Ex vivo study of the efficacy of H-files and rotary Ni-Ti instruments to remove gutta-percha and four types of sealer

AIM: To compare the efficacy of ProFile rotary Nickel-Titanium (Ni-Ti) instruments and Hedstroem-files (H-files) combined with Gates-Glidden (GG) drills during removal of gutta-percha root fillings used in combination with one of the four representative sealers. METHODOLOGY: Forty-eight single-rooted human teeth, with fully formed apices and straight root canals were used. The root canals were accessed and instrumented using a stepback technique with H-files. They were randomly assigned to four groups and subsequently filled with a combination of lateral and vertical condensation of gutta-percha and one of the following sealers: Roth 811, AH26, Endion and Roekoseal. The root fillings were removed 1 year later, using either H-files in combination with GG drills or the ProFile Ni-Ti system. Teeth were then grooved longitudinally and split. The amount of gutta-percha and sealer remaining on the root canal walls was traced and scored visually with the aid of a stereomicroscope. The scores were analysed and statistically compared with the Kruskal-Wallis test between the ProFile and H-file groups, as well as among the four sealer subgroups. Two samples from each group were studied under the scanning electron microscope to enhance inspection of canal walls and remaining material. RESULTS: Sealer remnants were observed with both techniques mainly in the middle and apical third of the root canal. The ProFile system and the H-files were associated with similar amounts of remaining filling material (P > 0.05). In the cervical third of the root canal all sealer remnants were removed with both techniques. In the middle and apical third AH26 was associated with a statistically significant greater quantity of remnants on the root canal walls with both removal techniques (P < 0.05). Endion, Roth 811 and Roekoseal were associated with approximately the same amount of filling material in the middle third of the root canal (P > 0.05), whereas in the apical third Endion was associated with significantly more remnants of filling material than the other two sealers with either ProFile or H-files (P < 0.05). CONCLUSIONS: None of the methods used for the removal of root fillings was totally effective, especially in the apical third of the root canal.     

Specific inhibition of the mitochondrial permeability transition prevents lethal reperfusion injury

The aim of the present study was to determine whether specific inhibition of mitochondrial permeability transition (MPT) by NIM811 at the time of reperfusion following acute myocardial infarction may protect the heart. MPT pore opening appears to be a pivotal event in cell death following acute myocardial infarction. Recently, MPT pore opening has been involved in ischemic preconditioning. In protocol 1, NZW rabbits underwent either no intervention (sham) or 10 min of ischemia followed by 5 min of reperfusion, preceded (preconditioned, PC) or not (control, C) by 5 min of ischemia and 5 min of reperfusion. Additional rabbits were treated by cyclosporin A (CsA) or its non-immunosuppressive and more specific derivative (NIM811) (10 mg kg(-1), IV bolus), either 10 min before ischemia or 1 min before reperfusion. Hearts were excised and mitochondria isolated for further assessment of Ca(2+)-induced MPT. In protocol 2, animals were randomly assigned into similar experimental groups and underwent 30 min of ischemia and 4 h of reperfusion. Infarct size was assessed by TTC staining, and apoptosis by TUNEL assay. The Ca2+ overload required to induce MPT pore opening was significantly higher in NIM811, CsA and PC groups than in controls. Both necrotic and apoptotic cardiomyocyte death were significantly reduced by NIM811, CsA and PC. In both protocols, administration of NIM811 at reperfusion provided full protection. These data indicate that specific inhibition of MPT pore opening at reperfusion following acute myocardial infarction provides a powerful antinecrotic and antiapoptotic protection.     

Phase I/II Study of Osimertinib With Bevacizumab in EGFR-mutated,T790M-positive Patients With Progressed EGFR-TKIs: West Japan Oncology Group 8715L (WJOG8715L)

Osimertinib is a standard treatment for epidermal growth factor receptor (EGFR)-mutated, T790M-positive patients with progression during EGFR-tyrosine kinase inhibitor (TKI) therapy. Osimertinib, a third-generation EGFR-TKI, allows progression-free survival of around 10 months, but its toxicity is well-tolerated compared with other EGFR-TKIs. Preclinical and clinical evidence suggests that EGFR-TKI may work synergistically with vascular endothelial growth factor inhibitors.We therefore plan a phase I/II study to investigate this possibility. In phase I, the primary endpoint is assessment of the tolerability of osimertinib and bevacizumab in 6 patients. Phase II then explores the efficacy of combined treatment compared with osimertinib monotherapy with progression-free survival as the primary endpoint. Secondary endpoints are overall response rate, time to treatment failure, overall survival, and safety. Eighty patients will be enrolled in phase II.