ABL kinase inhibition promotes lung regeneration through expansion of an SCGB1A1+ SPC+ cell population following bacterial pneumonia

Current therapeutic interventions for the treatment of respiratory infections are hampered by the evolution of multidrug resistance in pathogens as well as the lack of effective cellular targets. Despite the identification of multiple region-specific lung progenitor cells, the identity of molecules that might be therapeutically targeted in response to infections to promote activation of progenitor cell types remains elusive. Here, we report that loss of Abl1 specifically in SCGB1A1-expressing cells leads to a significant increase in the proliferation and differentiation of bronchiolar epithelial cells, resulting in dramatic expansion of an SCGB1A1+ airway cell population that coexpresses SPC, a marker for type II alveolar cells that promotes alveolar regeneration following bacterial pneumonia. Furthermore, treatment with an Abl-specific allosteric inhibitor enhanced regeneration of the alveolar epithelium and promoted accelerated recovery of mice following pneumonia. These data reveal a potential actionable target that may be exploited for efficient recovery after pathogen-induced infections

Laryngeal radionecrosis and hyperbaric oxygen therapy: Report of 18 cases and review of the literature

Laryngeal radionecrosis is a difficult late complication of radiotherapy. It is associated with hoarseness, edema, pain, weight loss, and upper airway obstruction. The medical treatment options are limited, and in severe cases, the patient may require tracheostomy or laryngectomy. We report clinical results in 18 patients treated with adjunctive hyperbaric oxygen (HBO) therapy for severe radionecrosis of the larynx. Of these 18 patients, 2 had grade 3 and 16 had grade 4 radionecrosis. The patients received a mean number of 41 HBO treatments (range, 6 to 80) at 2 atmospheres absolute for 2 hours, twice a day, 6 days a week. Thirteen patients (72.2%) had a major improvement after HBO therapy, and none of them required total laryngectomy. All patients preserved their voice and deglutition in good or normal condition. Five patients (27.8%) failed to have a good response to HBO and underwent total laryngectomy. One of these patients had local recurrence of his cancer 4 months later, and the other 3 had significant concurrent medical problems. The remaining patient received only 6 HBO treatments because of emergency heart surgery. These encouraging results are comparable to those of smaller previous studies suggesting that HBO has a beneficial effect in the management of advanced laryngeal radionecrosis

Carbon monoxide inhalation reduces skeletal muscle fatigue resistance.

AIM: To determine whether inhalation of carbon monoxide (CO), resulting in carboxyhaemoglobin (COHb) levels observed in smokers, had an effect on muscle fatigue during electrically evoked and voluntary muscle contractions. METHODS: Young non-smoking males inspired CO from a Douglas bag until their COHb level reached 6%. During the control condition the same participants inspired ambient air from a Douglas bag for 6 min. Fatigue was assessed as the decline in torque in isometric knee extensions, during 2 min of electrically evoked contractions (30 Hz, 1 s on, 1 s off) and during 2 min of maximal isometric voluntary contractions (1 s on, 1 s off). A fatigue index (FI) was calculated as the ratio of final torque : initial torque. Time to peak torque (TPT) and half relaxation time ((1/2)RT) were also determined for the electrically evoked contractions. RESULTS: The FI during both the voluntary fatigue test (control: 0.80 +/- 0.09 vs. CO: 0.70 +/- 0.08; mean +/- SD) and that of the fatigue test with electrically evoked contractions (control: 0.61 +/- 0.09 vs. CO: 0.53 +/- 0.12) was significantly lower after CO inhalation than after inhalation of ambient air (P < 0.05). There was, however, no effect of CO on the changes in TPT or (1/2)RT during the fatigue test. CONCLUSION: Carbon monoxide inhalation resulting in COHb levels found in smokers has an acute impact on the ability of the muscle to resist fatigue