scholarly journals Altered steady state pharmacokinetics of levofloxacin in adult cystic fibrosis patients receiving calcium carbonate

2006 ◽  
Vol 5 (3) ◽  
pp. 153-157 ◽  
Author(s):  
Manjunath P. Pai ◽  
Sarah E. Allen ◽  
Guy W. Amsden
Keyword(s):  
Cystic Fibrosis ◽  
Steady State ◽  
Calcium Carbonate

Shunt resistance and ion permeabilities in normal and cystic fibrosis airway epithelia

1989 ◽  
Vol 256 (5) ◽  
pp. C1054-C1063 ◽  
Author(s):  
N. J. Willumsen ◽  
R. C. Boucher
Keyword(s):  
Cystic Fibrosis ◽  
Steady State ◽  
Apical Membrane ◽  
Short Circuit ◽  
Strongly Correlated ◽  
Shunt Resistance ◽  
Human Nasal Epithelium ◽  
Cystic Fibrosis Airway ◽  
Intracellular Ion Activities ◽  
Ion Activities

A method for determination of shunt resistance (Rs) and absolute conductive ion permeabilities of the apical membrane in epithelia from steady-state data is described. The method assumes that the currents are satisfactorily described by the Goldman-Hodgkin-Katz regime. Its application requires measurements of standard transepithelial electrophysiological parameters and of one or more intracellular ion activities. It is applicable under both open- and short-circuit conditions. The method was tested in an electrophysiological analysis of cultured normal and cystic fibrosis (CF) human nasal epithelium. In 15 normal and 10 CF preparations with mean transepithelial resistances of 338 and 427 omega.cm2, Rs was 412 and 623 omega.cm2, respectively. The Rs values determined with the present method were strongly correlated (r = 0.94) with those obtained with another method available in the electrophysiological literature but were as a mean 20% lower. Amiloride increased Rs by 25% in CF and by 8% in normal preparations. In normal preparations, the apical Cl permeability (PCla) was 3.6 x 10(-6) cm/s, and the apical Na permeability (PNaa) was 1.6 x 10(-6) cm/s. In CF preparations, PCla was reduced to a maximum of 2.3 x 10(-7) cm/s, whereas PNaa was increased to 6.2 x 10(-6) cm/s. The apical membrane electromotive force was -1 mV in normal and 43 mV in CF preparations. It is concluded that the method can be used to calculate Rs, apical membrane ion permeabilities, and electromotive forces from steady-state electrophysiological data.

scholarly journals Inhibition of ATP hydrolysis restores airway surface liquid production in cystic fibrosis airway epithelia

2020 ◽  
Vol 318 (2) ◽  
pp. L356-L365 ◽  
Author(s):  
Catharina van Heusden ◽  
Brian Button ◽  
Wayne H. Anderson ◽  
Agathe Ceppe ◽  
Lisa C. Morton ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Steady State ◽  
Atp Hydrolysis ◽  
Fluid Secretion ◽  
Pathological Feature ◽  
Airway Surface Liquid ◽  
Airway Epithelial ◽  
Airway Epithelia ◽  
Atp Levels ◽  
Surface Liquid

Airway surface dehydration is a pathological feature of cystic fibrosis (CF) lung disease. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR), a cyclic AMP-regulated Cl− channel controlled in part by the adenosine A2B receptor. An alternative CFTR-independent mechanism of fluid secretion is regulated by ATP via the P2Y2 receptor (P2Y2R) that activates Ca2+-regulated Cl− channels (CaCC/TMEM16) and inhibits Na+ absorption. However, due to rapid ATP hydrolysis, steady-state ATP levels in CF airway surface liquid (ASL) are inadequate to maintain P2Y2R-mediated fluid secretion. Therefore, inhibiting airway epithelial ecto-ATPases to increase ASL ATP levels constitutes a strategy to restore airway surface hydration in CF. Using [γ32P]ATP as radiotracer, we assessed the effect of a series of ATPase inhibitory compounds on the stability of physiologically occurring ATP concentrations. We identified the polyoxometalate [Co4(H2O)2(PW9O34)2]10− (POM-5) as the most potent and effective ecto-ATPase inhibitor in CF airway epithelial cells. POM-5 caused long-lasting inhibition of ATP hydrolysis in airway epithelia, which was reversible upon removal of the inhibitor. Importantly, POM-5 markedly enhanced steady-state levels of released ATP, promoting increased ASL volume in CF cell surfaces. These results provide proof of concept for ecto-ATPase inhibitors as therapeutic agents to restore hydration of CF airway surfaces. As a test of this notion, cell-free sputum supernatants from CF subjects were studied and found to have abnormally elevated ATPase activity, which was markedly inhibited by POM-5.

Effects of Calcium Source on Calcium-Metabolic Parameters in Healthy Women and Men

2021 ◽  
Vol 8 (2) ◽  
Author(s):  
Hitz MF ◽  
◽  
Dahl M ◽  
Jørgensen NR ◽  
◽  
...  
Keyword(s):  
Vitamin D ◽  
Steady State ◽  
Calcium Carbonate ◽  
Calcium Absorption ◽  
Menopausal Status ◽  
Daily Intake ◽  
Dietary Calcium ◽  
Calcium Excretion ◽  
Steady State Condition

Background/Objectives: Calcium and vitamin D are important for bone health. We compared 24-hour urinary calcium-excretion (Uca/24hrs), during dietary calcium steady-state condition, for different calcium-sources and effects of vitamin D, age and sex. Subjects/Methods: Fifty-two healthy pre- and postmenopausal women and men completed the regimens: placebo, calcium carbonate (400mg) +18μg vitamin D, calcium carbonate (400mg) +38μg vitamin D and 400mg calcium phosphate (milk). Uca/24hrs was measured during dietary calcium steady state as a surrogate measure of calcium-absorption. Serum-calcium, parathyroid hormone (PTH), 25-hydroxy-vitamin D, Procollagen Type 1 N-terminal Pro- Peptide (P1NP) and C-terminal Telopeptide of type 1 collagen (CTX) were measured. Results: Mean daily intake of calcium for the study group ± SD was 1105 ±396 mg. Mean-Uca ± SD: placebo 5.19 ± 2.04 mmol/24hrs, milk 5.88 ± 2.39 mmol/24hrs, (CaCO3+D) 6.19 ± 2.34 mmol/24hrs and (CaCO3 + DD) 6.26 ± 2.32 mmol/day. Uca were higher for all regimens compared to placebo (p <0.001), no difference was found between regimens. CTX was lower during all regimens compared to placebo (p <0.001): placebo 450 ± 243 μg/L, Milk 377 ± 248 μg/L, (CaCO3+D) 392 ± 266 μg/L and (CaCO3+DD) 361 ± 232 μg/L. Conclusions: Uca was higher during supplementation with calcium compared to placebo. Supplementation with calcium reduced bone resorption significantly without effecting PTH. Menopausal status, sex and supplement with vitamin d demonstrated no effect on calcium excretion.

scholarly journals Lung morphology assessment using MRI: A robust ultra-short TR/TE 2D steady state free precession sequence used in cystic fibrosis patients

2009 ◽  
Vol 61 (2) ◽  
pp. 299-306 ◽  
Author(s):  
Riccarda Failo ◽  
Piotr A. Wielopolski ◽  
Harm A.W.M. Tiddens ◽  
Wim C.J. Hop ◽  
Roberto Pozzi Mucelli ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Steady State ◽  
Steady State Free Precession ◽  
Free Precession ◽  
Lung Morphology

scholarly journals 248* Using an individualized treadmill protocol to assess maximal steady state exercise capacity in cystic fibrosis

2011 ◽  
Vol 10 ◽  
pp. S63
Author(s):  
A.R. Morris ◽  
Z.E. Evans ◽  
J. Greenwood ◽  
M.J. Ledson ◽  
M.J. Walshaw
Keyword(s):  
Cystic Fibrosis ◽  
Steady State ◽  
Exercise Capacity ◽  
Treadmill Protocol

Thiocyanate as a probe of the cystic fibrosis transmembrane conductance regulator chloride channel pore

2001 ◽  
Vol 79 (7) ◽  
pp. 573-579 ◽  
Author(s):  
Paul Linsdell
Keyword(s):  
Cystic Fibrosis ◽  
Steady State ◽  
Mole Fraction ◽  
Chloride Channel ◽  
Theory Model ◽  
Anion Binding ◽  
Rate Theory ◽  
Patch Clamp Recording ◽  
Channel Pore ◽  
Mammalian Cell Lines

Immediately following exposure to thiocyanate (SCN–)-containing solutions, the cystic fibrosis conductance regulator Cl– channel exhibits high unitary SCN– conductance and anomalous mole fraction behaviour, suggesting the presence of multiple anion binding sites within the channel pore. However, under steady-state conditions SCN– conductance is very low. Here I show, using patch clamp recording from CFTR-transfected mammalian cell lines, that under steady-state conditions neither SCN– conductance nor SCN– permeability show anomalous mole fraction behaviour. Instead, SCN– conductance, permeability, and block of Cl– permeation can all be reproduced by a rate theory model that assumes only a single intrapore anion binding site. These results suggest that under steady-state conditions the interaction between SCN– and the CFTR channel pore can be understood by a simple model whereby SCN– ions enter the pore more easily than Cl–, and bind within the pore more tightly than Cl–. The implications of these findings for investigating and understanding the mechanism of anion permeation are discussed.Key words: chloride channel, permeation, anion binding, multi-ion pore behaviour, rate theory model.

Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression

2017 ◽  
Vol 172 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Galina Shmarina ◽  
Alexander Pukhalsky ◽  
Lucine Avakian ◽  
Sergey Semykin ◽  
Daria Pukhalskaya ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Steady State ◽  
Disease Progression ◽  
Inflammatory Markers ◽  
Low Dose

scholarly journals Crystallization kinetics of amorphous calcium carbonate in confinement

2019 ◽  
Vol 10 (19) ◽  
pp. 5039-5043 ◽  
Author(s):  
Jack Cavanaugh ◽  
Michael L. Whittaker ◽  
Derk Joester
Keyword(s):  
Steady State ◽  
Calcium Carbonate ◽  
Crystal Nucleation ◽  
Amorphous Calcium Carbonate ◽  
Emulsion Droplets ◽  
Individual Crystal ◽  
Upper Limit ◽  
Kinetics Of

In situ observation of amorphous calcium carbonate (ACC) confined in ∼500 pL emulsion droplets allows determination of the timing of individual crystal nucleation events. Statistical analysis of events in hundreds of droplets establishes an upper limit for the steady-state nucleation rate of 1.2 cm−3 s−1 for the crystallization from ACC.

Planning the Development of Cystic Fibrosis Gene Carrier Screening

1996 ◽  
Vol 1 (2) ◽  
pp. 81-92 ◽  
Author(s):  
Roger Beech ◽  
Hilary Bekker
Keyword(s):  
Health Care ◽  
Cystic Fibrosis ◽  
Steady State ◽  
Direct Costs ◽  
Cystic Fibrosis Gene ◽  
Carrier Status ◽  
Planning Framework ◽  
Screening Strategies ◽  
Primary Practice ◽  
Number Of Individuals

Objectives: It is now possible to test individuals to assess their cystic fibrosis gene carrier status and a range of strategies for screening the population have been piloted. The objective of this research was to develop a planning framework which health care planners and purchasers can use to assess the overall quantifiable outcomes and direct costs resulting from a year of alternative screening strategies and the ways costs and outcomes evolve over time. Beyond broader ethical and clinical considerations the information provided by such a framework is needed to support decisions surrounding the development of screening programmes. Design: Operational Research modelling techniques were used to develop the planning framework. To help illustrate the framework it was then used to assess the quantifiable outcomes and direct costs of three of the main alternative screening strategies: From antenatal clinics, ‘2-step’ screening where females are tested first followed by a screening invitation to the partners of female carriers, and ‘couple’ screening where both partners must agree to be tested at the outset; and from primary practice clinics ‘active’ contact of attenders. Quantifiable outcomes are defined as the number of individuals informed of their carrier status and the number of carriers, carrier couples, and affected fetuses detected. Direct costs are those associated with the recruitment and testing of individuals and the subsequent counselling of any gene carriers or carrier couples identified. Results are based on services for a resident population of 250 000 at two time points, year one and a year at ‘steady state’. Results: The resultant framework estimates the number of individuals tested using data on the size of the target population, the proportion of that population alerted to the screening service, and the proportion who agree to be tested when approached. Given service users, prevalence data are used to assess service outcomes. Given the number of individuals approached and the subsequent demands for services, service costs can be estimated. Preliminary results indicate that in the short-term health care purchasers and planners who favour screening are likely to opt for antenatal strategies. Although the high coverage of the primary practice strategy leads to high outcomes in year one, relative to the antenatal strategies, it also leads to very high costs. At ‘steady state’, cost and outcome differences between the strategies are less marked. Conclusion: This paper provides a framework which can be used to provide information to support decision-making surrounding the development of screening services. The methodology fills an important void in the literature and complements research elsewhere by health economists and by geneticists and their research colleagues. Preliminary findings based upon use of the approach demonstrate the need for continued research to further refine and improve the methodology.

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