974 resultados para Doente em fase terminal


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O objetivo deste experimento foi avaliar diferenças na quantidade total de água armazenada no solo, na capacidade de armazenamento de água disponível às plantas e no consumo de água de plantas de milho cultivadas em solos de diferentes texturas. O experimento foi instalado em área do Departamento de Engenharia Rural da Universidade Federal de Santa Maria no ano agrícola 1995/1996. Utilizou-se um conjunto de 12 lisímetros de drenagem com dimensões de 156 cm de comprimento, 100 cm de largura e 80 cm de profundidade, protegidos das precipitações por uma cobertura móvel. Os tratamentos consistiram de dois níveis de manejos da água no solo (irrigado e déficit hídrico terminal aplicado durante a fase de crescimento vegetativo) e três texturas de solo (argila pesada, franco-argilo-siltosa e franco-arenosa). Os resultados demonstraram maior capacidade de armazenamento de água disponível às plantas para o solo de textura franco-arenosa (112 mm) do que para o solo de textura argila pesada (102 mm) e de textura franco-argilo-siltosa (94 mm). No entanto, esses valores representam 44, 41 e 77% da quantidade total de água armazenada nos solos argila pesada, franco-argilo-siltosa e franco-arenosa, respectivamente. Para uma mesma profundidade do solo e em condições de déficit hídrico, o solo de textura franco-arenosa apresenta maior capacidade de armazenamento de água disponível às plantas de milho do que os solos de textura argila pesada e franco-argilo-siltosa.

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Realizou-se, em Planaltina (DF), nos anos agrícolas 1995/96, 1996/97 e 1997/98, um experimento num Latossolo Vermelho-Amarelo franco-argilo-arenoso, para comparar o efeito de três métodos de aplicação de cobre (ao solo, em pulverização foliar e à semente) sobre a produção de soja (cv. Doko RC) e estabelecer níveis críticos para os teores de cobre no solo e na folha. No primeiro cultivo, não houve diferença significativa entre os tratamentos provavelmente pela ocorrência de déficit hídrico (veranico) na fase de enchimento de grãos. No segundo e no terceiro cultivo, as doses de 1,2 e 2,4 kg ha-1 de cobre aplicadas a lanço apenas por ocasião do primeiro cultivo ou no sulco de semeadura parceladamente, ou seja, 0,4 e 0,8 kg ha-1 de cobre por cultivo, respectivamente, propiciaram rendimentos máximos de grãos. A dose de 2,4 kg ha-1 de cobre misturada às sementes e a dose de 0,6 kg ha-1 de cobre aplicada nas folhas vinte dias após a emergência também tiveram rendimentos máximos de grãos no segundo e no terceiro cultivo. Os níveis críticos de cobre no solo para os extratores HCl 0,1 mol L-1, Mehlich-1, Mehlich-3 e DTPA pH 7,3, foram de 0,6, 0,5, 0,5 e 0,6 mg dm-3 de cobre, respectivamente. O nível crítico de cobre na folha foi de 3,9 mg kg-1.

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Background: Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by specific facial features, mild to moderate mental retardation, postnatal growth delay, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads. A 3.5 Mb duplication at 8p23.1-p22 was once reported as a specific alteration in KS but has not been confirmed in other patients. The molecular basis of KS remains unknown. Methods: We have studied 16 Spanish patients with a clinical diagnosis of KS or KS-like to search for genomic imbalances using genome-wide array technologies. All putative rearrangements were confirmed by FISH, microsatellite markers and/or MLPA assays, which also determined whether the imbalance was de novo or inherited. Results: No duplication at 8p23.1-p22 was observed in our patients. We detected complex rearrangements involving 2q in two patients with Kabuki-like features: 1) a de novo inverted duplication of 11 Mb with a 4.5 Mb terminal deletion, and 2) a de novo 7.2 Mb-terminal deletion in a patient with an additional de novo 0.5 Mb interstitial deletion in 16p. Additional copy number variations (CNV), either inherited or reported in normal controls, were identified and interpreted as polymorphic variants. No specific CNV was significantly increased in the KS group. Conclusion: Our results further confirmed that genomic duplications of 8p23 region are not a common cause of KS and failed to detect other recurrent rearrangement causing this disorder. The detection of two patients with 2q37 deletions suggests that there is a phenotypic overlap between the two conditions, and screening this region in the Kabuki-like patients should be considered.

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Abstract Purpose: XG-102, a TAT-coupled dextrogyre peptide inhibiting the c-Jun N-terminal kinase, was shown efficient in the treatment of experimental uveitis. Preclinical studies are now performed to determine optimal XG-102 dose and route of administration in endotoxin-induced uveitis (EIU) in rats with the purpose of clinical study design. METHODS: EIU was induced in Lewis rats by lipopolysaccharides (LPS) injection. XG-102 was administered at the time of LPS challenge by intravenous (IV; 3.2, 35 or 355 μg/injection), intravitreal (IVT; 0.08, 0.2 or 2.2 μg/eye), or subconjunctival (SCJ; 0.2, 1.8 or 22 μg/eye) routes. Controls received either the vehicle (saline) or dexamethasone phosphate injections. Efficacy was assessed by clinical scoring, infiltrating cells count, and expression of inflammatory mediators [inducible nitric oxide synthase (iNOS), cytokine-induced neutrophil chemoattractant-1 (CINC-1)]. The effect of XG-102 on phosphorylation of c-Jun was evaluated by Western blot. RESULTS: XG-102 demonstrated a dose-dependent anti-inflammatory effect in EIU after IV and SCJ administrations. Respective doses of 35 and 1.8 μg were efficient as compared with the vehicle-injected controls, but only the highest doses, respectively 355 and 22 μg, were as efficient as dexamethasone phosphate. After IVT injections, the anti-inflammatory effect of XG-102 was clinically evaluated similar to the corticoid's effect with all the tested doses. Regardless of the administration route, the lowest efficient doses of XG-102 significantly decreased the ration of phospho c-Jun/total c-Jun, reduced cells infiltration in the treated eyes, and significantly downregulated iNOS and CINC-1 expression in the retina. CONCLUSION: These results confirm that XG-102 peptide has potential for treating intraocular inflammation. SCJ injection appears as a good compromise to provide a therapeutic effect while limiting side effects.

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The proteasome produces MHC class I-restricted antigenic peptides carrying N-terminal extensions, which are trimmed by other peptidases in the cytosol or within the endoplasmic reticulum. In this study, we show that the N-terminal editing of an antigenic peptide with a predicted low TAP affinity can occur in the cytosol. Using proteomics, we identified two cytosolic peptidases, tripeptidyl peptidase II and puromycin-sensitive aminopeptidase, that trimmed the N-terminal extensions of the precursors produced by the proteasome, and led to a transient enrichment of the final antigenic peptide. These peptidases acted either sequentially or redundantly, depending on the extension remaining at the N terminus of the peptides released from the proteasome. Inhibition of these peptidases abolished the CTL-mediated recognition of Ag-expressing cells. Although we observed some proteolytic activity in fractions enriched in endoplasmic reticulum, it could not compensate for the loss of tripeptidyl peptidase II/puromycin-sensitive aminopeptidase activities.

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Aquest treball és la culminació de les pràctiques realitzades al sincrotró ALBA. Situat a Cerdanyola del Vallès, ALBA és un accelerador de 3a generació que permet emmagatzemar un feix d'electrons confinat de fins a 400 mA a 3GeV d'energia, amb l'objectiu d'obtenir llum a partir dels girs provocats al feix. Els sincrotrons moderns com el d'ALBA, el que pretenen és aconseguir un major control i estabilitat de la llum. Per aconseguir-ho, cal que el feix d'electrons que creen la llum estigui controlat al màxim i la seva òrbita sigui estable. Amb aquest objectiu els sincrotrons estant implementant sistemes de Fast Orbit FeedBack (FOFB) o sistemes realimentats de correcció ràpida de l'òrbita, per realitzar correccions d'almenys 100Hz que estabilitzin el feix d'electrons amb menys d'un 10% de l'amplada del feix (5-10μm). El treball exposa el desenvolupament d'una part del sistema de correcció ràpida de l'òrbita dels electrons (FOFB) que s'està duent a terme al sincrotró ALBA. Concretament, s’han revisat els estudis previs realitzats durant la fase de disseny del sincrotró, s’han recalculat funcions de transferència i retards de tots els elements involucrats al sistema. També s’han realitzat simulacions per confirmar la viabilitat del sistema amb les noves dades i finalment s’ha desenvolupat part de la unitat de control determinant el Hardware i s'ha adquirit dades que permetran analitzar el soroll de l'òrbita que en futurs treballs determinaran millor l'algorisme de la unitat de control.

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Apoptosis of pancreatic beta cells is implicated in the onset of type 1 and type 2 diabetes. Consequently, strategies aimed at increasing the resistance of beta cells toward apoptosis could be beneficial in the treatment of diabetes. RasGAP, a regulator of Ras and Rho GTPases, is an atypical caspase substrate, since it inhibits, rather than favors, apoptosis when it is partially cleaved by caspase-3 at position 455. The antiapoptotic signal generated by the partial processing of RasGAP is mediated by the N-terminal fragment (fragment N) in a Ras-phosphatidylinositol 3-kinase-Akt-dependent, but NF-kappaB-independent, manner. Further cleavage of fragment N at position 157 abrogates its antiapoptotic properties. Here we demonstrate that an uncleavable form of fragment N activates Akt, represses NF-kappaB activity, and protects the conditionally immortalized pancreatic insulinoma betaTC-tet cell line against various insults, including exposure to genotoxins, trophic support withdrawal, and incubation with inflammatory cytokines. Fragment N also induced Akt activity and protection against cytokine-induced apoptosis in primary pancreatic islet cells. Fragment N did not alter insulin cell content and insulin secretion in response to glucose. These data indicate that fragment N protects beta cells without affecting their function. The pathways regulated by fragment N are therefore promising targets for antidiabetogenic therapy.

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Hepatitis C virus (HCV) is an important human pathogen, persistently infecting more than 170 million individuals worldwide. Studies of the HCV life cycle have become possible with the development of cell culture systems supporting the replication of viral RNA and the production of infectious virus. However, the exact functions of individual proteins, especially of nonstructural protein 4B (NS4B), remain poorly understood. NS4B triggers the formation of specific, vesicular membrane rearrangements, referred to as membranous webs, which have been reported to represent sites of HCV RNA replication. However, the mechanism of vesicle induction is not known. In this study, a panel of 15 mutants carrying substitutions in the highly conserved NS4B C-terminal domain was generated. Five mutations had only a minor effect on replication, but two of them enhanced assembly and release of infectious virus. Ten mutants were replication defective and used for selection of pseudoreversions. Most of the pseudoreversions also localized to the highly conserved NS4B C-terminal domain and were found to restore replication competence upon insertion into the corresponding primary mutant. Importantly, pseudoreversions restoring replication competence also restored heterotypic NS4B self-interaction, which was disrupted by the primary mutation. Finally, electron microscopy analyses of membrane alterations induced by NS4B mutants revealed striking morphological abnormalities, which were restored to wild-type morphology by the corresponding pseudoreversion. These findings demonstrate the important role of the C-terminal domain in NS4B self-interaction and the formation of functional HCV replication complexes.

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Para a produção de mudas em substratos, é intenso o uso de fertilizante e de irrigação, o que pode gerar perdas elevadas de nutrientes. O P é muito utilizado na preparação de substratos, mas estudos modelando suas perdas ainda são escassos. Este trabalho objetivou avaliar atributos químicos do lixiviado na fase de enraizamento de estacas de cacaueiro cultivadas sob irrigação intermitente em diferentes substratos e doses de P. O delineamento experimental foi em blocos casualizados com três repetições, em esquema fatorial 5 x 5: cinco substratos (misturas, em volume, de 20, 35, 50, 65 e 80 % de fibra de coco - FC, complementadas com Plantmax®) e cinco doses de superfosfato triplo - SFT (P2O5 = 0; 0,23; 0,46; 0,92; e 1,84 g dm-3). A parcela foi formada por dois tubetes (288 cm³), com uma estaca herbácea de cacau por tubete. O total do lixiviado de 28 dias foi coletado e medido, sendo a condutividade elétrica (CE) e o pH analisados em três amostras semanais. Os nutrientes P, Ca, Mg e K foram quantificados em amostras médias semanais. Os resultados foram submetidos à análise de regressão. Com o decorrer dos dias, o pH do lixiviado aumentou e a CE diminuiu, alcançando valores próximos aos da água de irrigação. O incremento de SFT diminuiu o pH e aumentou a CE do lixiviado. As variações de pH e CE foram mais rápidas e maiores quanto maior foi a proporção de FC no substrato. O teor e o conteúdo dos nutrientes no lixiviado decresceram rapidamente com o tempo, independente do substrato. O fornecimento de SFT aumentou a lixiviação de todos os nutrientes analisados. As perdas de Ca, Mg e K foram proporcionais à riqueza desses nutrientes no substrato. A lixiviação do P aplicado variou de 39 a 74 % e foi inversamente proporcional à capacidade de adsorção de fosfato do substrato.

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This paper derives the HJB (Hamilton-Jacobi-Bellman) equation for sophisticated agents in a finite horizon dynamic optimization problem with non-constant discounting in a continuous setting, by using a dynamic programming approach. A simple example is used in order to illustrate the applicability of this HJB equation, by suggesting a method for constructing the subgame perfect equilibrium solution to the problem.Conditions for the observational equivalence with an associated problem with constantdiscounting are analyzed. Special attention is paid to the case of free terminal time. Strotz¿s model (an eating cake problem of a nonrenewable resource with non-constant discounting) is revisited.

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Peripheral inflammation induces persistent central sensitization characterized by mechanical allodynia and heat hyperalgesia that are mediated by distinct mechanisms. Compared to well-demonstrated mechanisms of heat hyperalgesia, mechanisms underlying the development of mechanical allodynia and contralateral pain are incompletely known. In this study, we investigated the distinct role of spinal JNK in heat hyperalgesia, mechanical allodynia, and contralateral pain in an inflammatory pain model. Intraplantar injection of complete Freund's adjuvant (CFA) induced bilateral mechanical allodynia but unilateral heat hyperalgesia. CFA also induced a bilateral activation (phosphorylation) of JNK in the spinal cord, and the phospho JNK1 (pJNK1) levels were much higher than that of pJNK2. Notably, both pJNK and JNK1 were expressed in GFAP-positive astrocytes. Intrathecal infusion of a selective peptide inhibitor of JNK, D-JNKI-1, starting before inflammation via an osmotic pump, reduced CFA-induced mechanical allodynia in the maintenance phase but had no effect on CFA-induced heat hyperalgesia. A bolus intrathecal injection of D-JNKI-1 or SP600126, a small molecule inhibitor of JNK also reversed mechanical allodynia bilaterally. In contrast, peripheral (intraplantar) administration of D-JNKI-1 reduced the induction of CFA-induced heat hyperalgesia but did not change mechanical allodynia. Finally, CFA-induced bilateral mechanical allodynia was attenuated in mice lacking JNK1 but not JNK2. Taken together, our data suggest that spinal JNK, in particular JNK1 plays an important role in the maintenance of persistent inflammatory pain. Our findings also reveal a unique role of JNK1 and astrocyte network in regulating tactile allodynia and contralateral pain.