RESUMO
Phimosis in boys is a common condition. In the majority of cases it is physiological without symptoms. Symptomatic phimosis can often be treated successfully with local steroid cream - only a minority of patients need surgery. This study concludes that diagnosis, information to patients and guardians, initiation and follow-up of local steroid treatment can successfully, and safely, be delegated to trained assistant nurses.
Assuntos
Betametasona , Fimose , Administração Tópica , Betametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Masculino , Fimose/diagnóstico , Fimose/tratamento farmacológico , Resultado do TratamentoRESUMO
Cystic fibrosis transmembrane conductance regulator (CFTR) potentiators and correctors are new drugs that target the basic CFTR protein defect and are expected to benefit cystic fibrosis patients. To optimize the substances so far proposed for human use, and to minimise unwanted side effects, it is essential to investigate possible interactions between the drugs and cell components. We used small-angle X-ray scattering with synchrotron radiation to analyse the effects of two representative drugs, the potentiator VX-770 (Ivacaftor), approved for human use, and the corrector VX-809 (Lumacaftor), on a model phospholipid membrane. By reconstruction of the electron density profile of unilamellar vesicles treated with VX-770 or VX-809 we found that these drugs penetrate the phospholipid bilayer. VX-809 becomes homogeneously distributed throughout the bilayer whereas VX-770 accumulates predominantly in the internal leaflet, behaviour probably favoured by the asymmetry of the bilayer, because of vesicle curvature. Penetration of the bilayer by these drugs, probably as part of the mechanisms of permeation, causes destabilization of the membrane; this must be taken into account during future drug development.
Assuntos
Aminofenóis/farmacologia , Aminopiridinas/farmacologia , Benzodioxóis/farmacologia , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Fosfolipídeos/metabolismo , Quinolonas/farmacologia , Ligação Proteica , Temperatura , Lipossomas Unilamelares/química , Lipossomas Unilamelares/metabolismoRESUMO
For children living with long-term illness, school age is a risk period with regard to psychosocial ill health and poor compliance with treatment. There is a need for methods to promote health, well-being, and self-esteem. This study describes a new concept for supporting children, person-centred web-based learning and support, which has been tested in 12 preschool children and incorporates learning about feelings, relationships, and the right to integrity. SKYPE was used for conversations between the child and the web teacher. Methods. The programme was developed and tested in two steps. The conversations were tape-recorded and analysed using phenomenography. The questions addressed concerned the quality of the intervention process: accessibility of intervention, learning content and support, and identification of measurable items and patterns. Findings. The children found it interesting to communicate with their web teacher using SKYPE. The story about Max and Sara served as a good basis for discussion, and development was found in the learning process. The children were able to talk about relations and feelings and developed an understanding for use in new situations in their daily lives. Items and patterns that are useful for research and documentation were identified, for example, well-being, resources, needs, and wishes.
RESUMO
We have exploited the intrinsic conformational flexibility of leghemoglobin to reengineer the heme active site architecture of the molecule by replacement of the mobile His61 residue with tyrosine (H61Y variant). The electronic absorption spectrum of the ferric derivative of H61Y is similar to that observed for the phenolate derivative of the recombinant wild-type protein (rLb), consistent with coordination of Tyr61 to (high-spin) iron. EXAFS data clearly indicate a 6-coordinate heme geometry and a Fe-O bond length of 185pm. MCD and EPR spectroscopies are consistent with this assignment and support ligation by an anionic (tyrosinate) group. The alteration in heme ligation leads to a 148mV decrease in the reduction potential for H61Y (-127+/-5mV) compared to rLb and destabilisation of the functional oxy-derivative. The results are discussed in terms of our wider understanding of other heme proteins with His-Tyr ligation.