Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma

BACKGROUND: Microbial intestinal colonization in early in life is regarded to play a major role for the maturation of the immune system. Application of non-pathogenic probiotic bacteria during early infancy might protect from allergic disorders but underlying mechanisms have not been analysed so far. OBJECTIVE: The aim of the current study was to investigate the immune effects of oral application of probiotic bacteria on allergen-induced sensitization and development of airway inflammation and airway hyper-reactivity, cardinal features of bronchial asthma. METHODS: Newborn Balb/c mice received orally 10(9) CFU every second day either Lactobacillus rhamnosus GG or Bifidobacterium lactis (Bb-12) starting from birth for consecutive 8 weeks, during systemic sensitization (six intraperitoneal injections, days 29-40) and airway challenge (days 54-56) with ovalbumin. RESULTS: The administration of either Bb-12 or LGG suppressed all aspects of the asthmatic phenotype: airway reactivity, antigen-specific immunoglobulin E production and pulmonary eosinophilia (mean: 137 vs. 17 and 13 cellsx10(3)/mL, respectively). Antigen-specific recall proliferation by spleen cells and T-helper type 2 cytokine production (IL-4, IL-5 and IL-10) by mesenteric lymph node cells also showed significant reduction, while TGF production remained unchanged. Oral LGG administration particularly suppressed allergen-induced proliferative responses and was associated with an increase in numbers of TGF-beta-secreting CD4+/CD3+ T cells in mesenteric lymph nodes (6.5, 16.7%) as well as nearly 2-fold up-regulation of Foxp3-expressing cells in peribronchial lymph nodes. CONCLUSIONS: Neonatal application of probiotic bacteria inhibits subsequent allergic sensitization and airway disease in a murine model of asthma by induction of T regulatory cells associated with increased TGF-beta production.     

Pulmonary sequelae of long-term ventilation of very low birth weight premature infants. Results of a follow-up study of 6-to-9-year-old children

Fifty six children with a birth weight of less than 1500 g and gestational age less than 34 weeks were studied at a mean age of 7.7 years. All had required mechanical ventilation, 36 suffered from hyaline membrane disease, 17 from atelectasis and three from pneumonia. Of these patients 37 developed broncho-pulmonary dysplasia (BPD). The study included skin prick test, measurement of ciliary beat frequency, chest X-ray, whole-body plethysmography and histamine challenge. Eight patients suffered from recurrent pulmonary infections up to the age of 4 years. Eleven children had a positive skin prick test. Three suffered from allergic asthma and six from hay-fever. The family history of atopy in these premature infants was no different from that of the general population. Ciliary beat frequency was normal in all cases (frequency: 11.8 +/- 1.8 Hz). In 34 patients X-rays showed minimal changes (peribronchial thickening n = 6, mild emphysema n = 28). Pulmonary function was normal except for an increase of thoracic gas volume which was correlated to grade of BPD according to Northway. There was a significant correlation between oxygen-score and radiological stage of BPD (r = 0.7). Histamine challenge showed hyperresponsiveness in 53% of the children. Eight patients showed a threshold similar of mild asthma (less than 1000 micrograms histamine per ml). The degree of airway hyperreactivity was correlated to the grade of BPD (r = 0.7; p less than 0.01) and the oxygen-score (r = -0.63; p less than 0.05). The oxygen-score may be considered a predictor of hyperresponsiveness and pulmonary outcome in later childhood.     

A model for sustainable short-term international medical trips.

The health status of many people in developing countries is often dismal compared with the norms in industrialized countries. Increasingly, medical practitioners in the United States and other industrialized countries have become interested in global health issues, an interest that often takes the form of short-term international medical trips. We discuss several ethical issues associated with participation in such trips and use our experiences in developing the Children's Health International Medical Project of Seattle (CHIMPS) to outline and illustrate a set of 7 guiding principles for making these trips. CHIMPS is a resident-run, faculty-supported international medical program founded in 2002 by pediatric residents at the University of Washington in Seattle. Members of CHIMPS work with a rural community in El Salvador to support ongoing public health interventions there and provide sustainable medical care in collaboration with the community and a local nongovernmental organization. The 7 principles developed as a result of this work-mission, collaboration, education, service, teamwork, sustainability, and evaluation-can be used as a model for health practitioners as they develop or select international medical trips. The importance of partnering with the community and working within the existing medical and public health infrastructure is emphasized. Many of the challenges of doing international medical work can be overcome when efforts are guided by a few specific principles, such as those we have outlined.     

Methylation of rat and mouse DNA by the mushroom poison gyromitrin and its metabolite monomethylhydrazine.

Consumption of false morel (Gyromitra esculenta Fr.) has been associated not only with acute poisoning, but also with a carcinogenic risk. The hydrolysis of acetaldehyde-N-methyl-N-formylhydrazone (gyromitrin, the main toxic component of false morel) results in the formation of the methylating agents N-methyl-N-formylhydrazine (MFH) and N-methylhydrazine (MMH) (by further hydrolysis of MFH). This study reports traces of N-7-methylguanine (N7MeGu) in liver DNA from mice and a rat treated with gyromitrin. After repeated administration of MMH, N7MeGu was identified in rat liver DNA. In mice exposed to MMH according to a dosing scheme identical to that reported to induce tumours in this species, O6-methylguanine was present in liver and kidney DNA. The results indicate that a relatively low carcinogenic risk is associated with false morel consumption. The risk may be greater in individuals with a decreased detoxification rate (acetylation) of MFH, in whom larger amounts of MMH are formed from gyromitrin.     

Validated 5' nuclease PCR assay for rapid identification of the genus Brucella

A real-time, genus-specific 5' nuclease PCR assay for amplification of a 322-bp fragment of the per gene was developed for rapid (<2 h) identification of Brucella spp. from agar plates. The assay, including an internal amplification control (116 bp), identified Brucella strains (n = 23) and did not detect non-Brucella strains (n = 174), indicating its usefulness, particularly for laboratories with stringent quality assurance programs.