Neonatal supplementation of processed supernatant from Lactobacillus rhamnosus GG improves allergic airway inflammation in mice later in life.

BACKGROUND: Oral supplementation with probiotic bacteria can protect against the development of allergic and inflammatory diseases. OBJECTIVE: The aim of this study was to investigate potential immunomodulatory and allergy-protective effects of processed Lactobacillus rhamnosus GG (LGG)-derived supernatants early in life in neonatal mice. METHODS: In vitro, RAW264.7 mouse macrophages were stimulated with viable LGG, LGG-derived supernatants, prepared from different growth phases, and different size fractions thereof, and pro- and anti-inflammatory cytokine production was analysed. Supernatant fractions were also treated with protease, DNAse or carbohydrate-digesting enzymes to define the nature of immunomodulatory components. In vivo, neonatal Balb/c mice were orally supplemented with differentially processed LGG supernatants. Starting at 4 weeks of age, a protocol of ovalbumin-induced acute allergic airway inflammation was applied and protective effects of processed LGG supernatants were assessed. RESULTS: Incubation of RAW264.7 cells with LGG-derived supernatants significantly increased TNFα and IL-10 production. These effects were not restricted to a particular molecular size fraction. Treatment with protease, but not with DNAse or carbohydrate-digesting enzymes, completely abolished the immunomodulatory activities. Incubation of TLR/NOD-transfected cells with LGG-derived supernatants revealed that recognition and signalling of bioactive components is mediated by TLR2 and NOD2. In vivo supplementation of newborn mice with processed LGG-derived supernatants resulted in pronounced protective effects on the allergic inflammatory response as reflected by reduced eosinophil numbers, modified T helper cell cytokine production, significantly less lung inflammation and reduced goblet cell numbers in comparison with sham-treated controls. CONCLUSION: LGG-derived supernatants exert immunomodulatory activities, and neonatal administration of specifically processed supernatants may provide an alternative to viable probiotics in reducing allergic inflammatory responses.

Suppression of adrenomedullin contributes to vascular leakage and altered epithelial repair during asthma.

BACKGROUND: The anti-inflammatory peptide, adrenomedullin (AM), and its cognate receptor are expressed in lung tissue, but its pathophysiological significance in airway inflammation is unknown. OBJECTIVES: This study investigated whether allergen-induced airway inflammation involves an impaired local AM response. METHODS: Airway AM expression was measured in acute and chronically sensitized mice following allergen inhalation and in airway epithelial cells of asthmatic and nonasthmatic patients. The effects of AM on experimental allergen-induced airway inflammation and of AM on lung epithelial repair in vitro were investigated. RESULTS: Adrenomedullin mRNA levels were significantly (P < 0.05) reduced in acute ovalbumin (OVA)-sensitized mice after OVA challenge, by over 60% at 24 h and for up to 6 days. Similarly, reduced AM expression was observed in two models of chronic allergen-induced inflammation, OVA- and house dust mite-sensitized mice. The reduced AM expression was restricted to airway epithelial and endothelial cells, while AM expression in alveolar macrophages was unaltered. Intranasal AM completely attenuated the OVA-induced airway hyperresponsiveness and mucosal plasma leakage but had no effect on inflammatory cells or cytokines. The effects of inhaled AM were reversed by pre-inhalation of the putative AM receptor antagonist, AM ((22-52)) . AM mRNA levels were significantly (P < 0.05) lower in human asthmatic airway epithelial samples than in nonasthmatic controls. In vitro, AM dose-dependently (10(-11) -10(-7) M) accelerated experimental wound healing in human and mouse lung epithelial cell monolayers and stimulated epithelial cell migration. CONCLUSION: Adrenomedullin suppression in T(H) 2-related inflammation is of pathophysiological significance and represents loss of a factor that maintains tissue integrity during inflammation.

Benign multicystic peritoneal mesothelioma (BMPM) presenting with ambiguous symptoms: A rare case report.

INTRODUCTION: Benign multicystic peritoneal mesothelioma (BMPM) represents a very rare clinical entity, with only 130 registered cases in the medical literature, therefore it is usually overlooked from the list of differential diagnoses. The treatment consists of surgery and other authors suggest complementing it with hyperthermic intraperitoneal chemotherapy. PRESENTATION OF CASE: A 25-year-old multiparous female experienced periodic abdominal discomfort for two weeks. She developed constipation, urinary urgency, and irregular menstruation. Family history was remarkable for endometrial and breast cancer. Abdominal examination revealed a palpable mass. Abdominal ultrasound and computed tomography scan identified the multicystic appearance of the mass. The diagnosis was unclear, therefore exploratory laparotomy was performed, which revealed multiple grape-like clusters of cysts that were excised immediately. BMPM was diagnosed based on the pathology report. Eventually, the follow-up did not reveal any recurrence. DISCUSSION: Mesothelial tumors include three pathological entities, including Benign multicystic peritoneal mesothelioma (BMPM). BMPM is an uncommon neoplasm and has a high recurrence rate after surgery. BMPM consists of clear cysts that take the shape of a grape-like cluster. Clinically, BMPM resembles a tangible abdominal mass and it is challenging to be diagnosed, due to its numerous differential diagnoses. CONCLUSION: The definitive diagnosis of intraperitoneal cystic masses is usually challenging. Therefore, BMPM -although very rare- should always be thought of when dealing with an intraperitoneal cystic mass, especially in women in the reproductive years. In our case cytoreductive surgery solely was sufficient to achieve a disease free follow up, however, further studies regarding treatment and follow-up are required.