Effects of 17beta-estradiol and flutamide on inflammatory response and distant organ damage following trauma-hemorrhage in metestrus females

We hypothesized that administration of androgen receptors antagonist flutamide following trauma-hemorrhage (T-H) in metestrus females will maintain immune function and reduce remote organ damage under those conditions. Female B57BL/J6 mice (metestrus state, 8-12 weeks old) underwent laparotomy and hemorrhagic shock (35.0+/-5.0 mmHg for 90 min) and then received 17beta-estradiol (E2; 50 microg/25 g), flutamide (625 microg/25 g), or E2 + flutamide. Four hours after resuscitation, plasma cytokine and chemokine (TNF-alpha, IL-6, IL-10, IFN-gamma, and MCP-1) concentrations and their release in vitro by hepatic and pulmonary tissue macrophages (M Phi) were determined by flow cytometry. Organ damage was assessed by edema formation (wet-to-dry weight ratio) and neutrophil infiltration [myeloperoxidase (MPO) activity]. Administration of E2, flutamide, or E2 + flutamide following T-H resulted in a significant decrease in systemic TNF-alpha, IL-6, and MCP-1 concentrations under those conditions. This was accompanied by significantly decreased in vitro TNF-alpha release by Kupffer cells after administration of E2, flutamide, or E2 + flutamide. The in vitro release of proinflammatory cytokines by alveolar M Phi, however, was reduced significantly only by the addition of E2 or E2 + flutamide but not by the addition of flutamide. A significant decrease in pulmonary and hepatic edema formation as well as neutrophil infiltration in the lung was observed after E2, flutamide and E2 + flutamide administration. In contrast, hepatic neutrophil infiltration was only significantly reduced following E2 and E2 + flutamide administration. Thus, although flutamide does not produce synergistic, salutary effects with E2, its administration in females following T-H also produces salutary effects on the immune and organ function, similar to E2 administration under those conditions.     

Applications for T-cell epitope queries and tools in the Immune Epitope Database and Analysis Resource

The Immune Epitope Database and Analysis Resource (IEDB, http://www.iedb.org) hosts a continuously growing set of immune epitope data curated from the literature, as well as data submitted directly by experimental scientists. In addition, the IEDB hosts a collection of prediction tools for both MHC class I and II restricted T-cell epitopes that are regularly updated. In this review, we provide an overview of T-cell epitope data and prediction tools provided by the IEDB. We then illustrate effective use of these resources to support experimental studies. We focus on two applications, namely identification of conserved epitopes in novel strains of a previously studied pathogen, and prediction of novel T-cell epitopes to facilitate vaccine design. We address common questions and concerns faced by users, and identify patterns of usage that have proven successful.     

Influence of prehospital volume replacement on outcome in polytraumatized children

Introduction

Severe bleeding after trauma frequently results in poor outcomes in children. Prehospital fluid replacement therapy is regarded as an important primary treatment option. Our study aimed, through a retrospective analysis of matched pairs, to assess the influence of prehospital fluid replacement therapy on the post-traumatic course of severely injured children.

Methods

The data for 67,782 patients from the TraumaRegister DGU^® of the German Trauma Society were analyzed. The following inclusion criteria were applied: injury severity score ≥16 points, primary admission, age 1 to 15 years old, systolic blood pressure ≥20 mmHg at the accident site and transfusion of at least one unit of packed red blood cells (pRBC) in the emergency trauma room prior to intensive care admission. As volume replacement therapy depends on age and body weight, especially in children, three subgroups were formed according to the mean value of the administered prehospital volume. The children were matched and enrolled into two groups according to the following criteria: intubation at the accident site (yes/no), Abbreviated Injury Scale (four body regions), accident year, systolic blood pressure and age group.

Results

A total of 31 patients in each group met the inclusion criteria. An increase in volume replacement was associated with an elevated need for a transfusion (≥10 pRBC: low volume, 9.7%; high volume, 25.8%; P = 0.18) and a reduction in the ability to coagulate (prothrombin time ratio: low volume, 58.7%; high volume, 55.6%; P = 0.23; prothrombin time: low volume, 42.2 seconds; high volume, 50.1 seconds; P = 0.38). With increasing volume, the mortality (low volume, 19.4%; high volume, 25.8%; P = 0.75) and multiple organ failure rates (group 1, 36.7%; group 2, 41.4%; P = 0.79) increased. With increased volume, the rescue time also increased (low volume, 62 minutes; high volume, 71.5 minutes; P = 0.21).

Conclusion

For the first time, a tendency was shown that excessive prehospital fluid replacement in children leads to a worse clinical course with higher mortality and that excessive fluid replacement has a negative influence on the ability to coagulate.     

Ab and T cell epitopes of influenza A virus, knowledge and opportunities

The Immune Epitope Database and Analysis Resources (IEDB) (www.immuneepitope.org) was recently developed to capture epitope related data. IEDB also hosts various bioinformatics tools that can be used to identify novel epitopes as well as to analyze and visualize existing epitope data. Herein, a comprehensive analysis was undertaken (i) to compile and inventory existing knowledge regarding influenza A epitopes and (ii) to determine possible cross-reactivities of identified epitopes among avian H5N1 and human influenza strains. At present, IEDB contains >600 different epitopes derived from 58 different strains and 10 influenza A proteins. By using the IEDB analysis resources, conservancy analyses were performed, and several conserved and possibly cross-reactive epitopes were identified. Significant gaps in the current knowledge were also revealed, including paucity of Ab epitopes in comparison with T cell epitopes, limited number of epitopes reported for avian influenza strains/subtypes, and limited number of epitopes reported from proteins other than hemagglutinin and nucleoprotein. This analysis provides a resource for researchers to access existing influenza epitope data. At the same time, the analysis illustrates gaps in our collective knowledge that should inspire directions for further study of immunity against the influenza A virus.