Iron Homeostasis during Cystic Fibrosis Pulmonary Exacerbation

BACKGROUND: Hypoferremia is a marker of disease severity in cystic fibrosis (CF). The effect of systemic antibiotics on iron homeostasis during CF pulmonary exacerbation (CFPE) is unknown. Our central hypotheses were that, by the completion of treatment, serum iron would increase, serum concentrations of interleukin-6 (IL-6) and hepcidin-25, two mediators of hypoferremia, would decrease, and sputum iron would decrease. METHODS: Blood and sputum samples were collected from 12 subjects with moderate-to-severe CF (median percentage-predicted forced expiratory volume in 1 second (FEV(1) %) = 29%; median weight = 56 kg) within 24 hours of starting and completing a course of systemic antibiotics. RESULTS: After treatment, subjects showed median FEV(1) % and body weight improvements of 4.5% and 2.0 kg, respectively (p \u3c 0.05). Median serum iron rose by 2.4 μmol/L (p \u3c 0.05), but 75% of patients remained hypoferremic. Median serum IL-6 and hepcidin-25 levels fell by 12.1 pg/mL and 37.5 ng/mL, respectively (p \u3c 0.05). Median serum erythropoietin (EPO) and hemoglobin levels were unaffected by treatment. We observed a trend toward lower sputum iron content after treatment. CONCLUSIONS: Hypoferremia is a salient characteristic of CFPE that improves with waning inflammation. Despite antibiotic treatment, many patients remain hypoferremic and anemic because of ineffective erythropoiesis

Competing ultrafast intersystem crossing and internal conversion in the "channel 3" region of benzene

We report new, detailed, femtosecond time-resolved photoelectron spectroscopy experiments and calculations investigating the competition between ultrafast internal conversion and ultrafast intersystem crossing in electronically and vibrationally excited benzene at the onset of “channel 3”. Using different probe energies to record the total photoelectron yield as a function of pump–probe delay we are able to confirm that S1, T1 and T2 electronic states are involved in the excited state dynamics. Time-resolved photoelectron spectroscopy measurements then allow us to unravel the evolution of the S1, T1 and T2 components of the excited state population and, together with complementary quantum chemistry and quantum dynamics calculations, support our earlier proposal that ultrafast intersystem crossing competes with internal conversion (Chem. Phys. Lett., 2009, 469, 43).<br/

Quantum dynamics study of the competing ultrafast intersystem crossing and internal conversion in the “channel 3” region of benzene

Time-resolved photoelectron spectroscopy can obtain detailed information about the dynamics of a chemical process on the femtosecond timescale. The resulting signal from such detailed experiments is often difficult to analyze and therefore theoretical calculations are important in providing support. In this paper we continue our work on the competing pathways in the photophysics and photochemistry of benzene after excitation into the “channel 3” region [R. S. Minns, D. S. N. Parker, T. J. Penfold, G. A. Worth, and H. H. Fielding, Phys. Chem. Chem. Phys. 12, 15607 (2010)] with details of the calculations shown previously, building on a vibronic coupling Hamiltonian [T. J. Penfold and G. A. Worth, J. Chem. Phys. 131, 064303 (2009)] to include the triplet manifold. New experimental data are also presented suggesting that an oscillatory signal is due to a hot band excitation. The experiments show that signals are obtained from three regions of the potential surfaces, three open channels, which are assigned with the help of simulations showing that following excitation into vibrationally excited-states of S1 the wavepacket not only crosses through the prefulvenoid conical intersection back to the singlet ground state, but also undergoes ultrafast intersystem crossing to low lying triplet states. The model is, however, not detailed enough to capture the full details of the oscillatory signal due to the hot band

Iron supplementation does not worsen respiratory health or alter the sputum microbiome in cystic fibrosis

Author Posting. © The Author(s), 2013. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Journal of Cystic Fibrosis 13 (2014): 311-318, doi:10.1016/j.jcf.2013.11.004.Iron supplementation for hypoferremic anemia could potentiate bacterial growth in the cystic fibrosis (CF) lung, but clinical trials testing this hypothesis are lacking. Twenty-two adults with CF and hypoferremic anemia participated in a randomized, double-blind, placebo-controlled, crossover trial of ferrous sulfate 325 mg daily for 6 weeks. Iron-related hematologic parameters, anthropometric data, sputum iron, Akron Pulmonary Exacerbation Score (PES), and the sputum microbiome were serially assessed. Fixed-effect models were used to describe how ferrous sulfate affected these variables. Ferrous sulfate increased serum iron by 22.3% and transferrin saturation (TSAT) by 26.8% from baseline (p < 0.05) but did not affect hemoglobin, sputum iron, Akron PES, and the sputum microbiome. Low-dose ferrous sulfate improved hypoferremia without correcting anemia after 6 weeks. We did not observe significant effects on sputum iron, Akron PES, and the sputum microbiome. Although we did not identify untoward health effects of iron supplementation, a larger blinded randomized controlled trial would be needed to fully demonstrate safety.Flatley Foundation of Boston, Massachusetts; NIH P20-GM103413-10 and R01-HL074185-09; Cystic Fibrosis Foundation Research Development Program; Hitchcock Foundation; and NIH R01 AI0911699

Iron supplementation does not worsen respiratory health or alter the sputum microbiome in cystic fibrosis.

BACKGROUND: Iron supplementation for hypoferremic anemia could potentiate bacterial growth in the cystic fibrosis (CF) lung, but clinical trials testing this hypothesis are lacking. METHODS: Twenty-two adults with CF and hypoferremic anemia participated in a randomized, double-blind, placebo-controlled, crossover trial of ferrous sulfate 325mg daily for 6weeks. Iron-related hematologic parameters, anthropometric data, sputum iron, Akron Pulmonary Exacerbation Score (PES), and the sputum microbiome were serially assessed. Fixed-effect models were used to describe how ferrous sulfate affected these variables. RESULTS: Ferrous sulfate increased serum iron by 22.3% and transferrin saturation (TSAT) by 26.8% from baseline (p CONCLUSIONS: Low-dose ferrous sulfate improved hypoferremia without correcting anemia after 6weeks. We did not observe significant effects on sputum iron, Akron PES, and the sputum microbiome. Although we did not identify untoward health effects of iron supplementation, a larger blinded randomized controlled trial would be needed to fully demonstrate safety