Plasma containment

Human blood plasma contains over 700 different proteins (qv) (1). Some of these are used in the treatment of illness and injury and form a set of pharmaceutical products that have become essential to modem medicine (Table 1). Preparation of these products is commonly referred to as blood plasma fractionation, an activity often regarded as a branch of medical technology, but which is actually a process industry engaged in the manufacture of speciaUst biopharmaceutical products derived from a natural biological feedstock (see Pharmaceuticals). 

In passive immunotherapy immune globulin (Ig) is an effective replacement in most forms of antibody deficiency (14). In the past, plasma was used instead of immune globulin, but plasma is rarely indicated in the 1990s because of the risk of disease, particularly AIDS, transmission. Because plasma contains many factors in addition to immunoglobulins (Igs), plasma is, however, of particular value in patients with protein-losing enteropathy, complement deficiencies, and refractory diarrhea. 

Pulsed plasmas containing hydrogen isotopes can produce bursts of alpha particles and neutrons as a consequence of nuclear reactions. The neutrons are useful for radiation-effects testing and for other materials research. A dense plasma focus filled with deuterium at low pressure has produced 10 neutrons in a single pulse (76) (see Deuterium AND TRITIUM). Intense neutron fluxes also are expected from thermonuclear fusion research devices employing either magnetic or inertial confinement. 

An hplc assay was developed suitable for the analysis of enantiomers of ketoprofen (KT), a 2-arylpropionic acid nonsteroidal antiinflammatory dmg (NSAID), in plasma and urine (59). Following the addition of racemic fenprofen as internal standard (IS), plasma containing the KT enantiomers and IS was extracted by Hquid-Hquid extraction at an acidic pH. After evaporation of the organic layer, the dmg and IS were reconstituted in the mobile phase and injected onto the hplc column. The enantiomers were separated at ambient temperature on a commercially available 250 x 4.6 mm amylose carbamate-packed chiral column (chiral AD) with hexane—isopropyl alcohol—trifluoroacetic acid (80 19.9 0.1) as the mobile phase pumped at 1.0 mL/min. The enantiomers of KT were quantified by uv detection with the wavelength set at 254 nm. The assay allows direct quantitation of KT enantiomers in clinical studies in human plasma and urine after adrninistration of therapeutic doses. 

Figure 5.67 Reconstructed ion chromatograms for Idoxifene and internal standard (ds-Idoxifene using LC-ToF-MS for (a) double-blank human plasma extract, (b) extract of blank human plasma containing internal standard (IS), and (c) control-blank human plasma spiked with Idoxifene at 5 gml , the LOQ of the method. Reprinted from 7. Chromatogr., B, 757, Comparison between liquid chromatography-time-of-flight mass spectrometry and selected-reaction monitoring liquid chromatography-mass spectrometry for quantitative determination of Idoxifene in human plasma , Zhang, H. and Henion, J., 151-159, Copyright (2001), with permission from Elsevier Science.

Plasma contains many proteins with a variety of functions. Most are synthesized in the liver and are glycosylated. 

For low-pressure plasmas containing mainly inert gases the electrons can be characterized by a Maxwellian electron energy distribution function (EEDF). How-... 

Inhibitors that block the protease activity of F-XIIa and kallikrein. Plasma contains two protease inhibitors that regulate contact activation Cl inhibitor (Cl-Inh) and a2-macroglobulin (a2-M). 

Egg yolk contains mainly lipids (32 34%), proteins (16%), saccharides, mineral compounds, vitamins, dyes and water (48%). It is formed by two distinguishable fractions plasma and granules. The plasma contains mostly lipids (90% of total solids) and proteins. Granules contain mainly acidic phosphoproteins (fosvitin, lipovitellins and low-density lipoproteins), which are soluble only in higher ionic strength water solutions. 

Other reverse-bias annealing experiments have been published that can be analyzed in the same way. Tavendale et al. (1985) used 10 ft cm boron-doped silicon passivated by exposure to plasmas containing or 2H. Schottky diodes formed with such specimens showed breakup of BH under heating at 80°C with reverse bias however, there was a persistence of passivation in the first two or three microns that must be attributed to some sort of near-surface reservoir of hydrogen. This effect was absent in an annealing experiment on a junction diode with an -type surface... 

FIGURE 11.2 Chromatograms of (A) blank plasma, (B) patients plasma containing 0.1 pg/mL voriconazole, and (C) 3.5 ug/mL voriconazole. Vori = voriconazole. IS = internal standard. (Source From Wenk, M. et al. J Chromatogr B. 832, 315, 2006. With permission.)... 

However, the reaction of NP with thiols may be a necessary but not sufficient cause for the release of NO from the ion as there are many thiols in frog heart tissue and NP is a vasodilator only under illumination. Furthermore Sogo et al. [50] could not detect NO generation from NP in human plasma containing cysteine, glutathione, homocysteine and reduced cysteine residues. Therefore, there must be a unique component of mammalian tissues which is involved in the release of NO from NP, and this reaction comes after reaction with thiol. Kowaluk et al. [51] report that NP is readily metabolised to NO in subcellular fractions of bovine coronary arterial smooth muscle and that the dominant site of metabolism is in the membrane fraction. This led to the isolation of a small membrane-bound protein or enzyme that can convert NP into NO. The mechanism shown in Scheme 8.2 combines the thiol reaction and that with an enzyme. 

Under normal conditions, plasma contains 155 mEq of cations and 155 mEq of anions. The total concentration of cations always equals the concentration of anions. Any number of milliequivalents of Na+, K+, Ca++, Mg++, or any cation always reacts with precisely the same number of mEq of Cl , HC03", S042-, or any other cation. 

If a radioactive-labelled form of a substrate (A ) is added to a plasma containing unlabelled-substrate (A) and a limited amount of its specific binding antibody (P), then assuming a dynamic equilibrium exists between (A) and (P), (A ) shall distribute itself evenly among the unlabelled substrate (A). If the binding affinity between (A) and (P) is very high, virtually all the (A ) added will be found until (P) is saturated and at equilibrium. Thus, we have ... 

Carboxylesterases (EC 3.1.1.1) can be detected in most mammalian tissues. Besides organs with high carboxylesterase activity such as liver, kidney, and small intestine, esterase activity is present, e.g., in the brain, nasal mucosa, lung, testicle, and saliva. Compared to rat plasma, human plasma contains little carboxylesterase, its esterase activity being essentially due to cholinesterase [61][73][79][89-91],... 

Even when hydrolysis and epimerization can be avoided during sample preparation and handling, it is not possible to conclude definitively whether the compounds found in plasma and urine are true metabolites or simply degradation products. Indeed, chemical degradation can also occur within the body since urine and plasma contain a wide variety of potential catalysts, including metal ions, phosphate ions, proteins, and sugars (see Sect. 5.2.6). Whereas the existence of mammalian enzymes that act on penicillins and cephalosporins is considered possible [155], no such mammalian enzyme appears to have been identified to date. 

An example of LC-MS separation of four racemic 3-blockers achieved on a TE CSPis reported in Figure 2.16. The chromatographic assay developed was applied in the direct HPLC injection of human plasma containing sotalol on a chiro-RAM-TE support [64] (Figure 2.17). 

In an atomic gas, electrons are held captive by atomic nnclei. In a plasma, they are free to move around. This freedom of the now-antonomous electrons makes the plasma a good electrical condnctor. The plasma contains a nuxtnre of free electrons and positive ions. 

Plasma contains a large variety of proteins, all of which have the potential to interact with drugs. Albumin is generally considered to be the most important contributor to the plasma protein binding of drugs (GIO, Gil, M16), but for some, e.g., steroids, other proteins play a major role. 

Electrochemical processes in plasmas have recently attracted renewed attention [97]. Plasmas contain ionic species in a... 

The preparation of film electrodes Prussian blue films are usually prepared by cycling an electrode in a freshly prepared solution containing iron(III) and hexacyanoferrate(III) ions [70-72]. As substrate, mostly platinum is used, sometimes glassy carbon [73] is used, and very frequently ITO electrodes [74] are used because the latter are very useful for electrochromism studies. Similar procedures using solutions containing metal ions and hexacyanoferrate(III) have been used to deposit cobalt hexacyanoferrate [75] and chromium hexacyanoferrate [76, 77]. Crumbliss et al. reported a plasma deposition of iron species from a plasma containing iron pentacarbonyl and ethane, followed by electrochemical derivatization of the deposited iron sites with the help of hexacyanoferrate solutions [78]. 

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