Plasma organization

Numerous studies have been published on the in vivo metabolism of peptides. However, these studies are concerned mainly with assessment of pharmacokinetic parameters such as half-life and clearance. Only seldom is the in vivo biotransformation of peptides that contain only common amino acids investigated in any detail, due to the difficulty of monitoring products of proteolysis that are identical to endogenous peptides and amino acids. More importantly, such studies fail to yield mechanistic and biochemical insights. For this reason, we begin here with a discussion of the metabolism of just a few peptides in some selected tissues, namely portals of entry (mouth, gastro-intestinal tract, nose, and skin), plasma, organs of elimination (liver, kidney), and pharmacodynamic sites (brain and cerebrospinal fluid). These examples serve as introduction for the presentation in Sect. 6.4.2 of the involvement of individual peptidases in peptide metabolism. 

At a plasma pH of 7.4, the ratio c HP047cH2P04 is 4/1 (plC = 6.8). The total concentration of this buffer in both erythrocytes and plasma is less than that of other major buffer systems, accounting for only about 5% of the nonbicarbonate buffer value of plasma. Organic phosphate, however, in the form of 2,3-diphosphoglycerate (present in erythrocytes in a concentration of about 4.5 mmol/L), accounts for about 16% of the nonbicarbonate buffer value of erythrocyte fluid. 

Since de Wilde (1) and Thenard (2) first reported the formation of solid products in a plasma of organic vapor more than a centrury ago, many workers in the field of plasma organic chemistry have observed the presence of high molecular weight materials as reaction by-products. These materials adhered tightly... 

The implementation of screening for HBV in blood banks since 1970s has greatly reduced the transfusion related infection. Screening of plasma, organ, tissue, and semen donors, virus inactivation of plasma-derived products and maintenance of strict control by the authorities over the precautions that need to be followed in healthcare, dental and cosmetic application centres are mandatory as shown by Schmunis et al. (2001). 

Very high values can be found during hepatic coma. The highest blood lactic acid concentration in a series of cases of hepatic coma studied by Carfagno et al. (C2) was thus 65.2 mg%, whereas Nordmann et al, (N18) found 195 mg% in another case characterized by a fall in the blood pH to pH 7.25 and the presence of a big inosase to 32 meq/ liter in the total plasma organic acids, of which the lactic acid represented about two-thirds (Fig. 14). 

Fig. 14.2 a. Diagnostic approach for patients with defects of fatty acid -oxidation associated with non-ketotic presentation. Instead of plasma acylcarnitines, similar results may be obtained by analyzing plasma organic acids... 

The choice between X-ray fluorescence and the two other methods will be guided by the concentration levels and by the duration of the analytical procedure X-ray fluorescence is usually less sensitive than atomic absorption, but, at least for petroleum products, it requires less preparation after obtaining the calibration curve. Table 2.4 shows the detectable limits and accuracies of the three methods given above for the most commonly analyzed metals in petroleum products. For atomic absorption and plasma, the figures are given for analysis in an organic medium without mineralization. 

The deposition of organic films by plasma polymerization is an important application of non-thennal plasmas 1301. Plasma polymers are fonned at the electrodes and the walls of electrical discharges containing organic vapours. Oily products, soft soluble films as well as hard brittle deposits and powders are fonned. The properties of plasma... 

Much of the energy deposited in a sample by a laser pulse or beam ablates as neutral material and not ions. Ordinarily, the neutral substances are simply pumped away, and the ions are analyzed by the mass spectrometer. To increase the number of ions formed, there is often a second ion source to produce ions from the neutral materials, thereby enhancing the total ion yield. This secondary or additional mode of ionization can be effected by electrons (electron ionization, El), reagent gases (chemical ionization. Cl), a plasma torch, or even a second laser pulse. The additional ionization is often organized as a pulse (electrons, reagent gas, or laser) that follows very shortly after the... 

The thermospray device produces a wide dispersion of droplet sizes and transfers much of sample solution in unit time to the plasma flame. Therefore, it is essential to remove as great a proportion of the bigger droplets and solvent as possible to avoid compromising the flame performance. Consequently, the thermospray device usually requires both spray and desolvation chambers, especially for analyte solutions in organic solvents. 

The flame can become unstable if too large an amount of vaporized liquid is introduced or if the sample contains substances that can interfere with the basic operation of the plasma. For example, water vapor, organic solvents, air, and hydrogen all lead to instability of the plasma flame if their concentrations become too high. 

The ablated vapors constitute an aerosol that can be examined using a secondary ionization source. Thus, passing the aerosol into a plasma torch provides an excellent means of ionization, and by such methods isotope patterns or ratios are readily measurable from otherwise intractable materials such as bone or ceramics. If the sample examined is dissolved as a solid solution in a matrix, the rapid expansion of the matrix, often an organic acid, covolatilizes the entrained sample. Proton transfer from the matrix occurs to give protonated molecular ions of the sample. Normally thermally unstable, polar biomolecules such as proteins give good yields of protonated ions. This is the basis of matrix-assisted laser desorption ionization (MALDI). 

Samples to be examined by inductively coupled plasma and mass spectrometry (ICP/MS) are frequently in the form of a solution of an analyte in a solvent that may be aqueous or organic. 

After image transfer, the patterned resist must be readily and completely removable without substrate damage. The pattern often can be stripped from the substrate with a mild organic solvent. Proprietary stripper formulations or plasma oxidation treatments are utilized when the imaging chemistry or image transfer process has iasolubilized the pattern. 

Solution polymerization of VDE in fluorinated and fluorochlorinated hydrocarbons such as CEC-113 and initiated with organic peroxides (99), especially bis(perfluoropropionyl) peroxide (100), has been claimed. Radiation-induced polymerization of VDE has also been investigated (101,102). Alkylboron compounds activated by oxygen initiate VDE polymerization in water or organic solvents (103,104). Microwave-stimulated, low pressure plasma polymerization of VDE gives polymer film that is <10 pm thick (105). Highly regular PVDE polymer with minimized defect stmcture was synthesized and claimed (106). Perdeuterated PVDE has also been prepared and described (107). 

The principal organs involved in the peripheral clearance of hGH from the plasma are the kidney and fiver. hGH is cleared via glomerular filtration at the kidney and by a receptor-mediated mechanism at the fiver (58,59). In animal models, derivatives of hGH such as the 20,000 mol wt variant, oligomeric forms, and hGH complexed with GH-binding protein have been shown to be cleared from the semm at significandy lower rates than 22,000 mol wt hGH (60—62). The prolonged plasma half-life of these derivatives probably reflects a combination of decreased receptor affinity and size constraints on glomerular filtration. 

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