Plasma water

The lag-phase measurement at 234 nm of the development of conjugated dienes on copper-stimulated LDL oxidation is used to define the oxidation resistance of different LDL samples (Esterbauer et al., 1992). During the lag phase, the antioxidants in LDL (vitamin E, carotenoids, ubiquinol-10) are consumed in a distinct sequence with a-tocopherol as the first followed by 7-tocopherol, thereafter the carotenoids cryptoxanthin, lycopene and finally /3-carotene. a-Tocopherol is the most prominent antioxidant of LDL (6.4 1.8 mol/mol LDL), whereas the concentration of the others 7-tocopherol, /3-carotene, lycopene, cryptoxanthin, zea-xanthin, lutein and phytofluene is only 1/10 to 1/300 of a-tocopherol. Since the tocopherols reside in the outer layer of the LDL molecule, protecting the monolayer of phospholipids and the carotenoids are in the inner core protecting the cholesterylesters, and the progression of oxidation is likely to occur from the aqueous interface inwards, it seems reasonable to assign to a-tocopherol the rank of the front-line antioxidant. In vivo, the LDL will also interact with the plasma water-soluble antioxidants in the circulation, not in the artery wall, as mentioned above. 

An interesting idea was to use a monolith column to perform dual functions of online SPE and chromatographic separation. Because of the porous structure of a monolith column and its very low backpressure, plasma or diluted plasma can be directly injected. Plumb et al. (2001) used this approach to quantitate an isoquinoline drug and 3 -azido-3 -deoxy thymidine (AZT). Diluted plasma samples (plasma water 1 1) were injected directly into a Chromolith Speed ROD RP-18e column... 

The glomerular membrane has pores of 70-80 A under the positive hydrostatic conditions in the glomerulus, all molecules smaller than about 20,000 Da are filtered. Proteins and protein-bound compounds thus remain in the plasma, and about 20% of the nonbound entity is carried with 20% of the plasma water into the glomular filtrate. 

Blood is supplied to the kidneys via the renal vein, a branch of the descending vena cava, at relatively high pressure to ensure rapid filtration of plasma across the membranes of the blood vessels in the glomeruli and the epithelial cells of the Bowman s capsule. The net filtration pressure of about 5-6 kPa, is the difference between the blood pressure forcing plasma water across the filtration barrier and the opposing osmotic and... 

The glomerular filtration rate (GFR) defines how much plasma water passes from the blood into the top of the nephron per minute. In health, the true GFR for a 70 kg adult is typically 100-120 ml/minute. Expressed another way, we can say that, in health, every minute each of the approximately 2 million glomeruli present in both adult kidneys filters between 0.05 and 0.06 pi of plasma water. The GFR is a good overall measure of renal function and the clinical laboratory has many ways of estimating its value. 

It is easiest to understand how clearance relates to the rate of decline of drug concentrahon (half-life) if we consider the model depicted in Figure 2.9. When a dose (D) is administered intravenously then the inihal free concentrahon achieved in plasma Cp(fo) is dependant on the volume of extracellular or total body water minus plasma water and the amount of drug bound to hssues and proteins. 

Ultracentrifugation Minimal non-specific binding and osmotic volume shifts. Large plasma volumes required, long assay time, issues such as sedimentation, back diffusion and viscosity. Potential for lipoprotein contamination of plasma water layer. [28, 29]... 

The total volume of the fluid compartments of the body into which drugs may be distributed is approximately 40 L in a 70-kg adult. These compartments include plasma water (approximately 10 L), interstitial fluid (10 L), and the intracellular fluid (20 L). Total extracellular water is the sum of the plasma and the interstitial water. Factors such as sex, age, edema, pregnancy, and body fat can influence the volume of these various compartments. 

Most drugs found in the vascular compartment are bound reversibly with one or more of the macromolecules in plasma. Although some drugs simply dissolve in plasma water, most are associated with plasma compo-... 

Since approximately 130 mL of plasma water is filtered across the porous glomerular capillary membranes each minute (190 L/day), the kidney is admirably suited for its role in drug excretion. As the ultrafiltrate is formed, any drug that is free in the plasma water, that is, not bound to plasma proteins or the formed elements in the blood (e.g., red blood cells), will be filtered as a result of the driving force provided by cardiac pumping. 

The total water in the body of an animal can be conveniently divided into three compartments the plasma water, the interstitial water, and the intracellular water. The way a foreign compound distributes into these compartments will profoundly affect the plasma concentration. If a compound is only distributed in the plasma water (which is 3 L in man), the plasma concentration will obviously be much higher than if it is distributed in all extracellular water ( 14 L) or the total body water 40 L). This may be quantified as a parameter known as the volume of distribution (VD), which can be calculated as follows ... 

The elements of the galvanic cell should not be influenced by the chemistry and/or number of samples measured. In particular, the sample should maintain its initial physical and chemical properties, even after storage. In other words such processes as the evaporation of plasma water, gas escape, denaturation of proteins, the cell lyses, etc. should be minimized to avoid analyte concentration changes and artifacts. 

However, in contrast to a direct measurement, where the analyte activity in the native sample is measured, in the indirect measurement (after dilution) this possibility is lost. In the latter case, only total concentration in a sample can be back-calculated . Additionally, because water plasma in a patient sample is not measured, the indirect method of measuring blood electrolytes in hyperlipemic/hyperproteinemic samples (i.e., in the cases of low plasma water vs. plasma volume) results in a negative bias compared to direct measurement (the bias is bigger with lower water content), while for samples with a high electrolyte content (i.e., high plasma water ionic strength) the indirect measurements will result in a positive bias. 

Experiments have been conducted to simulate leaching of phthalates from blood bags by allowing human plasma to extract added phthalates from coated Celite (Albro and Corbett 1978). It was found that more than 80% of the DEHP was associated with lipoproteins, in the order LDL > VLDL > HDL > chilomicrons. The remaining DEHP was adsorbed weakly and nonspecifically to other proteins including albumin. MEHP was in equilibrium between free in solution and adsorbed to albumin, no MEHP was bound to lipoproteins. Rock et al. (1986) reported that in human plasma, the lipase that hydrolyzes DEHP copurified with the albumin, and once in the plasma, the MEHP bound to albumin. An earlier study by Jaeger and Rubin (1972) reported that in human blood stored in PVC bags, the bulk of DEHP was associated with lipoproteins, but a substantial amount was in a fraction likely to represent DEHP soluble in plasma water as well as bound to plasma proteins and cell membranes. 

V, steady-state volume of distribution referenced to the unbound drug in plasma. Kp, partition coefficient of drug between plasma protein and plasma water, r, ratio of the fractions of the drug non renally and renally eliminated. 

Some relevant volumes of body compartments are (in liters) plasma water (3), erythrocyte water (3), extracellular water excluding blood (11), and intracellular water (24). The total body water is approximately 41 L. A comparison of selected drugs with apparent volumes of distribution (in liters) approximating various body compartments is shown in Table 2.6. 

Mixed Gas Plasmas. Water loading can be reduced by a desolvation system (condenser or membrane separator) only if the vast majority of the water can be removed. One way to eliminate the introduction of water into the plasma during measurement of the analyte signals is with electrothermal vaporization, laser ablation, or other direct solid sampling techniques. Mixed gas plasmas,... 

In addition, FFAs can be delivered to working muscles in the free form in solution. However, their extreme hydrophobicity limits their solubility in plasma water and the bulk of the plasma FFA pool is bound to albumin... 

Because of this extensive plasma protein binding, a method of variable plasma concentrations was devised (7) which took advantage of the competition between red blood cells and plasma protein for the free drug in plasma water. The red blood cell distribution coefficient, D = was 12.5 for the dog red blood... 

The partitioning of tetrahydrocannabinol from plasma water into red blood cells is enormously high since D = 12.5. This may also be ascribed to the high sur-... 

ANP is a 28-amino-acid peptide first discovered by de Bold et al. (2). It is released from heart atrial myocytes in response to a local arterial wall stretch. ANP acts on outer adrenal cells to decrease aldosterone production and blood pressure, increase salt and water excretion, and transudate plasma water to the interstitium (3). 

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