Flavonone treatment reverses airway inflammation and remodelling in an asthma murine model.

BACKGROUND AND PURPOSE: Asthma is an inflammatory disease that involves airway hyperresponsiveness and remodelling. Flavonoids have been associated to anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment of asthma. Our aim was to evaluate the effects of the sakuranetin treatment in several aspects of experimental asthma model in mice. EXPERIMENTAL APPROACH: Male BALB/c mice received ovalbumin (i.p.) on days 0 and 14, and were challenged with aerolized ovalbumin 1% on days 24, 26 and 28. Ovalbumin-sensitized animals received vehicle (saline and dimethyl sulfoxide, DMSO), sakuranetin (20 mg kg(-1) per mice) or dexamethasone (5 mg kg(-1) per mice) daily beginning from 24th to 29th day. Control group received saline inhalation and nasal drop vehicle. On day 29, we determined the airway hyperresponsiveness, inflammation and remodelling as well as specific IgE antibody. RANTES, IL-5, IL-4, Eotaxin, IL-10, TNF-α, IFN-γ and GMC-SF content in lung homogenate was performed by Bioplex assay, and 8-isoprostane and NF-kB activations were visualized in inflammatory cells by immunohistochemistry. KEY RESULTS: We have demonstrated that sakuranetin treatment attenuated airway hyperresponsiveness, inflammation and remodelling; and these effects could be attributed to Th2 pro-inflammatory cytokines and oxidative stress reduction as well as control of NF-kB activation. CONCLUSIONS AND IMPLICATIONS: These results highlighted the importance of counteracting oxidative stress by flavonoids in this asthma model and suggest sakuranetin as a potential candidate for studies of treatment of asthma.

A case of Goodpasture syndrome positive for anti-GBM antibody and MPO-ANCA complicated by a variety of serious infections.

A 62-year-old female was admitted to our hospital for investigation of acute progressive renal insufficiency and a systemic inflammatory reaction, despite treatment with several antibiotics. Laboratory data revealed severe renal insufficiency and positive titers for the myeloperoxidase anti-neutrophil cytoplasmic and anti-glomerular basement membrane antibodies. The deterioration of her general status did not allow us to perform the renal biopsy. Although corticosteroid therapy, hemodialysis, and plasma exchange were concomitantly initiated, pulmonary hemorrhage occurred several days after admission. Mechanical ventilation support was provided and continuous hemodiafiltration was carried out, following which the respiratory failure improved immediately. However, she developed clinical depression and suicidal behavior under the intensive therapy. Therefore, plasma exchange was discontinued and corticosteroid was tapered as quickly as possible. Four months after admission, platelet transfusion and short-term mechanical ventilation support improved the pulmonary hemorrhage; however, her mental status deteriorated despite psychiatric consultation and treatment with a tranquilizer. Thereafter, severe and serious systemic infection due to various pathogens including Staphylococcus aureus, Cytomegalovirus, Pneumocystis jiroveci, Pseudomonas aeruginosa, and Bacteroides recurred, and she died from systemic invasive aspergillosis (IA). We suspected severe immunosuppression caused by various factors, such as predonisolone administration, chronic renal failure on maintenance hemodialysis, depression, and malnutrition due to chronic inflammation and granulocytopenia as a side effect of ganciclovir. When treating rapidly progressive glomerulonephritis, immunosuppressive status should be carefully monitored regarding not only the dosage of therapeutic regimen but also the mental health status and nutrition of the patient.

Caecal fermentation and energy accumulation in the rat fed on indigestible oligosaccharides.

The energetic contribution from, and effects on the gastrointestinal tract of, indigestible oligosaccharides in growing rats were compared with those of sucrose (S). S and two types of oligosaccharides, fructo-oligosaccharide (Fru) and 6'-galacto-oligosaccharide (Gal) were added to a basal diet at a level of 100 g/kg. The basal diet was given either ad libitum (group B) or at a level approximately 90% of the ad libitum intakes of the Fru and Gal groups (group BR). During a 50 d feeding period, feed intake, digestibilities of nutrients, and digesta retention times using liquid (Co-EDTA) and particulate (Cr-cell-wall constituents) markers were measured. The carcass and the contents of the stomach and caecum were sampled on the last day of the experimental period. There was no significant difference in feed intake between groups other than BR. Addition of Fru and Gal to the basal diet resulted in increased crude ash digestibility and decreased crude protein and fat digestibilities. Mean retention times of digesta markers were increased by addition of Fru and Gal to the diet, and this was associated with enlargement of the caecum. Concentrations and amounts of total organic acids in the caecum were higher in groups Fru and Gal than the other groups. The amount of energy accumulated in the carcass of rats in the Gal group was significantly (P < 0.05) lower than that of rats fed on S but not Fru. Contributions to energy accumulation tended to be different between Fru and Gal; these were associated with differences in composition of caecal organic acids and of fatty acids in body fat.