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Pathological abdominal adhesions can cause bowel obstructions. A history of appendectomy (appy) increases patient rehospitalization risk directly related to adhesions. To potentially identify strategies for adhesion treatment, we characterized reactive ascites (rA) collected during appy or adhesiolysis for small bowel obstruction (SBO).This is a non-randomized, prospective observational study recruiting patients with non-perforated appendicitis or SBO from three Level 1 trauma centers in the United States. rA were analyzed via liquid chromatography-mass spectrometry (LC-MS) (n = 31), bead-based quantification cytokines and chemokines (n = 32) and soluble receptors (n = 30), and LC-MS metabolomics (n = 18).LC-MS showed that samples contained albumin, apolipoprotein A1, and transthyretin and that metabolites increased in SBO vs appy rA were biomarkers of oxidative stress. Multi-plex analyses showed levels of 17 cytokines/chemokines and 6 soluble receptors were significantly different in appy vs SBO rA. Top increased proteins in appy compared to SBO rA by 20.14-, 11.53-, and 8.18-fold were granulocyte-colony stimulating factor, C-X-C motif chemokine ligand 10, and interleukin-10, respectively.These data further define pro- and anti-inflammatory mediators and metabolites that may drive formation or perpetuate chronic abdominal adhesions. Future research is to further explore whether attenuation of these factors may decrease pathologic adhesion formation.

Background Commercial solutions of human serum albumin (HSA) are administered to critically ill patients for the treatment of shock, restoration of blood volume, and the acute management of burns. Previously, conflicting results on the effects of HSA administration have been reported varying from a favorable increase in total plasma antioxidant capacity to a higher mortality rate in traumatic brain injury (TBI) patients. These results could be partially explained due to the known heterogeneity of HSA solutions. We report the discovery of S-sulfonated human transthyretin (hTTR) in HSA solutions. Methods Proteomics was performed on commercially available solutions of 5% HSA by LC-MS analysis. The MS charge envelope for hTTR was deconvolved to the uncharged native hTTR parent mass (13,762 Da). The parent mass was then integrated, and relative proportions of the 2 major species of hTTR, native and S-sulfonated hTTR (13,842 Da), were calculated. Results The majority of hTTR found in 5% commercial HSA solutions is in the S-sulfonated form regardless of the age of the HSA solution. S-sulfonation of hTTR at the free cysteine residue in position 10 appears to be the result of a mixed disulfide exchange possibly with S-cysteinylated hTTR or S-cysteinylated HSA. hTTR is a tetramer composed of four identical monomers each containing a reduced cysteine residue in position 10. S-sulfonation of hTTR at this cysteine residue can destabilize the hTTR tetramer, an important step in the formation of TTR-related amyloid fibrils. Conclusions Administration of a commercial HSA solution that already contains S-sulfonated hTTR could potentially contribute to the development of amyloid-related/polyneuropathy in the critically ill.

Within the first few hours of a traumatic brain injury, the activity of extracellular matrix degradative enzymes increases. As a result, the blood brain barrier becomes disrupted as secondary white matter injury increases. Anoikis, a form of apoptosis, results from cells detaching from the extracellular matrix leading to cell death. This “homelessness” (anoikis) of cells hinders recovery progression, exacerbating brain injury while disrupting synaptic plasticity and other central nervous system functions. Here, we discuss the current knowledge of molecular pathways and proteins involved in both the activation and inhibition of anoikis.

Background We previously hypothesized that the N-terminus of human serum albumin (HSA) is altered during ischemic events, thus establishing the foundation for the cobalt–HSA binding assay phenomenon. In this investigation, we attempt to clarify the mode of action of the cobalt–HSA binding assay by direct observations of cobalt binding to HSA. Methods High pressure liquid chromatography coupled to positive electrospray ionization mass spectrometry (HPLC/MS) was used to study cobalt binding to HSA in the plasma of patients with and without evidence of myocardial ischemia. Results Strong binding of cobalt to the N-terminus of HSA occurs at pH > 7.0. No differences in cobalt binding to the N-terminus of HSA are observed in ischemic versus non-ischemic patients' plasma despite differences in the cobalt–HSA binding assay. Plasma free cysteine/cystine ratio appears to play a role in the quantitative response of the cobalt–HSA binding assay. Conclusions The main determinants of the cobalt–HSA binding assay mechanism of action include but are not limited to: the proportion of intact N-terminus of HSA, HSA concentration, plasma cysteine/cystine ratio, plasma pH, and the state of oxidation of cys34 of HSA. Assay improvements that consider and take these factors into account could lead to an improved cobalt–HSA binding assay with greater clinical utility.

Introduction Gaucher's disease (GD) is an inborn error, autosomal recessive lysosomal lipid storage disorder characterized by the lack of the enzyme glucocerebrosidase. We observed some abnormalities in the plasma of a traumatized patient with GD. Case Report We report of a traumatized patient with GD that developed a severe systemic immune response during the course of an extended hospital stay. Plasma paraoxonase (PON) activity was assayed and found to be extremely low possibly due to the existence of GD in this particular patient. Also, a potentially novel post-translational modification (PTM) of albumin was noticed in the patient's plasma that coincided with enzyme replacement therapy (ERT) with Cerezyme®. Conclusions The decreased plasma PON activity measured might be a contributive factor in the development of an accentuated systemic immune response in a traumatized patient with GD. A modified albumin species could serve as a biomarker for ERT in Gaucher patients.

Introduction Hypoalbuminemia is known to occur in critically ill patients and is associated with increased mortality. We observed a potentially novel, partial explanation for the hypoalbuminemia noticed in a severely traumatized patient. Case report We report of a severely, multi-system traumatized patient in whom hypoalbuminemia was present (1–2 g/dl). The plasma albumin (HSA) was analyzed by liquid chromatography/positive electrospray ionization mass spectrometry. A high percentage of a truncated albumin that lost its carboxy terminal amino acid leucine (HSA-L) associated with a 10-fold increase in plasma carboxypeptidase A (CPA) activity (R2 = 0.994) were found. We estimated the half life of this truncated albumin species to be Conclusions The increased CPA activity encountered following a traumatic event and subsequent rapid clearance of the resulting HSA-L from plasma might be a contributing factor to the hypoalbuminemia observed in the critically ill patients.

Introduction Purple urinary bag syndrome (PUBS) is considered to be a benign condition observed in the urinary catheter and bag in some catheterized patients with urinary tract infections. This syndrome is usually reported to occur in alkaline urine. Case report We report of a catheterized patient with PUBS and slightly acidic urine (pH 6–6.5). A novel analysis method was developed using high pressure liquid chromatography and mass spectrometry (HPLC/MS) to detect compounds that are thought to be associated with PUBS. Urine, urinary sediment, and the plastic collection system were assayed and quantitated using these methods. The potential toxicity of one of these compounds, indoxyl sulfate, is discussed. Conclusions The presence of PUBS in a catheterized patient with slightly acidic urine is reported. A novel method for the analysis of chemical components of PUBS and the first direct confirmation of the presence of indigo in the urine sediment and collecting system are described.