The Prognosis of Cystic Fibrosis - A Clinician\u27s Perspective

Living healthy is all one wants, but the genetics behind creation of every human is different. As a curse or human agony, some are born with congenital defects in their menu of the genome. Just one has to live with that! The complexity of cystic fibrosis condition, which is rather a slow-killer, affects various organ systems of the human body complicating further with secondary infections. That's what makes the disease so puzzling for which scientists around the world are trying to understand better and to find a cure. Though they narrowed down to a single target gene, the tentacles of the disease reach many unknown corners of the human body. Decades of scientific research in the field of chronic illnesses like this one surely increased the level of life expectancy. This book is the compilation of interesting chapters contributed by eminent interdisciplinary scientists around the world trying to make the life of cystic fibrosis patients better

The objective assessment of cough frequency: accuracy of the LR102 device

BACKGROUND: The measurement of cough frequency is problematic and most often based on subjective assessment. The aim of the study was to assess the accuracy of the automatic identification of cough episodes by LR102, a cough frequency meter based on electromyography and audio sensors. METHODS: Ten adult patients complaining of cough were recruited in primary care and hospital settings. Participants were asked to wear LR102 for 4 consecutive hours during which they were also filmed. RESULTS: Measures of cough frequency by LR102 and manual counting were closely correlated (r = 0.87 for number of cough episodes per hour; r = 0.89 for number of single coughs per hour) but LR102 overestimated cough frequency. Bland-Altman plots indicate that differences between the two measurements were not influenced by cough frequency. CONCLUSIONS: LR102 offers a useful estimate of cough frequency in adults in their own environment, while significantly reducing the time required for analysi

Use of molecular dynamics simulations to study the interactions between barley allelochemicals and plant plasma membrane

Gramine and hordenine, two alkaloids produced by barley, were shown to inhibit the growth of a common weed (Matricaria recutita L.). This feature could be useful in order to reach a more sustainable weeds management. In vitro experiments have proven that both molecules do interact with lipid bilayers (made of a phosphatidylglycerol (PG) lipid) mimicking plant plasma membranes and are able to modify some of their properties. Moreover, gramine was shown to be more effective than hordenine in both inhibiting weeds growth and altering lipid bilayers properties, suggesting that interactions with membranes could be linked to their mode of action. Molecular dynamics (MD) simulations are carried out in order to get an insight into the molecular mechanisms that underlie these interactions with model membranes and to discriminate between gramine behavior and hordenine behavior

Azithromycin fails to reduce increased expression of neutrophil-related cytokines in primary-cultured epithelial cells from cystic fibrosis mice

AbstractBackgroundBeneficial effects of azithromycin in cystic fibrosis (CF) have been reported, however, its mechanism of action remains unclear. The present study aimed at investigating the effect of azithromycin on CF airway epithelial cells.MethodsPrimary cultures of purified tracheal epithelial cells from F508del and normal homozygous mice were established. Responses to lipopolysaccharide from Pseudomonas aeruginosa (LPS, 0.1 µg/ml) on mRNA expression of neutrophil-related chemokines, pro- and anti-inflammatory cytokines were investigated in the presence or the absence of azithromycin (1 µg/ml).ResultsCF airway epithelial cells showed upregulation of MIP-2 and KC responses to LPS, and azithromycin failed to downregulate these responses. In contrast, in CF cells, azithromycin increased KC and TNF-α expression under non-stimulated and LPS-stimulated conditions, respectively. In non-CF cells, the macrolide potentiated the LPS response on MIP-2 and on IL-10.ConclusionsAirway epithelial cells contribute to the dysregulated immune processes in CF. Azithromycin rather stimulates cytokine expression in CF airway epithelial cells

Dysregulated Proinflammatory and Fibrogenic Phenotype of Fibroblasts in Cystic Fibrosis

Morbi-mortality in cystic fibrosis (CF) is mainly related to chronic lung infection and inflammation, uncontrolled tissue rearrangements and fibrosis, and yet the underlying mechanisms remain largely unknown. We evaluated inflammatory and fibrosis responses to bleomycin in F508del homozygous and wild-type mice, and phenotype of fibroblasts explanted from mouse lungs and skin. The effect of vardenafil, a cGMP-specific phosphodiesterase type 5 inhibitor, was tested in vivo and in culture. Responses of proinflammatory and fibrotic markers to bleomycin were enhanced in lungs and skin of CF mice and were prevented by treatment with vardenafil. Purified lung and skin fibroblasts from CF mice proliferated and differentiated into myofibroblasts more prominently and displayed higher sensitivity to growth factors than those recovered from wild-type littermates. Under inflammatory stimulation, mRNA and protein expression of proinflammatory mediators were higher in CF than in wild-type fibroblasts, in which CFTR expression reached similar levels to those observed in other non-epithelial cells, such as macrophages. Increased proinflammatory responses in CF fibroblasts were reduced by half with submicromolar concentrations of vardenafil. Proinflammatory and fibrogenic functions of fibroblasts are upregulated in CF and are reduced by vardenafil. This study provides compelling new support for targeting cGMP signaling pathway in CF pharmacotherapy

Comparison of culture and qPCR for the detection of Pseudomonas aeruginosa in not chronically infected cystic fibrosis patients

Pseudomonas aeruginosa is the major respiratory pathogen causing severe lung infections among CF patients, leading to high morbidity and mortality. Once infection is established, early antibiotic treatment is able to postpone the transition to chronic lung infection. In order to optimize the early detection, we compared the sensitivity of microbiological culture and quantitative PCR (qPCR) for the detection of P. aeruginosa in respiratory samples of not chronically infected CF patients.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Traitement de la tuberculose pulmonaire chez l'enfant : ce qui a changé

The therapy of tuberculosis has undergone major changes in the past 10 years, short course regimens emerging as recommended standard treatment. Historically, guidelines for treating tuberculosis in children have been extrapolated from studies in adults. However childhood tuberculosis differ from adult tuberculosis in several ways that may greatly affect the treatment. These differences include: a) smaller bacterial population (less contagiosity, less secondary resistance, less yielding of culture); b) propensity for extrapulmonary disease; c) differences in pharmacokinetics of antitiberculosis drugs. The basic principles that underlie the treatment of pulmonary tuberculosis are briefly discussed as well as current options for therapy in children

La toux persistante chez l’enfant

Une toux qui persiste plus de trois semaines chez l'enfant est une plainte commune mais souvent inquiétante, pour les parents comme pour le médecin. Une anamnèse détaillée reste l'élément-clef de la démarche qui permettra d’approcher un diagnostic différentiel varié et de sélectionner au mieux d’éventuels examens complémentaires. On ne peut oublier que la toux constitue un important mécanisme de défense du système respiratoire. Chaque fois que possible, le traitement sera donc étiologique. Les antitussifs ont fort peu d’indications et même dans un contexte aigu, leur efficacité chez l’enfant est mal documentée.The presence of a cough lasting longer than three weeks in a child is a common source of concern for both parents and physician. Anamnesis remains an essential tool for a specific diagnosis and an appropriate use of laboratory investigations. Therapy should be directed to the underlying cause. Cough suppressants should usually be avoided, because the symptom is also an important protective mechanism. In addition, their efficacy has been poorly studied in children