Atención integral al paciente en situación terminal. Sala de acompañamiento

Sección "Buenas prácticas en gestión clínica"

The N-terminal DNA-binding 'zinc finger' of the oestrogen and glucocorticoid receptors determines target gene specificity.

Steroid hormone receptors activate specific gene transcription by binding as hormone-receptor complexes to short DNA enhancer-like elements termed hormone response elements (HREs). We have shown previously that a highly conserved 66 amino acid region of the oestrogen (ER) and glucocorticoid (GR) receptors, which corresponds to part of the receptor DNA binding domain (region C) is responsible for determining the specificity of target gene activation. This region contains two sub-regions (CI and CII) analogous to the 'zinc-fingers' of the transcription factor TFIIIA. We show here that CI and CII appear to be separate domains both involved in DNA binding. Furthermore, using chimaeric ERs in which either the first (N-terminal) (CI) or second (CII) 'zinc finger' region has been exchanged with that of the GR, indicates that it is the first 'zinc finger' which largely determines target gene specificity. We suggest that receptor recognition of the HRE is analogous to that of the helix-turn-helix DNA binding motif in that the receptor binds to DNA as a dimer with the first 'zinc finger' lying in the major groove recognizing one half of the palindromic HRE, and that protein-DNA interaction is stabilized through non-specific DNA binding and dimer interactions contributed by the second 'zinc finger'.

The role of C-Jun N-terminal kinase in a mouse model of intracerebral hemorrhage

Background: Intracerebral hemorrhage (ICH) is a subtype of stroke characterized by a haematoma within the brain parenchyma resulting from blood vessel rupture and with a poor outcome. In ICH, the blood entry into the brain triggers toxicity resulting in a substantial loss of neurons and an inflammatory response. At the same time, blood-brain barrier (BBB) disruption increases water content (edema) leading to growing intracranial pressure, which in turn worsens neurological outcome. Although the clinical presentation is similar in ischemic and hemorrhagic stroke, the treatment is different and the stroke type needs to be determined beforehand by imaging which delays the therapy. C-Jun N-terminal kinases (JNKs) are a family of kinases activated in response to stress stimuli and involved in several pathways such as apoptosis. Specific inhibition of JNK by a TAT-coupled peptide (XG-102) mediates strong neuroprotection in several models of ischemic stroke in rodents. Recently, we have observed that the JNK pathway is also activated in a mouse model of ICH, raising the question of the efficacy of XG-102 in this model. Method: ICH was induced in the mouse by intrastriatal injection of bacterial collagenase (0,1 U). Three hours after surgery, animals received an intravenous injection of 100 mg/kg of XG-102. The neurological outcome was assessed everyday until sacrifice using a score (from 0 to 9) based on 3 behavioral tests performed daily until sacrifice. Then, mice were sacrificed at 6 h, 24 h, 48 h, and 5d after ICH and histological studies performed. Results: The first 24 h after surgery are critical in our ICH mice model, and we have observed that XG-102 significantly improves neurological outcome at this time point (mean score: 1,8 + 1.4 for treated group versus 3,4+ 1.8 for control group, P<0.01). Analysis of the lesion volume revealed a significant decrease of the lesion area in the treated group at 48h (29+ 11mm3 in the treated group versus 39+ 5mm3 in the control group, P=0.04). XG-102 mainly inhibits the edema component of the lesion. Indeed, a significant inhibition Journal of Cerebral Blood Flow & Metabolism (2009) 29, S490-S493 & 2009 ISCBFM All rights reserved 0271-678X/09 $32.00 www.jcbfm.com of the brain swelling was observed in treated animals at 48h (14%+ 13% versus 26+ 9% in the control group, P=0.04) and 5d (_0.3%+ 4.5%versus 5.1+ 3.6%in the control group, P=0.01). Conclusions: Inhibition of the JNK pathway by XG- 102 appears to lead to several beneficial effects. We can show here a significant inhibition of the cerebral edema in the ICH model providing a further beneficial effect of the XG-102 treatment, in addition to the neuroprotection previously described in the ischemic model. This result is of interest because currently, clinical treatment for brain edema is limited. Importantly, the beneficial effects observed with XG-102 in models of both stroke types open the possibility to rapidly treat stroke patients before identifying the stroke subtype by imaging. This will save time which is precious for stroke outcome.

Thyrotropin-releasing hormone-stimulated thyrotropin expression involves islet-brain-1/c-Jun N-terminal kinase interacting protein-1.

Islet-brain-1 (IB1)/c-Jun N-terminal kinase interacting protein 1 (JIP-1) is a scaffold protein that is expressed at high levels in neurons and the endocrine pancreas. IB1/JIP-1 interacts with the c-Jun N-terminal kinase and mediates the specific physiological stimuli (such as cytokines). However, the potential role of the protein in the pituitary has not been evaluated. Herein, we examined expression of the gene encoding IB1/JIP-1 and its translated product in the anterior pituitary gland and a pituitary cell line, GH3. We then examined the potential role of IB1/JIP-1 in controlling TSH-beta gene expression. Exposure of GH3 cells to TRH stimulated the expression of IB1/JIP-1 protein levels, mRNA, and transcription of the promoter. The increase of IB1/JIP-1 content by transient transfection study of a vector encoding IB1/JIP-1 or by the stimulation of TRH stimulates TSH-beta promoter activity. This effect is not found in the presence of a mutated nonfunctional (IB1S59N) IB1/JIP-1 protein. Together, these facts point to a central role of the IB1/JIP-1 protein in the control of TRH-mediated TSH-beta stimulation.

The region of mouse mammary tumor virus DNA containing the long terminal repeat includes a long coding sequence and signals for hormonally regulated transcription.

Starting from a biologically active recombinant DNA clone of exogenous unintegrated GR mouse mammary tumor virus, we have generated three subclones of PstI fragments of 1.45, 1.1, and 2.0 kb in the plasmid vector PBR322. The nucleotide sequence has been determined for the clone of 1.45 kb which includes almost the complete region of the long terminal repeat (LTR) plus an adjacent stretch of unique sequence DNA. A short region of the 2.0 kb clone, containing the beginning of the LTR, has also been sequenced. Starting with the A of an initiation codon outside the LTR, we detected an open reading frame of 960 nucleotides, potentially coding for a protein of 320 amino acids (36K). Two hundred nucleotides downstream from the termination codon, and approximately 25 nucleotides upstream from the presumptive initiation site of viral RNA synthesis, we found a promoter-like sequence. The sequence AGTAAA was detected approximately 15-20 nucleotides upstream from the 3' end of virion RNA and probably serves as a polyadenylation signal. The 1.45 kb PstI fragment has been transfected into Ltk- cells together with a plasmid containing the thymidine kinase gene of herpes simplex virus. The virus-specific RNA synthesis detected in a Tk+ cell clone was strongly stimulated by the addition of dexamethasone.

A implantação do projeto de atendimento Móvel de Urgência em Salvador/BA: panorama e desafios

O estudo objetivou relatar a experiência na implantação e estruturação do projeto do Serviço Móvel de Urgência (SAMU-192), em Salvador, cujas bases legais foram portarias do Ministério da Saúde e a Norma Operacional de Assistência à Saúde 02/2002. O serviço tem como finalidade prestar assistência gratuita ao indivíduo, em um primeiro nível de atenção, com agravos de natureza clínica, cirúrgica, traumática e psiquiátrica que acarretam sofrimento, seqüelas ou morte e ocorrem fora do ambiente hospitalar. O objetivo específico foi garantir o atendimento às situações de urgência e emergência por meio do SAMU-192, regulado, hierarquizado e integrado ao Sistema Único de Saúde, assegurando recursos públicos inclusive integrados à rede complementar de assistência. Despesas para sua instalação foram pactuadas no município e em comissões intergestoras federal e estadual. Os desafios do serviço incluem educação comunitária, capacitação profissional, avaliação de recursos humanos e materiais, na dinâmica e qualidade da atenção.

Cuidando de pacientes em fase terminal: a perspectiva de alunos de enfermagem

Este estudo busca compreender como alunos de graduação em Enfermagem percebem a si mesmos ao cuidar de pacientes em fase terminal e expor os significados da experiência vivida. Foram entrevistados 14 alunos, respondendo à questão: Como se mostra a você o cuidar do paciente na fase terminal? Para os alunos, é sempre uma experiência dolorosa, que os coloca face a face com suas fragilidades e inseguranças. Eles atribuem suas dificuldades à própria incapacidade de aceitar a morte e ao despreparo e inexperiência. Relatam que falta apoio dos profissionais com quem compartilham esse cuidado. No que se refere à formação profissional, para alguns a experiência foi positiva, apesar das dificuldades; outros a avaliam negativamente, resultando em rejeição a situações semelhantes. Novas investigações sobre o tema são necessárias para aprofundar e ampliar a reflexão para o âmbito da formação dos enfermeiros em nível nacional.

Essential role of the N-terminal region of TFII-I in viability and behavior

Background: GTF2I codes for a general intrinsic transcription factor and calcium channel regulator TFII-I, with high and ubiquitous expression, and a strong candidate for involvement in the morphological and neuro-developmental anomalies of the Williams-Beuren syndrome (WBS). WBS is a genetic disorder due to a recurring deletion of about 1,55-1,83 Mb containing 25-28 genes in chromosome band 7q11.23 including GTF2I. Completed homozygous loss of either the Gtf2i or Gtf2ird1 function in mice provided additional evidence for the involvement of both genes in the craniofacial and cognitive phenotype. Unfortunately nothing is now about the behavioral characterization of heterozygous mice. Methods: By gene targeting we have generated a mutant mice with a deletion of the first 140 amino-acids of TFII-I. mRNA and protein expression analysis were used to document the effect of the study deletion. We performed behavioral characterization of heterozygous mutant mice to document in vivo implications of TFII-I in the cognitive profile of WBS patients. Results: Homozygous and heterozygous mutant mice exhibit craniofacial alterations, most clearly represented in homozygous condition. Behavioral test demonstrate that heterozygous mutant mice exhibit some neurobehavioral alterations and hyperacusis or odynacusis that could be associated with specific features of WBS phenotype. Homozygous mutant mice present highly compromised embryonic viability and fertility. Regarding cellular model, we documented a retarded growth in heterozygous MEFs respect to homozygous or wild-type MEFs. Conclusion: Our data confirm that, although additive effects of haploinsufficiency at several genes may contribute to the full craniofacial or neurocognitive features of WBS, correct expression of GTF2I is one of the main players. In addition, these findings show that the deletion of the fist 140 amino-acids of TFII-I altered it correct function leading to a clear phenotype, at both levels, at the cellular model and at the in vivo model.

FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces FADD phosphorylation and inhibits fas-mediated Jun NH(2)-terminal kinase activation.

Fas is a cell surface death receptor that signals apoptosis. Several proteins have been identified that bind to the cytoplasmic death domain of Fas. Fas-associated death domain (FADD), which couples Fas to procaspase-8, and Daxx, which couples Fas to the Jun NH(2)-terminal kinase pathway, bind independently to the Fas death domain. We have identified a 130-kD kinase designated Fas-interacting serine/threonine kinase/homeodomain-interacting protein kinase (FIST/HIPK3) as a novel Fas-interacting protein. Binding to Fas is mediated by a conserved sequence in the COOH terminus of the protein. FIST/HIPK3 is widely expressed in mammalian tissues and is localized both in the nucleus and in the cytoplasm. In transfected cell lines, FIST/HIPK3 causes FADD phosphorylation, thereby promoting FIST/HIPK3-FADD-Fas interaction. Although Fas ligand-induced activation of Jun NH(2)-terminal kinase is impaired by overexpressed active FIST/HIPK3, cell death is not affected. These results suggest that Fas-associated FIST/HIPK3 modulates one of the two major signaling pathways of Fas.

Sistema NAS: Nursing Activities Score em tecnologia móvel

Este estudo objetivou apresentar a estrutura informatizada que viabiliza a utilização do Nursing Activities Score (NAS) em tecnologia móvel. Trata-se de um projeto de desenvolvimento de produção tecnológica baseado na engenharia de software, fundamentada na teoria do ciclo de vida de desenvolvimento de sistema. O Sistema NAS foi construído em dois módulos: módulo de pesquisa, cujo acesso é realizado através de computador pessoal (PC) e módulo de coleta de dados, acessado por meio de dispositivo móvel (smartphone). O Sistema NAS foi construído de modo a permitir que outros formulários, além do instrumento NAS, sejam incluídos futuramente. Assim, entende-se que o desenvolvimento do Sistema NAS permitirá a aproximação entre os enfermeiros e a tecnologia móvel facilitando o acesso imediato aos dados do instrumento referentes aos pacientes, auxiliando na tomada de decisão e na adequação do quantitativo de pessoal de enfermagem para prestação da assistência.

Increased plasma levels of N-terminal brain natriuretic peptide (NT-proBNP) in type 2 diabetic patients with vascular complications

Résumé : Les concentrations plasmatiques du peptide natriurétique de type B sont augmentées chez les diabétiques de type 2 atteints de complications vasculaires. But : Les concentrations plasmatiques du peptide natriurétique de type B (NT-proBNP) sont augmentées chez les diabétiques de type 2 atteints de complications vasculaires. Les concentrations plasmatiques du peptide natriurétique de type B (BNP), ou de sa pro-hormone (NT-proBNP), sont reconnues depuis peu comme marqueur de choix de la dysfonction cardiaque. Les diabétiques de type 2 sont à haut risque de développer des complications cardiovasculaires. L'objectif de cette étude a été de déterminer si les concentrations plasmatiques de NT-proBNP étaient comparables chez des diabétiques de type 2 avec ou sans complications vasculaires. Méthodes : Nous avons mesuré le NT-proBNP plasmatique chez 54 diabétiques de type 2, 27 sans complications micro- ou macrovasculaires et 27 présentant des complications soit micro- soit macrovasculaires, soit les deux. Le même dosage a été effectué chez 38 témoins sains, appariés pour l'âge et le sexe avec les diabétiques. Résultat : Le NT-proBNP plasmatique était plus élevé chez les diabétiques avec complications (médiane 121 pg/ml, intervalle interquartile 50-240 pg/ml) que chez ceux sans complications (37 pg/ml, 21-54 pg/ml, P < 0,01). Comparés au groupe témoin (55 pg/ml, 40-79 pg/ml), seuls les diabétiques avec complications vasculaires avaient un NT-proBNP plasmatique significativement augmenté (P < 0,001). Chez les diabétiques la maladie coronarienne et la néphropathie (définie selon l'excrétion urinaire d'albumine) étaient chacune associée de façon indépendante avec une augmentation des concentrations plasmatiques de NT-proBNP. Conclusion : Chez les diabétiques de type 2 souffrant de complications micro- ou macrovasculaires, les concentrations plasmatiques de NT-proBNP sont augmentées par rapport à celles des malades indemnes de complications vasculaires. L'augmentation de sécrétion de ce peptide est associée de façon indépendante avec la maladie coronarienne et la néphropathie. La mesure du NT-proBNP plasmatique pourrait donc être utile pour dépister la présence de complications micro- ou macrovasculaires.

Sufrimiento en infantes con enfermedad terminal: perspectiva de padres y profesionales

Diagnóstico de situación con una metodología científica de carácter exploratorio y descriptivo (observación participante con tratamiento estadístico descriptivo) con el fin de identificar las prácticas de enfermería en el ámbito de la promoción de la salud durante la consulta de enfermería para la salud infantil. De las 31 consultas observadas (n = 31) se mostró que la mayoría de las observaciones se produjeron en niños menores de 2 años siendo que el tema más discutido és alimentación con el uso predominante de la metodología expositiva. Se verificó poca utilización de apoyo informativo y cuando se utilizan se refieren a temas de seguridad y nutrición. La mayoría de los proveedores ha hecho preguntas y se verifico reducido registro de la interacción proveedores/niños con un expendio promedio de 23 minutos por consulta. Teniendo en cuenta los resultados y reflectando en ellos se destaca como intervención la elaboración de un manual para la promoción de la salud con la integración de la teoría y la evidencia de las buenas prácticas en este ámbito.

A peptide inhibitor of c-Jun N-terminal kinase for the treatment of endotoxin-induced uveitis.

PURPOSE: To evaluate the effect of XG-102 (formerly D-JNKI1), a TAT-coupled dextrogyre peptide that selectively inhibits the c-Jun N-terminal kinase, in the treatment of endotoxin-induced uveitis (EIU). METHODS: EIU was induced in Lewis rats by LPS injection. XG-102 was administered at the time of LPS challenge. The ocular biodistribution of XG-102 was evaluated using immunodetection at 24 hours after either 20 microg/kg IV (IV) or 0.2 microg/injection intravitreous (IVT) administrations in healthy or uveitic eyes. The effect of XG-102 on EIU was evaluated using clinical scoring, infiltration cell quantification, inducible nitric oxide synthase (iNOS) expression and immunohistochemistry, and cytokines and chemokines kinetics at 6, 24, and 48 hours using multiplex analysis on ocular media. Control EIU eyes received vehicle injection IV or IVT. The effect of XG-102 on c-Jun phosphorylation in EIU was evaluated by Western blot in eye tissues. RESULTS: After IVT injection, XG-102 was internalized in epithelial cells from iris/ciliary body and retina and in glial and microglial cells in both healthy and uveitic eyes. After IV injection, XG-102 was concentrated primarily in inflammatory cells of uveitic eyes. Using both routes of administration, XG-102 significantly inhibited clinical signs of EIU, intraocular cell infiltration, and iNOS expression together with reduced phosphorylation of c-Jun. The anti-inflammatory effect of XG-102 was mediated by iNOS, IFN-gamma, IL-2, and IL-13. CONCLUSIONS: This is the first evidence that interfering with the JNK pathway can reduce intraocular inflammation. Local administration of XG-102, a clinically evaluated peptide, may have potential for treating uveitis.

Aplicativo multimídia em plataforma móvel para o ensino da mensuração da pressão venosa central

O objetivo do estudo foi desenvolver e avaliar um aplicativo multimídia em plataforma móvel para o ensino da Mensuração da Pressão Venosa Central (PVC). A pesquisa foi desenvolvida em três fases (Levantamento das necessidades; Metodologia de desenvolvimento do aplicativo multimídia e Avaliação do aplicativo multimídia). A multimídia foi o método escolhido por favorecer um ambiente motivador e dinâmico, integrar imagens e textos num aplicativo disponível para celulares, constituindo-se um meio móvel e autônomo de aprendizagem. Os resultados permitem demonstrar a viabilidade do desenvolvimento da ferramenta para subsidiar a prática pedagógica e abrem perspectivas para acreditar que, na educação em Enfermagem, a tecnologia disponível pode descortinar novos modos de aprender significativamente.

A estrutura representacional do cuidado intensivo para profissionais de Unidade de Terapia Intensiva móvel

O presente trabalho trata-se de pesquisa qualitativa baseada na Teoria das Representações Sociais em sua abordagem estrutural, que objetivou analisar as representações sociais do cuidado intensivo para profissionais que atuam em Unidade de Terapia intensiva móvel mediante a determinação do núcleo central e do sistema periférico. Envolveu 73 profissionais de saúde de um Serviço de Atendimento Móvel de Urgência. Os dados foram coletados através de evocações livres ao termo indutor cuidado a pessoa em risco de vida e tratados pelo software EVOC. Observa-se um núcleo estruturado no conhecimento e na responsabilidade, ao mesmo tempo que os elementos de contraste apresentam léxicos como agilidade, atenção, estresse e humanização. A estrutura representacional revelada pelos participantes refere-se especialmente à funcionalidade do cuidado intensivo, distinguindo-o pelos desafios e estímulos que proporciona a quem desempenha funções nessa área.