RESUMO
Background: Chronic calcium channel blockers (CCBs) are indicated in children with idiopathic/heritable pulmonary arterial hypertension (IPAH/HPAH) and positive response to acute vasodilator challenge. However, minimal safety data are available on the long-term high-dose exposure to CCBs in this population. Methods: Patients aged 3 months to 18 years who were diagnosed with IPAH/HPAH and treated with CCB in the past 15 years were retrospectively reviewed. The maximum tolerated dose and the long-term safety of high-dose CCBs on the cardiovascular and noncardiovascular systems were assessed. Results: Thirty-two eligible children were enrolled in the study, with a median age of 9 (6-11) years old. Thirty-one patients were treated with diltiazem after diagnosis. The median maximum tolerated dose was 12.9 (9.8-16.8) mg/kg/day. Children younger than 7 years used higher doses than children in the older age group, 16.4 (10.5-28.5) mg/kg/day vs. 12.7 (6.6-14.4) mg/kg/day, P < 0.05. Patients were followed up for a median period of 6.2 (2.6-10.8) years. One patient died from a traffic accident, and others showed a stable or improved WHO functional class status. Thirteen (40.6%) and 10 (31.3%) patients developed arrhythmias and hypotension. Nine (28.1%) patients had sinus bradycardia, five (21.9%) had first-degree or second-degree type II atrial-ventricular blocks, and two (6.3%) had second-degree type II atrial-ventricular blocks. Most of these arrhythmias were transient and relieved after CCB dose adjustment. The most reported noncardiovascular adverse effect was gingival hyperplasia (13, 40.6%), accompanied by different degrees of dental dysplasia. No liver or kidney dysfunction was reported. Conclusion: Diltiazem was used in a very high dose for eligible children with IPAH/HPAH. The toxicity of long-term CCB use on the cardiovascular system is mild and controllable. Clinicians should also monitor the noncardiovascular adverse effects associated with drug therapy.
RESUMO
The study aimed to obtain chitosan composite films with gratifying physical and functional properties. First, we developed a Pickering emulsion containing clove essential oil (CEO)-loaded nanoparticles with 1:2 (w/w) zein and sodium caseinate (NaCas). We found that in this ratio, the CEO-loaded zein-NaCas (C/ZN) nanoparticles had smaller particle size, proper polydispersity index (PDI) and zeta potential as well as higher encapsulation efficiency. Then, the acquired C/ZN nanoparticles were incorporated into chitosan film at three levels (0.2%, 0.4% and 0.6%), reducing the water vapor permeability to 4.62 × 10-6 g·s-1·m-1·Pa. Also, the tensile strength and break elongation of chitosan films were increased, reaching 38.67 MPa and 1.56%, respectively. The infrared spectroscopy verified that the intermolecular hydrogen bonds exist between chitosan and C/ZN nanoparticles. The chitosan composite films showed a controlled-release property of CEO in 96 h. Finally, the chitosan composite films showed the improved antibacterial property by creating larger inhibition zones against Escherichia coli (3.29 mm) and Staphylococcus aureus (6.15 mm). In general, we improved the water resistance, light blocking, mechanical strength, controlled-release and antibacterial properties of chitosan film with C/ZN nanoparticles. The current edible antibacterial films have great potential on applications for food preservation and food delivery system.