Repeated quantitative measurements of De Novo synthesis of albumin and fibrinogen

Abstract

The possibility of using two different isotopomers, for the incorporation of isotopically labeled amino acids, was explored to enable longitudinal studies of de novo synthesis of two export liver proteins, albumin and fibrinogen. The agreement of the synthesis rates between the two different labels was evaluated along with the reproducibility of repeated experiments using different time intervals. Healthy volunteers were studied in a standardized fed state. Protocol A (n = 10) involved two measurements 48 hours apart. Protocol B (n = 6) involved three measurements at baseline and five hours and then seven days after the initial measurement. De novo synthesis of albumin and fibrinogen by the incorporation of D5-phenylalanine or D8-phenylalanine were measured using the flooding dose technique. Albumin and fibrinogen were isolated from plasma using standard techniques. Fractional and absolute synthesis rates were calculated. Repeated measurements employing the two isotoptomers showed good agreement for albumin fractional synthesis rate after 48 hours (p = 0.92) and after 7 days (p = 0.99), with a coefficient of variation of 5.9% when using the same isotopic label. For fibrinogen, the coefficient of variation for the fractional synthesis rate employing the same isotopic label was 16.6%. Repeated measurements after 48 hours and seven days showed less agreement although there was no statistical difference (P = 0.32 and P = 0.30 respectively). Repeated measurement after five hours showed a statistical significant difference for the fractional synthesis rate of fibrinogen (p = 0.008) but not for albumin (p = 0.12). Repeated measurements of albumin de novo synthesis more than 48 hours apart show acceptable agreement using either one or two different isotopic labels. For fibrinogen the larger intra-individual scatter necessitates larger study groups to detect changes in longitudinal studies. Repeated measurements within 48 hours need to be validated further.

Albumin mass balance and kinetics in liver transplantation

“…c Spearman rank correlation between absolute synthesis rates (ASR) of albumin and fibrinogen, respectively. Red dotted lines denote normal values in healthy volunteers ( b and c ) [ 22 ] …”

“…the fraction of the intravascular pool that is synthesized every day, was calculated as previously described [ 12 ], and the absolute synthesis rate (ASR) was calculated as the product of FSR and the total plasma pool of albumin obtained from plasma volume and P-alb. The principle of determination of fibrinogen FSR and ASR was similar to that of albumin, although blood samples were taken in citrate tubes, but the process of separation of fibrinogen from other plasma proteins was different from that of albumin [ 22 ].…”

Intra‐ and inter‐Individual variability in nerve block duration: A randomized cross‐over trial in the common peroneal nerve of healthy volunteers

“…Therefore, a more likely explanation for the initial decline and subsequent plateau in duration is the upregulation of LA‐binding proteins and increased washout which are both fast‐acting and long‐lasting . This would make the individual profile of protein‐upregulation and washout the reason for the individual duration plateaus and such explain why a blockade with the same dose and LA show different durations of effect in different individuals.…”

Factors affecting perioperative ∆ALB and short term complications in pediatric patients undergoing major gastroenterology surgery

“…An sharp decrease by 33% of serum ALB within 2 days was observed after major abdominal surgery, which occurred earlier than the another acute-phase protein, CRP [2,10]. The transcapillary leakage of albumin could elevated more than 300% in the systemic inflammatory pathogenesis [11,12].…”