scholarly journals Cystic fibrosis-related diabetes and lung disease: an update

2021 ◽  
Vol 30 (159) ◽  
pp. 200293
Author(s):  
Bernadette J. Prentice ◽  
Adam Jaffe ◽  
Shihab Hameed ◽  
Charles F. Verge ◽  
Shafagh Waters ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
High Glucose ◽  
Potential Role ◽  
Early Mortality ◽  
Genetic Modifiers ◽  
Immunomodulatory Effects ◽  
Glucose Levels ◽  
The Many

The development of cystic fibrosis-related diabetes (CFRD) often leads to poorer outcomes in patients with cystic fibrosis including increases in pulmonary exacerbations, poorer lung function and early mortality. This review highlights the many factors contributing to the clinical decline seen in patients diagnosed with CFRD, highlighting the important role of nutrition, the direct effect of hyperglycaemia on the lungs, the immunomodulatory effects of high glucose levels and the potential role of genetic modifiers in CFRD.

scholarly journals Ceramide in Cystic Fibrosis: A Potential New Target for Therapeutic Intervention

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Gabriella Wojewodka ◽  
Juan B. De Sanctis ◽  
Danuta Radzioch
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Inflammatory Response ◽  
Therapeutic Intervention ◽  
Bacterial Infections ◽  
Potential Role ◽  
Cell Signalling ◽  
Membrane Microdomains ◽  
Molecular Processes

Patients with cystic fibrosis (CF) are afflicted with many symptoms but the greatest challenge is the fight against chronic bacterial infections, leading to decreased lung function and ultimately death. Our group has recently found reduced levels of ceramides in CF patients and mice. Ceramides are sphingolipids involved in the structure of cell membranes but also participate in the inflammatory response, in cell signalling through membrane microdomains (lipid rafts), and in apoptosis. These characteristics of ceramides make them strong candidates for therapeutic intervention in CF. As more studies have come to evaluate the role of ceramide in CF, conflicting results have been described. This paper discusses various views regarding the potential role of ceramide in CF, summarizes methods of ceramide detection and their role in the regulation of cellular and molecular processes.

Potential role of the cellular allergen stimulation test (CAST) in diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis

2007 ◽  
Vol 42 (4) ◽  
pp. 314-318 ◽  
Author(s):  
Stephanie Ringer ◽  
Uta-Christina Hipler ◽  
Peter Elsner ◽  
Felix Zintl ◽  
Jochen Mainz
Keyword(s):  
Cystic Fibrosis ◽  
Potential Role ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Stimulation Test

scholarly journals Risk factors for respiratory Aspergillus fumigatus in German Cystic Fibrosis patients and impact on lung function

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Uta Düesberg ◽  
Julia Wosniok ◽  
Lutz Naehrlich ◽  
Patience Eschenhagen ◽  
Carsten Schwarz
Keyword(s):  
Risk Factors ◽  
Cystic Fibrosis ◽  
Lung Function ◽  
Aspergillus Fumigatus ◽  
Age Groups ◽  
Antibiotic Use ◽  
Lower Lung ◽  
Lung Infections ◽  
The Impact

Abstract Airway inflammation and chronic lung infections in cystic fibrosis (CF) patients are mostly caused by bacteria, e.g. Pseudomonas aeruginosa (PA). The role of fungi in the CF lung is still not well elucidated, but evidence for a harmful and complex role is getting stronger. The most common filamentous fungus in CF is Aspergillus fumigatus (AF). Age and continuous antibiotic treatment have been discussed as risk factors for AF colonisation but did not differentiate between transient and persistent AF colonisation. Also, the impact of co-colonisation of PA and AF on lung function is still under investigation. Data from patients with CF registered in the German Cystic Fibrosis Registry database in 2016 and 2017 were retrospectively analysed, involving descriptive and multivariate analysis to assess risk factors for transient or persistent AF colonisation. Age represented an independent risk factor for persistent AF colonisation. Prevalence was low in children less than ten years, highest in the middle age and getting lower in higher age (≥ 50 years). Continuous antibiotic lung treatment was significantly associated with AF prevalence in all age groups. CF patients with chronic PA infection had a lower lung function (FEV1%predicted), which was not influenced by an additional AF colonisation. AF colonisation without chronic PA infection, however, was significantly associated with a lower function, too. Older age up to 49 years and continuous antibiotic use were found to be the main risk factors for AF permanent colonisation. AF might be associated with decrease of lung function if not disguised by chronic PA infection.

scholarly journals Role of p90RSK in regulating the Crabtree effect: implications for cancer

2013 ◽  
Vol 41 (1) ◽  
pp. 124-126 ◽  
Author(s):  
Emily K. Redman ◽  
Paul S. Brookes ◽  
Marcin K. Karcz
Keyword(s):  
Cancer Cell ◽  
High Glucose ◽  
Cell Metabolism ◽  
Cell Signalling ◽  
Cell Types ◽  
Crabtree Effect ◽  
Glucose Levels ◽  
Mitogen Activated Protein ◽  
Ribosomal S6 Kinase

High glucose inhibits mitochondrial respiration, known as the ‘Crabtree effect’, in cancer cells and possibly other cell types. The upstream pathways regulating this phenomenon are poorly understood. In diabetes, where glucose levels are elevated, the p90RSK (p90 ribosomal S6 kinase) has received much attention as a potential upstream mediator of the effects of high glucose. Evidence is also emerging that p90RSK may play a role in cancer cell signalling, although the role of p90RSK in regulating cancer cell metabolism is unclear. In the present paper, we provide an overview of the Crabtree effect and its relationship to mitochondrial metabolism. Furthermore, preliminary data are presented suggesting a role for p90RSK and its upstream components, the ERK (extracellular-signal-regulated kinase) family of MAPKs (mitogen-activated protein kinases), in the Crabtree effect.

scholarly journals Gene expression of epithelial glucose transporters: the role of diabetes mellitus.

1994 ◽  
Vol 5 (5) ◽  
pp. S29
Author(s):  
J H Dominguez ◽  
B Song ◽  
L Maianu ◽  
W T Garvey ◽  
M Qulali
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Small Intestine ◽  
High Glucose ◽  
Glucose Transporter ◽  
Basolateral Membrane ◽  
Glucose Levels ◽  
Uncontrolled Diabetes ◽  
Extracellular Level

The functions of absorption of dietary glucose by the small intestine and reabsorption of filtered glucose by the renal proximal tubule are strikingly similar in their organization and in the way they adapt to uncontrolled diabetes mellitus. In both cases, transepithelial glucose and Na+ fluxes are augmented. The epithelial adaptations to hyperglycemia of uncontrolled diabetes are accomplished by increasing the glucose transport surface area and the number of the efflux glucose transporter GLUT2 located in the basolateral membrane. The signals that modify the size of the epithelium and the overexpression of basolateral GLUT2 are not known. It was speculated that high glucose levels and enhanced Na+ flux may be important factors in the signaling event that culminates in a renal and intestinal epithelium that is modified to transport higher rates of glucose against a higher extracellular level of glucose.

scholarly journals Case Report: Dual nebulised antibiotics among adults with cystic fibrosis and chronic Pseudomonas infection

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2079
Author(s):  
Nina Mann ◽  
Shirley Murray ◽  
Zhe Hui Hoo ◽  
Rachael Curley ◽  
Martin J. Wildman
Keyword(s):  
Cystic Fibrosis ◽  
Case Report ◽  
Adverse Effects ◽  
Best Practice ◽  
Potential Role ◽  
Concomitant Administration ◽  
Intravenous Antibiotics ◽  
Inhaled Antibiotics ◽  
Pseudomonas Infection

Pulmonary exacerbations in adults with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa (Psae) infection are usually treated with dual intravenous antibiotics for 14 days, despite the lack of evidence for best practice. Intravenous antibiotics are commonly associated with various systemic adverse effects, including renal failure and ototoxicity. Inhaled antibiotics are less likely to cause systematic adverse effects, yet can achieve airway concentrations well above conventional minimum inhibitory concentrations. Typically one inhaled antibiotic is used at a time, but dual inhaled antibiotics (i.e. concomitant use of two different inhaled antibiotics) may have synergistic effect and achieve better results in the treatment of exacerbations. We presented anecdotal evidence for the use of dual inhaled antibiotics as an acute treatment for exacerbations, in the form of a case report. A female in her early thirties with CF and chronic Psae infection improved her FEV1 by 5% and 2% with two courses of dual inhaled antibiotics to treat exacerbations in 2016. In contrast, her FEV1 changed by 2%, –2%, 0% and 2%, respectively, with four courses of dual intravenous antibiotics in 2016. Baseline FEV1 was similar prior to all six courses of treatments. The greater FEV1 improvements with dual inhaled antibiotics compared to dual intravenous antibiotics suggest the potential role of using dual inhaled antibiotics to treat exacerbations among adults with CF and chronic Psae infection, especially since a greater choice of inhaled anti-pseudomonal antibiotics is now available. A previous study in 1985 has looked at the concomitant administration of inhaled tobramycin and carbenicillin, by reconstituting antibiotics designed for parenteral administration. To our knowledge, this is the first literature to describe the concomitant use of two different antibiotics specifically developed for delivery via the inhaled route.

Direct quantification of norepinephrine spillover and hormone output from the pancreas of the conscious dog

1997 ◽  
Vol 272 (5) ◽  
pp. E746-E755 ◽  
Author(s):  
B. E. Dunning ◽  
M. F. Scott ◽  
D. W. Neal ◽  
A. D. Cherrington
Keyword(s):  
Neural Activity ◽  
Potential Role ◽  
Hormone Secretion ◽  
Intravenous Glucose ◽  
Concentration Difference ◽  
Conscious Dog ◽  
Glucose Levels ◽  
Norepinephrine Spillover ◽  
Neural Signaling

To estimate pancreatic neural activity and to assess the potential role of the pancreatic nerves in the regulation of hormone secretion, the methodology necessary to quantify neurotransmitter spillover and hormone output in the conscious dog was developed. A femoral artery and the superior pancreaticoduodenal vein (SPDV) were chronically cannulated, and a flow probe was placed on the SPDV. Hormone output was calculated using the pancreatic arteriovenous concentration difference and the SPDV plasma flow. Basal glucose levels were 103 +/- 1 mg/dl; the pancreatic outputs of insulin, glucagon, and pancreatic polypeptide (PP, an index of parasympathetic neural activity) were 2,900 +/- 700 microU/min, 1,900 +/- 400 pg/min, and 9.3 +/- 4.6 ng/min, respectively. Pancreatic norepinephrine (NE) spillover was calculated similarly; however, pancreatic extraction of epinephrine was used as an index of NE extraction. Basal NE spillover was 3,600 +/- 700 pg/min, greatly exceeding that reported using anesthetized, laparotomized dogs. Intravenous glucose infusion increased plasma glucose to 146 +/- 13 mg/dl, increased insulin output approximately twofold, and suppressed glucagon output by approximately 50%. Hyperglycemia markedly reduced PP output. Hyperglycemia failed to influence pancreatic NE spillover. Insulin-induced hypoglycemia (36 +/- 2 mg/dl) completely suppressed insulin output and stimulated glucagon output (> 10-fold). Hypoglycemia increased NE spillover and PP output to 19,900 +/- 4,600 pg/min and 117 +/- 22 ng/min, respectively. We conclude that pancreatic neurotransmitter spillover in the basal state is much higher than previously appreciated and that neural signaling to the pancreas is responsive to physiological and pathophysiological changes in the metabolic state.

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