RESUMEN
The larynx is an essential organ in the respiratory tract and necessary for airway protection, respiration, and phonation. Cigarette smoking is a significant risk factor associated with benign and malignant laryngeal diseases. Despite this association, the underlying mechanisms by which cigarette smoke (CS) drives disease development are not well elucidated. In the current study, we developed a short-term murine whole body inhalation model to evaluate the first CS-induced cellular responses in the glottic [i.e. vocal fold (VF)] and subglottic regions of the larynx. Specifically, we investigated epithelial cell proliferation, cell death, surface topography, and mucus production, at various time points (1 day, 5 days, 10 days) after â¼ 2 h exposure to 3R4F cigarettes (Delivered dose: 5.6968 mg/kg per cigarette) and following cessation for 5 days after a 5 day CS exposure (CSE). CSE elevated levels of BrdU labeled proliferative cells and p63 labeled epithelial basal cells on day 1 in the VF. CSE increased proliferative cells in the subglottis at days 5, 10 and following cessation in the subglottis. Cleaved caspase-3 apoptotic activity was absent in VF at all time points and increased at day 1 in the subglottis. Evaluation of the VF surface by scanning electron microscopy (SEM) revealed significant epithelial microprojection damage at day 10 and early signs of necrosis at days 5 and 10 post-CSE. SEM visualizations additionally indicated the presence of deformed cilia at days 5 and 10 after CSE and post-cessation in the respiratory epithelium lined subglottis. In terms of mucin content, the impact of short-term CSE was observed only at day 10, with decreasing acidic mucin levels and increasing neutral mucin levels. Overall, these findings reveal regional differences in murine laryngeal cellular responses following short-term CSE and provide insight into potential mechanisms underlying CS-induced laryngeal disease development.
RESUMEN
Severe inborn cardiac malformations are typically corrected in cardioplegia, with a cardio-pulmonary bypass (CPB) taking over body circulation. During the operation the arrested hearts are subjected to a global ischemia/reperfusion injury. Although the applied cardioplegic solutions have a certain protective effect, application of additional substances to reduce cardiac damage are of interest.18 domestic piglets (10-15â¯kg) were subjected to a 90â¯min CPB and a 120â¯min reperfusion phase without or with the application of epigallocatechin-3-gallate (10â¯mg/kg body weight) or minocycline (4â¯mg/kg body weight), with both drugs given before and after CPB. 18 additional sham-operated piglets without or with epigallocatechin-3-gallate or minocycline served as controls. In total 36 piglets were analyzed (3 CPB-groups and 3 control groups without or with epigallocatechin-3-gallate or minocycline respectively; 6 piglets per group). Hemodynamic and blood parameters and ATP-measurements were assessed. Moreover, a histological evaluation of the heart muscle was performed. RESULTS: Piglets of the CPB-group needed more catecholamine support to achieve sufficient blood pressure. Ejection fraction and cardiac output were not different between the 6 groups. However, cardiac ATP-levels and blood lactate were significantly lower and creatine kinase was significantly higher in the three CPB-groups. Markers of apoptosis, hypoxia, nitrosative and oxidative stress were significantly elevated in hearts of the CPB-group. Nevertheless, addition of epigallocatechin-3-gallate or minocycline significantly reduced markers of myocardial damage. Noteworthy, EGCG was more effective in reducing markers of hypoxia, whereas minocycline more efficiently decreased inflammation. CONCLUSIONS: While epigallocatechin-3-gallate or minocycline did not improve cardiac hemodynamics, markers of myocardial damage were significantly lower in the CPB-groups with epigallocatechin-3-gallate or minocycline supplementation.