Improvement of porphyrins for G-quadruplex DNA targeting.

G-quadruplex nucleic acids are emerging as therapeutic targets for small molecules referred to as small-molecule G-quadruplex ligands. The porphyrin H(2)-TMPyP4 was early reported to be a suitable motif for G-quadruplex DNA recognition. It probably binds to G-quadruplex nucleic acid through π-π stacking with the external G-quartets. We explored chemical modifications of this porphyrin such as insertion of various metal ions in the centre of the aromatic core and addition of bulky substituents that may improve the specificity of the compound toward G-quadruplex DNA. Porphyrin metallation, affording a G4-ligand with two symmetric faces, allowed the conclusion that the presence of an axial water molecule perpendicular to the aromatic plane lowered but did not hamper π-π stacking interactions between the aromatic parts of the ligand on the one hand and the external G-quartet on the other. The charge introduced in the centre of the porphyrin had little influence on binding. Thus, the ionic channel in the centre of G-quadruplex nucleic acids was not found to provide clear additional molecular clues for G-quadruplex nucleic acids targeting by porphyrins tested in the present study. Furthermore, we confirmed the unique G-quadruplex selectivity of a porphyrin modified with four bulky substituents at the meso positions and showed that although the compound is not "drug-like" it was capable of entering cells in culture and mediated some of the typical cellular effects of small-molecule G-quadruplex ligands.

Interaction of cationic nickel and manganese porphyrins with the minor groove of DNA.

The capacity of a series of new cationic nickel and manganese metalloporphyrins to bind in the minor groove of DNA was evaluated by binding competition experiments with manganese(III)-bis-aqua-meso-tetrakis(4-N-methylpyridiniumyl)porphyrin, Mn-TMPyP, a powerful artificial nuclease when associated with KHSO(5). The four N-methylpyridiniumyl substituents on this porphyrin macrocycle are responsible for a strong binding affinity for the minor groove of AT-rich DNA. The inhibition of DNA cleavage mediated by Mn-TMPyP/KHSO(5) by the various tested porphyrins correlated with their competitive occupancy of the minor groove site of Mn-TMPyP. Introduction of long and flexible cationic substituents at the periphery of the porphyrin macrocycle precluded the interaction of the porphyrin derivative in the minor groove and resulted in low affinity for DNA. On the other hand, introduction of phenylpyridiniumyl substituents on the porphyrin macrocycle surprisingly conferred the new porphyrin derivative with a tight binding in the minor groove of a six consecutive AT base pairs sequence. These data on structural requirements for minor groove DNA binding will help the rational design of porphyrin derivatives for selective targeting of quadruplex DNA versus double-stranded DNA.

Cylindrical dental implants with hydroxyapatite- and titanium plasma spray-coated surfaces: 5-year results.

Clinical follow-up was conducted on 127 cylindrical implants placed in 21 patients after 5 years of function: 75 implants were coated with titanium plasma spray (TPS) and 52 implants were coated with hydroxyapatite (HA). The aim of the study was to assess possible differences in clinical function and success rates for each implant type. Clinical and radiographic evaluations were conducted, and the periodontal indices of gingival bleeding, plaque, and calculus were measured. Cumulative data were analyzed for differences by implant type and jaw location. No significant differences were found between the 2 implant systems according to the periodontal parameters studied; however, 5-year success rates were 86.7% for TPS-coated implants and 94.3% for HA-coated implants. The periodontal probe index presented abnormal values in the patients with systemic disease and those who were provisionally restored with single-tooth restorations, complete screw-retained dentures, and fixed partial dentures. There were no differences regarding implant placement when mandibles and maxillae were compared. Long-term success rates were outstanding for HA-coated implants and acceptable for TPS-coated implants after 5 years of function. No significant differences were found between the 2 surfaces.

Estenosis congénita de la abertura piriforme nasal como causa de distrés respiratorio en el recién nacido: aportación de cuatro casos diagnosticados mediante TC / Congenital nasal pyriform aperture stenosis as a cause of respiratory distress in newborns: presentation diagnosed by menas of CT

La estenosis congénita de la abertura piriforme nasal es una causa rara de obstrucción de la vía aérea en el recién nacido, que puede ser indistinguible clínicamente de la atresia de coanas, entidad esta última mucho más frecuente. La tomografía computarizada (TC) confirma el diagnóstico de esta anomalía, demostrando en detalle la alteración anatómica subyacente, pudiendo manifestarse de forma aislada o asociada a otras alteraciones. Aportamos cuatro casos de estenosis congénita de la abertura piriforme, los cuales presentaban distrés respiratorio y síntomas clínicos semejantes a los de la atresia de coanas en recién nacidos, en los cuales el diagnóstico precoz y un tratamiento conservador colocando un tubo para mantener permeable la luz, hasta que el crecimiento de la abertura piriforme permita realizar una respiración normal, consiguió la recuperación de los pacientes (AU)

Cordoma cervical: a propósito de un caso / Cervical chordoma: a case report

Los cordomas se originan a partir de restos de la notocorda, pudiendo aparecer en cualquier localización desde el clivus hasta el sacro y constituyen el 3-4 por ciento de los tumores óseos primarios. Presentamos un caso de cordoma cervical a la altura de C2 en un varón de 45 años, constituyendo la localización vertebral menos frecuente en la bibliografía. Aportamos los hallazgos radiológicos en TC y RM cervical (AU)