RESUMO
Although polypharmacy is a major problem in the elderly, very few data have been published from Australasia. We retrospectively audited 68% of elderly patients admitted acutely to our medical unit (n= 424, mean age 80.3 ± 8 years) during a 30-day period (September, 2008). We found that long-term medications increased during hospital stay from 6.6 ± 4 to 7.7 ± 4 (P < 0.001). Adverse drug reactions were responsible for 24 admissions (5.7%). Polypharmacy is made worse by acute admission to hospital.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Admissão do Paciente/tendências , Polimedicação , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Hospitalização/tendências , Humanos , Masculino , Preparações Farmacêuticas/administração & dosagemRESUMO
The replication initiator protein RepA of the IncB plasmid pMU720 was shown to induce localized unwinding of its cognate origin of replication in vitro. DnaA, the initiator protein of Escherichia coli, was unable to induce localized unwinding of this origin of replication on its own but enhanced the opening generated by RepA. The opened region lies immediately downstream of the last of the three binding sites for RepA (RepA boxes) and covers one turn of DNA helix. A 6-mer sequence, 5'-TCTTAA-3', which lies within the opened region, was essential for the localized unwinding of the origin in vitro and origin activity in vivo. In addition, efficient unwinding of the origin of replication of pMU720 in vitro required the native positioning of the binding sites for the initiator proteins. Interestingly, binding of RepA to RepA box 1, which is essential for origin activity, was not required for the localized opening of the origin in vitro.
Assuntos
Proteínas de Bactérias/metabolismo , Replicação do DNA , Proteínas de Ligação a DNA/metabolismo , Plasmídeos/metabolismo , Proteínas/metabolismo , Origem de Replicação/fisiologia , Pegada de DNA , DNA Helicases , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Dosagem de Genes , Plasmídeos/genética , Origem de Replicação/genética , TransativadoresRESUMO
The replication initiator protein RepA of the IncB plasmid pMU720 was purified and used in DNase I protection assays in vitro. RepA protected a 68-bp region of the origin of replication of pMU720. This region, which lies immediately downstream of the DnaA box, contains four copies of the sequence motif 5'AANCNGCAA3'. Mutational analyses identified this sequence as the binding site specifically recognized by RepA (the RepA box). Binding of RepA to the RepA boxes was ordered and sequential, with the box closest to the DnaA binding site (box 1) occupied first and the most distant boxes (boxes 3 and 4) occupied last. However, only boxes 1, 2, and 4 were essential for origin activity, with box 3 playing a lesser role. Changing the spacing between box 1 and the other three boxes affected binding of RepA in vitro and origin activity in vivo, indicating that the RepA molecules bound to ori(B) interact with one another.
