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Extracorporeal membrane oxygenation
Published in Mark Davenport, James D. Geiger, Nigel J. Hall, Steven S. Rothenberg, Operative Pediatric Surgery, 2020
Thomas Pranikoff, Ronald B. Hirschl
Blood is drained from the right atrium via the venous cannula into a small bladder by siphon/gravity. As long as venous drainage is adequate to fill the bladder, blood enters the raceway (tubing within the pump head) where it is actively pumped into the membrane lung. Here, blood travels in a countercurrent fashion to the sweep gas, separated by a thin silicone membrane. Oxygen enters the blood and carbon dioxide enters the sweep gas by simple diffusion along a concentration gradient. Blood then enters the heat exchanger where it is warmed to body temperature before entering the arterial cannula. This blood may enter either the arterial (VA bypass) or the venous system (VV support) (Figure 14.1).
Effect of Solute Structure on Transport of Radiotracers
Published in Lelio G. Colombetti, Biological Transport of Radiotracers, 2020
Since nonspecific migration across cellular membranes depends more on the lipid solubility of the solute than on simple diffusion, there is relatively good correlation between permeability and the partition coefficient of the solute distribution between olive oil and water. Apolar bonding of the molecule assists the entry of the molecule into the apolar environment of the cell membrane.
The Electrical Properties of Cells
Published in Richard C. Niemtzow, Transmembrane Potentials and Characteristics of Immune and Tumor Cell, 2020
To summarize the physical-chemical model: membrane potentials can be thought of as simple diffusion potentials produced by unequal concentrations of permeable ions on the two sides of the membrane. The magnitude of the membrane potential and relationship to the ion concentrations and permeabilities is described by the Goldman-Hodgkin-Katz Equation, or occasionally a simplified case for one permeable ion, the Nernst Equation. Despite the simple statement that the membrane potential is “merely” a diffusion potential, we must not lose sight of the fact that the diffusion potential exists in the first place, and continues to exist only because of metabolic energy expenditure of the cell to maintain the ion gradients which produce the diffusion potentials.
Improving cellular uptake of therapeutic entities through interaction with components of cell membrane
Published in Drug Delivery, 2019
Renshuai Zhang, Xiaofei Qin, Fandong Kong, Pengwei Chen, Guojun Pan
Cholesterol, diacylglycerol, and ceramide are the main hydrophobic components of lipid bilayer. The cellular uptake of many chemic entities, especially small molecules, is closely related to the hydrophobicity of cell membranes. Small molecules can cross plasma membrane into cells by simple diffusion as they can be soluble in the hydrophobic region of phospholipid bilayer. Lipophilicity is one of the main parameters that determine cell uptake of small molecules. Generally, when small molecules cross lipid bilayer by simple diffusion, they firstly accumulate in the hydrophobic regions of lipid bilayer at high concentration through hydrophobic interaction. Thus, small molecules must have moderate lipophilicity in order to internalize into cells. On the other hand, some membrane anchoring moieties (e.g. cholesterol, squalene, and fatty acids) can interact with the hydrophobic tail regions of the lipid bilayers and promote the cellular internalization of chemic entities. In some cases, hydrophobicity and lipophilicity could be used interchangeably although they are not synonyms. Thus, some strategies (including pro-drug and anchoring moieties modification) improved cellular uptake by interacting with hydrophobic portion were displayed in this section, without discussing whether they increase hydrophobicity or lipophilicity.
The therapeutic potential of RNA regulation in neurological disorders
Published in Expert Opinion on Therapeutic Targets, 2018
Jolien Roovers, Peter De Jonghe, Sarah Weckhuysen
Next to viral vectors, several non-viral approaches have been developed. Nanoparticles consist of a group of diverse structures with a similar nanometric size. They protect the compound by encapsulating it and aid in facilitating cellular uptake [21]. The ideal nanoparticle for biological use is polar at the surface, to give high aqueous solubility and to prevent aggregation. Additionally, it should be biodegradable with a limited life span, so that it is only present as long as therapeutically needed [22]. Many types of nanoparticles exist and include cationic polymeric, solid-lipid, nano-emulsions and liposomes [23]. Cationic polyethylenimine (PEI)-DNA complexes are the golden standard for mammalian cell transfections [24,25]. Nanoparticles can cross the BBB either by: (i) direct penetration also known as absorptive transcytosis, (ii) simple diffusion, or by (iii) receptor-mediated endocytosis [26]. When nanoparticles are taken up by the cell, they are often encapsulated in endosomes, after which endosomal escape is a major limiting factor. Positively charged nanoparticles are more efficiently able to escape from endosomes in neurons and are thus more frequently used [26].
Evaluation of a novel biocompatible magnetic nanomedicine based on beta-cyclodextrin, loaded doxorubicin-curcumin for overcoming chemoresistance in breast cancer
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Roghayeh Rastegar, Hamid Akbari Javar, Mehdi Khoobi, Poua Dehghan Kelishadi, Gholam Hossein Yousefi, Mahmoud Doosti, Mohammad Hossien Ghahremani, Ahmad Shariftabrizi, Fatemeh Imanparast, Elham Gholibeglu, Mahdi Gholami
Cellular uptake is a key step for chemotherapeutics to reach the pharmacologic target. Nevertheless, this process is impaired in resistant breast cancer cells. NCs internalization in MCF-7/adr cells was assessed using CLSM and flowcytometric analyses (Figure 4). Untreated cells was used as negative control. Uptake of free DOX seems to be negligible. Small molecules such as DOX and CUR are internalized via simple diffusion which is a relatively slow process compared to active transport mechanisms. DOX loaded NCs are taken-up more efficiently. In CLSM study, more intense DOX related red florescent signal is detected (nucleus is stained in blue with DAPI). In flowcytometric analyses, DOX related red signal is plotted against CUR related green signal. In case of DOX loaded NCs data points are shifted up toward more intense red signals which confirms enhanced internalization of DOX. As it is reported in literature, surface functionalized SPIONs are internalized via active endocytosis [27]. There are some reports which shows that protein corona impairs nanoparticle-internalization by covering surface of nanoparticle [10]. However, as it is confirmed by protein corona analyses, β-CD coating reduce the protein corona which lead to the enhanced uptake of NCs. P-gps which are overexpressed in MCF-7/adr cells pump out free DOX. On the other hand, DOX encapsulated within cross-linked β-CDs is released in sustained release pattern which reduce drug efflux via P-gps.