Pharmacokinetics, biodistribution, and in vivo toxicity of 7-nitroindazole loaded in pegylated and non-pegylated nanoemulsions in rats.

Sepsis is a life-threatening condition caused by a dysregulated host response to infection. The development of sepsis is associated with excessive nitric oxide (NO) production, which plays an important role in controlling vascular homeostasis. 7-nitroindazole (7-NI) is a selective inhibitor of neuronal nitric oxide synthase (NOS-1) with potential application for treating NO imbalance conditions. However, 7-NI exhibits a low aqueous solubility and a short plasma half-life. To circumvent these biopharmaceutical limitations, pegylated (NEPEG7NI) and non-pegylated nanoemulsions (NENPEG7NI) containing 7-NI were developed. This study evaluates the pharmacokinetic profiles and toxicological properties of 7-NI loaded into the nanoemulsions. After a single intravenous administration of the free drug and the nanoemulsions at a dose of 10 mg.kg-1 in Wistar rats, 7-NI was widely distributed in the organs. The pharmacokinetic parameters of Cmax, t1/2, and AUC0-t were significantly increased after administration of the NEPEG7NI, compared to both free 7-NI and NENPEG7NI (p < 0.05). No observable adverse effects were observed after administering the free 7-NI, NEPEG7NI, or NENPEG7NI in the animals after a single dose of up to 3.0 mg.kg-1. The results indicated that 7-NI-loaded nanoemulsions are safe, constituting a promising approach to treating sepsis.

Effect of Endodontic Sealer in Young Molars Treated by Undergraduate Students - A Randomized Clinical Trial.

The progression of caries in permanent molar teeth of young patients, frequently result in endodontic treatment. This randomized blinded clinical trial assessed the effect of two endodontic sealers (Sealer 26 and AH Plus) on the incidence of pain and apical repair after endodontic treatment of young molar teeth, and secondly identify factors associated with the outcomes. Endodontic treatment was performed by undergraduate students in molar teeth (n=69) of young patients (n=54) at the Endodontic and Restorative Public Extension Clinic Service. Protaper Next was used and the endodontic sealers were allocated which were restored with direct composite resin. Two primary clinical outcomes - apical repair and postoperative pain, were assessed after 12 and 24 months for blinded operators. Description of incidence rates and mixed-model regression using Generalized Estimation Equations (GEE). After 2 years 69 molar teeth of 54 patients were evaluated. No effect of the endodontic sealer was observed irrespective of period of evaluation. Apical repair incidences and asymptomatic teeth were, respectively, 90.5 and 89.3, 96.8 and 90.0% during 1 and 2 years of follow-up. Failed apical repair was associated with unsatisfactory pulpectomy (p=0.003) and periapical conditions (p=0.007) as well as their interaction (p=0.016). None of these independent variables was able to predict the occurrence of pain in both periods. Prognosis of apical repair is dependent on the initial conditions. Endodontic treatment of young molars associated with composite resin restorations performed by undergraduate students have satisfactory results after 2 years and was effective to prevent the risk of permanent teeth loss.