cortisol-succinate--sodium-salt and Inflammation

Improvements in asthma diagnosis and management require deeper understanding of the heterogeneity of the complex airway inflammation. We hypothesise that differences in the two major inflammatory phenotypes of asthma; eosinophilic and neutrophilic asthma, will be reflected in the lung protein expression profile of murine asthma models and can be delineated using proteomics of bronchoalveolar lavage (BAL).. BAL from mice challenged with ovalbumin (OVA/OVA) alone (standard model of asthma, here considered eosinophilic) or OVA in combination with endotoxin (OVA/LPS, model of neutrophilic asthma) was analysed using liquid chromatography coupled to high resolution mass spectrometry, and compared with steroid-treated animals and healthy controls. In addition, conventional inflammatory markers were analysed using multiplexed ELISA (Bio-Plex™ assay). Multivariate statistics was performed on integrative proteomic fingerprints using principal component analysis. Proteomic data were complemented with lung mechanics and BAL cell counts.. Several of the analysed proteins displayed significant differences between the controls and either or both of the two models reflecting eosinophilic and neutrophilic asthma. Most of the proteins found with mass spectrometry analysis displayed a considerable increase in neutrophilic asthma compared with the other groups. Conversely, the larger number of the inflammatory markers analysed with Bio-Plex™ analysis were found to be increased in the eosinophilic model. In addition, major inflammation markers were correlated to peripheral airway closure, while commonly used asthma biomarkers only reflect central inflammation.. Our data suggest that the commercial markers we are currently relying on to diagnose asthma subtypes are not giving us comprehensive or specific enough information. The analysed protein profiles allowed to discriminate the two models and may add useful information for characterization of different asthma phenotypes.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Biomarkers; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Eosinophils; Female; Hydrocortisone; Inflammation; Inflammation Mediators; Leukocyte Count; Lipopolysaccharides; Mass Spectrometry; Methacholine Chloride; Mice; Mice, Inbred BALB C; Neutrophils; Ovalbumin; Phenotype; Protein Array Analysis; Proteome; Respiratory Mechanics

To analyse the efficacy and safety of systemic infusion of hydrocortisone hemisuccinate in children admitted to the intensive care unit with severe scorpion envenomation, we assessed the impact on mortality and length of hospital stay.. We conducted a pair-wise, case-control study with 1:1 matching, reviewing records over a 13-year period (1990-2002) for the intensive care unit (ICU) of the Habib Bourguiba University Hospital, Sfax, Tunisia. A total of 184 children were included in the study (92 cases and 92 controls); cases received hydrocortisone hemisuccinate during hospitalization and controls received no steroids. Patients were matched according to age (±2 years), severity factors at admission (pulmonary edema and grades of severity of scorpion envenomation) and scorpion antivenom administration.. Cases and controls did not differ significantly in age (4.9 ± 5.5 years vs 6.2 ± 3.8 years; p > 0.05), mean temperature on admission (37.2 ± 1.2 vs 37.2 ± 1.06; p = 0.99) or presence of systemic inflammatory response syndrome (SIRS) (77 vs 70; p = 0.198). The proportion of patients with pulmonary edema was similar in the two groups (77 vs 71; p > 0.05), and in each group 46 patients (50%) received scorpion antivenom (p > 0.05). The use of mechanical ventilation, ICU length of stay and ICU mortality was not significantly different between the studied groups.. We detected no significant difference between patients receiving steroids and steroid-free patients in terms of mortality and ICU length of stay. The hydrocortisone hemisuccinate regimen described here had a limited effect in critically ill envenomated children and, therefore, we suggest that it should not be recommended.

Topics: Anti-Inflammatory Agents; Antivenins; Bites and Stings; Case-Control Studies; Child; Child, Preschool; Female; Humans; Hydrocortisone; Infant; Inflammation; Length of Stay; Male; Scorpion Venoms

This protocol describes microsphere-based protease assays for use in flow cytometry and high-throughput screening. This platform measures a loss of fluorescence from the surface of a microsphere due to the cleavage of an attached fluorescent protease substrate by a suitable protease enzyme. The assay format can be adapted to any site or protein-specific protease of interest and results can be measured in both real time and as endpoint fluorescence assays on a flow cytometer. Endpoint assays are easily adapted to microplate format for flow cytometry high-throughput analysis and inhibitor screening.

Topics: Animals; Biotinylation; Flow Cytometry; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; High-Throughput Screening Assays; Humans; Inflammation; Kinetics; Microspheres; Peptide Hydrolases; Peptides; Reproducibility of Results; Temperature

Our study investigated the effects of Melilotus officinalis L. extract, containing 0.25% coumarin, on acute inflammation induced with oil of turpentine in male rabbits. The results were compared with those from a group treated with hydrocortisone sodium hemisuccinate and one injected with coumarin before inflammation was induced. The effects were evaluated by measuring serum citrulline, a test of in vitro phagocytosis, total leukocyte count and differential leukocyte count expressed as a percentage. M. officinalis had antiinflammatory effects because it reduced the activation of circulating phagocytes and lowered citrulline production. These properties were similar to those of hydrocortisone sodium hemisuccinate and coumarin. In the bone marrow acute phase response, M. officinalis had an inhibitory action that was lower than that of hydrocortisone sodium hemisuccinate and similar to coumarin.

Topics: Acute-Phase Reaction; Animals; Anti-Inflammatory Agents; Citrulline; Coumarins; Hydrocortisone; Inflammation; Leukocyte Count; Male; Melilotus; Nitric Oxide; Phagocytosis; Phytotherapy; Plant Extracts; Plant Structures; Rabbits; Turpentine

We sought to develop an experimental animal model in order to study the effects of hypothermia on host defences under conditions which were similar to those used for humans. We required a large animal which could tolerate arterial and venous catheters and serial blood sampling without significantly altering its blood volume and blood pressure. The animal should be intubated and ventilated to control blood gases and fluid and electrolyte balance. Finally the model should have anatomic, metabolic and physiologic similarities to humans. We describe an experimental pig model which appears to fulfill these criteria and provide important information relevant to man.

Topics: Animals; Blood Gas Analysis; Cell Movement; Disease Models, Animal; Epinephrine; Hydrocortisone; Inflammation; Leukocyte Count; Neutrophils; Pleurisy; Research Design; Swine