids, folate, ascorbic acid, myo-inositol, organic anions, glucose and lactate. 

A monocyte is a mononuclear phagocyte in the blood. Monocytes have free access via fenestrated capillaries to most organs in the body where they can become tissue-specific macrophages. The CNS represents an exceptional organ in that its capillaries are nonfenestrated and the endothelial cells form tight junctions which, in essence, constitute the blood-brain barrier. Thus, all blood leukocytes, including monocytes, are normally prohibited from entering the CNS. 

The blood-nerve barrier is not an impediment to the actions of circulating IGFs on peripheral neurons. Sensory and sympathetic ganglia are served by special fenestrated capillaries which permit molecules as large as Mr 44 000 to leave the circulation and enter the ganglia (Jacobs et al., 1976 ... 

In the glomerular capillaries, a portion of the plasma water is forced through a filter that has three basic components fenestrated capillary endothelial cells, a basement membrane lying just beneath the endothelial cells, and the filtration slit diaphragms formed by the epithelial cells that cover the basement membrane on its urinary space side. Solutes of small size flow with filtered water (solvent drag) into the urinary (Bowman s) space, whereas formed elements and macromolecules are retained by the filtration barrier. 

Glomerular Filtration Drugs pass from the blood into the nephron by perfusing across the fenestrated capillaries of Bowmans Capsule. Diffusion Process. Small, nonionic drugs pass more readily. Drugs bound to plasma proteins cannot pass. Rate of filtration depends in part on blood pressure. 

Doxorubicin Commercially available as a stable, lyophilized liposomal formulation rv administered liposomes concentrate in fenestrated capillaries such as liver, spleen, and the bone marrow. IV doxorubicin liposomes have been shown to reduce its cardiotoxicity... 

---