Quantum mechanical interpretation of nitrite reduction by cytochrome cd1 nitrite reductase from Paracoccus pantotrophus.

The reduction of nitrite to nitric oxide in respiratory denitrification is catalyzed by a cytochrome cd(1) nitrite reductase in Paracoccus pantotrophus (formerly known as Thiosphaera pantotropha LMD 92.63). High-resolution structures are available for the fully oxidized [Fülöp, V., Moir, J. W., Ferguson, S. J., and Hajdu, J. (1995) Cell 81, 369-377; Baker, S. C., Saunders, N. F., Willis, A. C., Ferguson, S. J., Hajdu, J., and Fülöp, V. (1997) J. Mol. Biol. 269, 440-455] and fully reduced forms of this enzyme, as well as for various intermediates in its catalytic cycle [Williams, P. A., Fülöp, V., Garman, E. F., Saunders, N. F., Ferguson, S. J., and Hajdu, J. (1997) Nature 389, 406-412]. On the basis of these structures, quantum mechanical techniques (QM), including density functional methods (DFT), were combined with simulated annealing (SA) and molecular mechanics techniques (MM) to calculate the electronic distribution of molecular orbitals in the active site during catalysis. The results show likely trajectories for electrons, protons, substrates, and products in the process of nitrite reduction, and offer an interpretation of the reaction mechanism. The calculations indicate that the redox state of the d(1) heme and charges on two histidines in the active site orchestrate catalysis locally. Binding of nitrite to the reduced iron is followed by proton transfer from His345 and His388 to one of the oxygens of nitrite, creating a water molecule and an [Fe(II)-NO(+)] complex. Valence isomerization within this complex gives [Fe(III)-NO]. The release of NO from the ferric iron is influenced by the protonation state of His345 and His388, and by the orientation of NO on the d(1) heme. Return of Tyr25 to a hydrogen-bonding position between His345 and His388 facilitates product release, but a rebinding of Tyr25 to the oxidized iron may be bypassed in steady-state catalysis.

Malformaciones congénitas mayores del tubo digestivo-atresia del esófago asociada a obstrucción duodenal por páncreas anular / Congenital malformation mayority of the digestive tubes-esophageal atresia associated at duodenal obstruction due to anular pancreas

Se presenta un caso de Atresia de Esófago con Fístula Traqueoesofágica Inferior (Tipo III de la clasificación de Gross), que presentó como malformación congénita asociada Obstrucción Duodenal por Páncreas Anular, a quien no se pudo realizar anostomosis esofágica primaria por separación importante entre ambos segmentos esofágicos, practicándose en el primer tiempo quirurugico Ligadura de Fístula Traqueoesofágica Inferior, Duodenoduodenoanastomosis laterolateral en forma de Diamante más Gastrostomía. En un segundo tiempo quirurgico, a los tres meses de edad, se practica Anastomosis Esofágica, presentando como complicación postoperatoria, perforación esofágica por encima de la anastomosis, que requirió reintervención quirúrgica, alimentación parenteral y tratamiento con Anfotericina por presentar Cultivos de Hongos positivos para Cándida albicans. Actualmente paciente en buenas condiciones tolerando adecuadamente vía oral. Se analizan las Malformaciones Congénitas más frecuentes asociadas a al Atresia de Esófago y las complicaciones postoperatorias, sus causas y manejo

Dementia care-receiver needs and their impact on caregivers.

This study examines home-based persons with dementia, their needs associated with activities of daily living (ADL), cognitive impairment, and disruptive behaviors, and the relationship of these needs to caregiver distress and burden. Findings suggest that selected disruptive behaviors were most distressing to caregivers, and that when disruptive behaviors occurred more frequently, caregivers were significantly more distressed with these behaviors and reported higher levels of burden. The frequency of cognitive impairment behaviors and level of ADL impairment were not significantly related to caregiver burden, but caregiver distress with these needs was significantly related to caregiver burden.