Induction of cardiovascular pathology in a novel model of low-grade chronic inflammation.

OBJECTIVE: Epidemiological and clinical evidence indicate that inflammatory processes play a pivotal role in a number of conditions associated with aging, including osteoporosis and cardiovascular diseases. The purpose of this study was to evaluate cardiovascular pathology and select inflammatory mediators of interest in a model of low-grade inflammation-induced osteopenia. METHODS: Slow-release pellets were subcutaneously implanted in male rats to deliver 0, 3.3, or 33.3 microg of lipopolysaccharide (LPS)/day for 90 days. Tail blood was collected at 1, 2, and 3 months for differential white cell counts, and at the end of the study, hearts were harvested for histological and immunohistochemical evaluation. RESULTS: The low-grade inflammatory response was characterized by elevated peripheral blood neutrophils and monocytes. Histological examination of heart cross sections revealed increased fibrous tissue, infiltration of lymphocytes, accumulation of mast cells, and roughened intimal borders within the arteries and arterioles, consistent with vascular disease. Inflammatory mediators (cyclooxygenase-2, tumor necrosis factor-alpha, and interleukin-1 beta) were up-regulated, and increased expression of platelet endothelial cell adhesion molecule-1 and receptor activator for NF-kappaB ligand was localized to the microvasculature endothelium. CONCLUSIONS: These findings suggest that inflammation induced by chronic exposure to LPS produces cardiovascular pathology in the smaller intramural arteries and arterioles and support the utility of this model for further mechanistic and therapeutic studies focused on the role of chronic inflammation in cardiovascular disease.

Biomarker identification in human pancreatic cancer sera.

OBJECTIVE: The aim of this study is to identify biomarkers in sera of pancreatic cancer patients using mass spectrometry (MS) approaches. METHODS: Sera from patients diagnosed with pancreatic adenocarcinoma and sera from normal volunteers were subjected to gel electrophoresis to resolve and quantify differences in protein levels. Protein bands that differed quantitatively were digested with trypsin, and peptides were identified by electrospray ionization (ESI) ion-trap tandem MS. Mass spectra were also collected directly from pancreatic cancer sera as well as healthy control sera using ESI-MS. RESULTS: Three large-mass proteins were found to be elevated in pancreatic cancer sera versus normal sera, alpha-2 macroglobulin, ceruloplasmin, and complement 3C. Complement 3C is a major regulator of inflammatory responses. The ESI-MS of human pancreatic cancer sera versus normal sera revealed greater heterogeneity in cancer sera than control sera, especially in the low-mass region. Bootstrapping statistical analysis identified 20 low-mass serum peaks that correlated with control sera and 20 different peaks that correlated with pancreatic cancer sera. CONCLUSIONS: The fact that inflammation-sensitive proteins were identified as increased in pancreatic cancer sera supports the hypothesis that inflammatory-driven processes are involved in pancreatic carcinogenesis. Liquid ESI-MS analyses of sera hold promise for future pancreatic cancer blood tests as well as for understanding mechanisms of pancreatic carcinogenesis. The variability observed between the low-mass regions of normal versus pancreatic cancer spectra may aid in diagnosis and therapy.

A comparison of the Ranson, Glasgow, and APACHE II scoring systems to a multiple organ system score in predicting patient outcome in pancreatitis.

BACKGROUND: Systems for evaluating acute pancreatitis are useful in hospitalized patients. Traditional systems of evaluation are well established but might be outdated. We propose a Multiple Organ System Score (MOSS) containing data that are more consistently collected and which are accurate in predicting patient outcome. METHODS: A retrospective chart review of 49 patients was completed. We determined if the physician obtained all of the variables necessary to calculate Ranson, Glasgow, or APACHE II scores, if these scores were predictive of patient outcome in the form of length of hospital stay (LOS), and if new, more frequently evaluated variables could be used. RESULTS: None of the patients could be assigned complete scores. According to Spearman rank correlation, both Glasgow and MOSS showed correlation with patient outcome when APACHE II and Ranson did not. CONCLUSIONS: Although larger studies should be performed, the MOSS is useful in predicting outcomes of patients with acute pancreatitis.