Cystic Fibrosis Research - Symptoms, Genetics, Treatment, Information

Cystic Fibrosis Research Today is a free monthly online journal that collates and summarizes the latest research about Cystic Fibrosis, including details on symptoms, genetics, treatment, information.


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Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs.

Stoltz DA, Rokhlina T, Ernst SE, Pezzulo AA, Ostedgaard LS, Karp PH, Samuel MS, Reznikov LR, Rector MV, Gansemer ND, Bouzek DC, Alaiwa MH, Hoegger MJ, Ludwig PS, Taft PJ, Wallen TJ, Wohlford-Lenane C, McMenimen JD, Chen JH, Bogan KL, Adam RJ, Hornick EE, Nelson GA, Hoffman EA, Chang EH, Zabner J, McCray PB, Prather RS, Meyerholz DK, Welsh MJ

Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, USA. michael-welsh@uiowa.edu

Cystic fibrosis (CF) pigs develop disease with features remarkably similar to those in people with CF, including exocrine pancreatic destruction, focal biliary cirrhosis, micro-gallbladder, vas deferens loss, airway disease, and meconium ileus. Whereas meconium ileus occurs in 15% of babies with CF, the penetrance is 100% in newborn CF pigs. We hypothesized that transgenic expression of porcine CF transmembrane conductance regulator (pCFTR) cDNA under control of the intestinal fatty acid-binding protein (iFABP) promoter would alleviate the meconium ileus. We produced 5 CFTR-/-;TgFABP>pCFTR lines. In 3 lines, intestinal expression of CFTR at least partially restored CFTR-mediated anion transport and improved the intestinal phenotype. In contrast, these pigs still had pancreatic destruction, liver disease, and reduced weight gain, and within weeks of birth, they developed sinus and lung disease, the severity of which varied over time. These data indicate that expressing CFTR in intestine without pancreatic or hepatic correction is sufficient to rescue meconium ileus. Comparing CFTR expression in different lines revealed that approximately 20% of wild-type CFTR mRNA largely prevented meconium ileus. This model may be of value for understanding CF pathophysiology and testing new preventions and therapies.

Published 31 May 2013 in J Clin Invest, 123(6): 2685-93.
Full-text of this article is available online (may require subscription).


Articles on Cystic Fibrosis published 19 June 2012:

Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis: the ISIS randomized controlled trial.   JAMA, 307(21): 2269-77.

[Abstract] [Full-text]


Articles on Cystic Fibrosis published 7 June 2012:

Multiple apical plasma membrane constituents are associated with susceptibility to meconium ileus in individuals with cystic fibrosis.   Nat Genet, 44(5): 562-9.

Variants associated with meconium ileus in cystic fibrosis were identified in 3,763 affected individuals by genome-wide association study (GWAS). Five SNPs at two loci near SLC6A14 at Xq23-24 (minimum P = 1.28 × 10(-12) at rs3788766) and SLC26A9 at 1q32.1 (minimum P = 9.88 × 10(-9) at rs4077468) accounted for ~5% of phenotypic variability and were replicated in an independent sample of affected individuals (n = 2,372; P = 0.001 and 0.0001, respectively). By incorporating the knowledge that ... [Abstract] [Full-text]


Articles on Cystic Fibrosis published 2 May 2012:

Ursodeoxycholate modulates bile flow and bile salt pool independently from the cystic fibrosis transmembrane regulator (Cftr) in mice.   Am J Physiol Gastrointest Liver Physiol, 302(9): G1035-42.

Cystic fibrosis liver disease (CFLD) is treated with ursodeoxycholate (UDCA). Our aim was to evaluate, in cystic fibrosis transmembrane regulator knockout (Cftr(-/-)) mice and wild-type controls, whether the supposed therapeutic action of UDCA is mediated via choleretic activity or effects on bile salt metabolism. Cftr(-/-) mice and controls, under general anesthesia, were intravenously infused with tauroursodeoxycholate (TUDCA) in increasing dosage or were fed either standard or UDCA-enriched ... [Abstract] [Full-text]


Articles on Cystic Fibrosis published 27 April 2012:

Vitamin D bioavailability in cystic fibrosis: a cause for concern?   Nutr Rev, 70(5): 280-93.

Despite the inclusion of extra vitamin D in their regimen of fat-soluble vitamin supplementation, cystic fibrosis patients remain chronically depleted of vitamin D. The persistence of suboptimal vitamin D status is often blamed on the maldigestion and malabsorption of fat. However, the mitigated success of recent clinical trials with high-dose vitamin D supplementation suggests that vitamin D bioavailability might be impaired in these patients. Given the growing understanding of the importance ... [Abstract] [Full-text]


Articles on Cystic Fibrosis published 16 April 2012:

Early cystic fibrosis lung disease detected by bronchoalveolar lavage and lung clearance index.   Am J Respir Crit Care Med, 185(8): 862-73.

[Abstract] [Full-text]

Future directions in early cystic fibrosis lung disease research: an NHLBI workshop report.   Am J Respir Crit Care Med, 185(8): 887-92.

Since the 1989 discovery that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), there has been substantial progress toward understanding the molecular basis for CF lung disease, leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation are poorly understood. Universal ... [Abstract] [Full-text]


Articles on Cystic Fibrosis published 12 April 2012:

Decade-long bacterial community dynamics in cystic fibrosis airways.   Proc Natl Acad Sci U S A, 109(15): 5809-14.

The structure and dynamics of bacterial communities in the airways of persons with cystic fibrosis (CF) remain largely unknown. We characterized the bacterial communities in 126 sputum samples representing serial collections spanning 8-9 y from six age-matched male CF patients. Sputum DNA was analyzed by bar-coded pyrosequencing of the V3-V5 hypervariable region of the 16S rRNA gene, defining 662 operational taxonomic units (OTUs) from >633,000 sequences. Bacterial community diversity ... [Abstract] [Full-text]


Articles on Cystic Fibrosis published 11 April 2012:

An update on the screening, diagnosis, management, and treatment of vitamin D deficiency in individuals with cystic fibrosis: evidence-based recommendations from the Cystic Fibrosis Foundation.   J Clin Endocrinol Metab, 97(4): 1082-93.

[Abstract] [Full-text]


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Cystic Fibrosis Research Today Archive:

Volume 1 (2004)
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Volume 7 (2010)
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Volume 9 (2012)
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Volume 10 (2013)
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Cystic Fibrosis Books

Cystic Fibrosis: Nutri-tional and Intestinal Disorders

Cystic Fibrosis: Nutri-tional and Intestinal Disorders