Zn/Ga-DFO iron-chelating complex attenuates the inflammatory process in a mouse model of asthma.

BACKGROUND: Redox-active iron, a catalyst in the production of hydroxyl radicals via the Fenton reaction, is one of the key participants in ROS-induced tissue injury and general inflammation. According to our recent findings, an excess of tissue iron is involved in several airway-related pathologies such as nasal polyposis and asthma. OBJECTIVE: To examine the anti-inflammatory properties of a newly developed specific iron-chelating complex, Zn/Ga-DFO, in a mouse model of asthma. MATERIALS AND METHODS: Asthma was induced in BALBc mice by ovalbumin, using aluminum hydroxide as an adjuvant. Mice were divided into four groups: (i) control, (ii) asthmatic and sham-treated, (iii) asthmatic treated with Zn/Ga-DFO [intra-peritoneally (i/p) and intra-nasally (i/n)], and (iv) asthmatic treated with Zn/Ga-DFO, i/n only. Lung histology and cytology were examined. Biochemical analysis of pulmonary levels of ferritin and iron-saturated ferritin was conducted. RESULTS: The amount of neutrophils and eosinophils in bronchoalveolar lavage fluid, goblet cell hyperplasia, mucus secretion, and peri-bronchial edema, showed markedly better values in both asthmatic-treated groups compared to the asthmatic non-treated group. The non-treated asthmatic group showed elevated ferritin levels, while in the two treated groups it returned to baseline levels. Interestingly, i/n-treatment demonstrated a more profound effect alone than in a combination with i/p injections. CONCLUSION: In this mouse model of allergic asthma, Zn/Ga-DFO attenuated allergic airway inflammation. The beneficial effects of treatment were in accord with iron overload abatement in asthmatic lungs by Zn/Ga-DFO. The findings in both cellular and tissue levels supported the existence of a significant anti-inflammatory effect of Zn/Ga-DFO.

Highly sensitive monitoring of chest wall dynamics and acoustics provides diverse valuable information for evaluating ventilation and diagnosing pneumothorax.

Current practice of monitoring lung ventilation in neonatal intensive care units, utilizing endotracheal tube pressure and flow, end-tidal CO2, arterial O2 saturation from pulse oximetry, and hemodynamic indexes, fails to account for asymmetric pathologies and to allow for early detection of deteriorating ventilation. This study investigated the utility of bilateral measurements of chest wall dynamics and sounds, in providing early detection of changes in the mechanics and distribution of lung ventilation. Nine healthy New Zealand rabbits were ventilated at a constant pressure, while miniature accelerometers were attached to each side of the chest. Slowly progressing pneumothorax was induced by injecting 1 ml/min air into the pleural space on either side of the chest. The end of the experiment (tPTX) was defined when arterial O2 saturation from pulse oximetry dropped <90% or when vigorous spontaneous breathing began, since it represents the time of clinical detection using common methods. Consistent and significant changes were observed in 15 of the chest dynamics parameters. The most meaningful temporal changes were noted for features extracted from subsonic dynamics (<10 Hz), e.g., tidal amplitude, energy, and autoregressive poles. Features from the high-frequency band (10-200 Hz), e.g., energy and entropy, exhibited smaller but significant changes. At 70% tPTX, identification of asymmetric ventilation was attained for all animals. Side identification of the pneumothorax was achieved at 50% tPTX, within a 95% confidence interval. Diagnosis was, on average, 34.1 ± 18.8 min before tPTX. In conclusion, bilateral monitoring of the chest dynamics and acoustics provide novel information that is sensitive to asymmetric changes in ventilation, enabling early detection and localization of pneumothorax.