Protein volume increase rate

CF patients have larger volumes of distribution of many antibiotics due to an increased ratio of lean body mass to total body mass and lower fat stores. CF patients also have an enhanced total body clearance, although the exact mechanism has not been determined. Increased renal clearance, increased glomerular filtration rate, decreased protein binding, increased tubular secretion, decreased tubular reabsorption, extrarenal elimination, and increased metabolism have all been proposed as possible reasons for the increased clearance. 

Recently, Arner and coworkers investigated the amount of perilipin protein and lipolysis rates in human subcutaneous adipocytes of non-obese and obese women [523]. A polymorphism in intron 6 (rs891460 A/G) in the perilipin gene seems to be associated with a 50% decrease in perilipin expression and increased basal lipolysis (AA vs. GG carriers) in adipocytes of the obese women, which in subjects matched for body mass index and adipocyte volume was inversely correlated with the plasma concentrations of NEFA and glycerol and thus may contribute to the development of insulin resistance. Furthermore, they found two- to four-fold increases in noradrenaline-induced lipolysis [523]. These data also reinforce the role of perilipin for the regulation of lipolysis in human fat cells. 

The macroscopic geometry of a matrix can influence the rate and pattern of protein release. Increasing the surface-area-to-volume ratio of the matrix increases the release rate by allowing more particles direct access to the matrix exterior. The common matrix form of a slab has a release rate proportional to the square root of time (Fig. lb). However, if the matrix is... 

A retardation in the rate of denaturation of a pure protein in solution, comparable to the pressure effect on the thermal destruction of the luminescent system, thus assumes particular interest. Qualitative observations have recently shown that this phenomenon takes place in solutions of highly purified egg albumin and serum globulin (120). A pressure of 10,000 lb. per sq. in. practically pi events the precipitation of the latter protein at 65°C. and pH near neutrality. Quantitative studies of the kinetics of this denaturation have not been completely analyzed, but the indications are that a volume increase of activation on the order of 100 cc. per mole is involved (121). Small concentrations of ethyl alcohol accelerate the precipitation under both normal and increased pressure, as shown in Figure 17 the denaturation proceeds with a large volume increase of activation, of the order of 100 cc. per mole, as in the destruction of the... 

Because it is a small protein, the factor IX molecule passes into the intravascular and the extravascular spaces. Therefore, the volume of distribution of recombinant factor IX is twice that of factor VIII. Consequently, 1 unit of factor IX administered per kilogram of body weight yields a 1% rise in the plasma factor IX level (0.01 unit/mL, or 1 IU/dL). Thus 1750 units of factor IX provides an incremental increase of 50% of normal (0.5 unit/mL, or 50 IU/dL), that is, 1750 units/70 kg x 0.01 unit/mL (1 IU/dL).12 Additionally, the recovery rate with recombinant factor IX is 20% lower than that with the plasma-derived products. Therefore, initial and subsequent maintenance doses should be adjusted accordingly. 

The potent antidiuretic hormone AVP orchestrates the regulation of free water absorption, body fluid osmolality, cell contraction, blood volume, and blood pressure through stimulation of three G-protein-coupled receptor subtypes Vi-vascular types a and b, V2-renal, and V3-pituitary. Increased AVP secretion is the trademark of several pathophysiological disorders, including heart failure, impaired renal function, liver cirrhosis, and SIADH. As a consequence, these patients experience excess water retention or inadequate free-water excretion, which results in the dilution of sodium concentrations, frequently manifesting as clinical hyponatremia (serum sodium concentration <135mmol/L). This electrolyte imbalance increases mortality rates by 60-fold. Selective antagonism of the AVP V2 receptor promotes water... 

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