Intraoral extra-mucosal fixation of fractures in the atrophic edentulous mandible.

Atrophy of the mandible leads to a decrease in the bone mass, making it more vulnerable to fractures. A direct relationship has been demonstrated between the height of the bone in the area of the fracture and the incidence of postoperative complications of bone healing. Basic principles of fracture management in both edentulous and non edentulous patients are open reduction and internal fixation with osteosynthesis of the fracture to achieve restoration in terms of aesthetics and functionality. Several authors have discussed the advantages and disadvantages of the transoral and extraoral approaches. Between January 2007 and June 2011, 13 patients affected by bilateral fractures of atrophic mandibles were treated by extra-mucosal intraoral stabilization with satisfactory results. This approach reduces the risks of damage of the marginalis mandibulae nerve with low operation time, while avoiding unsightly scars

Novel C-3-(N-alkyl-aryl)-aminomethyl rifamycin SV derivatives exhibit activity against rifampicin-resistant Mycobacterium tuberculosis RpoBS522L strain and display a different binding mode at the RNAP β-subunit site compared to rifampicin

Antimicrobial resistance is a main concern in tuberculosis treatment and is often associated with the emergence of Mycobacterium tuberculosis strains resistant to rifampicin (RIF), which is one of the cornerstones of tuberculosis chemotherapy. In this study, aminoalkyl-aromatic ring tails were appended to the C3 position of rifamycin core to assess the role of C3 substitutions to the anti-mycobacterial activity of the rifamycin antibiotics. The typical hydrazone unit of RIF was replaced by an amino-alkyl linkage to connect the aromatic ring tails with the rifamycin naphthoquinone core. Eight novel C3-(N-alkyl-aryl)-aminoalkyl analogues of rifamycin SV were synthesised and screened in vitro against wild-type HR37Rv and “hypervirulent” HN-878 strains, and a panel of rifampicin-resistant M. tuberculosis clinical isolates carrying mutations at the 522, 531 and 455 positions of the rpoB gene (RpoBS522L, RpoBS531L and RpoBH455D strains). The analogues exhibited anti-tubercular activity against H37Rv and HN-878 at submicromolar or nanomolar concentrations, and against clinical H37Rv isolates bearing the S522L mutations at low micromolar concentration. Benzylamine moiety-including analogue 8 was as active as rifampicin against HN-878 with a MIC90 value of 0.02 μM, whereas 14 and 15, which included tryptamine and para-methyl-sulfonylbenzylamine C3-substituents, respectively, showed higher anti-tubercular activity (MIC90 = 3 μM) compared to rifampicin against the S522L mutated H37Rv strain. Detailed in silico analysis of different RNAP molecular systems predicted a distinct, possibly novel, binding mode for the new rifamycin analogues. These were found to occupy a different space in the binding pockets of both wild type and mutated RNAP proteins compared to that of rifampicin. Moreover, the molecular modelling experiments investigated the ability of the novel analogues aromatic tails to establish key interactions at the RNAP binding site. These interesting findings might pave the way for generating rifamycin analogues that can overcome anti-microbial resistance in M. tuberculosis