Iron homeostasis and oxidative stress in idiopathic pulmonary alveolar proteinosis: a case-control study

<p>Abstract</p> <p>Background</p> <p>Lung injury caused by both inhaled dusts and infectious agents depends on increased availability of iron and metal-catalyzed oxidative stress. Because inhaled particles, such as silica, and certain infections can cause secondary pulmonary alveolar proteinosis (PAP), we tested the hypothesis that idiopathic PAP is associated with an altered iron homeostasis in the human lung.</p> <p>Methods</p> <p>Healthy volunteers (n = 20) and patients with idiopathic PAP (n = 20) underwent bronchoalveolar lavage and measurements were made of total protein, iron, tranferrin, transferrin receptor, lactoferrin, and ferritin. Histochemical staining for iron and ferritin was done in the cell pellets from control subjects and PAP patients, and in lung specimens of patients without cardiopulmonary disease and with PAP. Lavage concentrations of urate, glutathione, and ascorbate were also measured as indices of oxidative stress.</p> <p>Results</p> <p>Lavage concentrations of iron, transferrin, transferrin receptor, lactoferrin, and ferritin were significantly elevated in PAP patients relative to healthy volunteers. The cells of PAP patients had accumulated significant iron and ferritin, as well as considerable amounts of extracellular ferritin. Immunohistochemistry for ferritin in lung tissue revealed comparable amounts of this metal-storage protein in the lower respiratory tract of PAP patients both intracellularly and extracellularly. Lavage concentrations of ascorbate, glutathione, and urate were significantly lower in the lavage fluid of the PAP patients.</p> <p>Conclusion</p> <p>Iron homeostasis is altered in the lungs of patients with idiopathic PAP, as large amounts of catalytically-active iron and low molecular weight anti-oxidant depletion are present. These findings suggest a metal-catalyzed oxidative stress in the maintenance of this disease.</p

Treatment of hypoplastic anemia in mice with placental transplants

Abstract A genetic mutation in mice (W/Wv) causes an autosomal recessive disease characterized by hypoplastic anemia which lasts throughout life. Double- dominant W/Wv anemic mice were sublethally irradiated to facilitate repopulation of marrow with transplanted cells and were injected intravenously with suspensions of 5–10 million placental cells of 15 days gestation derived from normal, isogeneic donors. Red cell counts fell promptly after irradiation and then rose progressively over a period of weeks, reaching normal levels of the nonmutant. Mean corpuscular volume and hemoglobin electrophoresis patterns of red cells in recipient W/Wv mice resembled those of normal donor animals. The therapeutic effect lasted for the duration of the observation period, in some instances over 9 mo. W/Wv mice that were administered Hanks' solution or fetal blood, instead of placental transplants, remained anemic. Late gestation placentas (18 days) were also ineffective.</jats:p

Treatment of hypoplastic anemia in mice with placental transplants

A genetic mutation in mice (W/Wv) causes an autosomal recessive disease characterized by hypoplastic anemia which lasts throughout life. Double- dominant W/Wv anemic mice were sublethally irradiated to facilitate repopulation of marrow with transplanted cells and were injected intravenously with suspensions of 5–10 million placental cells of 15 days gestation derived from normal, isogeneic donors. Red cell counts fell promptly after irradiation and then rose progressively over a period of weeks, reaching normal levels of the nonmutant. Mean corpuscular volume and hemoglobin electrophoresis patterns of red cells in recipient W/Wv mice resembled those of normal donor animals. The therapeutic effect lasted for the duration of the observation period, in some instances over 9 mo. W/Wv mice that were administered Hanks' solution or fetal blood, instead of placental transplants, remained anemic. Late gestation placentas (18 days) were also ineffective.</jats:p

Evaluation of high resolution simulated and OMI retrieved tropospheric NO2 column densities over South-Eastern Europe

High resolution model estimates (10 × 10 km2) of tropospheric NO2 column amounts from the Comprehensive Air Quality Model (CAMx) for the Balkan Peninsula are compared with OMI/Aura measurements (13 × 24 km2 at nadir) for the year April 2009 to March 2010. The Balkan area contributes significantly to the NO2 burden in European air and so numerous urban, industrial and rural regions are studied aiming to investigate the consistency of both satellite retrievals and model predictions at high spatial resolution. It has already been shown that OMI can detect the tropospheric column of NO2 over polluted Balkan cities due to its fine horizontal resolution and instrument sensitivity (Zyrichidou et al., 2009). In this study the improved OMI DOMINO v2.0 satellite retrievals showed that over South-Eastern Europe the monthly mean NO2 tropospheric column density fluctuated between 2.0 and 5.7 ± 1.1 × 1015 molecules/cm2 over urban areas, 1.6–5.0 ± 0.7 × 1015 molecules/cm2 over large industrial complexes and 1.1–2.2 ± 0.4 × 1015 molecules/cm2 over rural areas for the year studied. The Comprehensive Air Quality Model with extensions (CAMx) version 4.40 is a publicly available open-source computer modeling system for the integrated assessment of gaseous and particulate air pollution. The anthropogenic emissions used in CAMx for the Greek domain being studied were compiled employing bottom-up approaches (road transport sector, off-road machinery, etc.) as well as other national registries and international databases. The rest of the Balkan domain has natural and anthropogenic emissions based on the TNO emission inventory of 2003. The high-resolution CAMx simulations reveal consistent spatial and temporal patterns with the OMI/Aura data. The annual spatial correlation coefficient between OMI and CAMx computed in this high spatial resolution analysis is of the order of 0.6, somewhat improved over those estimated in Zyrichidou et al. (2009) (R ˜ 0.5). However, in such a validation study it is important to take into account the averaging kernel (AK) information in order to achieve the creation of comparable data sets. Minor differences are found for area-averaged model columns with and without applying the kernel, which shows that the impact of limiting the effect of the a priori profile on the comparison is on average small. The main aim of the paper, which was to evaluate OMI retrieved and high resolution simulated tropospheric NO2 column densities over South-Eastern Europe and to assess the use of the averaging kernels, is achieved and the two data sources are being employed further in an inverse emission inventory creation study (Zyrichidou et al., in preparation)