Inflammation has classically been defined histopathologically, especially by the presence of immune cell infiltrates. However, more recent studies suggest a role for "low-grade" inflammation in a variety of disorders ranging from metabolic syndrome to cancer, which is defined by modest elevations in pro-inflammatory gene expression. Consequently, there is a need for cost-effective, non-invasive biomarkers that, ideally, would have the sensitivity to detect low-grade inflammation and have a dynamic range broad enough to reflect classic robust intestinal inflammation. Herein, we report that, for assessment of intestinal inflammation, fecal lipocalin 2 (Lcn-2), measured by ELISA, serves this purpose. Specifically, using a well-characterized mouse model of DSS colitis, we observed that fecal Lcn-2 and intestinal expression of pro-inflammatory cytokines (IL-1β, CXCL1, TNFα) are modestly but significantly induced by very low concentrations of DSS (0.25 and 0.5%), and become markedly elevated at higher concentrations of DSS (1.0 and 4.0%). As expected, careful histopathologic analysis noted only modest immune infiltrates at low DSS concentration and robust colitis at higher DSS concentrations. In accordance, increased levels of the neutrophil product myeloperoxidase (MPO) was only detected in mice given 1.0 and 4.0% DSS. In addition, fecal Lcn-2 marks the severity of spontaneous colitis development in IL-10 deficient mice. Unlike histopathology, MPO, and q-RT-PCR, the assay of fecal Lcn-2 requires only a stool sample, permits measurement over time, and can detect inflammation as early as 1 day following DSS administration. Thus, assay of fecal Lcn-2 by ELISA can function as a non-invasive, sensitive, dynamic, stable and cost-effective means to monitor intestinal inflammation in mice.
Abstract. From July to December 1998, a hospital-and health center-based surveillance system for dengue was established at selected sites in Nicaragua to better define the epidemiology of this disease. Demographic and clinical information as well as clinical laboratory results were obtained, and virus isolation, reverse transcriptase-polymerase chain reaction, and serologic assays were performed. World Health Organization criteria were used to classify disease severity; however, a number of patients presented with signs of shock in the absence of thrombocytopenia or hemoconcentration. Therefore, a new category was designated as ''dengue with signs associated with shock'' (DSAS). Of 1,027 patients enrolled in the study, 614 (60%) were laboratory-confirmed as positive cases; of these, 268 (44%) were classified as dengue fever (DF); 267 (43%) as DF with hemorrhagic manifestations (DFHem); 40 (7%) as dengue hemorrhagic fever (DHF); 20 (3%) as dengue shock syndrome (DSS); and 17 (3%) as DSAS. Interestingly, secondary infection was not significantly correlated with DHF/DSS, in contrast to previous studies in Southeast Asia. DEN-3 was responsible for the majority of cases, with a minority due to DEN-2; both serotypes contributed to severe disease. As evidenced by the analysis of this epidemic, the epidemiology of dengue can differ according to geographic region and viral serotype.
Background: Coagulopathies detected in horses with gastrointestinal problems seem to be associated with poor outcome. Plasma D-Dimer concentration is a sensitive test for assessing coagulopathies.Hypothesis: Plasma D-Dimer concentration tested on admission is related to diagnosis and outcome in horses with colic. Animals: Four hundred and ninety three horses referred for evaluation of abdominal pain. Methods: Prospective observational clinical study. Horses were grouped according to diagnosis (medical and surgical intestinal obstructions, ischemic disorders with and without intestinal resection, enteritis, peritonitis), outcome (survivors, nonsurvivors), and number of coagulopathies (normal profile, 1 or 2 coagulopathies, subclinical disseminated intravascular coagulation [DIC]). Blood samples were collected on admission and plasma D-Dimer concentration, clotting times (PT and aPTT), and antithrombin activity were determined. Positive likelihood ratios (LR1) were calculated for evaluation of D-Dimer cut-off values, which were later tested in a logistic regression model.Results: Horses with enteritis or peritonitis had significantly (P o .001) higher plasma D-Dimer concentrations and more severe coagulopathies on admission than horses with other diagnoses. Nonsurvivors also had significantly (P o .001) higher plasma D-Dimer concentrations at presentation than did survivors, and those horses with subclinical DIC on presentation had an odds ratio (OR) 8.6 (95% confidence interval [CI], 3.3-22.5, P o .001) for nonsurvival. Finally, D-Dimer concentrations 44,000 ng/mL had a LR1 of 5.9 and an OR 8.8 (95% CI, 4.5-17.1, P o .001) for nonsurvival.Conclusion and Clinical Importance: Plasma D-Dimer concentration measured on admission can be used to facilitate diagnosis and outcome prediction in horses with colic. A potential cut-off value for nonsurvival was found at approximately 4,000 ng/mL.
Peritoneal D-dimer concentration is markedly higher in severe GI disorders, and it can be used to assess peritoneal fibrinolytic activity in horses with colic.
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