Protein metabolism in burned rats

Abstract

Incorporation of [2-14C]glycine was used to estimate serum protein synthesis in four groups of rats. These were the control (group C); 20% body surface burn (group B); 20% burn, seeded with Pseudomonas aeruginosa (group BI); and burned-infected treated topically with mafenide (alpha-amino-p-toluenesulfonamide) acetate (group BIS), a treatment which controls P, aeruginosa burn-wound infection in humans. On the 6th day postburn the relative specific activities of all fractions were increased in the order BI greater than BIS greater than B greater than C, as were the concentrations of the globulins; Serum albumin concentration fell, being lowest in BI. Tissue albumin contents, measured by radioimmunoassay, of eviscerated blood-free bodies of rats were (mg/100 g rat wt): C, 207; B, 294; BI, 256. Analyses of individual tissues showed that the difference was due to increased albumin content in the burn-wound area. The tissue albumin was of normal molecular size and was immunologically reactive. We conclude that the prolonged hypoalbuminemia following burn injury is not a consequence of impaired albumin synthesis, but a result of altered compartmentation.

A Priori Prediction of Tissue:Plasma Partition Coefficients of Drugs to Facilitate the Use of Physiologically‐Based Pharmacokinetic Models in Drug Discovery

“…The differences observed between predicted and experimental P t:p values could be explained by the fact that experimental values for each drug were obtained only from one or two studies published in the literature, and/or by the fact that an important mechanism governing P t:p has probably been omitted in specific tissues for particular drugs (see the Regression Analysis section of Results). Furthermore, (i) only a single value of log K vo:w experimentally determined or calculated for a pH of 7.4 and the mean data on tissue composition obtained following a review of the literature, have been used in eqs 11 and 14 for predicting P t:p , (ii) some of the experimental P t:p for non‐fatty tissues (<4.5% lipids) that have been used in the validation exercise may not have been determined at true steady state in the case of lipophilic drugs, and (iii) C m tissue / C m plasma for albumin, globulins and lipoproteins can vary from 0.3 to 1 in mammalian tissues 15–31. Consequently, this contributing factor to the predictions has not been considered in this present study (i.e., only a single value of 0.5 for C m tissue / C m plasma has been used to calculate the term fu p /fu t used in eqs 11 and 14).…”

“…Therefore, the value of fu p /fu t should be similar to the value of C m tissue / C m plasma for drugs binding significantly to the plasma macromolecules (i.e., for drugs with fu p near zero). For albumin, globulins, and lipoproteins, C m tissue / C m plasma ranged from 0.3 to 1 in several tissues of mammals 15–31. The fact that the value of C m tissue / C m plasma has been fixed at 0.5 instead of 0.3 or 1, may have an impact for predicting P t:p (= S t / S p fu p /fu t or F t / F p fu p /fu t ), but only for drugs with low values of fu p , for which fu p /fu t has been estimated equal to C m tissue / C m plasma .…”

“…In this study, it was hypothesized that the reversible macromolecular binding of drugs in plasma and tissues is driven by the main binding macromolecules present in these two matrices, i.e., albumin, globulins and/or lipoproteins (HDL, LDL). The values of C m tissue / C m plasma for each of these macromolecules ranged from 0.3 to 1 in several mammalian tissues 15–31. Therefore, an intermediate value of 0.5 (which is the most often reported value for mammalian tissues) was considered for each macromolecule and tissue.…”

“…The species‐specific parameters refer to (i) the fractional content of wet tissue weight of neutral lipid ( V n ), phospholipid ( V ph ), and water ( V w ) in tissues and plasma, and (ii) the fractional content of wet tissue weight of interstitial space in tissues ( F t ) and the fractional content of plasma in blood ( F p ). The mean data of each of these parameters in rabbits, rats, and mice were obtained following a review of the biomedical literature 9, 15–31, 40, 90–101 . V n , V ph , and V w in tissues and plasma are presented in Table II.…”

Increased albumin plasma efflux contributes to hypoalbuminemia only during early phase of sepsis in rats

“…The increased movement of albumin across the capillary wall can lead to a redistribution of albumin between the intravascular and the extravascular pools. It has been shown that the ratio of extravascular to intravascular albumin increased after injury (2,8). However, the variation of the total albumin pool of the body is unclear.…”