Polymorphism of human telomeric quadruplexes with drugs: a multi-technique biophysical study.

The human telomeric G-quadruplex structural motif of DNA has come to be known as a new and stimulating target for anticancer drug discovery. Small molecules that interact with G-quadruplex structures in a selective way have gained impressive interest in recent years as they may serve as potential therapeutic agents. Here, we show how circular dichroism, UV resonance Raman and small angle X-ray scattering spectroscopies can be effectively combined to provide insights into structural and molecular aspects of the interaction between human telomeric quadruplexes and ligands. This study focuses on the ability of berberine and palmatine to bind with human telomeric quadruplexes and provides analysis of the conformational landscape visited by the relevant complexes upon thermal unfolding. With increasing temperature, both free and bound G-quadruplexes undergo melting through a multi-state process, populating different intermediate states. Despite the structural similarity of the two ligands, valuable distinctive features characterising their interaction with the G-quadruplex emerged from our multi-technique approach.

[Surgical risk in patients with heart valve disease in non-cardiac surgery]. / Rischio operatorio nel valvulopatico per gli interventi di chirurgia non cardiaca.

Our purpose was to retrospectively evaluate major risk of non cardiac surgery in patients with valvular heart disease. We studied retrospectively 136 patients, 44 affected by aortic, 81 by mitral and 11 by mitroaortic valve disease. NYHA class was I-II in 130 and III in 6 patients. Sixty four patients underwent orthopedic surgery, 57 patients occulistic surgery and 5 patients urological surgery. There were no hospital deaths. Fifteen patients developed major perioperative complication: 7 serious ventricular arrhythmias, 6 hypotension, 2 "hypertensive attacks". We conclude that non cardiac surgery is safe in patients with valvular heart disease.

The association of cleidocranial dysostosis with hearing loss.

Three new cases of cleidocranial dysostosis with hearing loss are reported in this paper. The significant points concerning this association are: (1) the hearing deficit is predominantly a middle ear conduction problem secondary to structural abnormalities of the ossicles; (2) there is sometimes a small bone conduction deficit indicating either a cochlear or an eighth nerve problem; (3) the middle ear hearing loss was corrected surgically in one reported case; (4) there is dense sclerosis of the temporal bone which makes a middle ear operation technically difficult; and (5) hearing loss with cleidocranial dysostosis may be more common than the number of cases in the literature suggests.