scholarly journals Cystic fibrosis growth retardation is not correlated with loss of Cftr in the intestinal epithelium

2011 ◽  
Vol 301 (3) ◽  
pp. G528-G536 ◽  
Author(s):  
Craig A. Hodges ◽  
Brian R. Grady ◽  
Kirtishri Mishra ◽  
Calvin U. Cotton ◽  
Mitchell L. Drumm
Keyword(s):  
Cystic Fibrosis ◽  
Intestinal Obstruction ◽  
Mouse Models ◽  
Intestinal Epithelium ◽  
Growth Retardation ◽  
Short Circuit ◽  
Pancreatic Insufficiency ◽  
Exocrine Pancreatic Insufficiency ◽  
Cell Hyperplasia ◽  
Enzyme Replacement

Maldigestion due to exocrine pancreatic insufficiency leads to intestinal malabsorption and consequent malnutrition, a mechanism proposed to cause growth retardation associated with cystic fibrosis (CF). However, although enzyme replacement therapy combined with increased caloric intake improves weight gain, the effect on stature is not significant, suggesting that growth retardation has a more complex etiology. Mouse models of CF support this, since these animals do not experience exocrine pancreatic insufficiency yet are growth impaired. Cftr absence from the intestinal epithelium has been suggested as a primary source of growth retardation in CF mice, a concept we directly tested by generating mouse models with Cftr selectively inactivated or restored in intestinal epithelium. The relationship between growth and functional characteristics of the intestines, including transepithelial electrophysiology, incidence of intestinal obstruction, and histopathology, were assessed. Absence of Cftr exclusively from intestinal epithelium resulted in loss of cAMP-stimulated short-circuit current, goblet cell hyperplasia, and occurrence of intestinal obstructions but only slight and transient impaired growth. In contrast, specifically restoring Cftr to the intestinal epithelium resulted in restoration of ion transport and completely protected against obstruction and histopathological anomalies, but growth was indistinguishable from CF mice. These results indicate that absence of Cftr in the intestinal epithelium is an important contributor to the intestinal obstruction phenotype in CF but does not correlate with the observed growth reduction in CF.

scholarly journals Efficacy and Safety of a New Formulation of Pancrelipase (Ultrase MT20) in the Treatment of Malabsorption in Exocrine Pancreatic Insufficiency in Cystic Fibrosis

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Michael W. Konstan ◽  
Theodore G. Liou ◽  
Steven D. Strausbaugh ◽  
Richard Ahrens ◽  
Jamshed F. Kanga ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pancreatic Insufficiency ◽  
Pancreatic Enzyme ◽  
Gastrointestinal Symptoms ◽  
Signs And Symptoms ◽  
Exocrine Pancreatic Insufficiency ◽  
Efficacy And Safety ◽  
Protein Nitrogen ◽  
Enzyme Replacement ◽  
New Formulation

Background. Pancreatic enzyme replacement therapy is the standard of care for treatment of malabsorption in patients with cystic fibrosis (CF) and exocrine pancreatic insufficiency (PI).Aim. To evaluate efficacy and safety of a new formulation of pancrelipase (Ultrase MT20) in patients with CF and PI. Coefficients of fat absorption (CFA%) and nitrogen absorption (CNA%) were the main efficacy parameters. Safety was evaluated by monitoring laboratory analyses, adverse events (AEs), and overall signs and symptoms.Methods. Patients (n=31) were randomized in a crossover design comparing this pancrelipase with placebo during 2 inpatient evaluation periods (6-7 days each). Fat and protein/nitrogen ingestion and excretion were measured from food diaries and 72-hour stool collections. CFA% and CNA% were calculated for each period and compared.Results. Twenty-four patients provided analyzable data. This pancrelipase increased mean CFA% and CNA% (+34.7% and +25.7%, resp.,P<.0001for both), reduced stool frequency, and improved stool consistency compared with placebo. Placebo-treated patients reported more AEs, with gastrointestinal symptoms being the most frequently reported AE.Conclusions. This pancrelipase is a safe and effective treatment for malabsorption associated with exocrine PI in patients with CF.

scholarly journals Cystic Fibrosis Treatment Options Discrepancy Globally

2022 ◽  
Vol 1 ◽  
Author(s):  
Rifa Gowani ◽  
Keyword(s):  
Cystic Fibrosis ◽  
Pancreatic Insufficiency ◽  
Treatment Options ◽  
Pancreatic Enzyme ◽  
Genetic Mutation ◽  
Exocrine Pancreatic Insufficiency ◽  
Monogenic Disease ◽  
Obstructive Pulmonary Disease ◽  
Enzyme Replacement ◽  
Proactive Therapy

Cystic fibrosis, or rather known as CF, is a common monogenic disease caused by genetic mutation on CFTR on chromosome 7. Progressive obstructive pulmonary disease, sinusitis, exocrine pancreatic insufficiency leading to malabsorption and malnutrition, liver and pancreatic dysfunction, and male infertility are all characteristics of the disease. Persistent pulmonary infections are caused by a lack of CFTR or its decreased function, leading to bronchiectasis and progressive lung destruction. Despite the fact that CF patients' lives are shortening, early diagnosis has helped improve patients' life span to a median age of around 50 years, including newborn screening, mild form identification, and a proactive therapy approach. Pancreatic enzyme replacement, respiratory physiotherapy, mucolytics, and strong antibiotic therapy are among treatments for CF. For the majority of people with severe symptoms, a lung or liver transplant is necessary. The CFTR protein is affected by a large number of mutations, each of which have diverse effects. Despite advances in our understanding of CFTR function and contemporary therapy, most of our knowledge of cystic fibrosis remains unclear. With the recent addition of mutation-specific treatments, future advances in health and quality of life for people with CF are likely to improve. The focus of research is on novel medications that restore CFTR function, some of which are now accessible and have a positive therapeutic impact, while others are showing promising preliminary results.

scholarly journals Bruising as the first sign of exocrine pancreatic insufficiency

2019 ◽  
Author(s):  
Csilla Enikő Szabo ◽  
Oana Iulia Man ◽  
Radu Sorin Șerban ◽  
Eva Kiss ◽  
Călin Florin Lazăr
Keyword(s):  
Cystic Fibrosis ◽  
Vitamin K ◽  
Pancreatic Insufficiency ◽  
Pancreatic Enzyme ◽  
Exocrine Pancreatic Insufficiency ◽  
Nutritional Deficiencies ◽  
Deficiency Anemia ◽  
Serum Lipase ◽  
Pancreatic Elastase ◽  
Enzyme Replacement

Exocrine pancreatic insufficiency is an important cause of chronic malnutrition, secondary to maldigestion-malabsorption, which can be caused in children especially by cystic fibrosis, but also by other much rarer diseases. The case of a 6 months and 3 weeks old male pediatric patient is reported, who was admitted to the clinic for head and forearms bruising. Laboratory findings identified vitamin K deficiency as the cause of the cutaneous hemorrhagic syndrome. Further investigations revealed association of steatorrhea (which is a marker of fat malabsorption), iron-deficiency anemia and hypovitaminosis D, which had been produced by nutritional deficiencies caused by malabsorption syndrome. From the numerous disorders that could be associated with pancreatic insufficiency in children, the following conditions had been excluded: cystic fibrosis (mucoviscidosis), cow`s milk protein intolerance, gluten-sensitive enteropathy (coeliac disease), Shwachman-Diamond syndrome, abetalipoproteinemia, etc. Based upon decreased levels of stool pancreatic elastase in repeated measurements, together with low serum lipase, the final diagnosis of exocrine pancreatic insufficiency was established. Treatment of this case consisted mainly in pancreatic enzyme replacement therapy, but also oral iron supplementation and dietary supplements with fat-soluble vitamins (A, D, E, K). The outcome was favorable, characterized by normalization of intestinal passage, ascending growth curve and normalization of the majority of laboratory tests values that were modified between the time of patient admission to our clinic and initiation of specific therapy (serum level of vitamin K, vitamin D and lipase, coagulation profile, hemoglobin and red blood cell indexes), as well as higher value of fecal pancreatic elastase.    

scholarly journals Digestive enzyme replacement relieves growth failure in preterm infants with poor exocrine pancreatic function: a retrospective case series

2021 ◽  
Author(s):  
Annette Münch ◽  
Christoph Bührer ◽  
Ann Carolin Longardt
Keyword(s):  
Weight Gain ◽  
Preterm Infants ◽  
Digestive Enzyme ◽  
Pancreatic Insufficiency ◽  
Growth Failure ◽  
Exocrine Pancreatic Function ◽  
Exocrine Pancreatic Insufficiency ◽  
Very Preterm Infants ◽  
Enzyme Replacement ◽  
Fecal Pancreatic Elastase

AbstractIn orally fed preterm infants, poor weight gain may be linked to low fecal pancreatic elastase-1 (FPE-1) activity, indicative of exocrine pancreatic insufficiency. The objective of this study was the retrospective assessment of the effect of exogenous digestive enzyme replacement by gavage in preterm infants with growth failure and low FPE-1 (<200 μg/g). We analyzed weight gain relative to baseline and caloric intake during 14-day periods before and after institution of digestive enzyme replacement containing 6000 U lipase and 240 U protease kg−1 d−1. Among 46 of 132 preterm infants < 1250g birth weight surviving to at least 14 days in whom FPE-1 was determined, 38 infants had low FPE-1 (< 200 μg/g), and 33 infants received exogenous digestive enzyme replacement. Average daily weight gain significantly increased from 14.4 [range 2.6–22.4] g kg−1 d−1 to 17.4 [8.4–29.0] g kg−1 d−1 (P = 0.001), as did weight gain per kcal, from 0.08 [0.02–0.13] g kcal−1 d−1 to 0.11 [0.05–0.18] g kcal−1 d−1.Conclusion: In preterm infants with signs and symptoms of exocrine pancreatic insufficiency, exogenous digestive enzyme replacement is associated with improved growth. What is Known:• Very preterm infants on full enteral nutrition may display growth failure linked to transient poor exocrine pancreatic function.• Porcine pancreatic enzymes covered with an acid-resistant coating are too large to pass the internal diameter of most gavage tubes used in very preterm infants.What is New:• Administration of a liquid formulation of acid-resistant microbial digestive enzymes in preterm infants with growth failure and low fecal pancreatic elastase-1 values was associated with improved weight gain.• Response to exogenous digestive enzyme replacement was associated with the prior extent of growth failure.

scholarly journals 2 The syndrome of exocrine pancreatic insufficiency – cystic fibrosis or other disease?

2012 ◽  
Vol 11 ◽  
pp. S55
Author(s):  
A. Sobczynska-Tomaszewska ◽  
K. Czerska ◽  
A. Szpecht-Potocka ◽  
D. Popielarz ◽  
K. Wertheim-Tysarowska ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pancreatic Insufficiency ◽  
Exocrine Pancreatic Insufficiency
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