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1 2 3 4 5 6 7 8 9 10 Several hypotheses have been - - PDF document
1 2 3 4 5 6 7 8 9 10 Several hypotheses have been - - PDF document
1 2 3 4 5 6 7 8 9 10 Several hypotheses have been proposed for the mechanism of CFRD pathogenesis Pancreatic destruction leads to loss if islet cells, fibrosis, and amyloid deposits in islets 1 Defective CFTR activity led to
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- Several hypotheses have been proposed for the mechanism of CFRD
pathogenesis – Pancreatic destruction leads to loss if islet cells, fibrosis, and amyloid deposits in islets1 – Defective CFTR activity led to insufficient depolarization and Ca2+ mobilization in response to glucose in cultured β-cells2 – β-cells synthesize large amounts of protein. Chronic accumulation of misfolded CFTR may overwhelm the β-cell proteolytic degradation pathways leading to sustained endoplasmic reticulum stress responses (unfolded protein response, endoplasmic reticulum-associated protein degradation) and β-cell apoptosis3 – A chronic inflammatory state produced by oxidative stress, ROS production,4 elevated pro-inflammatory cytokines,1 defective fat-soluble antioxidant absorption, and possibly vitamin D deficiency contribute to β- cell destruction and dysfunction and insulin resistance1,4 – Insulin sensitivity is normal in patients with CF in most studies,1,5 and in studies showing reduced insulin sensitivity, issues of study populations, methods, and interpretation may be factors5 – Insulin resistance in CF may develop because of abnormal localization of the GLUT-4 glucose transporter and/or elevated tumor necrosis factor alpha (TNF-α) levels6 References 1. Barrio R. Eur J Endocrinol. 2015;172(4):R131-R141. 2. Guo JH et al. Nat Commun. 2014;5:4420. 3. Ali BR. Med Hypotheses. 2009;72(1):55-57. 4. Galli F et al. Biochimica et Biophysica Acta. 2012;1822(5):690-713. 5. Mohan K et al. Diabet Med. 2009;26(6):582-588. 6. Hardin DS et al. Am J Physiol Endocrinol Metab. 2001;281(5):E1022-E1028.
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- Normal: Lumen of the pancreatic duct with balanced fluid volume and
pH1
- CF: Pancreatic ducts are obstructed with viscous secretions, leading
to inability to secrete digestive enzymes into the gut2,3 References
- 1. Pandol SJ. The Exocrine Pancreas. San Rafael (CA): Morgan &
Claypool Life Sciences; 2010.
- 2. Wilschanski M et al. Gut. 2007;56(8):1153-1163.
- 3. Derichs N. Eur Respir Rev. 2013;22(127):58-65.
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- PAP is proposed as a less costly alternative to the DNA testing or IRT
retesting after the initial elevated IRT test results in newborns1,2
- Blood from neonatal samples (pinpricks/bloodspots) are analyzed
using ELISA method2
- According to one proposed screening strategy (France), all newborns
are tested for IRT. Newborns with IRT >50 ng/mL are tested for PAP. Those with PAP >1.8 ng/mL and those with PAP >1.0 ng/mL and IRT > 100 ng/mL are recalled for sweat testing2 References
- 1. Sarles J et al. Arch Dis Child Fetal Neonatal Ed. 1999;80(2):F118-
F122.
- 2. Sarles J et al. J Pediatr. 2005;147(3):302-305.
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- Wireless motility capsule system
– Measures pH and transit time – Use of pH capsule devise is limited in young children and infants due to its size Reference Bodewes FA et al. J Cyst Fibros. 2015;14(2):169-177. 42
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