Spatial Mapping of Pyocyanin in Pseudomonas Aeruginosa Bacterial Communities Using Surface Enhanced Raman Scattering.

Appl Spectrosc. 2016 Jun 28;

Authors: Polisetti S, Baig NF, Morales-Soto N, Shrout JD, Bohn PW

Abstract
Surface enhanced Raman spectroscopy (SERS) imaging was used in conjunction with principal component analysis (PCA) for the in situ spatiotemporal mapping of the virulence factor pyocyanin in communities of the pathogenic bacterium Pseudomonas aeruginosa. The combination of SERS imaging and PCA analysis provides a robust method for the characterization of heterogeneous biological systems while circumventing issues associated with interference from sample autofluorescence and low reproducibility of SERS signals. The production of pyocyanin is found to depend both on the growth carbon source and on the specific strain of P. aeruginosa studied. A cystic fibrosis lung isolate strain of P. aeruginosa synthesizes and secretes pyocyanin when grown with glucose and glutamate, while the laboratory strain exhibits detectable production of pyocyanin only when grown with glutamate as the source of carbon. Pyocyanin production in the laboratory strain grown with glucose was below the limit of detection of SERS. In addition, the combination of SERS imaging and PCA can elucidate subtle differences in the molecular composition of biofilms. PCA loading plots from the clinical isolate exhibit features corresponding to vibrational bands of carbohydrates, which represent the mucoid biofilm matrix specific to that isolate, features that are not seen in the PCA loading plots of the laboratory strain.

PMID: 27354400 [PubMed - as supplied by publisher]

Functional Recovery of a Human Neonatal Heart After Severe Myocardial Infarction.

Circ Res. 2016 Jan 22;118(2):216-21

Authors: Haubner BJ, Schneider J, Schweigmann U, Schuetz T, Dichtl W, Velik-Salchner C, Stein JI, Penninger JM

Abstract
RATIONALE: Cardiac remodeling and subsequent heart failure remain critical issues after myocardial infarction despite improved treatment and reperfusion strategies. Recently, cardiac regeneration has been demonstrated in fish and newborn mice after apex resection or cardiac infarctions. Two key issues remain to translate findings in model organisms to future therapies in humans: what is the mechanism and can cardiac regeneration indeed occur in newborn humans?
OBJECTIVE: To assess whether human neonatal hearts can functionally recover after myocardial infarction.
METHODS AND RESULTS: Here, we report the case of a newborn child having a severe myocardial infarction due to coronary artery occlusion. The child developed massive cardiac damage as defined by serum markers for cardiomyocyte cell death, electrocardiograms, echocardiography, and cardiac angiography. Remarkably, within weeks after the initial ischemic insult, we observed functional cardiac recovery, which translated into long-term normal heart function.
CONCLUSIONS: These data indicate that, similar to neonatal rodents, newborn humans might have the intrinsic capacity to repair myocardial damage and completely recover cardiac function.

PMID: 26659640 [PubMed - indexed for MEDLINE]

Impact of Long-Term Tiotropium Bromide Therapy on Annual Lung Function Decline in Adult Patients with Cystic Fibrosis.

PLoS One. 2016;11(6):e0158193

Authors: Brandt C, Thronicke A, Roehmel JF, Krannich A, Staab D, Schwarz C

Abstract
BACKGROUND: Chronic lung disease is the leading cause of death in patients with Cystic Fibrosis (CF) and is often treated with bronchodilators. It is not known whether long-term tiotropium bromide treatment may have a positive impact on lung function.
METHODS: This retrospective cohort study estimated annual lung function decline utilizing longitudinal data for forced expiratory volume in 1 s (FEV1).
RESULTS: A total of 160 adult patients with CF were analyzed. The subjects treated for 24 months with tiotropium bromide had a significantly slower decline of mean annual change of FEV1 (treated: -0.3±4.0%; control: -2.3±5.0%; p = 0.0130). In patients with FEV1 ≥70% predicted, long-term tiotropium bromide treatment was associated with greater improvements in annual lung function decline (FEV1 ≥70% predicted: treated: +0.5±4.7%; control: -4.0±6.3%; p = 0.0132; FEV1 50-69% predicted: treated: -0.5±4.4%; control: -0.8±3.8%; p = 0.7142; FEV1 ≤49% predicted: treated: -0.6±3.4%; control: -2.4±4.8%; p = 0.0898).
CONCLUSION: This study suggests that long-term tiotropium bromide treatment may be associated with reduced annual decline of FEV1 in patients with CF, particularly in adults with a mild degree of severity.

PMID: 27351829 [PubMed - as supplied by publisher]

Bacterial evolution in PCD and CF patients follows the same mutational steps.

Sci Rep. 2016;6:28732

Authors: Sommer LM, Alanin MC, Marvig RL, Nielsen KG, Høiby N, von Buchwald C, Molin S, Johansen HK

Abstract
Infections with Pseudomonas aeruginosa increase morbidity in primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) patients. Both diseases are associated with a defect of the mucociliary clearance; in PCD caused by non-functional cilia, in CF by changed mucus. Whole genome sequencing of P. aeruginosa isolates from CF patients has shown that persistence of clonal lineages in the airways is facilitated by genetic adaptation. It is unknown whether this also applies to P. aeruginosa airway infections in PCD. We compared within-host evolution of P. aeruginosa in PCD and CF patients. P. aeruginosa isolates from 12 PCD patients were whole genome sequenced and phenotypically characterised. Ten out of 12 PCD patients were infected with persisting clone types. We identified convergent evolution in eight genes, which are also important for persistent infections in CF airways: genes related to antibiotic resistance, quorum sensing, motility, type III secretion and mucoidity. We document phenotypic and genotypic parallelism in the evolution of P. aeruginosa across infected patients with different genetic disorders. The parallel changes and convergent adaptation and evolution may be caused by similar selective forces such as the intensive antibiotic treatment and the inflammatory response, which drive the evolutionary processes.

PMID: 27349973 [PubMed - in process]

Treatment of pulmonary exacerbations in cystic fibrosis-could do better?

Paediatr Respir Rev. 2016 Jun 15;

Authors: Smyth A

Abstract
This article describes the nature and significance of pulmonary exacerbations in cystic fibrosis (CF). The effectiveness and safety of current exacerbation treatment are explored. The article concludes with a summary of clinical trials (completed and ongoing) which aim to improve the efficacy and safety of exacerbation treatment.

PMID: 27349725 [PubMed - as supplied by publisher]

Lifestyle treatments in CF-the NHS should not pay.

Paediatr Respir Rev. 2016 Jun 15;

Authors: Hull J

Abstract
Lifestyle treatments can be defined as those which may have in impact on quality of life but do not affect health outcomes. Particular treatment options may be preferred by patients because they are for example, easier to use, take up less time or taste better. The impact on adherence needs to be considered. Treatment options that promote greater adherence to therapy are likely to be more efficacious and so are not, by definition, lifestyle treatments. The NHS is facing unprecedented financial pressure and resources are limited. When lifestyle treatments are more expensive than standard therapy, they should not be funded by the NHS.

PMID: 27349724 [PubMed - as supplied by publisher]

Abnormal activation of calpain and protein kinase Cα promotes a constitutive release of matrix metalloproteinase 9 in peripheral blood mononuclear cells from cystic fibrosis patients.

Arch Biochem Biophys. 2016 Jun 24;

Authors: Averna M, Bavestrello M, Cresta F, Pedrazzi M, De Tullio R, Minicucci L, Sparatore B, Salamino F, Pontremoli S, Melloni E

Abstract
Matrix metalloproteinase 9 (MMP9) is physiologically involved in remodeling the extracellular matrix components but its abnormal release has been observed in several human pathologies. We here report that peripheral blood mononuclear cells (PBMCs), isolated from cystic fibrosis (CF) patients homozygous for F508del-cystic fibrosis transmembrane conductance regulator (CFTR), express constitutively and release at high rate MMP9 due to the alteration in their intracellular Ca(2+) homeostasis. This spontaneous and sustained MMP9 secretion may contribute to the accumulation of this protease in fluids of CF patients. Conversely, in PBMCs isolated from healthy donors, expression and secretion of MMP9 are undetectable but can be evoked, after 12 h of culture, by paracrine stimulation which also promotes an increase in [Ca(2+)]i. We also demonstrate that in both CF and control PBMCs the Ca(2+)-dependent MMP9 secretion is mediated by the concomitant activation of calpain and protein kinase Cα (PKCα), and that MMP9 expression involves extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) phosphorylation. Our results are supported by the fact that either the inhibition of Ca(2+) entry or chelation of [Ca(2+)]i as well as the inhibition of single components of the signaling pathway or the restoration of CFTR activity all promote the reduction of MMP9 secretion.

PMID: 27349634 [PubMed - as supplied by publisher]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2016/06/28

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Clinical chronic pancreatitis.

Curr Opin Gastroenterol. 2016 Jun 22;

Authors: Park WG

Abstract
PURPOSE OF REVIEW: To summarize observations in clinical chronic pancreatitis in the past year.
RECENT FINDINGS: A predisposing genetic mutation was identified in 67% of cases of pediatric chronic pancreatitis. A novel susceptibility gene involving a hybrid allele is associated with idiopathic chronic pancreatitis. ABO blood type B and FUT2 nonsecretor status is associated with asymptomatic hyperlipasemia and chronic pancreatitis. Alcohol consumption impairs cystic fibrosis transmembrane conductance regulator (CFTR) activity leading to decreased bicarbonate secretion and patients with susceptible CFTR mutations can develop clinical pancreatitis. Computed tomography imaging findings in chronic pancreatitis correlate poorly with pain patterns. Endoscopic ultrasound features correlate poorly with fibrosis. Circulating epithelial cells are present in chronic pancreatitis patients but not healthy volunteers. Surgery is superior to endoscopic treatment in providing durable pain relief (>5 years). Repetitive pancreatic duct stent placements and chronic narcotic use are preoperative predictors of poor outcome after total pancreatectomy with islet cell auto transplantation.
SUMMARY: Novel genetic mutations for idiopathic chronic pancreatitis are being identified. Alcohol impairs CFTR activity and may explain a mechanism for pancreatitis. Current imaging modalities correlate poorly with clinical pain presentation and fibrosis in chronic pancreatitis. Novel imaging modalities are needed. As total pancreatectomy with islet cell auto transplantation grows, rigorous outcomes analysis is needed to drive patient selection.

PMID: 27341355 [PubMed - as supplied by publisher]

Animal Models of Cystic Fibrosis Pathology: Phenotypic Parallels and Divergences.

Biomed Res Int. 2016;2016:5258727

Authors: Lavelle GM, White MM, Browne N, McElvaney NG, Reeves EP

Abstract
Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The resultant characteristic ion transport defect results in decreased mucociliary clearance, bacterial colonisation, and chronic neutrophil-dominated inflammation. Much knowledge surrounding the pathophysiology of the disease has been gained through the generation of animal models, despite inherent limitations in each. The failure of certain mouse models to recapitulate the phenotypic manifestations of human disease has initiated the generation of larger animals in which to study CF, including the pig and the ferret. This review will summarise the basic phenotypes of three animal models and describe the contributions of such animal studies to our current understanding of CF.

PMID: 27340661 [PubMed - in process]

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2016/06/24

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

An unusual case of disseminated adenovirus infection in a cystic fibrosis, liver transplant patient.

J Clin Virol. 2016 Jun 13;81:64-67

Authors: Mitchell SL, Kajon AE, Kaplan SL, Kim J, Cárdenas AM

PMID: 27331823 [PubMed - as supplied by publisher]

Inflammation induced by inhaled lipopolysaccharide depends on particle size in healthy volunteers.

Br J Clin Pharmacol. 2016 Jun 22;

Authors: Doyen VA, Pilcer G, Huy Duc Dinh P, Corazza F, Bernard A, Bergmann P, Lefevre N, Amighi K, Michel O

Abstract
AIM: In drug development, lung anti-inflammatory properties of new molecules are currently tested on the inhaled LPS model. The total and regional lung bioavailability of inhaled particles depends significantly on their size. The objective was to compare inflammatory responses in healthy volunteers after the inhalation of lipopolysaccharide (LPS) of varying droplet size.
METHODS: Three nebulizers were characterized by different droplet size distributions [mean mass median aerodynamic diameters: Microcirrus (2.0 µm), MB2 (3.2 µm), and Pari (7.9 µm)]. Participants inhaled three boluses of 20 µg (technetium 99 m-labeled) solution of LPS, randomly delivered by each nebulizer. We measured the lung deposition of the nebulized LPS by gamma-scintigraphy, while blood and sputum biomarkers were evaluated before and after challenges.
RESULTS: MB2 and Pari achieved greater lung deposition than Microcirrus [171.5 (±72.9) and 217.6 (±97.8) counts/pixel, respectively, versus 67.9 (±20.6) counts/pixel; p < 0.01]. MB2 and Pari caused greater blood C-reactive protein and more total cells and neutrophils in sputum compared to Microcirrus (p < 0.05). C-reactive protein level correlated positively with lung deposition (p < 0.01).
CONCLUSIONS: Inhalation of large droplets of LPS featured greater lung deposition and induced a more pronounced systemic and bronchial inflammatory response than small droplets. The systemic inflammatory response correlated with lung deposition. NCT01081392.

PMID: 27331367 [PubMed - as supplied by publisher]

Gastrointestinal Manifestations of Cystic Fibrosis.

Gastroenterol Hepatol (N Y). 2016 Jan;12(1):43-7

Authors: Sabharwal S

Abstract
Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis.

PMID: 27330503 [PubMed]

Diagnosis and Early Life Risk Factors for Bronchiectasis in Cystic Fibrosis: a Review.

Expert Rev Respir Med. 2016 Jun 22;

Authors: Sly PD, Wainwright CE

Abstract
INTRODUCTION: Lung disease in cystic fibrosis begins in early life with neutrophil-dominated inflammation and infection, is progressive and results in structural lung damage characterised by bronchial dilation and bronchiectasis. Preventative strategies must be employed in early life but require a better understanding of how bronchiectasis develops.
AREAS COVERED: In this review we have addressed the diagnosis and early life risk factors for bronchiectasis in young children with cystic fibrosis. A systematic review was not performed and the literature reviewed was known to the authors. Expert commentary: Bronchiectasis represents a process of progressive dilatation and damage of airway walls and is traditionally considered to be irreversible. Diagnosis is primarily by detecting a bronchial:arterial ratio of >1 on chest CT scan. Lung volume has a greater influence on airway diameter than on arterial making control of lung volume during scanning critical. Early life risk factors for the onset and progression bronchiectasis include: severe cystic fibrosis genotype; neutrophilic inflammation with free neutrophil elastase activity in the lung; and pulmonary infection. Bronchiectasis develops in the majority of children before they reach school age despite the best current therapy. To prevent bronchiectasis novel therapies are going to have to be given to infants.

PMID: 27329819 [PubMed - as supplied by publisher]

Paediatric nasal polyps in cystic fibrosis.

BMJ Case Rep. 2016;2016

Authors: Mohd Slim MA, Dick D, Trimble K, McKee G

Abstract
Patients with cystic fibrosis (CF) are at increased risk of nasal polyps. We present the case of a 17-month-old Caucasian patient with CF who presented with hypertelorism causing cycloplegic astigmatism, right-sided mucoid discharge, snoring and noisy breathing. Imaging suggested bilateral mucoceles in the ethmoid sinuses. Intraoperatively, bilateral soft tissue masses were noted, and both posterior choanae were patent. Polypectomy and bilateral mega-antrostomies were performed. Histological examination revealed inflammatory nasal polyposis typical of CF. The role of early functional endoscopic sinus surgery (FESS) in children with CF nasal polyposis remains questionable as the recurrence rate is higher, and no improvement in pulmonary function has been shown. Our case, however, clearly demonstrates the beneficial upper airway symptom relief and normalisation of facial appearance following FESS in a child with this condition.

PMID: 27329094 [PubMed - in process]

13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2016/06/22

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

8 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2016/06/21

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Identification and characterization of sulfated glycoproteins from small cell lung carcinoma cells assisted by management of molecular charges.

Glycoconj J. 2016 Jun 18;

Authors: Toyoda M, Kaji H, Sawaki H, Togayachi A, Angata T, Narimatsu H, Kameyama A

Abstract
Proteins carrying sulfated glycans (i.e., sulfated glycoproteins) are known to be associated with diseases, such as cancer, cystic fibrosis, and osteoarthritis. Sulfated glycoproteins, however, have not been isolated or characterized from complex biological samples due to lack of appropriate tools for their enrichment. Here, we describe a method to identify and characterize sulfated glycoproteins that are involved in chemical modifications to control the molecular charge of the peptides. In this method, acetohydrazidation of carboxyl groups was performed to accentuate the negative charge of the sulfate group, and Girard's T modification of aspartic acid was performed to assist in protein identification by MS tagging. Using this approach, we identified and characterized the sulfated glycoproteins: Golgi membrane protein 1, insulin-like growth factor binding protein-like 1, and amyloid beta precursor-like protein 1 from H2171 cells, a small cell lung carcinoma cell line. These sulfated glycoproteins carry a complex-type N-glycan with a core fucose and 4'-O-sulfated LacdiNAc as the major glycan.

PMID: 27318476 [PubMed - as supplied by publisher]

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2016/06/19

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.