895 resultados para Wnt-3a


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OBJETIVO: Comparar os resultados da hernioplastia inguinal pelas técnicas de Shouldice modificada por Berliner (SB), que realiza dois planos de sutura superpostos e de Falci-Lichtenstein (FL) que utiliza prótese de polipropileno. MÉTODO: Foram estudados prospectivamente 312 pacientes operados pelo mesmo cirurgião entre 1997 e 2004. O Grupo 1 constou de 84 pacientes operados pela técnica de FL e o Grupo 2 foi formado por 228 pacientes operados pela técnica de SB. Todos eram masculinos, maiores de 18 anos e portadores de hérnias inguinais tipo 3A, 3B e 4 da classificação de Nyhus. Os grupos foram semelhantes em relação a idade, lado operado, tipo de hérnia, anestesia empregada e tempo de seguimento (média de 3,5 anos). RESULTADOS: A duração média dos procedimentos foi de 53 min no Grupo 1 e de 57 min no Grupo 2 (p=0,2982); a permanência hospitalar foi menor que 24h para 94% dos pacientes do Grupo 1 e 92% do Grupo 2 (p=0,8050); a incidência de complicações foi de 9,5% no Grupo 1 e de 12,3% no Grupo 2 (p=0,5557) sendo a mais comum o hematoma/equimose e a taxa de recidiva foi de 1,2% no Grupo 1 e de 5,4% no Grupo 2 (p=0,0935). Nenhum desses resultados apresentou diferença significante. CONCLUSÃO: A técnica SB mostrou-se comparável à técnica de FL em homens, maiores de 18 anos com hérnias tipo 3 A, 3 B e 4 de Nyhus, além de não exigir material protético.

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Tankyrases belong to the Diphtheria toxin-like ADP-ribosyltransferase (ARTD) enzyme superfamily, also known as poly(ADP-ribose) polymerases (PARPs). They catalyze a covalent post-translational modification reaction where they transfer ADP-ribose units from NAD+ to target proteins. Tankyrases are involved in many cellular processes and their roles in telomere homeostasis, Wnt signaling and in several diseases including cancers have made them interesting drug targets. In this thesis project, selective inhibition of human tankyrases was studied. A homogeneous fluorescence-based assay was developed to screen the compound libraries. The assay is inexpensive, operationally easy, and performs well according to the statistical analysis. Assay suitability was confirmed by screening a natural product library. Flavone was identified as the most potent inhibitor in the library and this motivated us to screen a larger flavonoid library. Results showed that flavones were indeed the best inhibitor of tankyrases among flavonoids. To further study the structure-activity relationship, a small library of flavones containing single substitution was screened and potency measurements allowed us to generate structure-activity relationship. Compounds containing substitutions at 4´-position were more potent in comparison to other substitutions, and importantly, hydrophobic groups improved isoenzyme selectivity as well as the potency. A flavone derivative containing a hydrophobic isopropyl group (compound 22), displayed 6 nM potency against TNKS1, excellent isoenzyme selectivity and Wnt signaling inhibition. Protein interactions with compounds were studied by solving complex crystal structures of the compounds with TNKS2 catalytic domain. A novel tankyrase inhibitor (IWR-1) was also crystallized in complex with TNKS2 catalytic domain. The crystal structure of TNKS2 in complex with IWR-1 showed that the compound binds to adenosine site and it was the first known ARTD inhibitor of this kind. To date, there is no structural information available about the substrate binding with any of the ARTD family members; therefore NAD+ was soaked with TNKS2 catalytic domain crystals. However, analysis of crystal structure showed that NAD+ was hydrolyzed to nicotinamide. Also, a co-crystal structure of NAD+ mimic compound, EB-47, was solved which was used to deduce some insights about the substrate interactions with the enzyme. Like EB-47, other ARTD1 inhibitors were also shown to inhibit tankyrases. It indicated that selectivity of the ARTD1 inhibitors should be considered as some of the effects in cells could come from tankyrase inhibition. In conclusion, the study provides novel information on tankyrase inhibition and presents new insight into the selectivity and potency of compounds.

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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Konferenssin nimi: ICEIRD 2014 : The 7th International Conference for Entrepreneurship, Innovation and Regional Development. 5–6 June 2014, Nicosia, Cyprus. Julkaisumaa: 196 CY CYP Kypros

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Laatukustannusten seurantaa ja vähentämistä pidetään yrityksen kilpailukyvyn kannalta merkityk-sellisinä. Laatukustannusten perinteinen PAF -malli on yleisesti hyväksytyin ja käytetyin malli ra-portoimaan näkyvissä olevia laatukustannuksia, mutta mallilla laskettavissa olevat laatukustannuk-set ovat vain jäävuoren huippu kaikista laatukustannuksista. Piilevänä voi olla vaikeasti raportoita-vissa olevia laatukustannuksia, joiden olemassaolon ymmärtäminen ja vähentäminen on tärkeää yhä kiristyvässä kilpailussa. Laatukustannuslaskentaa on aihepiirinä tutkittu paljon, mutta hyvin vähän on kuitenkin yritetty ymmärtää, miten hankalasti raportoitaviin piileviin laatukustannuksiin liittyvää laskentaa tulisi soveltaa käytännössä. Tämän tutkimuksen tarkoituksena oli kuvailla tätä piilevien laatukustannusten problematiikka case-yrityksen laatukustannuslaskentaprosessissa tutkimuksessa käytetyn yhteistyöhön perustuvan 3A-Workshop -menetelmän avulla sekä tutkia piilevien laatukus-tannusten raportoinnissa huomioon otettavia seikkoja ja haasteita. Tutkimus suoritettiin yhdessä tuotantoyrityksessä toiminta-analyyttisenä case-tutkimuksena. Tutki-mus on luonteeltaan niin normatiivinen kuin deskriptiivinen. Tarkoituksena oli selvittää, miten tulisi toimia, mutta myös kuvailla ja selittää tutkittavaa ilmiötä. Tutkimuksessa käytettiin rinnakkaisia menetelmiä aineiston hankkimisessa, joilla pyrittiin case-yrityksen kokonaisvaltaiseen analysoin-tiin. Aineiston keruussa käytettiin pääasiassa ryhmähaastatteluja tietyistä teemoista, osallistuvaa havainnointia sekä tietyille henkilöille lähetettävää kyselyä. 3A-Workshop -menetelmällä kohdeyri-tyksessä löydetyt ongelma-alueet olivat tuotannonsuunnittelu, materiaalinhallinta, tiedonkulku, do-kumentointi, toiminnanohjausjärjestelmä sekä työvälineet. Näiden kautta määriteltiin pääasiassa piileviä laatukustannuksia. 3A-Workshop -menetelmällä saadun informaation perusteella voidaan todeta, että piilevien laatu-kustannusten raportoinnin kannalta on saatu merkittävää tietoa niiden ilmentymisestä yrityksen toi-minnan eri osa-alueilla, vaikkakin suurimpia piileviä laatukustannuksia on vaikea ottaa tällä mene-telmällä huomioon. Tässä tutkimuksessa nostettiin esille piilevien laatukustannusten ilmentäminen tuotantoyrityksessä havaituilla eri ongelma-alueilla pääasiassa niihin menetettynä aikana. Menetet-tyjä myyntejä pyrittiin myös arvioimaan. Piilevien laatukustannusten lähestymisessä on otettava huomioon erilaisia seikkoja verrattuna perinteisten PAF -mallilla huomioitavien laatukustannusten lähestymiseen. Tämän tutkimuksen tuloksina saatiin piilevien laatukustannusten raportoinnin kan-nalta merkityksellisiä ja käytännönläheisiä seikkoja neljällä eri osa-alueella: suorittavan tason työn-tekijöiden ja johdon sitouttaminen, laskentamenetelmät, laatukustannuslaskennan käyttötarkoitus ja lähestymistapa sekä omasta, asiakkaan ja/tai toimittajan kautta syntyneet laatukustannukset.

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Patients with sickle-cell anemia submitted to frequent blood transfusions are at risk of contamination with hepatitis C virus (HCV). Determination of HCV RNA and genotype characterization are parameters that are relevant for the treatment of the viral infection. The objective of the present study was to determine the frequency of HCV infection and the positivity for HCV RNA and to identify the HCV genotype in patients with sickle-cell anemia with a history of blood transfusion who had been treated at the Hospital of the HEMOPE Foundation. Sera from 291 patients were tested for anti-HCV antibodies by ELISA 3.0 and RIBA 3.0 Chiron and for the presence of HCV RNA by RT-PCR. HCV genotyping was performed in 19 serum samples. Forty-one of 291 patients (14.1%) were anti-HCV positive by ELISA and RIBA. Both univariate and multivariate analysis showed a greater risk of anti-HCV positivity in those who had started a transfusion regime before 1992 and received more than 10 units of blood. Thirty-four of the anti-HCV-positive patients (34/41, 82.9%) were also HCV RNA positive. Univariate analysis, used to compare HCV RNA-negative and -positive patients, did not indicate a higher risk of HCV RNA positivity for any of the variables evaluated. The genotypes identified were 1b (63%), 1a (21%) and 3a (16%). A high prevalence of HCV infection was observed in our patients with sickle-cell anemia (14.1%) compared to the population in general (3%). In the literature, the frequency of HCV infection in sickle-cell anemia ranges from 2 to 30%. The serological screening for anti-HCV at blood banks after 1992 has contributed to a better control of the dissemination of HCV infection. Because of the predominance of genotype 1, these patients belong to a group requiring special treatment, with a probable indication of new therapeutic options against HCV.