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Little information is available on the patterns of changes and significance of plasma alpha-amino-n-butyric acid (ABA, μmol/L) in various conditions, particularly in sepsis. This study has been performed to assess the patterns of correlation among ABA, other amino acids, and other variables in a group of septic patients with various degrees of illness. More than 400 determinations of ABA, other amino acids, and simultaneously collected blood variables were obtained in 17 patients with sepsis. The distribution of ABA was characterized by the clustering of most measurements within the normal range (<41 μmol/L), with the spreading of abnormally increased values up to 151 μmol/L. Abnormal increases in ABA were related directly to alanine, serine, tyrosine, histidine, proline, threonine, glycine, glutamine, cysteine, lysine, cystathionine, leucine, valine, phenylalanine, arginine, and citrulline (r(2) from 0.86 to 0.32) and related inversely to aspartate, taurine, and phosphoethanolamine (r(2) from 0.62 to 0.50) (P < 0.001 for all). Furthermore, increased ABA was correlated with increasing total aminoacidemia, lactate, neutrophil concentration, creatinine, ammonia, osmolarity, glucose, and bilirubin and with decreasing AA Fischer ratio and peripheral O(2) extraction (r(2) from 0.87 to 0.16) (P < 0.001 for all). High ABA was also associated with low cholesterol, taurine, and platelet count, and with high 3-methylhistidine (partly anticipating the increase), high blood urea nitrogen, and pulmonary shunt (P < 0.001 for all). Finally, high ABA was related to the worsening of sepsis-related organ failure assessment score (SOFA score) and of most plasma AA clearances (P < 0.001 for all). Abnormally increased ABA may signal and partly anticipate the transition to an extreme derangement of septic metabolic patterns, characterized by the worsening of protein hypercatabolism with hyperaminoacidemia and by signs of impaired hepatic amino acid metabolism and oxidative metabolism. Increased ABA may represent an additional landmark of transition to extreme illness, compelling the need for the aggressive resolution of sepsis., (Copyright © 2011 Mosby, Inc. All rights reserved.)

This study was performed to obtain a characterization of the changes in plasma transferrin (Tf, g/L) in sepsis. More than four hundred determinations of Tf, and of a large series of simultaneously collected blood and hemodynamic variables, were obtained in 17 patients with post-traumatic sepsis. Tf during sepsis was consistently low (mean +/- SD = 1.46 +/- 0.46) however fluctuated markedly according to changes in metabolic and hemodynamic patterns. Regression analysis showed that decreases in Tf were simultaneously correlated with the plasma lipid pattern (in particular with decreasing cholesterol and increasing triglycerides), with decreases in albumin and peripheral O2 extraction, and with increasing cardiac index (p < 0.001 for all). Decreases in Tf were moderated by increasing the parenteral amino acid dose (p < 0.001). Combinations of these variables in multiple regressions explained nearly 80% of the variability of Tf. There were no similar correlations for other acute phase proteins except ceruloplasmin, which showed opposite changes compared to those of Tf. These results show that within the hypotransferrinemia which characterizes sepsis, Tf may oscillate remaining strongly correlated with changes in metabolic and hemodynamic patterns, which may account for nearly 80% of the variability of Tf.

Background: In sepsis, plasma ceruloplasmin (Cp, mg/L) is known to increase as part of the acute phase response. However, there is poor knowledge of the patterns of increase and correlation with changes in other biochemical variables, and our study has been performed to investigate this aspect., Materials and Methods: A total of 213 simultaneous measurements of Cp and other acute phase proteins, biochemical variables, and amino acids were performed on nine patients with severe sepsis, and processed by regression analysis., Results: Mean Cp was 478 +/- 119 mg/L (median 488, range 242-784). Significant direct correlations between Cp and C-reactive protein, alpha-1-antitrypsin and alpha-2-macroglobulin (P < 0.001 for all) were all simultaneously influenced by the level of alkaline phosphatase, which was an independent determinant of increased Cp (P < 0.001). Cp increased further with decreasing plasma pH and increasing triglyceride, taurine levels, and distance from the onset of sepsis (P < 0.001 for all). The maximum increases in Cp were associated with the presence of cholestasis, increasing triglyceride levels, and metabolic acidosis. With regard to septic liver dysfunction, while signs of cholestasis were mostly reflected in greater increases in Cp, increasing bilirubin in the presence of normal alkaline phosphatase was mostly correlated with abnormal increases in cyst(e)ine, cystathionine, and tyrosine levels., Conclusions: These data characterize the patterns of correlation of Cp within the biochemical abnormalities of sepsis, and may provide new insights into the pathophysiology of septic hepatobiliary dysfunction.

An acute septic inflammatory response with access to the portal circulation was created in a rat model using an intra-abdominal abscess composed of a sterile agar pellet, or one contaminated with 102 Escherichia coli (E. coli) and 109 Bacteriodes fragilis (B. fragilis). After 3 days postimplantation, a well-formed intra-abdominal abscess occurred whose wall showed IL-6 DNA by PCR and IL-6 mRNA by in situ hybridization. Portal venous blood draining into the liver from the intra-abdominal abscess had increased levels of TNF-alpha, IL-1beta, and IL-6 in both sterile and septic groups compared with a control normal animal group. Increased levels of these cytokines were also found in suprahepatic inferior vena caval blood, but were correlated with the higher portal vein levels, suggesting a gradient from abscess wall to portal vein into the systemic circulation via the liver. Liver histology demonstrated sinusoidal congestion centering on the central vein, growing worse with progression from normal in control, to sterile, to septic. Similarly, the degree of intrahepatic myeloperoxidase-positive inflammatory cell infiltration and hepatocellular lipid deposition and apoptosis also increased from control, to sterile, to septic. Gene expression by in situ hybridization demonstrated a significant increase in IL-6 and fibrinogen mRNAs in cells surrounding the central vein in sterile and septic animals, being greatest in animals with sepsis, associated with an increased deposition of collagen in the central vein area, most prominent in the septic liver. The pericentral vein cells with IL-6 and fibrinogen mRNA increases paralleled the increases in cells containing IL-6 and fibrinogen mRNAs in the abscess walls of sterile and septic animals, respectively. The data suggest that an intra-abdominal abscess, especially when contaminated with gram-negative bacteria, induces mRNA-generated cytokine responses in the abscess wall that are related to increased portal venous levels of the inflammatory cytokines TNF-alpha, IL-1beta, and IL-6 perfusing the liver. These, in turn, induce localized production of IL-6 and fibrinogen mRNAs in cells at the central vein area with resultant outflow fibrosis and increased inflammatory cell sequestration within the liver lobular sinuses. This is associated with a generalized inflammatory response and intrahepatic portal sinusoid congestion. There is also increased hepatocellular lipid deposition and apoptosis. Thus, the cytokine production of the abscess wall itself appears to be a major mediator of the septic hepatic response.