DNA-minor groove binding agents as anti-tubercular probes. Old tools for a new challenge?

Tuberculosis, an ancient infectious disease caused by Mycobacterium tuberculosis, ranks as one of the top ten killers worldwide. The limited number of validated targets and scarce therapeutic options demand that renewed efforts should be made to identify tuberculosis drugs with novel mechanisms of action. To this end, mycobacterial DNA might represent a potential target for the development of effective anti-tubercular compounds. In particular, the minor groove of DNA offers an important recognition site for small-molecules that can be programmed to bind to this region in a sequence-selective manner to disrupt mycobacterial transcription factors activity and ultimately cause bacterial cell death. This review describes the structural features of the DNA-minor groove, the requirements for small-molecules to bind to this site and the remarkable biophysical and antibacterial properties of DNA-minor groove binding agents, including netropsin, distamycin and their poly-heterocyclic analogues, diamidines, benzimidazole-containing molecules, duocarmycins and pyrrolo[2,1-c][1,4]benzodiazepines (PBDs). Furthermore, the ability of selected heterocyclic-polyamides and PBDs to significantly inhibit the growth of pathogenic, slow-growing M. tuberculosis and other non-pathogenic mycobacterial strains is highlighted. In summary, DNA-minor groove binding agents may serve as molecular scaffolds for the design of highly efficient probes to treat M. tuberculosis infections

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