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Sample records for nuclear cofactor dor

  1. Nuclear Receptor Cofactors in PPARγ-Mediated Adipogenesis and Adipocyte Energy Metabolism

    Directory of Open Access Journals (Sweden)

    Emily Powell

    2007-01-01

    Full Text Available Transcriptional cofactors are integral to the proper function and regulation of nuclear receptors. Members of the peroxisome proliferator-activated receptor (PPAR family of nuclear receptors are involved in the regulation of lipid and carbohydrate metabolism. They modulate gene transcription in response to a wide variety of ligands, a process that is mediated by transcriptional coactivators and corepressors. The mechanisms by which these cofactors mediate transcriptional regulation of nuclear receptor function are still being elucidated. The rapidly increasing array of cofactors has brought into focus the need for a clear understanding of how these cofactors interact in ligand- and cell-specific manners. This review highlights the differential effects of the assorted cofactors regulating the transcriptional action of PPARγ and summarizes the recent advances in understanding the physiological functions of corepressors and coactivators.

  2. RNAi-Based Identification of Gene-Specific Nuclear Cofactor Networks Regulating Interleukin-1 Target Genes

    Directory of Open Access Journals (Sweden)

    Johanna Meier-Soelch

    2018-04-01

    Full Text Available The potent proinflammatory cytokine interleukin (IL-1 triggers gene expression through the NF-κB signaling pathway. Here, we investigated the cofactor requirements of strongly regulated IL-1 target genes whose expression is impaired in p65 NF-κB-deficient murine embryonic fibroblasts. By two independent small-hairpin (shRNA screens, we examined 170 genes annotated to encode nuclear cofactors for their role in Cxcl2 mRNA expression and identified 22 factors that modulated basal or IL-1-inducible Cxcl2 levels. The functions of 16 of these factors were validated for Cxcl2 and further analyzed for their role in regulation of 10 additional IL-1 target genes by RT-qPCR. These data reveal that each inducible gene has its own (quantitative requirement of cofactors to maintain basal levels and to respond to IL-1. Twelve factors (Epc1, H2afz, Kdm2b, Kdm6a, Mbd3, Mta2, Phf21a, Ruvbl1, Sin3b, Suv420h1, Taf1, and Ube3a have not been previously implicated in inflammatory cytokine functions. Bioinformatics analysis indicates that they are components of complex nuclear protein networks that regulate chromatin functions and gene transcription. Collectively, these data suggest that downstream from the essential NF-κB signal each cytokine-inducible target gene has further subtle requirements for individual sets of nuclear cofactors that shape its transcriptional activation profile.

  3. A live zebrafish-based screening system for human nuclear receptor ligand and cofactor discovery.

    Science.gov (United States)

    Tiefenbach, Jens; Moll, Pamela R; Nelson, Meryl R; Hu, Chun; Baev, Lilia; Kislinger, Thomas; Krause, Henry M

    2010-03-22

    Nuclear receptors (NRs) belong to a superfamily of transcription factors that regulate numerous homeostatic, metabolic and reproductive processes. Taken together with their modulation by small lipophilic molecules, they also represent an important and successful class of drug targets. Although many NRs have been targeted successfully, the majority have not, and one third are still orphans. Here we report the development of an in vivo GFP-based reporter system suitable for monitoring NR activities in all cells and tissues using live zebrafish (Danio rerio). The human NR fusion proteins used also contain a new affinity tag cassette allowing the purification of receptors with bound molecules from responsive tissues. We show that these constructs 1) respond as expected to endogenous zebrafish hormones and cofactors, 2) facilitate efficient receptor and cofactor purification, 3) respond robustly to NR hormones and drugs and 4) yield readily quantifiable signals. Transgenic lines representing the majority of human NRs have been established and are available for the investigation of tissue- and isoform-specific ligands and cofactors.

  4. A live zebrafish-based screening system for human nuclear receptor ligand and cofactor discovery.

    Directory of Open Access Journals (Sweden)

    Jens Tiefenbach

    2010-03-01

    Full Text Available Nuclear receptors (NRs belong to a superfamily of transcription factors that regulate numerous homeostatic, metabolic and reproductive processes. Taken together with their modulation by small lipophilic molecules, they also represent an important and successful class of drug targets. Although many NRs have been targeted successfully, the majority have not, and one third are still orphans. Here we report the development of an in vivo GFP-based reporter system suitable for monitoring NR activities in all cells and tissues using live zebrafish (Danio rerio. The human NR fusion proteins used also contain a new affinity tag cassette allowing the purification of receptors with bound molecules from responsive tissues. We show that these constructs 1 respond as expected to endogenous zebrafish hormones and cofactors, 2 facilitate efficient receptor and cofactor purification, 3 respond robustly to NR hormones and drugs and 4 yield readily quantifiable signals. Transgenic lines representing the majority of human NRs have been established and are available for the investigation of tissue- and isoform-specific ligands and cofactors.

  5. A dor

    Directory of Open Access Journals (Sweden)

    Manoel Tosta Berlinck

    Full Text Available Este trabalho relata pesquisa sobre a natureza psicopatológica da dor partindo da noção de que o humano habita na dor. Esta passa, assim, a ser um conceito-limite do humano que não consegue ultrapassá-la, apesar dos recursos farmacológicos e psíquicos disponíveis para dela se proteger. Nesta perspectiva, o corpo humano solicita uma concepção que seja capaz de levar em consideração tanto a dor física como a psíquica.

  6. Panning for SNuRMs: using cofactor profiling for the rational discovery of selective nuclear receptor modulators.

    Science.gov (United States)

    Kremoser, Claus; Albers, Michael; Burris, Thomas P; Deuschle, Ulrich; Koegl, Manfred

    2007-10-01

    Drugs that target nuclear receptors are clinically, as well as commercially, successful. Their widespread use, however, is limited by an inherent propensity of nuclear receptors to trigger beneficial, as well as adverse, pharmacological effects upon drug activation. Hence, selective drugs that display reduced adverse effects, such as the selective estrogen receptor modulator (SERM) Raloxifene, have been developed by guidance through classical cell culture assays and animal trials. Full agonist and selective modulator nuclear receptor drugs, in general, differ by their ability to recruit certain cofactors to the receptor protein. Hence, systematic cofactor profiling is advancing into an approach for the rationally guided identification of selective NR modulators (SNuRMs) with improved therapeutic ratio.

  7. Solution Structure of LXXLL-related Cofactor Peptide of Orphan Nuclear Receptor FTZ-F1

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Ji Hye; Lee, Chul Jin; Jung, Jin Won; Lee, Weon Tae [Yonsei University, Seoul (Korea, Republic of)

    2012-02-15

    Functional interaction between Drosophila orphan receptor FTZ-F1 (NR5A3) and a segmentation gene product fushi tarazu (FTZ) is crucial for regulating genes related to define the identities of alternate segmental regions in the Drosophila embryo. FTZ binding to the ligand-binding domain (LBD) of FTZ-F1 is of essence in activating its transcription process. We determined solution structures of the cofactor peptide (FTZ{sup PEP}) derived from FTZ by NMR spectroscopy. The cofactor peptide showed a nascent helical conformation in aqueous solution, however, the helicity was increased in the presence of TFE. Furthermore, FTZ{sup PEP} formed α- helical conformation upon FTZ-F1 binding, which provides a receptor bound structure of FTZ{sup PEP}. The solution structure of FTZ{sup PEP} in the presence of FTZ-F1 displays a long stretch of the α-helix with a bend in the middle of helix.

  8. Solution Structure of LXXLL-related Cofactor Peptide of Orphan Nuclear Receptor FTZ-F1

    International Nuclear Information System (INIS)

    Yun, Ji Hye; Lee, Chul Jin; Jung, Jin Won; Lee, Weon Tae

    2012-01-01

    Functional interaction between Drosophila orphan receptor FTZ-F1 (NR5A3) and a segmentation gene product fushi tarazu (FTZ) is crucial for regulating genes related to define the identities of alternate segmental regions in the Drosophila embryo. FTZ binding to the ligand-binding domain (LBD) of FTZ-F1 is of essence in activating its transcription process. We determined solution structures of the cofactor peptide (FTZ PEP ) derived from FTZ by NMR spectroscopy. The cofactor peptide showed a nascent helical conformation in aqueous solution, however, the helicity was increased in the presence of TFE. Furthermore, FTZ PEP formed α- helical conformation upon FTZ-F1 binding, which provides a receptor bound structure of FTZ PEP . The solution structure of FTZ PEP in the presence of FTZ-F1 displays a long stretch of the α-helix with a bend in the middle of helix

  9. Functional analysis of the interaction of the human immunodeficiency virus type 1 Rev nuclear export signal with its cofactors

    International Nuclear Information System (INIS)

    Kiss, A.; Li, L.; Gettemeier, T.; Venkatesh, L.K.

    2003-01-01

    Human immunodeficiency virus type 1 (HIV-1) Rev-mediated nuclear export of viral RNAs involves the interaction of its leucine-rich nuclear export sequence (NES) with nuclear cofactors. In yeast two-hybrid screens of a human lymph node derived cDNA expression library, we identified the human nucleoporin Nup98 as a highly specific and potent interactor of the Rev NES. Using an extensive panel of nuclear export positive and negative mutants of the functionally homologous NESs of the HIV-1 Rev, human T cell leukemia virus type 1 (HTLV-1) Rex, and equine infectious anemia virus (EIAV) Rev proteins, physiologically significant interaction of hNup98 with the various NESs was demonstrated. Missense mutations in the yeast nuclear export factor Crm1p that abrogated Rev NES interaction with the XXFG repeat-containing nucleoporin, Rab/hRIP, had minimal effects on the interaction of GLFG repeat-containing hNup98. Functional analysis of Nup98 domains required for nuclear localization demonstrated that the entire ORF was required for efficient incorporation into the nuclear envelope. A putative nuclear localization signal was identified downstream of the GLFG repeat region. Whereas overexpression of both full-length Nup98 and the amino-terminal GLFG repeat region, but not the unique carboxy-terminal region, induced significant suppression of HIV unspliced RNA export, lower levels of exogenous Nup98 expression resulted in a relatively modest increase in unspliced RNA export. These results suggest a physiological role for hNup98 in modulating Rev-dependent RNA export during HIV infection

  10. Protein Cofactors Are Essential for High-Affinity DNA Binding by the Nuclear Factor κB RelA Subunit.

    Science.gov (United States)

    Mulero, Maria Carmen; Shahabi, Shandy; Ko, Myung Soo; Schiffer, Jamie M; Huang, De-Bin; Wang, Vivien Ya-Fan; Amaro, Rommie E; Huxford, Tom; Ghosh, Gourisankar

    2018-05-22

    Transcription activator proteins typically contain two functional domains: a DNA binding domain (DBD) that binds to DNA with sequence specificity and an activation domain (AD) whose established function is to recruit RNA polymerase. In this report, we show that purified recombinant nuclear factor κB (NF-κB) RelA dimers bind specific κB DNA sites with an affinity significantly lower than that of the same dimers from nuclear extracts of activated cells, suggesting that additional nuclear cofactors might facilitate DNA binding by the RelA dimers. Additionally, recombinant RelA binds DNA with relatively low affinity at a physiological salt concentration in vitro. The addition of p53 or RPS3 (ribosomal protein S3) increases RelA:DNA binding affinity 2- to >50-fold depending on the protein and ionic conditions. These cofactor proteins do not form stable ternary complexes, suggesting that they stabilize the RelA:DNA complex through dynamic interactions. Surprisingly, the RelA-DBD alone fails to bind DNA under the same solution conditions even in the presence of cofactors, suggesting an important role of the RelA-AD in DNA binding. Reduced RelA:DNA binding at a physiological ionic strength suggests that multiple cofactors might be acting simultaneously to mitigate the electrolyte effect and stabilize the RelA:DNA complex in vivo. Overall, our observations suggest that the RelA-AD and multiple cofactor proteins function cooperatively to prime the RelA-DBD and stabilize the RelA:DNA complex in cells. Our study provides a mechanism for nuclear cofactor proteins in NF-κB-dependent gene regulation.

  11. RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

    International Nuclear Information System (INIS)

    Huang, Feng; Zhang, Junsong; Zhang, Yijun; Geng, Guannan; Liang, Juanran; Li, Yingniang; Chen, Jingliang; Liu, Chao; Zhang, Hui

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.

  12. RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Feng; Zhang, Junsong; Zhang, Yijun; Geng, Guannan; Liang, Juanran; Li, Yingniang; Chen, Jingliang [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Liu, Chao, E-mail: liuchao9@mail.sysu.edu.cn [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Zhang, Hui [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China)

    2015-12-15

    Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.

  13. DORS: DDC Online Retrieval System.

    Science.gov (United States)

    Liu, Songqiao; Svenonius, Elaine

    1991-01-01

    Describes the Dewey Online Retrieval System (DORS), which was developed at the University of California, Los Angeles (UCLA), to experiment with classification-based search strategies in online catalogs. Classification structures in automated information retrieval are discussed; and specifications for a classification retrieval interface are…

  14. Dor oncológica

    Directory of Open Access Journals (Sweden)

    Carla Alves Costa

    2007-11-01

    Full Text Available Resumo: A dor pode ser definida de várias formas, sendo habitualmente descrita como uma experiência sensorial e emocional desagradável associada a lesão tecidular real ou potencial, ou descrita em função de tal lesão. No doente oncológico, a dor pode estar relacionada com a neoplasia, com o seu tratamento, ou não ter relação com a doença neoplásica. A dor tem grande impacto no doente oncológico, significando agravamento do prognóstico ou morte próxima, daí a importância de uma abordagem e tratamento correctos. As opções para o tratamento farmacológico são várias, estando disponíveis analgésicos não opióides, opióides e co-analgésicos. Os autores pretendem com este artigo rever o tratamento farmacológico da dor e alertar para a importância do reconhecimento da dor como doença e da possibilidade de tratar e aliviar os doentes.Rev Port Pneumol 2007; XIII (6: 855-867 Abstract: Pain can be defined by several ways, but is usually describes as an unpleasant sensorial or emotional experience related to real or potential tissue damage, or described in terms of such damage. The cancer patient may experience pain related to the cancer itself, its treatment or not related at all with the oncologic disease. It has an extreme importance to the patient, as it is interpreted as a worsening of the prognosis or near death. Therefore it is extremely important a correct approach and treatment of cancer pain. Pain can be treated by pharmacologic, non-pharmacologic means and by more invasive procedures. The options for pharmacologic treatment are various, since nonopioid, opioid analgesics and co-analgesics. The authors present a review of the pharmacological treatment of cancer pain and alert to the importance of the recognition of pain as an illness and the possibility to be relieved.Rev Port Pneumol 2007; XIII (6: 855-867 Palavras-chave: Dor, dor oncológica, analgésicos, opióides, Key-words: Pain, cancer pain, analgesics, opioids

  15. Dor oncológica

    Directory of Open Access Journals (Sweden)

    Carla Alves Costa

    2007-11-01

    Full Text Available Resumo: A dor pode ser definida de várias formas, sendo habitualmente descrita como uma experiência sensorial e emocional desagradável associada a lesão tecidular real ou potencial, ou descrita em função de tal lesão. No doente oncológico, a dor pode estar relacionada com a neoplasia, com o seu tratamento, ou não ter relação com a doença neoplásica. A dor tem grande impacto no doente oncológico, significando agravamento do prognóstico ou morte próxima, daí a importância de uma abordagem e tratamento correctos. As opções para o tratamento farmacológico são várias, estando disponíveis analgésicos não opióides, opióides e co-analgésicos. Os autores pretendem com este artigo rever o tratamento farmacológico da dor e alertar para a importância do reconhecimento da dor como doença e da possibilidade de tratar e aliviar os doentes. Abstract: Pain can be defined by several ways, but is usually describes as an unpleasant sensorial or emotional experience related to real or potential tissue damage, or described in terms of such damage. The cancer patient may experience pain related to the cancer itself, its treatment or not related at all with the oncologic disease. It has an extreme importance to the patient, as it is interpreted as a worsening of the prognosis or near death. Therefore it is extremely important a correct approach and treatment of cancer pain. Pain can be treated by pharmacologic, non-pharmacologic means and by more invasive procedures. The options for pharmacologic treatment are various, since nonopioid, opioid analgesics and co-analgesics. The authors present a review of the pharmacological treatment of cancer pain and alert to the importance of the recognition of pain as an illness and the possibility to be relieved. Palavras-chave: Dor, dor oncológica, analgésicos, opióides, Key-words: Pain, cancer pain, analgesics, opioids

  16. Tratamento da dor em queimados

    Directory of Open Access Journals (Sweden)

    Rodrigo José Alencar de Castro

    2013-02-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Apesar dos avanços, ainda é observado manejo analgésico inadequado dos pacientes com queimaduras. O objetivo desta revisão foi coletar dados sobre tratamento da dor em queimados. CONTEÚDO: Foi feita revisão sobre os mecanismos de dor, avaliação do paciente com queimadura e o tratamento farmacológico e não farmacológico. CONCLUSÕES: O manejo da dor em pacientes vítimas de queimaduras ainda é um desafio por parte da equipe multiprofissional. A avaliação frequente e contínua da resposta apresentada pelo paciente é muito importante, tendo em vista os vários momentos por que passa o paciente internado em decorrência de uma queimadura, além de uma terapêutica combinada com medicações analgésicas e medidas não farmacológicas. Entender a complexidade de alterações fisiopatológicas, psicológicas e bioquímicas apresentadas por um paciente em tratamento de queimadura é o primeiro passo para alcançar o sucesso no seu manejo analgésico.

  17. Lanthanide Cofactors for Triphosphorylation Ribozymes

    Science.gov (United States)

    Sweeney, K. J.; Müller, U. F.

    2017-07-01

    RNA world organisms could have used trimetaphosphate as energy source for thermodynamically unfavorable RNA polymerization. Using in vitro selection we show here that Lanthanides can serve as cofactors for ribozyme-catalyzed RNA triphosphorylation.

  18. Studies of the variability of the hepatocyte nuclear factor-1beta (HNF-1beta / TCF2) and the dimerization cofactor of HNF-1 (DcoH / PCBD) genes in relation to type 2 diabetes mellitus and beta-cell function

    DEFF Research Database (Denmark)

    Ek, J; Grarup, N; Urhammer, S A

    2001-01-01

    Mutations in the homeodomain-containing transcription factor hepatocyte nuclear factor-1beta (HNF-1beta) are known to cause a rare subtype of maturity-onset diabetes of the young (MODY5), which is associated with early-onset progressive non-diabetic renal dysfunction. To investigate whether...... mutations in HNF-1 are implicated in the pathogenesis of MODY or late-onset diabetes with and without nephropathy in Danish Caucasians we examined the HNF-1beta (TCF2) and the dimerization cofactor of HNF-1 (DCoH, PCBD) genes for mutations in 11 MODY probands, 28 type 2 diabetic patients with nephropathy...... comprising the DCoH gene revealed a previously described A-->G polymorphism located in the 3' untranslated region, which was not investigated further. In conclusion, mutations in HNF-1beta and DCoH are not a major cause of MODY or late onset type 2 diabetes in Danish Caucasian subjects....

  19. O psicanalista no tratamento da dor

    Directory of Open Access Journals (Sweden)

    Sueli Pinto Minatti

    2012-12-01

    Full Text Available A dor se manifesta como mal-estar do corpo e no corpo, e tende a ser encaminhada para tratamento médico. O objetivo deste trabalho é analisar a queixa dolorosa do ponto de vista do tratamento psicanalítico, retomando algumas acepções relacionadas ao tratamento da dor, encontradas na obra de Freud. Partimos da experiência no trabalho em hospital pediátrico, utilizando a análise do atendimento de pacientes com queixas de dor para definir e situar a dor no campo da psicanálise, e distingui-la do campo da medicina. No texto, pode-se acompanhar a dor como signo de sofrimento e diversas formas de abordá-la tanto pelo sujeito que a porta quanto pelas instituições que propõem seu cuidado.

  20. [Small scale direct oxide reduction (DOR) experiments

    International Nuclear Information System (INIS)

    1987-01-01

    Objectives were to provide process design information to the Plutonium Recovery Project and to produce DOR (direct oxide reduction) product which meets Foundry purity specifications and Oh-0 Foundry specifications

  1. Optimization Strategies for Hardware-Based Cofactorization

    Science.gov (United States)

    Loebenberger, Daniel; Putzka, Jens

    We use the specific structure of the inputs to the cofactorization step in the general number field sieve (GNFS) in order to optimize the runtime for the cofactorization step on a hardware cluster. An optimal distribution of bitlength-specific ECM modules is proposed and compared to existing ones. With our optimizations we obtain a speedup between 17% and 33% of the cofactorization step of the GNFS when compared to the runtime of an unoptimized cluster.

  2. Cofactor engineering for advancing chemical biotechnology.

    Science.gov (United States)

    Wang, Yipeng; San, Ka-Yiu; Bennett, George N

    2013-12-01

    Cofactors provide redox carriers for biosynthetic reactions, catabolic reactions and act as important agents in transfer of energy for the cell. Recent advances in manipulating cofactors include culture conditions or additive alterations, genetic modification of host pathways for increased availability of desired cofactor, changes in enzyme cofactor specificity, and introduction of novel redox partners to form effective circuits for biochemical processes and biocatalysts. Genetic strategies to employ ferredoxin, NADH and NADPH most effectively in natural or novel pathways have improved yield and efficiency of large-scale processes for fuels and chemicals and have been demonstrated with a variety of microbial organisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Engineering redox balance through cofactor systems.

    Science.gov (United States)

    Chen, Xiulai; Li, Shubo; Liu, Liming

    2014-06-01

    Redox balance plays an important role in the production of enzymes, pharmaceuticals, and chemicals. To meet the demands of industrial production, it is desirable that microbes maintain a maximal carbon flux towards target metabolites with no fluctuations in redox. This requires functional cofactor systems that support dynamic homeostasis between different redox states or functional stability in a given redox state. Redox balance can be achieved by improving the self-balance of a cofactor system, regulating the substrate balance of a cofactor system, and engineering the synthetic balance of a cofactor system. This review summarizes how cofactor systems can be manipulated to improve redox balance in microbes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Beclometasone oral--DOR BioPharma.

    Science.gov (United States)

    2007-01-01

    orBec is an oral enteric-coated tablet formulation of the corticosteroid beclometasone, which has been developed by Enteron Pharmaceuticals, a subsidiary of Corporate Technology Development (now DOR BioPharma). orBec is being developed for the treatment of gastrointestinal graft-versus-host disease (GVHD) and an NDA has been filed in the US. DOR BioPharma has also filed an MAA in Europe for the same indication.orBec is designed to reduce the need for systemic immunosuppressive drugs, thereby improving the outcome of bone marrow and stem cell transplantation.DOR BioPharma may seek a marketing partner in the US and elsewhere for orBec in GVHD and will seek a partner for other potential indications of the drug.In December 2001, Corporate Technology Development was acquired by Endorex Corporation (now DOR BioPharma). In October 1998, Enteron Pharmaceuticals (DOR BioPharma) entered into an exclusive, worldwide, royalty bearing license agreement with George B. McDonald, MD, including the right to grant sublicenses, for the rights to the intellectual property and know-how relating to orBec. In January 2007, DOR BioPharma received $US3 million under a non-binding letter of intent from Sigma-Tau Pharmaceuticals. The agreement grants Sigma-Tau an exclusive right to negotiate terms and conditions for a possible business transaction or strategic alliance regarding orBec and potentially other DOR pipeline compounds until 1 March 2007. Under the terms of the agreement, Sigma-Tau purchased $US1 million of DOR's common stock, with an additional $US2 million paid in cash. If no agreement is reached by 1 March 2007, DOR will return the $US2 million to Sigma-Tau within 60 days. DOR BioPharma received an unsolicited proposal from Cell Therapeutics, Inc. to acquire DOR BioPharma in January 2007. Because of the non-binding agreement already signed with Sigma-Tau, DOR BioPharma's board of directors cannot consider Cell Therapeutics' merger proposal at this time. orBec has been filed for

  5. Co-factor activated recombinant adenovirus proteinases

    Science.gov (United States)

    Anderson, Carl W.; Mangel, Walter F.

    1996-08-06

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  6. Dor oncológica Oncologic pain

    Directory of Open Access Journals (Sweden)

    Carla Alves Costa

    2007-12-01

    Full Text Available A dor pode ser definida de várias formas, sendo habitualmente descrita como uma experiência sensorial e emocional desagradável associada a lesão tecidular real ou potencial, ou descrita em função de tal lesão. No doente oncológico, a dor pode estar relacionada com a neoplasia, com o seu tratamento, ou não ter relação com a doença neoplásica. A dor tem grande impacto no doente oncológico, significando agravamento do prognóstico ou morte próxima, daí a importância de uma abordagem e tratamento correctos. As opções para o tratamento farmacológico são várias, estando disponíveis analgésicos não opióides, opióides e co-analgésicos. Os autores pretendem com este artigo rever o tratamento farmacológico da dor e alertar para a importância do reconhecimento da dor como doença e da possibilidade de tratar e aliviar os doentes.Pain can be defined by several ways, but is usually describes as an unpleasant sensorial or emotional experience related to real or potential tissue damage, or described in terms of such damage. The cancer patient may experience pain related to the cancer itself, its treatment or not related at all with the oncologic disease. It has an extreme importance to the patient, as it is interpreted as a worsening of the prognosis or near death. Therefore it is extremely important a correct approach and treatment of cancer pain. Pain can be treated by pharmacologic, non-pharmacologic means and by more invasive procedures. The options for pharmacologic treatment are various, since nonopioid, opioid analgesics and co-analgesics. The authors present a review of the pharmacological treatment of cancer pain and alert to the importance of the recognition of pain as an illness and the possibility to be relieved.

  7. Remaining challenges in cellular flavin cofactor homeostasis and flavoprotein biogenesis

    Science.gov (United States)

    Giancaspero, Teresa Anna; Colella, Matilde; Brizio, Carmen; Difonzo, Graziana; Fiorino, Giuseppina Maria; Leone, Piero; Brandsch, Roderich; Bonomi, Francesco; Iametti, Stefania; Barile, Maria

    2015-04-01

    The primary role of the water-soluble vitamin B2 (riboflavin) in cell biology is connected with its conversion into FMN and FAD, the cofactors of a large number of dehydrogenases, oxidases and reductases involved in energetic metabolism, epigenetics, protein folding, as well as in a number of diverse regulatory processes. The problem of localisation of flavin cofactor synthesis events and in particular of the FAD synthase (EC 2.7.7.2) in HepG2 cells is addressed here by confocal microscopy in the frame of its relationships with kinetics of FAD synthesis and delivery to client apo-flavoproteins. FAD synthesis catalysed by recombinant isoform 2 of FADS occurs via an ordered bi-bi mechanism in which ATP binds prior to FMN, and pyrophosphate is released before FAD. Spectrophotometric continuous assays of the reconstitution rate of apo-D-aminoacid oxidase with its cofactor, allowed us to propose that besides its FAD synthesising activity, hFADS is able to operate as a FAD "chaperone". The physical interaction between FAD forming enzyme and its clients was further confirmed by dot blot and immunoprecipitation experiments carried out testing as a client either a nuclear or a mitochondrial enzyme that is lysine specific demethylase 1 (LSD1, EC 1.-.-.-) and dimethylglycine dehydrogenase (Me2GlyDH, EC 1.5.8.4), respectively which carry out similar reactions of oxidative demethylation, assisted by tetrahydrofolate used to form 5,10-methylene-tetrahydrofolate. A direct transfer of the cofactor from hFADS2 to apo-dimethyl glycine dehydrogenase was also demonstrated. Thus, FAD synthesis and delivery to these enzymes are crucial processes for bioenergetics and nutri-epigenetics of liver cells.

  8. Subjetividade e samba: a dor pede passage

    Directory of Open Access Journals (Sweden)

    Tânia Maia Barcelos

    2010-04-01

    Full Text Available Este artigo busca problematizar a subjetividade contemporânea, especialmente os modos hegemônicos de experimentação da dor, a partir de um encontro com o samba, gênero musical brasileiro, criado, oficialmente, nas primeiras décadas do século XX. O artigo parte da hipótese de que esse encontro pode potencializar a subjetividade brasileira nos processos de invenção e resistência à política do “evitamento da dor”, tão presente no contexto do capitalismo cultural, que, nas últimas décadas, vem acionando novas estratégias de produção de subjetividade que capturam e mercantilizam os afetos. Nesse encontro, autores como Deleuze, Guattari, Rolnik, Jurandir Freire, entre outros, auxiliam a apreensão das letras e versos de samba como possibilidades de experimentação da dor, na contramão das formas predominantes, historicamente, na cultura moderna e ocidental.

  9. Cytosolic iron chaperones: Proteins delivering iron cofactors in the cytosol of mammalian cells.

    Science.gov (United States)

    Philpott, Caroline C; Ryu, Moon-Suhn; Frey, Avery; Patel, Sarju

    2017-08-04

    Eukaryotic cells contain hundreds of metalloproteins that are supported by intracellular systems coordinating the uptake and distribution of metal cofactors. Iron cofactors include heme, iron-sulfur clusters, and simple iron ions. Poly(rC)-binding proteins are multifunctional adaptors that serve as iron ion chaperones in the cytosolic/nuclear compartment, binding iron at import and delivering it to enzymes, for storage (ferritin) and export (ferroportin). Ferritin iron is mobilized by autophagy through the cargo receptor, nuclear co-activator 4. The monothiol glutaredoxin Glrx3 and BolA2 function as a [2Fe-2S] chaperone complex. These proteins form a core system of cytosolic iron cofactor chaperones in mammalian cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Dor lombar crônica e dor nos membros inferiores em idosas: etiologia em revisão

    Directory of Open Access Journals (Sweden)

    Renata Maraschin

    Full Text Available INTRODUÇÃO: A relação entre dor lombar crônica, dor nos membros inferiores e dependência funcional em idosos evidencia-se pelo comportamento da dor durante a execução de atividades da vida diária. Permanecer em pé, puxar ou empurrar objetos grandes e caminhar podem desencadear dor e causar grande sofrimento para os idosos. OBJETIVO: Identificar as causas descritas na literatura relativas à dor lombar crônica e à dor nos membros inferiores em idosas. MÉTODO: Realizou-se busca, nas bases de dados Medline e Pubmed, de literatura em inglês publicada entre 1992 e 2008. RESULTADOS: Dos 48 artigos encontrados, 33 foram analisados. Entre as causas não mecânicas de dor, foram mencionadas fraturas vertebrais por compressão relacionadas à osteoporose, estenose espinhal lombar, metástases, malignidade, síndrome da cauda equina, bacteremia, infecções geniturinárias, tuberculose, polimialgia reumática, aneurisma aórtico, Doença de Paget e Doença de Parkinson. Entre as causas mecânicas, prevalentes em idosos e relacionadas ao sistema musculoesquelético, foram encontradas indefinições quanto à relação de causa e efeito estabelecida entre osteoartrite e dor. Em mulheres, a relação entre menopausa, uso de estrogênio e ocorrência de osteoporose-fratura-dor parece ainda pouca esclarecida. Associação entre dor lombar e dor nos membros inferiores pode sugerir causas mecânicas ou outras causas, visto que osteoartrite e distúrbios circulatórios, comuns em idosas, nem sempre são fontes de dor. CONCLUSÃO: Pela análise da literatura concluiu-se que, além da etiologia mencionada, outras possibilidades de causas, ainda não completamente identificadas e compreendidas, podem estar na origem da dor lombar e da dor nos membros inferiores de idosas.

  11. Replacing Electron Transport Cofactors with Hydrogenases

    KAUST Repository

    Laamarti, Rkia

    2016-12-01

    Enzymes have found applications in a broad range of industrial production processes. While high catalytic activity, selectivity and mild reaction conditions are attractive advantages of the biocatalysts, particularly costs arising from required cofactors pose a sever limitation. While cofactor-recycling systems are available, their use implies constraints for process set-up and conditions, which are a particular problem e.g. for solid-gas-phase reactions. Several oxidoreductases are able to directly exchange electrons with electrodes. Hence, the co-immobilization of both, an electron-utilizing and an electron-generating oxidoreductase on conductive nanoparticles should facilitate the direct electron flow from an enzymatic oxidation to a reduction reaction circumventing redox-cofactors requirements. In such a set-up, hydrogenases could generate and provide electrons directly form gaseous hydrogen. This thesis describes the co-immobilization of the oxygen tolerant hydrogenases from C. eutropha or C. metallidurans and cytochrome P450BM3 as test system. Conductive material in the form of carbon nanotubes (CNT) serves as a suitable support. A combination of the hydrogenase and the catalytic domain of P450BM3 immobilized on carbon nanotubes were tested for the oxidation of lauric acid in the presence of hydrogen instead of an electron-transport cofactor. The GC-MS analysis reveals the conversion of 4% of lauric acid (LA) into three products, which correspond to the hydroxylated lauric acid in three different positions with a total turnover (TON) of 34. The product distribution is similar to that obtained when using the wildtype P450BM3 with the nicotinamide adenine dinucleotide phosphate (NADPH) cofactor. Such electronic coupling couldn’t be achieved for the conversion of other substrates such as propane and cyclohexane, probably due to the high uncoupling rate within the heme-domain of cytochrome P450BM3 when unnatural substrates are introduced.

  12. O ensino da dor para os graduandos de enfermagem

    OpenAIRE

    Romanek, Flávia Alves Ribeiro Monclùs; Avelar, Maria do Carmo Querido

    2012-01-01

    A responsabilidade do enfermeiro frente ao gerenciamento da dor do paciente é um processo de avaliação e de tratamento adequado e efetivo. Desta constatação emergiu a questão norteadora que motivou a elaboração deste estudo: “Como vem sendo implementado o ensino da dor como 5° sinal vital nos Cursos de Graduação em Enfermagem?” O objetivo foi compreender a percepção dos docentes enfermeiros de um Curso de Graduação em Enfermagem sobre o ensino da dor no desenvolvimento das suas Disciplinas. R...

  13. Co-factors necessary for PPAR mediated transactivation of endogenous target genes

    DEFF Research Database (Denmark)

    Grøntved, Lars; Nielsen, Ronni; Stunnenberg, Henk

    of endogenous target gene in different cell types are elusive. To mutually compare the ability of the PPAR subtypes to activate endogenous target genes in a given cell, PPARa, PPARb/d and PPARg2 were HA tagged and rapidly, equally and synchronously expressed using adenoviral delivery. Within a few hours after...... subtype specific activation of target genes. Accumulating evidence suggests that transcriptional co-factors can function as master regulators for nuclear receptors and impose promoter selectivity. To study co-factor necessity for PPAR mediated transactivation of endogenous target genes, specific co...

  14. Heller Myotomy Versus Heller Myotomy With Dor Fundoplication for Achalasia

    Science.gov (United States)

    Richards, William O.; Torquati, Alfonso; Holzman, Michael D.; Khaitan, Leena; Byrne, Daniel; Lutfi, Rami; Sharp, Kenneth W.

    2004-01-01

    Objective: We sought to determine the impact of the addition of Dor fundoplication on the incidence of postoperative gastroesophageal reflux (GER) after Heller myotomy. Summary Background Data: Based only on case series, many surgeons believe that an antireflux procedure should be added to the Heller myotomy. However, no prospective randomized data support this approach. Patients and Methods: In this prospective, randomized, double-blind, institutional review board-approved clinical trial, patients with achalasia were assigned to undergo Heller myotomy or Heller myotomy plus Dor fundoplication. Patients were studied via 24-hour pH study and manometry at 6 months postoperatively. Pathologic GER was defined as distal esophageal time acid exposure time greater than 4.2% per 24-hour period. The outcome variables were analyzed on an intention-to-treat basis. Results: Forty-three patients were enrolled. There were no differences in the baseline characteristics between study groups. Pathologic GER occurred in 10 of 21 patients (47.6%) after Heller and in 2 of 22 patients (9.1%) after Heller plus Dor (P = 0.005). Heller plus Dor was associated with a significant reduction in the risk of GER (relative risk 0.11; 95% confidence interval 0.02–0.59; P = 0.01). Median distal esophageal acid exposure time was lower in the Heller plus Dor (0.4%; range, 0–16.7) compared with the Heller group (4.9%; range, 0.1–43.6; P = 0.001). No significant difference in surgical outcome between the 2 techniques with respect to postoperative lower-esophageal sphincter pressure or postoperative dysphagia score was observed. Conclusions: Heller Myotomy plus Dor Fundoplication was superior to Heller myotomy alone in regard to the incidence of postoperative GER. PMID:15319712

  15. Determinantes psicossociais da dor sexual na mulher portuguesa

    OpenAIRE

    Oliveira, Cátia Margarida dos Santos Pereira de

    2013-01-01

    A dor é uma experiência perceptualmente complexa, influenciada por um conjunto variado de fatores biológicos e também psicossociais. A sua vivência varia de pessoa para pessoa, havendo diferentes níveis de impacto no funcionamento emocional, interpessoal, motivacional e físico. A dor sexual, mais conhecida por dispareunia e vaginismo, é uma problemática de natureza habitualmente crónica que afeta muitas mulheres. Apesar de ser um importante alvo de estudo nas últimas décadas...

  16. Ansiedade, depressão e stress em doentes com dor crónica

    OpenAIRE

    Almeida, João Henrique Gonçalves de

    2014-01-01

    O presente estudo tem como objetivo principal perceber em que medida é que as dimensões ansiedade, depressão, vulnerabilidade ao stress, intensidade da dor e incapacidade relacionadas com a dor, afetam os doentes com dor crónica. Para o efeito, foi utilizada uma amostra de 53 doentes que frequentam a Consulta de Psicologia Clínica – Dor Crónica da Unidade de Dor Crónica do Pólo Hospital Geral do Centro Hospitalar e Universitário de Coimbra (CHUC), com idades compreendidas entre os 25 e os ...

  17. Relocalization of human chromatin remodeling cofactor TIP48 in mitosis

    International Nuclear Information System (INIS)

    Sigala, Barbara; Edwards, Mina; Puri, Teena; Tsaneva, Irina R.

    2005-01-01

    TIP48 is a highly conserved eukaryotic AAA + protein which is an essential cofactor for several complexes involved in chromatin acetylation and remodeling, transcriptional and developmental regulation and nucleolar organization and trafficking. We show that TIP48 abundance in HeLa cells did not change during the cell cycle, nor did its distribution in various biochemical fractions. However, we observed distinct changes in the subcellular localization of TIP48 during M phase using immunofluorescence microscopy. Our studies demonstrate that in interphase cells TIP48 was found mainly in the nucleus and exhibited a distinct localization in the nuclear periphery. As the cells entered mitosis, TIP48 was excluded from the condensing chromosomes but showed association with the mitotic apparatus. During anaphase, some TIP48 was detected in the centrosome colocalizing with tubulin but the strongest staining appeared in the mitotic equator associated with the midzone central spindle. Accumulation of TIP48 in the midzone and the midbody was observed in late telophase and cytokinesis. This redeployment of TIP48 during anaphase and cytokinesis was independent of microtubule assembly. The relocation of endogenous TIP48 to the midzone/midbody under physiological conditions suggests a novel and distinct function for TIP48 in mitosis and possible involvement in the exit of mitosis

  18. Enzyme cofactors: Double-edged sword for catalysis

    Science.gov (United States)

    Ivanov, Ivaylo

    2013-01-01

    The metal cofactors responsible for the activity of CDK2 -- a representative member of the kinase superfamily of enzymes -- have now been shown to also have inhibitory effects during the catalytic cycle.

  19. The ultraviolet extinction properties of the 30 Dor Nebula

    Science.gov (United States)

    De Marchi, Guido; Panagia, Nino

    2018-01-01

    Recent investigation of the extinction law in 30 Dor and the Tarantula Nebula, at optical and near infrared wavelengths, has revealed a ratio of total to selective extinction RV=AV/E(B-V) of about 4.5. This indicates a larger proportion of large grains than in the Galactic diffuse interstellar medium. Possible origins include coalescence of small grains, grain growth, selective destruction of small grains, and fresh injection of large grains. From a study of the ultraviolet extinction properties of three Wolf-Rayet stars in 30 Dor (R 139, R 140, R 145), observed with the International Ultraviolet Explorer, we show that the excess of large grains does not come at the expense of small grains, which are still present. Fresh injection of large grains by supernova explosions appears to be the dominant mechanism.

  20. Implementation of an ESA delta-DOR capability

    Science.gov (United States)

    James, Nick; Abello, Ricard; Lanucara, Marco; Mercolino, Mattia; Maddè, Roberto

    2009-06-01

    This paper describes the implementation of delta-DOR (delta-differential one-way ranging) receivers within the ESA Deep Space ground station network. Delta-DOR provides very accurate plane-of-sky measurements of spacecraft position which complement existing line-of-sight ranging and Doppler measurements. We discuss how this technique has been adapted and implemented at the two ESA deep-space ground stations using existing equipment and infrastructure. These new capabilities were added by writing new software modules for the standard ESA digital receiver (the intermediate frequency modem system—IFMS). With these upgrades the receiver has the ability to record accurately timetagged signals from up to eight IF sub-channels. These sub-channels can have bandwidths of 50 kHz-2 MHz with a sample quantization of 1-16 bits per component. The IF samples are stored locally for subsequent retrieval over a WAN by the correlator facility at ESOC.

  1. Metabolic and Transcriptional Response to Cofactor Perturbations in Escherichia coli

    DEFF Research Database (Denmark)

    Holm, Anders Koefoed; Blank, L.M.; Oldiges, M.

    2010-01-01

    Metabolic cofactors such as NADH and ATP play important roles in a large number of cellular reactions, and it is of great interest to dissect the role of these cofactors in different aspects of metabolism. Toward this goal, we overexpressed NADH oxidase and the soluble F1-ATPase in Escherichia coli...... of redox and energy metabolism and should help in developing metabolic engineering strategies in E. coli....

  2. Prevalência de sintomas depressivos e ansiosos em pacientes com dor crônica

    Directory of Open Access Journals (Sweden)

    Ricardo Cardoso Pinheiro

    2014-09-01

    Full Text Available Objetivos O presente estudo objetivou avaliar a prevalência de sintomas ansiosos e depressivos e relacioná-los com os diferentes tipos e magnitudes de dor crônica; também objetivou caracterizar a população de casos novos agendados para atendimento no ambulatório de dor crônica, no serviço onde o estudo foi realizado. Métodos Estudo de corte transversal, realizado em um ambulatório docente-assistencial para tratamento de dor crônica, realizado entre maio de 2012 e abril de 2013, com 125 pacientes. Instrumentos utilizados Questionário sociodemográfico, Escala Hospitalar de Ansiedade e Depressão (HAD e Escala Visual Numérica (EVN para aferir a intensidade de dor. Resultados Dor intensa foi referida por 64% (n = 80 dos pacientes. Ansiedade atingiu 65% (N = 82 dos pacientes e a depressão, 48% (N = 60. Houve correlação significante entre os mais altos escores de ansiedade (p < 0,001 e depressão (p < 0,001 com a intensidade de dor. A correlação entre intensidade de dor e sintomas ansiosos e depressivos foi positiva para dor crônica neuropática e mista. Os fatores sociodemográficos associados à intensidade de dor crônica foram: renda e religião para depressão, e tempo de dor para ansiedade. Conclusão O estudo mostrou elevada prevalência de sintomas depressivos e ansiosos em pacientes com dor crônica, assim como relação significante desses sintomas psiquiátricos com alguns tipos e intensidade de dor.

  3. [Voix d'Or, an audio tool to revive memories].

    Science.gov (United States)

    Braunschweig, Lina

    2010-01-01

    Voix d'Or is an audio tool designed to awaken the affective memory of elderly people and particularly those suffering from Alzheimer's disease. Every month it offers new radio programmes to initiate or facilitate leisure and entertainment activities, memory workshops or provide the basis of quiet moments. The tool has a double objective: to procure well-being, boost the individual's self-esteem and recognise his/her history and to facilitate exchange and communication between the residents and the staff of a care home.

  4. Metabolic impact of redox cofactor perturbations in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Hou, Jin; Lages, Nuno; Oldiges, M.

    2009-01-01

    to induce widespread changes in metabolism. We present a detailed analysis of the impact of perturbations in redox cofactors in the cytosol or mitochondria on glucose and energy metabolism in Saccharomyces cerevisiae to aid metabolic engineering decisions that involve cofactor engineering. We enhanced NADH...... oxidation by introducing NADH oxidase or alternative oxidase, its ATP-mediated conversion to NADPH using NADH kinase as well as the interconversion of NADH and NADPH independent of ATP by the soluble, non-proton-translocating bacterial transhydrogenase. Decreasing cytosolic NADH level lowered glycerol...

  5. Dor na psicanálise - física ou psíquica?

    Directory of Open Access Journals (Sweden)

    Natália Amendola Santos

    2014-09-01

    Full Text Available A dor tem se apresentado contemporaneamente como um tema importante para a psicanálise. Um dos móveis desse interesse é a fibromialgia, descrita por profissionais da medicina como uma síndrome caracterizada pela dor crônica na ausência de lesões ou sinais de anormalidade na maquinaria biológica. Levanta-se o impasse - como pensar psicanaliticamente uma dor que é física? Algumas leituras são propostas, tais como associações da dor com o estado melancólico, com inibições psíquicas e com a hipocondria. A dor é tomada como expressão de uma vivência traumática e não simbolizada.

  6. Time-resolved fluorescence analysis of the mobile flavin cofactor

    Indian Academy of Sciences (India)

    Conformational heterogeneity of the FAD cofactor in -hydroxybenzoate hydroxylase (PHBH) was investigated with time-resolved polarized flavin fluorescence. For binary enzyme/substrate (analogue) complexes of wild-type PHBH and Tyr222 mutants, crystallographic studies have revealed two distinct flavin conformations ...

  7. Cofactory: Sequence-based prediction of cofactor specificity of Rossmann folds

    DEFF Research Database (Denmark)

    Geertz-Hansen, Henrik Marcus; Blom, Nikolaj; Feist, Adam

    2014-01-01

    Obtaining optimal cofactor balance to drive production is a challenge metabolically engineered microbial strains. To facilitate identification of heterologous enzymes with desirable altered cofactor requirements from native content, we have developed Cofactory, a method for prediction of enzyme...

  8. Dor nas unidades de internação de um hospital universitário

    Directory of Open Access Journals (Sweden)

    Sonia B. Felix Ribeiro

    2012-10-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Estudo exploratório-descritivo, transversal, com objetivo de determinar a prevalência, caracterização, localização, mensuração e discussão de medidas farmacológicas analgésicas em dor aguda em cinco unidades de internação de um hospital universitário. MÉTODO: Participaram 856 sujeitos, dos quais 272 com dor no momento. As informações relacionadas à dor foram obtidas através de entrevista estruturada junto ao leito. Usou-se a escala numérica de dor e diagrama corporal. RESULTADOS: A analgesia foi verificada no prontuário. A prevalência geral de dor foi de 31,8%, sendo intensa em 44,2% e a média de 6,6 na escala numérica de dor. O motivo principal foi traumatismo, o local mais frequente, o abdômen. O analgésico mais usado foi a dipirona em 76,1%, com/sem associação. Opioide forte foi prescrito em 4,4%. Para 27,5% não houve melhoria. CONCLUSÃO: Conclui-se que a dor é de alta prevalência, pouco avaliada, subtratada, com uso incorreto de analgésicos.

  9. A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev

    International Nuclear Information System (INIS)

    Fang Jianhua; Kubota, Satoshi; Yang Bin; Zhou Naiming; Zhang Hui; Godbout, Roseline; Pomerantz, Roger J.

    2004-01-01

    HIV-1 Rev escorts unspliced viral mRNAs out of the nucleus of infected cells, which allows formation of infectious HIV-1 virions. We have identified a putative DEAD box (Asp-Glu-Ala-Asp) RNA helicase, DDX1, as a cellular co-factor of Rev, through yeast and mammalian two-hybrid systems using the N-terminal motif of Rev as 'bait'. DDX1 is not a functional homolog of HIV-1 Rev, but down-regulation of DDX1 resulted in an alternative splicing pattern of Rev-responsive element (RRE)-containing mRNA, and attenuation of Gag p24 antigen production from HLfb rev(-) cells rescued by exogenous Rev. Co-transfection of a DDX1 expression vector with HIV-1 significantly increased viral production. DDX1 binding to Rev, as well as to the RRE, strongly suggest that DDX1 affects Rev function through the Rev-RRE axis. Moreover, down-regulation of DDX1 altered the steady state subcellular distribution of Rev, from nuclear/nucleolar to cytoplasmic dominance. These findings indicate that DDX1 is a critical cellular co-factor for Rev function, which maintains the proper subcellular distribution of this lentiviral regulatory protein. Therefore, alterations in DDX1-Rev interactions could induce HIV-1 persistence and targeting DDX1 may lead to rationally designed and novel anti-HIV-1 strategies and therapeutics

  10. Insight into cofactor recognition in arylamine N-acetyltransferase enzymes

    DEFF Research Database (Denmark)

    Xu, Ximing; Li de la Sierra-Gallay, Inés; Kubiak, Xavier Jean Philippe

    2015-01-01

    Arylamine N-acetyltransferases (NATs) are xenobiotic metabolizing enzymes that catalyze the acetyl-CoA-dependent acetylation of arylamines. To better understand the mode of binding of the cofactor by this family of enzymes, the structure of Mesorhizobium loti NAT1 [(RHILO)NAT1] was determined...... for Bacillus anthracis NAT1 and Homo sapiens NAT2. Therefore, in contrast to previous data, this study shows that different orthologous NATs can bind their cofactors in a similar way, suggesting that the mode of binding CoA in this family of enzymes is less diverse than previously thought. Moreover......, it supports the notion that the presence of the `mammalian/eukaryotic insertion loop' in certain NAT enzymes impacts the mode of binding CoA by imposing structural constraints....

  11. Dor odontogênica como motivo para procura de atendimento odontológico : uso de medicamentos para controle de dor e outros fatores associados

    OpenAIRE

    Maria Rachel Figueiredo Penalva Monteiro

    2015-01-01

    Resumo: A dor de origem dental é caracterizada como uma dor aguda e está intimamente relacionada com a necessidade da administração de fármacos para alívio do sintoma, na tentativa de retardar a procura por atendimento odontológico. Nesse contexto, o uso de fármacos ocorre, muitas vezes, sem diagnóstico, prescrição ou orientação feitos pelo dentista. Desta forma, este trabalho teve por objetivo avaliar a prática da automedicação com a dor odontogênica, em pacientes que procuram o serviço univ...

  12. A Kine-chemical Investigation of the AB Dor Moving Group "Stream"

    Science.gov (United States)

    Barenfeld, Scott A.; Bubar, Eric J.; Mamajek, Eric E.; Young, Patrick A.

    2013-03-01

    The AB Dor Moving Group consists of a "nucleus" of ~10 stars at d ~= 20 pc, along with dozens of purported "stream" members distributed across the sky. We perform a chemical and kinematic analysis of a subsample of AB Dor stream stars to test whether they constitute a physical stellar group. We use the NEMO Galactic kinematic code to investigate the orbits of the stream members, and perform a chemical abundance analysis using high resolution spectra taken with the Magellan Clay 6.5 m telescope. Using a χ2 test with the measured abundances for 10 different elements, we find that only half of the purported AB Dor stream members could possibly constitute a statistically chemically homogeneous sample. Some stream members with three-dimensional velocities were hundreds of parsecs from the AB Dor nucleus ~108 yr ago, and hence were unlikely to share a common origin. We conclude that the published lists of AB Dor moving group stream members are unlikely to represent the dispersed remnant of a single star formation episode. A subsample of the stream stars appears to be both statistically chemically homogeneous and in the vicinity of the AB Dor nucleus at birth. Their mean metallicity is [Fe/H] = 0.02 ± 0.02 dex, which we consider representative for the AB Dor group. Finally, we report a strong lower limit on the age of the AB Dor nucleus of >110 Myr based on the pre-main sequence contraction times for K-type members which have reached the main sequence.

  13. Results of a search for γ Dor and δ SCT stars with the Kepler spacecraft

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, P. A.; Miles, L. F. [XCP-6, MS F-699 Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Guzik, J. A. [XTD-NTA, MS T-086 Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Uytterhoeven, K. [Instituto de Astrofisica de Canarias, 38200 La Laguna, Tenerife, Spain and Departamento de Astrofisica, Universidad de La Laguna, E-38200 La Laguna, Tenerife (Spain); Jackiewicz, J. [New Mexico State University, Las Cruces, NM 88003 (United States); Kinemuchi, K., E-mail: pbradley@lanl.gov [Apache Point Observatory, Sunspot, NM 88349 (United States)

    2015-02-01

    The light curves of 2768 stars with effective temperatures and surface gravities placing them near the gamma Doradus (γ Dor)/delta Scuti (δ Sct) instability region were observed as part of the Kepler Guest Observer program from Cycles 1 through 5. The light curves were analyzed in a uniform manner to search for γ Dor, δ Sct, and hybrid star pulsations. The γ Dor, δ Sct, and hybrid star pulsations extend asteroseismology to stars slightly more massive (1.4–2.5 M{sub ⊙}) than our Sun. We find 207 γ Dor, 84 δ Sct, and 32 hybrid candidate stars. Many of these stars are cooler than the red edge of the γ Dor instability strip as determined from ground-based observations made before Kepler. A few of our γ Dor candidate stars lie on the hot side of the ground-based γ Dor instability strip. The hybrid candidate stars cover the entire region between 6200 K and the blue edge of the ground-based δ Sct instability strip. None of our candidate stars are hotter than the hot edge of the ground-based δ Sct instability strip. Our discoveries, coupled with the work of others, show that Kepler has discovered over 2000 γ Dor, δ Sct, and hybrid star candidates in the 116 square degree Kepler field of view. We found relatively few variable stars fainter than magnitude 15, which may be because they are far enough away to lie between spiral arms in our Galaxy, where there would be fewer stars.

  14. Is Dor fundoplication optimum after laparoscopic Heller myotomy for achalasia? A meta-analysis.

    Science.gov (United States)

    Wei, Ming-Tian; He, Ya-Zhou; Deng, Xiang-Bing; Zhang, Yuan-Chuan; Yang, Ting-Han; Jin, Cheng-Wu; Hu, Bing; Wang, Zi-Qiang

    2013-11-21

    To compare the outcome of acid reflux prevention by Dor fundoplication after laparoscopic Heller myotomy (LHM) for achalasia. Electronic database PubMed, Ovid (Evidence-Based Medicine Reviews, EmBase and Ovid MEDLINE) and Cochrane Library were searched between January 1995 and September 2012. Bibliographic citation management software (EndNote X3) was used for extracted literature management. Quality assessment of random controlled studies (RCTs) and non-RCTs was performed according to the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 and a modification of the Newcastle-Ottawa Scale, respectively. The data were analyzed using Review Manager (Version 5.1), and sensitivity analysis was performed by sequentially omitting each study. Finally, 6 studies, including a total of 523 achalasia patients, compared Dor fundoplication with other types of fundoplication after LHM (Dor-other group), and 8 studies, including a total of 528 achalasia patients, compared Dor fundoplication with no fundoplication after LHM (Dor-no group). Dor fundoplication was associated with a significantly higher recurrence rate of clinical regurgitation and pathological acid reflux compared with the other fundoplication group (OR = 7.16, 95%CI: 1.25-40.93, P = 0.03, and OR = 3.79, 95%CI: 1.23-11.72, P = 0.02, respectively). In addition, there were no significant differences between Dor fundoplication and no fundoplication in all subjects. Other outcomes, including complications, dysphagia, postoperative physiologic testing, and operation-related data displayed no significant differences in the two comparison groups. Dor fundoplication is not the optimum procedure after LHM for achalasia. We suggest more attention should be paid on quality of life among different fundoplications.

  15. Results of a search for γ Dor and δ SCT stars with the Kepler spacecraft

    International Nuclear Information System (INIS)

    Bradley, P. A.; Miles, L. F.; Guzik, J. A.; Uytterhoeven, K.; Jackiewicz, J.; Kinemuchi, K.

    2015-01-01

    The light curves of 2768 stars with effective temperatures and surface gravities placing them near the gamma Doradus (γ Dor)/delta Scuti (δ Sct) instability region were observed as part of the Kepler Guest Observer program from Cycles 1 through 5. The light curves were analyzed in a uniform manner to search for γ Dor, δ Sct, and hybrid star pulsations. The γ Dor, δ Sct, and hybrid star pulsations extend asteroseismology to stars slightly more massive (1.4–2.5 M ⊙ ) than our Sun. We find 207 γ Dor, 84 δ Sct, and 32 hybrid candidate stars. Many of these stars are cooler than the red edge of the γ Dor instability strip as determined from ground-based observations made before Kepler. A few of our γ Dor candidate stars lie on the hot side of the ground-based γ Dor instability strip. The hybrid candidate stars cover the entire region between 6200 K and the blue edge of the ground-based δ Sct instability strip. None of our candidate stars are hotter than the hot edge of the ground-based δ Sct instability strip. Our discoveries, coupled with the work of others, show that Kepler has discovered over 2000 γ Dor, δ Sct, and hybrid star candidates in the 116 square degree Kepler field of view. We found relatively few variable stars fainter than magnitude 15, which may be because they are far enough away to lie between spiral arms in our Galaxy, where there would be fewer stars.

  16. Insights into hydrocarbon formation by nitrogenase cofactor homologs.

    Science.gov (United States)

    Lee, Chi Chung; Hu, Yilin; Ribbe, Markus W

    2015-04-14

    The L-cluster is an all-iron homolog of nitrogenase cofactors. Driven by europium(II) diethylenetriaminepentaacetate [Eu(II)-DTPA], the isolated L-cluster is capable of ATP-independent reduction of CO and CN(-) to C1 to C4 and C1 to C6 hydrocarbons, respectively. Compared to its cofactor homologs, the L-cluster generates considerably more CH4 from the reduction of CO and CN(-), which could be explained by the presence of a "free" Fe atom that is "unmasked" by homocitrate as an additional site for methanation. Moreover, the elevated CH4 formation is accompanied by a decrease in the amount of longer hydrocarbons and/or the lengths of the hydrocarbon products, illustrating a competition between CH4 formation/release and C-C coupling/chain extension. These observations suggest the possibility of designing simpler synthetic clusters for hydrocarbon formation while establishing the L-cluster as a platform for mechanistic investigations of CO and CN(-) reduction without complications originating from the heterometal and homocitrate components. Nitrogenase is a metalloenzyme that is highly complex in structure and uniquely versatile in function. It catalyzes two reactions that parallel two important industrial processes: the reduction of nitrogen to ammonia, which parallels the Haber-Bosch process in ammonia production, and the reduction of carbon monoxide to hydrocarbons, which parallels the Fischer-Tropsch process in fuel production. Thus, the significance of nitrogenase can be appreciated from the perspective of the useful products it generates: (i) ammonia, the "fixed" nitrogen that is essential for the existence of the entire human population; and (ii) hydrocarbons, the "recycled" carbon fuel that could be used to directly address the worldwide energy shortage. This article provides initial insights into the catalytic characteristics of various nitrogenase cofactors in hydrocarbon formation. The reported assay system provides a useful tool for mechanistic

  17. Prevalência de dor cervical e incapacidade funcional na Escola Superior de Tecnologia da Saúde do Porto

    OpenAIRE

    Marques, André; Mesquita, Cristina

    2010-01-01

    A dor cervical é cada vez mais um problema comum e incapacitante nos países industrializados. O objectivo do estudo foi determinar a prevalência de dor cervical nos últimos seis meses, intensidade da dor e incapacidade funcional em indivíduos com dor cervical. O estudo do tipo observacional, descritivo e transversal. Amostra constituída por alunos, docentes, administrativos e auxiliares da ESTSP (n=285). Os instrumentos utilizados foram: questionário de caracterização da amostra, escala visua...

  18. On the Metal Cofactor in the Tyrosinase Family

    Directory of Open Access Journals (Sweden)

    Francisco Solano

    2018-02-01

    Full Text Available The production of pigment in mammalian melanocytes requires the contribution of at least three melanogenic enzymes, tyrosinase and two other accessory enzymes called the tyrosinase-related proteins (Trp1 and Trp2, which regulate the type and amount of melanin. The last two proteins are paralogues to tyrosinase, and they appeared late in evolution by triplication of the tyrosinase gene. Tyrosinase is a copper-enzyme, and Trp2 is a zinc-enzyme. Trp1 has been more elusive, and the direct identification of its metal cofactor has never been achieved. However, due to its enzymatic activity and similarities with tyrosinase, it has been assumed as a copper-enzyme. Recently, recombinant human tyrosinase and Trp1 have been expressed in enough amounts to achieve for the first time their crystallization. Unexpectedly, it has been found that Trp1 contains a couple of Zn(II at the active site. This review discusses data about the metal cofactor of tyrosinase and Trps. It points out differences in the studied models, and it proposes some possible points accounting for the apparent discrepancies currently appearing. Moreover, some proposals about the possible flexibility of the tyrosinase family to uptake copper or zinc are discussed.

  19. Oxygen diffusion pathways in a cofactor-independent dioxygenase

    Science.gov (United States)

    Di Russo, Natali V.; Condurso, Heather L.; Li, Kunhua; Bruner, Steven D.; Roitberg, Adrian E.

    2015-01-01

    Molecular oxygen plays an important role in a wide variety of enzymatic reactions. Through recent research efforts combining computational and experimental methods a new view of O2 diffusion is emerging, where specific channels guide O2 to the active site. The focus of this work is DpgC, a cofactor-independent oxygenase. Molecular dynamics simulations, together with mutagenesis experiments and xenon-binding data, reveal that O2 reaches the active site of this enzyme using three main pathways and four different access points. These pathways connect a series of dynamic hydrophobic pockets, concentrating O2 at a specific face of the enzyme substrate. Extensive molecular dynamics simulations provide information about which pathways are more frequently used. This data is consistent with the results of kinetic measurements on mutants and is difficult to obtain using computational cavity-location methods. Taken together, our results reveal that although DpgC is rare in its ability of activating O2 in the absence of cofactors or metals, the way O2 reaches the active site is similar to that reported for other O2-using proteins: multiple access channels are available, and the architecture of the pathway network can provide regio- and stereoselectivity. Our results point to the existence of common themes in O2 access that are conserved among very different types of proteins. PMID:26508997

  20. Reproductive ovarian testing and the alphabet soup of diagnoses: DOR, POI, POF, POR, and FOR.

    Science.gov (United States)

    Pastore, Lisa M; Christianson, Mindy S; Stelling, James; Kearns, William G; Segars, James H

    2018-01-01

    There are large variations in the number of oocytes within each woman, and biologically, the total quantity is at its maximum before the woman is born. Scientific knowledge is limited about factors controlling the oocyte pool and how to measure it. Within fertility clinics, there is no uniform agreement on the diagnostic criteria for each common measure of ovarian reserve in women, and thus, studies often conflict. While declining oocyte quantity/quality is a normal physiologic occurrence as women age, some women experience diminished ovarian reserve (DOR) much earlier than usual and become prematurely infertile. Key clinical features of DOR are the presence of regular menstrual periods and abnormal-but-not-postmenopausal ovarian reserve test results. A common clinical challenge is counseling patients with conflicting ovarian reserve test results. The clinical diagnosis of DOR and the interpretation of ovarian reserve testing are complicated by changing lab testing options and processing for anti-mullerian hormone since 2010. Further, complicating the diagnostic and research scenario is the existence of other distinct yet related clinical terms, specifically premature ovarian failure, primary ovarian insufficiency, poor ovarian response, and functional ovarian reserve. The similarities and differences between the definitions of DOR with each of these four terms are reviewed. We recommend greater medical community involvement in terminology decisions, and the addition of DOR-specific medical subject-heading search terms.

  1. Tecnologia tátil para a avaliação da dor em cegos

    Directory of Open Access Journals (Sweden)

    Ana Cláudia de Souza Toniolli

    Full Text Available Trata-se de um estudo descritivo e exploratório das percepções dos cegos acerca do protótipo chamado Escala Tátil, para avaliação da intensidade da dor. Por meio de uma entrevista semi-estruturada, foram obtidos os relatos de cegos da Associação dos Cegos do Ceará, para descrever a natureza do protótipo, estabelecendo relações entre as suas experiências dolorosas e buscando significados para a sua utilização na cultura dos cegos. Dos relatos, foram identificados e analisados três temas: intensidade da dor na ponta dos dedos, percepção da escala tátil da dor, destacando-se textura, forma e tamanho, lapidando-se a Escala Tátil. A percepção sensorial tátil dos cegos gerou novos parâmetros de reflexão para o estudo da dor e direcionou a performance do protótipo para um processo de comunicação da dor mais satisfatório.

  2. Outcome of Achalasia Cardia Managed with Transabdominal Hellers Cardiomyotomy and Anterior Dor Patch

    International Nuclear Information System (INIS)

    Wyne, A.; Majeed, F. A.; Khan, M. I.; Rahim, K.

    2013-01-01

    Objectives: To evaluate relief of dysphagia and apprearance of reflux symptoms in patients of achalasia cardia treated with Trans abdominal cardiomyotomy and anterior Dor patch. Study Design: Quasi experimental study. Place and duration of study: Combined Military Hospital Quetta and Combined Military Hospital Rawalpindi from Jan 2006 to Jan 2012. Methodology: Twenty three cases were diagnosed to have achalasia cardia on barium swallow, upper GI endoscopy and CT scan chest in selective cases. They were treated with transabdominal modified Hellers cardiomyotomy and anterior Dor patch as an antireflux procedure. Relief of dysphagia and occurrence of reflux symptoms were evaluated clinically. Results: All (100%) operated patients had symptomatic relief of dysphagia over follow up of six months. No patient had post op reflux symptoms. Conclusion: Transabdominal Hellers cardiomyotomy with anterior Dor patch is a safe and effective surgical option for achalasia cardia. (author)

  3. Zinc is the metal cofactor of Borrelia burgdorferi peptide deformylase.

    Science.gov (United States)

    Nguyen, Kiet T; Wu, Jen-Chieh; Boylan, Julie A; Gherardini, Frank C; Pei, Dehua

    2007-12-15

    Peptide deformylase (PDF, E.C. 3.5.1.88) catalyzes the removal of N-terminal formyl groups from nascent ribosome-synthesized polypeptides. PDF contains a catalytically essential divalent metal ion, which is tetrahedrally coordinated by three protein ligands (His, His, and Cys) and a water molecule. Previous studies revealed that the metal cofactor is a Fe2+ ion in Escherichia coli and many other bacterial PDFs. In this work, we found that PDFs from two iron-deficient bacteria, Borrelia burgdorferi and Lactobacillus plantarum, are stable and highly active under aerobic conditions. The native B. burgdorferi PDF (BbPDF) was purified 1200-fold and metal analysis revealed that it contains approximately 1.1 Zn2+ ion/polypeptide but no iron. Our studies suggest that PDF utilizes different metal ions in different organisms. These data have important implications in designing PDF inhibitors and should help address some of the unresolved issues regarding PDF structure and catalytic function.

  4. Quality of life comparing dor and toupet after heller myotomy for achalasia.

    Science.gov (United States)

    Tomasko, Jonathan M; Augustin, Toms; Tran, Tung T; Haluck, Randy S; Rogers, Ann M; Lyn-Sue, Jerome R

    2014-01-01

    Laparoscopic Heller cardiomyotomy (LHC) is standard therapy for achalasia. Traditionally, an antireflux procedure has accompanied the myotomy. This study was undertaken to compare quality-of-life outcomes between patients undergoing myotomy with Toupet versus Dor fundoplication. In addition, we investigated overall patient satisfaction after LHC in the treatment of achalasia. One hundred thirty-five patients who underwent LHC over a 13-year period were identified for inclusion. Symptoms queried included dysphagia, heartburn, and bloating using the Gastroesophageal Reflux Disease-Health-Related Quality of Life Scale and a second published scale for the assessment of gastroesophageal reflux disease and dysphagia symptoms. The patients' overall satisfaction after surgery was also rated. Data were compared on the basis of type of fundoplication. Symptom scores were analyzed using chi-square tests and Fisher's exact tests. Sixty-three patients completed the survey (47%). There were no perioperative deaths or reoperations. The mean length of stay was 2.8 days. The mean operative time for LHC with Toupet fundoplication was 137.3±30.91 minutes and for LHC with Dor fundoplication was 111.5±32.44 minutes (P=.006). There was no difference with respect to the incidence or severity of postoperative heartburn, dysphagia, or bloating. Overall satisfaction with Toupet fundoplication was 87.5% and with Dor fundoplication was 93.8% (P>.999). LHC with either Toupet or Dor fundoplication gave excellent patient satisfaction. Postoperative symptoms of heartburn and dysphagia were equivalent when comparing LHC with either antireflux procedure. Dor and Toupet fundoplication were found to have equivalent outcomes in the short term. We prefer Dor to Toupet fundoplication because of its decreased need for extensive dissection and better mucosal protection.

  5. Adaptacao e validacao do WHODAS 2.0 em utentes com dor musculoesqueletica

    Directory of Open Access Journals (Sweden)

    Carla Silva

    2013-08-01

    Full Text Available OBJETIVO Validar a versão em português do World Health Organization Disability Assessment Schedule (WHODAS 2.0. MÉTODOS A versão original de 36 itens do WHODAS 2.0, administrada por entrevista, foi traduzida para o português de acordo com orientações internacionais e testada em nove participantes da população em geral. A versão em português foi administrada em 204 pacientes com patologia musculoesquelética. Foram coletados os dados sociodemográficos e de saúde dos pacientes, assim como o número de locais onde apresentavam dor e sua intensidade. O WHODAS 2.0 foi novamente administrado por um segundo entrevistador, um a três dias após a primeira entrevista, para avaliar a confiabilidade interavaliadores. A validade de constructo foi avaliada quanto a: capacidade do WHODAS 2.0 para diferenciar participantes com diferentes locais com dor e associação entre o WHODAS 2.0 e a intensidade da dor. A consistência interna também foi avaliada. RESULTADOS A versão portuguesa do WHODAS 2.0 teve fácil compreensão, apresentou boa consistência interna (α = 0,84 e confiabilidade interavaliadores (CCI = 0,95. Mostrou ser capaz de detectar diferenças estatisticamente significativas entre indivíduos com diferente número de locais com dor (p < 0,01 e indicar que maior incapacidade está associada à maior intensidade da dor (r = 0,44, p < 0,01, indicando validade de constructo. CONCLUSÕES A versão portuguesa do WHODAS 2.0 mostrou-se confiável e válida quando utilizada em pacientes com dor associada à patologia musculoesquelética.

  6. Invalidez por dor nas costas entre segurados da Previdência Social do Brasil

    Directory of Open Access Journals (Sweden)

    Ney Meziat Filho

    2011-06-01

    Full Text Available OBJETIVO: Descrever as aposentadorias por invalidez decorrente de dor nas costas. MÉTODOS: Estudo descritivo com dados do Sistema Único de Informações de Benefícios e dos Anuários Estatísticos da Previdência Social em 2007. A taxa de incidência de dor nas costas como causa das aposentadorias por invalidez foi calculada segundo as variáveis idade e sexo, nos estados. Os dias de trabalho perdidos por invalidez decorrente de dor nas costas foram calculados segundo atividade profissional. RESULTADOS: A dor nas costas idiopática foi a primeira causa de invalidez entre as aposentadorias previdenciárias e acidentárias. A maioria dos beneficiários residia em área urbana e era comerciário. A taxa de incidência de dor nas costas como causa das aposentadorias por invalidez no Brasil foi de 29,96 por 100.000 contribuintes. Esse valor foi mais elevado entre os homens e entre as pessoas mais velhas. Rondônia exibiu taxa quatro vezes superior ao esperado (RT = 4,05 e a segunda maior taxa, referente à Bahia, foi de aproximadamente duas vezes o esperado (RT = 2,07. Os comerciários foram responsáveis por 96,9% dos dias perdidos por invalidez. CONCLUSÕES: A dor nas costas foi uma importante causa de invalidez em 2007, sobretudo entre comerciários, com grandes diferenças entre os estados.

  7. Recruitment of RNA polymerase II cofactor PC4 to DNA damage sites

    Science.gov (United States)

    Mortusewicz, Oliver; Roth, Wera; Li, Na; Cardoso, M. Cristina; Meisterernst, Michael; Leonhardt, Heinrich

    2008-01-01

    The multifunctional nuclear protein positive cofactor 4 (PC4) is involved in various cellular processes including transcription, replication, and chromatin organization. Recently, PC4 has been identified as a suppressor of oxidative mutagenesis in Escherichia coli and Saccharomyces cerevisiae. To investigate a potential role of PC4 in mammalian DNA repair, we used a combination of live cell microscopy, microirradiation, and fluorescence recovery after photobleaching analysis. We found a clear accumulation of endogenous PC4 at DNA damage sites introduced by either chemical agents or laser microirradiation. Using fluorescent fusion proteins and specific mutants, we demonstrated that the rapid recruitment of PC4 to laser-induced DNA damage sites is independent of poly(ADP-ribosyl)ation and γH2AX but depends on its single strand binding capacity. Furthermore, PC4 showed a high turnover at DNA damages sites compared with the repair factors replication protein A and proliferating cell nuclear antigen. We propose that PC4 plays a role in the early response to DNA damage by recognizing single-stranded DNA and may thus initiate or facilitate the subsequent steps of DNA repair. PMID:19047459

  8. Qualificação da dor em trabalhadoras de uma malharia no sul do Brasil

    Directory of Open Access Journals (Sweden)

    Marina Cauz

    2016-03-01

    Full Text Available Objetivo: Analisar e qualificar a dor em mulheres de uma malharia do sul do Brasil. Métodos: Estudo transversal, descritivo, com abordagem quantitativa, em que foram entrevistadas 15 trabalhadoras em um único dia de maio de 2012. As avaliações para qualificação e análise da dor aconteceram por meio de três questionários: multidimensional adaptado, inventário para dor de Wisconsin (análise da dor e o questionário de McGill (qualificação. Para análise dos dados, foi realizada a estatística descritiva, com o calculo da média, desvio padrão, percentual e números absolutos. Resultados: As participantes apresentavam média de idade de 33,4 (±14,9 anos e trabalhavam 9 horas diárias. Referente à postura dolorosa no posto de trabalho, observou-se maior queixa em ombros abduzidos e cotovelos flexionados (n=7, 46,6%. Os locais anatômicos dolorosos mais frequentes foram ombros (n=8, 22,2%, coluna cervical (n=7, 19,4% e cotovelos (n=7, 19,4%. A análise da dor pelo inventário de Wisconsin, classificada por meio da Escala Visual Analógica de Dor (EVA, demonstrou interferência moderada no trabalho, sono, humor, apreciação da vida e na atividade geral. De acordo com o questionário de McGill, houve destaque para o nível sensorial, com maior frequência para dor latejante (n=10, 50%, agulhada (n=4, 20% e formigamento (n=4, 20%. Conclusão: A amostra apresentou alta frequência de dor nos ombros, cotovelos, coluna cervical e sintomatologia dolorosa considerada moderada na maioria dos itens avaliados, o que pode levar a uma interferência importante nas atividades laborais e do cotidiano.

  9. Prevalência de dor associada ao transporte de material escolar

    Directory of Open Access Journals (Sweden)

    Windsor Ramos da Silva Júnior

    2014-10-01

    Full Text Available http://dx.doi.org/10.5007/1980-0037.2014v16n6p680 O objetivo do trabalho foi verificar a prevalência de dor associada ao transporte de material escolar por estudantes universitários. Realizou-se pesquisa transversal, quantitativa, descritiva-analítica, na qual foram avaliados 373 estudantes universitários da Universidade Estadual da Paraíba, entre fevereiro e setembro de 2012. As informações foram coletadas através de questionário sobre dados sociodemográficos, acadêmicos, transporte do material escolar e presença de dor, sendo ainda realizada a medição de dados antropométricos e pesagem de todos os volumes transportados pelo indivíduo. Os dados foram analisados de forma descritiva e inferencial através do software SPSSÒ 17.0. Utilizou-se modelo de Regressão Logística Hierárquica Binária, pelo método Backward LR, no qual o poder de influência das variáveis preditoras – divididas em blocos – foi testado na presença de dor musculoesquelética. Constatou-se uma prevalência de dor de 82,84%, com média geral de 5,21 pontos na Escala Visual Analógica (EVA para avaliação de dor. Nas mulheres, a influência exercida pela massa relativa dos volumes sobre a presença de dor foi 45,1% maior que entre os homens (OR = 0,689; IC95% = 0,503 – 0,942 para cada 1% de incremento. O tempo de carga, por sua vez, aumentou em 22,9% a probabilidade da presença de dor, a cada 15 minutos decorridos (OR = 1,229; IC95% = 1,090 – 1,386. Verificou-se alta prevalência de dor relacionada ao transporte de material escolar e a influência preditora de variáveis como peso relativo da carga transportada e tempo de transporte desse material, especialmente nos indivíduos do sexo feminino.

  10. Cofactors in allergic reactions to food : physical exercise and alcohol are the most important

    NARCIS (Netherlands)

    Versluis, Astrid; van Os-Medendorp, Harmieke; Kruizinga, Astrid G; Blom, W Marty; Houben, Geert F; Knulst, André C

    2016-01-01

    INTRODUCTION: Involvement of cofactors, like physical exercise, alcohol consumption and use of several types of medication, are associated with more severe food allergic symptoms. However, there is limited evidence on how often cofactors play a role in food allergic reactions. The study aimed to get

  11. Application of NAD(P)H oxidase for cofactor regeneration in dehydrogenase catalyzed oxidations

    DEFF Research Database (Denmark)

    Rehn, Gustav; Pedersen, Asbjørn Toftgaard; Woodley, John

    2016-01-01

    alcohol dehydrogenases. However, their effective use requires an effective regeneration of the oxidized nicotinamide cofactor (NAD(P)+), which is critical for the economic feasibility of the process. NAD(P)H oxidase is an enzyme class of particular interest for this cofactor regeneration since it enables...

  12. Beyond the Protein Matrix : Probing Cofactor Variants in a Baeyer-Villiger Oxygenation Reaction

    NARCIS (Netherlands)

    Martinoli, Christian; Dudek, Hanna M.; Orru, Roberto; Edmondson, Dale E.; Fraaije, Marco W.; Mattevi, Andrea

    2013-01-01

    A general question in biochemistry is the interplay between the chemical properties of cofactors and the surrounding protein matrix. Here, the functions of NADP(+) and FAD are explored by investigation of a representative monooxygenase reconstituted with chemically modified cofactor analogues. Like

  13. Molybdenum-cofactor deficiency: an easily missed cause of neonatal convulsions

    NARCIS (Netherlands)

    Slot, H. M.; Overweg-Plandsoen, W. C.; Bakker, H. D.; Abeling, N. G.; Tamminga, P.; Barth, P. G.; van Gennip, A. H.

    1993-01-01

    Intractable seizures in the neonatal period may be caused by molybdenum-cofactor deficiency, an inborn error which combines the deficiencies of sulphite oxidase and xanthine dehydrogenase. The neurological symptoms of molybdenum cofactor and isolated sulphite oxidase deficiencies are identical. Two

  14. Esquema de Desamparo em Paciente com Dor Crônica e Sintomas Depressivos

    Directory of Open Access Journals (Sweden)

    Elisangela Ferreira Santana

    2015-12-01

    Full Text Available A fibromialgia caracteriza-se por dor generalizada e crônica, de modo geral, associada à incapacidade funcional e quadros depressivos. Por suas repercussões, esta síndrome dolorosa pode ativar e/ou potencializar esquemas de desamparo e desvalor, o que por sua vez pode contribuir para o surgimento de sintomas depressivos. Neste artigo, analisa-se o processo de manejo da dor por meio da identificação de crenças de incapacidade e da alteração de humor numa paciente com dor crônica e sintomas depressivos. Para tanto, são descritas as estratégias e técnicas utilizadas em seu processo terapêutico, realizado em 13 sessões, que teve como embasamento a terapia cognitiva. Além disto, apresenta-se a conceituação cognitiva referente ao esquema de desamparo da paciente. Embora Laura não tenha apresentado mudanças significativas na percepção álgica, os sintomas depressivos tiveram uma remissão importante, o que contribuiu para aquisição de comportamentos mais funcionais para manejo da dor, como solicitar ajuda e evitar o esforço físico.

  15. Fundoplication after heller myotomy: a retrospective comparison between nissen and dor.

    Science.gov (United States)

    Cuttitta, Antonello; Tancredi, Antonio; Andriulli, Angelo; De Santo, Ermelinda; Fontana, Andrea; Pellegrini, Fabio; Scaramuzzi, Roberto; Scaramuzzi, Gerardo

    2011-12-01

    A retrospective comparison between Nissen and Dor fundoplication after laparoscopic Heller myotomy for achalasia. From 1998 to 2004 a first group of 48 patients underwent Heller myotomy and Nissen fundoplication for idiopathic achalasia (H+N group). From 2004 to 2010 a second group of 40 patients underwent Heller myotomy followed by Dor fundoplication (H+D group). Some patients received a previous endoscopic treatment with pneumatic dilatation or endoscopic injection of botulinum toxin that provided them only a temporary clinical benefit. Changes in clinical and instrumental examinations from before to after surgery were evaluated in all patients. Clinical evaluation was carried out using a modified DeMeester symptom score system. Dor fundoplication treatment reduced both dysphagia and regurgitation severity scores significantly more than Nissen fundoplication (pHeller myotomy followed by Dor fundoplication is a safe and valuable treatment. The procedure showed a lower incidence of postoperative dysphagia versus Nissen fundoplication and a negligible incidence of postoperative GERD in a long-term postoperative follow-up.

  16. Laparoscopic Heller Myotomy and Dor Fundoplication for Esophageal Achalasia: Technique and Perioperative Management.

    Science.gov (United States)

    Andolfi, Ciro; Fisichella, P Marco

    2016-11-01

    Surgical correction of achalasia using laparoscopic Heller myotomy with Dor fundoplication is argued to be the gold standard treatment for patients with achalasia. The goal of this technical report is to illustrate our preferred approach to patients with achalasia and to provide the reader with a detailed description of our operative technique, its rationale, and our pre and postoperative management.

  17. 76 FR 24934 - Magnum d'Or Resources, Inc.; Order of Suspension of Trading

    Science.gov (United States)

    2011-05-03

    ... press releases to investors concerning, among other things: (1) The company's current financial... lack of current and accurate information concerning the securities of Magnum d'Or Resources, Inc... interest and the protection of investors require a suspension of trading in the securities of the above...

  18. Dor posterior baixa e dor pélvica: o que interessa ao proctologista? Lower back and pelvic pain: what does concern to the proctologist?

    Directory of Open Access Journals (Sweden)

    Júlio César M Santos Jr

    2009-09-01

    Full Text Available Um do mais intrigante e frequente sintoma de doenças agudas ou crônicas é a dor, sobretudo quando aparece sem um substrato anatomo-patológico facilmente identificável, o que dificulta o tratamento e favorece sua persistência. A dor crônica, generalizada ou localizada, transtorna a vida da pessoa, cuja qualidade é significativamente afetada na proporção da intensidade e continuidade da dor. A dor pélvica e a dor posterior baixa são sintomas relativamente comuns, principalmente por estarem relacionados etiologicamente com mais de uma centena de doenças - desde as que são de origem infecciosa até as inflamatórias inespecíficas, passando pelas que são decorrentes de alterações osteomusculares carências ou funcionais, até às neoplásicas eàs de causas indeterminadas. Além disso, há fatores estruturais sobrecarregados pelos atuais estilos de vida, não só em relaçãoà postura física, como permanecer sentado por longo período de tempo, mas também por falta de exercícios que deveriam ser praticados como preparo para o cotidiano. Soma-se, ainda, a estimativa de que 60% das pessoas estão na faixa do sobrepeso e 25% são obesas. Pela frequência de aparecimento e por sua relação com os órgãos pélvicos, a dor pélvica e a dor posterior baixa, cuja investigação pode envolver profissionais de várias áreas, devem ser do obrigatório interesse do médico coloproctologista.Pain is one the most intriguing and frequent symptom of diseases, above all when it appears without an easily identifiable anatomic pathological substratum. Widespread or located chronic pain upsets the person's life whose quality is significantly affected. Chronic pelvic pain syndrome is a conundrum that may be only partly explained; it is relatively common and etiologically related with more than a hundred diseases (infectious and/or inflammatory perceived in structures related to the pelvis. "Add to that a general lack of exercise, poor diet, and

  19. INFLUÊNCIA DA LASERTERAPIA NA DOR E QUALIDADE DE VIDA EM MULHERES COM FIBROMIALGIA

    Directory of Open Access Journals (Sweden)

    Renato Canevari Dutra da Silva

    2015-01-01

    Full Text Available A fibromialgia é uma síndrome dolorosa, não inflamatória, cujo principal sintoma é a dor crônica musculoesquelética generalizada, causando um impacto negativo na qualidade de vida destes pacientes. O objetivo deste estudo foi investigar a influência da laserterapia na dor e qualidade de vida em mulheres com fibromialgia. Participaram do estudo 9 mulheres com diagnóstico confirmado de fibromialgia, as quais foram submetidas a 10 sessões consecutivas com laser 830nm e dosimetria de 5 J/cm² aplicado apenas nos tender points dolorosos à palpação digital. Foi realizada a avaliação da intensidade da dor, antes e após a intervenção com laserterapia, utilizando a escala visual analógica (EVA e, para avaliar qualidade de vida, foram utilizados dois questionários, o Medical Outcomes Study 36-item Short-Form Health Survey (SF-36 e o Fibromyalgia Impact Questionnaire (FIQ, sendo realizados antes e após o tratamento com laserterapia. Na avaliação da intensidade da dor através da EVA, não foi observado diferença significativa após o tratamento (p=3,03. Em relação ao SF-36, houve diferenças estatisticamente significantes do escore geral (p=0,018 e observaram-se diferenças estatisticamente significantes nas variáveis dor (p=0,032 e estado geral de saúde (p=0,027. No FIQ, o escore geral apresentou diferença estatisticamente significante, sendo (p=0,002 e, em relação às variáveis do FIQ, houve diferença estatisticamente significante no bem estar (p=0,007, dificuldade no trabalho (p=0,048, dor (p=0,000, rigidez (p=0,033 e sono (p=0,021. Foi observado que a intervenção fisioterapêutica com laserterapia promove melhora da dor e da qualidade de vida de mulheres com fibromialgia.

  20. Results after laparoscopic Heller-Dor operation for esophageal achalasia in 100 consecutive patients.

    Science.gov (United States)

    Tsuboi, Kazuto; Omura, Nobuo; Yano, Fumiaki; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

    2009-01-01

    The laparoscopic Heller-Dor operation has been the procedure of choice for the treatment of achalasia. However, because the incidence of achalasia is low, reports on the outcome of surgical treatment for achalasia are limited. In this study, the therapeutic results after laparoscopic Heller-Dor operation for achalasia at a single university hospital were evaluated. Between August 1994 and July 2006, 100 consecutive patients underwent laparoscopic Heller-Dor operation. The therapeutic results after laparoscopic Heller-Dor operation were assessed based on complications, operation time, blood loss, postoperative hospital stay, and the standardized questionnaire for satisfaction by telephone or outpatient clinic interview. With respect to perioperative complications, lower esophageal mucosal perforation occurred in 14 patients, but all of them could be suture-obliterated laparoscopically. One patient was converted to laparotomy because of uncontrolled bleeding from the short gastric artery. The mean operative time was 169 minutes, and the mean perioperative blood loss was 22 mL. The median postoperative hospital stay was 7 days. Reflux esophagitis, which was seen in five patients, was treated successfully with a proton pump inhibitor. According to the standardized questionnaire for satisfaction, 77 patients rated their recovery as 'excellent', 17 as 'good', 4 as 'fair', and 2 as 'poor'; thus, the overall success rate was 94%. There were no significant differences in surgical outcomes by morphologic type and severity of esophageal dilatation; however, the success rate deteriorated significantly with progression of the morphologic type. Laparoscopic Heller-Dor operation is a safe and effective surgical treatment for achalasia.

  1. Emissive Synthetic Cofactors: An Isomorphic, Isofunctional, and Responsive NAD+ Analogue.

    Science.gov (United States)

    Rovira, Alexander R; Fin, Andrea; Tor, Yitzhak

    2017-11-08

    The synthesis, photophysics, and biochemical utility of a fluorescent NAD + analogue based on an isothiazolo[4,3-d]pyrimidine core (N tz AD + ) are described. Enzymatic reactions, photophysically monitored in real time, show N tz AD + and N tz ADH to be substrates for yeast alcohol dehydrogenase and lactate dehydrogenase, respectively, with reaction rates comparable to that of the native cofactors. A drop in fluorescence is seen as N tz AD + is converted to N tz ADH, reflecting a complementary photophysical behavior to that of the native NAD + /NADH. N tz AD + and N tz ADH serve as substrates for NADase, which selectively cleaves the nicotinamide's glycosidic bond yielding tz ADP-ribose. N tz AD + also serves as a substrate for ribosyl transferases, including human adenosine ribosyl transferase 5 (ART5) and Cholera toxin subunit A (CTA), which hydrolyze the nicotinamide and transfer tz ADP-ribose to an arginine analogue, respectively. These reactions can be monitored by fluorescence spectroscopy, in stark contrast to the corresponding processes with the nonemissive NAD + .

  2. Acute TNF-induced repression of cell identity genes is mediated by NFκB-directed redistribution of cofactors from super-enhancers

    DEFF Research Database (Denmark)

    Schmidt, Søren Fisker; Larsen, Bjørk Ditlev; Loft, Anne

    2015-01-01

    The proinflammatory cytokine tumor necrosis factor (TNF) plays a central role in low-grade adipose tissue inflammation and development of insulin resistance during obesity. In this context, nuclear factor κ-light-chain-enhancer of activated B cells (NFκB) is directly involved and required for the...... specifically repressing super-enhancer-associated cell identity genes....... binding to the associated enhancers but rather loss of cofactors and enhancer RNA (eRNA) selectively from high-occupancy sites within super-enhancers. Based on these data, we have developed models that, with high accuracy, predict which enhancers and genes are repressed by TNF in adipocytes. We show...... that these models are applicable to other cell types where TNF represses genes associated with super-enhancers in a highly cell-type-specific manner. Our results propose a novel paradigm for NFκB-mediated repression, whereby NFκB selectively redistributes cofactors from high-occupancy enhancers, thereby...

  3. Cofactor requirement of HpyAV restriction endonuclease.

    Directory of Open Access Journals (Sweden)

    Siu-Hong Chan

    Full Text Available BACKGROUND: Helicobacter pylori is the etiologic agent of common gastritis and a risk factor for gastric cancer. It is also one of the richest sources of Type II restriction-modification (R-M systems in microorganisms. PRINCIPAL FINDINGS: We have cloned, expressed and purified a new restriction endonuclease HpyAV from H. pylori strain 26695. We determined the HpyAV DNA recognition sequence and cleavage site as CCTTC 6/5. In addition, we found that HpyAV has a unique metal ion requirement: its cleavage activity is higher with transition metal ions than in Mg(++. The special metal ion requirement of HpyAV can be attributed to the presence of a HNH catalytic site similar to ColE9 nuclease instead of the canonical PD-X-D/EXK catalytic site found in many other REases. Site-directed mutagenesis was carried out to verify the catalytic residues of HpyAV. Mutation of the conserved metal-binding Asn311 and His320 to alanine eliminated cleavage activity. HpyAV variant H295A displayed approximately 1% of wt activity. CONCLUSIONS/SIGNIFICANCE: Some HNH-type endonucleases have unique metal ion cofactor requirement for optimal activities. Homology modeling and site-directed mutagenesis confirmed that HpyAV is a member of the HNH nuclease family. The identification of catalytic residues in HpyAV paved the way for further engineering of the metal binding site. A survey of sequenced microbial genomes uncovered 10 putative R-M systems that show high sequence similarity to the HpyAV system, suggesting lateral transfer of a prototypic HpyAV-like R-M system among these microorganisms.

  4. Eletroestimulação e core training sobre dor e arco de movimento na lombalgia

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    Fernando Campbell Bordiak

    Full Text Available INTRODUÇÃO: Eletrotermofototerapia e cinesioterapia são opções para o tratamento de lombalgias. Exercícios voltados para a musculatura paravertebral visam ao aumento de força e arco de movimento (ADM. A eletroestimulação neuromuscular (EENM incrementa a função muscular. OBJETIVOS: Apurar a influência da EENM associada a um programa de core training (CT sobre a lombalgia inespecífica crônica, com as variáveis de dor e ADM da coluna vertebral. MATERIAIS E MÉTODOS: Foi realizado ensaio clínico controlado randomizado duplo cego, com 27 pacientes atendidos na Clínica-Escola FIT-UGF, com diagnóstico médico relacionado a lombalgias. Foram formados dois grupos aleatoriamente: controle ativo (CORE; n = 13 e experimental (CORE + EENM; n = 14. O questionário de McGill e a fotogrametria foram aplicados antes da primeira e após a última sessão de tratamentos para medir dor e ADM, respectivamente. RESULTADOS: Os grupos eram homogêneos quanto à dor inicial (p = 0,99; a dor final do grupo CORE + EENM foi significativamente menor que a do grupo CORE (p = 0,03; a dor final do grupo CORE não apresentou diferença significativa em relação à inicial (p = 0,93; a dor final do grupo CORE + EENM foi significativamente menor que a inicial (p = 0,00. O ADM não apresentou diferença significativa intragrupos e intergrupos (p = 0,10. CONCLUSÃO: A aplicação de EENM em região lombar após CT foi eficaz, causando diminuição significativa da lombalgia inespecífica. Entretanto, não ocorreu diferença significativa do ADM entre os grupos.

  5. Molybdenum cofactor deficiency: Identification of a patient with homozygote mutation in the MOCS3 gene

    NARCIS (Netherlands)

    Huijmans, Jan G. M.; Schot, Rachel; de Klerk, Johannis B. C.; Williams, Monique; de Coo, René F. M.; Duran, Marinus; Verheijen, Frans W.; van Slegtenhorst, Marjon; Mancini, Grazia M. S.

    2017-01-01

    We describe the clinical presentation and 17 years follow up of a boy, born to consanguineous parents and presenting with intellectual disability (ID), autism, "marfanoid" dysmorphic features, and moderate abnormalities of sulfite metabolism compatible with molybdenum cofactor deficiency, but normal

  6. Organic cofactors participated more frequently than transition metals in redox reactions of primitive proteins.

    Science.gov (United States)

    Ji, Hong-Fang; Chen, Lei; Zhang, Hong-Yu

    2008-08-01

    Protein redox reactions are one of the most basic and important biochemical actions. As amino acids are weak redox mediators, most protein redox functions are undertaken by protein cofactors, which include organic ligands and transition metal ions. Since both kinds of redox cofactors were available in the pre-protein RNA world, it is challenging to explore which one was more involved in redox processes of primitive proteins? In this paper, using an examination of the redox cofactor usage of putative ancient proteins, we infer that organic ligands participated more frequently than transition metals in redox reactions of primitive proteins, at least as protein cofactors. This is further supported by the relative abundance of amino acids in the primordial world. Supplementary material for this article can be found on the BioEssays website. (c) 2008 Wiley Periodicals, Inc.

  7. Redox cofactor engineering in industrial microorganisms: strategies, recent applications and future directions.

    Science.gov (United States)

    Liu, Jiaheng; Li, Huiling; Zhao, Guangrong; Caiyin, Qinggele; Qiao, Jianjun

    2018-05-01

    NAD and NADP, a pivotal class of cofactors, which function as essential electron donors or acceptors in all biological organisms, drive considerable catabolic and anabolic reactions. Furthermore, they play critical roles in maintaining intracellular redox homeostasis. However, many metabolic engineering efforts in industrial microorganisms towards modification or introduction of metabolic pathways, especially those involving consumption, generation or transformation of NAD/NADP, often induce fluctuations in redox state, which dramatically impede cellular metabolism, resulting in decreased growth performance and biosynthetic capacity. Here, we comprehensively review the cofactor engineering strategies for solving the problematic redox imbalance in metabolism modification, as well as their features, suitabilities and recent applications. Some representative examples of in vitro biocatalysis are also described. In addition, we briefly discuss how tools and methods from the field of synthetic biology can be applied for cofactor engineering. Finally, future directions and challenges for development of cofactor redox engineering are presented.

  8. Bleaching herbicide norflurazon inhibits phytoene desaturase by competition with the cofactors.

    Science.gov (United States)

    Breitenbach, J; Zhu, C; Sandmann, G

    2001-11-01

    Cofactor requirement was determined for the heterologous expressed phytoene desaturases from the cyanobacterium Synechococcus and the higher plant Gentiana lutea. The cyanobacterial enzyme is dependent on either NAD(P) or plastoquinone, whereas only quinones such as plastoquinone can function as a cofactor for the phytoene desaturase from G. lutea. Enzyme kinetic studies were carried out to determine a possible competition between the cofactors and the bleaching herbicide norflurazon. For the Synechococcus enzyme, competition between norflurazon and NADP, as well as plastoquinone, could be demonstrated. The K(m) values for these cofactors were 6.6 mM and 0.23 microM, respectively. Inhibition of the phytoene desaturase from G. lutea by norflurazon was also competitive with respect to plastoquinone. The K(m) values of both enzymes for plastoquinone were very close.

  9. Investigation of Υ Dor - δ Sct hybrid stars based on high precission space photometry and complementary ground based spectroscopy

    International Nuclear Information System (INIS)

    Hareter, M.

    2013-01-01

    Stellar pulsation carries information on the physical condition within the star. While pressure modes (p modes) probe the outer layers of a star, gravity modes (g modes) penetrate deep into the radiative zone and thus carry valuable information on the physical conditions there. gamma Dor stars are stars that pulsate in such modes, apart from white dwarfs and slowly pulsating B (SPB) stars. Therefore, these stars are important test benches for stellar evolution and pulsation theory. delta Sct - gamma Dor hybrids are stars that pulsate like gamma Dor stars with g modes but also with p modes as the delta Sct stars do. This makes them even more suited for asteroseismology. The CoRoT long runs offer a great opportunity to analyse a large sample of stars observed homogeneously, uninterrupted and long time base of about 150 days, which is practically unachievable with ground based observation. Since space missions avoid the scintillation caused by the Earth's atmosphere, they allow to detect stellar oscillations on a sub-millimagnitude level even for stars as faint as 15th magnitude. The photometric data is supplemented by AAOmega classification spectroscopy, allowing to determine effective tem- peratures and surface gravity. With these data a statistical approach was adopted to describe the pulsation behaviour gamma Dor and delta Sct - gamma Dor hybrid stars. A temperature - period relation was found for gamma Dor and delta Sct stars, but none for delta Sct - gamma Dor hybrid stars, when considering their strongest g mode or p mode, respectively. The instability domain of hybrid stars is equal to that of delta Sct stars and is not con- fined to the overlapping region of the delta Sct and gamma Dor IS in the Hertzsprung- Russell diagram. Hybrid stars behave differently in the g mode regime than gamma Dor stars, which poses a serious question on how to define properly a delta Sct - gamma Dor hybrid. The convective flux blocking mechanism is supposed to work for stars

  10. A General Tool for Engineering the NAD/NADP Cofactor Preference of Oxidoreductases.

    Science.gov (United States)

    Cahn, Jackson K B; Werlang, Caroline A; Baumschlager, Armin; Brinkmann-Chen, Sabine; Mayo, Stephen L; Arnold, Frances H

    2017-02-17

    The ability to control enzymatic nicotinamide cofactor utilization is critical for engineering efficient metabolic pathways. However, the complex interactions that determine cofactor-binding preference render this engineering particularly challenging. Physics-based models have been insufficiently accurate and blind directed evolution methods too inefficient to be widely adopted. Building on a comprehensive survey of previous studies and our own prior engineering successes, we present a structure-guided, semirational strategy for reversing enzymatic nicotinamide cofactor specificity. This heuristic-based approach leverages the diversity and sensitivity of catalytically productive cofactor binding geometries to limit the problem to an experimentally tractable scale. We demonstrate the efficacy of this strategy by inverting the cofactor specificity of four structurally diverse NADP-dependent enzymes: glyoxylate reductase, cinnamyl alcohol dehydrogenase, xylose reductase, and iron-containing alcohol dehydrogenase. The analytical components of this approach have been fully automated and are available in the form of an easy-to-use web tool: Cofactor Specificity Reversal-Structural Analysis and Library Design (CSR-SALAD).

  11. The glmS ribozyme cofactor is a general acid-base catalyst.

    Science.gov (United States)

    Viladoms, Júlia; Fedor, Martha J

    2012-11-21

    The glmS ribozyme is the first natural self-cleaving ribozyme known to require a cofactor. The d-glucosamine-6-phosphate (GlcN6P) cofactor has been proposed to serve as a general acid, but its role in the catalytic mechanism has not been established conclusively. We surveyed GlcN6P-like molecules for their ability to support self-cleavage of the glmS ribozyme and found a strong correlation between the pH dependence of the cleavage reaction and the intrinsic acidity of the cofactors. For cofactors with low binding affinities, the contribution to rate enhancement was proportional to their intrinsic acidity. This linear free-energy relationship between cofactor efficiency and acid dissociation constants is consistent with a mechanism in which the cofactors participate directly in the reaction as general acid-base catalysts. A high value for the Brønsted coefficient (β ~ 0.7) indicates that a significant amount of proton transfer has already occurred in the transition state. The glmS ribozyme is the first self-cleaving RNA to use an exogenous acid-base catalyst.

  12. A dor no recém-nascido e na criança

    Directory of Open Access Journals (Sweden)

    Marialda Moreira Christoffel

    2001-03-01

    Full Text Available Este estudo procura analisar as representações das enfermeiras cursando Especialização em Saúde da Criança e Enfermagem Neonatal de diferentes Universidades da Cidade do Rio de Janeiro. Desenvolvido à luz da Teoria das Representações Sociais, através da dinâmica de criatividade e sensibilidade e da entrevista semi-estruturada. Os resultados evidenciaram que as enfermeiras apresentam uma representação subjetiva em relação a dor, influenciada por sua própria experiência de vida, e que esses fatores interferem em sua postura enquanto profissional para estar mais sensibilizada para as reações de dor do recém nascido e da criança submetidos a um procedimento doloroso.

  13. Laparoscopic Dor versus Toupet fundoplication following Heller myotomy for achalasia: results of a multicenter, prospective, randomized-controlled trial.

    Science.gov (United States)

    Rawlings, Arthur; Soper, Nathaniel J; Oelschlager, Brant; Swanstrom, Lee; Matthews, Brent D; Pellegrini, Carlos; Pierce, Richard A; Pryor, Aurora; Martin, Valeria; Frisella, Margaret M; Cassera, Maria; Brunt, L Michael

    2012-01-01

    The type of fundoplication that should be performed in conjunction with Heller myotomy for esophageal achalasia is controversial. We prospectively compared anterior fundoplication (Dor) with partial posterior fundoplication (Toupet) in patients undergoing laparoscopic Heller myotomy. A multicenter, prospective, randomized-controlled trial was initiated to compare Dor versus Toupet fundoplication after laparoscopic Heller myotomy. Outcome measures were symptomatic GERD scores (0-4, five-point Likert scale questionnaire) and 24-h pH testing at 6-12 months after surgery. Data are mean ± SD. Statistical analysis was by Mann-Whitney U test, Wilcoxon signed rank test, and Freidman's test. Sixty of 85 originally enrolled and randomized patients who underwent 36 Dor and 24 Toupet fundoplications had follow-up data per protocol for analysis. Dor and Toupet groups were similar in age (46.8 vs. 51.7 years) and gender (52.8 vs. 62.5% male). pH studies at 6-12 months in 43 patients (72%: Dor n = 24 and Toupet n = 19) showed total DeMeester scores and % time pH Heller myotomy provides significant improvement in dysphagia and regurgitation symptoms in achalasia patients regardless of the type of partial fundoplication. Although a higher percentage of patients in the Dor group had abnormal 24-h pH test results compared to those of patients who underwent Toupet, the differences were not statistically significant.

  14. Dor aguda no joelho do paciente idoso Acute knee pain in elderly patients

    Directory of Open Access Journals (Sweden)

    Gilberto Luís Camanho

    2008-09-01

    Full Text Available A dor aguda no joelho de pacientes idosos é freqüente, sendo caracterizada por seu aparecimento súbito, sem causa aparente, com exame radiográfico dentro dos padrões da normalidade, na maioria dos casos. A etiologia da dor aguda no joelho é decorrente de insuficiência das estruturas, e seu quadro clínico difere completamente daquele determinado pela osteoartrose, sendo sempre unilateral e ocorre na grande maioria em pacientes do sexo feminino, após a quinta década de vida, e na região medial do joelho (local de maior carga. Com o propósito de analisar as possíveis etiologias para a dor aguda do joelho de pacientes acima de 60 anos de idade, suas características e tratamento, os autores discutem as etiologias relacionadas à dor aguda: lesão meniscal, fratura por fadiga e osteonecrose idiopática.Acute knee pain in elderly patients is not uncommon, and is characterized by a sudden onset, no apparent cause, and by normal radiographic findings in most cases. The etiology of acute knee pain is the result of insufficient structures, and clinical symptoms are totally different from the symptoms seen in osteoarthrosis. This acute pain in the knee is always unilateral and in the medial region of the knee joint (site with the heaviest load, predominantly in females after the fifth decade of live. In order to consider the possible etiologies for acute knee joint pain in patients older than 60 years, its characteristics and treatment, the authors discuss etiologies related to acute pain: lesion of the meniscus, stress fracture, and idiopathic osteonecrosis.

  15. Tecnicas de fisioterapia respiratoria: efeito nos parametros cardiorrespiratorios e na dor do neonato estavel em UTIN

    Directory of Open Access Journals (Sweden)

    Renata Martins

    2013-12-01

    Full Text Available OBJETIVOS: verificar os efeitos de técnicas de fisioterapia respiratória (TFR na dor e na função cardiorrespiratória de recém-nascidos (RN clinicamente estáveis com prescrição de TFR, internados em unidade de terapia intensiva neonatal. MÉTODOS: ensaio clínico randomizado cego. Os RN foram alocados em três grupos: G1-controle; G2- fisioterapia convencional; G3-reequilíbrio tóracoabdominal. Neonatos do G2 e G3 receberam intervenção em atendimento único. Todos foram avaliados antes, imediatamente após e 15 minutos após o término da intervenção/repouso quanto aos parâmetros cardiorrespiratórios (saturação periférica de oxigênio/SpO2, frequências cardíaca/fc e respiratória/fr e dor (escalas específicas: NIPS, NFCS e PIPP. Para análise dos dados foram aplicados: testes qui-quadrado, Friedman, Kruskal- Wallis e, posteriormente, análise de comparações múltiplas, com p0,05 e em relação à dor houve mudanças significativas nas escalas NIPS (G1 e G2, p=0,037 e p=0,011, respectivamente e PIPP (G2, p=0,005. CONCLUSÕES: técnicas de fisioterapia respiratória não desencadearam dor, nem instabilidade cardiorrespiratória nos RN estudados.

  16. EFEITO DA ACUPUNTURA SISTÊMICA NA INTENSIDADE DA DOR DE PACIENTES COM CERVICALGIA

    Directory of Open Access Journals (Sweden)

    Aryanna Kelly Carneiro Rios Passos Alves

    2013-09-01

    Full Text Available Dor é uma qualidade sensorial complexa, puramente subjetiva, difícil de ser definida, descrita ou interpretada. É um mecanismo de proteção do corpo, ocorre sempre que qualquer tecido estiver sendo lesado. As dores cervicais afetam 30% de homens e 43% de mulheres em algum momento de suas vidas. Para o alívio da cervicalgia existem evidências de que a acupuntura é efetiva através de sua técnica em estimular pontos reflexos que tenham a propriedade de restabelecer o equilíbrio, alcançando, assim, resultados na diminuição do quadro álgico. O objetivo deste estudo foi avaliar a influência de um protocolo de acupuntura sistêmica para tratamento de cervicalgia na intensidade de dor, pressão arterial e frequência cardíaca. Realizou-se um estudo clínico com 11 sujeitos, de ambos os sexos, com idade média de 32,0 ± 13,2 anos. O tratamento foi composto por 4 sessões de atendimento segmentadas em uma sessão semanal e a avaliação da dor foi realizada antes e após cada sessão através da escala visual analogica (EVA. Os resultados encontrados sugerem que a acupuntura reduziu a dor em pacientes portadores de cervicalgia após 4 semanas de tratamento.

  17. Fadiga óssea: causa de dor em joelhos na osteoartrite

    Directory of Open Access Journals (Sweden)

    Wilson Campos Tavares Júnior

    2012-10-01

    Full Text Available A dor no joelho é o sintoma mais comum na osteoartrite, sendo a principal causa de incapacidade crônica em idosos e uma das principais fontes de morbidade atribuível à osteoartrite em geral. As causas de dor no joelho em pessoas com osteoartrite não são facilmente entendidas e o conhecimento sobre as causas da dor é fundamental para que futuramente sejam realizadas intervenções específicas. A fadiga óssea representa o remodelamento do osso subcondral na osteoartrite, levando a uma consequente alteração na forma do osso e/ou perda óssea. No entanto, a fadiga óssea não é algo facilmente interpretado, pois é de difícil detecção na ausência de defeitos claros da cortical e pela sobreposição de estruturas ósseas nas radiografias convencionais. A fadiga óssea está associada não apenas a dor no joelho, mas também a rigidez e incapacidade. Se a fadiga ocorre antes da osteoartrite avançada, isso sugere que alterações no osso subcondral podem ocorrer simultaneamente a alterações da cartilagem e que tratamentos visando sua preservação podem não ser eficazes. Lesões com padrão de edema ósseo estão associadas e são fatores preditivos para fadiga óssea. Este trabalho tem por objetivo rever a literatura mostrando a importância da fadiga óssea e de como diagnosticar esta alteração nos exames de imagem.

  18. A dor e o protagonismo da mulher na parturição

    Directory of Open Access Journals (Sweden)

    Raquel da Rocha Pereira

    2011-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVO: Compreender pela teoria das representações sociais, as dimensões socioculturais da dor e seu impacto no protagonismo da mulher na parturição. MÉTODO: Para a investigação, utilizou-se a metodologia qualitativa, com o referencial teórico da fenomenologia e da teoria da representação social. Foram realizadas 45 entrevistas semiestruturadas com gestantes dos serviços público e privado de saúde de Joinville, SC, com no mínimo quatro consultas de pré-natal e que estavam no terceiro trimestre de gestação. RESULTADOS: Da análise de conteúdo das falas, emergiram três categorias empíricas: medos e preocupações, vivências e influência sociocultural, as quais possibilitaram construir três categorias interpretativas: modelo biomédico, desinformação e papel da mulher na decisão pela via de parto. Os achados relatados neste artigo evidenciam a dor como um dos elementos construtores das representações sociais feminina sobre a parturição. Observou-se que a dor influencia o comportamento da gestante a partir do medo e se torna a gênese de outros sentimentos aversivos e preocupações que envolvem o evento da parturição. CONCLUSÃO: Nesse contexto, a dor revela-se como um dos principais construtores das atuais representações sociais femininas sobre a parturição e contribui para a curva ascendente nos índices de cesárea no Brasil.

  19. Prevalência de dor nos nadadores de São Vaetano do Sul

    Directory of Open Access Journals (Sweden)

    Bárbara Oliveira Venâncio

    2012-12-01

    Full Text Available OBJECTIVE: A natação é um esporte que vem se destacando nos últimos anos, sendo reconhecido que requer um elevado nível de treinamento e que gera sobrecarga musculoesquelética, a qual predispõe os nadadores a lesões. OBJETIVO: Verificar a prevalência e as regiões corporais com dor, correlacionando com o estilo principal e o tempo de prática nos nadadores do SERC em São Caetano do Sul. Método: Aplicação de um questionário com 19 perguntas em 71 atletas, sendo 30 do sexo feminino e 41 do masculino, nas categorias petiz (10 a 12 anos, infantil (12 a 14 anos, juvenil (14 a 16 anos, júnior (16 a 18 anos e sênior (a partir dos 18 anos. As variáveis foram analisadas pelo teste de igualdade de duas proporções e Mann-Whitney. RESULTADOS: A prevalência de dor foi de 74,6% (n = 53; p < 0,001, sendo 39,6% (n = 21 no ombro e 22,6% (n = 12; p = 0,059 na coxa e o nado costas foi o único estilo que não apresentou correlação com a dor (p = 1,000, bem como com o tempo de prática (p = 0,075. CONCLUSION: Na população estudada houve alta prevalência de dor, sendo as regiões do ombro e da coxa as mais acometidas, não tendo correlação nem com o nado costas e tampouco com o tempo de prática esportiva.

  20. A subjetividade permeando o processo de cuidar em enfermagem à criança com dor

    Directory of Open Access Journals (Sweden)

    Karin Rosa Persegona

    2007-08-01

    Full Text Available Artigo de reflexão que teve como objetivo discutir sobre a subjetividade que permeia o processo de cuidar de enfermagem à criança com dor pós-operatória, construído a partir da prática profissional e do referencial teórico acerca do tema. Cuidar da criança com dor pós-operatória requer habilidades e posturas peculiares, como a observação, a perspicácia, a escuta, a presença. Somente assim é possível perceber a subjetividade da criança que vivencia a dor, o que determinará a melhor forma de planejar o cuidado humano e adequá-lo às necessidades apresentadas. O reconhecimento da subjetividade que permeia o processo de cuidar apresenta-se como mais uma ferramenta para o processo de lapidação do cuidado humano e solidário, que tem sido a grande busca da enfermagem ao longo da sua história.

  1. Incapacidade relacionada à dor lombar crônica: prevalência e fatores associados

    Directory of Open Access Journals (Sweden)

    Marina de Góes Salvetti

    2012-10-01

    Full Text Available A incapacidade relacionada à dor lombar crônica (DLC é um fenômeno complexo e multifatorial. O objetivo desse estudo foi identificar a prevalência e os fatores associados à incapacidade em pacientes com dor lombar crônica. Estudo transversal com amostra composta por 177 pacientes com DLC, de três serviços de saúde; que responderam ao formulário com dados demográficos, ao Inventário de Depressão de Beck, às Escalas Oswestry Disability Index, de autoeficácia para dor crônica, Tampa de Cinesiofobia e de Fadiga de Piper. A prevalência de incapacidade foi de 65% (IC95%: 57,5 - 72,0 e era de moderada a grave em 80,7% dos pacientes. O modelo de regressão múltipla identificou três fatores independentemente associados à incapacidade: ausência de trabalho remunerado, autoeficácia baixa e depressão. Os fatores associados à incapacidade identificados são modificáveis. Intervenções como recolocação no trabalho, tratamento para a depressão e reconceitualização da crença de autoeficácia podem ter um impacto importante na prevenção e redução de incapacidade.

  2. Laparoscopic Heller-Dor for primary esophageal achalasia: outcomes in 173 patients.

    Science.gov (United States)

    Rosati, Riccardo; Fumagalli Romario, Uberto; Ceolin, Martina; Massaron, Simonetta; Peracchia, Alberto

    2013-01-01

    Laparoscopic Heller myotomy combined with anterior (Dor) fundoplication is the most widely-used surgical procedure for treating esophageal achalasia in Europe From November 1992 through May 2010 we performed laparoscopic Heller-Dor on 173 patients Conversion to laparotomy was required in three cases (1.7%) at the beginning of the experience (for mucosal) perforation which was the most frequent intraoperative complication, managed laparoscopically with the increasing experience. Five (2.9%) cases had minor postoperative complications. Clinical results were satisfactory in 99.4% of cases. One patient (0.6%) had severe persistent dysphagia. Mean esophageal diameter decreased from 50 mm ± 12 (range 20- 90) to 25 mm ± 7 (range 15-80). Lower esophageal sphincter pressure decreased from 32 mmHg (median, range 10- 93) pre-operatively to 11 mmHg (median, range 5-21) at one year follow up and residual pressure from 12 mmHg (median, range 3-30) to 4 mmHg (median, range 1-8). Impedance and pH monitoring showed normal levels in 39/47 (83%) patients who agreed to testing. The good outcomes of this experience, in part due to careful adherence to technical aspects of the operation, confirm that the laparoscopic Heller-Dor is the gold standard surgical treatment for esophageal achalasia.

  3. A dor no cotidiano de cuidadores e crianças com anemia falciforme

    Directory of Open Access Journals (Sweden)

    Tatiane Lebre Dias

    2013-12-01

    Full Text Available As crises de dor crônica ou aguda, de diferente intensidade e recorrência imprevisível, são um dos sintomas mais frequentes na Anemia Falciforme (AF e tendem a afetar a qualidade de vida dos portadores da doença. Este estudo procurou descrever e comparar a percepção do episódio doloroso da AF entre crianças e seus cuidadores. Participaram 27 pares de cuidador-criança, sendo 11 pares formados por crianças atendidas no Ambulatório de Pediatria do Hospital Universitário Cassiano Antônio de Moraes de Vitória/ES e 16 pares compostos por crianças que frequentavam o Hemocentro de Cuiabá/MT. Os resultados revelaram diferença na percepção de cuidador e criança sobre a caracterização da dor no que se refere ao tipo e à intensidade. As crises de dor interferem, sobretudo, nas atividades do cotidiano. A estratégia de enfrentamento mais utilizada por ambos os grupos centrou-se em pensamentos que envolveram os aspectos negativos da experiência indesejada, o que indica a necessidade de intervenção psicológica com esta população

  4. Genome-scale consequences of cofactor balancing in engineered pentose utilization pathways in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Amit Ghosh

    Full Text Available Biofuels derived from lignocellulosic biomass offer promising alternative renewable energy sources for transportation fuels. Significant effort has been made to engineer Saccharomyces cerevisiae to efficiently ferment pentose sugars such as D-xylose and L-arabinose into biofuels such as ethanol through heterologous expression of the fungal D-xylose and L-arabinose pathways. However, one of the major bottlenecks in these fungal pathways is that the cofactors are not balanced, which contributes to inefficient utilization of pentose sugars. We utilized a genome-scale model of S. cerevisiae to predict the maximal achievable growth rate for cofactor balanced and imbalanced D-xylose and L-arabinose utilization pathways. Dynamic flux balance analysis (DFBA was used to simulate batch fermentation of glucose, D-xylose, and L-arabinose. The dynamic models and experimental results are in good agreement for the wild type and for the engineered D-xylose utilization pathway. Cofactor balancing the engineered D-xylose and L-arabinose utilization pathways simulated an increase in ethanol batch production of 24.7% while simultaneously reducing the predicted substrate utilization time by 70%. Furthermore, the effects of cofactor balancing the engineered pentose utilization pathways were evaluated throughout the genome-scale metabolic network. This work not only provides new insights to the global network effects of cofactor balancing but also provides useful guidelines for engineering a recombinant yeast strain with cofactor balanced engineered pathways that efficiently co-utilizes pentose and hexose sugars for biofuels production. Experimental switching of cofactor usage in enzymes has been demonstrated, but is a time-consuming effort. Therefore, systems biology models that can predict the likely outcome of such strain engineering efforts are highly useful for motivating which efforts are likely to be worth the significant time investment.

  5. PERCEPÇÃO E ENFRENTAMENTO DA DOR EM CRIANÇAS E ADOLESCENTES COM FIBROMIALGIA JUVENIL E ARTRITE IDIOPÁTICA JUVENIL POLIARTICULAR

    Directory of Open Access Journals (Sweden)

    Melissa Mariti Fraga

    2018-06-01

    Full Text Available RESUMO Objetivo: Mensurar e comparar a dor musculoesquelética em pacientes com fibromialgia juvenil (FMJ e em pacientes com artrite idiopática juvenil poliarticular (AIJ; e avaliar e comparar a percepção e o enfrentamento da dor. Métodos: Foram avaliados, em estudo transversal, 150 crianças e adolescentes (e seus respectivos pais, divididos em três grupos: FMJ, AIJ e controles saudáveis. A mensuração e o enfrentamento da dor foram realizados por meio de instrumentos específicos. Para a avaliação da percepção da dor, desenvolveram-se três vinhetas com simulação de situações que pudessem gerar dor: aplicação de injeção, queda de bicicleta e isolamento social. Os pais e os pacientes responderam individualmente quanto à percepção da dor em cada situação. Resultados: As maiores notas de dor, os menores escores de enfrentamento da dor, as maiores notas para a percepção da dor nas vinhetas e os piores índices de qualidade de vida relacionada à saúde foram observados nos pacientes com FMJ, quando comparados aos pacientes com AIJ e aos controles. O mesmo padrão foi observado com os respectivos pais. Conclusões: Pacientes com AIJ e FMJ se comportam diferentemente em relação à percepção da dor e ao desenvolvimento de técnicas para o enfrentamento da dor. A dor deve ser avaliada sob diferentes perspectivas para um planejamento mais individualizado e efetivo do tratamento desses pacientes.

  6. Investigation of the cofactor controlled substrate specificity of yeast inorganic pyrophosphatase

    International Nuclear Information System (INIS)

    Dunaway-Mariano, D.; Barry, R.J.; Brush, T.; Ting, S.J.

    1986-01-01

    The PPase reaction requires the participation of three metal ion cofactors. One metal ion binds to PP activating it for reaction and the other two bind to the enzyme activating it for catalysis. Of the metal ions tested only Mg 2+ , Zn 2+ , Co 2+ , Mn 2+ can perform all these roles. Most trivalent metal ions can function to activate the PP for reaction but cannot activate the enzyme for catalysis. The Mg 2+ activated enzyme is specific for M-PP and M-PPS complexes while the Zn 2+ activated enzyme also acts on metal complexes of PPP, PPPOR, PPOR and PPF. 18 O-Incorporation studies show that the substituted phosphoryl group of the unsymmetrical PP complexes always serves as the leaving group. To gain insight into the mechanism of the cofactor control over the substrate specificity the order of substrate/cofactor binding to the enzyme was examined. Dead end inhibition studies in which Cr(III)PP served as substrate and Mg 2+ as cofactor indicate that the mechanism is rapid equilibrium ordered (CrPP binds first) while dead end inhibitor induced activator inhibition studies with Mg 2+ and MgPP indicate that the kinetic mechanism is steady state preferred order. Cofactor-enzyme binding was studied as a function of substrate structure and the results obtained rule out interference of Mg 2+ binding by substrate analogs as an explanation for the different substrate specificities of the Zn 2+ and Mg 2+ activated enzymes

  7. Expression and localization of tubulin cofactors TBCD and TBCE in human gametes.

    Science.gov (United States)

    Jiménez-Moreno, Victoria; Agirregoitia, Ekaitz

    2017-06-01

    The tubulin cofactors TBCD and TBCE play an essential role in regulation of the microtubule dynamics in a wide variety of somatic cells, but little information is known about the expression of these cofactors in human sperm and oocytes. In this study, we focused on the investigation of the presence of, and the differential distribution of, the tubulin cofactors TBCD and TBCE in human sperm and during human oocyte maturation. We performed expression assays for TBCD and TBCE by reverse transcription-polymerase chain reaction (RT-PCR), western blot and immunofluorescence and verified the presence of both cofactors in human gametes. TBCD and TBCE were located mainly in the middle region and in the tail of the sperm while in the oocyte the localization was cytosolic. The mRNA of both tubulin cofactors were present in the human oocytes but not in sperm cells. This finding gives a first insight into where TBCD and TBCE could carry out their function in the continuous changes that the cytoskeleton experiences during gametogenesis and also prior to fertilization.

  8. [On the influence of local molecular environment on the redox potential of electron transfer cofactors in bacterial photosynthetic reaction centers].

    Science.gov (United States)

    Krasil'nikov, P M; Noks, P P; Rubin, A B

    2011-01-01

    The addition of cryosolvents (glycerol, dimethylsulfoxide) to a water solution containing bacterial photosynthetic reaction centers changes the redox potential of the bacteriochlorophyll dimer, but does not affect the redox potential of the quinone primary acceptor. It has been shown that the change in redox potential can be produced by changes of the electrostatic interactions between cofactors and the local molecular environment modified by additives entered into the solution. The degree of influence of a solvent on the redox potential of various cofactors is determined by degree of availability of these cofactors for molecules of solvent, which depends on the arrangement of cofactors in the structure of reaction centers.

  9. Separation of xylose and glucose using an integrated membrane system for enzymatic cofactor regeneration and downstream purification

    DEFF Research Database (Denmark)

    Morthensen, Sofie Thage; Sigurdardóttir, Sigyn Björk; Meyer, Anne S.

    2017-01-01

    Mixtures of xylose, glucose and pyruvate were fed to a membrane bioreactor equipped with a charged NF membrane (NTR 7450). Value-added products were obtained in the reactor via enzymatic cofactor-dependent catalysis of glucose to gluconic acid and pyruvate to lactic acid, respectively. The initial...... cofactor (NADH) concentration could be decreased to 10% of the stoichiometric value (relative to glucose) without compromising process time and substrate conversion via i) efficient cofactor regeneration and ii) high retention of cofactor (R=0.98) in the membrane bioreactor. Furthermore, accumulation...

  10. Synthesis, delivery and regulation of eukaryotic heme and Fe-S cluster cofactors.

    Science.gov (United States)

    Barupala, Dulmini P; Dzul, Stephen P; Riggs-Gelasco, Pamela Jo; Stemmler, Timothy L

    2016-02-15

    In humans, the bulk of iron in the body (over 75%) is directed towards heme- or Fe-S cluster cofactor synthesis, and the complex, highly regulated pathways in place to accomplish biosynthesis have evolved to safely assemble and load these cofactors into apoprotein partners. In eukaryotes, heme biosynthesis is both initiated and finalized within the mitochondria, while cellular Fe-S cluster assembly is controlled by correlated pathways both within the mitochondria and within the cytosol. Iron plays a vital role in a wide array of metabolic processes and defects in iron cofactor assembly leads to human diseases. This review describes progress towards our molecular-level understanding of cellular heme and Fe-S cluster biosynthesis, focusing on the regulation and mechanistic details that are essential for understanding human disorders related to the breakdown in these essential pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Chemomimetic biocatalysis: exploiting the synthetic potential of cofactor-dependent enzymes to create new catalysts.

    Science.gov (United States)

    Prier, Christopher K; Arnold, Frances H

    2015-11-11

    Despite the astonishing breadth of enzymes in nature, no enzymes are known for many of the valuable catalytic transformations discovered by chemists. Recent work in enzyme design and evolution, however, gives us good reason to think that this will change. We describe a chemomimetic biocatalysis approach that draws from small-molecule catalysis and synthetic chemistry, enzymology, and molecular evolution to discover or create enzymes with non-natural reactivities. We illustrate how cofactor-dependent enzymes can be exploited to promote reactions first established with related chemical catalysts. The cofactors can be biological, or they can be non-biological to further expand catalytic possibilities. The ability of enzymes to amplify and precisely control the reactivity of their cofactors together with the ability to optimize non-natural reactivity by directed evolution promises to yield exceptional catalysts for challenging transformations that have no biological counterparts.

  12. Acupuntura na fibromialgia: um estudo randomizado-controlado abordando a resposta imediata da dor

    Directory of Open Access Journals (Sweden)

    Rebecca Saray Marchesini Stival

    2014-12-01

    Full Text Available Objetivo Avaliar a eficácia da acupuntura no tratamento da fibromialgia, considerando-se como desfecho primário a resposta imediata da escala visual analógica (VAS para avaliação da dor. Material e métodos Estudo randomizado, controlado e duplo-cego incluindo 36 pacientes portadores de fibromialgia (ACR 1990 selecionados no ambulatório de Reumatologia da Santa Casa de Misericórdia de Ponta Grossa, PR. Vinte e um pacientes foram submetidos a uma sessão de acupuntura, nos moldes da Medicina Tradicional Chinesa, e 15 pacientes foram submetidos a um procedimento placebo (acupuntura sham. Para avaliação da dor, os indivíduos preencheram uma Escala Visual Analógica (VAS antes e imediatamente após o procedimento proposto. As médias na variação da VAS foram comparadas entre os grupos. Resultados A variação entre o valor da EVA final e da EVA inicial foi de –4,36±3,23 (P=0,0001 no grupo de tratamento e de –1,70±1,55 no grupo de controle (P=0,06. A diferença na amplitude de variação da EVA (EVA inicial – final entre os grupos favoreceu o procedimento verdadeiro (P=0,005. O tamanho de efeito (effect size – ES para o grupo de tratamento foi de d=1,7, o que é considerado um efeito grande. Embora com uma amostra reduzida, seu poder estatístico para esses resultados foi bastante relevante (94,8%. Conclusão A acupuntura mostrou ser eficaz na redução imediata da dor em pacientes portadores de fibromialgia, com um tamanho de efeito (effect size bastante significativo.

  13. Simulacra, Symbolic Exchange and Technology in Michel Tournier's La Goutte d'Or

    Directory of Open Access Journals (Sweden)

    David W. Price

    1993-06-01

    Full Text Available In La Goutte d'Or , Michel Tournier offers a critique of Western culture by constructing a novel that reflects both Jean Baudrillard's theories of simulacra and the political economy of the sign and Martin Heidegger's meditations on technology. Tournier's novel explores the relationship between Heidegger's explanation of technology as an act of Enframing ( Ge-stell and Baudrillard's description of an economy based upon exchange-sign value. Thus, through La Goutte d 'Or , Michel Tournier depicts the violent confrontation between a symbolic exchange economy based on poietic acts and late capitalist economies of autonomized signs.

  14. Bol d'Or success for all-women crew from CERN

    CERN Multimedia

    2001-01-01

    The boat 'Mic Mac' and its CERN's all-woman crew (left to right), Christine Theurillat, Ursula Haenger , Paola Catapano, Petra Riedler, and skipper Cristina Morone. Spectacular highlight of the Lake Leman sailing calendar is the annual Bol d'Or race. Held this year on 16 and 17 June, the event attracted nearly 500 teams who competed under extreme weather conditions for the honours. Among the competitors was an all-woman crew from the CERN Yachting Club, sailing their Surprise boat, Mic Mac. The team was not only among the 397 boats to finish, but also the first all-woman crewed single hull boat to cross the line.

  15. Tecnologia tátil para a avaliação da dor em cegos

    OpenAIRE

    Toniolli, Ana Cláudia de Souza; Pagliuca, Lorita Marlena Freitag

    2003-01-01

    Trata-se de um estudo descritivo e exploratório das percepções dos cegos acerca do protótipo chamado Escala Tátil, para avaliação da intensidade da dor. Por meio de uma entrevista semi-estruturada, foram obtidos os relatos de cegos da Associação dos Cegos do Ceará, para descrever a natureza do protótipo, estabelecendo relações entre as suas experiências dolorosas e buscando significados para a sua utilização na cultura dos cegos. Dos relatos, foram identificados e analisados três temas: inten...

  16. Robotic heller myotomy and Dor fundoplication for achalasia in a woman with morbid obesity.

    Science.gov (United States)

    Bedirli, Abdulkadir; Dogan, Ibrahim; Kozan, Ramazan

    2012-12-01

    Achalasia is a relatively rare condition with a prevalence estimated at less than 0.001 %. Laparoscopic or robotic Heller myotomy is an effective surgical treatment for achalasia. We present the first published case of a morbidly obese achalasia patient treated with robotic Heller myotomy and Dor fundoplication. The operative time was 175 min, with an estimated blood loss of 110 ml. The patient had a normal bowel transit on postoperative day 2, and he was discharged on postoperative day 4 on a liquid diet. A follow-up at 2 months showed significant resolved symptoms of achalasia.

  17. La cage qui cache : La Cage Dorée de Ruben Alves

    Directory of Open Access Journals (Sweden)

    Cristina Marinho

    2015-01-01

    Full Text Available The French Comedy La Cage Dorée (produced by the luso descendant Ruben Alves, 2013 success seems to be mainly due to its clichés of Portuguese epics in Paris, and its miseries may not have been underlined enough. Thus, under this apparently naif portrait an intriguing painting of Portuguese immigrants’ French dis-integration may really be hiding, which is the aim of this essay, on one hand, to bring out and, on the other one, to clarify, by questioning comparative critical common denominators of the two countries.

  18. La cage qui cache : La Cage Dorée de Ruben Alves

    Directory of Open Access Journals (Sweden)

    Cristina Marinho

    2015-12-01

    Full Text Available The French Comedy La Cage Dorée (produced by the luso descendant Ruben Alves, 2013 success seems to be mainly due to its clichés of Portuguese epics in Paris, and its miseries may not have been underlined enough. Thus, under this apparently naif portrait an intriguing painting of Portuguese immigrants’ French dis-integration may really be hiding, which is the aim of this essay, on one hand, to bring out and, on the other one, to clarify, by questioning comparative critical common denominators of the two countries.

  19. Journey to DOR: A Retro Science-Fiction Story on Researching ePrescribing

    OpenAIRE

    Lichtner , Valentina; Venters , Will

    2011-01-01

    Part 5: Section 4: The Future of Information Technology and Work-Related Practices in Health Care; International audience; The core of this paper is a science fiction short story. We are on planet DOR. A group of scientists are working on an experiment, changing underlying mechanisms of transmissions of a colossus machine(a complex system of gears and levers, wires and pipes. Some of its mechanisms are also known as D for doctors, F for pharmacists, P for patients. Observers travel from Earth...

  20. O efeito da hidroterapia na dor, qualidade de vida e funcionalidade em pacientes com fibromialgia

    OpenAIRE

    Rocha, Virgílio

    2016-01-01

    Projeto de Graduação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Licenciado em Fisioterapia Objetivo: Sistematizar a evidência científica existente sobre o papel do efeito da Hidroterapia na Dor, Qualidade de Vida e Funcionalidade em pacientes com Fibromialgia Métodos: Estudo de revisão incluindo estudos randomizados controlados, pesquisados nas bases de dados PubMed, EBSCO, PEDro e Web of Science, com doentes com fibromialgia, cujo tipo de...

  1. Dor neuropática em paciente com porfiria: relato de caso

    OpenAIRE

    Santos, Alysson B O; Gozzani, Judymara L; Groke, Daniela F

    2010-01-01

    JUSTIFICATIVA E OBJETIVOS: As porfirias são um grupo de distúrbios herdados ou adquiridos que envolvem enzimas participantes do processo de síntese do heme. As manifestações agudas afetam o sistema nervoso, resultando em dor abdominal, vômitos, neuropatia aguda, convulsões e distúrbios mentais. A fisiopatogenia resulta do efeito tóxico dos precursores de porfirina, podendo ser desencadeada por fármacos usados de rotina na prática médica, restrição intensa de carboidratos e estresse metabólico...

  2. Clinical study of patients with persistent orofacial pain Estudo clínico de pacientes com dor orofacial persistente

    Directory of Open Access Journals (Sweden)

    José Tadeu Tesseroli de Siqueira

    2004-12-01

    Full Text Available OBJETIVE: To evaluate a sample of patients with persistent facial pain unresponsive to prior treatments. METHODS: Hospital records of 26 patients with persistent facial pain were reviewed (20 female and 6 male. RESULTS: Patients were classified into three groups according to their presenting symptoms: aGroup I, eight patients (30.7% with severe, diffuse pain at the face, teeth or head; bGroup II, eight patients (30.7% with chronic non-myofascial pain and; cGroup III, ten patients with chronic myofascial pain (38.4%. We find 11 different diagnoses among the 26 patients: pulpitis(7, leukemia(1, oropharyngeal tumor(1, atypical odontalgia(1, Eagle's syndrome(1, trigeminal neuralgia(4, continuous neuralgia(1, temporomandibular disorders (9, fibromyalgia (2, tension-type headache(1, conversion hysteria(2. After the treatment program all patients had a six-month follow-up period with pain relief, except the patient with tumor. CONCLUSION: The wide variability of orofacial pain diagnosis (benign to life-threatening diseases indicates the necessity to reevaluate patients presenting recurrent pain that is refractory to the usual treatments.OBJETIVO: Avaliar uma amostra de doentes com dor facial persistente. MÉTODO: Foram revisados 26 prontuários de doentes com dor facial persistente (20 mulheres e 6 homens. RESULTADOS: Classificação dos doentes, após o diagnóstico: aGrupo I, oito pacientes (30,7% com dor facial difusa de fortíssima intensidade; bGrupo II, oito pacientes (30,7% com dor crônica de natureza não-miofascial e; cGrupo III, dez pacientes com dor crônica miofascial (38,4%. Foram encontrados 11 diagnósticos diferentes entre os 26 pacientes: pulpites(7, leucemia(1, tumor de orofaringe(1, odontalgia atípica(1, síndrome de Eagle(1, neuralgia idiopática do trigêmeo(4, neuralgia atípica(1, disordens temporomandibular (9, fibromialgia(2 cefaléia tipo-tensão(1, histeria de conversão(2. O acompanhamento dos doentes, após receberem a

  3. Switching an O2 sensitive glucose oxidase bioelectrode into an almost insensitive one by cofactor redesign.

    Science.gov (United States)

    Tremey, Emilie; Suraniti, Emmanuel; Courjean, Olivier; Gounel, Sébastien; Stines-Chaumeil, Claire; Louerat, Frédéric; Mano, Nicolas

    2014-06-04

    In the 5-8 mM glucose concentration range, of particular interest for diabetes management, glucose oxidase bioelectrodes are O2 dependent, which decrease their efficiencies. By replacing the natural cofactor of glucose oxidase, we succeeded in turning an O2 sensitive bioelectrode into an almost insensitive one.

  4. Engineering cofactor flexibility enhanced 2,3-butanediol production in Escherichia coli.

    Science.gov (United States)

    Liang, Keming; Shen, Claire R

    2017-12-01

    Enzymatic reduction of acetoin into 2,3-butanediol (2,3-BD) typically requires the reduced nicotinamide adenine dinucleotide (NADH) or its phosphate form (NADPH) as electron donor. Efficiency of 2,3-BD biosynthesis, therefore, is heavily influenced by the enzyme specificity and the cofactor availability which varies dynamically. This work describes the engineering of cofactor flexibility for 2,3-BD production by simultaneous overexpression of an NADH-dependent 2,3-BD dehydrogenase from Klebsiella pneumoniae (KpBudC) and an NADPH-specific 2,3-BD dehydrogenase from Clostridium beijerinckii (CbAdh). Co-expression of KpBudC and CbAdh not only enabled condition versatility for 2,3-BD synthesis via flexible utilization of cofactors, but also improved production stereo-specificity of 2,3-BD without accumulation of acetoin. With optimization of medium and fermentation condition, the co-expression strain produced 92 g/L of 2,3-BD in 56 h with 90% stereo-purity for (R,R)-isoform and 85% of maximum theoretical yield. Incorporating cofactor flexibility into the design principle should benefit production of bio-based chemical involving redox reactions.

  5. Reorientational properties of fluorescent analogues of the protein kinase C cofactors diacylglycerol and phorbol ester.

    NARCIS (Netherlands)

    Pap, E.H.W.; Ketelaars, M.; Borst, J.W.; Hoek, van A.; Visser, A.J.W.G.

    1996-01-01

    The reorientational properties of the fluorescently labelled protein kinase C (PKC) cofactors diacylglycerol (DG) and phorbol ester (PMA) in vesicles and mixed micelles have been investigated using time-resolved polarised fluorescence. The sn-2 acyl chain of DG was replaced by diphenylhexatriene-

  6. Dimensoes da vulnerabilidade para as familias da crianca com dor oncologica em ambiente hospitalar

    Directory of Open Access Journals (Sweden)

    Maria da Graca Corso da Motta

    2013-09-01

    Full Text Available Identificar aspectos que demonstrem as dimensões da vulnerabilidade no universo familiar na ótica da família de crianças com dor oncológica em ambiente hospitalar Trata-se de um estudo descritivo exploratório com abordagem qualitativa, realizada na Unidade de Hematologia e Oncologia Pediátrica, de um hospital de grande porte da cidade de Porto Alegre - RS. Participaram do estudo nove famílias, utilizando-se para coleta dos dados o Método Criativo Sensível, por meio das dinâmicas de criatividade e sensibilidade, analisadas conforme o referencial da Análise de Conteúdo de Minayo, nos meses de Maio e Junho de 2010 Constatou-se que a doença traz à tona situações de vulnerabilidade, conferindo à criança e à família, sofrimento, dor, medo, angústia, desgaste físico e mental, causados pelo câncer. Assim, a Enfermagem, ao apropriar-se do marco conceitual da vulnerabilidade, pode visualizar novas dimensões do processo saúde/doença auxiliando a criança doente e sua família.

  7. Health-related quality of life after laparoscopic Heller myotomy and Dor fundoplication for achalasia.

    Science.gov (United States)

    Asti, Emanuele; Sironi, Andrea; Lovece, Andrea; Bonavina, Giulia; Fanelli, Melania; Bonitta, Gianluca; Bonavina, Luigi

    2017-04-01

    In addition to symptom scores, a person's perception of health and quality of life assessment is an important indicator of quality of treatment and can provide an efficient index to compare different therapeutic modalities in chronic disease states. Only a few studies have investigated quality of life comprehensively in patients with achalasia, and therefore the controversy regarding the best treatment algorithm continues. The primary study outcome was pre- and postoperative quality of life in patients with achalasia undergoing laparoscopic Heller myotomy and Dor fundoplication. The study is a retrospective, observational cohort. The hospital registry and the updated research database were reviewed to identify all patients who were treated for achalasia between 2010 and 2015. Patients were eligible for the study if they had a minimum 1-year follow-up and had pre-and postoperative Eckardt, Short Form-36, and Gastro-Esophageal Reflux Disease Health-Related Quality of Life scores. Patients with previous operative and/or endoscopic treatments for achalasia were excluded. One-hundred and eighteen patients were identified. The median follow-up was 40 months (interquartile range 27). The proportion of patients with Eckardt stage II-III decreased from 94.9-13% (P Heller myotomy combined with Dor fundoplication. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Pain control in small animalsControle da dor em pequenos animais

    Directory of Open Access Journals (Sweden)

    Julia Duarte Penter

    2011-12-01

    Full Text Available Pain is an unpleasant sensory or emotional experience that follows the application of a noxious stimulus. Can be experienced with or without the concomitant occurrence of physical stress signs, which occurs frequently in animals caused by trauma, systemic disease or surgical procedures. The control depends on length, where there are painful impulses and mental status of the animal. It is an important clinical condition, resulting in suffer that will affect quality life. This paper is a review of pathophysiology and pain control in small animals.A dor é uma experiência sensorial ou emocional desagradável que se segue à aplicação de um estímulo nocivo. Pode ser vivenciada com ou sem o acontecimento concomitante de sinais físicos de estresse, trauma, doença sistêmica ou procedimento cirúrgico. Seu controle depende de sua duração, de onde surgem os impulsos dolorosos e do estado de consciência do animal. É uma condição clinicamente importante, que resulta em sofrimento e afeta a qualidade de vida dos animais. O objetivo deste trabalho é a revisão da fisiopatologia e controle da dor em pequenos animais.

  9. Nuclear

    International Nuclear Information System (INIS)

    2014-01-01

    This document proposes a presentation and discussion of the main notions, issues, principles, or characteristics related to nuclear energy: radioactivity (presence in the environment, explanation, measurement, periods and activities, low doses, applications), fuel cycle (front end, mining and ore concentration, refining and conversion, fuel fabrication, in the reactor, back end with reprocessing and recycling, transport), the future of the thorium-based fuel cycle (motivations, benefits and drawbacks), nuclear reactors (principles of fission reactors, reactor types, PWR reactors, BWR, heavy-water reactor, high temperature reactor of HTR, future reactors), nuclear wastes (classification, packaging and storage, legal aspects, vitrification, choice of a deep storage option, quantities and costs, foreign practices), radioactive releases of nuclear installations (main released radio-elements, radioactive releases by nuclear reactors and by La Hague plant, gaseous and liquid effluents, impact of releases, regulation), the OSPAR Convention, management and safety of nuclear activities (from control to quality insurance, to quality management and to sustainable development), national safety bodies (mission, means, organisation and activities of ASN, IRSN, HCTISN), international bodies, nuclear and medicine (applications of radioactivity, medical imagery, radiotherapy, doses in nuclear medicine, implementation, the accident in Epinal), nuclear and R and D (past R and D programmes and expenses, main actors in France and present funding, main R and D axis, international cooperation)

  10. Densidade mineral óssea em crianças: associação com dor músculo-esquelética e/ou hipermobilidade articular

    Directory of Open Access Journals (Sweden)

    Roberto Adriana Madureira

    2002-01-01

    Full Text Available Introdução: a hipermobilidade articular pode estar associada à dor músculo-esquelética. A relação da hipermobilidade com a redução da densidade mineral óssea ainda é desconhecida. Existem relatos de osteoporose em associação com doenças genéticas que cursam com hipermobilidade articular. O nosso objetivo foi detectar a possível associação entre hipermobilidade articular e alterações na densidade mineral óssea (DMO em crianças com e sem dor músculo-esquelética. Casuística e métodos: foram avaliadas 93 crianças, com idade entre 5 e 10 anos, quanto à presença de hipermobilidade articular e quanto à presença de dor músculo-esquelética, através de questionário dirigido aos pais. Todas as crianças realizaram densitometria óssea de coluna lombar ao nível das vértebras L2-L4. Resultados: as crianças foram distribuídas de acordo com a presença ou não de hipermobilidade articular associada ou não à dor músculo-esquelética: 29 (31,2% com hipermobilidade e com dor músculo-esquelética, 20 (21,5% com hipermobilidade e sem dor, 22 (23,6% sem hipermobilidade e com dor e 22 (23,6% sem hipermobilidade e sem dor (grupo controle. Vinte e quatro (25,8% crianças apresentaram perda de DMO maior que 10% com relação à DMO adequada para a idade e sexo. A DMO mostrou-se significantemente menor em relação ao grupo controle nos grupos: com hipermobilidade (independente da presença de dor, com dor (independente da presença de hipermobilidade, com hipermobilidade e sem dor e sem hipermobilidade e com dor. Conclusão: a DMO pode estar diminuída em crianças com hipermobilidade (independente da presença de dor músculo-esquelética e em crianças com dor (independente da presença de hipermobilidade em relação aos controles.

  11. A dor como quinto sinal vital: utilização da escala de avaliação por enfermeiros de um hospital geral

    OpenAIRE

    Bottega, Fernanda Hanke; Fontana, Rosane Teresinha

    2010-01-01

    Pesquisa descritiva, que objetivou descrever as impressões dos enfermeiros sobre o uso de uma escala visual analógica de avaliação da dor em adultos. Os dados foram coletados por meio de um questionário aplicado a 14 enfermeiros de um hospital e analisados mediante análise temática, resultando em seis categorias: a avaliação da dor e sua importância; a avaliação da dor oportunizando humanização do cuidado; a escala da dor medindo subjetividade; a avaliação da dor oportunizando humanização do ...

  12. O Efeito da Música e a Importância da Musicalidade na Dor do Pós-operatório

    OpenAIRE

    Calado, Carlos

    2015-01-01

    Efectuámos um estudo quase-experimental em que se investigou o efeito da música na dor do pós-operatório, comparando o efeito da música da preferência individual, a música chamada de “relaxante”, e “sem música”; investigámos a influência nesse efeito das variáveis dor e incapacidade pré-operatórias, aptidão musical, preferência musical, estratégias de coping perante a dor e valores individuais. A dor pós-operatória foi avaliada segundo a dor autoava...

  13. Proteolytic cleavage orchestrates cofactor insertion and protein assembly in [NiFe]-hydrogenase biosynthesis.

    Science.gov (United States)

    Senger, Moritz; Stripp, Sven T; Soboh, Basem

    2017-07-14

    Metalloenzymes catalyze complex and essential processes, such as photosynthesis, respiration, and nitrogen fixation. For example, bacteria and archaea use [NiFe]-hydrogenases to catalyze the uptake and release of molecular hydrogen (H 2 ). [NiFe]-hydrogenases are redox enzymes composed of a large subunit that harbors a NiFe(CN) 2 CO metallo-center and a small subunit with three iron-sulfur clusters. The large subunit is synthesized with a C-terminal extension, cleaved off by a specific endopeptidase during maturation. The exact role of the C-terminal extension has remained elusive; however, cleavage takes place exclusively after assembly of the [NiFe]-cofactor and before large and small subunits form the catalytically active heterodimer. To unravel the functional role of the C-terminal extension, we used an enzymatic in vitro maturation assay that allows synthesizing functional [NiFe]-hydrogenase-2 of Escherichia coli from purified components. The maturation process included formation and insertion of the NiFe(CN) 2 CO cofactor into the large subunit, endoproteolytic cleavage of the C-terminal extension, and dimerization with the small subunit. Biochemical and spectroscopic analysis indicated that the C-terminal extension of the large subunit is essential for recognition by the maturation machinery. Only upon completion of cofactor insertion was removal of the C-terminal extension observed. Our results indicate that endoproteolytic cleavage is a central checkpoint in the maturation process. Here, cleavage temporally orchestrates cofactor insertion and protein assembly and ensures that only cofactor-containing protein can continue along the assembly line toward functional [NiFe]-hydrogenase. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Liga de Dor: uma experiência de ensino extracurricular League Against Pain: an undergraduate extracurricular program

    Directory of Open Access Journals (Sweden)

    Cibele Andrucioli de Mattos Pimenta

    1998-10-01

    Full Text Available Os objetivos deste estudo foram descrever um programa extracurricular de educação em dor, organizado na forma de Liga, e identificar a opinião dos alunos sobre esse modelo de ensino. O Estatuto e o Regimento Interno da Liga de Dor foram as fontes e dados para a descrição da sua organização e funcionamento. Todos os alunos que frequentaram a Liga de Dor nos anos de 1995 e 1996 foram solicitados a responder um questionário sobre suas experiências na Liga. A Liga de Dor foi organizada sob o patrocínio do Centro Acadêmico Osvaldo Cruz, da Faculdade de Medicina da USP, e Centro Acadêmico XXXI de Outubro, da Escola de Enfermagem da USP, em 1995. É composta por alunos dessas duas faculdades e profissionais enfermeiros e médicos, de várias especialidades. Todas as atividades são voluntárias, desenvolvidas em período extracurricular e os estudantes dirigem a Liga. Os objetivos da Liga são: melhorar a qualidade do ensino sobre dor nas escolas médica e de enfermagem, desenvolver pesquisas relativas à epidemiologia, clínica e controle da dor e promover modelo de assistência multidisciplinar e multiprofissional. A maioria dos alunos expressou ter alcançado seus objetivos, total ou parcialmente; ter aumentado seu conhecimento sobre as síndromes álgicas e sobre o manejo do doente com dor; sentir-se gratificado com sua atividade; que o tema dor deveria ser incluído no currículo de modo mais específico e que recomendaria a outros colegas a participação na Liga de Dor. As opiniões dos estudantes mostraram que a Liga de Dor pode ser um modelo útil para a introdução do ensino da dor nos cursos de graduação e enfermagem e de medicina.Although anatomical and physiological base of pain are subject of the basic sciences in health undergraduate curriculum, it is not usually to have pain, concepts and therapy into undergraduate programs. Describing the League Against Pain objectives and organization and the students' opinions about

  15. Fisioterapia no tratamento da dor orofacial de pacientes com disfunção temporomandibular crônica

    Directory of Open Access Journals (Sweden)

    Ana Lúcia Franco

    2011-03-01

    Full Text Available Estudos recentes têm demonstrado resultados consistentes com o uso das terapias físicas nos casos de dor e limitação de movimentos em Disfunção Temporomandibular (DTM. Dessa forma, nosso objetivo foi avaliar o efeito de dez sessões de fisioterapia, exercícios e laserterapia no tratamento da dor muscular e da artralgia em uma mulher com DTM. O alívio médio dos sintomas dolorosos obtidos por sessão foi de 20%, atingindo valor zero nas últimas semanas e mantendo-se estável por 60 dias após o término do tratamento. Os resultados demonstraram que o protocolo de tratamento utilizado foi efetivo no alívio da dor da região articular, assim como da tensão do músculo masseter, levando a paciente a reduzir a ingestão de medicamentos para controle da dor. Entretanto, estudos adicionais são necessários para se definir com maior precisão o efeito de outros programas de fisioterapia, assim como sua interação com as demais modalidades de tratamento.

  16. A enfermagem na avaliação e controle da dor pós-operatória

    Directory of Open Access Journals (Sweden)

    Viviane Silvestre de Souza

    2018-02-01

    Full Text Available A dor é o quinto sinal vital que deve ser registrado ao mesmo tempo e no mesmo ambiente clínico em que também são avaliados os outros sinais. Uma avaliação segura e eficaz do paciente, na qual alterações endócrinas e metabólicas decorrentes do trauma anestésico-cirúrgico sejam consideradas e, ainda, a criação de padrões e critérios de avaliação para a assistência prestada ao paciente neste período e avaliação dos mesmos. O controle da dor pós-operatória envolve basicamente o uso de AINEs, opióides, por diversas vias e métodos, uso de meios físicos e intervenções de natureza comportamental cognitiva, como técnicas educativas, de relaxamento, distração e imaginação dirigida entre outras. O presente estudo foi desenvolvido através de pesquisas bibliográfica indexados nas bases de dados: Scielo e Lilacs, com os seguintes descritores: Dor, Pós-operatório, Avaliação, Controle e Enfermagem. O objetivo deste estudo é descrever sobre a atuação da enfermagem na avaliação e controle da dor pós-operatória. É função da enfermagem implementar a terapêutica adequada visando a prevenção e o alívio da dor, responsabilizando-se pela avaliação da mesma no período pós-operatório visando a promoção do conforto ao paciente com o alivio da dor.. Descritores: Dor; Pós-operatório; Avaliação; Controle; Enfermagem.

  17. Conhecimento dos acadêmicos e profissionais da fisioterapia sobre dor: uma revisão sistemática

    Directory of Open Access Journals (Sweden)

    Alan Carlos Nery dos Santos

    2017-08-01

    Full Text Available Estudos demonstram que acadêmicos e profissionais da fisioterapia apresentam limitações no conhecimento sobre diversos aspectos do tema “dor”. Isso pode implicar em abordagens inadequadas e em maior sofrimento dos pacientes. Assim, objetivou-se revisar estudos que investigaram o conhecimento de acadêmicos e profissionais da fisioterapia sobre dor, bem como os que propuseram estratégias para modificar tal conhecimento. Trata-se de uma revisão sistemática, e foram consultadas as bases de dados EBSCOhost, LILACS, PubMed, REDALYC e SciELO, por meio do cruzamento das palavras-chave: “pain”, “knowledge”, “education”, “curriculum”, “physical therapy specialty” e os seus correspondentes em português. Foram considerados elegíveis os estudos observacionais ou experimentais que analisaram o conhecimento sobre aspectos clínicos, fisiopatológicos e manejo da dor. Também foram elegíveis os que testaram estratégias para modificar o conhecimento sobre dor. A triagem pelos títulos e resumo resultou em 84 estudos. Contudo, apenas cinco foram incluídos. Esses analisaram o conhecimento sobre aspectos gerais da dor, sendo publicados entre 2003 e 2016. Apenas 60% dos estudos investigaram participantes da fisioterapia, sendo que 100% deles verificaram o conhecimento por meio de questionários autoaplicáveis. Quatro estudos utilizaram questionários validados. Somente 20% testaram estratégias para modificar o conhecimento sobre dor. Os resultados desta revisão indicam que o tema “dor” é abordado apenas como subtema complementar, o que, embora permita o aprendizado, não tem sido suficiente para garanti-lo. Profissionais da fisioterapia apresentam inconsistência entre o conhecimento teórico e os seus papeis no manuseio e na assistência humanizada da dor. Estratégias de ensino-aprendizagem ativas podem aprimorar o conhecimento acadêmico sobre dor.

  18. Wound healing of laparoscopic Heller's myotomy with and without an added dor's fundoplication, in pigs

    OpenAIRE

    Azevedo, João Luiz Moreira Coutinho [UNIFESP; Kozu, Fábio Okutani [UNIFESP; Azevedo, Otávio Cansanção [UNIFESP; Paiva, Vanessa Carla [UNIFESP; Silva, Cássio Edvan Paulino da [UNIFESP; Simões, Manuel de Jesus [UNIFESP

    2004-01-01

    OBJETIVO: Comparar a cicatrização da miotomia esofagiana laparoscópica associada ou não à fundocardioplastia de Dor. MÉTODO: Foram utilizados 18 porcos, em três grupos de seis animais. No grupo A foi realizada miotomia esofagiana. No grupo B associou-se plicatura gástrica à miotomia. O grupo C foi sem miotomia. No 21º dia pós-operatório houve moldagem do lume para obter índices de estenose (IE) na região da miotomia (RM) e na transição esôfago-gástrica (I'E'). Foram também estudados aspectos ...

  19. A circulação da experiência da dor em narrativas no Facebook

    Directory of Open Access Journals (Sweden)

    Marlon Santa Maria Dias

    2017-07-01

    Full Text Available Este trabalho reflete alguns aspectos da problemática da circulação na ambiência da midiatização. A partir de material coletado em um grupo de discussão no Facebook sobre a mobilização “Eu não mereço ser estuprada”, analisamos as estratégias discursivas que compõem os processos de enunciação da mobilização dos atores sociais. Apontamos a reconfiguração narrativa na circulação da experiência da dor e a criação de redes interativas de apoio e aconselhamento.

  20. Asaia symbionts interfere with infection by Flavescence dorée phytoplasma in leafhoppers

    KAUST Repository

    Gonella, Elena

    2018-03-20

    The transmission of microbial pathogens by insect vectors can be affected by the insect’s microbial symbionts, which may compete in colonizing organs, express antagonistic factors or activate host immune response. Acetic acid bacteria of the genus Asaia are symbionts of the leafhopper Scaphoideus titanus, which transmits Flavescence dorée phytoplasma. These bacteria could be used as control agents against the disease. Here, we experimentally investigated the interaction between different strains of Asaia and phytoplasma transmission in the laboratory by using the model leafhopper Euscelidius variegatus and the plant host Vicia faba. We found that uncultivable and low concentrations of Asaia phylotypes were associated with E. variegatus. When we supplied different Asaia strains isolated from other insects and exhibiting different phenotypes to E. variegatus orally, the bacteria stably colonized the leafhopper, reached relatively higher densities and could then be isolated from the host. We conducted transmission trials of Flavescence dorée phytoplasma with individuals colonized with three exogenous Asaia strains. When the phytoplasma became established in the bodies of E. variegatus, leafhoppers were able to transmit it to broad beans, with transmission rates ranging from 33 to 76% in different experiments. However, leafhoppers that were colonized by one of the Asaia strains producing an air–liquid interface biofilm exhibited significantly reduced phytoplasma acquisition, with infection rates at 5–28%, whereas they were 25–77% in control insects. Although the mechanisms regulating this interference remain to be elucidated, our results provide evidence of the potential use of Asaia as a biocontrol agent.

  1. Asaia symbionts interfere with infection by Flavescence dorée phytoplasma in leafhoppers

    KAUST Repository

    Gonella, Elena; Crotti, Elena; Mandrioli, Mauro; Daffonchio, Daniele; Alma, Alberto

    2018-01-01

    The transmission of microbial pathogens by insect vectors can be affected by the insect’s microbial symbionts, which may compete in colonizing organs, express antagonistic factors or activate host immune response. Acetic acid bacteria of the genus Asaia are symbionts of the leafhopper Scaphoideus titanus, which transmits Flavescence dorée phytoplasma. These bacteria could be used as control agents against the disease. Here, we experimentally investigated the interaction between different strains of Asaia and phytoplasma transmission in the laboratory by using the model leafhopper Euscelidius variegatus and the plant host Vicia faba. We found that uncultivable and low concentrations of Asaia phylotypes were associated with E. variegatus. When we supplied different Asaia strains isolated from other insects and exhibiting different phenotypes to E. variegatus orally, the bacteria stably colonized the leafhopper, reached relatively higher densities and could then be isolated from the host. We conducted transmission trials of Flavescence dorée phytoplasma with individuals colonized with three exogenous Asaia strains. When the phytoplasma became established in the bodies of E. variegatus, leafhoppers were able to transmit it to broad beans, with transmission rates ranging from 33 to 76% in different experiments. However, leafhoppers that were colonized by one of the Asaia strains producing an air–liquid interface biofilm exhibited significantly reduced phytoplasma acquisition, with infection rates at 5–28%, whereas they were 25–77% in control insects. Although the mechanisms regulating this interference remain to be elucidated, our results provide evidence of the potential use of Asaia as a biocontrol agent.

  2. Abordagens comportamentais para a dor crônica Behavioral approaches for chronic pain

    Directory of Open Access Journals (Sweden)

    Luc Vandenberghe

    2005-04-01

    Full Text Available A terapia comportamental da dor crônica se destaca por um ecletismo técnico, assentando-se em procedimentos provenientes das diferentes abordagens terapêuticas que se desenvolveram no seio da tradição comportamental. Trata-se da Terapia Comportamental Clássica, da Terapia Cognitiva Comportamental, da Análise Aplicada do Comportamento e da Análise Clínica do Comportamento. Estes 4 grandes movimentos que representam o desenvolvimento histórico e a pluralidade paradigmática da terapia comportamental são resgatados como eixos teóricos para servir como pontos cardeais na exposição das opções oferecidas pela terapia comportamental para a clínica da dor. Nesta revisão de literatura, divergências entre as 4 abordagens são identificadas, as quais têm implicações importantes para a atuação do terapeuta.Behavior therapy of chronic pain is marked by technical eclecticism, building upon procedures derived from different therapeutic directions that were developed in the behavioral tradition. These are Classical Behavior Therapy, Cognitive Behavior Therapy, Applied Behavior Analysis and Clinical Behavior Analysis. These 4 broad movements that represent the historical development and the paradigmatic plurality of behavior therapy, are used as theoretical axes to serve as directions of reference in the exposition of the options behavior therapy offers for the treatment of pain. In this literature review, divergences are identified between the 4 approaches, which have important implications for the therapist's practice.

  3. Optimal cofactor swapping can increase the theoretical yield for chemical production in Escherichia coli and Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    King, Zachary A.; Feist, Adam

    2014-01-01

    Maintaining cofactor balance is a critical function in microorganisms, but often the native cofactor balance does not match the needs of an engineered metabolic flux state. Here, an optimization procedure is utilized to identify optimal cofactor-specificity "swaps" for oxidoreductase enzymes...... specificity of central metabolic enzymes (especially GAPD and ALCD2x) is shown to increase NADPH production and increase theoretical yields for native products in E. coli and yeast-including l-aspartate, l-lysine, l-isoleucine, l-proline, l-serine, and putrescine-and non-native products in E. coli-including 1...

  4. DEAH-RHA helicase•Znf cofactor systems in kinetoplastid RNA editing and evolutionarily distant RNA processes

    Science.gov (United States)

    Cruz-Reyes, Jorge; Mooers, Blaine H.M.; Abu-Adas, Zakaria; Kumar, Vikas; Gulati, Shelly

    2016-01-01

    Multi-zinc finger proteins are an emerging class of cofactors in DEAH-RHA RNA helicases across highly divergent eukaryotic lineages. DEAH-RHA helicase•zinc finger cofactor partnerships predate the split of kinetoplastid protozoa, which include several human pathogens, from other eukaryotic lineages 100–400 Ma. Despite a long evolutionary history, the prototypical DEAH-RHA domains remain highly conserved. This short review focuses on a recently identified DEAH-RHA helicase•zinc finger cofactor system in kinetoplastid RNA editing, and its potential functional parallels with analogous systems in embryogenesis control in nematodes and antivirus protection in humans. PMID:27540585

  5. Kinetics based reaction optimization of enzyme catalysed reduction of formaldehyde to methanol with synchronous cofactor regeneration

    DEFF Research Database (Denmark)

    Marpani, Fauziah Binti; Sárossy, Zsuzsa; Pinelo, Manuel

    2017-01-01

    regeneration of the reducing equivalents during reaction is required. Herein, we report the optimization of the enzymatic conversion of formaldehyde (CHOH) to CH3 OH by alcohol dehydrogenase, the final step of the enzymatic redox reaction of CO2 to CH3 OH, with kinetically synchronous enzymatic cofactor...... regeneration using either glucose dehydrogenase (System I) or xylose dehydrogenase (System II). A mathematical model of the enzyme kinetics was employed to identify the best reaction set-up for attaining optimal cofactor recycling rate and enzyme utilization efficiency. Targeted process optimization...... experiments were conducted to verify the kinetically modelled results. Repetitive reaction cycles were shown to enhance the yield of CH3 OH, increase the total turnover number (TTN) and the biocatalytic productivity rate (BPR) value for both system I and II whilst minimizing the exposure of the enzymes...

  6. A toxic imbalance of Hsp70s in Saccharomyces cerevisiae is caused by competition for cofactors.

    Science.gov (United States)

    Keefer, Kathryn M; True, Heather L

    2017-09-01

    Molecular chaperones are responsible for managing protein folding from translation through degradation. These crucial machines ensure that protein homeostasis is optimally maintained for cell health. However, 'too much of a good thing' can be deadly, and the excess of chaperones can be toxic under certain cellular conditions. For example, overexpression of Ssa1, a yeast Hsp70, is toxic to cells in folding-challenged states such as [PSI+]. We discovered that overexpression of the nucleotide exchange factor Sse1 can partially alleviate this toxicity. We further argue that the basis of the toxicity is related to the availability of Hsp70 cofactors, such as Hsp40 J-proteins and nucleotide exchange factors. Ultimately, our work informs future studies about functional chaperone balance and cautions against therapeutic chaperone modifications without a thorough examination of cofactor relationships. © 2017 John Wiley & Sons Ltd.

  7. Crystallization and preliminary X-ray analysis of tubulin-folding cofactor A from Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Lu, Lu; Nan, Jie; Mi, Wei; Wei, Chun-Hong; Li, Lan-Fen; Li, Yi

    2010-01-01

    Tubulin-folding cofactor A from A. thaliana has been crystallized and preliminarily analyzed using X-ray diffraction. Tubulin-folding cofactor A (TFC A) is a molecular post-chaperonin that is involved in the β-tubulin-folding pathway. It has been identified in many organisms including yeasts, humans and plants. In this work, Arabidopsis thaliana TFC A was expressed in Escherichia coli and purified to homogeneity. After thrombin cleavage, a well diffracting crystal was obtained by the sitting-drop vapour-diffusion method at 289 K. The crystal diffracted to 1.6 Å resolution using synchrotron radiation and belonged to space group I4 1 , with unit-cell parameters a = 55.0, b = 55.0, c = 67.4 Å

  8. Probing the structural basis of oxygen binding in a cofactor-independent dioxygenase.

    Science.gov (United States)

    Li, Kunhua; Fielding, Elisha N; Condurso, Heather L; Bruner, Steven D

    2017-07-01

    The enzyme DpgC is included in the small family of cofactor-independent dioxygenases. The chemistry of DpgC is uncommon as the protein binds and utilizes dioxygen without the aid of a metal or organic cofactor. Previous structural and biochemical studies identified the substrate-binding mode and the components of the active site that are important in the catalytic mechanism. In addition, the results delineated a putative binding pocket and migration pathway for the co-substrate dioxygen. Here, structural biology is utilized, along with site-directed mutagenesis, to probe the assigned dioxygen-binding pocket. The key residues implicated in dioxygen trafficking were studied to probe the process of binding, activation and chemistry. The results support the proposed chemistry and provide insight into the general mechanism of dioxygen binding and activation.

  9. Kinetics based reaction optimization of enzyme catalyzed reduction of formaldehyde to methanol with synchronous cofactor regeneration.

    Science.gov (United States)

    Marpani, Fauziah; Sárossy, Zsuzsa; Pinelo, Manuel; Meyer, Anne S

    2017-12-01

    Enzymatic reduction of carbon dioxide (CO 2 ) to methanol (CH 3 OH) can be accomplished using a designed set-up of three oxidoreductases utilizing reduced pyridine nucleotide (NADH) as cofactor for the reducing equivalents electron supply. For this enzyme system to function efficiently a balanced regeneration of the reducing equivalents during reaction is required. Herein, we report the optimization of the enzymatic conversion of formaldehyde (CHOH) to CH 3 OH by alcohol dehydrogenase, the final step of the enzymatic redox reaction of CO 2 to CH 3 OH, with kinetically synchronous enzymatic cofactor regeneration using either glucose dehydrogenase (System I) or xylose dehydrogenase (System II). A mathematical model of the enzyme kinetics was employed to identify the best reaction set-up for attaining optimal cofactor recycling rate and enzyme utilization efficiency. Targeted process optimization experiments were conducted to verify the kinetically modeled results. Repetitive reaction cycles were shown to enhance the yield of CH 3 OH, increase the total turnover number (TTN) and the biocatalytic productivity rate (BPR) value for both system I and II whilst minimizing the exposure of the enzymes to high concentrations of CHOH. System II was found to be superior to System I with a yield of 8 mM CH 3 OH, a TTN of 160 and BPR of 24 μmol CH 3 OH/U · h during 6 hr of reaction. The study demonstrates that an optimal reaction set-up could be designed from rational kinetics modeling to maximize the yield of CH 3 OH, whilst simultaneously optimizing cofactor recycling and enzyme utilization efficiency. © 2017 Wiley Periodicals, Inc.

  10. Potential role of Arabidopsis PHP as an accessory subunit of the PAF1 transcriptional cofactor.

    Science.gov (United States)

    Park, Sunchung; Ek-Ramos, Maria Julissa; Oh, Sookyung; van Nocker, Steven

    2011-08-01

    Paf1C is a transcriptional cofactor that has been implicated in various transcription-associated mechanisms spanning initiation, elongation and RNA processing, and is important for multiple aspects of development in Arabidopsis. Our recent studies suggest Arabidopsis Paf1C is crucial for proper regulation of genes within H3K27me3-enriched chromatin, and that a protein named PHP may act as an accessory subunit of Paf1C that promotes this function.

  11. Metabolic Regulation of Histone Acetyltransferases by Endogenous Acyl-CoA Cofactors

    OpenAIRE

    Montgomery, David C.; Sorum, Alexander W.; Guasch, Laura; Nicklaus, Marc C.; Meier, Jordan L.

    2015-01-01

    The finding that chromatin modifications are sensitive to changes in cellular cofactor levels potentially links altered tumor cell metabolism and gene expression. However, the specific enzymes and metabolites that connect these two processes remain obscure. Characterizing these metabolic-epigenetic axes is critical to understanding how metabolism supports signaling in cancer, and developing therapeutic strategies to disrupt this process. Here, we describe a chemical approach to define the met...

  12. S-Adenosyl-L-Homocysteine Hydrolase Inhibition by a Synthetic Nicotinamide Cofactor Biomimetic

    Directory of Open Access Journals (Sweden)

    Lyn L. Kailing

    2018-03-01

    Full Text Available S-adenosyl-L-homocysteine (SAH hydrolases (SAHases are involved in the regulation of methylation reactions in many organisms and are thus crucial for numerous cellular functions. Consequently, their dysregulation is associated with severe health problems. The SAHase-catalyzed reaction is reversible and both directions depend on the redox activity of nicotinamide adenine dinucleotide (NAD+ as a cofactor. Therefore, nicotinamide cofactor biomimetics (NCB are a promising tool to modulate SAHase activity. In the present in vitro study, we investigated 10 synthetic truncated NAD+ analogs against a SAHase from the root-nodulating bacterium Bradyrhizobium elkanii. Among this set of analogs, one was identified to inhibit the SAHase in both directions. Isothermal titration calorimetry (ITC and crystallography experiments suggest that the inhibitory effect is not mediated by a direct interaction with the protein. Neither the apo-enzyme (i.e., deprived of the natural cofactor, nor the holo-enzyme (i.e., in the NAD+-bound state were found to bind the inhibitor. Yet, enzyme kinetics point to a non-competitive inhibition mechanism, where the inhibitor acts on both, the enzyme and enzyme-SAH complex. Based on our experimental results, we hypothesize that the NCB inhibits the enzyme via oxidation of the enzyme-bound NADH, which may be accessible through an open molecular gate, leaving the enzyme stalled in a configuration with oxidized cofactor, where the reaction intermediate can be neither converted nor released. Since the reaction mechanism of SAHase is quite uncommon, this kind of inhibition could be a viable pharmacological route, with a low risk of off-target effects. The NCB presented in this work could be used as a template for the development of more potent SAHase inhibitors.

  13. Escherichia coli class Ib ribonucleotide reductase contains a dimanganese(III)-tyrosyl radical cofactor in vivo†

    Science.gov (United States)

    Cotruvo, Joseph A.; Stubbe, JoAnne

    2011-01-01

    Escherichia coli class Ib ribonucleotide reductase (RNR) converts nucleoside 5′-diphosphates to deoxynucleoside 5′-diphosphates in iron-limited and oxidative stress conditions. We have recently demonstrated in vitro that this RNR is active with both diferric-tyrosyl radical (FeIII2-Y•) and dimanganese(III)-Y• (MnIII2-Y•) cofactors in the β2 subunit, NrdF [Cotruvo J.A., Jr. and Stubbe J., Biochemistry (2010) 49, 1297–1309]. Here we demonstrate, by purification of this protein from its endogenous levels in an E. coli strain deficient in its five known iron uptake pathways and grown under iron-limited conditions, that the MnIII2-Y• cofactor is assembled in vivo. This is the first definitive determination of the active cofactor of a class Ib RNR purified from its native organism without overexpression. From 88 g of cell paste, 150 μg of NrdF was isolated with ~95% purity, with 0.2 Y•/β2, 0.9 Mn/β2, and a specific activity of 720 nmol/min/mg. In these conditions, the class Ib RNR is the primary active RNR in the cell. Our results strongly suggest that E. coli NrdF is an obligate manganese protein in vivo and that the MnIII2-Y• cofactor assembly pathway we have identified in vitro involving the flavodoxin-like protein NrdI, present inside the cell at catalytic levels, is operative in vivo. PMID:21250660

  14. CD/MCD/VTVH-MCD Studies of Escherichia coli Bacterioferritin Support a Binuclear Iron Cofactor Site.

    Science.gov (United States)

    Kwak, Yeonju; Schwartz, Jennifer K; Huang, Victor W; Boice, Emily; Kurtz, Donald M; Solomon, Edward I

    2015-12-01

    Ferritins and bacterioferritins (Bfrs) utilize a binuclear non-heme iron binding site to catalyze oxidation of Fe(II), leading to formation of an iron mineral core within a protein shell. Unlike ferritins, in which the diiron site binds Fe(II) as a substrate, which then autoxidizes and migrates to the mineral core, the diiron site in Bfr has a 2-His/4-carboxylate ligand set that is commonly found in diiron cofactor enzymes. Bfrs could, therefore, utilize the diiron site as a cofactor rather than for substrate iron binding. In this study, we applied circular dichroism (CD), magnetic CD (MCD), and variable-temperature, variable-field MCD (VTVH-MCD) spectroscopies to define the geometric and electronic structures of the biferrous active site in Escherichia coli Bfr. For these studies, we used an engineered M52L variant, which is known to eliminate binding of a heme cofactor but to have very minor effects on either iron oxidation or mineral core formation. We also examined an H46A/D50A/M52L Bfr variant, which additionally disrupts a previously observed mononuclear non-heme iron binding site inside the protein shell. The spectral analyses define a binuclear and an additional mononuclear ferrous site. The biferrous site shows two different five-coordinate centers. After O2 oxidation and re-reduction, only the mononuclear ferrous signal is eliminated. The retention of the biferrous but not the mononuclear ferrous site upon O2 cycling supports a mechanism in which the binuclear site acts as a cofactor for the O2 reaction, while the mononuclear site binds the substrate Fe(II) that, after its oxidation to Fe(III), migrates to the mineral core.

  15. Quantum localization and protein-assisted vibrational energy flow in cofactors

    International Nuclear Information System (INIS)

    Leitner, David M

    2010-01-01

    Quantum effects influence vibrational dynamics and energy flow in biomolecules, which play a central role in biomolecule function, including control of reaction kinetics. Lifetimes of many vibrational modes of proteins and their temperature dependence, as determined by quantum golden-rule-based calculations, exhibit trends consistent with experimental observation and distinct from estimates based on classical modeling. Particularly notable are quantum coherence effects that give rise to localization of vibrational states of sizable organic molecules in the gas phase. Even when such a molecule, for instance a cofactor, is embedded in a protein, remnants of quantum localization survive that influence vibrational energy flow and its dependence on temperature. We discuss these effects on the mode-damping rates of a cofactor embedded in a protein, using the green fluorescent protein chromophore as a specific example. We find that for cofactors of this size embedded in their protein and solvent environment at room temperature a golden-rule calculation often overestimates the mode-damping rate.

  16. Crystallization and preliminary crystallographic analysis of molybdenum-cofactor biosynthesis protein C from Thermus thermophilus

    International Nuclear Information System (INIS)

    Kanaujia, Shankar Prasad; Ranjani, Chellamuthu Vasuki; Jeyakanthan, Jeyaraman; Baba, Seiki; Chen, Lirong; Liu, Zhi-Jie; Wang, Bi-Cheng; Nishida, Masami; Ebihara, Akio; Shinkai, Akeo; Kuramitsu, Seiki; Shiro, Yoshitsugu; Sekar, Kanagaraj; Yokoyama, Shigeyuki

    2006-01-01

    The molybdenum-cofactor biosynthesis protein C from T. thermophilus has been crystallized in two different space groups, P2 1 and R32; the crystals diffracted to 1.9 and 1.75 Å resolution, respectively. The Gram-negative aerobic eubacterium Thermus thermophilus is an extremely important thermophilic microorganism that was originally isolated from a thermal vent environment in Japan. The molybdenum cofactor in this organism is considered to be an essential component required by enzymes that catalyze diverse key reactions in the global metabolism of carbon, nitrogen and sulfur. The molybdenum-cofactor biosynthesis protein C derived from T. thermophilus was crystallized in two different space groups. Crystals obtained using the first crystallization condition belong to the monoclinic space group P2 1 , with unit-cell parameters a = 64.81, b = 109.84, c = 115.19 Å, β = 104.9°; the crystal diffracted to a resolution of 1.9 Å. The other crystal form belonged to space group R32, with unit-cell parameters a = b = 106.57, c = 59.25 Å, and diffracted to 1.75 Å resolution. Preliminary calculations reveal that the asymmetric unit contains 12 monomers and one monomer for the crystals belonging to space group P2 1 and R32, respectively

  17. CoFactor: Folate Requirement for Optimization of 5-Fluouracil Activity in Anticancer Chemotherapy

    Directory of Open Access Journals (Sweden)

    Muhammad Wasif Saif

    2010-01-01

    Full Text Available Intracellular reduced folate exists as a “pool” of more than 6 interconvertable forms. One of these forms, 5,10 methylenetetrahydrofolic acid (CH2THF, is the key one-carbon donor and reduced folate substrate for thymidylate synthase (TS. This pathway has been an important target for chemotherapy as it provides one of the necessary nucleotide substrates for DNA synthesis. The fluoropyrimidine 5-fluorouracil (5-FU exerts its main cytotoxic activity through TS inhibition. Leucovorin (5-formyltetrahydrofolate; LV has been used to increase the intracellular reduced folate pools and enhance TS inhibition. However, it must be metabolized within the cell through multiple intracellular enzymatic steps to form CH2THF. CoFactor (USAN fotrexorin calcium, (dl-5,10,-methylenepteroyl-monoglutamate calcium salt is a reduced folate that potentiates 5-FU cytotoxicity. According to early clinical trials, when 5-FU is modulated by CoFactor instead of LV, there is greater anti-tumor activity and less toxicity. This review presents the emerging role of CoFactor in colorectal and nongastrointestinal malignancies.

  18. Cofactor engineering to regulate NAD+/NADH ratio with its application to phytosterols biotransformation.

    Science.gov (United States)

    Su, Liqiu; Shen, Yanbing; Zhang, Wenkai; Gao, Tian; Shang, Zhihua; Wang, Min

    2017-10-30

    Cofactor engineering is involved in the modification of enzymes related to nicotinamide adenine dinucleotides (NADH and NAD + ) metabolism, which results in a significantly altered spectrum of metabolic products. Cofactor engineering plays an important role in metabolic engineering but is rarely reported in the sterols biotransformation process owing to its use of multi-catabolic enzymes, which promote multiple consecutive reactions. Androst-4-ene-3, 17-dione (AD) and androst-1, 4-diene-3, 17-dione (ADD) are important steroid medicine intermediates that are obtained via the nucleus oxidation and the side chain degradation of phytosterols by Mycobacterium. Given that the biotransformation from phytosterols to AD (D) is supposed to be a NAD + -dependent process, this work utilized cofactor engineering in Mycobacterium neoaurum and investigated the effect on cofactor and phytosterols metabolism. Through the addition of the coenzyme precursor of nicotinic acid in the phytosterols fermentation system, the intracellular NAD + /NADH ratio and the AD (D) production of M. neoaurum TCCC 11978 (MNR M3) were higher than in the control. Moreover, the NADH: flavin oxidoreductase was identified and was supposed to exert a positive effect on cofactor regulation and phytosterols metabolism pathways via comparative proteomic profiling of MNR cultured with and without phytosterols. In addition, the NADH: flavin oxidoreductase and a water-forming NADH oxidase from Lactobacillus brevis, were successfully overexpressed and heterologously expressed in MNR M3 to improve the intracellular ratio of NAD + /NADH. After 96 h of cultivation, the expression of these two enzymes in MNR M3 resulted in the decrease in intracellular NADH level (by 51 and 67%, respectively) and the increase in NAD + /NADH ratio (by 113 and 192%, respectively). Phytosterols bioconversion revealed that the conversion ratio of engineered stains was ultimately improved by 58 and 147%, respectively. The highest AD (D

  19. Efficacy and safety of cyclic pyranopterin monophosphate substitution in severe molybdenum cofactor deficiency type A : a prospective cohort study

    NARCIS (Netherlands)

    Schwahn, Bernd C.; Van Spronsen, Francjan J.; Belaidi, Abdel A.; Bowhay, Stephen; Christodoulou, John; Derks, Terry G.; Hennermann, Julia B.; Jameson, Elisabeth; Koenig, Kai; McGregor, Tracy L.; Font-Montgomery, Esperanza; Santamaria-Araujo, Jose A.; Santra, Saikat; Vaidya, Mamta; Vierzig, Anne; Wassmer, Evangeline; Weis, Ilona; Wong, Flora Y.; Veldman, Alex; Schwarz, Guenter

    2015-01-01

    Background Molybdenum cofactor deficiency (MoCD) is characterised by early, rapidly progressive postnatal encephalopathy and intractable seizures, leading to severe disability and early death. Previous treatment attempts have been unsuccessful. After a pioneering single treatment we now report the

  20. Redox-dependent substrate-cofactor interactions in the Michaelis-complex of a flavin-dependent oxidoreductase

    Science.gov (United States)

    Werther, Tobias; Wahlefeld, Stefan; Salewski, Johannes; Kuhlmann, Uwe; Zebger, Ingo; Hildebrandt, Peter; Dobbek, Holger

    2017-07-01

    How an enzyme activates its substrate for turnover is fundamental for catalysis but incompletely understood on a structural level. With redox enzymes one typically analyses structures of enzyme-substrate complexes in the unreactive oxidation state of the cofactor, assuming that the interaction between enzyme and substrate is independent of the cofactors oxidation state. Here, we investigate the Michaelis complex of the flavoenzyme xenobiotic reductase A with the reactive reduced cofactor bound to its substrates by X-ray crystallography and resonance Raman spectroscopy and compare it to the non-reactive oxidized Michaelis complex mimics. We find that substrates bind in different orientations to the oxidized and reduced flavin, in both cases flattening its structure. But only authentic Michaelis complexes display an unexpected rich vibrational band pattern uncovering a strong donor-acceptor complex between reduced flavin and substrate. This interaction likely activates the catalytic ground state of the reduced flavin, accelerating the reaction within a compressed cofactor-substrate complex.

  1. A water-forming NADH oxidase from Lactobacillus pentosus and its potential application in the regeneration of synthetic biomimetic cofactors

    Directory of Open Access Journals (Sweden)

    Claudia eNowak

    2015-09-01

    Full Text Available The cell-free biocatalytic production of fine chemicals by oxidoreductases has continuously grown over the past years. Since especially dehydrogenases depend on the stoichiometric use of nicotinamide pyridine cofactors, an integrated efficient recycling system is crucial to allow process operation under economic conditions. Lately, the variety of cofactors for biocatalysis was broadened by the utilization of totally synthetic and cheap biomimetics. Though, to date the regeneration has been limited to chemical or electrochemical methods. Here, we report an enzymatic recycling by the flavoprotein NADH-oxidase from Lactobacillus pentosus (LpNox. Since this enzyme has not been described before, we first characterized it in regard to its optimal reaction parameters. We found that the heterologously overexpressed enzyme only contained 13 % FAD. In vitro loading of the enzyme with FAD, resulted in a higher specific activity towards its natural cofactor NADH as well as different nicotinamide derived biomimetics. Apart from the enzymatic recycling, which gives water as a by-product by transferring four electrons onto oxygen, unbound FAD can also catalyse the oxidation of biomimetic cofactors. Here a two electron process takes place yielding H2O2 instead. The enzymatic and chemical recycling was compared in regard to reaction kinetics for the natural and biomimetic cofactors. With LpNox and FAD, two recycling strategies for biomimetic cofactors are described with either water or hydrogen peroxide as a by-product.

  2. Ocorrência de dor lombar e fatores associados em crianças e adolescentes de uma escola privada do sul do Brasil

    OpenAIRE

    Lemos, Adriana Torres de; Santos, Fábio Rosa dos; Moreira, Rodrigo Baptista; Machado, Débora Teixeira; Braga, Fernando Cesar Camargo; Gaya, Adroaldo Cezar Araujo

    2013-01-01

    Estudos têm demonstrado que indivíduos que apresentam dor lombar na infância e adolescência são acometidos também na vida adulta, reforçando a importância de que as causas sejam investigadas desde a idade escolar. Avaliou-se a ocorrência de dor lombar e fatores associados em 770 escolares de 7 a 17 anos de idade de uma escola privada de Porto Alegre, Rio Grande do Sul, Brasil. A dor lombar foi definida como dor ou desconforto na região lombar no último mês e avaliada por meio de questionário....

  3. Nuclear

    International Nuclear Information System (INIS)

    Anon.

    2000-01-01

    The first text deals with a new circular concerning the collect of the medicine radioactive wastes, containing radium. This campaign wants to incite people to let go their radioactive wastes (needles, tubes) in order to suppress any danger. The second text presents a decree of the 31 december 1999, relative to the limitations of noise and external risks resulting from the nuclear facilities exploitation: noise, atmospheric pollution, water pollution, wastes management and fire prevention. (A.L.B.)

  4. Tratamento da dor em queimados Tratamiento del dolor en quemados Pain management in burn patients

    Directory of Open Access Journals (Sweden)

    Rodrigo José Alencar de Castro

    2013-02-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Apesar dos avanços, ainda é observado manejo analgésico inadequado dos pacientes com queimaduras. O objetivo desta revisão foi coletar dados sobre tratamento da dor em queimados. CONTEÚDO: Foi feita revisão sobre os mecanismos de dor, avaliação do paciente com queimadura e o tratamento farmacológico e não farmacológico. CONCLUSÕES: O manejo da dor em pacientes vítimas de queimaduras ainda é um desafio por parte da equipe multiprofissional. A avaliação frequente e contínua da resposta apresentada pelo paciente é muito importante, tendo em vista os vários momentos por que passa o paciente internado em decorrência de uma queimadura, além de uma terapêutica combinada com medicações analgésicas e medidas não farmacológicas. Entender a complexidade de alterações fisiopatológicas, psicológicas e bioquímicas apresentadas por um paciente em tratamento de queimadura é o primeiro passo para alcançar o sucesso no seu manejo analgésico.JUSTIFICATIVA Y OBJETIVOS: Pese a los progresos alcanzados, todavía se observa un manejo analgésico inadecuado de los pacientes con quemaduras. El objetivo de esta revisión, fue la recolección de datos sobre el tratamiento del dolor en pacientes quemados. CONTENIDO: Se efectuó una revisión sobre los mecanismos de dolor, evaluación del paciente con quemadura, y el tratamiento farmacológico y no farmacológico. CONCLUSIONES: El manejo del dolor en los pacientes víctimas de quemaduras todavía es un reto por parte del equipo multiprofesional. La evaluación frecuente y continua de la respuesta presentada por el paciente es muy importante, teniendo en cuenta los diversos momentos por los que pasa el paciente ingresado en razón de una quemadura, además de una terapéutica combinada con medicaciones analgésicas y con medidas no farmacológicas. Entender la complejidad de las alteraciones fisiopatológicas, psicológicas y bioquímicas presentadas por un

  5. Laparoscopic Collis gastroplasty and Dor fundoplication for reflux esophagitis complicated by a penetrating ulcer and shortened esophagus: a case report.

    Science.gov (United States)

    Yano, Fumiaki; Omura, Nobuo; Tsuboi, Kazuto; Nakada, Koji; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

    2007-08-01

    The patient was a 72-year-old man, who was referred to us at the beginning of July 2005 with a chief complaint of difficulty with swallowing. After a thorough medical examination, the patient was diagnosed with a penetrating ulcer due to reflux esophagitis, lower esophageal stricture, Barrett esophagus, and shortened esophagus. After administration of a proton pump inhibitor and 2 sessions of endoscopic dilatation, esophagitis was cured and the stricture was eliminated. Subsequently, Collis gastroplasty and Dor fundoplication, which seemed appropriate to certainly avoid injuring communication with the mediastinum created by the penetrating ulcer and provide radical cure, were performed laparoscopically. The patient made a good postoperative progress, was discharged on the 11th hospital day, and is now being followed up on an outpatient basis. There have been no signs of recurrence of esophagitis, and the penetrating ulcer was cured. To our knowledge, this is the first report of simultaneous laparoscopic Collis gastroplasty and Dor fundoplication in the English literature.

  6. Avaliação da dor pós-operatória em dentes tratados endodonticamente

    OpenAIRE

    Ademar Luiz Waskievicz; Flávia Baldissarelli; José Roberto Vanni; Mateus Silveira Martins Hartmann; Volmir João Fornari

    2015-01-01

    O sucesso do tratamento endodôntico está diretamente relacionado ao domínio da anatomia e ao controle da infecção endodôntica. Alguns fatores, como erros de procedimento (sobre instrumentação, obturação, desvios apicais e perfurações) podem causar dor pós-operatória. Objetivo: Este trabalho teve como objetivo avaliar a dor pós-operatória em dentes que foram tratados endodonticamente na Unidade de Pós-Graduação em Odontologia da Faculdade Meridional – IMED CEOM, de Passo Fundo, no período de j...

  7. Petrogenetic and geodynamic origin of the Neoarchean Doré Lake Complex, Abitibi subprovince, Superior Province, Canada

    DEFF Research Database (Denmark)

    Polat, Ali; Frei, Robert; Longstaffe, Fred J.

    2018-01-01

    Group, which is composed of two cycles of tholeiitic-to-calc-alkaline volcanic and volcaniclastic rocks, siliciclastic and chemical sedimentary rocks, and layered mafic-to-ultramafic sills. In this study, we report major and trace element results, and Nd, Sr, Pb and O isotope data for anorthosites......, leucogabbros, gabbros and mafic dykes from the Doré Lake Complex and spatially associated basalts and gabbros of the Obatogamau Formation to assess their petrogenetic origin and geodynamic setting. Field and petrographic observations indicate that the Doré Lake Complex and associated volcanic rocks underwent...... extensive metamorphic alteration under greenschist facies conditions, resulting in widespread epidotization (20–40%) and chloritization (10–40%) of many rock types. Plagioclase recrystallized mainly to anorthite and albite endmembers, erasing intermediate compositions. Metamorphic alteration also led...

  8. Petrogenetic and geodynamic origin of the Neoarchean Doré Lake Complex, Abitibi subprovince, Superior Province, Canada

    Science.gov (United States)

    Polat, Ali; Frei, Robert; Longstaffe, Fred J.; Woods, Ryan

    2018-04-01

    The Neoarchean (ca. 2728 Ma) anorthosite-bearing Doré Lake Complex in the northeastern Abitibi subprovince, Quebec, was emplaced into an association of intra-oceanic tholeiitic basalts and gabbros known as the Obatogamau Formation. The Obatogamau Formation constitutes the lower part of the Roy Group, which is composed of two cycles of tholeiitic-to-calc-alkaline volcanic and volcaniclastic rocks, siliciclastic and chemical sedimentary rocks, and layered mafic-to-ultramafic sills. In this study, we report major and trace element results, and Nd, Sr, Pb and O isotope data for anorthosites, leucogabbros, gabbros and mafic dykes from the Doré Lake Complex and spatially associated basalts and gabbros of the Obatogamau Formation to assess their petrogenetic origin and geodynamic setting. Field and petrographic observations indicate that the Doré Lake Complex and associated volcanic rocks underwent extensive metamorphic alteration under greenschist facies conditions, resulting in widespread epidotization (20-40%) and chloritization (10-40%) of many rock types. Plagioclase recrystallized mainly to anorthite and albite endmembers, erasing intermediate compositions. Metamorphic alteration also led to the mobilization of many elements (e.g., LILE and transition metals) and to significant disturbance of the Rb-Sr and U-Pb isotope systems, resulting in 1935 ± 150 and 3326 ± 270 Ma errorchron ages, respectively. The Sm-Nd isotope system was less disturbed, yielding an errorchron age of 2624 ± 160 Ma. On many binary major and trace element diagrams, the least altered anorthosites and leucogabbros, and the gabbros and mafic dykes of the Doré Lake Complex plot in separate fields, signifying the presence of two distinct magma types in the complex. The gabbros and mafic dykes in the Doré Lake Complex share the geochemical characteristics of tholeiitic basalts and gabbros in the Obatogamau Formation, suggesting a possible genetic link between the two rock associations. Initial

  9. NMR analysis of the dynamic exchange of the NS2B cofactor between open and closed conformations of the West Nile virus NS2B-NS3 protease.

    Directory of Open Access Journals (Sweden)

    Xun-Cheng Su

    Full Text Available BACKGROUND: The two-component NS2B-NS3 proteases of West Nile and dengue viruses are essential for viral replication and established targets for drug development. In all crystal structures of the proteases to date, the NS2B cofactor is located far from the substrate binding site (open conformation in the absence of inhibitor and lining the substrate binding site (closed conformation in the presence of an inhibitor. METHODS: In this work, nuclear magnetic resonance (NMR spectroscopy of isotope and spin-labeled samples of the West Nile virus protease was used to investigate the occurrence of equilibria between open and closed conformations in solution. FINDINGS: In solution, the closed form of the West Nile virus protease is the predominant conformation irrespective of the presence or absence of inhibitors. Nonetheless, dissociation of the C-terminal part of the NS2B cofactor from the NS3 protease (open conformation occurs in both the presence and the absence of inhibitors. Low-molecular-weight inhibitors can shift the conformational exchange equilibria so that over 90% of the West Nile virus protease molecules assume the closed conformation. The West Nile virus protease differs from the dengue virus protease, where the open conformation is the predominant form in the absence of inhibitors. CONCLUSION: Partial dissociation of NS2B from NS3 has implications for the way in which the NS3 protease can be positioned with respect to the host cell membrane when NS2B is membrane associated via N- and C-terminal segments present in the polyprotein. In the case of the West Nile virus protease, discovery of low-molecular-weight inhibitors that act by breaking the association of the NS2B cofactor with the NS3 protease is impeded by the natural affinity of the cofactor to the NS3 protease. The same strategy can be more successful in the case of the dengue virus NS2B-NS3 protease.

  10. Caracterização da dor em mulheres após tratamento do câncer de mama

    Directory of Open Access Journals (Sweden)

    Vânia Tie Koga Ferreira

    2014-03-01

    Full Text Available Este estudo pretendeu caracterizar e localizar a dor nas mulheres submetidas ao tratamento por câncer de mama. Estudo de caráter exploratório, descritivo, com abordagem quantitativa, pelas medidas de tendência central e percentual. Pesquisa desenvolvida no Núcleo de Ensino e Pesquisa e Assistência na Reabilitação de Mastectomizadas com 30 mulheres. Os dados foram coletados no período de fevereiro a agosto de 2008, por meio de instrumento contendo variáveis capazes de caracterizar e localizar a dor, e foram tratados por meio de média, mediana, moda e desvio-padrão e percentual. Destacou-se que 56,7% mulheres referiram que a dor é diária, 46,7% mulheres referiram que a dor teve início após a cirurgia da mama, e para 40% a dor é constante. Conhecimento, reconhecimento e manejo do sintoma permitem ofertas terapêuticas alternativas para o alívio da dor, minimizando efeitos físicos e emocionais que podem ser causados na vida de mulheres submetidas ao tratamento por câncer de mama.

  11. ‘Where is the Prince?’ Unlocking Doré’s Illustration of Perrault’s Cinderella

    Directory of Open Access Journals (Sweden)

    Emilie Sitzia

    2010-12-01

    Full Text Available This article proposes to consider illustrations as “intersemiotic translation” from words into images. Using this methodology, illustrations give particular insights into the reception and interpretation of Perrault’s fairy tales in a specific cultural, social and political environment. The question then becomes what do Doré’s illustrations say about the reception of Perrault’s fairy tales in 19th‐century France?

  12. Dor Vs Toupet Fundoplication After Laparoscopic Heller Myotomy: Long-Term Randomized Controlled Trial Evaluated by High-Resolution Manometry.

    Science.gov (United States)

    Torres-Villalobos, Gonzalo; Coss-Adame, Enrique; Furuzawa-Carballeda, Janette; Romero-Hernández, Fernanda; Blancas-Breña, Blanca; Torres-Landa, Samuel; Palacios-Ramírez, Axel; Alejandro-Medrano, Edgar; Hernández-Ávila, Axel; Flores-Najera, Athenea; Ávila Escobedo, Lourdes Margarita; Ramírez Angulo, Cecilia; Rodríguez-Garcés, Angélica; Valdovinos, Miguel Ángel

    2018-01-01

    Laparoscopic Heller myotomy (LHM) with partial fundoplication is an effective treatment for achalasia. However, the type of fundoplication is still a subject of debate. The aim of the study is to identify which partial fundoplication leads to better control of acid exposure, manometric parameters, and symptoms scores. A randomized controlled trial was performed to compare Dor vs Toupet fundoplication after LHM. The preoperative diagnosis was made by high-resolution manometry (HRM), upper endoscopy, and barium esophagogram. Preoperative and postoperative symptoms were evaluated with Eckardt, GERD-HRQL, and EAT-10 questionnaires. Seventy-three patients were randomized, 38 underwent Dor and 35 Toupet. Baseline characteristics were similar between groups. Postoperative HRM showed that the integrated relaxation pressure (IRP) and basal lower esophageal sphincter (LES) pressure were similar at 6 and 24 months. The number of patients with abnormal acid exposure was significantly lower for Dor (6.9%) than that of Toupet (34.0%) at 6 months, but it was not different at 12 or 24 months. No differences were found in postoperative symptom scores at 1, 6, or 24 months. There were no differences in symptom scores or HRM between fundoplications in the long term. A higher percentage of abnormal 24-h pH test were found for the Toupet group, with no difference in the long term.

  13. Improving metabolic efficiency of the reverse beta-oxidation cycle by balancing redox cofactor requirement.

    Science.gov (United States)

    Wu, Junjun; Zhang, Xia; Zhou, Peng; Huang, Jiaying; Xia, Xiudong; Li, Wei; Zhou, Ziyu; Chen, Yue; Liu, Yinghao; Dong, Mingsheng

    2017-11-01

    Previous studies have made many exciting achievements on pushing the functional reversal of beta-oxidation cycle (r-BOX) to more widespread adoption for synthesis of a wide variety of fuels and chemicals. However, the redox cofactor requirement for the efficient operation of r-BOX remains unclear. In this work, the metabolic efficiency of r-BOX for medium-chain fatty acid (C 6 -C 10 , MCFA) production was optimized by redox cofactor engineering. Stoichiometric analysis of the r-BOX pathway and further experimental examination identified NADH as a crucial determinant of r-BOX process yield. Furthermore, the introduction of formate dehydrogenase from Candida boidinii using fermentative inhibitor byproduct formate as a redox NADH sink improved MCFA titer from initial 1.2g/L to 3.1g/L. Moreover, coupling of increasing the supply of acetyl-CoA with NADH to achieve fermentative redox balance enabled product synthesis at maximum titers. To this end, the acetate re-assimilation pathway was further optimized to increase acetyl-CoA availability associated with the new supply of NADH. It was found that the acetyl-CoA synthetase activity and intracellular ATP levels constrained the activity of acetate re-assimilation pathway, and 4.7g/L of MCFA titer was finally achieved after alleviating these two limiting factors. To the best of our knowledge, this represented the highest titer reported to date. These results demonstrated that the key constraint of r-BOX was redox imbalance and redox engineering could further unleash the lipogenic potential of this cycle. The redox engineering strategies could be applied to acetyl-CoA-derived products or other bio-products requiring multiple redox cofactors for biosynthesis. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  14. Dissociation of activated protein C functions by elimination of protein S cofactor enhancement.

    LENUS (Irish Health Repository)

    Harmon, Shona

    2008-11-07

    Activated protein C (APC) plays a critical anticoagulant role in vivo by inactivating procoagulant factor Va and factor VIIIa and thus down-regulating thrombin generation. In addition, APC bound to the endothelial cell protein C receptor can initiate protease-activated receptor-1 (PAR-1)-mediated cytoprotective signaling. Protein S constitutes a critical cofactor for the anticoagulant function of APC but is not known to be involved in regulating APC-mediated protective PAR-1 signaling. In this study we utilized a site-directed mutagenesis strategy to characterize a putative protein S binding region within the APC Gla domain. Three single amino acid substitutions within the APC Gla domain (D35T, D36A, and A39V) were found to mildly impair protein S-dependent anticoagulant activity (<2-fold) but retained entirely normal cytoprotective activity. However, a single amino acid substitution (L38D) ablated the ability of protein S to function as a cofactor for this APC variant. Consequently, in assays of protein S-dependent factor Va proteolysis using purified proteins or in the plasma milieu, APC-L38D variant exhibited minimal residual anticoagulant activity compared with wild type APC. Despite the location of Leu-38 in the Gla domain, APC-L38D interacted normally with endothelial cell protein C receptor and retained its ability to trigger PAR-1 mediated cytoprotective signaling in a manner indistinguishable from that of wild type APC. Consequently, elimination of protein S cofactor enhancement of APC anticoagulant function represents a novel and effective strategy by which to separate the anticoagulant and cytoprotective functions of APC for potential therapeutic gain.

  15. Biochemical and genetic characterization of three molybdenum cofactor hydroxylases in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Hoff, Tine; Frandsen, Gitte Inselmann; Rocher, Anne

    1998-01-01

    Aldehyde oxidases and xanthine dehydrogenases/oxidases belong to the molybdenum cofactor dependent hydroxylase class of enzymes. Zymograms show that Arabidopsis thaliana has at least three different aldehyde oxidases and one xanthine oxidase. Three different cDNA clones encoding putative aldehyde...... oxidases (AtAO1, 2, 3) were isolated. An aldehyde oxidase is the last step in abscisic acid (ABA) biosynthesis. AtAO1 is mainly expressed in seeds and roots which might reflect that it is involved in ABA biosynthesis....

  16. Crystallographic investigation of the cooperative interaction between trimethoprim, reduced cofactor and dihydrofolate reductase

    International Nuclear Information System (INIS)

    Champness, J.N.; Stammers, D.K.; Beddell, C.R.

    1986-01-01

    The structure of the complex between E. coli form I dihydrofolate reductase, the antibacterial trimethoprim and NADPH has been determined by X-ray crystallography. The inhibitor and cofactor are in mutual contact. A flexible chain segment which includes Met 20 is in contact with the inhibitor in the presence of NADPH, but more distant in its absence. By contrast, the inhibitor conformation is little changed with NADPH present. The authors discuss these observations with regard to the mutually cooperative binding of these ligands to the protein, and to the associated enhancement of inhibitory selectivity shown by trimethoprim for bacterial as opposed to vertebrate enzyme. (Auth.)

  17. Markers, Cofactors and Staging Systems in the Study of HIV Disease Progression: A Review

    Directory of Open Access Journals (Sweden)

    MC Portela

    1997-07-01

    Full Text Available This paper is aimed at providing a comprehensive review of markers, cofactors and staging systems used for HIV disease, focusing on some aspects that nowadays could even be considered historical, and advancing in current issues such as the prognostic value of viral load measurements, viral genotypic and phenotypic characterization, and new HIV disease treatment protocols. CD4+ cell values, combined with the new viral markers mentioned are promising as a parsimonious predictor set for defining both severity and progression. An adequate predictor of patient resource use for planning purposes still needs to be defined

  18. Cofactor-binding sites in proteins of deviating sequence: comparative analysis and clustering in torsion angle, cavity, and fold space.

    Science.gov (United States)

    Stegemann, Björn; Klebe, Gerhard

    2012-02-01

    Small molecules are recognized in protein-binding pockets through surface-exposed physicochemical properties. To optimize binding, they have to adopt a conformation corresponding to a local energy minimum within the formed protein-ligand complex. However, their conformational flexibility makes them competent to bind not only to homologous proteins of the same family but also to proteins of remote similarity with respect to the shape of the binding pockets and folding pattern. Considering drug action, such observations can give rise to unexpected and undesired cross reactivity. In this study, datasets of six different cofactors (ADP, ATP, NAD(P)(H), FAD, and acetyl CoA, sharing an adenosine diphosphate moiety as common substructure), observed in multiple crystal structures of protein-cofactor complexes exhibiting sequence identity below 25%, have been analyzed for the conformational properties of the bound ligands, the distribution of physicochemical properties in the accommodating protein-binding pockets, and the local folding patterns next to the cofactor-binding site. State-of-the-art clustering techniques have been applied to group the different protein-cofactor complexes in the different spaces. Interestingly, clustering in cavity (Cavbase) and fold space (DALI) reveals virtually the same data structuring. Remarkable relationships can be found among the different spaces. They provide information on how conformations are conserved across the host proteins and which distinct local cavity and fold motifs recognize the different portions of the cofactors. In those cases, where different cofactors are found to be accommodated in a similar fashion to the same fold motifs, only a commonly shared substructure of the cofactors is used for the recognition process. Copyright © 2011 Wiley Periodicals, Inc.

  19. Dor-desprazer-trabalho docente: como desfazer essa tríade

    Directory of Open Access Journals (Sweden)

    Maria Elizabeth Barros de Barros

    2007-12-01

    Full Text Available O artigo apresenta a experiência do Programa de Formação e Investigação Sobre a Saúde e o Trabalho (PFST de docentes de escolas públicas, desenvolvido na Universidade Federal do Espírito Santo. Trata da problemática da saúde do conjunto de docentes que trabalham nas escolas públicas do município da Serra/ES, visando a desfazer a tríade dor-desprazer-trabalho docente, vivida de forma naturalizada pelo coletivo de docentes. Pretende avançar na compreensão das relações saúde-trabalho nas escolas e investigar as estratégias utilizadas por esses professores para resistirem às tentativas de desqualificação do trabalho docente. Afirma a possibilidade de se abrirem espaços de discussão no cotidiano dos docentes para que a luta pela saúde se constitua em redes de cooperação entre sujeitos e escolas, inaugurando-se outras formas de atuação desses estabelecimentos. Com esse objetivo, propõe uma metodologia de trabalho que tem se pautado na abordagem ergológica, construída na Universidade de Provença, em AIX/ França.

  20. Learning curve for laparoscopic Heller myotomy and Dor fundoplication for achalasia.

    Science.gov (United States)

    Yano, Fumiaki; Omura, Nobuo; Tsuboi, Kazuto; Hoshino, Masato; Yamamoto, Seryung; Akimoto, Shunsuke; Masuda, Takahiro; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

    2017-01-01

    Although laparoscopic Heller myotomy and Dor fundoplication (LHD) is widely performed to address achalasia, little is known about the learning curve for this technique. We assessed the learning curve for performing LHD. Of the 514 cases with LHD performed between August 1994 and March 2016, the surgical outcomes of 463 cases were evaluated after excluding 50 cases with reduced port surgery and one case with the simultaneous performance of laparoscopic distal partial gastrectomy. A receiver operating characteristic (ROC) curve analysis was used to identify the cut-off value for the number of surgical experiences necessary to become proficient with LHD, which was defined as the completion of the learning curve. We defined the completion of the learning curve when the following 3 conditions were satisfied. 1) The operation time was less than 165 minutes. 2) There was no blood loss. 3) There was no intraoperative complication. In order to establish the appropriate number of surgical experiences required to complete the learning curve, the cut-off value was evaluated by using a ROC curve (AUC 0.717, p < 0.001). Finally, we identified the cut-off value as 16 surgical cases (sensitivity 0.706, specificity 0.646). Learning curve seems to complete after performing 16 cases.

  1. Learning curve for laparoscopic Heller myotomy and Dor fundoplication for achalasia.

    Directory of Open Access Journals (Sweden)

    Fumiaki Yano

    Full Text Available Although laparoscopic Heller myotomy and Dor fundoplication (LHD is widely performed to address achalasia, little is known about the learning curve for this technique. We assessed the learning curve for performing LHD.Of the 514 cases with LHD performed between August 1994 and March 2016, the surgical outcomes of 463 cases were evaluated after excluding 50 cases with reduced port surgery and one case with the simultaneous performance of laparoscopic distal partial gastrectomy. A receiver operating characteristic (ROC curve analysis was used to identify the cut-off value for the number of surgical experiences necessary to become proficient with LHD, which was defined as the completion of the learning curve.We defined the completion of the learning curve when the following 3 conditions were satisfied. 1 The operation time was less than 165 minutes. 2 There was no blood loss. 3 There was no intraoperative complication. In order to establish the appropriate number of surgical experiences required to complete the learning curve, the cut-off value was evaluated by using a ROC curve (AUC 0.717, p < 0.001. Finally, we identified the cut-off value as 16 surgical cases (sensitivity 0.706, specificity 0.646.Learning curve seems to complete after performing 16 cases.

  2. Masoquismo e mensagem enigmática: para que rimar amor e dor?

    Directory of Open Access Journals (Sweden)

    Fernando Cézar Bezerra de Andrade

    2012-09-01

    Full Text Available Discute-se neste trabalho um caso clínico cujo sintoma principal envolvia a realização de desejos masoquistas, expressos tanto em uma cena erótica específica, que envolve riscos, dor e humilhação, quanto em uma psicodinâmica fundada no culto ao sofrimento e dirigida à autodestruição, o que interferia em outras dimensões da vida do paciente: trabalho, formação intelectual e vínculos amorosos. Inicialmente, resume-se a metapsicologia do masoquismo na obra de Freud, bem como sua reavaliação da perspectiva da Teoria da Sedução Generalizada, formulada por Jean Laplanche. Em seguida, são discutidos a etiologia e o arranjo psíquico do paciente, bem como o processo psicanalítico, com seus principais momentos de atuação e de repetição das fantasias de sedução no contexto transferencial. A elaboração dos sintomas ao longo da análise é entendida como resultando de uma nova tradução para o enigma da sexualidade, formulado, sobretudo, pelas mensagens maternas e paternas, caracterizadas por traços de sadismo e perversão.

  3. A maior dor do mundo: o luto materno em uma perspectiva fenomenológica

    Directory of Open Access Journals (Sweden)

    Joanneliese Lucas de Freitas

    2014-06-01

    Full Text Available O presente trabalho busca refletir sobre a vivência do luto materno na sociedade brasileira contemporânea, a partir da perspectiva fenomenológico-existencial. Foi realizada uma pesquisa qualitativa com três mães enlutadas. Utilizou-se o método fenomenológico de entrevistas, com uso de pergunta disparadora. A análise dos dados seguiu os quatro passos metodológicos de Giorgi. O relato das mães evidenciou diferentes temáticas, descritas por meio de dez elementos constituintes da vivência de luto materno, a saber: dor; perda de um modo de existir; espiritualidade; culpa; perda do sentido do mundo-da-vida; vontade de morrer; fragmentação dos laços afetivos; engajamento em projetos relacionados ao filho; perpetuação da memória do filho; estreitamento de laços com pessoas significativas para o morto. Os resultados obtidos na pesquisa indicam que, embora o luto se modifique ao longo do tempo, a perda de um filho jamais é superada, sendo este sofrimento compreendido não mais como uma condição patológica, mas como especificidades a serem compreendidas.

  4. Dor torácica não-cardiogênica Non-cardiac chest pain

    Directory of Open Access Journals (Sweden)

    Gerson Ricardo de Souza Domingues

    2009-09-01

    Full Text Available CONTEXTO: Dor torácica não-cardiogênica ou dor torácica funcional é síndrome clínica com elevada prevalência no mundo ocidental, podendo estar presente entre 15% a 30% dos pacientes com coronariografias normais. Tem importante impacto na qualidade de vida dos pacientes e associa-se com considerável aumento da utilização dos serviços de saúde. FONTES DE INFORMAÇÃO: Para esta revisão, foram utilizadas as seguintes bases de dados: Medline, the Cochrane Library, LILACS e livros nacionais. Das publicações dos últimos 5 anos foram selecionadas fontes relevantes como artigos originais, artigos de revisão, consensos, diretrizes e revisões sistemáticas de literatura com meta-análise. Publicações relevantes anteriores ao período de tempo analisado, foram também incluídas. RESULTADOS: Foram incluídas 44 publicações, sendo 28 artigos originais, 12 trabalhos de revisão, 2 diretrizes, 1 meta-análise e 1 consenso. CONCLUSÕES: A dor torácica não-cardiogênica abrange a investigação do trato digestório, do aparelho musculoesquelético, do aparelho respiratório e de distúrbios psicológicos. O objetivo do tratamento é o alívio ou eliminação do sintoma e deve estar voltado para o principal mecanismo gerador. A base do tratamento é medicamentosa, entretanto, pode ser necessária intervenção de natureza psicológica e, nos pacientes com acalásia a terapia endoscópica ou cirúrgica. Considerando-se que a maioria dos pacientes apresentarão causas relacionadas ao esôfago, sendo as principais, a doença do refluxo gastroesofágico e distúrbios motores, as principais medicações utilizadas no controle da dor torácica não-cardiogênica são os inibidores da bomba de prótons e os antidepressivos tricíclicos. Recentemente, novas modalidades diagnósticas e também formas de tratamento, tais como, a injeção por endoscopia de toxina botulínica no esôfago e a hipnose, estão em investigação e algumas poder

  5. Specific esophagogram to assess functional outcomes after Heller's myotomy and Dor's fundoplication for esophageal achalasia.

    Science.gov (United States)

    Tsoukali, E; Gouvas, N; Tsiaoussis, J; Pechlivanides, G; Zervakis, N; Mantides, A; Xynos, E

    2011-09-01

    Esophageal emptying assessed at the 'timed barium' esophagogram correlates well with symptomatic outcomes after pneumatic dilation for esophageal achalasia, although 30% of patients with satisfactory outcome exhibit partial improvement in emptying. The aim of the study was to investigate any correlation of esophageal emptying to symptomatic response after laparoscopic Heller's myotomy and Dor's fundoplication. 'Bread and barium' (transit time of a barium opaque bread bolus) and 'timed barium' (height of esophageal barium column 5 minutes after ingestion of 200-250 mL of barium suspension) esophagogram was used to assess esophageal emptying in 73 patients with esophageal achalasia before 1 and 5 years (31 cases) after laparoscopic myotomy and anterior fundoplication. Symptoms assessment was based to a specific score. At 1-year follow-up, excellent and good symptomatic results were obtained in 95% of the cases. Esophageal maximum diameter, esophageal transit time, and esophageal barium column were significantly correlated to each other and to symptom score postoperatively (P achalasia. Complete symptomatic relief does not necessarily reflect complete esophageal emptying. Outcomes do not deteriorate by time. Because of wide availability, esophagogram can be applied in follow-up of postmyotomy patients in conjunction with symptomatic evaluation. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

  6. Dor e Gozo: relatos de mulheres jovens sobre automutilações

    Directory of Open Access Journals (Sweden)

    José Juliano Cedaro

    2013-08-01

    Full Text Available Este artigo discute a prática da automutilação, destacando os relatos de mulheres jovens (entre 15 e 21 anos, atendidas em um Centro de Atenção Psicossocial (CAPS. Tais atitudes consistem em provocar, de forma consciente, feridas no próprio corpo, como cortes, arranhões, queimaduras ou perfurações, não havendo nessas ações o desejo manifesto de suicídio, embora seja comum aparecerem ideações nesse sentido nas falas das pacientes. Os relatos acerca de tal comportamento são apresentados por meio de fragmentos de falas, registrados após atendimentos psicológicos, que esboçam a descrição dos sentimentos expostos dentro do setting terapêutico. As questões suscitadas são discutidas a partir das concepções psicanalíticas a respeito do gozo e do masoquismo, com ênfase nas proposições de Freud e Lacan, focalizando a seguinte indagação: qual é a função da dor autoprovocada - e das marcas corporais autoinflingidas - na dinâmica psíquica das pacientes com histórico de automutilações?

  7. Cervical carcinogenesis: the role of co-factors and generation of reactive oxygen species Carcinogénesis cervical: co-factores y antioxidantes

    Directory of Open Access Journals (Sweden)

    Anna Giuliano

    2003-01-01

    Full Text Available Several HPV co-factors have been proposed, some more or less consistently associated with cervical dysplasia and cancer risk. More research, using prospective cohort designs, is needed to further describe where in carcinogenesis these factors are working and to assess the biological mechanism of these factors. In addition, further research is needed to define the role of various hormonal contraceptive formulations in promoting cervical carcinogenesis. While many interesting scientific questions remain to be answered, results from the numerous epidemiological studies conducted to date indicate that cervical dysplasia and cancer may be reduced if the oxidant antioxidant ratio is shifted to more of and antioxidant profile. In addition to cervical cancer screening, a reduction in cervical cancer incidence may be accomplished by reducing tobacco use, increasing nutritional status, and utilizing barrier contraception to prevent infection with other sexually acquired infections.Diversos co-factores de riesgo han sido asociados consistentemente con displasia cervical y cáncer invasor. Es necesario un mayor número de investigaciones que utilicen diseños de cohorte prospectivos para describir el proceso de carcinogénesis y el mecanismo biológico de cada uno de estos factores. Adicionalmente, futuras investigaciones serán necesarias para definir el papel de los anticonceptivos hormonales en la promoción de la carcinogénesis cervical. Mientras que muchas preguntas científicas interesantes permanecen sin ser respondidas, resultados de numerosos estudios epidemiológicos que se desarrollan actualmente, indican que la displasia cervical y cáncer podrán ser reducidos si la tasa de oxidantes-antioxidantes es cambiada a más de un perfil antioxidante. Además de la detección oportuna de cáncer cervical, puede lograrse una reducción de la incidencia de esta enfermedad disminuyendo el consumo de tabaco, incrementando el estatus nutricional, y

  8. Perfil epidemiológico de pacientes atendidos em um Serviço de Controle da Dor Orofacial

    Directory of Open Access Journals (Sweden)

    Alana Moura Xavier Dantas

    Full Text Available ResumoIntroduçãoA Disfunção Temporomandibular (DTM se manifesta clinicamente como diversos problemas envolvendo a musculatura mastigatória, as articulações temporomandibulares e/ou suas estruturas associadas. Atualmente, essas disfunções apresentam elevada prevalência na população e afetam a qualidade de vida de seus portadores.ObjetivoDescrever as principais características e os sinais e sintomas de pacientes atendidos em um serviço especializado de Dor Orofacial.Material e métodoA pesquisa foi realizada no Ambulatório do Serviço de Controle da Dor Orofacial do Hospital Universitário de uma universidade federal, contendo uma amostra de 236 fichas de pacientes atendidos no período entre 2005 e 2011. Realizou-se a coleta de dados contidos na ficha clínica específica do serviço, elaborada pelos próprios pesquisadores com base no RDC/TMD e no Índice Anamnésico Simplificado de Fonseca. A ficha clínica foi elaborada de acordo com a realidade deste ambulatório e dos seus pacientes, para facilitar o diagnóstico destas desordens. Em seguida, foi procedida a análise descritiva dos dados.ResultadoEntre os pacientes atendidos, houve predomínio do gênero feminino, faixa etária entre 41 a 60 anos, grau de escolaridade Ensino Médio completo, vínculo empregatício e encaminhamento por cirurgiões-dentistas. A presença de dor diária com intensidade 5 e dor do tipo pulsátil, e o cansaço muscular foram as características mais prevalentes.ConclusãoDe acordo com os resultados obtidos, pode-se concluir que as mulheres procuram mais o serviço especializado e que os pacientes com DTM normalmente possuem elevados níveis de tensão e dor, sendo necessário um tratamento multidisciplinar.

  9. Prevalência de dor musculoesquelética em professores Prevalence of musculoskeletal pain among teachers

    Directory of Open Access Journals (Sweden)

    Jefferson Paixão Cardoso

    2009-12-01

    Full Text Available Este artigo descreve a prevalência de dor musculoesquelética segundo variáveis sociodemográficas e ocupacionais de professores do ensino básico. Um estudo epidemiológico de corte transversal, de caráter censitário, incluiu todos os 4.496 professores do ensino fundamental da rede municipal de Salvador, Bahia, Brasil. As prevalências de dor musculoesquelética em membros inferiores (41,1%, membros superiores (23,7% e dorso (41,1% foram elevadas. A prevalência global de dor musculoesquelética relacionada a qualquer um dos três segmentos corporais foi de 55%. A dor musculoesquelética foi mais prevalente, nos três segmentos investigados, entre as mulheres, os mais velhos, de nível educacional médio, casados, com três ou mais filhos e que trabalhavam mais de quatorze anos como docente. A prevalência de dor músculoesquelética associou-se às seguintes variáveis ocupacionais: tempo de trabalho superior a cinco anos na escola estudada, elevado esforço físico, outra atividade remunerada não docente e calor em sala de aula. Esses achados alertam para a necessidade de adoção de políticas públicas para melhoria das condições de trabalho do professor.The article describes the prevalence of musculoskeletal pain according to socio-demographic and occupational variables among elementary school teachers. A cross-sectional study included all 4,496 school teachers of the municipal elementary education network of Salvador, Bahia, Brazil. There was a high prevalence of musculoskeletal pain in lower limbs (41.1%, upper limbs (23.7% and back (41.1%. The overall prevalence of musculoskeletal pain related to any of the three body segments was 55%. Musculoskeletal pain was more prevalent in the three body segments investigated: among women, the elderly, those with high-level school education, married, with three or more children, and who had worked over fourteen years as teachers. The prevalence of musculoskeletal pain was associated with the

  10. Dor crônica em pacientes esquizofrênicos: prevalência e características Chronic pain in schizophrenic patients: prevalence and characteristics

    Directory of Open Access Journals (Sweden)

    Jouce Gabriela de Almeida

    2010-03-01

    Full Text Available A prevalência de dor crônica entre pacientes com transtornos psiquiátricos é, possivelmente, no mínimo igual à encontrada entre a população geral. Para estimar a prevalência de dor crônica em pacientes com esquizofrenia, comparar os grupos com e sem dor crônica e caracterizar a dor foi realizado um estudo transversal, com uma amostra probabilística de 205 pacientes adultos, com diagnóstico de esquizofrenia (idade média 37 anos; 65% homens; média de escolaridade de nove anos; 87% sem companheiro(a; 65% residentes com os pais, atendidos em hospital público do Município de São Paulo, Brasil. A prevalência de dor foi de 36,6%; a dor foi mais presente no abdômen (30,7%, seguida da dor de cabeça, face e boca (24% e região lombar, sacra e cóccix (14,7%. Com relação à freqüência, 24% dos entrevistados referiram ter dor todos os dias. O tempo médio de dor foi de 41 meses, com intensidade moderada. A prevalência de dor crônica em pacientes esquizofrênicos foi semelhante à encontrada para a população geral, e o quadro álgico foi significativo em termos de duração, intensidade e freqüência dos episódios dolorosos.Chronic pain may be at least as prevalent in psychiatric patients as in the general population. To estimate the prevalence of chronic pain in schizophrenic patients, compare the groups with and without chronic pain, and characterize the pain, a cross-sectional study was performed on a probabilistic sample of 205 adult patients with a diagnosis of schizophrenia (mean age 37 years; 65% men; mean schooling nine years; 87% single; 65% living with parents, treated at a public hospital in the city of São Paulo, Brazil. Prevalence of pain was 36.6%, and the most frequent sites were abdomen (30.7%, head, face, and mouth (24%, and lower back (14.7%. Twenty-four percent of patients reported feeling pain every day. Mean duration of pain was 41 months, with moderate intensity. Prevalence of chronic pain in

  11. ESTUDO DA FARMACOTERAPIA DA DOR EM PACIENTES PÓS-CIRÚRGICOS DO HOSPITAL DE CLÍNICAS DA UNIVERSIDADE FEDERAL DO PARANÁ

    Directory of Open Access Journals (Sweden)

    Vladimir ANTONINI, Elizabeth TAMBARA, Marcelo Martins BAVIERA, Carolina Rizzoni SILVEIRA, Eduardo Dias de SOUZA

    2013-12-01

    Full Text Available A dor pós-operatória é uma dor aguda de difícil controle efetivo. O objetivo deste estudo foi avaliar, comparativamente com a literatura internacional, a incidência de dor pós-operatória nos pacientes submetidos a operações do aparelho digestivo, tratados com os analgésicos e anti-inflamatórios padronizados no Hospital de Clínicas da UFPR. Cem pacientes de ambos os sexos, com idade entre 19 e 65 anos, foram acompanhados desde a Unidade de Recuperação Pós-Anestésica Imediata até a alta hospitalar, ou até 72 horas após a cirurgia, através de ensaio duplamente encoberto com perguntas verbais sobre a presença e a intensidade da dor. Foi comparado o índice de dor dos pacientes que receberam dipirona e dipirona associada a cetoprofeno ou dipirona associada a tramadol ou dipirona associada a cetoprofeno e tramadol nos momentos determinados. De 91 pacientes analisados na Unidade de Recuperação Pós-anestésica Imediata, 33 reportaram dor. Entre os 93 pacientes observados desde o retorno à unidade de internação até a primeira administração de medicação do dia seguinte, 30 apresentaram dor. No primeiro dia do período pós operatório, 93 pacientes foram acompanhados, sendo encontrados 24 pacientes com dor. No segundo dia, de 37 pacientes internados, 11 continuavam com dor. Não houve diferença estatisticamente significativa entre os pacientes que receberam dipirona isolada ou associada a outros medicamentos. O presente estudo demonstrou que a incidência de dor aguda contínua pós-operatória nos pacientes do Hospital de Clínicas da Universidade Federal do Paraná tratados com os analgésicos e antiinflamatórios padronizados foi de trinta por cento, margem mínima indicada na literatura internacional.

  12. Comorbidade de sintomas ansiosos e depressivos em pacientes com dor crônica e o impacto sobre a qualidade de vida

    Directory of Open Access Journals (Sweden)

    Martha M. C. Castro

    2011-01-01

    Full Text Available CONTEXTO: Dor é uma experiência emocional e sensorial desagradável. Tanto a dor crônica como a depressão reduzem de forma significativa a qualidade de vida, além de aumentar muito os custos dos cuidados com a saúde. OBJETIVOS: Analisar a associação entre sintomas depressivos e de ansiedade em relação à dor crônica e investigar o impacto desses sintomas na saúde e na qualidade de vida em indivíduos com dor crônica. MÉTODOS: A dor foi avaliada por meio de uma Escala Analógica Visual (VAS. Os sintomas depressivos e a ansiedade foram avaliados pela Escala Hospitalar de Ansiedade e Depressão (HAD. A qualidade de vida foi avaliada por meio do SF-36. RESULTADOS: Quatrocentos pacientes foram estudados, com idade média de 45,6 ± 11,4 anos e 82,8% são do sexo feminino. De acordo com a HAD, 70% tinham ansiedade e 60%, os sintomas de depressão. A SF-36 apresentou escores < 50% para todos os domínios. Os pacientes com dor intensa/ extrema apresentaram maior frequência (70,4% de ansiedade do que aqueles com dor selvagem/moderada (59,5%. Essa foi uma associação estatisticamente significante (p = 0,027. No entanto, a frequência de depressão não atingiu significância estatística quando ambos os grupos foram comparados (p = 0,109. CONCLUSÃO: Os sintomas depressivos/ansiedade e dor, em conjunto, apresentaram piores desfechos clínicos de cada estado sozinho. É necessária mais investigação para determinar se o tratamento da dor ajuda os sintomas dos pacientes depressivos e se o alívio dos sintomas depressivos melhora a dor e sua morbidade.

  13. Discovery and validation of information theory-based transcription factor and cofactor binding site motifs.

    Science.gov (United States)

    Lu, Ruipeng; Mucaki, Eliseos J; Rogan, Peter K

    2017-03-17

    Data from ChIP-seq experiments can derive the genome-wide binding specificities of transcription factors (TFs) and other regulatory proteins. We analyzed 765 ENCODE ChIP-seq peak datasets of 207 human TFs with a novel motif discovery pipeline based on recursive, thresholded entropy minimization. This approach, while obviating the need to compensate for skewed nucleotide composition, distinguishes true binding motifs from noise, quantifies the strengths of individual binding sites based on computed affinity and detects adjacent cofactor binding sites that coordinate with the targets of primary, immunoprecipitated TFs. We obtained contiguous and bipartite information theory-based position weight matrices (iPWMs) for 93 sequence-specific TFs, discovered 23 cofactor motifs for 127 TFs and revealed six high-confidence novel motifs. The reliability and accuracy of these iPWMs were determined via four independent validation methods, including the detection of experimentally proven binding sites, explanation of effects of characterized SNPs, comparison with previously published motifs and statistical analyses. We also predict previously unreported TF coregulatory interactions (e.g. TF complexes). These iPWMs constitute a powerful tool for predicting the effects of sequence variants in known binding sites, performing mutation analysis on regulatory SNPs and predicting previously unrecognized binding sites and target genes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. How Diverse are the Protein-Bound Conformations of Small-Molecule Drugs and Cofactors?

    Science.gov (United States)

    Friedrich, Nils-Ole; Simsir, Méliné; Kirchmair, Johannes

    2018-03-01

    Knowledge of the bioactive conformations of small molecules or the ability to predict them with theoretical methods is of key importance to the design of bioactive compounds such as drugs, agrochemicals and cosmetics. Using an elaborate cheminformatics pipeline, which also evaluates the support of individual atom coordinates by the measured electron density, we compiled a complete set (“Sperrylite Dataset”) of high-quality structures of protein-bound ligand conformations from the PDB. The Sperrylite Dataset consists of a total of 10,936 high-quality structures of 4548 unique ligands. Based on this dataset, we assessed the variability of the bioactive conformations of 91 small molecules—each represented by a minimum of ten structures—and found it to be largely independent of the number of rotatable bonds. Sixty-nine molecules had at least two distinct conformations (defined by an RMSD greater than 1 Å). For a representative subset of 17 approved drugs and cofactors we observed a clear trend for the formation of few clusters of highly similar conformers. Even for proteins that share a very low sequence identity, ligands were regularly found to adopt similar conformations. For cofactors, a clear trend for extended conformations was measured, although in few cases also coiled conformers were observed. The Sperrylite Dataset is available for download from http://www.zbh.uni-hamburg.de/sperrylite_dataset.

  15. Human HOX Proteins Use Diverse and Context-Dependent Motifs to Interact with TALE Class Cofactors.

    Science.gov (United States)

    Dard, Amélie; Reboulet, Jonathan; Jia, Yunlong; Bleicher, Françoise; Duffraisse, Marilyne; Vanaker, Jean-Marc; Forcet, Christelle; Merabet, Samir

    2018-03-13

    HOX proteins achieve numerous functions by interacting with the TALE class PBX and MEIS cofactors. In contrast to this established partnership in development and disease, how HOX proteins could interact with PBX and MEIS remains unclear. Here, we present a systematic analysis of HOX/PBX/MEIS interaction properties, scanning all paralog groups with human and mouse HOX proteins in vitro and in live cells. We demonstrate that a previously characterized HOX protein motif known to be critical for HOX-PBX interactions becomes dispensable in the presence of MEIS in all except the two most anterior paralog groups. We further identify paralog-specific TALE-binding sites that are used in a highly context-dependent manner. One of these binding sites is involved in the proliferative activity of HOXA7 in breast cancer cells. Together these findings reveal an extraordinary level of interaction flexibility between HOX proteins and their major class of developmental cofactors. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. Neutrino mass matrices with two vanishing cofactors and Fritzsch texture for charged lepton mass matrix

    Science.gov (United States)

    Wang, Weijian; Guo, Shu-Yuan; Wang, Zhi-Gang

    2016-04-01

    In this paper, we study the cofactor 2 zero neutrino mass matrices with the Fritzsch-type structure in charged lepton mass matrix (CLMM). In the numerical analysis, we perform a scan over the parameter space of all the 15 possible patterns to get a large sample of viable scattering points. Among the 15 possible patterns, three of them can accommodate the latest lepton mixing and neutrino mass data. We compare the predictions of the allowed patterns with their counterparts with diagonal CLMM. In this case, the severe cosmology bound on the neutrino mass set a strong constraint on the parameter space, rendering two patterns only marginally allowed. The Fritzsch-type CLMM will have impact on the viable parameter space and give rise to different phenomenological predictions. Each allowed pattern predicts the strong correlations between physical variables, which is essential for model selection and can be probed in future experiments. It is found that under the no-diagonal CLMM, the cofactor zeros structure in neutrino mass matrix is unstable as the running of renormalization group (RG) from seesaw scale to the electroweak scale. A way out of the problem is to propose the flavor symmetry under the models with a TeV seesaw scale. The inverse seesaw model and a loop-induced model are given as two examples.

  17. Live Cell Discovery of Microbial Vitamin Transport and Enzyme-Cofactor Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Lindsey N.; Koech, Phillip K.; Plymale, Andrew E.; Landorf, Elizabeth V.; Konopka, Allan; Collart, Frank; Lipton, Mary S.; Romine, Margaret F.; Wright, Aaron T.

    2016-02-02

    The rapid completion of microbial genomes is inducing a conundrum in functional gene discovery. Novel methods are critically needed to shorten the gap between characterizing a microbial genome and experimentally validating bioinformatically-predicted functions. Of particular importance are transport mechanisms, used to shuttle nutrients and metabolites across cell mem-branes, such as B vitamins, which are indispensable to metabolic reactions crucial to the survival of diverse microbes ranging from members of environmental microbial communities to human pathogens. Methods to accurately assign function and specificity for a wide range of experimentally unidentified and/or predicted membrane-embedded transport proteins, and characterization of intra-cellular enzyme-cofactor/nutrient associations are needed to enable a significantly improved understanding of microbial biochemis-try and physiology, how microbes associate with others, and how they sense and respond to environmental perturbations. Chemical probes derived from B vitamins B1, B2, and B7 have allowed us to experimentally address the aforementioned needs by identifying B vitamin transporters and intracellular protein-cofactor associations through live cell labeling of the filamentous anoxygenic pho-toheterotroph, Chloroflexus aurantiacus J-10-fl, known for both B vitamin biosynthesis and environmental salvage. Our probes provide a unique opportunity to directly link cellular activity and protein function back to ecosystem and/or host dynamics by iden-tifying B vitamin transport and disposition mechanisms required for survival.

  18. Influence of common mucosal co-factors on HIV infection in the female genital tract.

    Science.gov (United States)

    Ferreira, Victor H; Kafka, Jessica K; Kaushic, Charu

    2014-06-01

    Women constitute almost half of HIV-infected population globally, and the female genital tract (FGT) accounts for approximately 40% of all new HIV infections worldwide. The FGT is composed of upper and lower parts, distinct in their morphological and functional characteristics. Co-factors in the genital microenvironment, such as presence of hormones, semen, and other sexually transmitted infections, can facilitate or deter HIV infection and play a critical role in determining susceptibility to HIV. In this review, we examine some of these co-factors and their potential influence. Presence of physical and chemical barriers such as epithelial tight junctions, mucus, and anti-microbial peptides can actively block and inhibit viral replication, presenting a significant deterrent to HIV. Upon exposure, HIV and other pathogens first encounter the genital epithelium: cells that express a wide repertoire of pattern recognition receptors that can recognize and directly initiate innate immune responses. These and other interactions in the genital tract can lead to direct and indirect inflammation and enhance the number of local target cells, immune activation, and microbial translocation, all of which promote HIV infection and replication. Better understanding of the dynamics of HIV transmission in the female genital tract would be invaluable for improving the design of prophylactic strategies against HIV. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Deducing the temporal order of cofactor function in ligand-regulated gene transcription: theory and experimental verification.

    Science.gov (United States)

    Dougherty, Edward J; Guo, Chunhua; Simons, S Stoney; Chow, Carson C

    2012-01-01

    Cofactors are intimately involved in steroid-regulated gene expression. Two critical questions are (1) the steps at which cofactors exert their biological activities and (2) the nature of that activity. Here we show that a new mathematical theory of steroid hormone action can be used to deduce the kinetic properties and reaction sequence position for the functioning of any two cofactors relative to a concentration limiting step (CLS) and to each other. The predictions of the theory, which can be applied using graphical methods similar to those of enzyme kinetics, are validated by obtaining internally consistent data for pair-wise analyses of three cofactors (TIF2, sSMRT, and NCoR) in U2OS cells. The analysis of TIF2 and sSMRT actions on GR-induction of an endogenous gene gave results identical to those with an exogenous reporter. Thus new tools to determine previously unobtainable information about the nature and position of cofactor action in any process displaying first-order Hill plot kinetics are now available.

  20. Cofactor Editing by the G-protein Metallochaperone Domain Regulates the Radical B12 Enzyme IcmF.

    Science.gov (United States)

    Li, Zhu; Kitanishi, Kenichi; Twahir, Umar T; Cracan, Valentin; Chapman, Derrell; Warncke, Kurt; Banerjee, Ruma

    2017-03-10

    IcmF is a 5'-deoxyadenosylcobalamin (AdoCbl)-dependent enzyme that catalyzes the carbon skeleton rearrangement of isobutyryl-CoA to butyryl-CoA. It is a bifunctional protein resulting from the fusion of a G-protein chaperone with GTPase activity and the cofactor- and substrate-binding mutase domains with isomerase activity. IcmF is prone to inactivation during catalytic turnover, thus setting up its dependence on a cofactor repair system. Herein, we demonstrate that the GTPase activity of IcmF powers the ejection of the inactive cob(II)alamin cofactor and requires the presence of an acceptor protein, adenosyltransferase, for receiving it. Adenosyltransferase in turn converts cob(II)alamin to AdoCbl in the presence of ATP and a reductant. The repaired cofactor is then reloaded onto IcmF in a GTPase-gated step. The mechanistic details of cofactor loading and offloading from the AdoCbl-dependent IcmF are distinct from those of the better characterized and homologous methylmalonyl-CoA mutase/G-protein chaperone system. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. La Rencontre à la Porte dorée. Image, texte et contexte

    Directory of Open Access Journals (Sweden)

    Réjane Gay-Canton

    2012-04-01

    Full Text Available À travers l’analyse d’une série de manuscrits allemands illustrés entre le dernier quart du xive siècle et la seconde moitié du xve siècle, l’essai montre que seules de rares images de la Rencontre d’Anne et Joachim à la Porte dorée renvoient à l’Immaculée Conception. Lors de son intégration à la Weltchronik de Heinrich von München et à la Historienbibel, le Marienleben de Bruder Philipp conserve sa position maculiste. Mais dans le second texte, l’image de la Rencontre à la Porte dorée prend une signification différente par l’ajout ou la suppression d’un titulus mentionnant le baiser fécondant. Après avoir observé les résonnances de ces changements sur l’image et souligné l’indépendance de cette dernière face au texte narratif comme à la doctrine théologique, l’essai revient sur l’origine de l’idée du baiser fécondant. Il indique qu’elle n’est ni directement issue des premiers textes littéraires de la conception de Marie que sont les récits apocryphes chrétiens, ni des développements théologiques, mais bien d’un amalgame entre ces deux supports et l’image de la Rencontre à la Porte dorée. L’idée du baiser fécondant reste le propre des illitterati qui trouvèrent en elle un moyen de contourner la théorie augustienne de la transmission du péché originel en attribuant à la future mère de Dieu une conception exempte de toute concupiscence charnelle. Lue sous ce prisme, l’image devient le lieu de projection de l’image mentale. Elle est alors chargée d’un sens nouveau et vient dialoguer avec le texte qu’elle n’illustre plus, mais dont elle offre une lecture parallèle. Au final, seule sa mise en contexte permet de déterminer, au cas par cas, si l’image de la Rencontre renvoie au baiser fécondant et ainsi à l’Immaculée Conception.By analysing a series of illustrated German manuscripts between the last quarter of the xivth century and the second half of the

  2. Quantification of methanogenic biomass by enzyme-linked immunosorbent assay and by analysis of specific methanogenic cofactors

    Energy Technology Data Exchange (ETDEWEB)

    Gorris, L G.M.; Kemp, H A; Archer, D B

    1987-01-01

    The reliability and accuracy with which enzyme-linked immunosorbent assay (ELISA) and an assay of methanogenic cofactors detect and quantify methanogenic species were investigated. Both assays required standardization with laboratory cultures of methanogenic bacteria and were applied to mixtures of pure cultures and samples from anaerobic digesters. ELISA was shown to be a simple method for detecting and quantifying individual methanogenic species. The range of species which can be assayed is limited by the range of antisera available but, potentially, ELISA can be applied to all methanogens. Although the cofactor assay is not species-specific it can distinguish hydrogenotrophic and acetotrophic methanogens and is quantitative.

  3. The γ Dor stars as revealed by Kepler: A key to reveal deep-layer rotation in A and F stars

    Directory of Open Access Journals (Sweden)

    Salmon S. J. A. J.

    2017-01-01

    Full Text Available The γ Dor pulsating stars present high-order gravity modes, which make them important targets in the intermediate-and low-mass main-sequence region of the Hertzsprung-Russell diagram. Whilst we have only access to rotation in the envelope of the Sun, the g modes of γ Dor stars can in principle deliver us constraints on the inner layers. With the puzzling discovery of unexpectedly low rotation rates in the core of red giants, the γ Dor stars appear now as unique targets to explore internal angular momentum transport in the progenitors of red giants. Yet, the γ Dor pulsations remain hard to detect from the ground for their periods are close to 1 day. While the CoRoT space mission first revealed intriguing frequency spectra, the almost uninterrupted 4-year photometry from the Kepler mission eventually shed a new light on them. It revealed regularities in the spectra, expected to bear signature of physical processes, including rotation, in the shear layers close to the convective core. We present here the first results of our effort to derive exploitable seismic diagnosis for mid- to fast rotators among γ Dor stars. We confirm their potential to explore the rotation history of this early phase of stellar evolution.

  4. Randomized controlled trial of laparoscopic Heller myotomy plus Dor fundoplication versus Nissen fundoplication for achalasia: long-term results.

    Science.gov (United States)

    Rebecchi, Fabrizio; Giaccone, Claudio; Farinella, Eleonora; Campaci, Roberto; Morino, Mario

    2008-12-01

    To compare in a prospective, randomized trial the long-term results of laparoscopic Heller myotomy plus Dor fundoplication versus laparoscopic Heller myotomy plus floppy-Nissen for achalasia. Anterior fundoplication is usually performed after Heller myotomy to control GER; however, the incidence of postoperative GER ranges between 10% and 30%. Total fundoplication may aid in reducing GER rates. From December 1993 to September 2002, 153 patients with achalasia underwent Heller laparoscopic myotomy plus antireflux fundoplication. Of these, 9 were excluded from the study. The remaining 144 patients were randomly assigned to 2 treatment groups: Heller laparoscopic myotomy plus anterior fundoplication (Dor procedure) or Heller laparoscopic myotomy plus total fundoplication (floppy-Nissen procedure). The primary end point was incidence of clinical and instrumental GER after a minimum of 60 months follow-up. The secondary end point was recurrence of dysphagia. Follow-up clinical assessments were performed at 1, 3, 12, and 60 months using a modified DeMeester Symptom Scoring System (MDSS). Esophageal manometry and 24-hour pH monitoring were performed at 3, 12, and 60 months postoperative. Of the 144 patients originally included in the study, 138 were available for long-term analysis: 71 (51%) underwent antireflux fundoplication plus a Dor procedure (H + D group) and 67 (49%) antireflux fundoplication plus a Nissen procedure (H + N group). No mortality was observed. The mean follow-up period was 125 months. No statistically significant differences in clinical (5.6% vs. 0%) or instrumental GER (2.8% vs. 0%) were found between the 2 groups; however, a statistically significant difference in dysphagia rates was noted (2.8% vs. 15%; P Heller myotomy.

  5. Opióides no manejo da dor - uso correto ou subestimado? Dados de um hospital universitário

    Directory of Open Access Journals (Sweden)

    Daudt A.W.

    1998-01-01

    Full Text Available OBJETIVO: O uso de opióides, principalmente no tratamento da dor intensa aguda (pacientes no pós-operatório e da dor crônica em pacientes oncológicos, tem sido subestimado na prática clínica em geral. Este trabalho tem o objetivo de verificar o perfil de prescrição de opióides (meperidina e morfina no Hospital de Clínicas de Porto Alegre (HCPA, RS. MATERIAIS E MÉTODOS: Análise da conduta das equipes médicas, pela revisão de 1.107 prescrições, relativas a 445 pacientes internados no HCPA, entre 20 de maio e 20 de julho de 1993. Os parâmetros básicos de análise, para conduta, incluíam: padrão de uso, a dose do fármaco, intervalo entre doses e analgésicos simultâneos. DISCUSSÃO E RESULTADOS: Foram encontradas apenas 6,5% de prescrições consideradas adequadas em relação aos parâmetros dose, intervalo e padrão, analisados conjuntamente. O padrão se necessário foi responsável por 74% do total de prescrições. CONCLUSÕES: Os resultados obtidos durante a realização do trabalho permitem-nos concluir que não há um manejo adequado da dor, tanto aguda como crônica, nos pacientes internados no HCPA.

  6. Halogens are key cofactors in building of collagen IV scaffolds outside the cell.

    Science.gov (United States)

    Brown, Kyle L; Hudson, Billy G; Voziyan, Paul A

    2018-05-01

    The purpose of this review is to highlight recent advances in understanding the molecular assembly of basement membranes, as exemplified by the glomerular basement membrane (GBM) of the kidney filtration apparatus. In particular, an essential role of halogens in the basement membrane formation has been discovered. Extracellular chloride triggers a molecular switch within non collagenous domains of collagen IV that induces protomer oligomerization and scaffold assembly outside the cell. Moreover, bromide is an essential cofactor in enzymatic cross-linking that reinforces the stability of scaffolds. Halogenation and halogen-induced oxidation of the collagen IV scaffold in disease states damage scaffold function. Halogens play an essential role in the formation of collagen IV scaffolds of basement membranes. Pathogenic damage of these scaffolds by halogenation and halogen-induced oxidation is a potential target for therapeutic interventions.

  7. Roles of Fe-S proteins: from cofactor synthesis to iron homeostasis to protein synthesis.

    Science.gov (United States)

    Pain, Debkumar; Dancis, Andrew

    2016-06-01

    Fe-S cluster assembly is an essential process for all cells. Impairment of Fe-S cluster assembly creates diseases in diverse and surprising ways. In one scenario, the loss of function of lipoic acid synthase, an enzyme with Fe-S cluster cofactor in mitochondria, impairs activity of various lipoamide-dependent enzymes with drastic consequences for metabolism. In a second scenario, the heme biosynthetic pathway in red cell precursors is specifically targeted, and iron homeostasis is perturbed, but lipoic acid synthesis is unaffected. In a third scenario, tRNA modifications arising from action of the cysteine desulfurase and/or Fe-S cluster proteins are lost, which may lead to impaired protein synthesis. These defects can then result in cancer, neurologic dysfunction or type 2 diabetes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Proteolytic activation transforms heparin cofactor II into a host defense molecule.

    Science.gov (United States)

    Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; Tollefsen, Douglas M; Malmsten, Martin; Mörgelin, Matthias; Schmidtchen, Artur

    2013-06-15

    The abundant serine proteinase inhibitor heparin cofactor II (HCII) has been proposed to inhibit extravascular thrombin. However, the exact physiological role of this plasma protein remains enigmatic. In this study, we demonstrate a previously unknown role for HCII in host defense. Proteolytic cleavage of the molecule induced a conformational change, thereby inducing endotoxin-binding and antimicrobial properties. Analyses employing representative peptide epitopes mapped these effects to helices A and D. Mice deficient in HCII showed increased susceptibility to invasive infection by Pseudomonas aeruginosa, along with a significantly increased cytokine response. Correspondingly, decreased levels of HCII were observed in wild-type animals challenged with bacteria or endotoxin. In humans, proteolytically cleaved HCII forms were detected during wounding and in association with bacteria. Thus, the protease-induced uncovering of cryptic epitopes in HCII, which transforms the molecule into a host defense factor, represents a previously unknown regulatory mechanism in HCII biology and innate immunity.

  9. Cofactor specificity switch in Shikimate dehydrogenase by rational design and consensus engineering.

    Science.gov (United States)

    García-Guevara, Fernando; Bravo, Iris; Martínez-Anaya, Claudia; Segovia, Lorenzo

    2017-08-01

    Consensus engineering has been used to design more stable variants using the most frequent amino acid at each site of a multiple sequence alignment; sometimes consensus engineering modifies function, but efforts have mainly been focused on studying stability. Here we constructed a consensus Rossmann domain for the Shikimate dehydrogenase enzyme; separately we decided to switch the cofactor specificity through rational design in the Escherichia coli Shikimate dehydrogenase enzyme and then analyzed the effect of consensus mutations on top of our design. We found that consensus mutations closest to the 2' adenine moiety increased the activity in our design. Consensus engineering has been shown to result in more stable proteins and our findings suggest it could also be used as a complementary tool for increasing or modifying enzyme activity during design. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Characterization of a "TRAMP-like" co-factor of the human RNA exosome

    DEFF Research Database (Denmark)

    Christensen, Marianne Skovgaard; Kristiansen, Maiken Søndergaard; Lubas, Michal Szymon

    Genome-wide studies in yeast, plants and humans have revealed numerous new transcripts in what was previously thought to be silent DNA or junk DNA. One class of non-coding transcript discovered recently is the PROMoter uPstream Transcripts (PROMPTs), which is only seen upon depletion of the RNA...... exosome, the major 3’-5’ exonuclease complex in human cells. PROMPTs have a lot in common with the yeast Cryptic Unstable Transcripts (CUTs), which are degraded by the concerted effort of the exosome, and its co-factor complex TRAMP (Trf4p/Air1p/Mtr4p). We have identified human proteins with functional...... similarities to components of the yeast TRAMP complex, and show that these are involved in the degradation of PROMPTs. While, these proteins form transient complexes with the exosome, our preliminary results also indicate that complex formation can occur directly with catalytic components of the exosome...

  11. Characterization of water-forming NADH oxidases for co-factor regeneration

    DEFF Research Database (Denmark)

    Rehn, Gustav; Pedersen, Asbjørn Toftgaard; J. Charnock, Simon

    an environmentaland economic perspective [1]. Alcohol dehydrogenases (ADH) offer one such alternative. However, the reaction requires the oxidized nicotinamide co-factor (NAD+) that must be recycled due to its high cost contribution. One regeneration method that offers certain advantages is the oxidation of NADH......Traditional chemical methods for alcohol oxidation are often associated with issues such as high consumption of expensive oxidizing agents, generation of metal waste and the use of environmentally undesirable organic solvents. Developing green, selective catalysts is therefore important from...... using water forming NADH oxidases (NOX-2). The implementation of the ADH/NOX system for alcohol oxidation, however, requires consideration of several different issues. Enzyme activity and stability at relevant pH and temperature conditions, but also the tolerance to the substrates and products present...

  12. Substrate- and Cofactor-independent Inhibition of Histone Demethylase KDM4C

    DEFF Research Database (Denmark)

    Leurs, Ulrike; Lohse, Brian; Rand, Kasper Dyrberg

    2014-01-01

    Inhibition of histone demethylases has within recent years advanced into a new strategy for treating cancer and other diseases. Targeting specific histone demethylases can be challenging as the active sites of KDM1A-B and KDM-4A-D histone demethylases, respectively, are highly conserved. Most...... inhibitors developed up-to-date target either the cofactor- or substrate-binding sites of these enzymes, resulting in a lack of selectivity and off-target effects. This study describes the discovery of the first peptide-based inhibitors of KDM4 histone demethylases that do not share the histone peptide...... sequence, or inhibit through substrate competition. Through screening of DNA-encoded peptide libraries against KDM1 and -4 histone demethylases by phage display, two cyclic peptides targeting the histone demethylase KDM4C were identified and developed as inhibitors by amino acid replacement, truncation...

  13. Identification and Characterization of the Novel p97 co-factors, Rep8 and ASPL

    DEFF Research Database (Denmark)

    Klausen, Louise Kjær

    to the ER membrane with the UBX domain situated in the cytosol. Mouse Rep8 is highly tissue-specific and abundant in gonads. In tests, Rep8 is expressed in post-meiotic round spermatids, whereas in ovaries Rep8 is expressed in granulosa cells. Additional precipitation experiments revealed that Rep8......The highly conserved and ubiquitin-specific AAA ATPase p97 acts on ubiquitylated substrates in diverse cellular mechanisms such as chromatin-associated degradation, fusion of homotypic membranes and ER-associated degradation. Different p97 cofactors associate with the ATPase, thereby constituting...... that ASPL localizes to the ER membrane and in vitro ASPL leads to disassembly of the p97 hexameric ATPase. Rep8 was found to interact with p97 both in vitro and in vivo, and the binding was mediated through the N-domain of p97 and the UBX domain of Rep8. Localization studies showed that Rep8 localizes...

  14. Income poverty, poverty co-factors, and the adjustment of children in elementary school.

    Science.gov (United States)

    Ackerman, Brian P; Brown, Eleanor D

    2006-01-01

    Since 1990, there have been great advances in how developmental researchers construct poverty. These advances are important because they may help inform social policy at many levels and help frame how American culture constructs poverty for children, both symbolically and in the opportunities children and families get to escape from poverty. Historically, developmental perspectives have embodied social address and main effects models, snapshot views of poverty effects at single points in time, and a rather narrow focus on income as the symbolic marker of the ecology of disadvantage. More recent views, in contrast, emphasize the diverse circumstances of disadvantaged families and diverse outcomes of disadvantaged children, the multiple sources of risk and the multiple determinants of poor outcomes for these children, dynamic aspects of that ecology, and change as well as continuity in outcome trajectories. The advances also consist of more powerful frames for understanding the ecology of disadvantage and the risk it poses for child outcomes. Most developmental researchers still tend to frame causal variables ultimately in terms of the dichotomy between social causation and social selection views, with a primary emphasis on the former. In part, this framing has reflected limitations of sample size and design, because the theoretical and empirical power of reciprocal selection models is clear (Kim et al., 2003). The conceptual advances that prompt such models include widespread acknowledgement of third variable problems in interpreting effects, of the clear need for multivariate approaches, and the need to pursue mechanisms and moderators of the relations between causal candidates and child outcomes. In the context of these advances, one of the core goals of our research program has been to construct robust representations of environmental adversity for disadvantaged families. Most of our research focuses on contextual co-factors at a family level (e.g., maternal

  15. Fluorescence spectroscopy studies of HEK293 cells expressing DOR-Gi1alfa fusion protein; the effect of cholesterol depletion

    Czech Academy of Sciences Publication Activity Database

    Brejchová, Jana; Sýkora, Jan; Dlouhá, Kateřina; Roubalová, Lenka; Ostašov, Pavel; Vošahlíková, Miroslava; Hof, Martin; Svoboda, Petr

    2011-01-01

    Roč. 1808, č. 12 (2011), s. 2819-2829 ISSN 0005-2736 R&D Projects: GA MŠk(CZ) LC06063; GA MŠk(CZ) LC554; GA ČR(CZ) GD305/08/H037 Grant - others:GA ČR(CZ) GAP208/10/1090 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z40400503 Keywords : plasma membrane * cholesterol depletion * fluorescence spectroscopy * hydrophobic membrane interior * delta-opioid receptor ( DOR ), * G protein Subject RIV: BO - Biophysics Impact factor: 3.990, year: 2011

  16. Abordagem da dor pélvica crônica em mulheres Management of chronic pelvic pain in women

    Directory of Open Access Journals (Sweden)

    Antonio Alberto Nogueira

    2006-12-01

    Full Text Available Dor pélvica crônica é uma doença debilitante e de alta prevalência, com grande impacto na qualidade de vida e produtividade, além de custos significantes para os serviços de saúde. O dilema no manejo da dor pélvica crônica continua a frustrar médicos confrontados com o problema, em parte porque sua fisiopatologia é pobremente compreendida. Conseqüentemente, seu tratamento é muitas vezes insatisfatório e limitado ao alívio temporário dos sintomas. Nesta revisão, nós discutimos uma abordagem ampliada da dor pélvica crônica. Salientamos que uma história clínica e exame físico adequados deveriam incluir atenção especial aos sistemas gastrintestinal, urinário, ginecológico, músculo-esquelético, neurológico, psicológico e endócrino. Dessa forma, uma abordagem multidisciplinar é recomendada. Adicionalmente, enfatizamos que, embora úteis, procedimentos cirúrgicos específicos, tais como a laparoscopia, deveriam ser indicados somente para pacientes selecionadas, após excluir principalmente síndrome do intestino irritável e dor de origem miofascial.Chronic pelvic pain is a debilitating and highly prevalent disease with a major impact on quality of life and work productivity, beyond significant costs to health services. The dilemma of managing patients with chronic pelvic pain continues to frustrate physicians confronted with these complaints, in part because its pathophysiology is poorly understood. Consequently, its treatment is often unsatisfactory and limited to temporary symptom relief. In the present revision, we discuss the adequate management of chronic pelvic pain. We point out that a comprehensive medical history and physical examination should include special attention to gastrointestinal, urological, gynecological, muscle-skeletal, neurological, psychiatric, and endocrine systems. Thus, a multidisciplinary approach is recommended. Additionally, we emphasize that, although useful, specific surgical

  17. Rice Bran Metabolome Contains Amino Acids, Vitamins & Cofactors, and Phytochemicals with Medicinal and Nutritional Properties.

    Science.gov (United States)

    Zarei, Iman; Brown, Dustin G; Nealon, Nora Jean; Ryan, Elizabeth P

    2017-12-01

    Rice bran is a functional food that has shown protection against major chronic diseases (e.g. obesity, diabetes, cardiovascular disease and cancer) in animals and humans, and these health effects have been associated with the presence of bioactive phytochemicals. Food metabolomics uses multiple chromatography and mass spectrometry platforms to detect and identify a diverse range of small molecules with high sensitivity and precision, and has not been completed for rice bran. This study utilized global, non-targeted metabolomics to identify small molecules in rice bran, and conducted a comprehensive search of peer-reviewed literature to determine bioactive compounds. Three U.S. rice varieties (Calrose, Dixiebelle, and Neptune), that have been used for human dietary intervention trials, were assessed herein for bioactive compounds that have disease control and prevention properties. The profiling of rice bran by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) identified 453 distinct phytochemicals, 209 of which were classified as amino acids, cofactors & vitamins, and secondary metabolites, and were further assessed for bioactivity. A scientific literature search revealed 65 compounds with health properties, 16 of which had not been previously identified in rice bran. This suite of amino acids, cofactors & vitamins, and secondary metabolites comprised 46% of the identified rice bran metabolome, which substantially enhanced our knowledge of health-promoting rice bran compounds provided during dietary supplementation. Rice bran metabolite profiling revealed a suite of biochemical molecules that can be further investigated and exploited for multiple nutritional therapies and medical food applications. These bioactive compounds may also be biomarkers of dietary rice bran intake. The medicinal compounds associated with rice bran can function as a network across metabolic pathways and this

  18. Qualidade de vida após a cardiomiotomia à Heller-Dor

    Directory of Open Access Journals (Sweden)

    Fernando A.V. Madureira

    Full Text Available OBJETIVOS: Avaliar os resultados da cardiomiotomia de Heller associada à fundoplicatura de Dor por Laparoscopia (HDL no tratamento cirúrgico da acalásia do esôfago, através de escores de qualidade de vida e dados da esofagomanometria. MÉTODOS: Foram estudados retrospectivamente 60 pacientes operados por acalasia do cárdia, de 2001 a 2007, sendo analisadas no pré-operatório as características desta população e os resultados das provas diagnósticas. Aplicamos um escore de disfagia e de qualidade de vida no pré e pós-operatório e realizamos o estudo do comportamento da pressão do esfíncter esofageano inferior (Peei no pré e pós operatório de todos os pacientes. RESULTADOS: Eram 37 do sexo feminino e 23 do masculino. A idade média foi 41,08 anos(12 a 87. Não houve mortalidade cirúrgica, nem conversões. Tempo médio de início da dieta foi de 1,6 dias. Considerado resultado excelente em 80% da série, resultados intermediários em 20%. A média do escore de disfagia no pré operatório foi de 9,03 pontos e a média de pós, foi de 1,7 pontos (máximo de 10 pontos, p=0,0001, sendo observada queda entre pré e pós-operatório de 7,33 pontos, 81,17%. A média da Peei no pré-operatório foi de 32,41 mmhg e no pós 12,7 mmhg. CONCLUSÃO: A cirurgia HDL é procedimento seguro de ser realizado e apresentou bons resultados, sendo capaz de modificar os escores de qualidade de vida subjetivos, e os dados objetivos da Peei, de forma significativa.

  19. Protein S binding to human endothelial cells is required for expression of cofactor activity for activated protein C

    NARCIS (Netherlands)

    Hackeng, T. M.; Hessing, M.; van 't Veer, C.; Meijer-Huizinga, F.; Meijers, J. C.; de Groot, P. G.; van Mourik, J. A.; Bouma, B. N.

    1993-01-01

    An important feedback mechanism in blood coagulation is supplied by the protein C/protein S anticoagulant pathway. In this study we demonstrate that the binding of human protein S to cultured human umbilical vein endothelial cells (HUVECs) is required for the expression of cofactor activity of

  20. Música e dor crônica músculoesquelética: o potencial evocativo de imagens mentais

    Directory of Open Access Journals (Sweden)

    Leão Eliseth Ribeiro

    2004-01-01

    Full Text Available Noventa mulheres com diagnósticos de fibromialgia, lesão por esforços repetitivos/doenças osteoarticulares, relacionadas ao trabalho (LER/DORT, e afecções relacionadas à coluna vertebral foram submetidas à audição individual de três peças musicais. Os dados foram obtidos por meio de entrevista e a intensidade da dor foi avaliada pela escala numérica verbal (0-10 antes e ao término da audição musical. As imagens mentais foram quantificadas mediante a análise de desenhos realizados durante cada audição. Os três grupos apresentaram redução estatisticamente significativa da intensidade da dor ao final da audição musical (p<0,001. As imagens mentais não diferiram quantitativamente, entre Ravel e Wagner. O Mix apresentou resultados quantitativamente inferiores. As estruturas musicais se relacionaram à produção de imagens e o efeito terapêutico observado, sugerindo que análises nesse sentido podem contribuir para a utilização da música pela Enfermagem.

  1. Involvement of the Cys-Tyr cofactor on iron binding in the active site of human cysteine dioxygenase.

    Science.gov (United States)

    Arjune, Sita; Schwarz, Guenter; Belaidi, Abdel A

    2015-01-01

    Sulfur metabolism has gained increasing medical interest over the last years. In particular, cysteine dioxygenase (CDO) has been recognized as a potential marker in oncology due to its altered gene expression in various cancer types. Human CDO is a non-heme iron-dependent enzyme, which catalyzes the irreversible oxidation of cysteine to cysteine sulfinic acid, which is further metabolized to taurine or pyruvate and sulfate. Several studies have reported a unique post-translational modification of human CDO consisting of a cross-link between cysteine 93 and tyrosine 157 (Cys-Tyr), which increases catalytic efficiency in a substrate-dependent manner. However, the reaction mechanism by which the Cys-Tyr cofactor increases catalytic efficiency remains unclear. In this study, steady-state kinetics were determined for wild type CDO and two different variants being either impaired or saturated with the Cys-Tyr cofactor. Cofactor formation in CDO resulted in an approximately fivefold increase in k cat and tenfold increase in k cat/K m over the cofactor-free CDO variant. Furthermore, iron titration experiments revealed an 18-fold decrease in K d of iron upon cross-link formation. This finding suggests a structural role of the Cys-Tyr cofactor in coordinating the ferrous iron in the active site of CDO in accordance with the previously postulated reaction mechanism of human CDO. Finally, we identified product-based inhibition and α-ketoglutarate and glutarate as CDO inhibitors using a simplified well plate-based activity assay. This assay can be used for high-throughput identification of additional inhibitors, which may contribute to understand the functional importance of CDO in sulfur amino acid metabolism and related diseases.

  2. Diverse coactivator recruitment through differential PPARγ nuclear receptor agonism

    Directory of Open Access Journals (Sweden)

    Fernando Lizcano

    2013-01-01

    Full Text Available The PPARγ nuclear receptor regulates the expression of genes involved in lipid and carbohydrate metabolism, and it has protective effects in some patients with type 2 diabetes. Nevertheless, the therapeutic value of the PPARγ nuclear receptor protein is limited due to the secondary effects of some PPARγ ligands. Because the downstream effects of PPARγ are determined by the binding of specific cofactors that are mediated by ligand-induced conformational changes, we evaluated the differential effects of various ligands on the binding of certain cofactors associated with PPARγ. The ligands used were rosiglitazone for treating type 2 diabetes and telmisartan for treating arterial hypertension. Functional, phenotypic, and molecular studies were conducted on pre-adipocyte 3T3-L1 and functional studies in U2OS cells. The moderating influence of various cofactor families was evaluated using transient transfection assays. Our findings confirm that telmisartan has a partial modulating effect on PPARγ activity compared to rosiglitazone. The cofactors SRC1 and GRIP1 mediate the activity of telmisartan and rosiglitazone and partially determine the difference in their effects. Studying the modulating activity of these cofactors can provide interesting insights for developing new therapeutic approaches for certain metabolic diseases.

  3. Rational modification of Corynebacterium glutamicum dihydrodipicolinate reductase to switch the nucleotide-cofactor specificity for increasing l-lysine production.

    Science.gov (United States)

    Xu, Jian-Zhong; Yang, Han-Kun; Liu, Li-Ming; Wang, Ying-Yu; Zhang, Wei-Guo

    2018-03-25

    l-lysine is an important amino acid in animals and humans and NADPH is a vital cofactor for maximizing the efficiency of l-lysine fermentation. Dihydrodipicolinate reductase (DHDPR), an NAD(P)H-dependent enzyme, shows a variance in nucleotide-cofactor affinity in bacteria. In this study, we rationally engineered Corynebacterium glutamicum DHDPR (CgDHDPR) to switch its nucleotide-cofactor specificity resulting in an increase in final titer (from 82.6 to 117.3 g L -1 ), carbon yield (from 0.35 to 0.44 g [g glucose] -1 ) and productivity (from 2.07 to 2.93 g L -1  hr -1 ) of l-lysine in JL-6 ΔdapB::Ec-dapB C115G,G116C in fed-batch fermentation. To do this, we comparatively analyzed the characteristics of CgDHDPR and Escherichia coli DHDPR (EcDHDPR), indicating that hetero-expression of NADH-dependent EcDHDPR increased l-lysine production. Subsequently, we rationally modified the conserved structure of cofactor-binding motif, and results indicated that introducing the mutation K11A or R13A in CgDHDPR and introducing the mutation R16A or R39A in EcDHDPR modifies the nucleotide-cofactor affinity of DHDPR. Lastly, the effects of these mutated DHDPRs on l-lysine production were investigated. The highest increase (26.2%) in l-lysine production was observed for JL-6 ΔdapB::Ec-dapB C115G,G116C , followed by JL-6 Cg-dapB C37G,G38C (21.4%) and JL-6 ΔdapB::Ec-dapB C46G,G47C (15.2%). This is the first report of a rational modification of DHDPR that enhances the l-lysine production and yield through the modulation of nucleotide-cofactor specificity. © 2018 Wiley Periodicals, Inc.

  4. A novel cofactor-binding mode in bacterial IMP dehydrogenases explains inhibitor selectivity.

    Science.gov (United States)

    Makowska-Grzyska, Magdalena; Kim, Youngchang; Maltseva, Natalia; Osipiuk, Jerzy; Gu, Minyi; Zhang, Minjia; Mandapati, Kavitha; Gollapalli, Deviprasad R; Gorla, Suresh Kumar; Hedstrom, Lizbeth; Joachimiak, Andrzej

    2015-02-27

    The steadily rising frequency of emerging diseases and antibiotic resistance creates an urgent need for new drugs and targets. Inosine 5'-monophosphate dehydrogenase (IMP dehydrogenase or IMPDH) is a promising target for the development of new antimicrobial agents. IMPDH catalyzes the oxidation of IMP to XMP with the concomitant reduction of NAD(+), which is the pivotal step in the biosynthesis of guanine nucleotides. Potent inhibitors of bacterial IMPDHs have been identified that bind in a structurally distinct pocket that is absent in eukaryotic IMPDHs. The physiological role of this pocket was not understood. Here, we report the structures of complexes with different classes of inhibitors of Bacillus anthracis, Campylobacter jejuni, and Clostridium perfringens IMPDHs. These structures in combination with inhibition studies provide important insights into the interactions that modulate selectivity and potency. We also present two structures of the Vibrio cholerae IMPDH in complex with IMP/NAD(+) and XMP/NAD(+). In both structures, the cofactor assumes a dramatically different conformation than reported previously for eukaryotic IMPDHs and other dehydrogenases, with the major change observed for the position of the NAD(+) adenosine moiety. More importantly, this new NAD(+)-binding site involves the same pocket that is utilized by the inhibitors. Thus, the bacterial IMPDH-specific NAD(+)-binding mode helps to rationalize the conformation adopted by several classes of prokaryotic IMPDH inhibitors. These findings offer a potential strategy for further ligand optimization. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. A Novel Cofactor-binding Mode in Bacterial IMP Dehydrogenases Explains Inhibitor Selectivity*

    Science.gov (United States)

    Makowska-Grzyska, Magdalena; Kim, Youngchang; Maltseva, Natalia; Osipiuk, Jerzy; Gu, Minyi; Zhang, Minjia; Mandapati, Kavitha; Gollapalli, Deviprasad R.; Gorla, Suresh Kumar; Hedstrom, Lizbeth; Joachimiak, Andrzej

    2015-01-01

    The steadily rising frequency of emerging diseases and antibiotic resistance creates an urgent need for new drugs and targets. Inosine 5′-monophosphate dehydrogenase (IMP dehydrogenase or IMPDH) is a promising target for the development of new antimicrobial agents. IMPDH catalyzes the oxidation of IMP to XMP with the concomitant reduction of NAD+, which is the pivotal step in the biosynthesis of guanine nucleotides. Potent inhibitors of bacterial IMPDHs have been identified that bind in a structurally distinct pocket that is absent in eukaryotic IMPDHs. The physiological role of this pocket was not understood. Here, we report the structures of complexes with different classes of inhibitors of Bacillus anthracis, Campylobacter jejuni, and Clostridium perfringens IMPDHs. These structures in combination with inhibition studies provide important insights into the interactions that modulate selectivity and potency. We also present two structures of the Vibrio cholerae IMPDH in complex with IMP/NAD+ and XMP/NAD+. In both structures, the cofactor assumes a dramatically different conformation than reported previously for eukaryotic IMPDHs and other dehydrogenases, with the major change observed for the position of the NAD+ adenosine moiety. More importantly, this new NAD+-binding site involves the same pocket that is utilized by the inhibitors. Thus, the bacterial IMPDH-specific NAD+-binding mode helps to rationalize the conformation adopted by several classes of prokaryotic IMPDH inhibitors. These findings offer a potential strategy for further ligand optimization. PMID:25572472

  6. A peptide of heparin cofactor II inhibits endotoxin-mediated shock and invasive Pseudomonas aeruginosa infection.

    Directory of Open Access Journals (Sweden)

    Martina Kalle

    Full Text Available Sepsis and septic shock remain important medical problems with high mortality rates. Today's treatment is based mainly on using antibiotics to target the bacteria, without addressing the systemic inflammatory response, which is a major contributor to mortality in sepsis. Therefore, novel treatment options are urgently needed to counteract these complex sepsis pathologies. Heparin cofactor II (HCII has recently been shown to be protective against Gram-negative infections. The antimicrobial effects were mapped to helices A and D of the molecule. Here we show that KYE28, a 28 amino acid long peptide representing helix D of HCII, is antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida albicans. Moreover, KYE28 binds to LPS and thereby reduces LPS-induced pro-inflammatory responses by decreasing NF-κB/AP-1 activation in vitro. In mouse models of LPS-induced shock, KYE28 significantly enhanced survival by dampening the pro-inflammatory cytokine response. Finally, in an invasive Pseudomonas infection model, the peptide inhibited bacterial growth and reduced the pro-inflammatory response, which lead to a significant reduction of mortality. In summary, the peptide KYE28, by simultaneously targeting bacteria and LPS-induced pro-inflammatory responses represents a novel therapeutic candidate for invasive infections.

  7. An antimicrobial helix A-derived peptide of heparin cofactor II blocks endotoxin responses in vivo.

    Science.gov (United States)

    Papareddy, Praveen; Kalle, Martina; Singh, Shalini; Mörgelin, Matthias; Schmidtchen, Artur; Malmsten, Martin

    2014-05-01

    Host defense peptides are key components of the innate immune system, providing multi-facetted responses to invading pathogens. Here, we describe that the peptide GKS26 (GKSRIQRLNILNAKFAFNLYRVLKDQ), corresponding to the A domain of heparin cofactor II (HCII), ameliorates experimental septic shock. The peptide displays antimicrobial effects through direct membrane disruption, also at physiological salt concentration and in the presence of plasma and serum. Biophysical investigations of model lipid membranes showed the antimicrobial action of GKS26 to be mirrored by peptide incorporation into, and disordering of, bacterial lipid membranes. GKS26 furthermore binds extensively to bacterial lipopolysaccharide (LPS), as well as its endotoxic lipid A moiety, and displays potent anti-inflammatory effects, both in vitro and in vivo. Thus, for mice challenged with ip injection of LPS, GKS26 suppresses pro-inflammatory cytokines, reduces vascular leakage and infiltration in lung tissue, and normalizes coagulation. Together, these findings suggest that GKS26 may be of interest for further investigations as therapeutic against severe infections and septic shock. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. A peptide of heparin cofactor II inhibits endotoxin-mediated shock and invasive Pseudomonas aeruginosa infection.

    Science.gov (United States)

    Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; van der Plas, Mariena J A; Mörgelin, Matthias; Malmsten, Martin; Schmidtchen, Artur

    2014-01-01

    Sepsis and septic shock remain important medical problems with high mortality rates. Today's treatment is based mainly on using antibiotics to target the bacteria, without addressing the systemic inflammatory response, which is a major contributor to mortality in sepsis. Therefore, novel treatment options are urgently needed to counteract these complex sepsis pathologies. Heparin cofactor II (HCII) has recently been shown to be protective against Gram-negative infections. The antimicrobial effects were mapped to helices A and D of the molecule. Here we show that KYE28, a 28 amino acid long peptide representing helix D of HCII, is antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida albicans. Moreover, KYE28 binds to LPS and thereby reduces LPS-induced pro-inflammatory responses by decreasing NF-κB/AP-1 activation in vitro. In mouse models of LPS-induced shock, KYE28 significantly enhanced survival by dampening the pro-inflammatory cytokine response. Finally, in an invasive Pseudomonas infection model, the peptide inhibited bacterial growth and reduced the pro-inflammatory response, which lead to a significant reduction of mortality. In summary, the peptide KYE28, by simultaneously targeting bacteria and LPS-induced pro-inflammatory responses represents a novel therapeutic candidate for invasive infections.

  9. Metabolic Regulation of Histone Acetyltransferases by Endogenous Acyl-CoA Cofactors.

    Science.gov (United States)

    Montgomery, David C; Sorum, Alexander W; Guasch, Laura; Nicklaus, Marc C; Meier, Jordan L

    2015-08-20

    The finding that chromatin modifications are sensitive to changes in cellular cofactor levels potentially links altered tumor cell metabolism and gene expression. However, the specific enzymes and metabolites that connect these two processes remain obscure. Characterizing these metabolic-epigenetic axes is critical to understanding how metabolism supports signaling in cancer, and developing therapeutic strategies to disrupt this process. Here, we describe a chemical approach to define the metabolic regulation of lysine acetyltransferase (KAT) enzymes. Using a novel chemoproteomic probe, we identify a previously unreported interaction between palmitoyl coenzyme A (palmitoyl-CoA) and KAT enzymes. Further analysis reveals that palmitoyl-CoA is a potent inhibitor of KAT activity and that fatty acyl-CoA precursors reduce cellular histone acetylation levels. These studies implicate fatty acyl-CoAs as endogenous regulators of histone acetylation, and suggest novel strategies for the investigation and metabolic modulation of epigenetic signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. AMOEBA Polarizable Force Field Parameters of the Heme Cofactor in Its Ferrous and Ferric Forms.

    Science.gov (United States)

    Wu, Xiaojing; Clavaguera, Carine; Lagardère, Louis; Piquemal, Jean-Philip; de la Lande, Aurélien

    2018-04-16

    We report the first parameters of the heme redox cofactors for the polarizable AMOEBA force field in both the ferric and ferrous forms. We consider two types of complexes, one with two histidine side chains as axial ligands and one with a histidine and a methionine side chain as ligands. We have derived permanent multipoles from second-order Møller-Plesset perturbation theory (MP2). The sets of parameters have been validated in a first step by comparison of AMOEBA interaction energies of heme and a collection of biologically relevant molecules with MP2 and Density Functional Theory (DFT) calculations. In a second validation step, we consider interaction energies with large aggregates comprising around 80 H 2 O molecules. These calculations are repeated for 30 structures extracted from semiempirical PM7 DM simulations. Very encouraging agreement is found between DFT and the AMOEBA force field, which results from an accurate treatment of electrostatic interactions. We finally report long (10 ns) MD simulations of cytochromes in two redox states with AMOEBA testing both the 2003 and 2014 AMOEBA water models. These simulations have been carried out with the TINKER-HP (High Performance) program. In conclusion, owing to their ubiquity in biology, we think the present work opens a wide array of applications of the polarizable AMOEBA force field on hemeproteins.

  11. Improved Method for the Incorporation of Heme Cofactors into Recombinant Proteins Using Escherichia coli Nissle 1917.

    Science.gov (United States)

    Fiege, Kerstin; Querebillo, Christine Joy; Hildebrandt, Peter; Frankenberg-Dinkel, Nicole

    2018-05-15

    Recombinant production of heme proteins in Escherichia coli is often limited by the availability of heme in the host. Therefore, several methods, including the reconstitution of heme proteins after production but prior to purification or the HPEX system, conferring the ability to take up external heme have been developed and used in the past. Here we describe the use of the apathogenic E. coli strain Nissle 1917 (EcN) as a suitable host for the recombinant production of heme proteins. EcN has an advantage over commonly used lab strains in that it is able to take up heme from the environment through the heme receptor ChuA. Expression of several heme proteins from different prokaryotic sources led to high yield and quantitative incorporation of the cofactor when heme was supplied in the growth medium. Comparative UV-vis and resonance Raman measurements revealed that the method employed has significant influence on heme coordination with the EcN system representing the most native situation. Therefore, the use of EcN as a host for recombinant heme protein production represents an inexpensive and straightforward method to facilitate further investigations of structure and function.

  12. The geochemical record of the ancient nitrogen cycle, nitrogen isotopes, and metal cofactors.

    Science.gov (United States)

    Godfrey, Linda V; Glass, Jennifer B

    2011-01-01

    The nitrogen (N) cycle is the only global biogeochemical cycle that is driven by biological functions involving the interaction of many microorganisms. The N cycle has evolved over geological time and its interaction with the oxygen cycle has had profound effects on the evolution and timing of Earth's atmosphere oxygenation (Falkowski and Godfrey, 2008). Almost every enzyme that microorganisms use to manipulate N contains redox-sensitive metals. Bioavailability of these metals has changed through time as a function of varying redox conditions, and likely influenced the biological underpinnings of the N cycle. It is possible to construct a record through geological time using N isotopes and metal concentrations in sediments to determine when the different stages of the N cycle evolved and the role metal availability played in the development of key enzymes. The same techniques are applicable to understanding the operation and changes in the N cycle through geological time. However, N and many of the redox-sensitive metals in some of their oxidation states are mobile and the isotopic composition or distribution can be altered by subsequent processes leading to erroneous conclusions. This chapter reviews the enzymology and metal cofactors of the N cycle and describes proper utilization of methods used to reconstruct evolution of the N cycle through time. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Dual utilization of NADPH and NADH cofactors enhances xylitol production in engineered Saccharomyces cerevisiae.

    Science.gov (United States)

    Jo, Jung-Hyun; Oh, Sun-Young; Lee, Hyeun-Soo; Park, Yong-Cheol; Seo, Jin-Ho

    2015-12-01

    Xylitol, a natural sweetener, can be produced by hydrogenation of xylose in hemicelluloses. In microbial processes, utilization of only NADPH cofactor limited commercialization of xylitol biosynthesis. To overcome this drawback, Saccharomyces cerevisiae D452-2 was engineered to express two types of xylose reductase (XR) with either NADPH-dependence or NADH-preference. Engineered S. cerevisiae DWM expressing both the XRs exhibited higher xylitol productivity than the yeast strain expressing NADPH-dependent XR only (DWW) in both batch and glucose-limited fed-batch cultures. Furthermore, the coexpression of S. cerevisiae ZWF1 and ACS1 genes in the DWM strain increased intracellular concentrations of NADPH and NADH and improved maximum xylitol productivity by 17%, relative to that for the DWM strain. Finally, the optimized fed-batch fermentation of S. cerevisiae DWM-ZWF1-ACS1 resulted in 196.2 g/L xylitol concentration, 4.27 g/L h productivity and almost the theoretical yield. Expression of the two types of XR utilizing both NADPH and NADH is a promising strategy to meet the industrial demands for microbial xylitol production. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Engineering of the glycerol decomposition pathway and cofactor regulation in an industrial yeast improves ethanol production.

    Science.gov (United States)

    Zhang, Liang; Tang, Yan; Guo, Zhongpeng; Shi, Guiyang

    2013-10-01

    Glycerol is a major by-product of industrial ethanol production and its formation consumes up to 4 % of the sugar substrate. This study modified the glycerol decomposition pathway of an industrial strain of Saccharomyces cerevisiae to optimize the consumption of substrate and yield of ethanol. This study is the first to couple glycerol degradation with ethanol formation, to the best of our knowledge. The recombinant strain overexpressing GCY1 and DAK1, encoding glycerol dehydrogenase and dihydroxyacetone kinase, respectively, in glycerol degradation pathway, exhibited a moderate increase in ethanol yield (2.9 %) and decrease in glycerol yield (24.9 %) compared to the wild type with the initial glucose concentration of 15 % under anaerobic conditions. However, when the mhpF gene, encoding acetylating NAD⁺-dependent acetaldehyde dehydrogenase from Escherichia coli, was co-expressed in the aforementioned recombinant strain, a further increase in ethanol yield by 5.5 % and decrease in glycerol yield by 48 % were observed for the resultant recombinant strain GDMS1 when acetic acid was added into the medium prior to inoculation compared to the wild type. The process outlined in this study which enhances glycerol consumption and cofactor regulation in an industrial yeast is a promising metabolic engineering strategy to increase ethanol production by reducing the formation of glycerol.

  15. Ntdin, a tobacco senescence-associated gene, is involved in molybdenum cofactor biosynthesis.

    Science.gov (United States)

    Yang, Seung Hwan; Berberich, Thomas; Miyazaki, Atsushi; Sano, Hiroshi; Kusano, Tomonobu

    2003-10-01

    To date, dozens of genes have been reported to be up-regulated with senescence in higher plants. Radish din1 and its ortholog sen1 of Arabidopsis are known as such, but their function is not clear yet. Here we have isolated their counterpart cDNA from tobacco and designated it as NTDIN: Its product, Ntdin, a 185 amino acid polypeptide with 56.8% and 54.2% identity to Atsen1 and Rsdin1, respectively, is localized in chloroplasts. Transcripts of Ntdin are induced by sulfate or nitrate but not by phosphate, suggesting its involvement in sulfur and nitrogen metabolism. A database search revealed that Ntdin shows similarity with the C-terminal region of Nicotiana plumbaginifolia Cnx5, which functions in molybdenum cofactor (Moco) biosynthesis. Transgenic tobacco plants with suppressed Ntdin are more tolerant to chlorate, a substrate analog of nitrate reductase, than controls, implying low nitrate reductase activity in the transgenic plants due to a deficiency of Moco. Indeed, enzymatic activities of two molybdoenzymes, nitrate reductase and xanthine dehydrogenase, in transgenic plants are found to be significantly lower than in control plants. Direct measurement of Moco contents reveals that those transgenic plants contain about 5% Moco of those of the control plants. Abscisic acid and indole-3-acidic acid, whose biosynthetic pathways require Moco, up-regulated Ntdin expression. Taken together, it is concluded that Ntdin functions in a certain step in Moco biosynthesis.

  16. DNA-binding protects p53 from interactions with cofactors involved in transcription-independent functions.

    Science.gov (United States)

    Lambrughi, Matteo; De Gioia, Luca; Gervasio, Francesco Luigi; Lindorff-Larsen, Kresten; Nussinov, Ruth; Urani, Chiara; Bruschi, Maurizio; Papaleo, Elena

    2016-11-02

    Binding-induced conformational changes of a protein at regions distant from the binding site may play crucial roles in protein function and regulation. The p53 tumour suppressor is an example of such an allosterically regulated protein. Little is known, however, about how DNA binding can affect distal sites for transcription factors. Furthermore, the molecular details of how a local perturbation is transmitted through a protein structure are generally elusive and occur on timescales hard to explore by simulations. Thus, we employed state-of-the-art enhanced sampling atomistic simulations to unveil DNA-induced effects on p53 structure and dynamics that modulate the recruitment of cofactors and the impact of phosphorylation at Ser215. We show that DNA interaction promotes a conformational change in a region 3 nm away from the DNA binding site. Specifically, binding to DNA increases the population of an occluded minor state at this distal site by more than 4-fold, whereas phosphorylation traps the protein in its major state. In the minor conformation, the interface of p53 that binds biological partners related to p53 transcription-independent functions is not accessible. Significantly, our study reveals a mechanism of DNA-mediated protection of p53 from interactions with partners involved in the p53 transcription-independent signalling. This also suggests that conformational dynamics is tightly related to p53 signalling. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. Tubulin cofactor B regulates microtubule densities during microglia transition to the reactive states

    International Nuclear Information System (INIS)

    Fanarraga, M.L.; Villegas, J.C.; Carranza, G.; Castano, R.; Zabala, J.C.

    2009-01-01

    Microglia are highly dynamic cells of the CNS that continuously survey the welfare of the neural parenchyma and play key roles modulating neurogenesis and neuronal cell death. In response to injury or pathogen invasion parenchymal microglia transforms into a more active cell that proliferates, migrates and behaves as a macrophage. The acquisition of these extra skills implicates enormous modifications of the microtubule and actin cytoskeletons. Here we show that tubulin cofactor B (TBCB), which has been found to contribute to various aspects of microtubule dynamics in vivo, is also implicated in microglial cytoskeletal changes. We find that TBCB is upregulated in post-lesion reactive parenchymal microglia/macrophages, in interferon treated BV-2 microglial cells, and in neonate amoeboid microglia where the microtubule densities are remarkably low. Our data demonstrate that upon TBCB downregulation both, after microglia differentiation to the ramified phenotype in vivo and in vitro, or after TBCB gene silencing, microtubule densities are restored in these cells. Taken together these observations support the view that TBCB functions as a microtubule density regulator in microglia during activation, and provide an insight into the understanding of the complex mechanisms controlling microtubule reorganization during microglial transition between the amoeboid, ramified, and reactive phenotypes

  18. Phenylalanine ammonia lyase catalyzed synthesis of amino acids by an MIO-cofactor independent pathway.

    Science.gov (United States)

    Lovelock, Sarah L; Lloyd, Richard C; Turner, Nicholas J

    2014-04-25

    Phenylalanine ammonia lyases (PALs) belong to a family of 4-methylideneimidazole-5-one (MIO) cofactor dependent enzymes which are responsible for the conversion of L-phenylalanine into trans-cinnamic acid in eukaryotic and prokaryotic organisms. Under conditions of high ammonia concentration, this deamination reaction is reversible and hence there is considerable interest in the development of PALs as biocatalysts for the enantioselective synthesis of non-natural amino acids. Herein the discovery of a previously unobserved competing MIO-independent reaction pathway, which proceeds in a non-stereoselective manner and results in the generation of both L- and D-phenylalanine derivatives, is described. The mechanism of the MIO-independent pathway is explored through isotopic-labeling studies and mutagenesis of key active-site residues. The results obtained are consistent with amino acid deamination occurring by a stepwise E1 cB elimination mechanism. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Christophe Couderc, dir., Le théâtre Espagnol du Siècle d'Or en France. De la traduction au transfert culturel

    Directory of Open Access Journals (Sweden)

    Christian Andrès

    2012-12-01

    Full Text Available Review of Christophe Couderc, Le théâtre Espagnol du Siècle d'Or en France. De la traduction au transfert culturel, Presses Universitaires de Paris Ouest, París, 2012, 299 pp. ISBN: 978-2-84016-102-8.

  20. Tratamento terapêutico multi-profissional para endometriose com dor pélvica - doi: 10.5102/ucs.v6i1.633

    Directory of Open Access Journals (Sweden)

    Raquel Pinto Caldeira

    2008-12-01

    Full Text Available O objetivo do trabalho foi citar os vários tipos de tratamentos de endometriose visando melhorar a dor pélvica presente. Realizamos uma revisão bibliográfica com artigos relacionados à dor pélvica e endometriose, e foram encontrados 65 artigos, excluídos 49, restando apenas 16. Concluímos que o uso de qualquer hormônio é eficaz no tratamento clínico medicamentoso para dor pélvica associada à endometriose. Dependendo da gravidade da doença encontrada, a prática ideal da laparoscopia consiste em realizar o diagnóstico e a extinção cirúrgica dos focos de endometriose no ato operatório. Toda paciente deve ser indicado ao tratamento multiprofissional que atenda às demandas físicas e psicológicas visando o alívio da dor, a melhora da qualidade de vida e principalmente a sua auto-estima.

  1. Long-term results of the Heller-Dor operation with intraoperative manometry for the treatment of esophageal achalasia.

    Science.gov (United States)

    Mattioli, Sandro; Ruffato, Alberto; Lugaresi, Marialuisa; Pilotti, Vladimiro; Aramini, Beatrice; D'Ovidio, Frank

    2010-11-01

    Quality of outcome of the Heller-Dor operation is sometimes different between studies, likely because of technical reasons. We analyze the details of myotomy and fundoplication in relation to the results achieved over a 30-year single center's experience. From 1979-2008, a long esophagogastric myotomy and a partial anterior fundoplication to protect the surface of the myotomy was routinely performed with intraoperative manometry in 202 patients (97 men; median age, 55.5 years; interquartile range, 43.7-71 years) through a laparotomy and in 60 patients (24 men; median age, 46 years; interquartile range, 36.2-63 years) through a laparoscopy. The follow-up consisted of periodical interview, endoscopy, and barium swallow, and a semiquantitative scale was used to grade results. Mortality was 1 of 202 in the laparotomy group and 0 of 60 in the laparoscopy group. Median follow-up was 96 months (interquartile range, 48-190.5 months) in the laparotomy group and 48 months (interquartile range, 27-69.5 months) in the laparoscopy group. At intraoperative manometry, complete abolition of the high-pressure zone was obtained in 100%. The Dor-related high-pressure zone length and mean pressure were 4.5 ± 0.4 cm and 13.3 ± 2.2 mm Hg in the laparotomy group and 4.5 ± 0.5 cm and 13.2 ± 2.2 mm Hg in the laparoscopy group (P = .75). In the laparotomy group poor results (19/201 [9.5%]) were secondary to esophagitis in 15 (7.5%) of 201 patients (in 2 patients after 184 and 252 months, respectively) and to recurrent dysphagia in 4 (2%) of 201 patients, all with end-stage sigmoid achalasia. In the laparoscopy group 2 (3.3%) of 60 had esophagitis. A long esophagogastric myotomy protected by means of Dor fundoplication cures or substantially reduces dysphagia in the great majority of patients affected by esophageal achalasia and effectively controls postoperative esophagitis. Intraoperative manometry is likely the key factor for achieving the reported results. Copyright © 2010 The

  2. A Spatial Study of X-ray Properties in Superbubble 30 Dor C with XMM-Newton

    Science.gov (United States)

    Babazaki, Yasunori; Mitsuishi, Ikuyuki; SANO, Hidetoshi; Yoshiike, Satoshi; Fukuda, Tatsuya; Maruyama, Shohei; Fujii, Kosuke; Fukui, Yasuo; Tawara, Yuzuru; Matsumoto, Hironori

    2015-08-01

    Supernova remnants (SNRs) in the Galaxy are believed to be most likely accelerators of cosmic-rays (CRs) in an energy range less than 3×10^15 eV. Thus SNRs emit synchrotron X-rays by high-energy electrons. Sano et al. (2014) investigated spatially-resolved X-ray spectral properties of a shell-type SNR RX1713.77-3946 which shows strong non-thermal X-ray emissions. A large variation in the photon index is found and the photon index tends to be hard with increasing an interstellar gas density, suggesting that CR electrons are efficiently accelerated in denser interstellar gas environments. Few studies have focused on a photon index variation in superbubbles which possess 100-1000 pc diameter shells of swept-up interstellar materials containing hot (~10^6 K) shock-heated gas. The superbubble 30 Dor C in the Large Magellanic Cloud is one of the best targets for examining the photon index variation, because 30 Dor C is by far strong non-thermal X-ray emissions, and thus provides an ideal laboratory for probing non-thermal emission mechanisms in the supperbubble. We investigated X-ray spectral properties of the superbubble with a high spatial resolution of on the order of 10 pc. Consequently, the spectra in the west region of 30 Dor C can be described with a combination of absorbed thermal and non-thermal models while the spectra in the east region can be fitted with an absorbed non-thermal model. The photon index and intensity in 2-10 keV show variations of 2.0-3.5 and (0.6-8.0) × 10^-7 erg/s/cm^2, respectively. The temperature of the thermal component ranges from ~0.1 to ~0.3 keV. We will discuss an interaction between the hot gas and an interstellar gas using mutiwavelength data.

  3. Efetividade de exercícios de estabilização segmentar sobre a dor lombar crônica mecânico-postural

    Directory of Open Access Journals (Sweden)

    Natália Toledo Pereira

    Full Text Available INTRODUÇÃO: A prevalência ao longo da vida de lombalgias mecânico-posturais é estimada em 60-70% em países industrializados. Um dos principais fatores para dor lombar é a instabilidade segmentar, e para manter a estabilidade é necessária a interação de três subsistemas: passivo, ativo e controle neural. Exercícios específicos que promovem a contração independente dos músculos profundos do tronco (transverso do abdômen e multífido têm demonstrado ter efeitos benéficos em indivíduos que sofrem de dor lombar inespecífica, sugerindo a estimulação desses subsistemas. OBJETIVO: Avaliar a efetividade de exercícios de estabilização segmentar sobre a dor e a capacidade funcional em indivíduos com lombalgia crônica. MATERIAIS E MÉTODOS: Participaram da pesquisa 12 mulheres jovens com idade média de 20,66 ± 3,74 anos. Foram realizadas 12 sessões de um programa de estabilização segmentar com frequência de duas vezes semanais, sendo avaliadas quanto à dor (questionário McGILL-Br e capacidade funcional (questionário Rolland-Morris Brasil antes e depois do período de intervenção. RESULTADOS: Houve melhora significativa dos valores médios do índice de dor (p < 0,0001, melhora do índice de dor sensitiva (p = 0,0024, afetiva (p = 0,048, avaliativo (p = 0,042 e miscelânea (p = 0,017 e melhora da capacidade funcional dos indivíduos (p < 0,0001, após o período de intervenção. DISCUSSÃO: Vários estudos relataram a eficácia de exercícios dos músculos profundos do tronco, apresentando efeitos benéficos em indivíduos com lombalgia, corroborando com o estudo proposto. CONCLUSÃO: Pode-se concluir que o programa de estabilização segmentar foi efetivo na redução da dor e na melhora da função nestes pacientes, demonstrando assim ser um método eficaz de tratamento de lombalgias.

  4. Fisiomotricidade e limiares de dor: efeitos de um programa de exercícios na autonomia funcional de idosas osteoporóticas

    Directory of Open Access Journals (Sweden)

    Karla Virgínia Bezerra de Castro

    Full Text Available INTRODUÇÃO: A atividade física é importante para a manutenção da autonomia funcional do homem e crucial em idosos. Todavia, alguns fatores, como a dor, limitam a participação deles em programas de atividade física. OBJETIVO: Investigar se, em função de um programa de atividades físicas estruturado de maneira a limitar a dor, poder-se-ia garantir a aderência de idosas sofrendo de osteoporose/osteopenia e, dessa forma, promover melhoras na autonomia funcional destas. DESENVOLVIMENTO: A amostra foi composta por 30 mulheres, entre 65 e 70 anos, divididas em dois grupos definidos em função de um diagnóstico de dor. MATERIAIS E MÉTODOS: Aplicou-se um programa definido pelo termo fisiomotriz, de baixo impacto, caracterizado por lentidão nas mudanças articulares, progredindo em quatro níveis que foram distribuídos em 48 encontros. Os dados da dor e da autonomia funcional, obtidos por meio do teste de dor em escala analógica visual e do protocolo de GDLAM foram estudados por estatística descritiva e inferencial, com o índice ALFA ± 0,05. O instrumento foi uma Análise de Variância de Kruskal Wallis com índice Qui-quadrado (Chi². RESULTADOS: Os resultados revelaram melhora da autonomia funcional e diminuição de dor relatada pelas participantes, fato que consequentemente implementou a aderência destas até ao final do programa. CONCLUSÃO: Conclui-se que o programa fisiomotriz, aplicado em idosas com osteopenia e/ou osteoporose, foi uma forma eficaz na promoção da melhora de sua autonomia funcional, que pode ser atribuída, pelo menos em parte, à diminuição de dor antes relatada pelas idosas.

  5. Estudo comparativo entre os métodos Pilates no solo e Water Pilates na qualidade de vida e dor de pacientes com lombalgia

    Directory of Open Access Journals (Sweden)

    Adriane Behring Bianchi

    2016-10-01

    Full Text Available Objetivo: comparar a eficácia dos métodos Pilates solo e Water Pilates, na qualidade de vida e dor de pacientes com lombalgia. Método: foram incluídos 20 pacientes do sexo feminino, com idade entre 18 a 25 anos, que apresentavam queixa de dor na região lombar. As participantes foram avaliadas, antes e após os protocolos de tratamento, em relação à qualidade de vida, pelo questionário Short Forms Health Survey (SF-36, e dor, pela Escala Visual Analógica (EVA. A amostra foi dividida aleatoriamente em dois grupos: Pilates Solo (PS e Water Pilates (WP. Cada grupo realizou dez sessões de tratamento, com frequência de duas vezes semanais e com duração de 40 minutos por sessão. Para a descrição dos dados foi utilizado média, desvio padrão, mínimo e máximo. Para comparar as variáveis inicias e finais foi utilizado o teste pareado de Wilcoxon e para comparação entre os dois grupos foi utilizado o teste de Mann-Whitney. O nível de significância adotado foi de 5%. Resultados: ao comparar as avaliações iniciais e finais no grupo PS, foi observado aumento estatisticamente significativo nos domínios capacidade funcional (p=0,015, dor (p=0,025 e saúde mental (p=0,012 do questionário de qualidade de vida. Já, ao comparar as avaliações iniciais e finais no grupo WP, ficou evidenciado aumento estatisticamente significativo nos domínios capacidade funcional (p=0,012, aspectos físicos (p=0,023, dor (p=0,012, vitalidade (p=0,008 e aspectos sociais (p=0,033. Em relação à variável dor pela EVA, também foi observada diminuição significativa em ambos os grupos (p=0,005. Na comparação dos resultados finais obtidos nos dois grupos não foi observada diferença estatisticamente significante em nenhuma das variáveis (p>0,05. Considerações finais: ambos os métodos Pilates solo e Water Pilates são eficazes para melhora da qualidade de vida e redução da dor de pacientes com lombalgia.

  6. Disfunção da articulação sacro-ilíaca em jovens com dor lombar

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    Carolina Ramírez Ramírez

    Full Text Available INTRODUÇÃO: A dor lombar representa um problema de saúde pública. Estima-se que uma elevada porcentagem de casos de dor lombar (85-90% não tem uma causa conhecida. Acredita-se que a disfunção da articulação sacro-ilíaca possa explicar, em parte, essa alta porcentagem. OBJETIVO: Determinar a frequência da disfunção da articulação sacro-ilíaca em jovens com dor lombar e descrever possíveis associações com características sócio-demográficas, clínicas e antropométricas da população estudada. METODOLOGIA: A amostra foi selecionada por meio de entrevista direta. Sessenta e sete sujeitos (92,5% mulheres com idade média de 21 ± 2,1 participaram do estudo. Foi realizado exame físico que incluiu a avaliação da dor à palpação, amplitude de movimento da flexão do quadril, funcionalidade avaliada por meio do Oswestry Disability Index, e realização de quatro provas de provocação de dor da articulação sacro-ilíaca (Gaenslen, thigh thrust, compressão ilíaca e compressão sacra. O diagnóstico para disfunção da articulação sacro-ilíaca foi considerado positivo se pelo menos três das provas foram positivas. RESULTADOS: A frequência de disfunção da articulação sacro-ilíaca foi de 35,8% IC 95% (24,0-47,6. Foi observada associação da disfunção da articulação com diminuição de flexibilidade dos isquiotibiais, pontuação do Oswestry Disability Index e dor à palpação. Não foram encontradas associações estatisticamente significativas com as variáveis sócio-demográficas. CONCLUSÃO: A alta frequência de disfunção da articulação sacro-ilíaca encontrada sugere a possibilidade de detectar e intervir precocemente uma possível causa de dor lombar, evitando alterações funcionais de maior severidade.

  7. Extracellular Hsp90 serves as a co-factor for MAPK activation and latent viral gene expression during de novo infection by KSHV

    International Nuclear Information System (INIS)

    Qin Zhiqiang; DeFee, Michael; Isaacs, Jennifer S.; Parsons, Chris

    2010-01-01

    The Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS), an important cause of morbidity and mortality in immunocompromised patients. KSHV interaction with the cell membrane triggers activation of specific intracellular signal transduction pathways to facilitate virus entry, nuclear trafficking, and ultimately viral oncogene expression. Extracellular heat shock protein 90 localizes to the cell surface (csHsp90) and facilitates signal transduction in cancer cell lines, but whether csHsp90 assists in the coordination of KSHV gene expression through these or other mechanisms is unknown. Using a recently characterized non-permeable inhibitor specifically targeting csHsp90 and Hsp90-specific antibodies, we show that csHsp90 inhibition suppresses KSHV gene expression during de novo infection, and that this effect is mediated largely through the inhibition of mitogen-activated protein kinase (MAPK) activation by KSHV. Moreover, we show that targeting csHsp90 reduces constitutive MAPK expression and the release of infectious viral particles by patient-derived, KSHV-infected primary effusion lymphoma cells. These data suggest that csHsp90 serves as an important co-factor for KSHV-initiated MAPK activation and provide proof-of-concept for the potential benefit of targeting csHsp90 for the treatment or prevention of KSHV-associated illnesses.

  8. Identificação de Zonas de Dor Relacionadas com Patologias Músculo- Esqueléticas num Grupo de Músicos

    Directory of Open Access Journals (Sweden)

    Mafalda Pires

    2016-12-01

    Full Text Available A dor relacionada com o uso excessivo dos músculos é um problema comum nos músicos (Steinmetz, Möller, Seidal e Rigotti, 2012. Esta, que pode variar desde um desconforto leve e passageiro a um desconforto prolongado e muito doloroso, é uma experiencia sensorial e emocional que normalmente se associa a uma lesão. Num artigo sobre esta temática, publicado em 2014, é afirmado que “o peso estático, os movimentos repetitivos, a ativação muscular excessiva, bem como a postura corporal extrema, são impostos ao corpo, causando danos, desde cedo na infância” (Nawrocka, Mynarski, Powerska, Grabara, Groffik e Borek, 2014: 29. Todos estes danos podem levar à dor crónica, sendo que, os músicos nestas condições têm mais tendência para atingir níveis elevados de ansiedade e pânico, do que músicos que não sofrem de dor (Zamorano, Riquelme,Kleber, Altenmüller, Hatem e Montoya, 2015. Também os anos de profissão, a frequência da prática musical e o tempo de estudo são os fatores que contribuem para o aumento de queixas da dor nos músicos. No sentido de perceber quais as principais queixas do foro músculo-esquelético apresentadas por músicos, o objetivo deste capítulo centra-se na identificação das zonas mais afetadas do corpo humano relacionadas com a prática instrumental, bem como as causas da dor que delas advém.

  9. Heller myotomy versus Heller myotomy with Dor fundoplication for achalasia: long-term symptomatic follow-up of a prospective randomized controlled trial.

    Science.gov (United States)

    Kummerow Broman, Kristy; Phillips, Sharon E; Faqih, Adil; Kaiser, Joan; Pierce, Richard A; Poulose, Benjamin K; Richards, William O; Sharp, Kenneth W; Holzman, Michael D

    2018-04-01

    Our prior randomized controlled trial of Heller myotomy alone versus Heller plus Dor fundoplication for achalasia from 2000 to 2004 demonstrated comparable postoperative resolution of dysphagia but less gastroesophageal reflux after Heller plus Dor. Patient-reported outcomes are needed to determine whether the findings are sustained long-term. We actively engaged participants from the prior randomized cohort, making up to six contact attempts per person using telephone, mail, and electronic messaging. We collected patient-reported measures of dysphagia and gastroesophageal reflux using the Dysphagia Score and the Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) instrument. Patient-reported re-interventions for dysphagia were verified by obtaining longitudinal medical records. Among living participants, 27/41 (66%) were contacted and all completed the follow-up study at a mean of 11.8 years postoperatively. Median Dysphagia Scores and GERD-HRQL scores were slightly worse for Heller than Heller plus Dor but were not statistically different (6 vs 3, p = 0.08 for dysphagia, 15 vs 13, p = 0.25 for reflux). Five patients in the Heller group and 6 in Heller plus Dor underwent re-intervention for dysphagia with most occurring more than five years postoperatively. One patient in each group underwent redo Heller myotomy and subsequent esophagectomy. Nearly all patients (96%) would undergo operation again. Long-term patient-reported outcomes after Heller alone and Heller plus Dor for achalasia are comparable, providing support for either procedure.

  10. Biocatalytic hydroxylation of n-butane with in situ cofactor regeneration at low temperature and under normal pressure

    Directory of Open Access Journals (Sweden)

    Svenja Staudt

    2012-02-01

    Full Text Available The hydroxylation of n-alkanes, which proceeds in the presence of a P450-monooxygenase advantageously at temperatures significantly below room temperature, is described. In addition, an enzymatic hydroxylation of the “liquid gas” n-butane with in situ cofactor regeneration, which does not require high-pressure conditions, was developed. The resulting 2-butanol was obtained as the only regioisomer, at a product concentration of 0.16 g/L.

  11. Elucidation of new condition-dependent roles for fructose-1,6-bisphosphatase linked to cofactor balances.

    Directory of Open Access Journals (Sweden)

    Du Toit W P Schabort

    Full Text Available The cofactor balances in metabolism is of paramount importance in the design of a metabolic engineering strategy and understanding the regulation of metabolism in general. ATP, NAD+ and NADP+ balances are central players linking the various fluxes in central metabolism as well as biomass formation. NADP+ is especially important in the metabolic engineering of yeasts for xylose fermentation, since NADPH is required by most yeasts in the initial step of xylose utilisation, including the fast-growing Kluyveromyces marxianus. In this simulation study of yeast metabolism, the complex interplay between these cofactors was investigated; in particular, how they may affect the possible roles of fructose-1,6-bisphosphatase, the pentose phosphate pathway, glycerol production and the pyruvate dehydrogenase bypass. Using flux balance analysis, it was found that the potential role of fructose-1,6-bisphosphatase was highly dependent on the cofactor specificity of the oxidative pentose phosphate pathway and on the carbon source. Additionally, the excessive production of ATP under certain conditions might be involved in some of the phenomena observed, which may have been overlooked to date. Based on these findings, a strategy is proposed for the metabolic engineering of a future xylose-fermenting yeast for biofuel production.

  12. O-, N-Atoms-Coordinated Mn Cofactors within a Graphene Framework as Bioinspired Oxygen Reduction Reaction Electrocatalysts.

    Science.gov (United States)

    Yang, Yang; Mao, Kaitian; Gao, Shiqi; Huang, Hao; Xia, Guoliang; Lin, Zhiyu; Jiang, Peng; Wang, Changlai; Wang, Hui; Chen, Qianwang

    2018-05-28

    Manganese (Mn) is generally regarded as not being sufficiently active for the oxygen reduction reaction (ORR) compared to other transition metals such as Fe and Co. However, in biology, manganese-containing enzymes can catalyze oxygen-evolving reactions efficiently with a relative low onset potential. Here, atomically dispersed O and N atoms coordinated Mn active sites are incorporated within graphene frameworks to emulate both the structure and function of Mn cofactors in heme-copper oxidases superfamily. Unlike previous single-metal catalysts with general M-N-C structures, here, it is proved that a coordinated O atom can also play a significant role in tuning the intrinsic catalytic activities of transition metals. The biomimetic electrocatalyst exhibits superior performance for the ORR and zinc-air batteries under alkaline conditions, which is even better than that of commercial Pt/C. The excellent performance can be ascribed to the abundant atomically dispersed Mn cofactors in the graphene frameworks, confirmed by various characterization methods. Theoretical calculations reveal that the intrinsic catalytic activity of metal Mn can be significantly improved via changing local geometry of nearest coordinated O and N atoms. Especially, graphene frameworks containing the Mn-N 3 O 1 cofactor demonstrate the fastest ORR kinetics due to the tuning of the d electronic states to a reasonable state. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Absorption and emission spectroscopic characterization of BLUF protein Slr1694 from Synechocystis sp. PCC6803 with roseoflavin cofactor.

    Science.gov (United States)

    Zirak, P; Penzkofer, A; Mathes, T; Hegemann, P

    2009-11-09

    The wild-type BLUF protein Slr1694 from Synechocystis sp. PCC6803 (BLUF=blue-light sensor using FAD) has flavin adenosine dinucleotide (FAD) as natural cofactor. This light sensor causes positive phototaxis of the marine cyanobacterium. In this study the FAD cofactor of the wild-type Slr1694 was replaced by roseoflavin (RoF) and the roseoflavin derivatives RoFMN and RoFAD during heterologous expression in a riboflavin auxotrophic E. coli strain. An absorption and emission spectroscopic characterization of the cofactor-exchanged-Slr1694 (RoSlr) was carried out both under dark conditions and under illuminated conditions. The behaviour of RoF embedded in RoSlr in aqueous solution at pH 8 is compared with the behaviour of RoF in aqueous solution. The fluorescence of RoF and RoSlr is quenched by photo-induced twisted intra-molecular charge transfer at room temperature with stronger effect for RoF. The fluorescence quenching is diminished at liquid nitrogen temperature. Light exposure of RoSlr causes irreversible conversion of the protein embedded roseoflavins to 8-methylamino-flavins, 8-dimethylamino-lumichrome and 8-methylamino-lumichrome.

  14. Catalase in peroxidase clothing: Interdependent cooperation of two cofactors in the catalytic versatility of KatG.

    Science.gov (United States)

    Njuma, Olive J; Ndontsa, Elizabeth N; Goodwin, Douglas C

    2014-02-15

    Catalase-peroxidase (KatG) is found in eubacteria, archaea, and lower eukaryotae. The enzyme from Mycobacterium tuberculosis has received the greatest attention because of its role in activation of the antitubercular pro-drug isoniazid, and the high frequency with which drug resistance stems from mutations to the katG gene. Generally, the catalase activity of KatGs is striking. It rivals that of typical catalases, enzymes with which KatGs share no structural similarity. Instead, catalatic turnover is accomplished with an active site that bears a strong resemblance to a typical peroxidase (e.g., cytochrome c peroxidase). Yet, KatG is the only member of its superfamily with such capability. It does so using two mutually dependent cofactors: a heme and an entirely unique Met-Tyr-Trp (MYW) covalent adduct. Heme is required to generate the MYW cofactor. The MYW cofactor allows KatG to leverage heme intermediates toward a unique mechanism for H2O2 oxidation. This review evaluates the range of intermediates identified and their connection to the diverse catalytic processes KatG facilitates, including mechanisms of isoniazid activation. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. EFFECTS OF CIGARETTE SMOKING ON ERYTHROCYTE ANTIOXIDATIVE ENZYME ACTIVITIES AND PLASMA CONCENTRATIONS OF THEIR COFACTORS

    Directory of Open Access Journals (Sweden)

    M. Zahraie

    2005-07-01

    Full Text Available Tobacco smoke contains numerous compounds, many ‎of which are oxidants and capable of producing free radical and enhancing ‎the oxidative stress. The aim of this study was to investigate the effect of cigarette smoking on the erythrocyte antioxidative enzyme activities and the plasma ‎concentration of their cofactors. ‎Sixty eight healthy men were enrolled, 32 of whom had never smoked and 36 had smoked at least 10 cigarettes per day for ‎at least one year. Hemolysate superoxide dismutase (Cu-Zn SOD, glutathione peroxidase (GSH-Px and ‎catalase (CAT activities were measured using spectrophotometer. Plasma copper, zinc and selenium concentrations were determined ‎using atomic absorption spectrophotometer. Plasma iron concentration was determined by colorimetric ‎method. We found that erythrocyte Cu-Zn SOD activity was significantly higher in tobacco smokers ‎compared with non-smokers (1294 ± 206.7 U/gHb in smokers vs. 1121.6 ± 237.8 U/gHb in non-‎smokers, P < 0.01. While plasma selenium concentration was significantly lower in tobacco ‎smokers (62.7±14.8 μg/L in smokers vs. 92.1 ± 17.5 μg/L in non-smokers, P < 0.01, there were no significant ‎differences in erythrocyte GSH-Px and CAT activities and plasma copper, zinc and iron concentrations between the two groups. ‎It seems that cigarette smoking can alter antioxidative enzymes activity and plasma concentration of some trace elements.

  16. Aspergillus fumigatus SidA is a highly specific ornithine hydroxylase with bound flavin cofactor.

    Science.gov (United States)

    Chocklett, Samuel W; Sobrado, Pablo

    2010-08-10

    Ferrichrome is a hydroxamate-containing siderophore produced by the pathogenic fungus Aspergillus fumigatus under iron-limiting conditions. This siderophore contains N(5)-hydroxylated l-ornithines essential for iron binding. A. fumigatus siderophore A (Af SidA) catalyzes the flavin- and NADPH-dependent hydroxylation of l-ornithine in ferrichrome biosynthesis. Af SidA was recombinantly expressed and purified as a soluble tetramer and is the first member of this class of flavin monooxygenases to be isolated with a bound flavin cofactor. The enzyme showed typical saturation kinetics with respect to l-ornithine while substrate inhibition was observed at high concentrations of NADPH and NADH. Increasing amounts of hydrogen peroxide were measured as a function of reduced nicotinamide coenzyme concentration, indicating that inhibition was caused by increased uncoupling. Af SidA is highly specific for its amino acid substrate, only hydroxylating l-ornithine. An 8-fold preference in the catalytic efficiency was determined for NADPH compared to NADH. In the absence of substrate, Af SidA can be reduced by NADPH, and a C4a-(hydro)peroxyflavin intermediate is observed. The decay of this intermediate is accelerated by l-ornithine binding. This intermediate was only stabilized by NADPH and not by NADH, suggesting a role for NADP(+) in the stabilization of intermediates in the reaction of Af SidA. NADP(+) is a competitive inhibitor with respect to NADPH, demonstrating that Af SidA forms a ternary complex with NADP(+) and l-ornithine during catalysis. The data suggest that Af SidA likely proceeds by a sequential kinetic mechanism.

  17. Importance of lipopolysaccharide aggregate disruption for the anti-endotoxic effects of heparin cofactor II peptides.

    Science.gov (United States)

    Singh, Shalini; Papareddy, Praveen; Kalle, Martina; Schmidtchen, Artur; Malmsten, Martin

    2013-11-01

    Lipid membrane and lipopolysaccharide (LPS) interactions were investigated for a series of amphiphilic and cationic peptides derived from human heparin cofactor II (HCII), using dual polarization interferometry, ellipsometry, circular dichroism (CD), cryoTEM, and z-potential measurements. Antimicrobial effects of these peptides were compared to their ability to disorder bacterial lipid membranes, while their capacity to block endotoxic effects of LPS was correlated to the binding of these peptides to LPS and its lipid A moiety, and to charge, secondary structure, and morphology of peptide/LPS complexes. While the peptide KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYTLR) displayed potent antimicrobial and anti-endotoxic effects, its truncated variants KYE21 (KYEITTIHNLFRKLTHRLFRR) and NLF20 (NLFRKLTHRLFRRNFGYTLR) provide some clues on structure-activity relations, since KYE21 retains both the antimicrobial and anti-endotoxic effects of KYE28 (although both attenuated), while NLF20 retains the antimicrobial but only a fraction of the anti-endotoxic effect, hence locating the anti-endotoxic effects of KYE28 to its N-terminus. The antimicrobial effect, on the other hand, is primarily located at the C-terminus of KYE28. While displaying quite different endotoxic effects, these peptides bind to a similar extent to both LPS and lipid A, and also induce comparable LPS scavenging on model eukaryotic membranes. In contrast, fragmentation and densification of LPS aggregates, in turn dependent on the secondary structure in the peptide/LPS aggregates, correlate to the anti-endotoxic effect of these peptides, thus identifying peptide-induced packing transitions in LPS aggregates as key for anti-endotoxic functionality. This aspect therefore needs to be taken into account in the development of novel anti-endotoxic peptide therapeutics. Copyright © 2013. Published by Elsevier B.V.

  18. Metal cofactor modulated folding and target recognition of HIV-1 NCp7.

    Science.gov (United States)

    Ren, Weitong; Ji, Dongqing; Xu, Xiulian

    2018-01-01

    The HIV-1 nucleocapsid 7 (NCp7) plays crucial roles in multiple stages of HIV-1 life cycle, and its biological functions rely on the binding of zinc ions. Understanding the molecular mechanism of how the zinc ions modulate the conformational dynamics and functions of the NCp7 is essential for the drug development and HIV-1 treatment. In this work, using a structure-based coarse-grained model, we studied the effects of zinc cofactors on the folding and target RNA(SL3) recognition of the NCp7 by molecular dynamics simulations. After reproducing some key properties of the zinc binding and folding of the NCp7 observed in previous experiments, our simulations revealed several interesting features in the metal ion modulated folding and target recognition. Firstly, we showed that the zinc binding makes the folding transition states of the two zinc fingers less structured, which is in line with the Hammond effect observed typically in mutation, temperature or denaturant induced perturbations to protein structure and stability. Secondly, We showed that there exists mutual interplay between the zinc ion binding and NCp7-target recognition. Binding of zinc ions enhances the affinity between the NCp7 and the target RNA, whereas the formation of the NCp7-RNA complex reshapes the intrinsic energy landscape of the NCp7 and increases the stability and zinc affinity of the two zinc fingers. Thirdly, by characterizing the effects of salt concentrations on the target RNA recognition, we showed that the NCp7 achieves optimal balance between the affinity and binding kinetics near the physiologically relevant salt concentrations. In addition, the effects of zinc binding on the inter-domain conformational flexibility and folding cooperativity of the NCp7 were also discussed.

  19. Cofactors involved in light-driven charge separation in photosystem I identified by subpicosecond infrared spectroscopy.

    Science.gov (United States)

    Di Donato, Mariangela; Stahl, Andreas D; van Stokkum, Ivo H M; van Grondelle, Rienk; Groot, Marie-Louise

    2011-02-01

    Photosystem I is one of the key players in the conversion of solar energy into chemical energy. While the chlorophyll dimer P(700) has long been identified as the primary electron donor, the components involved in the primary charge separation process in PSI remain undetermined. Here, we have studied the charge separation dynamics in Photosystem I trimers from Synechococcus elongatus by femtosecond vis-pump/mid-infrared-probe spectroscopy upon excitation at 700, 710, and 715 nm. Because of the high specificity of the infrared region for the redox state and small differences in the molecular structure of pigments, we were able to clearly identify specific marker bands indicating chlorophyll (Chl) oxidation. Magnitudes of chlorophyll cation signals are observed to increase faster than the time resolution of the experiment (~0.2 ps) upon both excitation conditions: 700 nm and selective red excitation. Two models, involving either ultrafast charge separation or charge transfer character of the red pigments in PSI, are discussed to explain this observation. A further increase in the magnitudes of cation signals on a subpicosecond time scale (0.8-1 ps) indicates the formation of the primary radical pair. Evolution in the cation region with time constants of 7 and 40 ps reveals the formation of the secondary radical pair, involving a secondary electron donor. Modeling of the data allows us to extract the spectra of the two radical pairs, which have IR signatures consistent with A+A₀- and P₇₀₀+A₁-. We conclude that the cofactor chlorophyll A acts as the primary donor in PSI. The existence of an equilibrium between the two radical pairs we interpret as concerted hole/electron transfer between the pairs of electron donors and acceptors, until after 40 ps, relaxation leads to a full population of the P₇₀₀+A₁. radical pair.

  20. Diversity and Functional Analysis of the FeMo-Cofactor Maturase NifB

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    Simon Arragain

    2017-11-01

    Full Text Available One of the main hurdles to engineer nitrogenase in a non-diazotrophic host is achieving NifB activity. NifB is an extremely unstable and oxygen sensitive protein that catalyzes a low-potential SAM-radical dependent reaction. The product of NifB activity is called NifB-co, a complex [8Fe-9S-C] cluster that serves as obligate intermediate in the biosyntheses of the active-site cofactors of all known nitrogenases. Here we study the diversity and phylogeny of naturally occurring NifB proteins, their protein architecture and the functions of the distinct NifB domains in order to understand what defines a catalytically active NifB. Focus is on NifB from the thermophile Chlorobium tepidum (two-domain architecture, the hyperthermophile Methanocaldococcus infernus (single-domain architecture and the mesophile Klebsiella oxytoca (two-domain architecture, showing in silico characterization of their nitrogen fixation (nif gene clusters, conserved NifB motifs, and functionality. C. tepidum and M. infernus NifB were able to complement an Azotobacter vinelandii (ΔnifB mutant restoring the Nif+ phenotype and thus demonstrating their functionality in vivo. In addition, purified C. tepidum NifB exhibited activity in the in vitro NifB-dependent nitrogenase reconstitution assay. Intriguingly, changing the two-domain K. oxytoca NifB to single-domain by removal of the C-terminal NifX-like extension resulted in higher in vivo nitrogenase activity, demonstrating that this domain is not required for nitrogen fixation in mesophiles.

  1. Dual functionality of β-tryptase protomers as both proteases and cofactors in the active tetramer.

    Science.gov (United States)

    Maun, Henry R; Liu, Peter S; Franke, Yvonne; Eigenbrot, Charles; Forrest, William F; Schwartz, Lawrence B; Lazarus, Robert A

    2018-04-16

    Human β-tryptase, a tetrameric trypsin-like serine protease, is an important mediator of the allergic inflammatory responses in asthma. During acute hypersensitivity reactions, mast cells degranulate, releasing active tetramer as a complex with proteoglycans. Extensive efforts have focused on developing therapeutic β-tryptase inhibitors, but its unique activation mechanism is less well explored. Tryptase is active only after proteolytic removal of the pro-domain followed by tetramer formation via two distinct symmetry-related interfaces. We show that the cleaved I16G mutant cannot tetramerize, likely due to impaired insertion of its N-terminus into its 'activation pocket', indicating allosteric linkage at multiple sites on each protomer. We engineered cysteines into each of the two distinct interfaces (Y75C for small or I99C for large) to assess the activity of each tetramer and disulfide-locked dimer. Using size-exclusion chromatography and enzymatic assays, we demonstrate that the two large tetramer interfaces regulate enzymatic activity, elucidating the importance of this protein-protein interaction for allosteric regulation. Notably, the I99C large interface dimer is active, even in the absence of heparin. We show that a monomeric β-tryptase mutant (I99C*:Y75A:Y37bA where C* is cysteinylated Cys99) cannot form a dimer or tetramer, yet is active, but only in the presence of heparin. Thus heparin both stabilizes the tetramer and allosterically conditions the active site. We hypothesize that each β-tryptase protomer in the tetramer has two distinct roles, acting both as a protease and as a cofactor for its neighboring protomer, to allosterically regulate enzymatic activity, providing a rationale for direct correlation of tetramer stability with proteolytic activity. Copyright © 2018, The American Society for Biochemistry and Molecular Biology.

  2. Metal cofactor modulated folding and target recognition of HIV-1 NCp7.

    Directory of Open Access Journals (Sweden)

    Weitong Ren

    Full Text Available The HIV-1 nucleocapsid 7 (NCp7 plays crucial roles in multiple stages of HIV-1 life cycle, and its biological functions rely on the binding of zinc ions. Understanding the molecular mechanism of how the zinc ions modulate the conformational dynamics and functions of the NCp7 is essential for the drug development and HIV-1 treatment. In this work, using a structure-based coarse-grained model, we studied the effects of zinc cofactors on the folding and target RNA(SL3 recognition of the NCp7 by molecular dynamics simulations. After reproducing some key properties of the zinc binding and folding of the NCp7 observed in previous experiments, our simulations revealed several interesting features in the metal ion modulated folding and target recognition. Firstly, we showed that the zinc binding makes the folding transition states of the two zinc fingers less structured, which is in line with the Hammond effect observed typically in mutation, temperature or denaturant induced perturbations to protein structure and stability. Secondly, We showed that there exists mutual interplay between the zinc ion binding and NCp7-target recognition. Binding of zinc ions enhances the affinity between the NCp7 and the target RNA, whereas the formation of the NCp7-RNA complex reshapes the intrinsic energy landscape of the NCp7 and increases the stability and zinc affinity of the two zinc fingers. Thirdly, by characterizing the effects of salt concentrations on the target RNA recognition, we showed that the NCp7 achieves optimal balance between the affinity and binding kinetics near the physiologically relevant salt concentrations. In addition, the effects of zinc binding on the inter-domain conformational flexibility and folding cooperativity of the NCp7 were also discussed.

  3. Horizontal acquisition of a hypoxia-responsive molybdenum cofactor biosynthesis pathway contributed to Mycobacterium tuberculosis pathoadaptation.

    Science.gov (United States)

    Levillain, Florence; Poquet, Yannick; Mallet, Ludovic; Mazères, Serge; Marceau, Michael; Brosch, Roland; Bange, Franz-Christoph; Supply, Philip; Magalon, Axel; Neyrolles, Olivier

    2017-11-01

    The unique ability of the tuberculosis (TB) bacillus, Mycobacterium tuberculosis, to persist for long periods of time in lung hypoxic lesions chiefly contributes to the global burden of latent TB. We and others previously reported that the M. tuberculosis ancestor underwent massive episodes of horizontal gene transfer (HGT), mostly from environmental species. Here, we sought to explore whether such ancient HGT played a part in M. tuberculosis evolution towards pathogenicity. We were interested by a HGT-acquired M. tuberculosis-specific gene set, namely moaA1-D1, which is involved in the biosynthesis of the molybdenum cofactor. Horizontal acquisition of this gene set was striking because homologues of these moa genes are present all across the Mycobacterium genus, including in M. tuberculosis. Here, we discovered that, unlike their paralogues, the moaA1-D1 genes are strongly induced under hypoxia. In vitro, a M. tuberculosis moaA1-D1-null mutant has an impaired ability to respire nitrate, to enter dormancy and to survive in oxygen-limiting conditions. Conversely, heterologous expression of moaA1-D1 in the phylogenetically closest non-TB mycobacterium, Mycobacterium kansasii, which lacks these genes, improves its capacity to respire nitrate and grants it with a marked ability to survive oxygen depletion. In vivo, the M. tuberculosis moaA1-D1-null mutant shows impaired survival in hypoxic granulomas in C3HeB/FeJ mice, but not in normoxic lesions in C57BL/6 animals. Collectively, our results identify a novel pathway required for M. tuberculosis resistance to host-imposed stress, namely hypoxia, and provide evidence that ancient HGT bolstered M. tuberculosis evolution from an environmental species towards a pervasive human-adapted pathogen.

  4. The Antioxidant Cofactor Alpha-Lipoic Acid May Control Endogenous Formaldehyde Metabolism in Mammals

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    Anastasia V. Shindyapina

    2017-12-01

    Full Text Available The healthy human body contains small amounts of metabolic formaldehyde (FA that mainly results from methanol oxidation by pectin methylesterase, which is active in a vegetable diet and in the gastrointestinal microbiome. With age, the ability to maintain a low level of FA decreases, which increases the risk of Alzheimer's disease and dementia. It has been shown that 1,2-dithiolane-3-pentanoic acid or alpha lipoic acid (ALA, a naturally occurring dithiol and antioxidant cofactor of mitochondrial α-ketoacid dehydrogenases, increases glutathione (GSH content and FA metabolism by mitochondrial aldehyde dehydrogenase 2 (ALDH2 thus manifests a therapeutic potential beyond its antioxidant property. We suggested that ALA can contribute to a decrease in the FA content of mammals by acting on ALDH2 expression. To test this assumption, we administered ALA in mice in order to examine the effect on FA metabolism and collected blood samples for the measurement of FA. Our data revealed that ALA efficiently eliminated FA in mice. Without affecting the specific activity of FA-metabolizing enzymes (ADH1, ALDH2, and ADH5, ALA increased the GSH content in the brain and up-regulated the expression of the FA-metabolizing ALDH2 gene in the brain, particularly in the hippocampus, but did not impact its expression in the liver in vivo or in rat liver isolated from the rest of the body. After ALA administration in mice and in accordance with the increased content of brain ALDH2 mRNA, we detected increased ALDH2 activity in brain homogenates. We hypothesized that the beneficial effects of ALA on patients with Alzheimer's disease may be associated with accelerated ALDH2-mediated FA detoxification and clearance.

  5. Terapias não farmacológicas no alívio da dor neuropática diabética: uma revisão bibliográfica

    OpenAIRE

    Franco, Letícia Cunha; Souza, Layz Alves Ferreira; Pessoa, Ana Paula da Costa; Pereira, Lílian Varanda

    2011-01-01

    A neuropatia diabética dolorosa caracteriza-se pela dor de difícil controle. O objetivo do estudo foi analisar a produção bibliográfica a respeito das terapias não farmacológicas utilizadas no alívio dessa dor. Pesquisa bibliográfica, por meio de seis (6) fontes de dados, nos últimos 12 anos (1998 a 2010), utilizando os descritores diabetes, diabetes mellitus, neuropatia dolorosa, dor neuropática, tratamento e similares. Foram selecionados 13 artigos, que abordaram o uso de acupuntura, reike,...

  6. Estudo prospectivo de pacientes pediátricos com dor abdominal crônica Prospective study of infants with chronic abdominal pain

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    Tatiana Kores Dorsa

    2007-09-01

    Full Text Available OBJETIVO: Classificar a dor abdominal crônica em crianças e adolescentes por meio dos critérios de Roma II e definir o desfecho diagnóstico em três anos de seguimento. MÉTODOS: Durante um ano, 71 pacientes com dor abdominal crônica foram atendidos como casos novos num ambulatório terciário de gastroenterologia pediátrica. Causas orgânicas foram excluídas por bases clínicas e laboratoriais, e relatos clínicos foram avaliados especificamente quanto à possibilidade de preencherem os Critérios de Roma II para dor abdominal em crianças. Para estabelecer o diagnóstico definitivo, os pacientes foram seguidos por três anos, em média. RESULTADOS: A alocação dos 71 pacientes segundo Roma II foi: doença orgânica (n=12, remissão dos sintomas após a primeira consulta (n=7, ou preencheram os critérios para dor funcional (n=52. Dos 12 pacientes de doença orgânica, nove foram diagnosticados como intolerantes à lactose, mas foram re-alocados para doença funcional no seguimento, visto que a dieta de isenção não aliviou a queixa. Dos 52 pacientes com doença funcional (idade mediana=9,3 anos, 50% meninos, nove, que inicialmente preencheram o critério para dor abdominal funcional, foram re-alocados no diagnóstico de constipação funcional e 43 mantiveram o diagnóstico funcional: 24 com dispepsia funcional, 18 com dor abdominal funcional e um com síndrome do intestino irritável. CONCLUSÕES: Dentre os casos de dor abdominal crônica, a dor do tipo funcional foi mais comum que as causas orgânicas e, dentre os seus subgrupos, a dispepsia funcional foi mais freqüente. O seguimento em longo prazo permitiu estabelecer o diagnóstico definitivo da origem da dor abdominal nessas crianças.OBJECTIVE: To classify chronic abdominal pain in children and adolescents, according to Rome II criteria and to define diagnosis outcome in a three-year follow-up period. METHODS: During one year, 71 consecutive new patients with abdominal pain

  7. Poderia a atividade física induzir analgesia em pacientes com dor crônica? Can exercise induce analgesia in patients with chronic pain?

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    Juliana Barcellos de Souza

    2009-04-01

    Full Text Available A dor crônica caracteriza-se pela persistência do sintoma além do período fisiológico de recuperação do tecido lesado. Essas dores causam incapacidade física e redução da performance cognitiva, reduzem a qualidade de vida e o bem-estar dos pacientes, cujo tratamento proposto contradiz o clássico binômio da terapia da dor aguda (repouso e fármacos. Para a dor crônica prescrevem-se exercícios físicos e sugerem-se tratamentos multidisciplinares. Embora a atividade física seja prescrita há mais de 20 anos, os mecanismos neurofisiológicos envolvidos ainda não são compreendidos. Descrevemos brevemente os mecanismos endógenos de controle da dor crônica e evidências da literatura científica que defendem o sistema opioide como mecanismo de ação na analgesia induzida pelo exercício em indivíduos sadios e atletas. Esse mecanismo também parece agir na população com dor crônica, embora haja controvérsias. Finalizamos o artigo com considerações clínicas para a prescrição do exercício para a população com dor crônica.Chronic pain is defined as persistent pain beyond normal tissue healing time. Chronic pain syndromes have a considerable impact on functional capacity, resulting in disrupted work and social activities; therefore, the impact of these syndromes affect the society at large and at a high economic cost. In contrast to rest and pharmacological treatment, multidisciplinary programs with exercises have shown to improve pain and function in chronic pain patients. A number of studies reported analgesia induced by exercise; however, the neurological mechanisms involved are not known yet. To explore this phenomenon, we describe endogenous pain control relating some studies on general population and chronic pain subjects, and we conclude this paper with some clinical consideration to determine optimal intensity of exercise to produce hypoalgesia.

  8. Comorbid anxiety and depression disorders in patients with chronic pain Transtornos ansiosos e depressivos em pacientes com dor crônica

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    Martha Castro

    2009-12-01

    Full Text Available OBJECTIVE: To evaluate the frequency of anxiety and depression disorders in patients with chronic pain. METHOD: Patients receiving care at the pain clinic of the Federal University of Bahia between February 2003 and November 2006. The MINI PLUS - Mini International Neuropsychiatric Interview was used to evaluate the patients and establish psychiatric diagnoses. RESULTS: 400 patients were evaluated mean age was 45.6±11.37 years; 82.8% were female, 17.3% male; 48.5% were married; 55.1% were Catholics; and 40.5% had only high school education. Of these 29.9% reported intense pain and 70.8% reported suffering pain daily. The most frequent medical diagnosis was herniated disc (24.5%, and 48.5% of patients had been undergoing treatment at the pain clinic for less than 3 months. Comorbidities found were depressive episodes (42%, dysthymia (54%, social phobia (36.5%, agoraphobia (8.5% and panic disorder (7.3%. CONCLUSION: Psychiatric comorbidities are prevalent in patients suffering chronic pain.OBJETIVO: Avaliar a freqüência de transtornos ansiosos e depressivos em pacientes com dor crônica. MÉTODO: Os pacientes foram avaliados na clínica da dor da Universidade Federal da Bahia entre fevereiro 2003 e novembro 2006. O Mini-plus - entrevista neuropsiquiátrica internacional foi usado para estabelecer diagnósticos psiquiátricos nos pacientes. RESULTADOS: Foram avaliados 400 pacientes com idade média de 45,6±11,37 anos; 82,8% eram mulheres, homens 17,3%; 48,5% eram casados; 55,1% católicos; e 40,5% concluíram o segundo grau, 29,9% relataram dor intensa e 70,8% relataram sentir dor diariamente. O diagnóstico médico o mais freqüente foi hérnia de disco (24,5%, e 48,5% dos pacientes submeteu-se ao tratamento na clínica da dor por menos de 3 meses. Comorbidades encontradas foram episódios depressivos (42%, distimia (54%, fobia social (36,5%, agorafobia (8,5% e transtorno de pânico (7,3%. CONCLUSÃO: Comorbidades psiquiátricas s

  9. Fibromyalgia patients' quality of life and pain intensity variation Variação da intensidade da dor e da qualidade de vida de pacientes com fibromialgia

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    José Eduardo Martinez

    2008-12-01

    Full Text Available INTRODUCTION: One of the most reported issues on the Fibromyalgia syndrome is the pain intensity variation and its impact on patients' life quality. OBJECTIVES: 1 to establish the correlation among pain, anxiety and depression intensity perception; 2 to determine whether there is a correlation between pain intensity variation and the impact of fibromyalgia on patients' quality of life. MATERIAL AND METHODS: A study was carried out with 21 patients, who received a diary to register their perceptions on pain, anxiety and depression intensity. The patients have made this procedure three times a day, for a fifteen-day period. The impact on life quality was measured by the the Fibromyalgia Impact Questionaire (FIQ. RESULTS: It was observed a significant variation on pain intensity during the day periods. There was not a significant variation for anxiety and depression through the day periods. It was not observed any significant correlation between pain and depression or pain and anxiety intensity perception at any time of the day, during the study period. When considering the whole study period, it was observed that there was a correlation between pain and anxiety and pain and depression in the morning. CONCLUSION: It is concluded that there is a significant pain variation through the day periods and there is a correlation between pain and anxiety and pain and depression in the morning. There is a significant correlation of life quality with pain in the morning, anxiety in the afternoon and evening; and depression in all periods of the day.INTRODUÇÃO: Uma das questões mais relatadas é a variação da intensidade da dor no decorrer do dia e seu impacto na qualidade de vida. OBJETIVOS: Estabelecer a correlação entre a percepção da intensidade da dor, da ansiedade e da depressão e determinar a correlação entre a variação da intensidade da dor e o impacto na qualidade de vida. MATERIAL E MÉTODOS: Estudou-se 21 pacientes com fibromialgia. As

  10. Iron Sulfur and Molybdenum Cofactor Enzymes Regulate the Drosophila Life Cycle by Controlling Cell Metabolism

    Science.gov (United States)

    Marelja, Zvonimir; Leimkühler, Silke; Missirlis, Fanis

    2018-01-01

    Iron sulfur (Fe-S) clusters and the molybdenum cofactor (Moco) are present at enzyme sites, where the active metal facilitates electron transfer. Such enzyme systems are soluble in the mitochondrial matrix, cytosol and nucleus, or embedded in the inner mitochondrial membrane, but virtually absent from the cell secretory pathway. They are of ancient evolutionary origin supporting respiration, DNA replication, transcription, translation, the biosynthesis of steroids, heme, catabolism of purines, hydroxylation of xenobiotics, and cellular sulfur metabolism. Here, Fe-S cluster and Moco biosynthesis in Drosophila melanogaster is reviewed and the multiple biochemical and physiological functions of known Fe-S and Moco enzymes are described. We show that RNA interference of Mocs3 disrupts Moco biosynthesis and the circadian clock. Fe-S-dependent mitochondrial respiration is discussed in the context of germ line and somatic development, stem cell differentiation and aging. The subcellular compartmentalization of the Fe-S and Moco assembly machinery components and their connections to iron sensing mechanisms and intermediary metabolism are emphasized. A biochemically active Fe-S core complex of heterologously expressed fly Nfs1, Isd11, IscU, and human frataxin is presented. Based on the recent demonstration that copper displaces the Fe-S cluster of yeast and human ferredoxin, an explanation for why high dietary copper leads to cytoplasmic iron deficiency in flies is proposed. Another proposal that exosomes contribute to the transport of xanthine dehydrogenase from peripheral tissues to the eye pigment cells is put forward, where the Vps16a subunit of the HOPS complex may have a specialized role in concentrating this enzyme within pigment granules. Finally, we formulate a hypothesis that (i) mitochondrial superoxide mobilizes iron from the Fe-S clusters in aconitase and succinate dehydrogenase; (ii) increased iron transiently displaces manganese on superoxide dismutase, which

  11. Hydrogen Activation by Biomimetic [NiFe]-Hydrogenase Model Containing Protected Cyanide Cofactors

    Science.gov (United States)

    Manor, Brian C.; Rauchfuss, Thomas B.

    2013-01-01

    Described are experiments that allow incorporation of cyanide cofactors and hydride substrate into active site models [NiFe]-hydrogenases (H2ases). Complexes of the type (CO)2(CN)2Fe(pdt)Ni(dxpe), (dxpe = dppe, 1; dxpe = dcpe, 2) bind the Lewis acid B(C6F5)3 (BArF3) to give the adducts (CO)2(CNBArF3)2Fe(pdt)Ni(dxpe), (1(BArF3)2, 2(BArF3)2). Upon decarbonylation using amine oxides, these adducts react with H2 to give hydrido derivatives Et4N[(CO)(CNBArF3)2Fe(H)(pdt)Ni(dxpe)], (dxpe = dppe, Et4N[H3(BArF3)2]; dxpe = dcpe, Et4N[H4(BArF3)2]). Crystallographic analysis shows that Et4N[H3(BArF3)2] generally resembles the active site of the enzyme in the reduced, hydride-containing states (Ni-C/R). The Fe-H…Ni center is unsymmetrical with rFe-H = 1.51(3) and rNi-H = 1.71(3) Å. Both crystallographic and 19F NMR analysis show that the CNBArF3− ligands occupy basal and apical sites. Unlike cationic Ni-Fe hydrides, [H3(BArF3)2]− and [H4(BArF3)2]− oxidize at mild potentials, near the Fc+/0 couple. Electrochemical measurements indicate that in the presence of base, [H3(BArF3)2]− catalyzes the oxidation of H2. NMR evidence indicates dihydrogen bonding between these anionic hydrides and ammonium salts, which is relevant to the mechanism of hydrogenogenesis. In the case of Et4N[H3(BArF3)2], strong acids such as HCl induce H2 release to give the chloride Et4N[(CO)(CNBArF3)2Fe(pdt)(Cl)Ni(dppe)]. PMID:23899049

  12. Iron Sulfur and Molybdenum Cofactor Enzymes Regulate the Drosophila Life Cycle by Controlling Cell Metabolism

    Directory of Open Access Journals (Sweden)

    Zvonimir Marelja

    2018-02-01

    Full Text Available Iron sulfur (Fe-S clusters and the molybdenum cofactor (Moco are present at enzyme sites, where the active metal facilitates electron transfer. Such enzyme systems are soluble in the mitochondrial matrix, cytosol and nucleus, or embedded in the inner mitochondrial membrane, but virtually absent from the cell secretory pathway. They are of ancient evolutionary origin supporting respiration, DNA replication, transcription, translation, the biosynthesis of steroids, heme, catabolism of purines, hydroxylation of xenobiotics, and cellular sulfur metabolism. Here, Fe-S cluster and Moco biosynthesis in Drosophila melanogaster is reviewed and the multiple biochemical and physiological functions of known Fe-S and Moco enzymes are described. We show that RNA interference of Mocs3 disrupts Moco biosynthesis and the circadian clock. Fe-S-dependent mitochondrial respiration is discussed in the context of germ line and somatic development, stem cell differentiation and aging. The subcellular compartmentalization of the Fe-S and Moco assembly machinery components and their connections to iron sensing mechanisms and intermediary metabolism are emphasized. A biochemically active Fe-S core complex of heterologously expressed fly Nfs1, Isd11, IscU, and human frataxin is presented. Based on the recent demonstration that copper displaces the Fe-S cluster of yeast and human ferredoxin, an explanation for why high dietary copper leads to cytoplasmic iron deficiency in flies is proposed. Another proposal that exosomes contribute to the transport of xanthine dehydrogenase from peripheral tissues to the eye pigment cells is put forward, where the Vps16a subunit of the HOPS complex may have a specialized role in concentrating this enzyme within pigment granules. Finally, we formulate a hypothesis that (i mitochondrial superoxide mobilizes iron from the Fe-S clusters in aconitase and succinate dehydrogenase; (ii increased iron transiently displaces manganese on superoxide

  13. Tubulin binding cofactor C (TBCC) suppresses tumor growth and enhances chemosensitivity in human breast cancer cells

    International Nuclear Information System (INIS)

    Hage-Sleiman, Rouba; Herveau, Stéphanie; Matera, Eva-Laure; Laurier, Jean-Fabien; Dumontet, Charles

    2010-01-01

    Microtubules are considered major therapeutic targets in patients with breast cancer. In spite of their essential role in biological functions including cell motility, cell division and intracellular transport, microtubules have not yet been considered as critical actors influencing tumor cell aggressivity. To evaluate the impact of microtubule mass and dynamics on the phenotype and sensitivity of breast cancer cells, we have targeted tubulin binding cofactor C (TBCC), a crucial protein for the proper folding of α and β tubulins into polymerization-competent tubulin heterodimers. We developed variants of human breast cancer cells with increased content of TBCC. Analysis of proliferation, cell cycle distribution and mitotic durations were assayed to investigate the influence of TBCC on the cell phenotype. In vivo growth of tumors was monitored in mice xenografted with breast cancer cells. The microtubule dynamics and the different fractions of tubulins were studied by time-lapse microscopy and lysate fractionation, respectively. In vitro sensitivity to antimicrotubule agents was studied by flow cytometry. In vivo chemosensitivity was assayed by treatment of mice implanted with tumor cells. TBCC overexpression influenced tubulin fraction distribution, with higher content of nonpolymerizable tubulins and lower content of polymerizable dimers and microtubules. Microtubule dynamicity was reduced in cells overexpressing TBCC. Cell cycle distribution was altered in cells containing larger amounts of TBCC with higher percentage of cells in G2-M phase and lower percentage in S-phase, along with slower passage into mitosis. While increased content of TBCC had little effect on cell proliferation in vitro, we observed a significant delay in tumor growth with respect to controls when TBCC overexpressing cells were implanted as xenografts in vivo. TBCC overexpressing variants displayed enhanced sensitivity to antimicrotubule agents both in vitro and in xenografts. These

  14. The human membrane cofactor CD46 is a receptor for species B adenovirus serotype 3.

    Science.gov (United States)

    Sirena, Dominique; Lilienfeld, Benjamin; Eisenhut, Markus; Kälin, Stefan; Boucke, Karin; Beerli, Roger R; Vogt, Lorenz; Ruedl, Christiane; Bachmann, Martin F; Greber, Urs F; Hemmi, Silvio

    2004-05-01

    Many human adenovirus (Ad) serotypes use the coxsackie B virus-Ad receptor (CAR). Recently, CD46 was suggested to be a receptor of species B Ad serotype 11 (Ad11), Ad14, Ad16, Ad21, Ad35, and Ad50. Using Sindbis virus-mediated cDNA library expression, we identify here the membrane cofactor protein CD46 as a surface receptor of species B Ad3. All four major CD46 transcripts and one minor CD46 transcript expressed in nucleated human cells were isolated. Rodent BHK cells stably expressing the BC1 form of CD46 bound radiolabeled Ad3 with a dissociation constant of 0.3 nM, identical to that of CD46-positive HeLa cells expressing twice as many Ad3 binding sites. Pull-down experiments with recombinant Ad3 fibers and a soluble form of the CD46 extracellular domain linked to the Fc portion of human immunoglobulin G (CD46ex-Fc) indicated direct interactions of the Ad3 fiber knob with CD46ex-Fc but not CARex-Fc (Fc-linked extracellular domain of CAR). Ad3 colocalized with cell surface CD46 in both rodent and human cells at the light and electron microscopy levels. Anti-CD46 antibodies and CD46ex-Fc inhibited Ad3 binding to CD46-expressing BHK cells more than 10-fold and to human cells 2-fold. In CD46-expressing BHK cells, wild-type Ad3 and a chimeric Ad consisting of the Ad5 capsid and the Ad3 fiber elicited dose-dependent cytopathic effects and transgene expression, albeit less efficiently than in human cells. Together, our results show that all of the major splice forms of CD46 are predominant and functional binding sites of Ad3 on CD46-expressing rodent and human cells but may not be the sole receptor of species B Ads on human cells. These results have implications for understanding viral pathogenesis and therapeutic gene delivery.

  15. O médico e a dor: aspectos da prescrição de analgésicos para pacientes internados no pós-operatório do Conjunto Hospitalar de Sorocaba

    Directory of Open Access Journals (Sweden)

    José Roberto Pretel Pereira Job

    2014-10-01

    Full Text Available Introdução: O trauma advindo do ato operatório implica em alterações fisiológicas e emocionais. Quando não aliviada, a dor no pós-operatório pode afetar os sistemas pulmonar, cardiovascular, gastrointestinal, endócrino e imunológico, sendo dessa forma prejudicial ao paciente e influenciar negativamente na recuperação do mesmo. O controle da dor e o alívio do sofrimento são responsabilidade do profissional da área de saúde. Objetivos: comparar a intensidade da dor referida por pacientes do Conjunto Hospitalar de Sorocaba, se há alteração da intensidade de dor durante o pós-operatório, avaliar o tratamento prescrito para aliviar essa dor, além de avaliar a influência da dor em atividades cotidianas como, o sono e o humor. Metodologia: Foi aplicado o questionário do Inventário da Dor de Wisconsin adaptado nas primeiras 24 horas e nas 72 horas do evento cirúrgico a 120 pacientes de ambos os sexos, maiores de 18 anos, internados no pós-operatório imediato de cirurgias, no CHS. Resultados: Houve significância no caso da percepção da dor mais forte sentida em pacientes que passaram por cirurgia no abdome, e no caso da percepção da dor mais fraca sentida em pacientes de cirurgias em membros inferiores. A percepção em ambos os casos diminuiu, do 1o para o 3o dia de pós-operatório. Conclusão: o tratamento não é totalmente efetivo, pois o ideal seria que a percepção da dor diminuísse em cirurgias de todas as áreas do corpo, e nos três tipos de dor (no momento, mais forte e mais fraca.

  16. Correlação entre alterações lombares e modificações no arco plantar em mulheres com dor lombar

    OpenAIRE

    Borges,Cláudia dos Santos; Fernandes,Luciane Fernanda Rodrigues Martinho; Bertoncello,Dernival

    2013-01-01

    OBJETIVO: Avaliar provável correlação entre arco plantar, curvatura lombar e dores lombares. MÉTODOS: Foram avaliadas 18 mulheres com queixa de dor lombar, submetidas a uma avaliação que constava de dados pessoais e de um exame físico com medidas antropométricas, avaliação do arco plantar por meio fotopodoscopia, avaliação da postura do paciente por meio do biofotogrametria, ambos utilizando o programa SAPO, além de avaliação da dor lombar pela escala visual analógica (EVA). A idade média dos...

  17. Avaliação da dor em portadores de hanseníase submetidos à mobilização neural

    OpenAIRE

    Véras,Larissa Sales Téles; Vale,Rodrigo Gomes de Souza; Mello,Danielli Braga de; Castro,José Adail Fonseca de; Dantas,Estélio Henrique Martin

    2011-01-01

    Este estudo tem como objetivo avaliar o efeito da técnica de mobilização neural sobre a percepção da dor em portadores de hanseníase. A amostra de 56 indivíduos portadores de hanseníase foi randomizada em: grupo experimental (GMN) composto por 29 indivíduos submetidos ao tratamento com mobilização neural e grupo controle (GC) composto por 27 indivíduos que foram submetidos ao tratamento convencional. A percepção da dor foi avaliada através da Escala Visual Analógica, indicando-se em uma extre...

  18. Estudo prospectivo de pacientes pediátricos com dor abdominal crônica Prospective study of infants with chronic abdominal pain

    OpenAIRE

    Tatiana Kores Dorsa; Gabriel Hessel; Magno Cardoso V. Neto; Elizete Aparecida L. C. Pinto

    2007-01-01

    OBJETIVO: Classificar a dor abdominal crônica em crianças e adolescentes por meio dos critérios de Roma II e definir o desfecho diagnóstico em três anos de seguimento. MÉTODOS: Durante um ano, 71 pacientes com dor abdominal crônica foram atendidos como casos novos num ambulatório terciário de gastroenterologia pediátrica. Causas orgânicas foram excluídas por bases clínicas e laboratoriais, e relatos clínicos foram avaliados especificamente quanto à possibilidade de preencherem os Critérios de...

  19. Uso de medicações por via subaracnóidea no tratamento da dor crônica

    Directory of Open Access Journals (Sweden)

    Rocha Anita Perpétua Carvalho

    2002-01-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A dor crônica é um desafio para a Medicina atual. Novos métodos e medicamentos têm sido propostos com o intuito de controlar os sintomas álgicos. A via de administração subaracnóidea tem se mostrado como uma alternativa viável e segura, embora necessite continuamente ser objeto de estudo de muitos pesquisadores. O objetivo deste trabalho é fazer uma revisão dos medicamentos disponíveis no arsenal terapêutico já consagrados pelo uso e os que se mostram promissores na atualidade para a prática clínica diária. CONTEÚDO: Nesta revisão são avaliados vários fármacos que apresentam ação analgésica quando utilizada via neuroeixo. Opióides, anestésicos locais, agonistas alfa2-adrenérgicos, antagonistas dos aminoácidos excitatórios e inibitórios, acetilcolina, inibidores da acetilcolinesterase, bloqueadores dos canais de cálcio, adenosina, serotonina, antidepressivos tricíclicos e inibidores da síntese de prostaglandinas são analisados no que concerne aos seus efeitos farmacológicos, incluindo os indesejáveis. CONCLUSÕES: Muitos avanços foram registrados no controle dos sintomas álgicos após a utilização das substâncias citadas por via raquidiana, onde certamente algumas serão aproveitadas e enriquecerão o arsenal terapêutico e outras relegadas temporária ou definitivamente. Entretanto, ainda serão necessários muitos estudos clínicos e experimentais para que estes conhecimentos possam ser incorporados e utilizados com segurança pelos profissionais que lidam com o tratamento da dor crônica.

  20. Controle da dor no pós-operatório de cirurgia cardíaca: uma breve revisão

    Directory of Open Access Journals (Sweden)

    Luciano Ramos de Lima

    2008-06-01

    Full Text Available Este estudo teve como objetivo identificar as terapêuticas analgésicas para controle da dor no pós-operatório de pacientes submetidos à cirurgia cardíaca e os instrumentos utilizados para mensurar a experiência dolorosa. Trata-se de uma pesquisa bibliográfica realizada por meio de revisão da literatura nas bases de dados eletrônicos LILACS, revistas eletrônicas da SciELO, dissertações e teses. Foram utilizados os descritores analgesia, analgesia controlada pelo paciente, cirurgia cardíaca, avaliação e dor pós-operatória. O levantamento dos dados ocorreu em maio de 2007 e foram selecionados estudos publicados no período de maio de 1997 a maio de 2007. Na análise realizou-se síntese reflexiva dos estudos. Dos 23 estudos levantados foram utilizados 8 artigos e uma dissertação de mestrado. A técnica de analgesia mais utilizada foi a Analgesia Controlada pelo Paciente (ACP e os medicamentos mais utilizado foram os opióides, como a morfina, seguidos por antiflamatórios não esteroidais (AINEs e dipirona. Não foram encontrados estudos que utilizaram a terapêutica não farmacológica. Os instrumentos de avaliação de dor frequentemente utilizados nestes estudos incluíram as escalas unidimensionais como a escala numérica verbal e a escala analógica visual. Ficou também evidenciado que os enfermeiros estão pouco envolvidos em pesquisas que abordam o controle da dor no período pós-operatório de cirurgia cardíaca.

  1. The Story of Dorćol: The “Jevremova – Street of Meetings” Manifestation and the Multicultural Construction of Place of Memory

    Directory of Open Access Journals (Sweden)

    Dragana Antonijević

    2016-02-01

    Full Text Available The paper considers the manifestation “Jevremova Street – Street of Meetings” as a new custom instated by the Belgrade municipality of Stari Grad (Old Town, as a means to promote the spirit of neighborly relations and tolerance, as well as evoke the collective memory of the multiethnic and multiconfessional makeup of the inhabitants of the oldest part of the city – Dorćol. The obvious intent to keep up with the global trend of multicultural policies initiated not only this manifestation, but also a specific kind of “branding” of Dorćol through a series of different activities and publications dedicated to emphasizing the cultural specificity of this part of the city which is characterized by a unique topography, the great age of the city center, and a multicultural past. The attempts made by administrative governments and cultural organizations to promote Dorćol and revitalize its significance as a “place of memory” and an attractive tourist, cultural, educational and commercial location, a multiethnic location rife with urban spirit was motivated, in this author’s opinion, by political reasons and was supposed to serve as a means to demonstrate the extent of the democratic and civil changes in Serbia after the year 2000. The data presented here was gathered through the ethnographic method of participant observation. The main characteristics of the “Jevremova – Street of Meetings” celebration have been described, and its function within the context of historical, ethnic and confessional specificities of Dorćol have been analyzed. The paper also includes an analysis of the urban semiotics of the neighborhood.

  2. Oxidation of the FAD cofactor to the 8-formyl-derivative in human electron-transferring flavoprotein

    Science.gov (United States)

    Augustin, Peter; Toplak, Marina; Fuchs, Katharina; Gerstmann, Eva Christine; Prassl, Ruth; Winkler, Andreas; Macheroux, Peter

    2018-01-01

    The heterodimeric human (h) electron-transferring flavoprotein (ETF) transfers electrons from at least 13 different flavin dehydrogenases to the mitochondrial respiratory chain through a non-covalently bound FAD cofactor. Here, we describe the discovery of an irreversible and pH-dependent oxidation of the 8α-methyl group to 8-formyl-FAD (8f-FAD), which represents a unique chemical modification of a flavin cofactor in the human flavoproteome. Furthermore, a set of hETF variants revealed that several conserved amino acid residues in the FAD-binding pocket of electron-transferring flavoproteins are required for the conversion to the formyl group. Two of the variants generated in our study, namely αR249C and αT266M, cause glutaric aciduria type II, a severe inherited disease. Both of the variants showed impaired formation of 8f-FAD shedding new light on the potential molecular cause of disease development. Interestingly, the conversion of FAD to 8f-FAD yields a very stable flavin semiquinone that exhibited slightly lower rates of electron transfer in an artificial assay system than hETF containing FAD. In contrast, the formation of 8f-FAD enhanced the affinity to human dimethylglycine dehydrogenase 5-fold, indicating that formation of 8f-FAD modulates the interaction of hETF with client enzymes in the mitochondrial matrix. Thus, we hypothesize that the FAD cofactor bound to hETF is subject to oxidation in the alkaline (pH 8) environment of the mitochondrial matrix, which may modulate electron transport between client dehydrogenases and the respiratory chain. This discovery challenges the current concepts of electron transfer processes in mitochondria. PMID:29301933

  3. Identification of the APC/C co-factor FZR1 as a novel therapeutic target for multiple myeloma.

    Science.gov (United States)

    Crawford, Lisa J; Anderson, Gordon; Johnston, Cliona K; Irvine, Alexandra E

    2016-10-25

    Multiple Myeloma (MM) is a haematological neoplasm characterised by the clonal proliferation of malignant plasma cells in the bone marrow. The success of proteasome inhibitors in the treatment of MM has highlighted the importance of the ubiquitin proteasome system (UPS) in the pathogenesis of this disease. In this study, we analysed gene expression of UPS components to identify novel therapeutic targets within this pathway in MM. Here we demonstrate how this approach identified previously validated and novel therapeutic targets. In addition we show that FZR1 (Fzr), a cofactor of the multi-subunit E3 ligase complex anaphase-promoting complex/cyclosome (APC/C), represents a novel therapeutic target in myeloma. The APC/C associates independently with two cofactors, Fzr and Cdc20, to control cell cycle progression. We found high levels of FZR1 in MM primary cells and cell lines and demonstrate that expression is further increased on adhesion to bone marrow stromal cells (BMSCs). Specific knockdown of either FZR1 or CDC20 reduced viability and induced growth arrest of MM cell lines, and resulted in accumulation of APC/CFzr substrate Topoisomerase IIα (TOPIIα) or APC/CCdc20 substrate Cyclin B. Similar effects were observed following treatment with proTAME, an inhibitor of both APC/CFzr and APC/CCdc20. Combinations of proTAME with topoisomerase inhibitors, etoposide and doxorubicin, significantly increased cell death in MM cell lines and primary cells, particularly if TOPIIα levels were first increased through pre-treatment with proTAME. Similarly, combinations of proTAME with the microtubule inhibitor vincristine resulted in enhanced cell death. This study demonstrates the potential of targeting the APC/C and its cofactors as a therapeutic approach in MM.

  4. Niveles plasmáticos e interacciones del sistema cofactor 2 de la heparina-trombina-dermatan sulfato

    OpenAIRE

    Rossi, Eleonora Beatriz

    1999-01-01

    El Cofactor II de la Heparina (HCII) es un inhibidor fisiológico del sistema de coagulación, miembro de la familia de serpinas. Inhibe específicamente trombina, una enzima clave del sistema hemostático. La capacidad del HCII de inhibir trombina es potenciada mas de 1000 veces por la presencia de glicosaminoglicano el Dermatán Sulfato (DS),. Aún no está claramente definido el papel que desempeña el HCII en la fisiología de la Hemostasia, postulándose su deficiencia corno leve factor de riesgo ...

  5. Streptococcus sanguinis class Ib ribonucleotide reductase: high activity with both iron and manganese cofactors and structural insights.

    Science.gov (United States)

    Makhlynets, Olga; Boal, Amie K; Rhodes, Delacy V; Kitten, Todd; Rosenzweig, Amy C; Stubbe, JoAnne

    2014-02-28

    Streptococcus sanguinis is a causative agent of infective endocarditis. Deletion of SsaB, a manganese transporter, drastically reduces S. sanguinis virulence. Many pathogenic organisms require class Ib ribonucleotide reductase (RNR) to catalyze the conversion of nucleotides to deoxynucleotides under aerobic conditions, and recent studies demonstrate that this enzyme uses a dimanganese-tyrosyl radical (Mn(III)2-Y(•)) cofactor in vivo. The proteins required for S. sanguinis ribonucleotide reduction (NrdE and NrdF, α and β subunits of RNR; NrdH and TrxR, a glutaredoxin-like thioredoxin and a thioredoxin reductase; and NrdI, a flavodoxin essential for assembly of the RNR metallo-cofactor) have been identified and characterized. Apo-NrdF with Fe(II) and O2 can self-assemble a diferric-tyrosyl radical (Fe(III)2-Y(•)) cofactor (1.2 Y(•)/β2) and with the help of NrdI can assemble a Mn(III)2-Y(•) cofactor (0.9 Y(•)/β2). The activity of RNR with its endogenous reductants, NrdH and TrxR, is 5,000 and 1,500 units/mg for the Mn- and Fe-NrdFs (Fe-loaded NrdF), respectively. X-ray structures of S. sanguinis NrdIox and Mn(II)2-NrdF are reported and provide a possible rationale for the weak affinity (2.9 μM) between them. These streptococcal proteins form a structurally distinct subclass relative to other Ib proteins with unique features likely important in cluster assembly, including a long and negatively charged loop near the NrdI flavin and a bulky residue (Thr) at a constriction in the oxidant channel to the NrdI interface. These studies set the stage for identifying the active form of S. sanguinis class Ib RNR in an animal model for infective endocarditis and establishing whether the manganese requirement for pathogenesis is associated with RNR.

  6. Integrating biocompatible chemistry and manipulating cofactor partitioning in metabolically engineeredLactococcus lactisfor fermentative production of (3S)-acetoin

    DEFF Research Database (Denmark)

    Liu, Jianming; Solem, Christian; Jensen, Peter Ruhdal

    2016-01-01

    Biocompatible chemistry (BC), i.e. non-enzymatic chemical reactions compatible with living organisms, is increasingly used in conjunction with metabolically engineered microorganisms for producing compounds that do not usually occur naturally. Here we report production of one such compound, (3S......)-acetoin, a valuable precursor for chiral synthesis, using a metabolically engineered Lactococcus lactis strain growing under respiratory conditions with ferric iron serving as a BC component. The strain used has all competing product pathways inactivated, and an appropriate cofactor balance is achieved by fine...

  7. Prevalência de dor musculoesquelética em corredores de rua no momento em que precede o início da corrida

    Directory of Open Access Journals (Sweden)

    Tiê Parma Yamato

    2011-06-01

    Full Text Available A participação em corridas de rua vem aumentando significativamente nos últimos anos, motivada pelos benefícios a saúde, fácil execução e baixo custo. Os objetivos desse estudo foram: analisar a prevalência de dor musculoesquelética em corredores de rua no momento em que precede o início da prova, além de discutir alguns fatores etiológicos relacionados à prática da corrida. Os participantes foram divididos em dois grupos, um grupo foi composto por corredores com queixa de dor musculoesquelética e outro sem queixa. Foi constatada uma diferença estatisticamente significante quando comparados o número de treinos por semana (p=0,03 e a quilometragem semanal percorrida (p=0,01. Concluímos que a prevalência de dor foi de aproximadamente 25% e estava diretamente associada ao volume de treino semanal.

  8. Uso e rotação de opioides para dor crônica não oncológica

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    Durval Campos Kraychete

    2012-08-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Para o tratamento da dor crônica existe a possibilidade de uso prolongado de opioides. Os opioides são eficazes para praticamente todas as síndromes dolorosas crônicas não oncológicas, porém podem causar dependência. O objetivo deste texto é fazer uma revisão sobre o uso e rotação de opioides para dor crônica não oncológica. CONTEÚDO: O uso de opioides potentes é controverso e não são recomendados como medicamentos de primeira linha devido à possibilidade de dependência. Foi descrita tolerância, vício, fatores de risco para vício, rotação ou troca, regras gerais para administração, tabelas de conversão e dicas para prescrição de opioides. CONCLUSÕES: Os opioides são fármacos com eficácia comprovada para dor crônica não oncológica, porém sua prescrição deve ser feita respeitando alguns critérios para reduzir a incidência de efeitos adversos e vício.

  9. DIAGNÓSTICO E TRATAMENTO NA DOR LOMBAR INESPECÍFICA ATRAVÉS DO MÉTODO MCKENZIE: UMA REVISÃO BIBLIOGRÁFICA

    Directory of Open Access Journals (Sweden)

    Marilia de Souza Vieira Fabre

    2017-02-01

    Full Text Available Resumo – Introdução: O método Mckenzie consiste em um programa de movimentos prescritos por fisioterapeuta, sem o auxílio de equipamentos específicos, onde o paciente aprende a identificar os movimentos, posturas e atividades que aumentam e pioram a sua dor, podendo tratá-las restaurando os mecanismos funcionais. Objetivo: Verificar as publicações na área da fisioterapia relacionadas aos benefícios do método Mckenzie no tratamento da dor lombar inespecífica. Método: Revisão bibliográfica na base de dados PubMed e Lilacs utilizando as palavras-chave: “Method Mckenzie”, “treatment”, “low back pain”. Resultados: foram encontrados 101 artigos, sendo que apenas 22 encontravam- se nos critérios de inclusão, palavra-chave, pesquisas realizadas nos ultimos 10 anos e em seres humanos com textos completo em inglês. Conclusão: O método Mckenzie apesar de ainda mostrar poucas evidências específicas, possui características próprias de autocuidado e de tratamento que agem de forma positiva na gestão da dor, mostrando à sua importância fundamental na avaliação e na classificação das disfunções.

  10. Fatores de risco associados à intensidade de dor nas costas em escolares do município de Teutônia (RS

    Directory of Open Access Journals (Sweden)

    Matias Noll

    2016-06-01

    Full Text Available Resumo Este estudo teve como objetivo verificar a prevalência e intensidade de dor nas costas (DC e os fatores de risco associados a um nível de elevada intensidade de dor em escolares do Ensino Fundamental de Teutônia, RS. Participaram deste estudo epidemiológico 1.597 escolares de 5ª a 8ª séries. Os dados foram coletados por meio de um questionário autoaplicável e analisados a partir de uma análise multivariável e do cálculo das razões de prevalência (RP (α=0,05. Verificou-se que a prevalência de DC nos últimos três meses foi de 55,7% (n = 802 e que a elevada intensidade de DC está associada com as variáveis: frequência de dor (RP = 1,37; p = 0,001, impedimento ao fazer atividades do dia a dia (RP = 1,25; p = 0,001 e meio de transporte do material escolar (RP = 1,10; p = 0,026. Estes resultados podem auxiliar os professores de educação física a planejar suas atividades curriculares.

  11. Structural evidence for the partially oxidized dipyrromethene and dipyrromethanone forms of the cofactor of porphobilinogen deaminase: structures of the Bacillus megaterium enzyme at near-atomic resolution

    International Nuclear Information System (INIS)

    Azim, N.; Deery, E.; Warren, M. J.; Wolfenden, B. A. A.; Erskine, P.; Cooper, J. B.; Coker, A.; Wood, S. P.; Akhtar, M.

    2014-01-01

    The enzyme porphobilinogen deaminase (PBGD; hydroxymethylbilane synthase; EC 2.5.1.61) catalyses a key early step in the biosynthesis of tetrapyrroles in which four molecules of the monopyrrole porphobilinogen are condensed to form a linear tetrapyrrole. Two near-atomic resolution structures of PBGD from B. megaterium are reported that demonstrate the time-dependent accumulation of partially oxidized forms of the cofactor, including one that possesses a tetrahedral C atom in the terminal pyrrole ring. The enzyme porphobilinogen deaminase (PBGD; hydroxymethylbilane synthase; EC 2.5.1.61) catalyses an early step of the tetrapyrrole-biosynthesis pathway in which four molecules of the monopyrrole porphobilinogen are condensed to form a linear tetrapyrrole. The enzyme possesses a dipyrromethane cofactor, which is covalently linked by a thioether bridge to an invariant cysteine residue (Cys241 in the Bacillus megaterium enzyme). The cofactor is extended during the reaction by the sequential addition of the four substrate molecules, which are released as a linear tetrapyrrole product. Expression in Escherichia coli of a His-tagged form of B. megaterium PBGD has permitted the X-ray analysis of the enzyme from this species at high resolution, showing that the cofactor becomes progressively oxidized to the dipyrromethene and dipyrromethanone forms. In previously solved PBGD structures, the oxidized cofactor is in the dipyromethenone form, in which both pyrrole rings are approximately coplanar. In contrast, the oxidized cofactor in the B. megaterium enzyme appears to be in the dipyrromethanone form, in which the C atom at the bridging α-position of the outer pyrrole ring is very clearly in a tetrahedral configuration. It is suggested that the pink colour of the freshly purified protein is owing to the presence of the dipyrromethene form of the cofactor which, in the structure reported here, adopts the same conformation as the fully reduced dipyrromethane form

  12. Kinetic Stability May Determine the Interaction Dynamics of the Bifunctional Protein DCoH1, the Dimerization Cofactor of the Transcription Factor HNF-1[alpha

    Energy Technology Data Exchange (ETDEWEB)

    Rho, H.; Jones, C.N.; Rose, R.B. (NCSU)

    2010-12-07

    The two disparate functions of DCoH1 (dimerization cofactor of HNF-1)/PCD (pterin-4a-carbinolamine dehydratase) are associated with a change in oligomeric state. DCoH dimers enhance the activity of the diabetes-associated transcription factor HNF-1{alpha} (hepatocyte nuclear factor-1{alpha}), while the PCD activity of DCoH1 homotetramers aids in aromatic amino acid metabolism. These complexes compete for the same interface of the DCoH dimer. Formation of the DCoH1/HNF-1{alpha} complex requires cofolding. The homotetramer of the DCoH1 paralogue, DCoH2, interacts with HNF-1{alpha} through simple mixing. To further investigate regulation of DCoH/HNF-1{alpha} complex formation, we measured the stability of the DCoH1 homotetramer through unfolding studies by intrinsic tryptophan fluorescence. DCoH2 unfolding is reversible. Surprisingly, the DCoH1 homotetramer is resistant to guanidine unfolding but refolds at a much lower guanidine concentration. We show that a point mutation at the DCoH1 tetramer interface, Thr 51 Ser, overcomes the dissociation barrier of the homotetramer and increases the interaction with HNF-1{alpha}. The 1.8 {angstrom} resolution crystal structure of DCoH1 T51S shows the presence of an ordered water molecule at the tetramer interface, as in DCoH2, which may destabilize the homotetramer. The equilibrium unfolding data were fit to a two-state model with no apparent intermediate. Folding intermediates were detectable by size exclusion chromatography. For wild-type DCoH1 the intermediates changed with time, suggesting a kinetic origin for the unfolding barrier of the homotetramer. We propose an unfolding pathway in which the tetramer unfolds slowly, but the dimer folds reversibly. Implications for regulation of DCoH1/HNF-1{alpha} complex formation are discussed.

  13. An astrophysical interpretation of the remarkable g-mode frequency groups of the rapidly rotating γ Dor star, KIC 5608334

    Science.gov (United States)

    Saio, Hideyuki; Bedding, Timothy R.; Kurtz, Donald W.; Murphy, Simon J.; Antoci, Victoria; Shibahashi, Hiromoto; Li, Gang; Takata, Masao

    2018-06-01

    The Fourier spectrum of the γ-Dor variable KIC 5608334 shows remarkable frequency groups at ˜3, ˜6, ˜9, and 11-12 d-1. We explain the four frequency groups as prograde sectoral g modes in a rapidly rotating star. Frequencies of intermediate-to-high radial order prograde sectoral g modes in a rapidly rotating star are proportional to |m| (i.e. ν ∝ |m|) in the corotating frame as well as in the inertial frame. This property is consistent with the frequency groups of KIC 5608334 as well as the period versus period-spacing relation present within each frequency group, if we assume a rotation frequency of 2.2 d-1, and that each frequency group consists of prograde sectoral g modes of |m| = 1, 2, 3, and 4, respectively. In addition, these modes naturally satisfy near-resonance conditions νi ≈ νj + νk with mi = mj + mk. We even find exact resonance frequency conditions (within the precise measurement uncertainties) in many cases, which correspond to combination frequencies.

  14. Prática social, hipnose e dor crônica: alternativas de compreensão

    Directory of Open Access Journals (Sweden)

    Mauricio da Silva Neubern

    2012-12-01

    Full Text Available O presente trabalho propõe, pela noção de prática social, uma alternativa de compreensão da relação entre hipnose e dor crônica. Partindo de uma crítica às pesquisas contemporâneas, são investigadas três importantes zonas de sentido dessa aplicação da hipnose: sua dimensão relacional; a fabricação do fenômeno hipnótico e o conto de histórias. Semelhantes zonas remetem à subjetividade presente em tais processos sociais, uma vez que implica a materialidade das relações, a construção de papéis, a diversidade de expressões do transe e a multiplicidade de sugestões presentes nos contos. Na conclusão, enfatiza-se a importância de que uma compreensão clínica e qualitativa das relações entre hipnose e dores crônicas subsidie as pesquisas com informações pertinentes dessa pratica social, para que os pesquisadores não descaracterizem com metodologias distanciadas de suas características.

  15. Recurrent abdominal pain: when an epileptic seizure should be suspected? Dor abdominal recorrente: quando suspeitar de crise epiléptica?

    Directory of Open Access Journals (Sweden)

    Renata C. Franzon

    2002-09-01

    Full Text Available Recurrent episodes of abdominal pain are common in childhood. Among the diagnostic possibilities are migraine and abdominal epilepsy (AE. AE is an infrequent syndrome with paroxystic episodes of abdominal pain, awareness disturbance, EEG abnormalities and positive results with the introduction of antiepileptic drugs. We present one 6 year-old girl who had short episodes of abdominal pain since the age of 4. The pain was followed by cry, fear and occasionally secondary generalization. MRI showed tumor in the left temporal region. As a differential diagnosis, we report a 10 year-old boy who had long episodes of abdominal pain accompanied by blurring of vision, vertigo, gait ataxia, dysarthria, acroparesthesias and vomiting. He received the diagnosis of basilar migraine. In our opinion, AE is part of a large group (partial epilepsies and does not require a special classification. Pediatric neurologists must be aware of these two entities that may cause abdominal pain.Episódios recorrentes de dor abdominal são freqüentes na infância e entre as causas neurológicas há migrânea e epilepsia abdominal (EA. EA é uma síndrome que consiste de episódios paroxísticos de dor abdominal associada à alteração de consciência, anormalidades eletrencefalográficas e boa resposta à terapia anticonvulsivante. Apresentamos uma menina de 6 anos que tinha desde os 4 anos episódios de curta duração de dor abdominal, seguidos por choro, medo e ocasional generalização secundária. A RM mostrou a presença de um tumor em região temporal esquerda. Como diagnóstico diferencial, apresentamos um menino de 10 anos que há 12 meses referia episódios de dor abdominal de longa duração acompanhados por turvação visual, vertigem, marcha atáxica, disartria, acroparestesia e vômito, recebendo posteriormente o diagnóstico de migrânia basilar. Em nossa opinião, EA faz parte de um grande grupo (epilepsias parciais e não requer uma classificação especial

  16. Estudo comparativo de dois protocolos de exercícios excêntricos sobre a dor e a função do joelho em atletas com tendinopatia patelar: estudo controlado e aleatorizado

    Directory of Open Access Journals (Sweden)

    Ronaldo Alves da Cunha

    2012-06-01

    Full Text Available INTRODUÇÃO: O agachamento excêntrico em plano inclinado tem-se mostrado eficaz no tratamento conservador da tendinopatia patelar, especialmente na população atlética. Entretanto, diversos aspectos, como intensidade e dor durante a realização da terapia, ainda apresentam divergências entre autores. Objetivos: Comparar a eficácia de dois protocolos de exercício excêntrico (executado com e sem dor, na melhora da função do joelho e na intensidade da dor em atletas com tendinopatia patelar. MÉTODOS: Foram selecionados 17 atletas de ambos os gêneros com diagnóstico de tendinopatia patelar e aleatoriamente distribuídos em dois grupos de tratamento. Os voluntários do primeiro grupo realizaram exercícios de agachamento excêntrico em plano inclinado com dor no tendão patelar. Os voluntários do segundo grupo foram orientados a realizar o mesmo exercício, porém sem apresentar dor no tendão patelar durante a realização. O tratamento teve a duração de 12 semanas e a avaliação de dor e função foi realizada pelo VISA-P e pela EVA antes de iniciar o tratamento, com oito semanas de intervenção e ao término do tratamento. RESULTADOS: Houve uma melhora em ambos os grupos quando comparados os resultados das avaliações realizadas após oito e 12 semanas do início do tratamento com a avaliação inicial, porém não houve diferença significativa entre o grupo que realizou exercício com dor e o grupo que executou os exercícios sem dor. Na análise da probabilidade de obtenção de uma melhora clínica para os escores de VISA e EVA em oito e 12 semanas, não houve nenhuma diferença entre os dois grupos. CONCLUSÃO: Um programa de exercício excêntrico usando agachamento em plano inclinado, realizado com ou sem a presença de dor, foi eficaz na melhora da dor e da função em atletas com tendinopatia patelar.

  17. Conformational control of cofactors in nature: The effect of methoxy group orientation on the electronic structure of ubisemiquinone

    Science.gov (United States)

    De Almeida, Wagner B.; O'Malley, Patrick J.

    2018-03-01

    Ubiquinone is the key electron and proton transfer agent in biology. Its mechanism involves the formation of its intermediate one-electron reduced form, the ubisemiquinone radical. This is formed in a protein-bound form which permits the semiquinone to vary its electronic and redox properties. This can be achieved by hydrogen bonding acceptance by one or both oxygen atoms or as we now propose by restricted orientations for the methoxy groups of the headgroup. We show how the orientation of the two methoxy groups of the quinone headgroup affects the electronic structure of the semiquinone form and demonstrate a large dependence of the ubisemiquinone spin density distribution on the orientation each methoxy group takes with respect to the headgroup ring plane. This is shown to significantly modify associated hyperfine couplings which in turn needs to be accounted for in interpreting experimental values in vivo. The study uncovers the key potential role the methoxy group orientation can play in controlling the electronic structure and spin density of ubisemiquinone and provides an electronic-level insight into the variation in electron affinity and redox potential of ubiquinone as a function of the methoxy orientation. Taken together with the already known influence of cofactor conformation on heme and chlorophyll electronic structure, it reveals a more widespread role for cofactor conformational control of electronic structure and associated electron transfer in biology.

  18. Structural insights into the cofactor-assisted substrate recognition of yeast methylglyoxal/isovaleraldehyde reductase Gre2.

    Science.gov (United States)

    Guo, Peng-Chao; Bao, Zhang-Zhi; Ma, Xiao-Xiao; Xia, Qingyou; Li, Wei-Fang

    2014-09-01

    Saccharomyces cerevisiae Gre2 (EC1.1.1.283) serves as a versatile enzyme that catalyzes the stereoselective reduction of a broad range of substrates including aliphatic and aromatic ketones, diketones, as well as aldehydes, using NADPH as the cofactor. Here we present the crystal structures of Gre2 from S. cerevisiae in an apo-form at 2.00Å and NADPH-complexed form at 2.40Å resolution. Gre2 forms a homodimer, each subunit of which contains an N-terminal Rossmann-fold domain and a variable C-terminal domain, which participates in substrate recognition. The induced fit upon binding to the cofactor NADPH makes the two domains shift toward each other, producing an interdomain cleft that better fits the substrate. Computational simulation combined with site-directed mutagenesis and enzymatic activity analysis enabled us to define a potential substrate-binding pocket that determines the stringent substrate stereoselectivity for catalysis. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Refining the reaction mechanism of O2 towards its co-substrate in cofactor-free dioxygenases

    Directory of Open Access Journals (Sweden)

    Pedro J. Silva

    2016-12-01

    Full Text Available Cofactor-less oxygenases perform challenging catalytic reactions between singlet co-substrates and triplet oxygen, in spite of apparently violating the spin-conservation rule. In 1-H-3-hydroxy-4-oxoquinaldine-2,4-dioxygenase, the active site has been suggested by quantum chemical computations to fine tune triplet oxygen reactivity, allowing it to interact rapidly with its singlet substrate without the need for spin inversion, and in urate oxidase the reaction is thought to proceed through electron transfer from the deprotonated substrate to an aminoacid sidechain, which then feeds the electron to the oxygen molecule. In this work, we perform additional quantum chemical computations on these two systems to elucidate several intriguing features unaddressed by previous workers. These computations establish that in both enzymes the reaction proceeds through direct electron transfer from co-substrate to O2 followed by radical recombination, instead of minimum-energy crossing points between singlet and triplet potential energy surfaces without formal electron transfer. The active site does not affect the reactivity of oxygen directly but is crucial for the generation of the deprotonated form of the co-substrates, which have redox potentials far below those of their protonated forms and therefore may transfer electrons to oxygen without sizeable thermodynamic barriers. This mechanism seems to be shared by most cofactor-less oxidases studied so far.

  20. Cofactor and CO2 donor regulation involved in reductive routes for polymalic acid production by Aureobasidium pullulans CCTCC M2012223.

    Science.gov (United States)

    Zou, Xiang; Tu, Guangwei; Zan, Zhanquan

    2014-10-01

    Polymalic acid (PMA) is a water-soluble polyester with many attractive properties for biomedical application. Its monomer L-malic acid is widely used in the food industry and also a potential C4 platform chemical. Cofactor and CO2 donor involved in the reductive routes were investigated for PMA production by Aureobasidium pullulans. Biotin as the key cofactor of pyruvate carboxylase was favor for the PMA biosynthesis. Na2CO3 as CO2 donor can obviously improved PMA titer when compared with no CO2 supplier NaOH, and also exhibit more advantages than the other donor CaCO3 because of its water-soluble characteristic. A combinational process with addition of biotin 70 mg/L and Na2CO3 as the CO2 donor was scaled-up in 50 L fermentor, achieving the high product 34.3 g/L of PMA and productivity of 0.41 g/L h. This process provides an efficient and economical way for PMA and malic acid production, and is promising for industrial application.

  1. Purification, crystallization and preliminary crystallographic analysis of a multiple cofactor-dependent DNA ligase from Sulfophobococcus zilligii

    International Nuclear Information System (INIS)

    Supangat, Supangat; An, Young Jun; Sun, Younguk; Kwon, Suk-Tae; Cha, Sun-Shin

    2010-01-01

    A recombinant multiple cofactor-dependent DNA ligase from S. zilligii has been purified and crystallized. X-ray diffraction data were collected to 2.9 Å resolution and the crystals belonged to space group P1. A recombinant DNA ligase from Sulfophobococcus zilligii that shows multiple cofactor specificity (ATP, ADP and GTP) was expressed in Escherichia coli and purified under reducing conditions. Crystals were obtained by the microbatch crystallization method at 295 K in a drop containing 1 µl protein solution (10 mg ml −1 ) and an equal volume of mother liquor [0.1 M HEPES pH 7.5, 10%(w/v) polyethylene glycol 10 000]. A data set was collected to 2.9 Å resolution using synchrotron radiation. The crystals belonged to space group P1, with unit-cell parameters a = 63.7, b = 77.1, c = 77.8 Å, α = 83.4, β = 82.4, γ = 74.6°. Assuming the presence of two molecules in the unit cell, the solvent content was estimated to be about 53.4%

  2. Lineage-Specific Viral Hijacking of Non-canonical E3 Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity

    Directory of Open Access Journals (Sweden)

    Joshua R. Kane

    2015-05-01

    Full Text Available HIV-1 encodes the accessory protein Vif, which hijacks a host Cullin-RING ubiquitin ligase (CRL complex as well as the non-canonical cofactor CBFβ, to antagonize APOBEC3 antiviral proteins. Non-canonical cofactor recruitment to CRL complexes by viral factors, to date, has only been attributed to HIV-1 Vif. To further study this phenomenon, we employed a comparative approach combining proteomic, biochemical, structural, and virological techniques to investigate Vif complexes across the lentivirus genus, including primate (HIV-1 and simian immunodeficiency virus macaque [SIVmac] and non-primate (FIV, BIV, and MVV viruses. We find that CBFβ is completely dispensable for the activity of non-primate lentiviral Vif proteins. Furthermore, we find that BIV Vif requires no cofactor and that MVV Vif requires a novel cofactor, cyclophilin A (CYPA, for stable CRL complex formation and anti-APOBEC3 activity. We propose modular conservation of Vif complexes allows for potential exaptation of functions through the acquisition of non-CRL-associated host cofactors while preserving anti-APOBEC3 activity.

  3. Intensidade da dor em pacientes com síndrome do ombro doloroso Pain severity in patients with painful shoulder syndrome

    Directory of Open Access Journals (Sweden)

    Daniela Dias da Silva Garzedin

    2008-01-01

    Full Text Available O objetivo do estudo é avaliar intensidade da dor e associações com características clínicas em grupo de pacientes com Síndrome do Ombro Doloroso (SOD. Realizou-se estudo descritivo utilizando dados retrospectivos de 77 prontuários. Como instrumento de avaliação utilizamos Escala Visual Numérica (EVN. Foram consideradas variáveis de interesse: EVN (77, diagnóstico (57, ombro acometido (77, sexo (77, idade (76, localização da dor (77, uso de medicamentos (59 e problema cervical associado (77. Destes 53,2% eram do sexo feminino com média de idade 50,4±15,7 anos. O ombro direito foi o mais afetado (57,1%. Dor intensa foi referida por 41,6% dos pacientes sendo mais freqüente no sexo feminino (56,1% vs 25,0%; p=0,006. Os pacientes queixaram-se de dor intensa com mais freqüência em ombro esquerdo (57,7% vs 31,8%, p=0,034. Dos pacientes estudados, 59 (81,3% usavam medicamentos, sendo mais freqüente o antinflamatório. A síndrome do manguito rotador estava presente em 80,7% (57 e dor cervical associada em 15,6% (77. Localização da dor exclusivamente no ombro correspondeu a 76,6%. Evidenciamos que a síndrome do manguito rotador foi causa mais freqüente da SOD, sendo mais comum e intensa em mulheres com idade próxima de 51 anos. A EVN mostrou-se instrumento relevante para mensurar a dor na SOD.The aim of this study was to assess the severity of pain and its correlations to clinical characteristics in Painful Shoulder Syndrome (PSS patients. A descriptive study was conducted using retrospective data from 77 medical record files. The Visual Numerical Scale (VNS was used as an assessment instrument. The following variables of interest were considered: VNS (77, diagnosis (57, affected shoulder (77, sex (77, age (76, pain site (77, use of medications (59 and associated cervical pain (77. 53.2% of the patients were females and the mean age was 50.4±15.7 years. The right shoulder was the most affected side (57.1%. Severe pain was

  4. Gerenciamento da dor na Síndrome Pós-poliomielite: estudo de caso Pain management in Postpoliomyelitis Syndrome: case study

    Directory of Open Access Journals (Sweden)

    Marco Orsini

    2011-12-01

    Full Text Available A Síndrome Pós-Pólio (SPP caracteriza-se por um novo episódio de fraqueza muscular e/ou fadiga muscular anormal em indivíduos que apresentaram poliomielite anterior aguda (PAA anos antes. Ainda são poucos os relatos na literatura sobre o gerenciamento da dor na SSP. O objetivo deste trabalho é analisar o controle da dor na síndrome pós-pólio por meio de um relato de caso. Um homem de 57 anos com SPP foi submetido a 24 sessões de fisioterapia para controle do quadro álgico na síndrome, baseada em recursos eletrotermofototerápicos e cinesioterapia. Para análise da dor pré e pós-intervenção fisioterapêutica foram aplicados dois instrumentos: a Escala Analógica Visual (EVA e a Intensidade de Dor Presente (ID. O quadro álgico no joelho direito sofreu redução de grau 8 para 4 pela EVA e grau 5 para 2 pela ID, enquanto a dor no tornozelo direito reduziu de grau 2 pela EVA e grau 1 pela ID para zero em ambas as escalas. A dor é apontada como um sintoma predominante por muitos pacientes com SPP. O sujeito deste relato, após o programa de tratamento, apresentou melhora expressiva da dor. Entretanto, devido à escassez da literatura sobre dados substanciais referentes ao seu gerenciamento, especialmente na fisioterapia, novos estudos devem ser propostos para gerar maior fundamentação teórica à abordagem fisioterapêutica na SPP.The Post-polio Syndrome (PPS is characterized by a new episode of muscular weakness and/or abnormal muscular fatigue in subjects that presented acute previous polio (APP years ago. There still are few studies about the pain management at PPS. The aim of this study is to analyze pain´s management in PPS by a case report. A men with PPS, 57 years, was submitted to 24 sessions of physical therapy for pain´s control in PPS, based at electro-thermo physical therapy features and therapeutics exercises. For pain´s analysis, pre and post physical therapy interventions were applied two instruments: the

  5. Avaliação da dor em criocirurgia de ceratoses actínicas Pain evaluation in the cryosurgery of actinic keratoses

    Directory of Open Access Journals (Sweden)

    Claudia Schermann Poziomczyk

    2011-08-01

    Full Text Available FUNDAMENTOS: a ceratose actínica é lesão pré-maligna frequente, que ocorre em áreas expostas à luz solar, em pessoas idosas ou adultas de meia-idade e pele clara. A criocirurgia com nitrogênio líquido é a modalidade mais comum para o tratamento de ceratoses actínicas. OBJETIVOS: o objetivo primário deste estudo foi medir a intensidade da dor durante a criocirurgia, por meio da Escala Visual Análoga. Também buscou-se identificar o nível de dor considerado adequado pelo paciente, avaliar a proporção de pacientes que consideram necessária a diminuição da dor sentida e verificar a necessidade ou não de analgesia suplementar. MÉTODOS: Estudo transversal com pacientes encaminhados para terapêutica criocirúrgica de ceratoses actínicas no Ambulatório de Dermatologia Sanitária. Foram avaliados 112 pacientes, após tratamento de ceratoses actínicas, aplicando-se um questionário com perguntas sobre a intensidade da dor sentida durante o procedimento cirúrgico, assim como a dor considerada confortável ou adequada ao procedimento. RESULTADOS: participaram 48 homens (42,8% e 64 mulheres (57,2%. A média da dor referida durante o procedimento cirúrgico, medida em milímetros na Escala Visual Análoga, foi de 32,85 mm; a média da dor considerada adequada pelos pacientes foi de 23,01 mm. A diferença entre as duas médias foi estatisticamente significativa (pBACKGROUND: Background: Actinic keratosis is a frequently-encountered premalignant lesion occurring in areas exposed to sunlight in fair-skinned elderly or middle-aged people. Cryosurgery with liquid nitrogen is the most common method for treating the lesions. OBJECTIVES: The primary objective of this study was to measure the intensity of pain during cryosurgery by using the Visual Analog Scale (VAS. We also sought to identify the pain level deemed appropriate by the patient, to assess the proportion of patients who considered it necessary to reduce the pain and, finally, to

  6. Pain in workers with shoulder impingement syndrome: an assessment using the DASH and McGill pain questionnaires Dor em trabalhadores portadores da síndrome do impacto do ombro: uma avaliação através dos questionários DASH e McGill de dor

    Directory of Open Access Journals (Sweden)

    PR Camargo

    2007-04-01

    Full Text Available OBJECTIVE: This study assessed physical function and pain in male and female workers with shoulder impingement syndrome using the Brazilian Portuguese versions of the Disabilities of the Arm, Shoulder and Hand (DASH and McGill pain questionnaires. METHODS: Twenty-seven assembly line workers (18 men and 9 women; mean age of 33.26 ± 6.49 years in the school supply industry were evaluated. The duration of the shoulder impingement pain was 31.74 ± 32.92 months and the amount of time of the workers in this industry was 11.08 ± 6.41 years. The DASH questionnaire was used to evaluate functional status and symptoms of the upper limbs of the workers. Using the McGill Pain Questionnaire, the pain was quantified by the number of words chosen and by the pain rating index (PRI. RESULTS: The women presented higher scores (POBJETIVO: Este estudo avaliou função física e dor em trabalhadores com síndrome do impacto através das versões brasileiras dos questionários "Disabilities of the Arm, Shoulder and Hand" (DASH e McGill de dor. MÉTODO: Vinte e sete trabalhadores (18 homens e 9 mulheres; idade média de 33,26 ± 6,49 anos de uma linha de produção de uma indústria de material escolar foram avaliados. O tempo de duração de dor no ombro era de 31,74 ± 32,92 meses e o tempo de trabalho na indústria era de 11,08 ± 6,41 anos. O questionário DASH foi utilizado para avaliar o estado funcional e os sintomas dos membros superiores dos trabalhadores. Através do questionário McGill de dor, a dor foi quantificada pelo número de palavras escolhidas e pelo índice de classificação da dor (ICD. RESULTADOS: As mulheres apresentaram maiores escores (P< 0,05 que os homens para ambos os módulos do DASH. As mulheres escolheram mais palavras (17,00 ± 2,59 que os homens (13,33 ± 3,16 e também apresentaram o maior ICD total (P< 0,05. CONCLUSÃO: Os resultados obtidos neste grupo de trabalhadores brasileiros com síndrome do impacto do ombro identificam os

  7. Site-Specific Bioconjugation of an Organometallic Electron Mediator to an Enzyme with Retained Photocatalytic Cofactor Regenerating Capacity and Enzymatic Activity

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    Sung In Lim

    2015-04-01

    Full Text Available Photosynthesis consists of a series of reactions catalyzed by redox enzymes to synthesize carbohydrates using solar energy. In order to take the advantage of solar energy, many researchers have investigated artificial photosynthesis systems mimicking the natural photosynthetic enzymatic redox reactions. These redox reactions usually require cofactors, which due to their high cost become a key issue when constructing an artificial photosynthesis system. Combining a photosensitizer and an Rh-based electron mediator (RhM has been shown to photocatalytically regenerate cofactors. However, maintaining the high concentration of cofactors available for efficient enzymatic reactions requires a high concentration of the expensive RhM; making this process cost prohibitive. We hypothesized that conjugation of an electron mediator to a redox enzyme will reduce the amount of electron mediators necessary for efficient enzymatic reactions. This is due to photocatalytically regenerated NAD(PH being readily available to a redox enzyme, when the local NAD(PH concentration near the enzyme becomes higher. However, conventional random conjugation of RhM to a redox enzyme will likely lead to a substantial loss of cofactor regenerating capacity and enzymatic activity. In order to avoid this issue, we investigated whether bioconjugation of RhM to a permissive site of a redox enzyme retains cofactor regenerating capacity and enzymatic activity. As a model system, a RhM was conjugated to a redox enzyme, formate dehydrogenase obtained from Thiobacillus sp. KNK65MA (TsFDH. A RhM-containing azide group was site-specifically conjugated to p-azidophenylalanine introduced to a permissive site of TsFDH via a bioorthogonal strain-promoted azide-alkyne cycloaddition and an appropriate linker. The TsFDH-RhM conjugate exhibited retained cofactor regenerating capacity and enzymatic activity.

  8. WISEP J004701.06+680352.1: AN INTERMEDIATE SURFACE GRAVITY, DUSTY BROWN DWARF IN THE AB DOR MOVING GROUP

    Energy Technology Data Exchange (ETDEWEB)

    Gizis, John E. [Department of Physics and Astronomy, University of Delaware, Newark, DE 19716 (United States); Allers, Katelyn N. [Department of Physics and Astronomy, Bucknell University, Lewisburg, PA 17837 (United States); Liu, Michael C. [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu HI 96822 (United States); Harris, Hugh C. [US Naval Observatory, Flagstaff Station, 10391 West Naval Observatory Road, Flagstaff, AZ 86001 (United States); Faherty, Jacqueline K. [Department of Terrestrial Magnetism, Carnegie Institution of Washington 5241 Broad Branch Road NW, Washington, DC 20015 (United States); Burgasser, Adam J. [Center for Astrophysics and Space Science, University of California San Diego, La Jolla, CA 92093 (United States); Kirkpatrick, J. Davy [Infrared Processing and Analysis Center, MS 100-22, California Institute of Technology, Pasadena, CA 91125 (United States)

    2015-02-01

    We present spectroscopy, astrometry, and photometry of the brown dwarf WISEP J004701.06+680352.1 (W0047+68), an unusually red field L dwarf at a distance of 12.2 ± 0.4 pc. The three-dimensional space motion identifies it as a member of the AB Dor Moving Group, an identification supported by our classification of W0047+68 as intermediate surface gravity (INT-G) using the Allers and Liu near-infrared classification system. This moving group membership implies near-solar metallicity, age ∼100-125 Myr, M ≈ 0.018 M {sub ☉}, and log g ≈ 4.5; the thick condensate clouds needed to explain the infrared spectrum are, therefore, a result of surface gravity that is lower than that of ordinary field brown dwarfs. From the observed luminosity and evolutionary model radius, we find T {sub eff} ≈ 1300 K, a temperature normally associated with early T dwarfs. Thick clouds are also used to explain the spectral properties of directly imaged giant planets, and we discuss the successes and challenges for such substellar models in matching the observed optical and infrared spectra. W0047+68 shows that cloud thickness is more sensitive to intermediate surface gravity than in most models. We also present a trigonometric parallax of the dusty L6 dwarf 2MASS J21481628+4003593. It lies at 8.060 ± 0.036 parsecs; its astrometry is consistent with the view that it is older and metal-rich.

  9. Ligand- and cell-dependent determinants of internalization and cAMP modulation by delta opioid receptor (DOR) agonists

    Science.gov (United States)

    Charfi, Iness; Nagi, Karim; Mnie-Filali, Ouissame; Thibault, Dominic; Balboni, Gianfranco; Schiller, Peter W.; Trudeau, Louis-Eric

    2014-01-01

    Signaling bias refers to G protein-coupled receptor ligand ability to preferentially activate one type of signal over another. Bias to evoke signaling as opposed to sequestration has been proposed as a predictor of opioid ligand potential for generating tolerance. Here we measured whether delta opioid receptor agonists preferentially inhibited cyclase activity over internalization in HEK cells. Efficacy (τ) and affinity (KA) values were estimated from functional data and bias was calculated from efficiency coefficients (log τ/KA). This approach better represented the data as compared to alternative methods that estimate bias exclusively from τ values. Log (τ/KA) coefficients indicated that SNC-80 and UFP-512 promoted cyclase inhibition more efficiently than DOR internalization as compared to DPDPE (bias factor for SNC-80: 50 and for UFP-512: 132). Molecular determinants of internalization were different in HEK293 cells and neurons with βarrs contributing to internalization in both cell types, while PKC and GRK2 activities were only involved in neurons. Rank orders of ligand ability to engage different internalization mechanisms in neurons were compared to rank order of Emax values for cyclase assays in HEK cells. Comparison revealed a significant reversal in rank order for cyclase Emax values and βarr-dependent internalization in neurons, indicating that these responses were ligand-specific. Despite this evidence, and because kinases involved in internalization were not the same across cellular backgrounds, it is not possible to assert if the magnitude and nature of bias revealed by rank orders of maximal responses is the same as the one measured in HEK cells. PMID:24022593

  10. Les scènes hivernales dans la peinture du Siècle d'or hollandais

    Directory of Open Access Journals (Sweden)

    Martine Tabeaud

    2010-10-01

    Full Text Available Les scènes d'hiver connaissent leur apogée au Siècle d'or hollandais. En se focalisant sur les représentations de la neige et du froid, il est possible de voir s'il existe un lien entre ces tableaux et le climat de l'époque, voire une concomitance entre les types d'hiver réels et peints. Le succès de ces scènes d'hiver aidant, il apparaît que nombre de peintres ont fait fi du climat de l'époque et ont réalisé des scènes de genre hivernales, au point de créer une véritable imagerie. C'est ainsi que la rudesse des hivers de la période froide du Petit Âge Glaciaire a globalement disparu dans les représentations au profit d'hivers festifs.The winter scenesare at their optimum during the Dutch Golden Age. When one focuses on the winter and coldness representations, one might wonder if the paintings and the real weather are correlated. If they are, do the paintings genuinely show how the weather was when they were painted? As the winter scenes became appreciated, the painters started to paint without taking into account the real weather. Eventually they painted genre scenes of the winter time and almost developed a series of winter scenes' image. Therefore the unusual rough coldness of the Little Ice Age winters has generally disappeared of the paintings, joyful winter scenes being preferred.

  11. Cofactor of BRCA1: A new genetic marker for common malignant liver cancer

    Directory of Open Access Journals (Sweden)

    Editorial Office

    2016-08-01

    Full Text Available A new study has identified a vital gene in the pathogenesis and progression of liver cancer hepatocellular carcinoma (HCC, according to a team of biotechnology researchers at The American University in Cairo, Egypt, in a scientific paper published recently by AMOR. The study on human gene ‘Cofactor of BRCA1’ (dubbed COBRA1 and its potential role as a reliable cancer predictor for HCC is especially important due to the disease’s grim outlook. HCC is “ranked as the second most common cause of cancer-related deaths in the world in 2012,” the authors said. “Thus, it is considered as a highly aggressive cancer with poor prognosis,” they added. According to data from the Surveillance Epidemiology and End Results (SEER program, hepatocellular carcinoma accounts for 90% of all liver cancers worldwide. In the United States, HCC represents the fastest growing cause of cancer mortality overall and the second fastest growing cause of cancer deaths among women. Globally, the incidence of HCC in developing nations is over twice that of in developed countries – East Asia having highest incidence of HCC with the rate of 35 male cases per 100,000, followed by the continent of Africa. HCC mortality statistics in the developing countries is also more than double compared to the First World nations, with the annual loss of 33.5 and 23.73 lives per 100,000 in Asia and Africa, respectively. In addition, “HCC is usually diagnosed in the late stages of the tumor where, at some point, treatment is of limited efficacy. Thus, prognoses and follow-ups are necessary to regularly assess the patients and to predict any risks before the deterioration of patients’ condition,” said researcher Aya Youssef and her fellow team members. The behaviour of COBRA1 in the development and progression of several cancers has previously been studied and established, the researchers wrote. “For example, cell lines and tissues isolated from late-stage metastatic breast

  12. The crystal structure of escherichia coli MoaB suggests a probable role in molybdenum cofactor synthesis

    International Nuclear Information System (INIS)

    Sanishvili, R.; Beasley, S.; Skarina, T; Glesne, D; Joachimiak, A; Edwards, A; Savchenko, A.; Univ. Health Network; Univ. of Toronto

    2004-01-01

    The crystal structure of Escherichia coli MoaB was determined by multiwavelength anomalous diffraction phasing and refined at 1.6 Angstrom resolution. The molecule displayed a modified Rossman fold. MoaB is assembled into a hexamer composed of two trimers. The monomers have high structural similarity with two proteins, MogA and MoeA, from the molybdenum cofactor synthesis pathway in E. Coli, as well as with domains of mammalian gephyrin and plant Cnx1, which are also involved in molybdopterin synthesis. Structural comparison between these proteins and the amino acid conservation patterns revealed a putative active site in MoaB. The structural analysis of this site allowed to advance several hypothesis which can be tested in further studies

  13. Dor musculoesquelética idiopática difusa na infância e na adolescência Diffuse idiopathic musculoskeletal pain in childhood and adolescence

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    Juliana Molina

    2011-06-01

    Full Text Available OBJETIVO: A dor musculoesquelética difusa idiopática persistente ou intermitente é definida pela presença de dor com duração de três meses ou mais, sem etiologia aparente, e tem acometido cada vez mais crianças e adolescentes. Este estudo objetivou relatar dois pacientes com dor incapacitante submetidos à abordagem e ao tratamento multiprofissional, além de discutir o tratamento conduzido, por meio de revisão da literatura atual. DESCRIÇÃO DO CASO: O primeiro caso é de uma menina com nove anos de idade, com histórico de cefaleia, dor mus-culoesquelética e dor abdominal há dois anos, período no qual apresentou quatro episódios de ausência de marcha, sem causas orgânicas aparentes. O segundo caso refere-se a uma adolescente de 14 anos com lombalgia diária há 14 meses de forte intensidade, com irradiação para membros inferiores, acompanhada de cefaleia, fadiga e adinamia. Ambas apresentavam exame físico normal, exceto pela presença de alodínia (caso 1 e pontos de fibromialgia (caso 2; além de exames subsidiários normais, sem justificativas orgânicas para as queixas dolorosas. Houve melhora clínica significativa após diagnóstico e tratamento diferencial por meio de abordagem multiprofissional (médico, psicólogo, fisioterapeuta e nutricionista, com retomada das atividades regulares pelas pacientes. COMENTÁRIOS: A atuação integrada da equipe em um curto período de tempo proporcionou às pacientes a retomada de suas atividades normais, visto que fatores emocionais, físicos e nutricionais relacionam-se à dor.OBJECTIVE: Persistent or intermittent diffuse idiopathic musculoskeletal pain is defined by the presence of pain over three months with no apparent etiology. The diagnosis of this condition in children and adolescents is increasing. The objective of this study was to report the cases of two patients with disabling pain that received multidiscipli-nary treatment and to review the current literature about this

  14. Diferential diagnosis in atypical facial pain: a clinical study Diagnóstico diferencial em dor facial atípica: estudo clínico

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    José Cláudio Marinho Nóbrega

    2007-06-01

    Full Text Available OBJETIVE: To evaluate a sample of patients with atypical facial pain (AFP in comparison to patients with symptomatic facial pain (SFP. METHOD: 41 patients with previous diagnostic of AFP were submitted to a standardized evaluation protocol, by a multidisciplinary pain team. RESULTS: 21 (51.2% were considered AFP and 20 (48.8% (SFP received the following diagnosis: 8 (40.0% had temporomandibular disorders (TMD; 3 (15.0% had TMD associated to systemic disease (fibromyalgia, systemic erythematosus lupus; 4 (20.0% had neuropathy after ear, nose and throat (ENT surgery for petroclival tumor; 2 (10.0% had Wallenberg syndrome; 1 (5.0% had intracranial tumor; 1 (5.0% had oral cancer (epidermoid carcinoma, and 1 (5.0% had burning mouth syndrome (BMS associated to fibromyalgia. Spontaneous descriptors of pain were not different between AFP and SFP groups (p=0.82. Allodynia was frequent in SFP (p=0.05 and emotion was the triggering factor most prevalent in AFP (p=0.06. AFP patients had more traumatic events previously to pain (p=0.001. CONCLUSION: AFP patients had more: a traumatic events previously to pain onset, and b emotions as a triggering factor for pain. These data support the need of trained health professionals in multidisciplinary groups for the accurate diagnosis and treatment of these patients.OBJETIVO: Avaliar uma amostra de pacientes com dor facial atípica (DFA e compará-la a outra com dor facial sintomática (DFS. MÉTODO: 41 pacientes com diagnóstico prévio de DFA foram submetidos a um protocolo padronizado de avaliação aplicado por uma equipe multidisciplinar. RESULTADOS: 21 (51,2% foram mantidos com o diagnóstico de DFA e 20 (48,8% (DFS receberam os seguintes diagnósticos: 8 (40.0% tinham disfunções temporomandibulares (DTM; 3 (15,0% tinham DTM associada a doença sistêmica (fibromialgia, lupus eritematoso sistêmico; 4 (20,0% tinham neuropatia após cirurgia otorrinolaringológica (ORL para tumor petroclival; 2 (10,0% tinham s

  15. Specificity of anti-phospholipid antibodies in infectious mononucleosis: a role for anti-cofactor protein antibodies

    Science.gov (United States)

    Sorice, M; Pittoni, V; Griggi, T; Losardo, A; Leri, O; Magno, M S; Misasi, R; Valesini, G

    2000-01-01

    The antigen specificity of anti-phospholipid antibodies in infectious mononucleosis (IM) was studied using ELISA for the detection of anti-β2-glycoprotein I (β2-GPI), anti-annexin V, anti-protein S and anti-prothrombin antibodies and TLC immunostaining for the detection of anti-phospholipid antibodies. This technique enabled us to look at antibodies reacting to ‘pure’ phospholipid antigens in the absence of protein contamination. Sera from 46 patients with IM, 18 with systemic lupus erythematosus (SLE), 21 with primary anti-phospholipid antibody syndrome (PAPS), 50 with Helicobacter pylori infection and 30 healthy blood donors were tested. This study highlights anti-phospholipid antibodies in patients with IM as specific ‘pure’ anti-cardiolipin antibodies, while in PAPS and SLE patients anti-phosphatidylserine and anti-phosphatidylethanolamine antibodies were also found. This investigation also shows that the anti-cardiolipin antibodies found in IM can be present with anti-cofactor protein antibodies. The higher prevalence of anti-cofactor antibodies found in IM sera than in Helicobacter pylori sera may be due to the immunostimulatory effect and/or the polyclonal activation often observed in course of Epstein–Barr virus infection. However, anti-β2-GPI and, to a lesser extent, anti-prothrombin antibodies occur with a significantly lower prevalence in IM than in PAPS patients. This finding suggests that these antibodies should be regarded as the expression of the broad autoimmune syndrome involving the phospholipid-binding plasma proteins. PMID:10792380

  16. TcoF-DB: dragon database for human transcription co-factors and transcription factor interacting proteins

    KAUST Repository

    Schaefer, Ulf

    2010-10-21

    The initiation and regulation of transcription in eukaryotes is complex and involves a large number of transcription factors (TFs), which are known to bind to the regulatory regions of eukaryotic DNA. Apart from TF-DNA binding, protein-protein interaction involving TFs is an essential component of the machinery facilitating transcriptional regulation. Proteins that interact with TFs in the context of transcription regulation but do not bind to the DNA themselves, we consider transcription co-factors (TcoFs). The influence of TcoFs on transcriptional regulation and initiation, although indirect, has been shown to be significant with the functionality of TFs strongly influenced by the presence of TcoFs. While the role of TFs and their interaction with regulatory DNA regions has been well-studied, the association between TFs and TcoFs has so far been given less attention. Here, we present a resource that is comprised of a collection of human TFs and the TcoFs with which they interact. Other proteins that have a proven interaction with a TF, but are not considered TcoFs are also included. Our database contains 157 high-confidence TcoFs and additionally 379 hypothetical TcoFs. These have been identified and classified according to the type of available evidence for their involvement in transcriptional regulation and their presence in the cell nucleus. We have divided TcoFs into four groups, one of which contains high-confidence TcoFs and three others contain TcoFs which are hypothetical to different extents. We have developed the Dragon Database for Human Transcription Co-Factors and Transcription Factor Interacting Proteins (TcoF-DB). A web-based interface for this resource can be freely accessed at http://cbrc.kaust.edu.sa/tcof/ and http://apps.sanbi.ac.za/tcof/. © The Author(s) 2010.

  17. Thiamin diphosphate in biological chemistry: new aspects of thiamin metabolism, especially triphosphate derivatives acting other than as cofactors.

    Science.gov (United States)

    Bettendorff, Lucien; Wins, Pierre

    2009-06-01

    Prokaryotes, yeasts and plants synthesize thiamin (vitamin B1) via complex pathways. Animal cells capture the vitamin through specific high-affinity transporters essential for internal thiamin homeostasis. Inside the cells, thiamin is phosphorylated to higher phosphate derivatives. Thiamin diphosphate (ThDP) is the best-known thiamin compound because of its role as an enzymatic cofactor. However, in addition to ThDP, at least three other thiamin phosphates occur naturally in most cells: thiamin monophosphate, thiamin triphosphate (ThTP) and the recently discovered adenosine thiamin triphosphate. It has been suggested that ThTP has a specific neurophysiological role, but recent data favor a much more basic metabolic function. During amino acid starvation, Escherichia coli accumulate ThTP, possibly acting as a signal involved in the adaptation of the bacteria to changing nutritional conditions. In animal cells, ThTP can phosphorylate some proteins, but the physiological significance of this mechanism remains unknown. Adenosine thiamin triphosphate, recently discovered in E. coli, accumulates during carbon starvation and might act as an alarmone. Among the proteins involved in thiamin metabolism, thiamin transporters, thiamin pyrophosphokinase and a soluble 25-kDa thiamin triphosphatase have been characterized at the molecular level, in contrast to thiamin mono- and diphosphatases whose specificities remain to be proven. A soluble enzyme catalyzing the synthesis of adenosine thiamin triphosphate from ThDP and ADP or ATP has been partially characterized in E. coli, but the mechanism of ThTP synthesis remains elusive. The data reviewed here illustrate the complexity of thiamin biochemistry, which is not restricted to the cofactor role of ThDP.

  18. Putative endogenous filovirus VP35-like protein potentially functions as an IFN antagonist but not a polymerase cofactor.

    Directory of Open Access Journals (Sweden)

    Tatsunari Kondoh

    Full Text Available It has been proposed that some non-retroviral RNA virus genes are integrated into vertebrate genomes. Endogenous filovirus-like elements (EFLs have been discovered in some mammalian genomes. However, their potential roles in ebolavirus infection are unclear. A filovirus VP35-like element (mlEFL35 is found in the little brown bat (Myotis lucifugus genome. Putative mlEFL35-derived protein (mlEFL35p contains nearly full-length amino acid sequences corresponding to ebolavirus VP35. Ebola virus VP35 has been shown to bind double-stranded RNA, leading to inhibition of type I interferon (IFN production, and is also known as a viral polymerase cofactor that is essential for viral RNA transcription/replication. In this study, we transiently expressed mlEFL35p in human kidney cells and investigated its biological functions. We first found that mlEFL35p was coimmunoprecipitated with itself and ebolavirus VP35s but not with the viral nucleoprotein. Then the biological functions of mlEFL35p were analyzed by comparing it to ebolavirus VP35s. We found that the expression of mlEFL35p significantly inhibited human IFN-β promoter activity as well as VP35s. By contrast, expression of mlEFL35p did not support viral RNA transcription/replication and indeed slightly decrease the reporter gene expression in a minigenome assay. These results suggest that mlEFL35p potentially acts as an IFN antagonist but not a polymerase cofactor.

  19. Molybdenum cofactor deficiency causes translucent integument, male-biased lethality, and flaccid paralysis in the silkworm Bombyx mori.

    Science.gov (United States)

    Fujii, Tsuguru; Yamamoto, Kimiko; Banno, Yutaka

    2016-06-01

    Uric acid accumulates in the epidermis of Bombyx mori larvae and renders the larval integument opaque and white. Yamamoto translucent (oya) is a novel spontaneous mutant with a translucent larval integument and unique phenotypic characteristics, such as male-biased lethality and flaccid larval paralysis. Xanthine dehydrogenase (XDH) that requires a molybdenum cofactor (MoCo) for its activity is a key enzyme for uric acid synthesis. It has been observed that injection of a bovine xanthine oxidase, which corresponds functionally to XDH and contains its own MoCo activity, changes the integuments of oya mutants from translucent to opaque and white. This finding suggests that XDH/MoCo activity might be defective in oya mutants. Our linkage analysis identified an association between the oya locus and chromosome 23. Because XDH is not linked to chromosome 23 in B. mori, MoCo appears to be defective in oya mutants. In eukaryotes, MoCo is synthesized by a conserved biosynthesis pathway governed by four loci (MOCS1, MOCS2, MOCS3, and GEPH). Through a candidate gene approach followed by sequence analysis, a 6-bp deletion was detected in an exon of the B. mori molybdenum cofactor synthesis-step 1 gene (BmMOCS1) in the oya strain. Moreover, recombination was not observed between the oya and BmMOCS1 loci. These results indicate that the BmMOCS1 locus is responsible for the oya locus. Finally, we discuss the potential cause of male-biased lethality and flaccid paralysis observed in the oya mutants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. TcoF-DB: dragon database for human transcription co-factors and transcription factor interacting proteins

    KAUST Repository

    Schaefer, Ulf; Schmeier, Sebastian; Bajic, Vladimir B.

    2010-01-01

    The initiation and regulation of transcription in eukaryotes is complex and involves a large number of transcription factors (TFs), which are known to bind to the regulatory regions of eukaryotic DNA. Apart from TF-DNA binding, protein-protein interaction involving TFs is an essential component of the machinery facilitating transcriptional regulation. Proteins that interact with TFs in the context of transcription regulation but do not bind to the DNA themselves, we consider transcription co-factors (TcoFs). The influence of TcoFs on transcriptional regulation and initiation, although indirect, has been shown to be significant with the functionality of TFs strongly influenced by the presence of TcoFs. While the role of TFs and their interaction with regulatory DNA regions has been well-studied, the association between TFs and TcoFs has so far been given less attention. Here, we present a resource that is comprised of a collection of human TFs and the TcoFs with which they interact. Other proteins that have a proven interaction with a TF, but are not considered TcoFs are also included. Our database contains 157 high-confidence TcoFs and additionally 379 hypothetical TcoFs. These have been identified and classified according to the type of available evidence for their involvement in transcriptional regulation and their presence in the cell nucleus. We have divided TcoFs into four groups, one of which contains high-confidence TcoFs and three others contain TcoFs which are hypothetical to different extents. We have developed the Dragon Database for Human Transcription Co-Factors and Transcription Factor Interacting Proteins (TcoF-DB). A web-based interface for this resource can be freely accessed at http://cbrc.kaust.edu.sa/tcof/ and http://apps.sanbi.ac.za/tcof/. © The Author(s) 2010.

  1. Structural basis of thermal stability of the tungsten cofactor synthesis protein MoaB from Pyrococcus furiosus.

    Directory of Open Access Journals (Sweden)

    Nastassia Havarushka

    Full Text Available Molybdenum and tungsten cofactors share a similar pterin-based scaffold, which hosts an ene-dithiolate function being essential for the coordination of either molybdenum or tungsten. The biosynthesis of both cofactors involves a multistep pathway, which ends with the activation of the metal binding pterin (MPT by adenylylation before the respective metal is incorporated. In the hyperthermophilic organism Pyrococcus furiosus, the hexameric protein MoaB (PfuMoaB has been shown to catalyse MPT-adenylylation. Here we determined the crystal structure of PfuMoaB at 2.5 Å resolution and identified key residues of α3-helix mediating hexamer formation. Given that PfuMoaB homologues from mesophilic organisms form trimers, we investigated the impact on PfuMoaB hexamerization on thermal stability and activity. Using structure-guided mutagenesis, we successfully disrupted the hexamer interface in PfuMoaB. The resulting PfuMoaB-H3 variant formed monomers, dimers and trimers as determined by size exclusion chromatography. Circular dichroism spectroscopy as well as chemical cross-linking coupled to mass spectrometry confirmed a wild-type-like fold of the protomers as well as inter-subunits contacts. The melting temperature of PfuMoaB-H3 was found to be reduced by more than 15 °C as determined by differential scanning calorimetry, thus demonstrating hexamerization as key determinant for PfuMoaB thermal stability. Remarkably, while a loss of activity at temperatures higher than 50 °C was observed in the PfuMoaB-H3 variant, at lower temperatures, we determined a significantly increased catalytic activity. The latter suggests a gain in conformational flexibility caused by the disruption of the hexamerization interface.

  2. Termo do 1º Consenso em Disfunção Temporomandibular e Dor Orofacial Statement of the 1st Consensus on Temporomandibular Disorders and Orofacial Pain

    Directory of Open Access Journals (Sweden)

    Simone Vieira Carrara

    2010-06-01

    Full Text Available O Termo do 1º Consenso em Disfunção Temporomandibular e Dor Orofacial* foi criado com o propósito de substituir divergências por evidência científica dentro dessa especialidade da Odontologia. O documento oferece informações claras e fundamentadas para orientar o cirurgião-dentista e demais profissionais de saúde sobre os cuidados demandados pelo paciente, tanto no processo de diagnóstico diferencial quanto na fase de aplicação das terapias de controle da dor e disfunção. O Termo foi aprovado no mês de janeiro de 2010 em reunião realizada durante o Congresso Internacional de Odontologia do Estado de São Paulo e converge o pensamento dos profissionais mais conceituados do Brasil na especialidade Disfunção Temporomandibular e Dor Orofacial.This Statement of the 1st Consensus on Temporomandibular Disorders and Orofacial Pain was created with the purpose of substituting controversies for scientific evidence within this specialty field of dentistry. The document provides clear and well-grounded guidance to dentists and other health professionals about the care required by patients both in the process of differential diagnosis and during the stage when they undergo treatment to control pain and dysfunction. The Statement was approved in January 2010 at a meeting held during the International Dental Congress of São Paulo and draws together the views of Brazil's most respected professionals in the specialty of Temporomandibular Disorders and Orofacial Pain.

  3. Meloxicam associado ou não ao tramadol no controle da dor após ovário-histerectomia videoassistida em cadelas

    Directory of Open Access Journals (Sweden)

    M.T. Oliveira

    2016-02-01

    Full Text Available O objetivo deste estudo foi avaliar a eficácia do meloxicam associado ou não ao tramadol, no controle da dor após ovário-histerectomia (OVH laparoscópica com dois portais. Foram selecionadas 14 cadelas hígidas. Os animais foram separados de forma aleatória, em dois grupos. O grupo M (GM recebeu meloxicam (0,2mg kg-1, s.i.d., enquanto os animais do grupo MT (GMT receberam a associação de meloxicam (0,2mg kg-1, s.i.d. e tramadol (4mg kg-1, t.i.d., ambos durante dois dias de pós-operatório. Para avaliação da dor pós-cirúrgica, foram utilizadas as escalas de Melbourne e escala visual analógica (EVA, além de mensurações de glicemia e cortisol sérico. Não houve diferença ao se avaliarem os grupos GM e GMT pela escala de Melbourne nem pela EVA. As mensurações de cortisol não atingiram valores superiores aos de referência para a espécie, enquanto os valores de glicemia não apresentaram variação significativa ao longo do tempo de avaliação nem entre grupos. Com os resultados deste estudo, foi possível concluir que a utilização de meloxicam associado ou não ao tramadol, nas doses e posologias propostas, é eficaz para controlar a dor pós-operatória de cadelas submetidas à OVH laparoscópica com dois portais.

  4. What do general neurologists need to know about neuropathic pain? O que os neurologistas gerais devem saber sobre dor neuropática?

    Directory of Open Access Journals (Sweden)

    Pedro Schestatsky

    2009-09-01

    Full Text Available Neuropathic pain (NP is defined as pain caused by lesion or dysfunction of the somatosensory system, as a result of abnormal activation of the nociceptive pathway (small fibers and spinothalamic tracts. The most common causes of this syndrome are the following: diabetes, post-herpetic neuralgia, trigeminal neuralgia, stroke, multiple sclerosis, spinal cord injury, HIV infection, cancer. In the last few years, the NP has been receiving special attention for two main reasons: (1 therapeutical refractoriness of a variety of pain syndromes with predominant neuropathic characteristics and (2 the development of diagnostic tools for neuropathic pain complaints. The present review article provides relevant information on the understanding and recognition of NP, as well as evidence-based therapeutic approaches.A dor neuropática (DN é definida como dor causada por lesão ou disfunção do sistema somatossensitivo, como resultado da ativação anormal da via nociceptiva (fibras de pequeno calibre e trato espinotalâmico. As principais causas desta síndrome são: diabetes, neuralgia pós-herpética, neuralgia trigeminal, acidente vascular encefálico, esclerose múltipla, trauma raquimedular, infecção por HIV, câncer. Nos últimos anos, a DN vem recebendo especial atenção por dois motivos principais: (1 refratariedade terapêutica de várias síndromes dolorosas com componentes neuropáticos predominantes e (2 desenvolvimento de ferramentas diagnósticas para o reconhecimento deste tipo de dor. O presente artigo de revisão fornece informações relevantes para o entendimento e reconhecimento da DN, bem como de abordagens terapêuticas baseadas em evidência.

  5. Working conditions and musculoskeletal pain among Brazilian pottery workers Condições de trabalho e dor osteomuscular entre ceramistas brasileiros

    Directory of Open Access Journals (Sweden)

    Adriana Cristina de Souza Melzer

    2010-03-01

    Full Text Available In the municipality of Pedreira in São Paulo State, Brazil, a large number of workers from the ceramic industry have left their jobs because of work related musculoskeletal disorders. The objectives of this study were to describe the work conditions pertaining to the ceramic industry, to determine the prevalence of musculoskeletal pain and to identify the associations between symptoms and organizational, biomechanical, psychosocial and individual variables. Nine ceramic manufacturers participated. The activities of 18 individuals were analyzed through direct observation. All workers answered a questionnaire about work and health (n = 235. The results found that the general working conditions in the pottery manufacturers were poor. A 38.5% prevalence of musculoskeletal pain was found. Repetition, tool use, lack of control over decisions, worries regarding work demands, relationship issues, work dissatisfaction and the wish to move on to another function were all associated with pain. We concluded that musculoskeletal pain is one of the outcomes of elevated human requirements resulting from working conditions and organization in the ceramic industry.No Município de Pedreira, São Paulo, Brasil, um grande número de trabalhadores das indústrias cerâmicas se afasta do trabalho em conseqüência de distúrbios osteomusculares relacionados ao trabalho. Os objetivos deste estudo foram descrever as condições de trabalho, determinar a prevalência de dor e identificar associações entre sintomas e variáveis organizacionais, biomecânicas, psicossociais e individuais. Nove indústrias participaram do estudo. As atividades de 18 pessoas foram analisadas através de observações diretas. Todos os trabalhadores responderam a um questionário sobre trabalho e saúde (n = 235. Os resultados indicaram que as condições de trabalho nas indústrias cerâmicas estudadas eram ruins. Foi encontrada uma prevalência de 38,5% de dor. Repetitividade, utiliza

  6. Sofrimento experiênciado pelo enfermeiro quando cuida o doente em fim de vida com dor não controlada

    OpenAIRE

    Viana, Aurora Maria Martins

    2014-01-01

    Dissertação de Mestrado em Cuidados Paliativos apresentada na Escola Superior de Saúde do Instituto Politécnico de Viana do Castelo A singularidade e individualidade da pessoa fazem com que a relação que o homem tem com a sua dor e sofrimento seja única e, que essa experiência seja vivida de uma forma muito particular. Os processos e a intervenção de enfermagem para o alívio do sofrimento, desenvolve-se através de um processo de acompanhamento inter-relacional, dinâmico, integr...

  7. Diminuição da dor em mulheres com dismenorreia primária, tratadas pelo método Pilates

    OpenAIRE

    Araújo, Luana Macêdo de; Silva, José Mário Nunes da; Bastos, Weltianne Tavares; Ventura, Patrícia Lima

    2012-01-01

    JUSTIFICATIVA E OBJETIVOS: A dismenorreia corresponde a um conjunto de manifestações de caráter doloroso que aparecem no dia anterior ou no primeiro dia de fluxo menstrual. O método Pilates, compreende uma série de exercícios baseados nos movimentos progressivos que o corpo é capaz de executar. O presente estudo teve como objetivo comparar a dor em mulheres com dismenorreia primária antes e após serem submetidas ao método Pilates. MÉTODO: Trata-se de um estudo descritivo, experimental, com ca...

  8. Dor pós-operatória em hospital universitário: perspectivas para promoção de saúde

    OpenAIRE

    Letícia Vivian de Souza Franco; Renata Ferreira Barbosa Sugai; Sarah Costa e Silva; Thaís de Carvalho da Silva; Roberta Bessa Veloso Silva; Roberto Salvador de Souza Guimarães; Cláudio Daniel Cerdeira; Gérsika Bittencourt Santos

    2017-01-01

    Objetivo: Avaliar a prevalência, os fatores influentes e a magnitude da dor pós-operatória (DPO) em pacientes atendidos em um hospital universitário. Métodos: Realizou-se estudo prospectivo e transversal envolvendo 100 pacientes submetidos a diferentes procedimentos cirúrgicos, no período de março a maio de 2016, entrevistados nas primeiras 24 horas do pós-operatório e avaliados através de uma escala visual numérica (EVN). Resultados: As cirurgias mais comuns encontradas são: cesárea, apendic...

  9. Perceção de falhas de memória, ansiedade e depressão em pacientes com dor crónica

    OpenAIRE

    Lobato, Filipa

    2012-01-01

    Dissertação apresentada à Universidade Fernando Pessoa como parte dos requisitos para a obtenção do grau de Mestre em Psicologia, ramo de Psicologia Clínica e da Saúde Diversos estudos têm mostrado que as alterações cognitivas e os estados de humor fazem parte dos quadros com pacientes com dor, o que acaba por limitar, ainda mais, a sua autonomia em termos funcionais das atividades do dia-a-dia. O principal objetivo do presente estudo foi analisar a perceção de falhas de memóri...

  10. Angiotomografia de coronárias na avaliação da dor torácica aguda na sala de emergência

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Elias dos Prazeres

    2013-12-01

    Full Text Available A angiotomografia de coronárias emergiu recentemente como uma ferramenta diagnóstica acurada na avaliação da doença arterial coronariana, fornecendo dados diagnósticos e prognósticos que se correlacionam diretamente com os dados fornecidos pela cineangiocoronariografia. Com a evolução tecnológica, permitindo melhora na resolução temporal, espacial, melhor cobertura do volume cardíaco com redução significativa da dose de radiação, somada à necessidade de protocolos de estratificação de risco mais efetivos para pacientes com dor torácica no pronto-socorro, sua aplicação passou a ser testada no cenário da dor torácica aguda, já que cerca de dois terços das angiografias coronarianas invasivas não demonstram doença coronariana obstrutiva significativa. Na prática diária, sem o uso de tecnologias mais eficientes, como a angiotomografia de coronárias, permanece um desafio ao médico do setor de emergência a estratificação segura e eficiente do paciente com dor torácica aguda. Recentemente, vários estudos, incluindo três randomizados, mostraram resultados favoráveis ao uso dessa tecnologia no pronto-socorro para pacientes com baixa a intermediária probabilidade de doença arterial coronariana. Nesta revisão, apresentamos os dados do uso da angiotomografia de coronárias na estratificação de risco de pacientes com dor torácica na sala de emergência, o seu valor diagnóstico, prognóstico e custo-efetividade e uma análise crítica dos recentes estudos multicêntricos publicados.

  11. Dor neuropática central após lesão medular traumática: capacidade funcional e aspectos sociais

    OpenAIRE

    Vall, Janaina; Braga, Violante Augusta Batista

    2005-01-01

    Estudo de caso comparativo com o objetivo de avaliar a capacidade funcional e os aspectos sociais de dois pacientes, ambos com lesão medular traumática, sem e com dor neuropática central associada, respectivamente. Para avaliar a capacidade funcional, foi utilizado como instrumento o Functional Independence Measure ou Escala de Independência Funcional. E para avaliar os aspectos sociais foi construído o ecomapa de cada paciente, preconizado pelo modelo Calgary de avaliação de famílias. Ambos ...

  12. Caracterização dos padrões de dor, sono e alexitimia em pacientes com fibromialgia atendidos em um centro terciário brasileiro

    Directory of Open Access Journals (Sweden)

    Lazslo A. Avila

    2014-10-01

    Full Text Available Objetivos: Fibromialgia (FM é uma síndrome complexa, caracterizada por uma dor musculoesquelética crônica duradoura e difusa, derivada de causas não inflamatórias e classicamente associada à presença de pontos sensíveis específicos. No entanto, estudos destacaram outros sintomas importantes associados à má qualidade de vida (QDV em pacientes com FM, por exemplo, distúrbios do sono e alexitimia. Esse estudo teve por objetivo investigar os padrões de dor, sono e alexitimia de pacientes com FM em um centro terciário brasileiro. Métodos: 20 pacientes com FM acompanhados na clínica ambulatorial de reumatologia de um centro terciário brasileiro (Faculdade de Medicina de São José do Rio Preto - FAMERP, São Paulo, Brasil e 20 pacientes sem FM provenientes de outros serviços ambulatoriais da FAMERP completaram um questionário clínico e sociodemográfico, o Fibromyalgia Impact Questionnaire (FIQ, o Pittsburgh Sleep Quality Index (PSQI, o Toronto Alexithymia Scale (TAS-20 e o SF-36 (WHOQOL. Resultados: Os pacientes com FM tiveram desempenhos piores em todas as dimensões de QDV do SF-36 e escores mais altos no PSQI (P = 0,01 e no TAS-20 (P = 0,02. Pacientes com FM também tiveram escores significativamente mais altos em todos os domínios específicos do PSQI e TAS-20. Discussão: Os presentes dados concordavam com a literatura, evidenciando pior desempenho de pacientes com FM no impacto da dor, queixas de sono e maior presença de alexitimia. Conclusão: Estudos evidenciaram, além das queixas de dor, a presença de sintomas importantes e frequentemente subdiagnosticados, em pacientes com FM, como queixas relativas ao sono e alexitimia. Um conhecimento mais aprofundado desses distúrbios poderia melhorar a abordagem e o tratamento dos pacientes com FM.

  13. Interaction Profiling Identifies the Human Nuclear Exosome Targeting Complex

    DEFF Research Database (Denmark)

    Lubas, Michal Szymon; Christensen, Marianne Skovgaard; Kristiansen, Maiken Søndergaard

    2011-01-01

    from nucleoli, and consistently NEXT is specifically required for the exosomal degradation of promoter upstream transcripts (PROMPTs). We also detect putative homolog TRAMP subunits hTRF4-2 (Trf4p) and ZCCHC7 (Air2p) in hRRP6 and hMTR4 precipitates. However, at least ZCCHC7 function is restricted...... to nucleoli. Our results suggest that human nuclear exosome degradation pathways comprise modules of spatially organized cofactors that diverge from the yeast model....

  14. Mechanism of the reaction of ebselen with endogenous thiols : dihydrolipoate is a better cofactor than glutathione in the peroxidase activity of ebselen

    NARCIS (Netherlands)

    Haenen, G R; De Rooij, B M; Vermeulen, N P; Bast, A

    The therapeutic effect of ebselen has been linked to its peroxidase activity. In the present study, the peroxidase activity of ebselen toward H2O2 with the endogenous thiols GSH and dihydrolipoate [L(SH)2] as cofactors was determined. When GSH was used, peroxide removal was described by a ter uni

  15. Relative contributions of decay accelerating factor (DAF), membrane cofactor protein (MCP) and CD59 in the protection of melanocytes from homologous complement

    NARCIS (Netherlands)

    Venneker, G. T.; Vodegel, R. M.; Okada, N.; Westerhof, W.; Bos, J. D.; Asghar, S. S.

    1998-01-01

    Complement regulatory molecules, membrane cofactor protein (MCP), decay accelerating factor (DAF) and CD59, protect body cells from autologous complement. They have wide tissue distribution but nothing is known about the expression of these molecules on human melanocytes. Since melanocytes are lysed

  16. CONTROLE DE SI, DOR E REPRESENTAÇÃO FEMININA ENTRE LUTADORES(AS DE MIXED MARTIAL ARTS (MMA

    Directory of Open Access Journals (Sweden)

    Samuel Oliveira Thomazini

    2008-12-01

    Full Text Available This papers aims to present results of a seven months ethnographic research in three gyms of Mixed Marcial Arts (MAA, focusing the identity construction of the fighters. Observations and interviews were done, as well as pictures and film takes in traing ans competition were also important. The results suggest the existence of bioidentities processes in sense of selfcontrol and rationalization of pain. The representations of the presence of females is quite ambiguous in this universe of masculinity. La investigación se ocupó de tres gimnasios especializados en Mixed Marcial Arts (MAA, analizando rasgos esenciales de la construcción de las identidades de luchadores y luchadoras. Fueran hecahs durante siete meses observaciones participantes (registradas en diario de campo y entrevistas semi-dirigidas. Fotos y filmages de entrenamientos y competiciones fueran también importantes. Los resultados sugieren la presencia de procesos bioidentitários vinculados al control de si mismo, a la racionalización del dolor y, además, representaciones ambiguas sobre la presencia femenina en este universo que es sobretodo masculino. Trata-se de uma pesquisa realizada em três academias especializadas em Mixed Marcial Arts (MMA. Analisa alguns elementos indispensáveis à forja identitária de lutadores(as desta modalidade. A etnografia durou sete meses, oportunidade para combinar uma observação participante (devidamente registrada no diário de notas com a realização de entrevistas semi-estruturadas com os(as atletas. Fotografias e filmagens dos locais de treinamento e de competição foram recursos metodológicos também úteis. Os resultados indicam a existência de processos bioidentitários vinculados ao controle de si e à racionalização da dor, apontando, além disso, para uma representação ambígua em relação à presença feminina em um universo ainda predominantemente masculino.

  17. Mediator-dependent Nuclear Receptor Functions

    Science.gov (United States)

    Chen, Wei; Roeder, Robert

    2011-01-01

    As gene-specific transcription factors, nuclear hormone receptors are broadly involved in many important biological processes. Their function on target genes requires the stepwise assembly of different coactivator complexes that facilitate chromatin remodeling and subsequent preinitiation complex (PIC) formation and function. Mediator has proved to be a crucial, and general, nuclear receptor-interacting coactivator, with demonstrated functions in transcription steps ranging from chromatin remodeling to subsequent PIC formation and function. Here we discuss (i) our current understanding of pathways that nuclear receptors and other interacting cofactors employ to recruit Mediator to target gene enhancers and promoters, including conditional requirements for the strong NR-Mediator interactions mediated by the NR AF2 domain and the MED1 LXXLLL motifs and (ii) mechanisms by which Mediator acts to transmit signals from enhancer-bound nuclear receptors to the general transcription machinery at core promoters to effect PIC formation and function. PMID:21854863

  18. O tumor experimental de Ehrlich induz comportamento nociceptivo em camundongos : padronização de um novo modelo para o estudo da fisiopatologia da dor no câncer e triagem de analgésicos

    OpenAIRE

    Cássia Calixto de Campos

    2013-01-01

    A dor afeta diretamente a qualidade de vida dos pacientes com câncer o que ressalta a importância deste campo de pesquisa. O tumor de Ehrlich foi descrito em 1905 como um adenocarcinoma mamário de camundongos fêmeas e pode ser desenvolvido em formas sólidas e ascítica, dependendo da administração em tecidos ou cavidades, respectivamente. O presente estudo investigou se a administração subcutânea plantar das células tumorais de Ehrlich induz o comportamento da dor manifesta (agitação da pata),...

  19. Avaliação da intensidade de dor e sinais vitais no pós-operatório de cirurgia cardíaca

    Directory of Open Access Journals (Sweden)

    Adriana de Fátima Alencar Miranda

    2011-04-01

    Full Text Available O objetivo do estudo é analisar as alterações nos sinais vitais de pacientes em pós-operatório de cirurgias cardíacas, mediante intensidade de dor referida. Trata-se de estudo descritivo-exploratório, que utilizou o método de análise quantitativa na investigação de 38 pacientes submetidos à primeira renovação de curativos. A análise dos dados, mensurados antes e após a realização do procedimento de enfermagem, indicaram que a manifestação da dor ocorreu em diferentes classificações. As principais alterações nos sinais vitais ocorreram na pressão arterial. Concluiu-se que a intensidade dolorosa mantém relações com os resultados dos sinais vitais e o cuidado prestado é imprescindível ao restabelecimento do estado de saúde do paciente no pós-operatório.

  20. Avaliação da freqüência de depressão em pacientes com endometriose e dor pélvica

    Directory of Open Access Journals (Sweden)

    LORENÇATTO CAROLINA

    2002-01-01

    Full Text Available OBJETIVO: Avaliar a freqüência de depressão em pacientes com endometriose e queixa atual de dor pélvica para determinar a necessidade ou não de atendimento psicológico. MÉTODOS: Participaram deste estudo 50 mulheres com idade entre 24 e 48 anos, com diagnóstico de endometriose e queixa atual de dor pélvica. Para avaliar a prevalência da depressão, utilizou-se o Inventário de Depressão de Beck, validado em nosso meio. RESULTADOS: Identificou-se a presença de depressão em 92% das pacientes avaliadas, sendo 56% de intensidade moderada a grave. Apesar de 66% das pacientes relatarem o uso de medicação, não foi observada correlação significativa entre a presença de depressão com o uso de hormônios. CONCLUSÃO: Os resultados demostraram uma alta prevalência de depressão, justificando-se, assim, a necessidade do atendimento psicológico a essas pacientes.

  1. Atuação dos enfermeiros na dor aguda torácica: Revisão integrativa

    Directory of Open Access Journals (Sweden)

    Joao Carlos Alves dos Santos

    2016-12-01

    Full Text Available A dor torácica é uma queixa comum nos serviços de saúde e os enfermeiros devem estar preparados para o primeiro atendimento bem como o cuidado de maior duração nas unidades especializadas ou não para o atendimento integral. Objetivou-se analisar a produção da literatura nacional sobre a realidade da ação do enfermeiro na dor torácica aguda sugestiva de síndrome coronariana aguda nos serviços de saúde. O trabalho trata-se de uma revisão integrativa realizada na base de dados da Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS no portal eletrônico da Biblioteca Virtual em Saúde (BVS. Utilizaram-se os descritores em português. Selecionaram-se publicações no corte temporal, de 2011 à 2016. Foram sistematizados por intermédio de um instrumento, seguido de leitura com análise textual, temática e interpretativa dos dados. Encontraram-se ao todo 359 produções científicas. Todavia, apenas 10 estudos foram selecionados e revisados conforme os critérios de inclusão. A maioria das produções fizeram apontamentos assinalando proposições ou lacunas sobre as contri­buições de sua pesquisa para literatura. Identificou-se que dentro da atuação do enfermeiro frente à síndrome coronariana aguda destacam-se o cuidado sistematizado individualizado; conhecimento sobre exames e medicações e aspectos de relação do paciente com o agravo cardíaco na perspectiva individual, socioeconômica e psicológica. Existem poucas produções nos últimos anos em detrimento da enorme relevância do tema e por se um tema constantemente atualizado. Vários domínios da enfermagem, em especial das atividades do enfermeiro, ainda não foram discutidas na literatura sobre a realidade do profissional com o tema abordado. Entretanto, a presente revisão integrativa pôde contribuir para a ampliação e disseminação de conhecimentos referentes à questão pesquisada, servindo de fonte de informação.The work of nurses in

  2. Prevalência de dor crônica em adultos Prevalencia de dolor cronico en adultos Prevalence of chronic pain in adult workers

    Directory of Open Access Journals (Sweden)

    Maria Clara Giorio Dutra Kreling

    2006-08-01

    Full Text Available A dor crônica é um problema de saúde pública que acarreta prejuízos pessoais e sociais. Estudos epidemiológicos de dor crônica no Brasil e no resto do mundo são escassos, principalmente em se tratando de dores não específicas e em populações não vinculadas a serviços de saúde. Foram objetivos desse estudo: identificar a prevalência de dor crônica em adultos trabalhadores; analisar a prevalência de dor crônica conforme o sexo; e analisar a prevalência de dor conforme locais do corpo. Esta pesquisa foi realizada com uma amostra de 505 funcionários da Universidade Estadual de Londrina (Paraná, Brasil, considerando-se uma prevalência esperada de 50%, margem de erro de 4% na estimativa e nível de confiança de 95%. Estabeleceram-se como significativos os valores de pEl dolor crónico es un problema de salud pública que puede acarrear prejuicios personales y sociales. Estudios epidemiológicos del dolor crónico en Brasil y en el resto del mundo son escasos, máxime cuando se trata de los dolores no específicos y en poblaciones que no se vinculam a los servícios de salud. Esse estudio tuvo como objetivos: identificar la prevalencia del dolor crónico em adultos trabajadores; analizar la prevalencia del dolor conforme regiones del cuerpo. Esa investigación fue realizada con una muestra de 505 funcionarios de la Universidad Estadual de Londrina, considerándose una prevalencia esperada de 50%, margen de error de 4% em la estimativa y nivel de confianza de 95%. Se estableció como significativo los valores de pChronic pain is a public health problem which causes personal and social losses. There are few epidemiological studies of chronic pain in Brazil and elsewhere in the world, especially those dealing with non-specific pain, in general population. The objectives of this study were: to identify the prevalence of chronic pain in adult workers; to analyze the prevalence of chronic pain according to gender, and local of pain

  3. O convivio com a dor: um enfoque existencial El convivio con el dolor: un enfoque existencial Living with pain: an existential focus

    Directory of Open Access Journals (Sweden)

    Luciane Maximiliano Sanches

    2002-12-01

    Full Text Available No cotidiano de um hospital, em meu sendo-enfermeira, cuidando de pacientes com dor, essa mostrou-se a mim para além de uma esfera biológica, inserindo-se em uma dimensão existencial. Deste conviver, algo me inquietou e senti necessidade de compreender essas pessoas em situação de dor passando a questionar: como a pessoa compreende a sua dor? Qual o significado de vivenciar situações dolorosas em sua cronicidade? . Na tentativa de encontrar um caminho para tal compreensão, busquei por algumas idéias da fenomenologia. Foram realizadas entrevistas individuais, fundamentada na questão norteadora: "Como vem sendo para o (a senhor (a o convívio com a dor? Conte-me sobre isto". Após análise, pude compreender que a dor é uma forma de estreitamento do horizonte de possibilidades, de transformações na existência. Não é somente o corpo físico que se encontra doente, mas a vida em suas várias dimensões ficam afetadas, fundamentalmente no que se refere ao mundo familiar, do trabalho e da auto-relação.En el cotidiano de un hospital, la actuación de la enfermera cuidando de pacientes con dolor, demuestra más que una esfera biológica, incluyendose en una dimensión existencial. A partir de este convivir, algo despertó a la autora que sentió la necesidad de comprender las personas en situación de dolor, cuestionando: como la persona comprende su dolor? Cuál es el significado de vivir situaciones dolorosas en su cronicidad? En la tentativa de encontrar un camino para esta comprensión, la autora buscó por algunas ideas de la fenomenologia. Fueron realizadas entrevistas individuales, fundamentadas en la cuestión norteadora: "Como es y ha sido su convivio con el dolor? Hable sobre esto. Después del análisis, la autora comprendió que el dolor es una forma de estrechamiento del horizonte de posibilidades, de transformaciones en la existencia. No es solamente el cuerpo físico que se encuentra enfermo, pero la vida en sus v

  4. X-ray absorption spectroscopy on the calcium cofactor to the manganese cluster in photosynthetic oxygen evolution

    Energy Technology Data Exchange (ETDEWEB)

    Cinco, Roehl M. [Univ. of California, Berkeley, CA (United States)

    1999-12-01

    Along with Mn, calcium and chloride ions are necessary cofactors for oxygen evolution in Photosystem II (PS II). To further test and verify whether Ca is close to the Mn cluster, the authors substituted strontium for Ca and probed from the Sr point of view for any nearby Mn. The extended X-ray absorption fine structure (EXAFS) of Sr-reactivated PS II indicates major differences between the intact and NH2OH-treated samples. In intact samples, the Fourier transform of the Sr EXAFS shows a Fourier peak that is missing in inactive samples. This peak II is best simulated by two Mn neighbors at a distance of 3.5 Angstrom, confirming the proximity of Ca (Sr) cofactor to the Mn cluster. In addition, polarized Sr EXAFS on oriented Sr-reactivated samples shows this peak II is dichroic: large magnitude at 10 degrees (angle between the PS II membrane normal and the x-ray electric field vector) and small at 80 degrees. Analysis of the dichroism yields the relative angle between the Sr-Mn vector and membrane normal (23 degrees ± 4 degrees), and the isotropic coordination number for these layered samples. X-ray absorption spectroscopy has also been employed to assess the degree of similarity between the manganese cluster in PS II and a family of synthetic manganese complexes containing the distorted cubane [Mn4O3X] core (X = benzoate, acetate, methoxide, hydroxide, azide, fluoride, chloride or bromide). In addition, Mn4O3Cl complexes containing three or six terminal Cl ligands at three of the Mn were included in this study. The EXAFS method detects the small changes in the core structures as X is varied in this series, and serves to exclude these distorted cubanes of C3v symmetry as a topological model for the Mn catalytic cluster. The sulfur K-edge x-ray absorption near-edge structure (XANES) spectra for the amino acids cysteine, methionine, their corresponding oxidized forms cystine and methionine sulfoxide, and

  5. Risk factors for human papillomavirus exposure and co-factors for cervical cancer in Latin America and the Caribbean.

    Science.gov (United States)

    Almonte, Maribel; Albero, Ginesa; Molano, Mónica; Carcamo, César; García, Patricia J; Pérez, Gonzalo

    2008-08-19

    The incidence of cervical cancer in Latin America and the Caribbean (LAC) is among the highest in the world. Because there are major demographic shifts happening in LAC countries (population growth, urbanization and ageing) cervical cancer incidence and mortality will likely continue to be a significant public health problem. Overall human papillomavirus (HPV) prevalence in the LAC general population has been found to be 2-fold higher than the average worldwide prevalence. The large HPV and cancer burden may be explained by the highly prevalent HPV variants of HPV types -16 and 18, which have an increased oncogenic potential. Given the major mode of transmission of genital HPV is sexual, certain, patterns of sexual behaviour (early age at first sexual intercourse, number of sexual partners and sexual behaviour of the partner) are associated with an increased risk of HPV genital acquisition. Although HPV infection is necessary for carcinogenesis, certain co-factors (high parity, long term use of oral contraceptives, smoking and co-infection with the human immunodeficiency virus (HIV)) help in the progression from infection to cancer. Many studies that have contributed to this evidence have been carried out in LAC and are reviewed and summarised in this article. Since HPV vaccines will likely take years to implement, and many more years to show impact on disease, cervical cancer screening programmes remain as the key intervention to control disease in LAC in the years to come.

  6. Development of CHARMM-Compatible Force-Field Parameters for Cobalamin and Related Cofactors from Quantum Mechanical Calculations.

    Science.gov (United States)

    Pavlova, Anna; Parks, Jerry M; Gumbart, James C

    2018-02-13

    Corrinoid cofactors such as cobalamin are used by many enzymes and are essential for most living organisms. Therefore, there is broad interest in investigating cobalamin-protein interactions with molecular dynamics simulations. Previously developed parameters for cobalamins are based mainly on crystal structure data. Here, we report CHARMM-compatible force field parameters for several corrinoids developed from quantum mechanical calculations. We provide parameters for corrinoids in three oxidation states, Co 3+ , Co 2+ , and Co 1+ , and with various axial ligands. Lennard-Jones parameters for the cobalt center in the Co(II) and Co(I) states were optimized using a helium atom probe, and partial atomic charges were obtained with a combination of natural population analysis (NPA) and restrained electrostatic potential (RESP) fitting approaches. The Force Field Toolkit was used to optimize all bonded terms. The resulting parameters, determined solely from calculations of cobalamin alone or in water, were then validated by assessing their agreement with density functional theory geometries and by analyzing molecular dynamics simulation trajectories of several corrinoid proteins for which X-ray crystal structures are available. In each case, we obtained excellent agreement with the reference data. In comparison to previous CHARMM-compatible parameters for cobalamin, we observe a better agreement for the fold angle and lower RMSD in the cobalamin binding site. The approach described here is readily adaptable for developing CHARMM-compatible force-field parameters for other corrinoids or large biomolecules.

  7. Discovery of cofactor-specific, bactericidal Mycobacterium tuberculosis InhA inhibitors using DNA-encoded library technology.

    Science.gov (United States)

    Soutter, Holly H; Centrella, Paolo; Clark, Matthew A; Cuozzo, John W; Dumelin, Christoph E; Guie, Marie-Aude; Habeshian, Sevan; Keefe, Anthony D; Kennedy, Kaitlyn M; Sigel, Eric A; Troast, Dawn M; Zhang, Ying; Ferguson, Andrew D; Davies, Gareth; Stead, Eleanor R; Breed, Jason; Madhavapeddi, Prashanti; Read, Jon A

    2016-12-06

    Millions of individuals are infected with and die from tuberculosis (TB) each year, and multidrug-resistant (MDR) strains of TB are increasingly prevalent. As such, there is an urgent need to identify novel drugs to treat TB infections. Current frontline therapies include the drug isoniazid, which inhibits the essential NADH-dependent enoyl-acyl-carrier protein (ACP) reductase, InhA. To inhibit InhA, isoniazid must be activated by the catalase-peroxidase KatG. Isoniazid resistance is linked primarily to mutations in the katG gene. Discovery of InhA inhibitors that do not require KatG activation is crucial to combat MDR TB. Multiple discovery efforts have been made against InhA in recent years. Until recently, despite achieving high potency against the enzyme, these efforts have been thwarted by lack of cellular activity. We describe here the use of DNA-encoded X-Chem (DEX) screening, combined with selection of appropriate physical properties, to identify multiple classes of InhA inhibitors with cell-based activity. The utilization of DEX screening allowed the interrogation of very large compound libraries (10 11 unique small molecules) against multiple forms of the InhA enzyme in a multiplexed format. Comparison of the enriched library members across various screening conditions allowed the identification of cofactor-specific inhibitors of InhA that do not require activation by KatG, many of which had bactericidal activity in cell-based assays.

  8. Relationship between intracellular pH, metabolic co-factors and caspase-3 activation in cancer cells during apoptosis.

    Science.gov (United States)

    Sergeeva, Tatiana F; Shirmanova, Marina V; Zlobovskaya, Olga A; Gavrina, Alena I; Dudenkova, Varvara V; Lukina, Maria M; Lukyanov, Konstantin A; Zagaynova, Elena V

    2017-03-01

    A complex cascade of molecular events occurs in apoptotic cells but cell-to-cell variability significantly complicates determination of the order and interconnections between different processes. For better understanding of the mechanisms of programmed cell death, dynamic simultaneous registration of several parameters is required. In this paper we used multiparameter fluorescence microscopy to analyze energy metabolism, intracellular pH and caspase-3 activation in living cancer cells in vitro during staurosporine-induced apoptosis. We performed metabolic imaging of two co-factors, NAD(P)H and FAD, and used the genetically encoded pH-indicator SypHer1 and the FRET-based sensor for caspase-3 activity, mKate2-DEVD-iRFP, to visualize these parameters by confocal fluorescence microscopy and two-photon fluorescence lifetime imaging microscopy. The correlation between energy metabolism, intracellular pH and caspase-3 activation and their dynamic changes were studied in CT26 cancer cells during apoptosis. Induction of apoptosis was accompanied by a switch to oxidative phosphorylation, cytosol acidification and caspase-3 activation. We showed that alterations in cytosolic pH and the activation of oxidative phosphorylation are relatively early events associated with the induction of apoptosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. A disulfide-stabilized conformer of methionine synthase reveals an unexpected role for the histidine ligand of the cobalamin cofactor

    Energy Technology Data Exchange (ETDEWEB)

    Datta, Supratim; Koutmos, Markos; Pattridge, Katherine A.; Ludwig, Martha L.; Matthews, Rowena G. (Michigan)

    2008-07-08

    B{sub 12}-dependent methionine synthase (MetH) from Escherichia coli is a large modular protein that is alternately methylated by methyltetrahydrofolate to form methylcobalamin and demethylated by homocysteine to form cob(I)alamin. Major domain rearrangements are required to allow cobalamin to react with three different substrates: homocysteine, methyltetrahydrofolate, and S-adenosyl-l-methionine (AdoMet). These same rearrangements appear to preclude crystallization of the wild-type enzyme. Disulfide cross-linking was used to lock a C-terminal fragment of the enzyme into a unique conformation. Cysteine point mutations were introduced at Ile-690 and Gly-743. These cysteine residues span the cap and the cobalamin-binding module and form a cross-link that reduces the conformational space accessed by the enzyme, facilitating protein crystallization. Here, we describe an x-ray structure of the mutant fragment in the reactivation conformation; this conformation enables the transfer of a methyl group from AdoMet to the cobalamin cofactor. In the structure, the axial ligand to the cobalamin, His-759, dissociates from the cobalamin and forms intermodular contacts with residues in the AdoMet-binding module. This unanticipated intermodular interaction is expected to play a major role in controlling the distribution of conformers required for the catalytic and the reactivation cycles of the enzyme.

  10. Cofactor balance by nicotinamide nucleotide transhydrogenase (NNT) coordinates reductive carboxylation and glucose catabolism in the tricarboxylic acid (TCA) cycle.

    Science.gov (United States)

    Gameiro, Paulo A; Laviolette, Laura A; Kelleher, Joanne K; Iliopoulos, Othon; Stephanopoulos, Gregory

    2013-05-03

    Cancer and proliferating cells exhibit an increased demand for glutamine-derived carbons to support anabolic processes. In addition, reductive carboxylation of α-ketoglutarate by isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) was recently shown to be a major source of citrate synthesis from glutamine. The role of NAD(P)H/NAD(P)(+) cofactors in coordinating glucose and glutamine utilization in the tricarboxylic acid (TCA) cycle is not well understood, with the source(s) of NADPH for the reductive carboxylation reaction remaining unexplored. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial enzyme that transfers reducing equivalents from NADH to NADPH. Here, we show that knockdown of NNT inhibits the contribution of glutamine to the TCA cycle and activates glucose catabolism in SkMel5 melanoma cells. The increase in glucose oxidation partially occurred through pyruvate carboxylase and rendered NNT knockdown cells more sensitive to glucose deprivation. Importantly, knocking down NNT inhibits reductive carboxylation in SkMel5 and 786-O renal carcinoma cells. Overexpression of NNT is sufficient to stimulate glutamine oxidation and reductive carboxylation, whereas it inhibits glucose catabolism in the TCA cycle. These observations are supported by an impairment of the NAD(P)H/NAD(P)(+) ratios. Our findings underscore the role of NNT in regulating central carbon metabolism via redox balance, calling for other mechanisms that coordinate substrate preference to maintain a functional TCA cycle.

  11. Shared Sulfur Mobilization Routes for tRNA Thiolation and Molybdenum Cofactor Biosynthesis in Prokaryotes and Eukaryotes

    Directory of Open Access Journals (Sweden)

    Silke Leimkühler

    2017-01-01

    Full Text Available Modifications of transfer RNA (tRNA have been shown to play critical roles in the biogenesis, metabolism, structural stability and function of RNA molecules, and the specific modifications of nucleobases with sulfur atoms in tRNA are present in pro- and eukaryotes. Here, especially the thiomodifications xm5s2U at the wobble position 34 in tRNAs for Lys, Gln and Glu, were suggested to have an important role during the translation process by ensuring accurate deciphering of the genetic code and by stabilization of the tRNA structure. The trafficking and delivery of sulfur nucleosides is a complex process carried out by sulfur relay systems involving numerous proteins, which not only deliver sulfur to the specific tRNAs but also to other sulfur-containing molecules including iron–sulfur clusters, thiamin, biotin, lipoic acid and molybdopterin (MPT. Among the biosynthesis of these sulfur-containing molecules, the biosynthesis of the molybdenum cofactor (Moco and the synthesis of thio-modified tRNAs in particular show a surprising link by sharing protein components for sulfur mobilization in pro- and eukaryotes.

  12. Expression of an Arabidopsis molybdenum cofactor sulphurase gene in soybean enhances drought tolerance and increases yield under field conditions.

    Science.gov (United States)

    Li, Yajun; Zhang, Jiachang; Zhang, Juan; Hao, Ling; Hua, Jinping; Duan, Liusheng; Zhang, Mingcai; Li, Zhaohu

    2013-08-01

    LOS5/ABA3 gene encoding molybdenum cofactor sulphurase is involved in aldehyde oxidase (AO) activity in Arabidopsis, which indirectly regulates ABA biosynthesis and increased stress tolerance. Here, we used a constitutive super promoter to drive LOS5/ABA3 overexpression in soybean (Glycine max L.) to enhance drought tolerance in growth chamber and field conditions. Expression of LOS5/ABA3 was up-regulated by drought stress, which led to increasing AO activity and then a notable increase in ABA accumulation. Transgenic soybean under drought stress had reduced water loss by decreased stomatal aperture size and transpiration rate, which alleviated leaf wilting and maintained higher relative water content. Exposed to drought stress, transgenic soybean exhibited reduced cell membrane damage by reducing electrolyte leakage and production of malondialdehyde and promoting proline accumulation and antioxidant enzyme activities. Also, overexpression of LOS5/ABA3 enhanced expression of stress-up-regulated genes. Furthermore, the seed yield of transgenic plants is at least 21% higher than that of wide-type plants under drought stress conditions in the field. These data suggest that overexpression of LOS5/ABA3 could improve drought tolerance in transgenic soybean via enhanced ABA accumulation, which could activate expression of stress-up-regulated genes and cause a series of physiological and biochemical resistant responses. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  13. Cooperation of decay-accelerating factor and membrane cofactor protein in regulating survival of human cervical cancer cells

    International Nuclear Information System (INIS)

    Gao, Ling-Juan; Guo, Shu-Yu; Cai, You-Qun; Gu, Ping-Qing; Su, Ya-Juan; Gong, Hui; Liu, Yun; Chen, Chen

    2009-01-01

    Decay-accelerating factor (DAF) and membrane cofactor protein (MCP) are the key molecules involved in cell protection against autologus complement, which restricts the action of complement at critical stages of the cascade reaction. The cooperative effect of DAF and MCP on the survival of human cervical cancer cell (ME180) has not been demonstrated. In this study we applied, for the first time, short hairpin RNA (shRNA) to knock down the expression of the DAF and MCP with the aim of exploiting complement more effectively for tumor cell damage. Meanwhile, we investigated the cooperative effects of DAF and MCP on the viability and migration, moreover the proliferation of ME180 cell. The results showed that shRNA inhibition of DAF and MCP expression enhanced complement-dependent cytolysis (CDC) up to 39% for MCP and up to 36% for DAF, and the combined inhibition of both regulators yielded further additive effects in ME180 cells. Thus, the activities of DAF and MCP, when present together, are greater than the sum of the two protein individually. These data indicated that combined DAF and MCP shRNA described in this study may offer an additional alternative to improve the efficacy of antibody-and complement-based cancer immunotherapy

  14. Nuclear law - Nuclear safety

    International Nuclear Information System (INIS)

    Pontier, Jean-Marie; Roux, Emmanuel; Leger, Marc; Deguergue, Maryse; Vallar, Christian; Pissaloux, Jean-Luc; Bernie-Boissard, Catherine; Thireau, Veronique; Takahashi, Nobuyuki; Spencer, Mary; Zhang, Li; Park, Kyun Sung; Artus, J.C.

    2012-01-01

    This book contains the contributions presented during a one-day seminar. The authors propose a framework for a legal approach to nuclear safety, a discussion of the 2009/71/EURATOM directive which establishes a European framework for nuclear safety in nuclear installations, a comment on nuclear safety and environmental governance, a discussion of the relationship between citizenship and nuclear, some thoughts about the Nuclear Safety Authority, an overview of the situation regarding the safety in nuclear waste burying, a comment on the Nome law with respect to electricity price and nuclear safety, a comment on the legal consequences of the Fukushima accident on nuclear safety in the Japanese law, a presentation of the USA nuclear regulation, an overview of nuclear safety in China, and a discussion of nuclear safety in the medical sector

  15. Avaliação da dor em neonatologia Evaluación del dolor en neonatología Pain evaluation in neonatology

    Directory of Open Access Journals (Sweden)

    Yerkes Pereira e Silva

    2007-10-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O estudo da dor avançou muito nas últimas décadas tornando a avaliação e a intervenção uma preocupação crescente entre os profissionais de saúde. O objetivo da avaliação da dor deve ser o de proporcionar dados acurados, para determinar quais ações devem ser feitas para aliviá-la ou aboli-la e, ao mesmo tempo, avaliar a eficácia dessas ações. A finalidade desta revisão foi discutir os métodos utilizados na avaliação da dor em neonatologia, uma vez que estratégias de tratamento utilizadas sem uma avaliação sistemática da dor não são eficazes ou adequadas. CONTEÚDO: Não existe nenhuma técnica amplamente aceita, de fácil realização e uniforme para a avaliação da dor em crianças, sobretudo em recém-nascidos e lactentes, que possa ser utilizada em todas as situações. Antes de se confiar na exatidão dos dados de avaliação, é necessário que os profissionais de saúde sintam-se seguros com os instrumentos usados na coleta de dados. Vários indicadores podem ser usados na avaliação, quantificação e qualificação do estímulo doloroso, e, quando analisados em conjunto, permitem a discriminação entre a dor e estímulos não-dolorosos. Ainda que seja desejável padronização objetiva para a medição da intensidade da dor, tal medida ainda não existe. A medição nessa faixa etária é feita por meio de parâmetros fisiológicos (freqüência cardíaca, freqüência respiratória, pressão arterial, etc. e comportamentais (expressão facial, postura e vocalização ou verbalização, utilizando-se escalas de avaliação, cada uma com suas vantagens e limitações. CONCLUSÕES: A atual atenção para melhores métodos de medida e avaliação da dor contribuiu para aumentar a sensibilidade dos profissionais de saúde em relação à natureza das experiências dolorosas. A dor deve ser valorizada como o quinto sinal vital e avaliada de maneira sistematizada também nos rec

  16. Enfrentando a Dor na Anemia Falciforme: Uma Proposta de Avaliação e Intervenção Psicológica com Criança

    OpenAIRE

    OLIVEIRA, C. G. T.

    2013-01-01

    A tese se constituiu em uma pesquisa que objetivou descrever e analisar o processo de enfrentamento da dor em crianças com Anemia Falciforme, com idade entre 8 a 10 anos, subsidiando uma proposta de intervenção psicológica baseada na abordagem cognitivo-comportamental e em atividades lúdicas.

  17. Hipnose e dor: proposta de metodologia clínica e qualitativa de estudo Hypnosis and pain: proposal of a clinical and qualitative research methodology

    Directory of Open Access Journals (Sweden)

    Maurício da Silva Neubern

    2009-08-01

    Full Text Available O presente trabalho visa apresentar uma proposta metodológica clínica e qualitativa para o estudo da relação entre hipnose e dor. Inicialmente, critica-se a pretensão de atribuir legitimidade científica exclusivamente para propostas estatísticas sobre o tema. Em seguida, são destacados alguns pressupostos da metodologia clínica e qualitativa, como a construção da realidade e das informações, as dimensões estética e técnica da relação terapêutica e a concepção da dor enquanto processo subjetivo. Uma vinheta clínica é utilizada de forma ilustrativa de modo a destacar as etapas e processos da pesquisa, como o uso dos registros e os processos interpretativos. Conclui-se o artigo ressaltando que a pertinência dessa metodologia se dá, basicamente, por abordar a dimensão subjetiva da relação entre dor e hipnose e por conceber o contexto como um conjunto de processos que não devem ser isolados, mas integrados à pesquisa.The purpose of this work is to present a proposal of clinical and qualitative methodology for the study of the relationship between hypnosis and pain. Initially, the pretension of attributing scientific legitimacy exclusively to statistical approaches on the theme is criticized. Then, some premises of the clinical and qualitative methodology are underlined, such as the construction of reality and information, esthetic and technical dimensions of therapeutic relationship and conception of pain as a subjective process. An illustrative clinical vignette is used so as to highlight the steps and processes of the research, such as the use of records and interpretative processes. The article is concluded emphasizing that the pertinence of this methodology is, basically, on its approach of relationship subjective dimension between pain and hypnosis and in its conceiving of the context as a set of processes that should not be isolated, but integrated into the research.

  18. Facilitação e dominância dos sintomas sôbre a dor da angina de peito e causalgia

    Directory of Open Access Journals (Sweden)

    Nelson Pires

    1962-09-01

    Full Text Available O autor traz à consideração clínica a "facilitação" que Sherrington apreciou nos experimentos de neurofisiologia, e que explica aspectos clínicos importantíssimos em psicologia e em neurologia visceral. Pretende o autor explicar seus casos de dor (um de causalgia no membro superior e três de angina de peito em portadores de esclerose coronária. Ora a anestesia terapêutica no gânglio estrelado, ora na cadeia ganglionar torácica simpática, ora a radioterapia, ora a psicoterapia removeram a dor "facilitada" a tal ponto que se tornara "dominante", isto é, mesmo estímulos inadequados a provocavam. Os doentes eram inválidos e recuperaram-se. A neurofisiologia moderna autoriza a interpretação dessa terapêutica: suprimiu-se - com a anestesia, com a radioterapia e com a psicoterapia - o circuito neural auto-alimentado reverberante, hiperfuncionante em todo ou em parte de seu trajeto, quer aferente ao córtex quer aferente às coronárias. O autor discute o valor clínico dos acessos anginosos apontando fatos que documentam que o acesso "ilegítimo" (psicógeno deve ter como causa a estimulação das aferências vegetativas ao córtex em qualquer ponto (ganglionar, medular ou cortical. Os acessos "legítimos", produzindo lesões transitórias ou definitivas e até morte,, devem ser explicados pela atividade das eferências vagais que executam os efetôres espásticos das coronárias. A dor é apresentada como fenômeno de "gravação neural", aprendido, memorizado e automatizado, ativado em feed-back ora nas aferências vegetativas ao córtex, ora nas eferências, mais perigosas e mortais. Debate-se a superestimada psicogenia da angina de peito.

  19. Dor, qualidade de vida, autopercepção de saúde e depressão de pacientes com fibromialgia, tratados com hidrocinesioterapia

    Directory of Open Access Journals (Sweden)

    Rubens Vinícius Letieri

    2013-12-01

    Full Text Available OBJETIVOS: Analisar os efeitos do tratamento hidrocinesioterapêutico na qualidade de vida, percepção de dor e gravidade de episódios depressivos em um grupo de pacientes com fibromialgia. MATERIAIS E MÉTODOS: Foram avaliados 64 indivíduos do sexo feminino, separados em dois grupos: hidrocinesioterapia (n = 33; 58,2 ± 10,6 anos e grupo controle (n = 31; 59,6 ± 9,4 anos, com diagnóstico de fibromialgia. Os indivíduos foram avaliados através da Escala Analógica Visual de Dor (EVA, o Fibromyalgia Impact Questionnaire (FIQ, e o Inventário de Beck. Os participantes foram submetidos a um tratamento hidrocinesioterápico numa piscina aquecida a 33ºC com duas sessões de 45 minutos por semana, ao longo 15 semanas, num total de 30 sessões. Os exercícios subaquáticos foram: de condicionamento cardiovascular, de força, de mobilidade, de coordenação, de equilíbrio, de alongamento e de relaxamento muscular. Utilizou-se a ANOVA 2×2 e Kruskal-Wallis para análise estatística. RESULTADOS: Foram observadas melhorias estatisticamente significativas na percepção da intensidade da dor (Δ% = -28,2%, p < 0,01, na qualidade de vida (Δ% = -32,4%, p < 0,05 e nos sintomas de depressão (Δ% = -35,4%, p < 0,05 favoráveis ao grupo hidrocinesioterapia comparado ao grupo controle. CONCLUSÕES: O estudo sugere que a hidrocinesioterapia mostrou-se eficaz como terapia alternativa da fibromialgia. No entanto, recomenda novos estudos que testem as associações existentes entre as variáveis analisadas e os programas de intervenção, utilizando as atividades aquáticas, bem como a modificabilidade dos parâmetros de saúde física e psíquica quando estes indivíduos são submetidos a programas de curta, média e longa duração.

  20. Structures of Saccharomyces cerevisiae D-arabinose dehydrogenase Ara1 and its complex with NADPH: implications for cofactor-assisted substrate recognition.

    Science.gov (United States)

    Hu, Xiao-Qian; Guo, Peng-Chao; Ma, Jin-Di; Li, Wei-Fang

    2013-11-01

    The primary role of yeast Ara1, previously mis-annotated as a D-arabinose dehydrogenase, is to catalyze the reduction of a variety of toxic α,β-dicarbonyl compounds using NADPH as a cofactor at physiological pH levels. Here, crystal structures of Ara1 in apo and NADPH-complexed forms are presented at 2.10 and 2.00 Å resolution, respectively. Ara1 exists as a homodimer, each subunit of which adopts an (α/β)8-barrel structure and has a highly conserved cofactor-binding pocket. Structural comparison revealed that induced fit upon NADPH binding yielded an intact active-site pocket that recognizes the substrate. Moreover, the crystal structures combined with computational simulation defined an open substrate-binding site to accommodate various substrates that possess a dicarbonyl group.

  1. The structure of tubulin-binding cofactor A from Leishmania major infers a mode of association during the early stages of microtubule assembly

    Energy Technology Data Exchange (ETDEWEB)

    Barrack, Keri L.; Fyfe, Paul K.; Hunter, William N., E-mail: w.n.hunter@dundee.ac.uk [University of Dundee, Dow Street, Dundee DD1 5EH, Scotland (United Kingdom)

    2015-04-21

    The structure of a tubulin-binding cofactor from L. major is reported and compared with yeast, plant and human orthologues. Tubulin-binding cofactor A (TBCA) participates in microtubule formation, a key process in eukaryotic biology to create the cytoskeleton. There is little information on how TBCA might interact with β-tubulin en route to microtubule biogenesis. To address this, the protozoan Leishmania major was targeted as a model system. The crystal structure of TBCA and comparisons with three orthologous proteins are presented. The presence of conserved features infers that electrostatic interactions that are likely to involve the C-terminal tail of β-tubulin are key to association. This study provides a reagent and template to support further work in this area.

  2. Crystal Structure of the Thermus thermophilus 16 S rRNA Methyltransferase RsmC in Complex with Cofactor and Substrate Guanosine

    Energy Technology Data Exchange (ETDEWEB)

    Demirci, H.; Gregory, S; Dahlberg, A; Jogl, G

    2008-01-01

    Post-transcriptional modification is a ubiquitous feature of ribosomal RNA in all kingdoms of life. Modified nucleotides are generally clustered in functionally important regions of the ribosome, but the functional contribution to protein synthesis is not well understood. Here we describe high resolution crystal structures for the N{sup 2}-guanine methyltransferase RsmC that modifies residue G1207 in 16 S rRNA near the decoding site of the 30 S ribosomal subunit. RsmC is a class I S-adenosyl-l-methionine-dependent methyltransferase composed of two methyltransferase domains. However, only one S-adenosyl-l-methionine molecule and one substrate molecule, guanosine, bind in the ternary complex. The N-terminal domain does not bind any cofactor. Two structures with bound S-adenosyl-l-methionine and S-adenosyl-l-homocysteine confirm that the cofactor binding mode is highly similar to other class I methyltransferases. Secondary structure elements of the N-terminal domain contribute to cofactor-binding interactions and restrict access to the cofactor-binding site. The orientation of guanosine in the active site reveals that G1207 has to disengage from its Watson-Crick base pairing interaction with C1051 in the 16 S rRNA and flip out into the active site prior to its modification. Inspection of the 30 S crystal structure indicates that access to G1207 by RsmC is incompatible with the native subunit structure, consistent with previous suggestions that this enzyme recognizes a subunit assembly intermediate.

  3. Differential developmental expression of transcription factors GATA-4 and GATA-6, their cofactor FOG-2 and downstream target genes in testicular carcinoma in situ and germ cell tumors

    DEFF Research Database (Denmark)

    Salonen, Jonna; Rajpert-De Meyts, E; Mannisto, Susanna

    2010-01-01

    Testicular germ cell cancer is the most common malignancy among young males. The pre-invasive precursor, carcinoma in situ testis (CIS), presumably originates from arrested and transformed fetal gonocytes. Given that GATA transcription factors have essential roles in embryonic and testicular deve...... development, we explored the expression of GATA-4, GATA-6, cofactor friend of GATA (FOG)-2, and downstream target genes during human testis development and addressed the question whether changes in this pathway may contribute to germ cell neoplasms....

  4. Quantum mechanics/molecular mechanics studies on the mechanism of action of cofactor pyridoxal 5'-phosphate in ornithine 4,5-aminomutase.

    Science.gov (United States)

    Pang, Jiayun; Scrutton, Nigel S; Sutcliffe, Michael J

    2014-09-01

    A computational study was performed on the experimentally elusive cyclisation step in the cofactor pyridoxal 5'-phosphate (PLP)-dependent D-ornithine 4,5-aminomutase (OAM)-catalysed reaction. Calculations using both model systems and a combined quantum mechanics/molecular mechanics approach suggest that regulation of the cyclic radical intermediate is achieved through the synergy of the intrinsic catalytic power of cofactor PLP and the active site of the enzyme. The captodative effect of PLP is balanced by an enzyme active site that controls the deprotonation of both the pyridine nitrogen atom (N1) and the Schiff-base nitrogen atom (N2). Furthermore, electrostatic interactions between the terminal carboxylate and amino groups of the substrate and Arg297 and Glu81 impose substantial "strain" energy on the orientation of the cyclic intermediate to control its trajectory. In addition the "strain" energy, which appears to be sensitive to both the number of carbon atoms in the substrate/analogue and the position of the radical intermediates, may play a key role in controlling the transition of the enzyme from the closed to the open state. Our results provide new insights into several aspects of the radical mechanism in aminomutase catalysis and broaden our understanding of cofactor PLP-dependent reactions. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Expression, purification, crystallization and preliminary phasing of the heteromerization domain of the tRNA-export and aminoacylation cofactor Arc1p from yeast

    International Nuclear Information System (INIS)

    Simader, Hannes; Suck, Dietrich

    2006-01-01

    The heteromerization domain of an aminoacyl-tRNA synthetase cofactor from yeast was crystallized, complete selenomethionine MAD data were collected to 2.8 Å resolution and preliminary phasing reveals the presence of 20 monomers in the asymmetric unit. Eukaryotic aminoacyl-tRNA synthetases (aaRSs) must be integrated into an efficient tRNA-export and shuttling machinery. This is reflected by the presence of additional protein–protein interaction domains and a correspondingly higher degree of complex formation in eukaryotic aaRSs. However, the structural basis of interaction between eukaryotic aaRSs and associated protein cofactors has remained elusive. The N-terminal heteromerization domain of the tRNA aminoacylation and export cofactor Arc1p has been cloned from yeast, expressed and purified. Crystals have been obtained belonging to space group C2, with unit-cell parameters a = 222.32, b = 89.46, c = 126.79 Å, β = 99.39°. Calculated Matthews coefficients are compatible with the presence of 10–25 monomers in the asymmetric unit. A complete multiple-wavelength anomalous dispersion data set has been collected from a selenomethionine-substituted crystal at 2.8 Å resolution. Preliminary phasing reveals the presence of 20 monomers organized in five tetramers per asymmetric unit

  6. Identification of an Isothiocyanate on the HypEF Complex Suggests a Route for Efficient Cyanyl-Group Channeling during [NiFe]-Hydrogenase Cofactor Generation.

    Directory of Open Access Journals (Sweden)

    Sven T Stripp

    Full Text Available [NiFe]-hydrogenases catalyze uptake and evolution of H2 in a wide range of microorganisms. The enzyme is characterized by an inorganic nickel/ iron cofactor, the latter of which carries carbon monoxide and cyanide ligands. In vivo generation of these ligands requires a number of auxiliary proteins, the so-called Hyp family. Initially, HypF binds and activates the precursor metabolite carbamoyl phosphate. HypF catalyzes removal of phosphate and transfers the carbamate group to HypE. In an ATP-dependent condensation reaction, the C-terminal cysteinyl residue of HypE is modified to what has been interpreted as thiocyanate. This group is the direct precursor of the cyanide ligands of the [NiFe]-hydrogenase active site cofactor. We present a FT-IR analysis of HypE and HypF as isolated from E. coli. We follow the HypF-catalyzed cyanation of HypE in vitro and screen for the influence of carbamoyl phosphate and ATP. To elucidate on the differences between HypE and the HypEF complex, spectro-electrochemistry was used to map the vibrational Stark effect of naturally cyanated HypE. The IR signature of HypE could ultimately be assigned to isothiocyanate (-N=C=S rather than thiocyanate (-S-C≡N. This has important implications for cyanyl-group channeling during [NiFe]-hydrogenase cofactor generation.

  7. Engineering Cofactor Preference of Ketone Reducing Biocatalysts: A Mutagenesis Study on a γ-Diketone Reductase from the Yeast Saccharomyces cerevisiae Serving as an Example

    Directory of Open Access Journals (Sweden)

    Michael Katzberg

    2010-04-01

    Full Text Available The synthesis of pharmaceuticals and catalysts more and more relies on enantiopure chiral building blocks. These can be produced in an environmentally benign and efficient way via bioreduction of prochiral ketones catalyzed by dehydrogenases. A productive source of these biocatalysts is the yeast Saccharomyces cerevisiae, whose genome also encodes a reductase catalyzing the sequential reduction of the γ-diketone 2,5-hexanedione furnishing the diol (2S,5S-hexanediol and the γ-hydroxyketone (5S-hydroxy-2-hexanone in high enantio- as well as diastereoselectivity (ee and de >99.5%. This enzyme prefers NADPH as the hydrogen donating cofactor. As NADH is more stable and cheaper than NADPH it would be more effective if NADH could be used in cell-free bioreduction systems. To achieve this, the cofactor binding site of the dehydrogenase was altered by site-directed mutagenesis. The results show that the rational approach based on a homology model of the enzyme allowed us to generate a mutant enzyme having a relaxed cofactor preference and thus is able to use both NADPH and NADH. Results obtained from other mutants are discussed and point towards the limits of rationally designed mutants.

  8. Acquisition of complement inhibitor serine protease factor I and its cofactors C4b-binding protein and factor H by Prevotella intermedia.

    Science.gov (United States)

    Malm, Sven; Jusko, Monika; Eick, Sigrun; Potempa, Jan; Riesbeck, Kristian; Blom, Anna M

    2012-01-01

    Infection with the Gram-negative pathogen Prevotella intermedia gives rise to periodontitis and a growing number of studies implies an association of P. intermedia with rheumatoid arthritis. The serine protease Factor I (FI) is the central inhibitor of complement degrading complement components C3b and C4b in the presence of cofactors such as C4b-binding protein (C4BP) and Factor H (FH). Yet, the significance of complement inhibitor acquisition in P. intermedia infection and FI binding by Gram-negative pathogens has not been addressed. Here we show that P. intermedia isolates bound purified FI as well as FI directly from heat-inactivated human serum. FI bound to bacteria retained its serine protease activity as shown in degradation experiments with (125)I-labeled C4b. Since FI requires cofactors for its activity we also investigated the binding of purified cofactors C4BP and FH and found acquisition of both proteins, which retained their activity in FI mediated degradation of C3b and C4b. We propose that FI binding by P. intermedia represents a new mechanism contributing to complement evasion by a Gram-negative bacterial pathogen associated with chronic diseases.

  9. Opções terapêuticas no tratamento da dor crónica na população idosa

    OpenAIRE

    Fernandes, Sofia Alexandra de Carvalho

    2009-01-01

    Os adultos acima de 65 anos de idade, são um grupo em grande crescimento demográfico no mundo ocidental e, nesta população, há uma grande prevalência de dor crónica. Esta leva a uma diminuição da capacidade funcional de um indivíduo e da sua qualidade de vida. O tratamento desta situação patológica nesta população é um desafio médico, já que as modificações fisiológicas condicionadas pelo envelhecimento, a frequente existência de comorbilidades e de polimedicação, conduzem caracteristicame...

  10. Photometric Determination of the Mass Accretion Rates of Pre-main-sequence Stars. V. Recent Star Formation in the 30 Dor Nebula

    Science.gov (United States)

    De Marchi, Guido; Panagia, Nino; Beccari, Giacomo

    2017-09-01

    We report on the properties of the low-mass stars that recently formed in the central ˜ 2\\buildrel{ \\prime}\\over{.} 7× 2\\buildrel{ \\prime}\\over{.} 7 of 30 Dor, including the R136 cluster. Using the photometric catalog of De Marchi et al., based on observations with the Hubble Space Telescope, and the most recent extinction law for this field, we identify 1035 bona fide pre-main-sequence (PMS) stars showing {{H}}α excess emission at the 4σ level with an {{H}}α equivalent width of 20 Å or more. We find a wide spread in age spanning the range ˜ 0.1{--}50 {Myr}. We also find that the older PMS objects are placed in front of the R136 cluster and are separated from it by a conspicuous amount of absorbing material, indicating that star formation has proceeded from the periphery into the interior of the region. We derive physical parameters for all PMS stars, including masses m, ages t, and mass accretion rates {\\dot{M}}{acc}. To identify reliable correlations between these parameters, which are intertwined, we use a multivariate linear regression fit of the type {log}{\\dot{M}}{acc}=a× {log}t+b× {log}m+c. The values of a and b for 30 Dor are compatible with those found in NGC 346 and NGC 602. We extend the fit to a uniform sample of 1307 PMS stars with 0.5contract NAS5-26555.

  11. Prevalência e fatores associados à dor lombar em escolares Prevalence of lower back pain and associated factors in students

    Directory of Open Access Journals (Sweden)

    Alberto De Vitta

    2011-08-01

    Full Text Available O objetivo foi verificar a prevalência de dor lombar em adolescentes e sua relação com a prática de esportes e atividades sedentárias. Realizou-se um estudo transversal com 1.236 escolares das 5ª a 8ª séries do Ensino Fundamental de Bauru, São Paulo, Brasil. Foram utilizados um protocolo estruturado e o questionário nórdico de sintomas musculoesqueléticos. A análise foi realizada mediante uma abordagem descritiva, bivariada e multivariada por regressão logística binária. Notou-se que a prevalência de dor lombar foi de 19,5%, sendo 7% nos meninos e 12,5% nas meninas, com diferença estatisticamente significante entre os gêneros (p The objective was to determine the prevalence of lower back pain in adolescents and its relationship to sports and sedentary activities. We conducted a cross-sectional study of 5th to 8th-grade students (n = 1,236 in Bauru, São Paulo State, Brazil. We used a structured protocol and the Nordic questionnaire for musculoskeletal symptoms. The analysis was performed using a descriptive approach and bivariate and multivariate binary logistic regression. Prevalence of lower back pain was 19.5% (7% in boys and 12.5% in girls, with statistically significant differences according to gender (p < 0.00001, age (p = 0.0057, and sports (p = 0.0001. Bivariate and multivariate analyses showed independent associations between lower back pain and female gender, time watching TV, and sports. Lower back pain in schoolchildren can persist as chronic pain in adults. Understanding the relationships between variables should provide useful measures for maintaining, improving, and promoting students' wellbeing.

  12. Interaction with the Redox Cofactor MYW and Functional Role of a Mobile Arginine in Eukaryotic Catalase-Peroxidase

    Science.gov (United States)

    2016-01-01

    Catalase-peroxidases (KatGs) are unique bifunctional heme peroxidases with an additional posttranslationally formed redox-active Met-Tyr-Trp cofactor that is essential for catalase activity. On the basis of studies of bacterial KatGs, controversial mechanisms of hydrogen peroxide oxidation were proposed. The recent discovery of eukaryotic KatGs with differing pH optima of catalase activity now allows us to scrutinize those postulated reaction mechanisms. In our study, secreted KatG from the fungus Magnaporthe grisea (MagKatG2) was used to analyze the role of a remote KatG-typical mobile arginine that was shown to interact with the Met-Tyr-Trp adduct in a pH-dependent manner in bacterial KatGs. Here we present crystal structures of MagKatG2 at pH 3.0, 5.5, and 7.0 and investigate the mobility of Arg461 by molecular dynamics simulation. Data suggest that at pH ≥4.5 Arg461 mostly interacts with the deprotonated adduct Tyr. Elimination of Arg461 by mutation to Ala slightly increases the thermal stability but does not alter the active site architecture or the kinetics of cyanide binding. However, the variant Arg461Ala lost the wild-type-typical optimum of catalase activity at pH 5.25 (kcat = 6450 s–1) but exhibits a broad plateau between pH 4.5 and 7.5 (kcat = 270 s–1 at pH 5.5). Moreover, significant differences in the kinetics of interconversion of redox intermediates of wild-type and mutant protein mixed with either peroxyacetic acid or hydrogen peroxide are observed. These findings together with published data from bacterial KatGs allow us to propose a role of Arg461 in the H2O2 oxidation reaction of KatG. PMID:27293030

  13. Structural rearrangements occurring upon cofactor binding in the Mycobacterium smegmatis β-ketoacyl-acyl carrier protein reductase MabA.

    Science.gov (United States)

    Küssau, Tanja; Flipo, Marion; Van Wyk, Niel; Viljoen, Albertus; Olieric, Vincent; Kremer, Laurent; Blaise, Mickaël

    2018-05-01

    In mycobacteria, the ketoacyl-acyl carrier protein (ACP) reductase MabA (designated FabG in other bacteria) catalyzes the NADPH-dependent reduction of β-ketoacyl-ACP substrates to β-hydroxyacyl-ACP products. This first reductive step in the fatty-acid biosynthesis elongation cycle is essential for bacteria, which makes MabA/FabG an interesting drug target. To date, however, very few molecules targeting FabG have been discovered and MabA remains the only enzyme of the mycobacterial type II fatty-acid synthase that lacks specific inhibitors. Despite the existence of several MabA/FabG crystal structures, the structural rearrangement that occurs upon cofactor binding is still not fully understood. Therefore, unlocking this knowledge gap could help in the design of new inhibitors. Here, high-resolution crystal structures of MabA from Mycobacterium smegmatis in its apo, NADP + -bound and NADPH-bound forms are reported. Comparison of these crystal structures reveals the structural reorganization of the lid region covering the active site of the enzyme. The crystal structure of the apo form revealed numerous residues that trigger steric hindrance to the binding of NADPH and substrate. Upon NADPH binding, these residues are pushed away from the active site, allowing the enzyme to adopt an open conformation. The transition from an NADPH-bound to an NADP + -bound form is likely to facilitate release of the product. These results may be useful for subsequent rational drug design and/or for in silico drug-screening approaches targeting MabA/FabG.

  14. The Orphan Nuclear Receptor TR4 Is a Vitamin A-activated Nuclear Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, X. Edward; Suino-Powell, Kelly M.; Xu, Yong; Chan, Cee-Wah; Tanabe, Osamu; Kruse, Schoen W.; Reynolds, Ross; Engel, James Douglas; Xu, H. Eric (Michigan-Med); (Van Andel)

    2015-11-30

    Testicular receptors 2 and 4 (TR2/4) constitute a subgroup of orphan nuclear receptors that play important roles in spermatogenesis, lipid and lipoprotein regulation, and the development of the central nervous system. Currently, little is known about the structural features and the ligand regulation of these receptors. Here we report the crystal structure of the ligand-free TR4 ligand binding domain, which reveals an autorepressed conformation. The ligand binding pocket of TR4 is filled by the C-terminal half of helix 10, and the cofactor binding site is occupied by the AF-2 helix, thus preventing ligand-independent activation of the receptor. However, TR4 exhibits constitutive transcriptional activity on multiple promoters, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, or ligand binding substantially reduce the transcriptional activity of this receptor. Importantly, both retinol and retinoic acid are able to promote TR4 to recruit coactivators and to activate a TR4-regulated reporter. These findings demonstrate that TR4 is a ligand-regulated nuclear receptor and suggest that retinoids might have a much wider regulatory role via activation of orphan receptors such as TR4.

  15. Dor orofacial e absenteísmo em trabalhadores da indústria metalúrgica e mecânica Orofacial pain and absenteeism in workers of the metallurgic and mechanics industry

    Directory of Open Access Journals (Sweden)

    Josimari Telino de Lacerda

    2008-12-01

    Full Text Available O objetivo do estudo foi verificar a prevalência de dor orofacial e sua relação com absenteísmo em trabalhadores do setor metalúrgico e mecânico do município de Xanxerê, Santa Catarina. Realizou-se um estudo transversal envolvendo todos os trabalhadores do sexo masculino (n = 480 das 13 indústrias do setor no município. As informações foram coletadas por meio de entrevistas estruturadas. Informações sócio-demográficas, prevalência, severidade e localização de dor orofacial no último semestre, bem como sobre falta ao trabalho devido à dor orofacial, compuseram o questionário. Dados de identificação, setor e turno de trabalho foram coletados nos departamentos de recursos humanos das empresas. Os dados foram analisados por meio de estatística descritiva e testes de associação de qui-quadrado de Pearson entre absenteísmo e dor orofacial. A prevalência de dor orofacial foi de 66,1%, sendo dor de dente provocada ou dor de dente espontânea os tipos mais frequentes. O absenteísmo devido a dor orofacial no último semestre foi relatado por 9,3% dos trabalhadores, mostrando-se associado à dor de dente espontânea (p The objective of this study was to assess the prevalence of orofacial pain and its association with absenteeism in worke rs of the metallurgic and mechanics industry of the city of Xanxerê, Brazil. A cross sectional study was performed involving all male workers(n=480 of the 13 industries of the sector in the city. The information was collected by means of structured interviews. Socio-demographic information, prevalence, severity and localization of orofacial pain in the last semester as well as on absenteeism due to orofacial pain formed the questionnaire. Identification data, work sector and shift were collected in the departments of human resources of the companies. The data were assessed using descriptive statistics and Pearson chi-squared tests between absenteeism and pain in the orofacial region. The

  16. Perfil antropométrico e a relação da flexibilidade com a dor e desconforto em trabalhadores da indústria de Santa Cruz do Sul – RS

    Directory of Open Access Journals (Sweden)

    Patrik Nepomuceno

    2016-10-01

    Full Text Available Trabalhadores industriários estão expostos a diversas situações que podem agravar a sua saúde. A promoção da saúde no trabalho é de extrema importância e exige intervenção interdisciplinar. Objetivo: identificar o perfil antropométrico e a relação de flexibilidade com a presença de dor e desconforto em trabalhadores da indústria do município de Santa Cruz do Sul, RS. Método: Trata-se de um estudo transversal com trabalhadores industriários. Na avaliação antropométrica foram analisados índice de massa corporal e percentual de gordura, já para a flexibilidade foram realizados os testes do manguito rotador e sentar e alcançar. A dor e desconforto foi identificada através de uma figura do corpo humano onde eles referiam estes sintomas. Resultados: a maioria dos industriários apresentam excesso de peso (56,4% e bom percentual de gordura (49,2%, porém possuem resultados inadequados de flexibilidade de ombro (71,0% e parte posterior de tronco e pernas (64,6% e presença de dor e desconforto em ombros (50% e costas (26,6%. Ao relacionar a flexibilidade com a presença de dor e desconforto, percebe-se que as variáveis não se relacionam diretamente. Considerações finais: o perfil dos trabalhadores da indústria se caracteriza por excesso de peso, baixa aptidão na flexibilidade e presença de dor e desconforto. Sobre a dor e desconforto observa-se uma tendência de associação entre níveis de flexibilidade inadequada e a presença destes sintomas.

  17. Benefícios sobre a intensidade da dor, qualidade de vida e incapacidade de mulheres com dismenorreia submetidas a exercícios gerais versus método de Pilates: estudo-piloto

    Directory of Open Access Journals (Sweden)

    Bruna Cristina Taques Peruzzo

    2015-05-01

    Full Text Available Introdução: Dismenorreia primária é um distúrbio ginecológico caracterizado por dor relacionada à menstruação, sem causa patológica. Objetivo: Verificar e comparar a intensidade da dor, a incapacidade e a qualidade de vida em mulheres com dismenorreia primária submetidas a exercícios gerais versus Pilates. Métodos: Participaram do estudo 14 mulheres aleatorizadas em grupo de exercícios gerais (19,14±1 anos e de Pilates (20,57±1,8 anos. Ambos os grupos realizaram duas sessões por semana durante 50 minutos, no período de dois meses e meio, totalizando 20 sessões. O grupo de exercícios gerais realizou alongamentos e fortalecimentos dos músculos abdominais, lombares e assoalho pélvico. O grupo de Pilates, por sua vez, praticou exercícios para conscientização de pelve, com contrações do transverso e reto do abdômen, glúteos, períneo e eretores da coluna. As participantes responderam aos questionários de índice de incapacitação de Oswestry para dor lombar, Escala Visual Analógica (EVA, para medir a intensidade da dor e ao Questionário de Qualidade de Vida SF-36, antes e após a intervenção. Os dados foram considerados estatisticamente significantes quando p<0,05. Resultados: Foram encontradas melhoras significativas após a intervenção em ambos os grupos, em todas as avaliações. Em relação à diferença entre os grupos, na avaliação sobre a incapacitação para dor lombar, o  grupo de exercícios gerais teve melhor resultado (p<0,003 do que o grupo de Pilates, assim como no domínio de estado da saúde (0,03 do Questionário SF-36. Conclusão: A prática de exercícios físicos gerais e Pilates por mulheres com dismenorreia podem reduzir a dor e a incapacidade e melhorar a qualidade de vida.

  18. Eletroestimulação neuromuscular, exercícios contrarresistência, força muscular, dor e função motora em pacientes com osteoartrite primária de joelho

    Directory of Open Access Journals (Sweden)

    Thais Varanda Dadalto

    Full Text Available INTRODUÇÃO: A osteoartrite (OA do joelho é um processo degenerativo e os sintomas são dor mecânica e períodos de dor inflamatória, rigidez articular e fraqueza muscular. Ela não tem cura. O objetivo do tratamento é aliviar os sinais e sintomas e, quando possível, retardar sua evolução. O fortalecimento muscular é indicado como tratamento da OA. OBJETIVO: Comparar a eficácia da eletroestimulação neuromuscular (EENM e de exercícios contrarresistência (ECR no ganho de força extensora de joelho, na diminuição da dor e na recuperação da função motora em pacientes com OA primária do joelho. MATERIAIS E MÉTODOS: Participaram da pesquisa 23 pacientes com diagnóstico de OA primária do joelho, segundo os critérios clínicos e radiológicos do American College of Rheumatology. Eles foram alocados aleatoriamente para um grupo de ECR (n = 9, um grupo de EENM (n = 8 e um grupo controle (n = 6, e foram submetidos aos procedimentos característicos de seu grupo três vezes por semana até completar 24 sessões. Foram avaliadas de forma cega a força extensora de joelho, a dor e a função motora. Foi utilizado o teste MANOVA 3 x 2 com medidas repetidas para P < 0,05. RESULTADOS: Foi encontrada diferença significativa (P < 0.05 somente nas comparações intragrupos para força extensora de joelho no grupo EENM e para dor nos grupos EENM e ECR. CONCLUSÃO: O fortalecimento da musculatura extensora de joelho pode auxiliar na diminuição da dor de pacientes com OA. A EENM, quando aplicada de acordo com o protocolo utilizado neste estudo, pode ser uma terapia interessante para o tratamento da OA do joelho.

  19. Uso da cintilografia miocárdica em repouso durante dor torácica para descartar infarto agudo do miocárdio Utilización de la centellografía miocárdica en reposo durante dolor torácico para descartar infarto agudo de miocardio Use of resting myocardial scintigraphy during chest pain to exclude diagnosis of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Gustavo Borges Barbirato

    2009-04-01

    Full Text Available FUNDAMENTO: A imagem de perfusão miocárdica adquirida durante episódio de dor torácica tem sido utilizada nos pacientes na sala de emergência. OBJETIVO: Avaliar as características operacionais da cintilografia com 99mTc-Tetrofosmin durante episódio de dor torácica para descartar o diagnóstico de infarto agudo do miocárdio. MÉTODOS: 108 pacientes admitidos com dor torácica ou até quatro horas do término dos sintomas e eletrocardiograma não diagnostico realizaram cintilografia em repouso e dosagens de troponina I. Pacientes com passado de infarto do miocárdio (IM não foram excluídos (24 pacientes. Troponina I foi dosada na admissão e seis horas após. Médicos nucleares realizaram análise cega das imagens. Infarto do miocárdio foi confirmado com elevação da troponina I maior que três vezes o controle. RESULTADOS: A imagem perfusional de repouso foi anormal em todos os seis pacientes com IM. Apenas um paciente apresentou imagem normal e elevação da troponina. Outros 55 pacientes obtiveram imagem positiva sem IM e 46 pacientes com imagens e troponinas normais. A prevalência da doença foi 6,5%. A sensibilidade da imagem de repouso durante dor torácica para a evidência de IM foi 85,7% e especificidade de 45,5%. O valor preditivo negativo foi 97,7%. CONCLUSÃO: Pacientes submetidos ao protocolo de dor torácica com cintilografia de perfusão miocárdica demonstraram um excelente valor preditivo negativo para afastar o diagnóstico de infarto do miocárdio. Estes resultados sugerem que a imagem de perfusão em repouso é uma ferramenta importante na unidade de dor torácica.FUNDAMENTO: La utilización en los pacientes de la imagen de perfusión miocárdica, adquirida durante episodio de dolor torácico, es frecuente en la sala de emergencia. OBJETIVO: Evaluar las características operacionales de la centellografía con 99mTc-Tetrofosmin, durante episodio de dolor torácico, para descartar el diagnóstico de infarto agudo de

  20. Nuclear Medicine

    Science.gov (United States)

    ... Parents/Teachers Resource Links for Students Glossary Nuclear Medicine What is nuclear medicine? What are radioactive tracers? ... funded researchers advancing nuclear medicine? What is nuclear medicine? Nuclear medicine is a medical specialty that uses ...

  1. Nuclear safety. Seguranca nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Aveline, A [Rio Grande do Sul Univ., Porto Alegre, RS (Brazil). Inst. de Fisica

    1981-01-01

    What is nuclear safety Is there any technical way to reduce risks Is it possible to put them at reasonable levels Are there competitiveness and economic reliability to employ the nuclear energy by means of safety technics Looking for answers to these questions the author describes the sources of potential risks to nuclear reactors and tries to apply the answers to the Brazilian Nuclear Programme. (author).

  2. Papel dos testes provocativos esofagianos na investigação de pacientes com dor torácica de origem indeterminada Role of esophageal provocative tests in the investigation of patients with chest pain of undetermined origin

    Directory of Open Access Journals (Sweden)

    Luiz J. Abrahão Jr.

    2005-09-01

    Full Text Available RACIONAL: As dores de origem esofagiana e coronariana são bastante semelhantes do ponto de vista clínico, havendo necessidade de exclusão desta última, que ocasiona risco de morte. A investigação esofagiana tradicional de pacientes com dor torácica de origem indeterminada, envolve emprego de endoscopia digestiva alta, esofagomanometria e pHmetria esofagiana prolongada. Esses métodos, embora de grande importância diagnóstica, muitas vezes, revelam alterações, em sua maioria, potenciais para a origem da dor. Os testes provocativos de dor esofagiana, ao reproduzirem-na em laboratório, apontam com segurança a sua origem. OBJETIVOS: Determinar a positividade dos testes de perfusão ácida, do edrofônio e da distensão esofagiana com balão em pacientes com dor torácica de origem indeterminada, e correlacionar os resultados com os testes habitualmente empregados, estabelecendo o ganho no diagnóstico da dor esofagiana comprovada. RESULTADOS: Estudaram-se 40 pacientes com dor torácica de origem indeterminada (angiografia coronária normal, sendo 80% do sexo feminino e média de idade de 54 anos. A endoscopia digestiva alta revelou esofagite erosiva em dois pacientes (5% e úlcera péptica em um (2,4%; a esofagomanometria foi anormal em 60%; a pHmetria prolongada foi anormal em 14 (35%, com índice de sintomas positivo em 7. A dor foi considerada de origem esofagiana comprovada (índice de sintomas positivo à pHmetria em 7 (17,5% pacientes e 19 (47,5% com origem esofagiana provável (8 por doença do refluxo gastroesofágico e 11 por distúrbios motores. Em 14 (35% a origem da dor não foi demonstrada. O teste de Bernstein foi positivo em 10 (25%, o teste do edrofônio em 8 (20% e o teste do balão em 15 (37,5%, sendo que 23 pacientes apresentaram, pelo menos, um teste provocativo positivo (57,5%. Com a adição dos testes provocativos foi possível apontar a dor como de origem esofagiana comprovada em 12 dos 19 pacientes (63,1% em que

  3. Influência da criação de um serviço de tratamento da dor aguda nos custos e no consumo de drogas analgésicas na sala de recuperação pós-anestésica

    OpenAIRE

    Gomes,Marcos Emanuel Wortmann; Evangelista,Paulo Ernani; Mendes,Florentino Fernandes

    2003-01-01

    JUSTIFICATIVA E OBJETIVOS: Sabe-se que a dor aguda pós-operatória apresenta grande influência na evolução dos pacientes cirúrgicos. Mobilização precoce, menor tempo de hospitalização, diminuição de custos e maior satisfação são resultados do adequado manuseio da dor. Observa-se uma tendência mundial ao surgimento de serviços especializados no tratamento da dor pós-operatória. O presente estudo visa descrever a influência da criação de um serviço de tratamento da dor aguda pós-operatória nos c...

  4. Dor neuropática: aspectos neuroquímicos Dolor neuropático: aspectos neuroquímicos Neuropathic pain: neurochemical aspects

    Directory of Open Access Journals (Sweden)

    Durval Campos Kraychete

    2008-10-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A dor neuropática é causada por lesão ou inflamação do sistema nervoso. É síndrome complexa, com mecanismos biológicos pouco esclarecidos, envolvendo teorias inflamatórias e imunes. O objetivo desta revisão foi descrever os principais fatores biológicos relacionados com a dor neuropática, associando de forma lógica as hipóteses sugeridas pela literatura. CONTEÚDO: Foram descritos os principais neuromediadores, canais iônicos e células, incluindo as do sistema imune envolvidos na excitabilidade neuronal, assim como enfatizada possível seqüência de ativação ou interação desses agentes na alteração neuroplástica decorrente da agressão ao nervo. CONCLUSÕES: Do estudo, foi possível concluir que os avanços no conhecimento da fisiopatologia da dor neuropática podem determinar novos alvos para abordagem farmacológica dessa síndrome.JUSTIFICATIVA Y OBJETIVOS: El dolor Neuropático lo causa la lesión o inflamación del sistema nervioso. Es un síndrome complejo, con mecanismos biológicos poco aclarados, que envuelve teorías inflamatorias e inmunes. El objetivo de esta revisión fue describir los principales factores biológicos relacionados con el dolor Neuropático, asociando de forma lógica a las hipótesis sugeridas por la literatura. CONTENIDO: Fueron descritos los principales neuromediadores, canales iónicos y células, incluyendo las del sistema inmune involucrados en la excitabilidad neuronal, como también la posible secuencia de activación o interacción de esos agentes en la alteración neuroplástica proveniente e la agresión al nervio. CONCLUSIONES: De ese estudio, se pudo concluir que los avances en el conocimiento de la fisiopatología del dolor Neuropático, pueden determinar nuevos objetivos para el abordaje farmacológico de ese síndrome.BACKGROUND AND OBJECTIVES: Neuropathic pain is caused by damage or inflammation of the nervous system. It is a complex syndrome and its

  5. Avaliação eletromiográfica e ressonância magnética do joelho de indivíduos com síndrome da dor femoropatelar Electromyographic and magnetic resonance imaging evaluations of individuals with patellofemoral pain syndrome

    Directory of Open Access Journals (Sweden)

    Alessandra C. S. Ribeiro

    2010-06-01

    Full Text Available OBJETIVOS: Analisar a atividade elétrica (EMG dos músculos vasto medial oblíquo (VMO, vasto lateral longo (VLL e vasto lateral oblíquo (VLO de indivíduos com síndrome da dor femoropatelar (SDFP durante contração isométrica voluntária máxima (CIVM de extensão da perna com o joelho a 30(0, a dor por meio da Escala Visual Analógica (EVA e o posicionamento da patela por meio da ressonância magnética nuclear por imagem (RMNI. MÉTODOS: Avaliaram-se 12 mulheres com SDFP e 12 clinicamente normais, que realizaram cinco CIVM de extensão da perna no ângulo de 30(0 para análise da EMG. Avaliou-se o ângulo do sulco (AS, ângulo de congruência (AC, ângulo de inclinação patelar (AIP e deslocamento patelar (DP pela RMNI. Utilizaram-se testes estatísticos: ANOVA, análise de variância de medidas repetidas para EMG; o teste Mann-Whitney U para análise da RMNI; o teste de correlação de Pearson (r entre EMG e RMNI e análise de variância one-way para avaliação da dor (pOBJECTIVES: To analyze the electrical activity of the vastus medialis obliquus (VMO, vastus lateralis longus (VLL and vastus lateralis obliquus (VLO muscles of individuals with patellofemoral pain syndrome (PFPS during maximum voluntary isometric contraction (MVIC of lower leg extension with the knee at 30°; to assess pain using a visual analogue scale (VAS; and to assess patellar positioning using magnetic resonance imaging (MRI. METHODS: Twelve women with PFPS and 12 clinically normal women were evaluated. They performed five MVICs of lower leg extension at 30° for electromyographic (EMG analysis. Using MRI, the sulcus angle (SA, congruence angle (CA, patellar tilt angle (PTA and patellar displacement (PD were obtained. The following statistical tests were used: analysis of variance (ANOVA for repeated measurements to assess EMGs; Mann-Whitney U test to analyze MRIs; Pearson's (r correlation test between EMGs and MRIs; and one-way ANOVA to evaluate pain (p<0

  6. Dynamic mechanistic modeling of the multienzymatic one-pot reduction of dehydrocholic acid to 12-keto ursodeoxycholic acid with competing substrates and cofactors.

    Science.gov (United States)

    Sun, Boqiao; Hartl, Florian; Castiglione, Kathrin; Weuster-Botz, Dirk

    2015-01-01

    Ursodeoxycholic acid (UDCA) is a bile acid which is used as pharmaceutical for the treatment of several diseases, such as cholesterol gallstones, primary sclerosing cholangitis or primary biliary cirrhosis. A potential chemoenzymatic synthesis route of UDCA comprises the two-step reduction of dehydrocholic acid to 12-keto-ursodeoxycholic acid (12-keto-UDCA), which can be conducted in a multienzymatic one-pot process using 3α-hydroxysteroid dehydrogenase (3α-HSDH), 7β-hydroxysteroid dehydrogenase (7β-HSDH), and glucose dehydrogenase (GDH) with glucose as cosubstrate for the regeneration of cofactor. Here, we present a dynamic mechanistic model of this one-pot reduction which involves three enzymes, four different bile acids, and two different cofactors, each with different oxidation states. In addition, every enzyme faces two competing substrates, whereas each bile acid and cofactor is formed or converted by two different enzymes. First, the kinetic mechanisms of both HSDH were identified to follow an ordered bi-bi mechanism with EBQ-type uncompetitive substrate inhibition. Rate equations were then derived for this mechanism and for mechanisms describing competing substrates. After the estimation of the model parameters of each enzyme independently by progress curve analyses, the full process model of a simple batch-process was established by coupling rate equations and mass balances. Validation experiments of the one-pot multienzymatic batch process revealed high prediction accuracy of the process model and a model analysis offered important insight to the identification of optimum reaction conditions. © 2015 American Institute of Chemical Engineers.

  7. La madre dice: el dolor de mi bebé es mi dolor A mãe diz: a dor do meu bebê é a minha dor Mother Says: My Baby´s Pain is my Pain

    Directory of Open Access Journals (Sweden)

    ROSA YOLANDA MUNÉVAR TORRES

    2010-10-01

    con su entorno cultural. Por tanto, el mundo del recién nacido incluye a la madre y demanda de enfermería intervención de cuidado para los dos, respetando sus sentimientos, valores, creencias, costumbres y prácticas de cuidado cultural.Objetivo: descrever os sentimentos das mães e o apoio social recebido quando seu recém-nascido sente dor. Metodologia: estudo qualitativo, de pequeno alcance, com metodologia etnográfica. Realizaram-se 22 entrevistas em profundidade a oito mães, com uma média dentre duas a quatro entrevistas por informante. A amostra consistiu da saturação de informação selecionada por pertinência e adequação; utilizaram-se notas de campo e observação aos participantes. Os dados foram analisados segundo a metodologia de James Spradley. Resultados: o tema central foi As mães conhecem, sentem e aliviam a dor do recém-nascido com apóio familiar. O primeiro sub-tema (já publicado: As mães conhecem e aliviam a dor do recém-nascido, e o segundo: A mãe sente a dor do recém-nascido e procura apoio na família; estão constituídos por duas áreas: Preocupação, dor e amor são os sentimentos maternos frente à dor do recém-nascido. A família e os amigos são classes de apoio da mãe. Conclusões: a dor do neonato e o desconhecimento da causa e forma adequada de aliviá-lo causam estresse na mãe e fortalecem a relação mãe-filho, sendo que ela acredita sofrer a mesma dor do que seu filho, quem lhe exige proteção e cuidado como resposta de alívio, ação que é prioritária frente aos seus próprios sentimentos e necessidades. Por tanto, a mãe deseja ser cuidada como ser humano que sofre, e precisa de familiares e pessoas próximas que providenciem apoio emocional expressado na companhia e na confiança e informação quando solicita orientação, conselho ou ajuda na tomada de decisões, sem desconhecer seu contexto cultural; esses aspectos são coerentes com a teoria proposta por Madeleine Leininger, visto que a perspectiva

  8. Invisible nuclear; converting nuclear

    International Nuclear Information System (INIS)

    Park, Jongmoon

    1993-03-01

    This book consists of 14 chapters which are CNN era and big science, from East and West to North and South, illusory nuclear strategy, UN and nuclear arms reduction, management of armaments, advent of petroleum period, the track of nuclear power generation, view of energy, internationalization of environment, the war over water in the Middle East, influence of radiation and an isotope technology transfer and transfer armament into civilian industry, the end of nuclear period and the nuclear Nonproliferation, national scientific and technological power and political organ and executive organ.

  9. Estudo das características epidemiológicas da dor de crescimento em crianças atendidas em unidade hospitalar do Distrito Federal : avaliação da fibromialgia materna como fator de risco

    OpenAIRE

    Ribeiro, Maria Custódia Machado

    2011-01-01

    Este estudo teve como objetivos avaliar a freqüência de fibromialgia em mães de crianças com dor de crescimento e sua provável associação em 153 crianças procedentes do ambulatório de Pediatria e Reumatologia Pediátrica do Hospital Universitário de Brasília, no período de fevereiro a setembro de 2005. Foram estudadas as características clínicas e epidemiológicas e avaliada a correlação entre enxaqueca materna e presença de dor de crescimento nessas crianças. Foram selecionadas 75 crianças que...

  10. O modelo bioético principialista aplicado no manejo da dor El principialismo bioético modelo aplicado en el tratamiento del dolor The bioethical principlism model applied in pain management

    Directory of Open Access Journals (Sweden)

    Layz Alves Ferreira Souza

    2013-03-01

    Full Text Available Trata-se de revisão integrativa da literatura, com o objetivo de analisar a produção científica referente às relações entre a dor e os princípios da bioética: autonomia, beneficência, não maleficência e justiça. Foram utilizados descritores controlados em três bases de dados internacionais (LILACS, SciELO, MEDLINE, em abril de 2012, resultando em 14 publicações, distribuídas nas categorias Dor e autonomia, Dor e beneficência, Dor e não maleficência, Dor e justiça. O alívio adequado da dor é um direito humano e uma questão moral que se relaciona diretamente com a bioética principialista. Entretanto, muitos profissionais negligenciam a dor de seus pacientes, desconsiderando seu papel ético frente ao sofrimento.Concluiu-se que o principialismo tem sido negligenciado no atendimento aos pacientes com dor, evidenciando a necessidade de novas práticas para mudança desse panorama.Se realizó una revisión de la literatura para analizar la producción científica relacionadas con el dolor y los principios de la bioética (autonomía, beneficencia, no maleficencia y justicia. Se utilizaron descriptores controlados en tres fuentes de datos internacionales (LILACS, SciELO, MEDLINE, en abril de 2012, totalizando14 publicaciones, distribuidas en las clases: el dolor y la autonomía, el dolor y la beneficencia, el dolor y no maleficencia, el dolor y la justicia. El adecuado alivio del dolor es un derecho humano y un problema moral relacionado directamente con el principialismo bioético (beneficencia, no maleficencia, autonomía y justicia. Sin embargo, muchos profesionales negligencian el dolor de sus pacientes, ignorando su papel ético frente al sufrimiento. Se concluyó que el principialismo ha sido descuidado en la atención de los pacientes con dolor evidenciando la necesidad de nuevas prácticas para cambiar este panorama.An integrative literature review was developed with the purpose to analyze the scientific production

  11. O que os pediatras conhecem sobre avaliação e tratamento da dor no recém-nascido? What do pediatricians know about pain assessment and treatment in newborn infants?

    Directory of Open Access Journals (Sweden)

    Aurimery G. Chermont

    2003-06-01

    Full Text Available OBJETIVO: analisar os conhecimentos dos pediatras que atuam com pacientes neonatais em relação à avaliação e o tratamento da dor do recém-nascido. MÉTODOS: estudo transversal com 104 pediatras (de um total de 110 que trabalhavam em 1999 a 2001, nas sete unidades de terapia intensiva e nos 14 berçários da cidade de Belém, e responderam a um questionário escrito com perguntas a respeito do seu perfil demográfico e do conhecimento de métodos de avaliação e de tratamento da dor no recém-nascido. RESULTADOS: cem por cento dos médicos referiram acreditar que o recém-nascido sente dor, mas apenas um terço deles conhecia alguma escala para avaliar a dor nessa faixa etária. A maioria dos entrevistados referia perceber a presença de dor no recém-nascido por meio de parâmetros comportamentais. O choro foi o preferido para avaliar a dor do bebê a termo; a mímica facial para o prematuro, e a freqüência cardíaca para o neonato em ventilação mecânica. Menos de 10% dos entrevistados diziam usar analgesia para punções venosas e capilares; 30 a 40% referiam empregar analgesia para punções lombares, dissecações venosas, drenagens de tórax e ventilação mecânica. Menos da metade dos entrevistados referiu aplicar medidas para o alívio da dor no pós-operatório de cirurgia abdominal em neonatos. O opióide foi o medicamento mais citado para a analgesia (60%, seguido pelo midazolam (30%. CONCLUSÃO: os pediatras demonstraram pouco conhecimento a respeito dos métodos de avaliação e tratamento da dor no período neonatal. Há necessidade de reciclagens e de atualização no tema para os profissionais de saúde que atuam com recém-nascidos doentes.OBJECTIVE: to analyze the knowledge of pediatricians who work with neonatal patients regarding the evaluation and treatment of pain in newborn infants. METHODS: cross-sectional study of 104 pediatricians (out of 110 who were working during 1999 to 2001 in seven intensive care units

  12. Pharmacoepidemiological assessment of adherence and influencing co-factors among primary open-angle glaucoma patients-An observational cohort study.

    Directory of Open Access Journals (Sweden)

    Stefanie Frech

    Full Text Available The goal of this study was to assess the adherence of primary open-angle glaucoma (POAG patients to medication, and to determine co-factors influencing adherence, using a representative sample of members of the largest German public health insurer. The observational cohort study was based on a longitudinal data set from 2010-2013 and included 250,000 insured persons aged 50 and older with 10,120 diagnosed POAG patients. Uni- and multivariate analysis was performed to investigate several aspects of glaucoma, such as prevalence, adherence, and co-factors influencing adherence. The main outcome measured adherence with prescriptions filled within a year. Multivariate panel regression analysis was used to determine the co-factors influencing this adherence. Prevalence of POAG was 3.36% [CI: 3.28-3.43%], with 2.91% [CI: 2.81-3.01%] for males and 3.71% [CI: 3.61-3.81%] for females, increasing with age. The mean level of adherence in terms of prescriptions filled was 66.5% [CI: 65.50-67.60%]. The results of this analysis revealed a significant influence of age, duration of the disease, care need, distance to death, and multimorbidity as co-factors of non-adherence, whereas gender had no influence. The analysis provided detailed information about POAG health care aspects concerning prevalence and adherence. The most endangered risk groups for non-adherence were patients aged 50-59, patients older than 80 years, patients with a longer duration of POAG, patients with care needs, and patients with three or more severe diseases in addition to glaucoma. To know the predictors responsible for an increased risk to develop POAG is of importance for all persons involved in health care management. Therefore effective strategies to increase awareness of patients and medical care personnel about non-adherence and the importance of a regular and continuous medication to avoid further nerve fiber damage and possible blindness have to be developed.

  13. Synthesis and characterization of sulfur-voided cubanes. Structural analogues for the MoFe(3)S(3) subunit in the nitrogenase cofactor.

    Science.gov (United States)

    Coucouvanis, Dimitri; Han, Jaehong; Moon, Namdoo

    2002-01-16

    A new class of Mo/Fe/S clusters with the MoFe(3)S(3) core has been synthesized in attempts to model the FeMo-cofactor in nitrogenase. These clusters are obtained in reactions of the (Cl(4)-cat)(2)Mo(2)Fe(6)S(8)(PR(3))(6) [R = Et (I), (n)Pr (II)] clusters with CO. The new clusters include those preliminarily reported: (Cl(4)-cat)MoFe(3)S(3)(PEt(3))(2)(CO)(6) (III), (Cl(4)-cat)(O)MoFe(3)S(3)(PEt(3))(3)(CO)(5) (IV), (Cl(4)-cat)(Pyr)MoFe(3)S(3)(PEt(3))(2)(CO)(6) (VI), and (Cl(4)-cat)(Pyr)MoFe(3)S(3)(P(n)Pr(3))(3)(CO)(4) (VIII). In addition the new (Cl(4)-cat)(O)MoFe(3)S(3)(P(n)Pr(3))(3)(CO)(5) cluster (IVa), the (Cl(4)-cat)(O)MoFe(3)S(3)(PEt(3))(2)(CO)(6)cluster (V), the (Cl(4)-cat)(O)MoFe(3)S(3)(P(n)Pr(3))(2)(CO)(6) cluster (Va), the (Cl(4)-cat)(Pyr)MoFe(3)S(3)(P(n)Pr(3))(2)(CO)(6) cluster (VIa), and the (Cl(4)-cat)(P(n)Pr(3))MoFe(3)S(3)(P(n)Pr(3))(2)(CO)(6) cluster (VII) also are reported. Clusters III-VIII have been structurally and spectroscopically characterized. EPR, zero-field (57)Fe-Mössbauer spectroscopic characterizations, and magnetic susceptibility measurements have been used for a tentative assignment of the electronic and oxidation states of the MoFe(3)S(3) sulfur-voided cuboidal clusters. A structural comparison of the clusters with the MoFe(3)S(3) subunit of the FeMo-cofactor has led to the suggestion that the storage of reducing equivalents into M-M bonds, and their use in the reduction of substrates, may occur with the FeMo-cofactor, which also appears to have M-M bonding. On the basis of this argument, a possible N(2)-binding and reduction mechanism on the FeMoco-cofactor is proposed.

  14. Aspectos psicossociais do trabalho e dor musculoesquelética em professores Psychosocial work-related factors and musculoskeletal pain among schoolteachers

    Directory of Open Access Journals (Sweden)

    Jefferson Paixão Cardoso

    2011-08-01

    Full Text Available Investigou-se a associação entre aspectos psicossociais do trabalho e queixas de dor musculoesquelética (DME em professores. Um estudo censitário de corte transversal investigou 4.496 professores da rede municipal de ensino infantil e fundamental de Salvador, Bahia, Brasil. Informações sobre queixas de dor musculoesquelética em membros superiores, membros inferiores e dorso (variáveis dependentes, categorias do Modelo Demanda-Controle (variáveis independentes e covariáveis foram coletadas num questionário padronizado autoaplicável. Análises de regressão logística multivariada revelaram que professores com trabalho de alta exigência apresentaram prevalência de DME mais elevada e professores em baixa exigência, prevalência mais baixa, em cada um dos três segmentos corporais estudados. Professores em trabalho ativo apresentaram prevalência de DME mais elevada do que professores em trabalho de baixa exigência, em membros superiores e dorso. Maiores taxas de prevalência de DME associaram-se à maior demanda psicológica nos três segmentos corporais e ao baixo controle sobre o trabalho em membros superiores, apenas.This study aimed to investigate the association between work-related psychosocial factors and musculoskeletal pain (MP among primary schoolteachers in the public school system in Salvador, Bahia State, Brazil. A cross-sectional epidemiological study included all 4,496 teachers from the system. A self-applied mail questionnaire was used to collect information on complaints of musculoskeletal pain in the upper limbs, lower limbs, and back (dependent variables, demand-control model quadrants (independent variables, and covariables. Multivariate logistic regression showed that teachers in high-stress jobs presented the highest MP rates, and that those with low-stress jobs had the lowest rates in all three body segments. Teachers in active jobs presented higher MP rates than those in low-stress jobs, particularly in the

  15. LOOKING FOR A CONNECTION BETWEEN THE Am PHENOMENON AND HYBRID {delta} Sct -{gamma} Dor PULSATION: DETERMINATION OF THE FUNDAMENTAL PARAMETERS AND ABUNDANCES OF HD 114839 AND BD +18 4914

    Energy Technology Data Exchange (ETDEWEB)

    Hareter, M.; Weiss, W. [Department of Astronomy, University of Vienna, Tuerkenschanzstrasse 17, A-1180 Wien (Austria); Fossati, L. [Department of Physics and Astronomy, Open University, Walton Hall, Milton Keynes MK6 7AA (United Kingdom); Suarez, J. C. [Instituto de Astrofisica de Andalucia (CSIC), Glorieta de la Astronomia S/N, 18008, Granada (Spain); Uytterhoeven, K. [Kiepenheuer-Institut fuer Sonnenphysik, Schoeneckstr. 6, D-79104 Freiburg (Germany); Rainer, M.; Poretti, E., E-mail: hareter@astro.univie.ac.at [INAF-Osservatorio Astronomico di Brera, Via E. Bianchi 46, 23807, Merate (Saint Lucia) (Italy)

    2011-12-20

    {delta} Sct-{gamma} Dor hybrids pulsate simultaneously in p- and g-modes, which carry information on the structure of the envelope as well as to the core. Hence, they are key objects for investigating A and F type stars with asteroseismic techniques. An important requirement for seismic modeling is small errors in temperature, gravity, and chemical composition. Furthermore, we want to investigate the existence of an abundance indicator typical for hybrids, something that is well established for the roAp stars. Previous to the present investigation, the abundance pattern of only one hybrid and another hybrid candidate has been published. We obtained high-resolution spectra of HD 114839 and BD +18 4914 using the SOPHIE spectrograph of the Observatoire de Haute-Provence and the HARPS spectrograph at ESO La Silla. For each star we determined fundamental parameters and photospheric abundances of 16 chemical elements by comparing synthetic spectra with the observations. We compare our results to that of seven {delta} Sct and nine {gamma} Dor stars. For the evolved BD +18 4914 we found an abundance pattern typical for an Am star, but could not confirm this peculiarity for the less evolved star HD 114839, which is classified in the literature as uncertain Am star. Our result supports the concept of evolved Am stars being unstable. With our investigation we nearly doubled the number of spectroscopically analyzed {delta} Sct-{gamma} Dor hybrid stars, but did not yet succeed in identifying a spectroscopic signature for this group of pulsating stars. A statistically significant spectroscopic investigation of {delta} Sct- {gamma} Dor hybrid stars is still missing, but would be rewarding considering the asteroseismological potential of this group.

  16. The influence of monovalent cations on trimeric G protein Gi1alfa activity in HEK293 cells stably expressing DOR-Gi1alfa (Cys351-Ile351) fusion protein

    Czech Academy of Sciences Publication Activity Database

    Vošahlíková, Miroslava; Svoboda, Petr

    2011-01-01

    Roč. 60, č. 3 (2011), s. 541-547 ISSN 0862-8408 R&D Projects: GA AV ČR(CZ) IAA500110606; GA MŠk(CZ) LC554; GA ČR(CZ) GD305/08/H037 Institutional research plan: CEZ:AV0Z50110509 Keywords : delta-opioid receptor (DOR) * monovalent ions * G(i)1alfa protein Subject RIV: CE - Biochemistry Impact factor: 1.555, year: 2011

  17. LOOKING FOR A CONNECTION BETWEEN THE Am PHENOMENON AND HYBRID δ Sct -γ Dor PULSATION: DETERMINATION OF THE FUNDAMENTAL PARAMETERS AND ABUNDANCES OF HD 114839 AND BD +18 4914

    International Nuclear Information System (INIS)

    Hareter, M.; Weiss, W.; Fossati, L.; Suárez, J. C.; Uytterhoeven, K.; Rainer, M.; Poretti, E.

    2011-01-01

    δ Sct-γ Dor hybrids pulsate simultaneously in p- and g-modes, which carry information on the structure of the envelope as well as to the core. Hence, they are key objects for investigating A and F type stars with asteroseismic techniques. An important requirement for seismic modeling is small errors in temperature, gravity, and chemical composition. Furthermore, we want to investigate the existence of an abundance indicator typical for hybrids, something that is well established for the roAp stars. Previous to the present investigation, the abundance pattern of only one hybrid and another hybrid candidate has been published. We obtained high-resolution spectra of HD 114839 and BD +18 4914 using the SOPHIE spectrograph of the Observatoire de Haute-Provence and the HARPS spectrograph at ESO La Silla. For each star we determined fundamental parameters and photospheric abundances of 16 chemical elements by comparing synthetic spectra with the observations. We compare our results to that of seven δ Sct and nine γ Dor stars. For the evolved BD +18 4914 we found an abundance pattern typical for an Am star, but could not confirm this peculiarity for the less evolved star HD 114839, which is classified in the literature as uncertain Am star. Our result supports the concept of evolved Am stars being unstable. With our investigation we nearly doubled the number of spectroscopically analyzed δ Sct-γ Dor hybrid stars, but did not yet succeed in identifying a spectroscopic signature for this group of pulsating stars. A statistically significant spectroscopic investigation of δ Sct- γ Dor hybrid stars is still missing, but would be rewarding considering the asteroseismological potential of this group.

  18. Effect of adding cofactors to exogenous fibrolytic enzymes on preingestive hydrolysis, in vitro digestibility, and fermentation of bermudagrass haylage.

    Science.gov (United States)

    Romero, J J; Ma, Z X; Gonzalez, C F; Adesogan, A T

    2015-07-01

    Our objectives were to examine if adding metal ion cofactors (COF) to exogenous fibrolytic enzymes (EFE) would increase the beneficial effects of the EFE on the preingestive hydrolysis and in vitro digestibility and fermentation of bermudagrass haylage. In experiment 1, 5 COF (Mn(2+), Co(2+), Fe(2+), Ca(2+), and Mg(2+)) were screened to select the best candidates for synergistically enhancing release of water-soluble carbohydrates (WSC) from bermudagrass haylage by 5 EFE. The 5 EFE (1A, 2A, 11C, 13D, and 15D) were sourced from Trichoderma reesei and Aspergillus oryzae and they were the most effective of 12 EFE at increasing the neutral detergent fiber digestibility of bermudagrass haylage in a previous trial. Adding 1mM of each of the COF to EFE 2A or 11C synergistically increased release of WSC from bermudagrass haylage, as did adding (1mM) Fe(2+) to 1A, Mn(2+), Co(2+), or Fe(2+) to 13D, or Co(2+)or Fe(2+) to 15D. The greatest release of WSC responses were obtained by adding Mn(2+) to 11C (38%) or by adding Fe(2+) to 2A or 13D (10 and 21.9%, respectively). In experiment 2, the effect of increasing the COF dose on in vitro digestibility and fermentation of bermudagrass haylage was examined using the best EFE-COF combinations from experiment 1. Effects of adding increasing doses of these COF on EFE-mediated changes in vitro digestibility depended on the COF-EFE combination. Adding 10mM Mn(2+) alone to bermudagrass haylage increased DMD and NDFD by 2.7 and 6.3% and adding 11C alone increased these measures by 6.6 and 15.5%, respectively. However, adding 10mM Mn(2+) with 11C resulted in 3.5 and 8.1% increases in DMD and NDFD, respectively, beyond the increases caused by adding 11C alone. Adding Fe(2+) to 2A had no effects on EFE-mediated digestibility responses, but 2A prevented adverse effects of adding Fe(2+) alone on DMD and NDFD. In contrast, adding Fe(2+) to 13D reduced the increases in DMD and NDFD caused by adding the EFE alone. This study shows that adding COF

  19. Desafios do enfermeiro diante da dor e do sofrimento da família de pacientes fora de possibilidades terapêuticas

    Directory of Open Access Journals (Sweden)

    Maria de Fátima Prado Fernandes

    Full Text Available O presente trabalho trata-se de um estudo de abordagem qualitativa com o objetivo de identificar os desafios dos enfermeiros para assistir às famílias de pacientes fora de possibilidades terapêuticas diante da dor e do sofrimento. A coleta de dados ocorreu no ano de 2008, mediante entrevista semiestruturada, com dezoito enfermeiros que trabalhavam em Unidades de Terapia Intensiva de um hospital privado localizado no município de São Paulo, após aprovação do Comitê de Ética em Pesquisa. Utilizou-se a análise de conteúdo para a avaliação dos dados. Obtiveram-se três categorias: enfrentando os desafios para assistir a família, posicionamento esperado e orientar-se a partir da experiência. Evidenciou-se que, para assistir às famílias, há necessidade dos enfermeiros refletirem a respeito dos valores pessoais e éticos, bem como sobre o processo do morrer. Espera-se que haja troca de experiências entre os enfermeiros já experientes com os que iniciam tal prática no âmbito do cuidar.

  20. Autorretratos da dor em profusão: diálogo entre o soneto Eu..., de Florbela espanca, e a pintura A coluna partida, de Frida Kahlo

    Directory of Open Access Journals (Sweden)

    Cícero Émerson do Nascimento Cardoso

    2013-05-01

    Full Text Available

    Este trabalho se pauta na análise de obras artísticas em dois campos específicos: Literatura e Arte Plástica. Busca estabelecer um diálogo entre o soneto “EU”, de Florbela Espanca, e a pintura “A coluna partida”, de Frida Kahlo. Em ambas as obras é perceptível o quanto a concepção de dor e de sofrimento, vinculado às experiências trágicas vividas por essas duas mulheres de espírito moderno, motivaram a realização de obras de significante valor estético. Essas obras em destaque se constituem como exemplos de autorretratos em que a feminilidade, a sensibilidade, as pulsões dolorosas da alma dessas artistas captam, de modo expressivo, os dramas existenciais vividos e redirecionados para a arte por elas produzidas.

  1. Efeito da acupuntura na dor lombar: revisão de literatura - doi: 105102/ucs.v12i1.2593

    Directory of Open Access Journals (Sweden)

    José Roberto Pimenta de Godoy

    2014-08-01

    Full Text Available A lombalgia é o acometimento mais frequente da coluna vertebral, sendo uma das principais queixas e uma das causas mais comuns de incapacidade e morbidade. Diversos tipos de tratamento são usados no combate à dor lombar, porém, muitos pacientes não apresentam resultados com a medicina convencional. Entre os tratamentos não convencionais, a acupuntura é uma das principais alternativas para o alívio e cura dessa patologia. Com isso, o objetivo do trabalho é analisar a eficácia da acupuntura no tratamento da lombalgia, comparando-a com outros tratamentos. Para isso, realizou-se uma revisão bibliográfica com 21 estudos, randomizados, revisões de literatura e meta-análises, publicados entre os anos de 1999 e 2011, com o tema deste estudo. A acupuntura foi eficaz no tratamento da lombalgia crônica e seus resultados foram superiores aos de outros tratamentos. Sugerimos que mais estudos sejam feitos para a comprovação dos efeitos da acupuntura na lombalgia aguda.

  2. MÉTODOS NÃO FARMACOLÓGICOS DE ALÍVIO DA DOR DURANTE TRABALHO DE PARTO E PARTO

    Directory of Open Access Journals (Sweden)

    Eveline Franco da Silva

    2011-01-01

    Full Text Available RESUMO: Objetivou-se analisar as produções científicas relacionadas aos métodos não farmacológicos de alívio da dor durante trabalho de parto e parto, por meio de uma revisão integrativa da literatura desenvolvida por meio das bases de dados Literatura Latino-Americana em Ciências de Saúde (LILACS e Scientific Electronic Library Online (SciELO. Foram incluídos 21 artigos, oriundos de estudos realizados no Brasil, publicados no período de 2003 e 2009. Os estudos abordaram: mobilidade, hidroterapia, crioterapia, estimulação elétrica transcutânea, técnicas de respiração e relaxamento. A região sudeste apresentou maior número de publicações, com maior incidência entre os anos de 2005 a 2007. Quanto à autoria, evidenciou-se maior empreendimento dos enfermeiros sobre os demais profissionais. A evidência da redução do medo e do uso de analgésicos e anestésicos possibilita sacramentar o uso destas terapias. O estudo permitiu a visibilidade às produções científicas sobre esta temática, apontando para a importância da realização de estudos exploratórios.

  3. Prevenção e manejo não farmacológico da dor no recém-nascido

    Directory of Open Access Journals (Sweden)

    Giordana de Cássia Pinheiro da Motta

    2015-02-01

    Full Text Available Objetivo: apresentar os principais métodos não farmacológicos de alívio da dor no recém-nascido disponíveis para utilização na Unidade de Tratamento Intensivo Neonatal. Método: pesquisa bibliográfica do tipo exploratória nas bases de dados online MEDLINE, LILACS e SciELO, no período de 2004 a 2013. Resultados: uma variedade de intervenções não farmacológicas se mostra efetiva, apresentando baixo risco para os neonatos e baixo custo operacional, sendo as mais discutidas na literatura: uso de glicose/sacarose via oral, sucção não nutritiva, amamentação, contato pele a pele, contenção facilitada e enrolamento. Conclusão: é importante que a equipe de saúde conheça os métodos para melhor utilizá-los no dia a dia da Unidade de Tratamento Intensivo Neonatal, garantindo um cuidado qualificado e humanizado ao recém-nascido.

  4. Peripheral T-Cell Reactivity to Heat Shock Protein 70 and Its Cofactor GrpE from Tropheryma whipplei Is Reduced in Patients with Classical Whipple's Disease.

    Science.gov (United States)

    Trotta, Lucia; Weigt, Kathleen; Schinnerling, Katina; Geelhaar-Karsch, Anika; Oelkers, Gerrit; Biagi, Federico; Corazza, Gino Roberto; Allers, Kristina; Schneider, Thomas; Erben, Ulrike; Moos, Verena

    2017-08-01

    Classical Whipple's disease (CWD) is characterized by the lack of specific Th1 response toward Tropheryma whipplei in genetically predisposed individuals. The cofactor GrpE of heat shock protein 70 (Hsp70) from T. whipplei was previously identified as a B-cell antigen. We tested the capacity of Hsp70 and GrpE to elicit specific proinflammatory T-cell responses. Peripheral mononuclear cells from CWD patients and healthy donors were stimulated with T. whipplei lysate or recombinant GrpE or Hsp70 before levels of CD40L, CD69, perforin, granzyme B, CD107a, and gamma interferon (IFN-γ) were determined in T cells by flow cytometry. Upon stimulation with total bacterial lysate or recombinant GrpE or Hsp70 of T. whipplei , the proportions of activated effector CD4 + T cells, determined as CD40L + IFN-γ + , were significantly lower in patients with CWD than in healthy controls; CD8 + T cells of untreated CWD patients revealed an enhanced activation toward unspecific stimulation and T. whipplei -specific degranulation, although CD69 + IFN-γ + CD8 + T cells were reduced upon stimulation with T. whipplei lysate and recombinant T. whipplei -derived proteins. Hsp70 and its cofactor GrpE are immunogenic in healthy individuals, eliciting effective responses against T. whipplei to control bacterial spreading. The lack of specific T-cell responses against these T. whipplei -derived proteins may contribute to the pathogenesis of CWD. Copyright © 2017 American Society for Microbiology.

  5. Pa2G4 is a novel Six1 co-factor that is required for neural crest and otic development☆

    Science.gov (United States)

    Neilson, Karen M.; Abbruzzesse, Genevieve; Kenyon, Kristy; Bartolo, Vanessa; Krohn, Patrick; Alfandari, Dominique; Moody, Sally A.

    2016-01-01

    Mutations in SIX1 and in its co-factor, EYA1, underlie Branchiootorenal Spectrum disorder (BOS), which is characterized by variable branchial arch, otic and kidney malformations. However, mutations in these two genes are identified in only half of patients. We screened for other potential co-factors, and herein characterize one of them, Pa2G4 (aka Ebp1/Plfap). In human embryonic kidney cells, Pa2G4 binds to Six1 and interferes with the Six1-Eya1 complex. In Xenopus embryos, knock-down of Pa2G4 leads to down-regulation of neural border zone, neural crest and cranial placode genes, and concomitant expansion of neural plate genes. Gain-of-function leads to a broader neural border zone, expanded neural crest and altered cranial placode domains. In loss-of-function assays, the later developing otocyst is reduced in size, which impacts gene expression. In contrast, the size of the otocyst in gain-of-function assays is not changed but the expression domains of several otocyst genes are reduced. Together these findings establish an interaction between Pa2G4 and Six1, and demonstrate that it has an important role in the development of tissues affected in BOS. Thereby, we suggest that pa2g4 is a potential candidate gene for BOS. PMID:27940157

  6. Tentative characterization of precursor compounds and co-factors of pigment formation in production of 'wu mi' from Vaccinium bracteatum Thunb. Leaves.

    Science.gov (United States)

    Fan, Mingcong; Fan, Yihui; Huang, Weiping; Wang, Li; Li, Yan; Qian, Haifeng; Zhang, Hui; Qi, Xiguang

    2018-10-01

    Vaccinium bracteatum leaves (VBTL) are traditionally used in China to dye rice grains, which assume a deep blue color, named 'Wu mi'. Information on the mechanism of pigment formation is limited. In this study, CIELAB color space parameters were used to represent the color of 'Wu mi'. Precursor compounds of pigments formed during the dyeing process were identified by UPLC Q-TOF MS analysis. The changes in co-factors for pigment formation in VBTL were measured at different growth stages. The L ∗ and b ∗ values of dyed rice increased as the leaves aged, whereas a ∗ values showed irregular changes. Six compounds were tentatively identified as pigment precursors by UPLC Q-TOF MS analysis. The pH and β-glucosidase activity at different growth stages of VBTL were indicated to be crucial co-factors for pigment formation. A tentative hypothesis is presented that iridoid glycosides are hydrolyzed by acids and β-glucosidases to form a dialdehyde structure that binds covalently with amino residues of lysine side chains in rice protein molecules. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Desigualdades contextuais e individuais da prevalência de dor dentária em adultos e idosos no Brasil Contextual and individual inequalities in dental pain prevalence among Brazilian adults and elders

    Directory of Open Access Journals (Sweden)

    Marco A. Peres

    2012-01-01

    Full Text Available O objetivo deste estudo foi conhecer a prevalência de dor dentária e fatores associados em adultos e idosos residentes nas capitais brasileiras usando os dados do Sistema de Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito Telefônico (VIGITEL, de 2009 (n = 54.367. Dor dentária foi a variável dependente. Macrorregião, idade, sexo, raça, escolaridade, posse de plano de saúde, tabagismo e consumo de refrigerantes foram as variáveis exploratórias. Foram realizadas regressões de Poisson multinível. A prevalência de dor dentária foi de 15,2%; Macapá e São Luís apresentaram prevalências maiores que 20% enquanto em todas as capitais do Sul e Sudeste, em Cuiabá, Campo Grande, Maceió, Recife e Natal foram encontradas prevalências menores que 15%. Residentes no Norte e Nordeste, mulheres, pretos e pardos, aqueles que não possuem plano de saúde, tabagistas e consumidores de refrigerantes apresentaram as maiores prevalências de dor dentária. A dor dentária é um problema de saúde pública que deve ser monitorado pelos sistemas de vigilância em saúde.This study aimed to assess the prevalence of dental pain among adults and older people living in Brazil's State capitals. Information was gathered from the Telephone Survey Surveillance System for Risk and Protective Factors for Chronic Diseases (VIGITEL in 2009 (n = 54,367. Dental pain was the outcome. Geographic region, age, gender, race, schooling, private health coverage, smoking, and soft drink consumption were the explanatory variables. Multilevel Poisson regression models were performed. Prevalence of dental pain was 15.2%; Macapá and São Luís had prevalence rates greater than 20%; all capitals in the South and Southeast, plus Cuiabá, Campo Grande, Maceió, Recife, and Natal had prevalence rates less than 15%. Factors associated with increased prevalence of dental pain were the North and Northeast regions, female gender, black/brown skin

  8. Toxina botulínica no tratamento da dor Toxina botulínica en el tratamiento del dolor Botulinum toxin in pain treatment

    Directory of Open Access Journals (Sweden)

    Orlando Carlos Gomes Colhado

    2009-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A toxina botulínica (TxB, uma das mais potentes toxinas bacterianas conhecidas, tem reconhecidamente ação terapêutica eficaz no tratamento de algumas síndromes dolorosas. Entretanto, algumas de suas indicações ainda estão em fase de comprovação com relação a sua eficácia. O objetivo deste estudo foi revisar o histórico, propriedades farmacológicas e aplicações clinicas da TxB, quando empregada no tratamento de dores de diferentes origens. CONTEÚDO: A TxB é o produto da fermentação do Clostridium Botulinum, uma bactéria anaeróbia Gram-positiva. Comercialmente, as TxB existem nas formas A e B, agentes biológicos obtidos laboratorialmente. A TxB, uma neurotoxina que possui alta afinidade pelas sinapses colinérgicas, ocasiona bloqueio na liberação de acetilcolina pelo terminal nervoso, sem alterar a condução neural de sinais elétricos ou síntese e armazenamento de acetilcolina. Comprovadamente, a TxB pode enfraquecer seletivamente a musculatura dolorosa, interrompendo o ciclo espasmo-dor. Com relação à dor, varias publicações têm demonstrado a eficácia e segurança da TxB-A no tratamento da cefaleia tipo tensão, migrânea, dor lombar crônica e dor miofascial. CONCLUSÕES: A TxB-A é segura e bem tolerada em desordens dolorosas crônicas, onde regimes de farmacoterapia podem sabidamente provocar efeitos colaterais. Outra vantagem é a redução do uso de analgésicos e o tempo de ação de 3 a 4 meses por dose. Entretanto pesquisas futuras serão necessárias para se estabelecer a eficácia da TxB-A em desordens dolorosas crônicas e seu exato mecanismo no alivio da dor, bem como seu potencial em tratamentos multifatoriais.JUSTIFICATIVA Y OBJETIVOS: La toxina botulínica (TxB, una de las más potentes toxinas bacterianas de que se tiene conocimiento, posee una reconocida acción terapéutica eficaz en el tratamiento de algunos síndromes dolorosos. Sin embargo, algunas de sus

  9. [Nuclear theory

    International Nuclear Information System (INIS)

    Haxton, W.

    1990-01-01

    This report discusses research in nuclear physics. Topics covered in this paper are: symmetry principles; nuclear astrophysics; nuclear structure; quark-gluon plasma; quantum chromodynamics; symmetry breaking; nuclear deformation; and cold fusion

  10. Chronic pain, associated factors, and impact on daily life: are there differences between the sexes? Dor crônica, fatores associados e influência na vida diária: existe diferença entre os sexos?

    Directory of Open Access Journals (Sweden)

    Érica Brandão de Moraes Vieira

    2012-08-01

    Full Text Available This pioneering cross-sectional study in São Luís, Maranhão State, Brazil, aimed to compare men and women with chronic pain by identifying associated factors and characterizing the pain and its impact on daily life. Considering an expected prevalence of 25%, 95% confidence interval, and 3% precision, a cluster sample of 1,597 individuals was selected. The descriptive analysis showed a predominance of women, age bracket of 18 to 29 years, and brown skin color. Prevalence of chronic pain was higher in women than in men. Risk factors were analyzed with logistic regression. Increasing age was an associated risk factor for chronic pain in both sexes. In women, 12 or more years of schooling were associated with lower prevalence of chronic pain, and divorce or widowhood was associated with higher prevalence. Lower back pain and headache were the two most frequently reported sites. There was no difference between the sexes in time since onset or intensity of pain. Chronic pain had a greater impact on daily life for women and generated more feelings of sadness.Estudo transversal, pioneiro em São Luís, Maranhão, Brasil, com o objetivo de comparar homens e mulheres com dor crônica por meio da identificação dos fatores associados, caracterização da dor e influência na vida diária. Considerando a prevalência de 25%, nível de 95% de confiança e precisão de 3% foram entrevistadas 1.597 pessoas selecionadas por amostragem do tipo conglomerado. Na análise descritiva houve predomínio do sexo feminino, faixa etária entre 18 e 29 anos e cor parda. A prevalência de dor crônica foi maior nas mulheres em relação aos homens. Utilizou-se regressão logística para análise dos fatores de risco. Maior idade foi um fator associado à dor crônica em ambos os sexos. Nas mulheres, escolaridade a partir de 12 anos de estudos associou-se à menor prevalência, e estar divorciada/viúva e desempregada à maior prevalência de dor crônica. As regi

  11. Prevalência de dor lombar crônica na população da cidade de Salvador Chronic low back pain prevalence in the population of the city of Salvador

    Directory of Open Access Journals (Sweden)

    Isabela Costa Guerra Barreto Almeida

    2008-03-01

    Full Text Available INTRODUÇÃO: A dor lombar crônica atinge níveis epidêmicos na população geral e informações sobre o perfil das pessoas atingidas podem ajudar a direcionar investimentos para seu controle. OBJETIVO: Estimar a prevalência de dor lombar crônica na população e identificar fatores associados. MÉTODOS: Estudo transversal com base em inquérito populacional, desenvolvido em setores censitários da cidade de Salvador classificados por nível socioeconômico. Foram entrevistados 2.297 indivíduos em que se avaliou a presença de dor lombar através do mapa corporal. A análise exploratória dos fatores associados foi realizada pela regressão logística. RESULTADOS: A prevalência de dor lombar crônica na população foi de 14,7%, com maior freqüência entre ex-fumantes (19,7%, pessoas com circunferência da cintura acima da normalidade (16,8% e com escolaridade baixa (17,4% em relação com as demais categorias. Fatores como atividade física, classe social, consumo excessivo de álcool, raça, sexo e ocupação na época da entrevista não estiveram associados à dor lombar. Na análise de regressão múltipla, estado civil solteiro associou-se negativamente com dor lombar crônica, enquanto associações positivas e estatisticamente significantes foram observadas entre o tabagismo atual ou no passado e a dor lombar (OR 1,47; IC95%; 1,11-1,96; p INTRODUCTION: Chronic low back pain has epidemic levels in the general population and profiling the individuals affected may help directing investments to control the problem. OBJECTIVE: To estimate the prevalence of chronic low back pain in the population and to identify associated factors. METHODS: Transversal study based on a population survey carried out in the sectors classified by the census in the city of Salvador according to socio-economic level. 2,297 individuals were interviewed in whom low back pain was evaluated through a bodily map. Exploratory analysis of associated factors was

  12. Nuclear topics

    International Nuclear Information System (INIS)

    Lukner, C.

    1982-07-01

    The pamphlet touches on all aspects of nuclear energy, from the world energy demands and consumption, the energy program of the Federal Government, nuclear power plants in the world, nuclear fusion, nuclear liability up to the nuclear fuel cycle and the shutdown of nuclear power plants. (HSCH) [de

  13. Nuclear power and nuclear weapons

    International Nuclear Information System (INIS)

    Vaughen, V.C.A.

    1983-01-01

    The proliferation of nuclear weapons and the expanded use of nuclear energy for the production of electricity and other peaceful uses are compared. The difference in technologies associated with nuclear weapons and nuclear power plants are described

  14. Co-ordinate variations in methylmalonyl-CoA mutase and methionine synthase, and the cobalamin cofactors in human glioma cells during nitrous oxide exposure and the subsequent recovery phase.

    Science.gov (United States)

    Riedel, B; Fiskerstrand, T; Refsum, H; Ueland, P M

    1999-07-01

    We investigated the co-ordinate variations of the two cobalamin (Cbl)-dependent enzymes, methionine synthase (MS) and methylmalonyl-CoA mutase (MCM), and measured the levels of their respective cofactors, methylcobalamin (CH3Cbl) and adenosylcobalamin (AdoCbl) in cultured human glioma cells during nitrous oxide exposure and during a subsequent recovery period of culture in a nitrous oxide-free atmosphere (air). In agreement with published data, MS as the primary target of nitrous oxide was inactivated rapidly (initial rate of 0.06 h(-1)), followed by reduction of CH3Cbl (to ordinate distribution of Cbl cofactors during depletion and repletion.

  15. Desempenho muscular, dor, rigidez e funcionalidade de idosas com osteoartrite de joelho Muscle performance, pain, stiffness, and functionality in elderly women with knee osteoarthritis

    Directory of Open Access Journals (Sweden)

    Mary Luci Avelar Di Sabatino Santos

    2011-01-01

    Full Text Available OBJETIVO: Verificar a correlação do desempenho dos músculos do joelho e os domínios dor, rigidez e funcionalidade do Questionário Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC de idosas com osteoartrite de joelho (OA. MÉTODOS: Estudo transversal observacional com uma amostra de 80 idosas (71,2 ± 5,3 anos com diagnóstico clínico de OA de joelho. Força, resistência e equilíbrio musculares foram avaliados por meio do dinamômetro isocinético Biodex System 3 Pro, nas velocidades angulares de 60º/s e 180º/s; a funcionalidade, presença de dor e rigidez foram avaliadas pelo questionário WOMAC. A correlação entre as variáveis foi analisada pelo teste de Spearman. RESULTADOS: Houve correlação inversa significativa da força e resistência musculares do quadríceps (QUA e isquiossurais (IQS nas velocidades de 60º/s e 180°/s, respectivamente, e da relação de equilíbrio muscular IQS/QUA a 180°/s com todos os domínios do WOMAC (pOBJECTIVE: To determinethe correlation between performance of the knee muscles and pain, stiffness, and functionality, through theWestern Ontario and McMaster Universities Osteoarthritis Index (WOMAC Questionnaire applied to an elderly population with osteoarthritis of the knee (OA. METHODS: This study uses an observational, cross-sectional approach applied to a convenience sample of 80 elderly individuals (71.2 ± 5.3 years of age with a clinical diagnosis of OA of the knee. Muscle strength, resistance, and balance of the knee were evaluated using the Biodex System 3 Pro isokinetic dynamometer at angularspeedsof 60º/s and 180º/s. The self-reported functionality, presence of pain, and stiffness were evaluated by the WOMAC questionnaire. The correlation between the variables was analyzed bySpearman's coefficient of correlation (α = 0.05. RESULTS: A significant inverse correlation was observed between muscle strength and resistance of the quadriceps muscle (Q and the hamstring

  16. Avaliação postural em mulheres com dor pélvica crônica Postural evaluation in women with chronic pelvic pain

    Directory of Open Access Journals (Sweden)

    Renata Miranda

    2009-07-01

    Full Text Available OBJETIVO: avaliar por meio da fotogrametria as alterações posturais de mulheres com dor pélvica crônica. MÉTODOS: foram avaliadas 30 mulheres com queixa de dor pélvica crônica e 37 sem essa queixa, totalizando 67 mulheres. A avaliação constituiu de anamnese, colocação de marcadores fixos em pontos anatômicos definidos e obtenção de fotografias em vista frontal, posterior, lateral esquerda e direita. A análise das fotos foi realizada com o software CorelDraw®, versão 11.0. Foram identificados valores para as variáveis de análise postural de tornozelo, joelho no plano sagital, pelve, lordose lombar, cifose torácica, escápula aduzida/abduzida, ombros, cabeça e teste do terceiro dedo ao chão. As variáveis qualitativas estudadas foram joelho (varo, valgo ou normal, presença ou não de escápula alada e de nivelamento de ombros. Para as análises estatísticas utilizamos o Statistical Package for Social Sciences, versão 16.0. Para a comparação entre as variáveis qualitativas foi utilizado o teste exato de Fisher e método de Monte-Carlo e, para a comparação de dados quantitativos foi utilizado o teste t ou o de Mann-Whitney. As comparações entre os dados contínuos corrigidos para possíveis variáveis de confusão foram feitas pela análise de covariância univariada. O nível de significância foi estabelecido como 0,05 ou 5%. RESULTADOS: foi observada diferença significante entre casos e controles para cabeça protusa (47,5 e 52,0º, respectivamente; pOBJECTIVE: to evaluate by photogrammetry, postural changes in women with chronic pelvic pain. METHODS: thirty women with complaint of chronic pelvic pain and 37 without it, in a total of 67 women, were evaluated. The evaluation was realized through anamnesis, fixed markers in defined anatomical sites, and frontal, posterior, left and right lateral photographies. Photo analysis has been done by the software CorelDraw®, version 11.0. Quantitative values for postural

  17. Dor no paciente com lesão medular: uma revisão Dolor en el paciente con lesión medular: una revisión Pain in patients with spinal cord injury: a review

    Directory of Open Access Journals (Sweden)

    Marcia de Miguel

    2009-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A dor crônica após a lesão medular é uma condição clínica de alta prevalência e de difícil tratamento. Desse modo, é importante que se conheça suas características clínicas e fatores causais para melhor abordagem diagnóstica e terapêutica. O objetivo desse trabalho foi revisar a literatura sobre a dor no paciente com lesão medular e sua possível associação com fatores físicos (nível da lesão, grau da lesão, tempo de início de dor e fatores psicológicos (humor e qualidade de vida. CONTEÚDO: Foram pesquisados trabalhos na base de dados Medline, publicados nos últimos seis anos e os critérios de inclusão foram os estudos originais em maiores de 18 anos. Foram discutidas as características clínicas da dor no paciente com lesão medular, comparando casuística de diversos autores. CONCLUSÕES: Apesar das diferenças conceituais e metodológicas entre os estudos, as prevalências de dor encontradas em pacientes com lesão medular foram altas, variando entre 64% e 82%. A dor neuropática ao nível da lesão tem início precoce (dias ou semanas e aquela abaixo do nível da lesão aparece mais tardiamente (meses ou anos. Não há associação entre dor e integridade da lesão e a porcentagem de pacientes que referem dor intensa varia entre 21 e 39%. Não foi possível concluir qual a relação entre a dor e o nível da lesão medular. A dor, no entanto, pode interferir de forma negativa no humor, na capacidade de realizar atividades cognitivas, sociais, recreacionais e laborativas.JUSTIFICATIVA Y OBJETIVOS: El dolor crónico después de la lesión medular es una condición clínica de alta prevalencia y de difícil tratamiento. De ese modo, es importante que se conozcan sus características clínicas y los factores causales para un mejor abordaje diagnóstico y terapéutico. El objetivo de este trabajo, fue revisar la literatura sobre el dolor en el paciente con lesión medular y su posible

  18. Nuclear rights - nuclear wrongs

    Energy Technology Data Exchange (ETDEWEB)

    Paul, E.F.; Miller, F.D.; Paul, J.; Ahrens, J.

    1986-01-01

    This book contains 11 selections. The titles are: Three Ways to Kill Innocent Bystanders: Some Conundrums Concerning the Morality of War; The International Defense of Liberty; Two Concepts of Deterrence; Nuclear Deterrence and Arms Control; Ethical Issues for the 1980s; The Moral Status of Nuclear Deterrent Threats; Optimal Deterrence; Morality and Paradoxical Deterrence; Immoral Risks: A Deontological Critique of Nuclear Deterrence; No War Without Dictatorship, No Peace Without Democracy: Foreign Policy as Domestic Politics; Marxism-Leninism and its Strategic Implications for the United States; Tocqueveille War.

  19. Nuclear moments

    CERN Document Server

    Kopferman, H; Massey, H S W

    1958-01-01

    Nuclear Moments focuses on the processes, methodologies, reactions, and transformations of molecules and atoms, including magnetic resonance and nuclear moments. The book first offers information on nuclear moments in free atoms and molecules, including theoretical foundations of hyperfine structure, isotope shift, spectra of diatomic molecules, and vector model of molecules. The manuscript then takes a look at nuclear moments in liquids and crystals. Discussions focus on nuclear paramagnetic and magnetic resonance and nuclear quadrupole resonance. The text discusses nuclear moments and nucl

  20. Réponses comportementales du brochet (Esox lucius L. à un extrait épidermique de carassin doré (Carassius auratus L. en olfactomètre

    Directory of Open Access Journals (Sweden)

    SAGLIO Ph.

    1993-04-01

    Full Text Available Les effets de solutions brutes (EE et d'une fraction d'acides aminés libres reconstituée (FAA, issues d'un extrait épidermique de Carassin doré (Carassius auratus L., ont été analysés sur l'attraction et le comportement exploratoire du Brochet (Esox lucius L. en olfactomètre. Des effets significatifs ont été observés en réponse aux différentes solutions et doses testées (EE = 0,005 ; 0,05 ; 0,5 équivalent-carassin/l ; FAA = 0,5 équivalent-carassin/l. L'effet stimulant des solutions épidermiques brutes sur l'exploration varie en raison inverse de la concentration testée. L'activité de ces solutions sur l'attraction augmente avec la concentration. L'effet stimulant de la fraction d'acides aminés libres reconstituée sur l'exploration et sur l'attraction est apparu inférieur à celui observé en réponse à la solution brute. Ces résultats sont discutés à la lueur de données sur le rôle des sécrétions de la peau et des acides aminés dans la communication chimique chez les poissons.

  1. Terapias não farmacológicas no alívio da dor neuropática diabética: uma revisão bibliográfica Terapias no farmacológicas en el alivio del dolor neuropático diabético: una revisión bibliográfica Nonpharmacologic therapies in diabetic neuropathic pain: a review

    OpenAIRE

    Letícia Cunha Franco; Layz Alves Ferreira Souza; Ana Paula da Costa Pessoa; Lílian Varanda Pereira

    2011-01-01

    A neuropatia diabética dolorosa caracteriza-se pela dor de difícil controle. O objetivo do estudo foi analisar a produção bibliográfica a respeito das terapias não farmacológicas utilizadas no alívio dessa dor. Pesquisa bibliográfica, por meio de seis (6) fontes de dados, nos últimos 12 anos (1998 a 2010), utilizando os descritores diabetes, diabetes mellitus, neuropatia dolorosa, dor neuropática, tratamento e similares. Foram selecionados 13 artigos, que abordaram o uso de acupuntura, reike,...

  2. Origin of the Proton-transfer Step in the Cofactor-free (1H)-3-Hydroxy-4-oxoquinaldine 2,4-Dioxygenase

    Science.gov (United States)

    Hernandez-Ortega, Aitor; Quesne, Matthew G.; Bui, Soi; Heuts, Dominic P. H. M.; Steiner, Roberto A.; Heyes, Derren J.; de Visser, Sam P.; Scrutton, Nigel S.

    2014-01-01

    Dioxygenases catalyze a diverse range of chemical reactions that involve the incorporation of oxygen into a substrate and typically use a transition metal or organic cofactor for reaction. Bacterial (1H)-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase (HOD) belongs to a class of oxygenases able to catalyze this energetically unfavorable reaction without any cofactor. In the quinaldine metabolic pathway, HOD breaks down its natural N-heteroaromatic substrate using a mechanism that is still incompletely understood. Experimental and computational approaches were combined to study the initial step of the catalytic cycle. We have investigated the role of the active site His-251/Asp-126 dyad, proposed to be involved in substrate hydroxyl group deprotonation, a critical requirement for subsequent oxygen reaction. The pH profiles obtained under steady-state conditions for the H251A and D126A variants show a strong pH effect on their kcat and kcat/Km constants, with a decrease in kcat/Km of 5500- and 9-fold at pH 10.5, respectively. Substrate deprotonation studies under transient-state conditions show that this step is not rate-limiting and yield a pKa value of ∼7.2 for WT HOD. A large solvent isotope effect was found, and the pKa value was shifted to ∼8.3 in D2O. Crystallographic and computational studies reveal that the mutations have a minor effect on substrate positioning. Computational work shows that both His-251 and Asp-126 are essential for the proton transfer driving force of the initial reaction. This multidisciplinary study offers unambiguous support to the view that substrate deprotonation, driven by the His/Asp dyad, is an essential requirement for its activation. PMID:24482238

  3. Protonation/reduction dynamics at the [4Fe-4S] cluster of the hydrogen-forming cofactor in [FeFe]-hydrogenases.

    Science.gov (United States)

    Senger, Moritz; Mebs, Stefan; Duan, Jifu; Shulenina, Olga; Laun, Konstantin; Kertess, Leonie; Wittkamp, Florian; Apfel, Ulf-Peter; Happe, Thomas; Winkler, Martin; Haumann, Michael; Stripp, Sven T

    2018-01-31

    The [FeFe]-hydrogenases of bacteria and algae are the most efficient hydrogen conversion catalysts in nature. Their active-site cofactor (H-cluster) comprises a [4Fe-4S] cluster linked to a unique diiron site that binds three carbon monoxide (CO) and two cyanide (CN - ) ligands. Understanding microbial hydrogen conversion requires elucidation of the interplay of proton and electron transfer events at the H-cluster. We performed real-time spectroscopy on [FeFe]-hydrogenase protein films under controlled variation of atmospheric gas composition, sample pH, and reductant concentration. Attenuated total reflection Fourier-transform infrared spectroscopy was used to monitor shifts of the CO/CN - vibrational bands in response to redox and protonation changes. Three different [FeFe]-hydrogenases and several protein and cofactor variants were compared, including element and isotopic exchange studies. A protonated equivalent (HoxH) of the oxidized state (Hox) was found, which preferentially accumulated at acidic pH and under reducing conditions. We show that the one-electron reduced state Hred' represents an intrinsically protonated species. Interestingly, the formation of HoxH and Hred' was independent of the established proton pathway to the diiron site. Quantum chemical calculations of the respective CO/CN - infrared band patterns favored a cysteine ligand of the [4Fe-4S] cluster as the protonation site in HoxH and Hred'. We propose that proton-coupled electron transfer facilitates reduction of the [4Fe-4S] cluster and prevents premature formation of a hydride at the catalytic diiron site. Our findings imply that protonation events both at the [4Fe-4S] cluster and at the diiron site of the H-cluster are important in the hydrogen conversion reaction of [FeFe]-hydrogenases.

  4. Prevalence of Anti Human Herpes Virus-6 IgG and its Receptor in Acute Leukemia (Membrane Cofactor Protein: MCP, CD46)

    International Nuclear Information System (INIS)

    Assem, M.M; El-Sharkawy, N.M.; Tarek, H.; Kamel, A.M.; Gad, W.H.; El-Rouby, M.N.; Ghaleb, F.M.

    2005-01-01

    CD46 is a membrane cofactor protein, which acts as a cofactor for factor I proteolytic cleavage of C3, so it protects the cells expressing it on their surface from autologous complement attack. It has been recently described as a receptor for HHV-6. Also, it has been shown to be highly expressed on malignant cells as compared to normal cells, thus playing a major role by which these cells, either cells of haematological malignancy or cells of other body cancers, can protect themselves against complement attack so they can survive and metastasize. Patients and methods: This study has been done to detect the sero prevalence of HHV-6 among 47 Egyptian adult cases of acute leukemia using the anti-HHV-6 IgG ELISA serological technique. CD46 receptor expression and immuno phenotyping technique were performed using FCM. Twenty nine of the cases were ANLL, while 18 were ALL cases. Sixteen age- and sex-matched control cases were also studied for both anti-HHV-6 IgG and CD46 receptor expression. HHV-6 IgG antibodies were encountered in 29 (100%), 14 (77.8%) and 12 (75%) of the ANLL, ALL and the control group, cases, respectively. CD46 expression was encountered in 21 (72.4%) of the ANLL cases and in 10 (55.6%) of the ALL cases. Concordance between HHV6 sero positivity and CD46 expression was encountered in 31 cases (29 positive and 2 negative). Dis concordance was encountered in 16 cases with 14 showing HHV-6 IgG sero positivity with no CD46 expression and 2 showing the reverse. The lack of significant correlation between CD46 expression and sero positivity would exclude CD46 expression as a cause of contracting HHV-6 infection in leukemic patients

  5. Down-regulation of viral replication by adenoviral-mediated expression of siRNA against cellular cofactors for hepatitis C virus

    International Nuclear Information System (INIS)

    Zhang Jing; Yamada, Osamu; Sakamoto, Takashi; Yoshida, Hiroshi; Iwai, Takahiro; Matsushita, Yoshihisa; Shimamura, Hideo; Araki, Hiromasa; Shimotohno, Kunitada

    2004-01-01

    Small interfering RNA (siRNA) is currently being evaluated not only as a powerful tool for functional genomics, but also as a potentially promising therapeutic agent for cancer and infectious diseases. Inhibitory effect of siRNA on viral replication has been demonstrated in multiple pathogenic viruses. However, because of the high sequence specificity of siRNA-mediated RNA degradation, antiviral efficacy of siRNA directed to viral genome will be largely limited by emergence of escape variants resistant to siRNA due to high mutation rates of virus, especially RNA viruses such as poliovirus and hepatitis C virus (HCV). To investigate the therapeutic feasibility of siRNAs specific for the putative cellular cofactors for HCV, we constructed adenovirus vectors expressing siRNAs against La, polypyrimidine tract-binding protein (PTB), subunit gamma of human eukaryotic initiation factors 2B (eIF2Bγ), and human VAMP-associated protein of 33 kDa (hVAP-33). Adenoviral-mediated expression of siRNAs markedly diminished expression of the endogenous genes, and silencing of La, PTB, and hVAP-33 by siRNAs substantially blocked HCV replication in Huh-7 cells. Thus, our studies demonstrate the feasibility and potential of adenoviral-delivered siRNAs specific for cellular cofactors in combating HCV infection, which can be used either alone or in combination with siRNA against viral genome to prevent the escape of mutant variants and provide additive or synergistic anti-HCV effects

  6. Effects of a psychoeducational program for chronic pain management Efectos de un programa psicoeducativo en el control del dolor crónico Efeitos de um programa psicoeducativo no controle da dor crônica

    Directory of Open Access Journals (Sweden)

    Marina de Góes Salvetti

    2012-10-01

    Full Text Available AIMS: to evaluate the impact of an eight-week psychoeducational program focused on pain intensity, disability and depressive symptoms of patients with chronic pain. METHOD: 79 patients with chronic pain of different etiologies composed the sample. Patients were assessed before, at the end of the intervention and six months after the intervention. The program was developed by a nurse using cognitive-behavioral strategies and was conducted by a multidisciplinary team. The Wilcoxon test was used to compare repeated measures. RESULTS: the participants' mean age was 53 years old, most were female (91%, with an average of 9.5 years of schooling and an average pain duration of 9.9 years. Significant reduction in pain intensity (pOBJETIVOS: evaluar el impacto de un Programa psicoeducativo de ocho semanas en la intensidad del dolor, incapacidad y síntomas depresivos de pacientes con dolor crónico. MÉTODO: 79 pacientes con dolor crónico de diferentes etiologías compusieron la muestra. Los participantes fueron evaluados antes y al final del Programa y seis meses después. El Programa fue desarrollado por una enfermera, utilizó estrategias cognoscitivo-comportamentales y fue aplicado por un equipo multidisciplinar. La prueba no paramétrico de Wilcoxon fue utilizado para comparar medidas repetidas. RESULTADOS: la mayoría de los participantes eran del sexo femenino (91%, con edad media de 53 años, escolaridad media de 9,5 años y duración media del dolor de 9,9 años. Al final del Programa se observó reducción significativa en la intensidad del dolor (pOBJETIVOS: avaliar o impacto de um programa programa psicoeducativo de oito semanas na intensidade da dor, incapacidade e sintomas depressivos de pacientes com dor crônica. MÉTODO: 79 setenta e nove pacientes com dor crônica de diferentes etiologias compuseram a amostra. Os participantes foram avaliados antes e ao final do pPrograma e seis meses após. O pPrograma foi desenvolvido por uma

  7. Influência de elementos meteorológicos na dor de pacientes com osteoartrite: revisão da literatura Influence of meteorological elements on osteoarthritis pain: a review of the literature

    Directory of Open Access Journals (Sweden)

    Evânia Claudino Queiroga de Figueiredo

    2011-12-01

    Full Text Available Apesar de frequente a afirmação de que as condições do tempo modificam a intensidade da dor na osteoartrite (OA, essa influência é controversa e de difícil mensuração. Esta revisão tem como objetivo analisar os artigos relacionados à influência de elementos meteorológicos na dor da OA. A revisão da literatura foi realizada com um levantamento bibliográfico junto aos bancos de dados MEDLINE e LILACS, e por busca ativa em lista de referências bibliográficas dos artigos e revisões recuperados. Os critérios de inclusão para esta análise foram estudos prospectivos que avaliaram a presença da dor em pacientes com OA relacionada a alguma variável meteorológica. Os artigos foram publicados em português, inglês e espanhol. Do total de 247 resumos analisados, foram incluídos oito (3,2% artigos, provenientes dos bancos de dados eletrônicos consultados (n = 7 e da busca ativa (n = 1. Em cinco dos estudos incluídos, pressão atmosférica foi a variável que apresentou influência na dor de pacientes com OA com mais frequência, enquanto precipitação foi a que menos apresentou relação com os sintomas de OA; vento foi pouco analisado. Apesar da diversidade metodológica e dos vieses dos estudos analisados, existe uma tendência à confirmação da influência das condições do tempo na intensidade da dor em pacientes com OA, em especial nas publicações mais recentes. Ainda são necessários mais estudos para se ter uma boa evidência do efeito dos elementos meteorológicos na dor dos pacientes com OA e para avaliar sua interferência na realização das atividades diárias e na qualidade de vida.Despite the frequent assertion that the weather conditions change the intensity of pain in osteoarthritis (OA, this influence is controversial and difficult to measure. This analysis aims to review articles related to the influence of meteorological elements in the OA pain. The literature review was performed with the bibliographical

  8. Efeito da acupuntura na melhora da dor, sono e qualidade de vida em pacientes fibromiálgicos: estudo preliminar Effect of acupuncture on pain, sleep and quality of life improvement in fibromyalgia patients: preliminary study

    Directory of Open Access Journals (Sweden)

    Raymond S. Takiguchi

    2008-09-01

    Full Text Available A fibromialgia é uma síndrome definida por dor crônica generalizada e em pelo menos 11 dos 18 tender points, pontos dolorosos específicos. Este ensaio clínico randômico visou verificar a eficácia da acupuntura na melhora da dor, sono e qualidade de vida de pacientes fibromiálgicas. Dentre 20 mulheres com média de idade 44 anos, com diagnóstico de fibromialgia segundo critérios do Colégio Americano de Reumatologia, finalizaram o estudo 12, distribuídas aleatoriamente em dois grupos: A (GA, n=5, que recebeu acupuntura segundo a medicina tradicional chinesa; e B (GB, n=7, que teve a inserção de agulhas nos tender points base do occipital, trapézio, supraespinhoso e epicôndilo lateral. A dor foi avaliada por escala visual analógica e dolorimetria; o sono, pelo Inventário do Sono; e a qualidade de vida, pelo Questionário de Impacto da Fibromialgia (QIF. Os grupos receberam acupuntura uma vez por semana, durante oito semanas, com inserção de oito agulhas por 25 minutos. Os dados foram tratados estatisticamente, adotando-se o nível de significância ±=0,05. No GA, houve melhora estatisticamente significante do sono; e no GB, na dor, limiar de dor nos tender points, no sono e nos itens do QIF dor, cansaço matinal, ansiedade e depressão (pFibromyalgia is a syndrome defined by chronic widespread pain and sensitivity to pressure at at least 11 of 18 tender points. The aim of this random blind clinical trial was to assess the effectiveness of acupuncture on pain relief, on quality of sleep and life in fibromyalgia patients. From 20 female fibromyalgic patients (diagnosed according to the American College of Rheumatology, mean aged 44 years, 12 completed the study, randomly assigned into two groups: group A (GA, n=5 received acupuncture according to the traditional Chinese medicine; and group B (GB, n=7 received acupuncture at eight tender points: at the occiput, trapezius muscle, supraspinatus muscle, and lateral epicondyle. Pain

  9. Relação entre intensidade de dor e capacidade funcional em indivíduos obesos com osteoartrite de joelho Relationship between pain intensity and functional capacity of obese individuals with knee osteoarthritis

    Directory of Open Access Journals (Sweden)

    KSS Vasconcelos

    2006-01-01

    Full Text Available CONTEXTUALIZAÇÃO: A osteoartrite (OA de joelho é uma doença crônica que acomete a cartilagem articular, provocando alterações ósseas, dor e rigidez à movimentação. A obesidade é um dos seus principais fatores de risco. As queixas de dificuldades funcionais são freqüentes, especialmente para a locomoção, que se torna mais lenta. Com os crescentes níveis de obesidade no Brasil, torna-se importante compreender como a OA de joelho afeta a capacidade funcional humana, a fim de se elaborar medidas de tratamento e prevenção. OBJETIVO: Analisar a influência da intensidade de dor, gravidade radiográfica, grau de obesidade e duração dos sintomas na capacidade funcional de indivíduos obesos com OA de joelho. MÉTODO: A intensidade de dor foi medida pelo questionário Western Ontario and McMaster Universities Index (WOMAC e durante os testes funcionais. A gravidade radiográfica foi analisada pela classificação Kellgren-Lawrence e o grau de obesidade pelo índice de massa corporal (IMC. Foram realizados quatro testes funcionais de velocidade: marcha usual e rápida, subir e descer escadas. RESULTADOS: A amostra foi constituída de 31 mulheres e 4 homens, com idade média de 51,65 ± 10,72 anos e IMC médio de 41,16 ± 8,37 kg/m². As atividades em escadas estavam associadas a níveis mais intensos de dor. Apenas a intensidade de dor apresentou correlações significativas com os resultados nos testes de velocidade. CONCLUSÃO: A intensidade de dor é um fator que influencia a realização de atividades funcionais em indivíduos obesos com OA de joelho, mas outros estudos são necessários para identificar os fatores determinantes de capacidade funcional nesta população.BACKGROUND: Knee osteoarthritis is a chronic disease that affects joint cartilage, causing bone structure alterations, pain and stiffness during movement. Obesity is one of its principal risk factors. Complaints about functional disability are frequent, especially

  10. A cultura permeando os sentimentos e as reações frente à dor La cultura permeando los sentimentos y las reacciones frente al dolor Culture permeating the feelings and the reactions in the face of pain

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes Denardin Budó

    2007-03-01

    Full Text Available Este estudo descreve a percepção e os significados da dor em adultos usuários do SUS. A popu-lação compreendeu 60 pacientes que buscaram o serviço no período. A pesquisa foi do tipo exploratório-descritiva, cujos dados foram coletados com entrevista semi-estruturada e analisados qualitativamente, constituindo temas que emergiram, sendo agrupados por categorias. Evidenciou-se que "o significado da dor" revelou o predomínio do entendimento da dor como uma questão física; apontou a dor relacionada também a questões emocionais e sentimentais, religiosas e humanas. "A reação de homens e mulheres frente à dor" é percebida diferentemente conforme o sexo feminino e masculino. Em "como você se sente nas situações em que tem dor?", as respostas variaram entre afetivas, cognitivas e comportamentais.Em este estudio se describe la percepción y los significados del dolor en adultos usuarios del Sistema Único de Salud (SUS. La población comprendió 60 pacientes que buscaron el servicio en el período. La investigación fue de tipo descriptivo exploratorio, cuyos datos fueron recolectados con una entrevista semi-estructurada y analizados cualitativamente, constituyendo temas que emergieron siendo agrupados por categorías. Se evidenció que "el significado del dolor" reveló el predominio del entendimiento del dolor como una cuestión física; apuntó el dolor relacionado también a cuestiones emocionales y sentimentales, religiosas y humanas. "La reacción de hombres y mujeres frente al dolor" es percibida de manera diferente conforme el sexo femenino y masculino. En "cómo se siente en situaciones en que tiene dolor?", las respuestas variaron entre afectivas, cognitivas y de comportamiento.This study describes the perception of pain and the meanings it has for adults who use the Brazilian public health system, the Sistema Único de Saúde (SUS. The sample was comprised of 60 patients who sought the service in the period. This is a

  11. Redução da dor em mulheres com osteoporose submetidas a um programa de atividade física Pain relief in women with osteoporosis after a physical activity program

    Directory of Open Access Journals (Sweden)

    Patricia Driusso

    2008-09-01

    Full Text Available Este estudo teve por objetivo avaliar a dor e o consumo de analgésicos em mulheres com osteoporose, após a realização de um programa de atividade física. Participaram do estudo 15 mulheres com média de idade 59±7,6 anos, com diagnóstico densitométrico em L2-L4 de osteoporose e que haviam feito uso de analgésicos para dorsalgia pelo menos três vezes por semana no mês precedente à avaliação inicial. A dor foi avaliada por questões extraídas do Osteoporosis Assessment Questionnaire, aplicadas antes e após um programa de atividade física; o escore variou de 0 (melhor, sem dor a 10 (pior, dor diária. O programa, que consistiu em caminhadas, exercícios livres de membros superiores e inferiores e relaxamento, foi realizado duas vezes por semana durante 28 semanas consecutivas. Os dados foram tratados estatisticamente. Comparando-se as pontuações obtidas, a dor apresentou uma diminuição significativa entre a avaliação inicial (7,33±3,05 e final (4,17±2,61, p=0,0007. Observou-se também uma redução no consumo de analgésicos. Esses resultados sugerem que o programa de atividade física foi efetivo para a diminuição da dor, contribuindo para a melhora da qualidade de vida das mulheres com osteoporose.This paper aimed at evaluating the effect of a physical activity program onto the level of pain as perceived by women with osteoporosis. Fifteen women (mean age 59±7.6 years old with bone-densitometry diagnosis of lumbar osteoporosis took part in the study; they all took analgesics at least thrice a week in the month prior to the study. Pain was assessed by questions extracted from the Osteoporosis Assessment Questionnaire both before and after the program; scores ranged from 0 (no pain to 10 (pain everyday. The program consisted of walking, lower and upper limb free exercises, massage, and relaxation, twice a week, during 28 weeks. Data were statistically analysed. A significant decrease in pain was found after the program

  12. The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals.

    Science.gov (United States)

    Nautiyal, Jaya; Steel, Jennifer H; Mane, Meritxell Rosell; Oduwole, Olayiwola; Poliandri, Ariel; Alexi, Xanthippi; Wood, Nicholas; Poutanen, Matti; Zwart, Wilbert; Stingl, John; Parker, Malcolm G

    2013-03-01

    Nuclear receptor interacting protein (Nrip1), also known as RIP140, is a co-regulator for nuclear receptors that plays an essential role in ovulation by regulating the expression of the epidermal growth factor-like family of growth factors. Although several studies indicate a role for RIP140 in breast cancer, its role in the development of the mammary gland is unclear. By using RIP140-null and RIP140 transgenic mice, we demonstrate that RIP140 is an essential factor for normal mammary gland development and that it functions by mediating oestrogen signalling. RIP140-null mice exhibit minimal ductal elongation with no side-branching, whereas RIP140-overexpressing mice show increased cell proliferation and ductal branching with age. Tissue recombination experiments demonstrate that RIP140 expression is required in both the mammary epithelial and stromal compartments for ductal elongation during puberty and that loss of RIP140 leads to a catastrophic loss of the mammary epithelium, whereas RIP140 overexpression augments the mammary basal cell population and shifts the progenitor/differentiated cell balance within the luminal cell compartment towards the progenitors. For the first time, we present a genome-wide global view of oestrogen receptor-α (ERα) binding events in the developing mammary gland, which unravels 881 ERα binding sites. Unbiased evaluation of several ERα binding sites for RIP140 co-occupancy reveals selectivity and demonstrates that RIP140 acts as a co-regulator with ERα to regulate directly the expression of amphiregulin (Areg), the progesterone receptor (Pgr) and signal transducer and activator of transcription 5a (Stat5a), factors that influence key mitogenic pathways that regulate normal mammary gland development.

  13. Unidades tectónicas y estructura general de la Sierra de Gádor y zonas adyacentes (Cordillera Bética, provincia de Almería: implicaciones paleogeográficas

    Directory of Open Access Journals (Sweden)

    Delgado Salazar, F.

    2007-06-01

    Full Text Available In the Sierra de Gádor (Almeria province terrains belonging to the Internal Betic Zone crop out. According to stratigraphic, structural and petrologic features we have recognised five tectonic units. These units are called, from bottom to top, Gádor-Turón, Laujar, Murtas, Felix and Chirán unit. The lower fourth are ascribed to the Alpujárride Complex, whilst the last one is ascribed to the Maláguide Complex. We also discuss if the Felix unit may be included in the Intermediate Units. The Felix unit represents the Triassic palaeogeographic transition between the Alpujárride and the Maláguide, and it was located between both complexes during the alpine tectono-metamorphic evolution of the Betic Cordillera.En la Sierra de Gádor (provincia del Almería afloran rocas pertenecientes a la Zona Interna de la Cordillera Bética. En este sector hemos reconocido un total de cinco unidades tectónicas, en función de sus características estratigráficas, estructurales y petrológicas. Estas unidades se denominan, de abajo a arriba, unidad de Gádor-Turón, unidad de Laujar, unidad de Murtas, unidad de Felix y unidad de Chirán. Las cuatro más bajas las asignamos al Complejo Alpujárride, mientras que la más alta la asignamos al Complejo Maláguide. Se discute además la posible inclusión de la unidad de Felix dentro de las denominadas Unidades Intermedias. La unidad de Felix representa el tránsito paleogeográfico durante el Triásico entre el dominio Alpujárride y el Maláguide, y estaría situada entre ambos complejos durante la evolución tectono-metamórfica alpina de la Cordillera Bética.

  14. Luto e Sociedade no Brasil do final do século XX. O imaginário sobre a morte e o morrer, a dor e a perda na cidade de João Pessoa, PB

    Directory of Open Access Journals (Sweden)

    Mauro Guilherme Pinheiro Koury

    2011-04-01

    Full Text Available Este artigo tem por objetivo a compreensão das apreensões imaginárias sobre as noções de perda, e de dor, da morte e do morrer entre os habitantes da cidade de João Pessoa, capital do estado brasileiro da Paraíba. O que se espera é a apreensão das formas societárias contidas no imaginário dos informantes sobre o processo de morte e o processo de perda enquanto significados socialmente esperados de conduta e de valores frente a esses processos.

  15. Musculoskeletal pain, profile and quality of life of individuals with sickle cell disease Dor osteomuscular, perfil e qualidade de vida de indivíduos com doença falciforme

    Directory of Open Access Journals (Sweden)

    Daniela G. Ohara

    2012-10-01

    ções ocasionam vaso-oclusão, resultando em isquemia, inflamação, disfunções, dor e hemólise crônica, gerando danos irreversíveis, comprometendo a qualidade de vida. OBJETIVO: Verificar a relação entre a dor osteomuscular, considerando sua localização corporal, e características sociais, econômicas e de qualidade de vida em indivíduos com doença falciforme. MÉTODOS: Foram coletadas informações pessoais, sociais e econômicas, além de dados do Questionário Nórdico de Sintomas Osteomusculares (QNSO e Short Form 36 em 27 indivíduos. Os dados foram analisados descritivamente por meio de frequências e porcentagens. A análise inferencial usou o teste do qui-quadrado (variáveis dicotômicas e t de Student (variáveis contínuas, com significância de 5%. Análises de regressão logística utilizaram como variáveis dependentes cada uma das que se relacionaram com dor. RESULTADOS: A média de idade foi de 31,77 anos, predominando sexo masculino, negros, emprego ativo, escolaridade média e rendimento inferior a três salários mínimos. Quadril/membros inferiores, região dorsal, lombar e braços foram mais acometidos pela dor. A capacidade funcional apresentou o maior valor, e saúde mental, o menor. Aspectos físicos foram comprometidos pela dor nos braços, coluna dorsal e lombar. Aspectos sociais não se associaram com a dor, indicando influência de outros fatores. A dor nos braços foi mais frequente entre os negros e os com baixa escolaridade. CONCLUSÃO: A dor nas regiões corporais analisadas relacionou-se com a raça e a escolaridade e com todos os domínios referentes ao componente físico do SF-36. Os componentes vitalidade e saúde mental apresentaram associação significativa com a dor.

  16. Pain in photodynamic therapy: mechanism of action and management strategies Dor na terapia fotodinâmica: mecanismo de ação e estratégias de manejo

    Directory of Open Access Journals (Sweden)

    Yuri Nogueira Chaves

    2012-08-01

    Full Text Available Photodynamic therapy involves administration of a photosensitizing drug and its subsequent activation by irradiation with a light source at wavelengths matching the absorption spectrum of the photosensitizer. In many countries around the world, topical photodynamic therapy has been approved for treatment of cutaneous oncologic conditions such as actinic keratosis, Bowen's disease, and superficial basal cell carcinoma. Multicenter, randomized, controlled studies have confirmed its efficacy and superior cosmetic outcomes compared to conventional therapies. Nevertheless, this therapeutic method presents some adverse effects, such as erythema, edema, pigmentation, pustules, and pain. There is no doubt that pain is the most severe of the adverse effects, being sometimes responsible for definitive treatment interruption. The pain mechanism has not yet been fully understood, which makes complete pain control a challenge to be conquered. In spite of that, this literature review presents some useful pain management strategies as well as the most important pain-related factors in photodynamic therapy.A terapia fotodinâmica consiste na administração de uma droga fotossensibilizante e sua subseqüente irradiação com uma fonte de luz de espectro correspondente ao do seu fotossensibilizador. Em diversos países do mundo, a terapia fotodinâmica tópica é aprovada para o tratamento de condições oncológicas cutâneas como queratoses actínicas, doença de Bowen e carcinoma basocelular superficial. Estudos multicêntricos controlados e randomizados confirmam sua eficácia e seus resultados cosméticos superiores em relação às terapias convencionais. No entanto, existem alguns efeitos adversos inerentes a esse método terapêutico, como eritema, edema, pigmentação, pústulas e dor. Essa última é, sem dúvida, a mais importante deles, chegando a ser responsável pela interrupção definitiva do tratamento em alguns casos. O mecanismo dessa dor

  17. Efeitos da terapia manual sobre a dor em mulheres com fibromialgia: uma revisão de literatura = Effects of manual therapy on pain in women with fibromyalgia: a literature review

    Directory of Open Access Journals (Sweden)

    Ziani, Marciele Monzon

    2017-01-01

    Full Text Available Objetivo: Avaliar, através de uma revisão de literatura, os efeitos da terapia manual sobre a dor em mulheres com fibromialgia (FM. Materiais e Métodos: Trata-se de uma revisão integrativa, realizada nas bases de dados Pubmed, Lilacs, PEDro e Scielo, selecionando ensaios clínicos ou estudos quase experimental, nos idiomas português, inglês e espanhol, que objetivassem avaliar os efeitos da terapia manual sobre a dor em mulheres com FM. As palavras-chave e os operadores boleanos utilizados foram: “Musculoskeletal Manipulations OR manual therapy AND Fibromyalgia”. Resultados: De um total de 133 artigos encontrados, 9 deles foram selecionados para inclusão final no presente estudo. Desses, grande parte (55,5% dos estudos foram realizados no continente Europeu e apenas um foi conduzido na população brasileira. O tamanho amostral dos artigos variou de 12 a 86 indivíduos entre cada grupo estudado, sendo que 8 (88,8% deles utilizaram os critérios do Colégio Americano de Reumatologia para diagnóstico clínico da FM. As técnicas mais utilizadas foram à liberação miofascial (33,3%, a massagem de tecido conjuntivo (22,2% e a drenagem linfática manual (22,2%, sendo que a duração total do tratamento oscilou entre 3 e 20 semanas. Todos os estudos verificaram melhora da dor através das técnicas de terapia manual, com efeitos positivos também sobre os sintomas de ansiedade, sono, função física e qualidade de vida. Conclusão: Os achados da presente revisão demonstram que as técnicas de terapia manual parecem benéficas para o tratamento da dor em mulheres portadoras de FM

  18. A associação de haloperidol, dexametasona e ondansetrona reduz a intensidade de náusea, dor e consumo de morfina após gastrectomia vertical laparoscópica

    Directory of Open Access Journals (Sweden)

    Márcio Luiz Benevides

    2013-10-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Náusea e vômito pós-operatório (NVPO ocorrem frequentemente após cirurgia bariátrica laparoscópica. A associação de haloperidol, dexametasona e ondansetrona pode reduzir esses eventos indesejáveis. O objetivo deste estudo foi avaliar a intensidade de náusea e dor, o número de episódios de vômito e o consumo de morfina no pós-operatório (PO de pacientes obesos submetidos à gastrectomia vertical laparoscópica (GVL. MÉTODO: Estudo clínico, aleatorizado, controlado e duplamente encoberto feito em 90 pacientes com índice de massa corporal > 35 kg.cm-2. Os pacientes foram distribuídos em três grupos de 30 para receberem no Grupo O: ondansetron 8 mg; no Grupo DO: ondansetron 8 mg e dexametasona 8 mg e no Grupo HDO: ondansetron 8 mg, dexametasona 8 mg e haloperidol 2 mg. Foram avaliados a intensidade de náusea e dor, por meio de escala numérica verbal, o número cumulativo de episódios de vômito e o consumo de morfina no período de 0-2, 2-12, 12-24 e 24-36 horas de PO. RESULTADOS: A intensidade de náusea foi menor no Grupo HDO comparado com o Grupo O (p = 0,001, a intensidade da dor foi menor no Grupo HDO comparado com o Grupo O (p = 0,046 e o consumo de morfina no Grupo HDO foi menor do que no Grupo O (p = 0,037. Não houve diferença do número de episódios de vômito entre os grupos (p = 0,052. CONCLUSÃO: A associação de haloperidol, dexametasona e ondansetron promoveu redução da intensidade de náusea, da dor e do consumo de morfina no PO de pacientes obesos submetidos à GVL.

  19. Controle da dor por bloqueio peridural e incidência de disritmias cardíacas no pós-operatório de procedimentos cirúrgicos torácicos e abdominais altos: estudo comparativo

    Directory of Open Access Journals (Sweden)

    Rohnelt Machado de Oliveira

    2012-02-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Operações no abdome superior e tórax provocam intensa dor. Entre as principais complicações da dor pós-operatória estão as complicações cardiocirculatórias. O objetivo deste trabalho foi testar a hipótese de que a analgesia pós-operatória com o emprego de anestésicos locais mais opioides espinhais pode reduzir a incidência de complicações cardiovasculares no pós-operatório de pacientes nessas condições, comparando-se a métodos clássicos de analgesia pós-operatória, opioides e AINES, administrados segundo demanda do paciente. MÉTODO: Oitenta pacientes adultos ASA I e II, sem alterações ECG, alocados em dois grupos de 40: Grupo A, sob anestesia geral com propofol, cisatracúrio e isoflurano, associado à anestesia peridural, com cateter e controle da analgesia pós-operatória com bupivacaína e morfina peridural; e Grupo B, sob anestesia geral com as mesmas drogas e doses que o Grupo A, mais analgesia pós-operatória realizada com AINES e morfina endovenosa no final da operação e em intervalos regulares. Em ambos foi aplicado Holter por 24 horas. A avaliação da dor foi realizada pela escala analógica visual. RESULTADOS: Na avaliação da dor observou-se no Grupo A evidente predomínio do escore 0 (p 50 anos (22,2% versus 0,0%. p = 0,26. Não se observou diferença significativa da frequência cardíaca entre os grupos (p > 0,05. CONCLUSÕES: A melhor qualidade da analgesia no pós-operatório, realizada nos pacientes do Grupo A, reduziu a incidência de complicações cardiovasculares

  20. Dor na criança desnutrida: percepção da mãe Dolor en el niño malnutrido: percepción de la madre Pain in undenourished children: the mother's perception

    Directory of Open Access Journals (Sweden)

    Larissa Coelho Barbosa

    2005-08-01

    Full Text Available O objetivo foi identificar a percepção da mãe quanto a dor no seu filho desnutrido. Pesquisa de natureza qualitativa, utilizando entrevistas semi-estruturadas no Instituto de Prevenção à Desnutrição e a Excepcionalidade - IPREDE (Fortaleza-Ceará. As informantes foram mães que acompanhavam seus filhos desnutridos. De acordo com a análise surgiram as categorias: Busca à Instituição; Descrição da dor e Como cuidar da dor. Conclui-se, a necessidade de um trabalho da sociedade, respeitando os direitos do cidadão e sua cultura, com o intuito de reverter a dor na criança desnutrida.El objetivo de esa investigación cualitativa era identificar la opinión de madres respecto al dolor de su hijo malnutrido. Se realizó entrevistas semiestructuradas en el Instituto para la Prevención a la Desnutrición y Excepcionalidad - IPREDE (Fortaleza-Ceará-Brasil. Los participantes fueron las madres que acompañaban a sus hijos malnutridos. El análisis reveló las siguientes categorías: Búsqueda de la institución; Descripción del dolor y Cómo cuidar del dolor. Se concluye que es necesario un trabajo de la sociedad, respetando los derechos del ciudadano y su cultura, con objeto de revertir el dolor del niño malnutrido.This qualitative study aimed to identify how mothers perceive pain in their undernourished children. Semistructured interviews were realized at the Institute for the Prevention of Malnutrition and Exceptionality - IPREDE (Fortaleza-Ceará-Brazil. Participants were mothers who accompanied their undernourished children. Data analysis revealed the following categories: Coming to the Institution; Pain description and How to take care of the pain. Society needs to take actions, in respect of citizens' rights and culture, with a view to reverting this picture of pain in undernourished children.

  1. Ser mulher dói: relato de um caso clínico de dor crônica vinculada à construção da identidade feminina

    Directory of Open Access Journals (Sweden)

    Josiane Bocchi

    Full Text Available O presente artigo apresenta um caso clínico de dor crônica atendido no Ambulatório de Psicologia Médica do HCFMRP-USP e discute o alcance da linguagem sobre o corpo, a presença de aspectos inconscientes na formação de sintomas físicos e a relação entre queixa somática e história afetiva. Propõe uma reflexão sobre a inter-relação entre os domínios médico e psicológico.

  2. Dor torácica no transtorno de pânico: sintoma somático ou manifestação de doença arterial coronariana?

    OpenAIRE

    Soares Filho,Gastão Luiz Fonseca; Valença,Alexandre Martins; Nardi,Antonio Egidio

    2007-01-01

    O transtorno do pânico (TP) pertence ao grupo dos transtornos de ansiedade caracterizado por repetidos e inesperados ataques de pânico, nos quais predominam os sintomas somáticos e intensa apreensão relacionada à idéia de perda de controle ou morte iminente. Entre os sintomas somáticos que o paciente pode apresentar, a dor torácica exerce papel preponderante, reforçando a idéia de que ele esteja desenvolvendo problema cardiovascular grave, ameaçador à vida, levando à repetida busca por atendi...

  3. Prevalência de dor nas costas e fatores associados em adultos do sul do Brasil: estudo de base populacional Prevalence and associated factors of back pain in adults from southern Brazil: a population-based study

    Directory of Open Access Journals (Sweden)

    Gustavo D. Ferreira

    2011-02-01

    Full Text Available OBJETIVOS: Determinar a prevalência de dor nas costas e fatores associados em uma amostra representativa da cidade de Pelotas, RS, Brasil. MÉTODOS: Estudo transversal que avaliou 972 adultos com idade entre 20 e 69 anos, de ambos os sexos, moradores da zona urbana do município. O questionário aplicado incluiu questões socioeconômicas, demográficas, comportamentais e de saúde. Dor nas costas foi definida como qualquer dor ou desconforto em algum local das costas nos últimos 12 meses, seja na região cervical, torácica ou lombar. RESULTADOS: A prevalência de dor nas costas foi de 63,1% (IC95% 60,0 a 66,1, sendo a região lombar a mais referenciada (40%. Sexo feminino 1,24 (1,12 a 1,37 e percepção ruim de saúde (pOBJECTIVES: To identify the prevalence of spinal pain and possible prognostic factors in a representative sample of Pelotas, RS, Brazil. METHODS: Cross-sectional study evaluated 972 adults aged between 20 and 69 years, of both sexes, residents in a urban area. The questionnaire included socio-economic, demographics, behavioral and health-related questions. Spinal pain was defined as any pain or discomfort in the spine somewhere in the last 12 months, either in the cervical, thoracic or lumbar area. RESULTS: The prevalence of spinal pain was 63.1% (95% CI 60.0 to 66.1 being lower back the most prevalent condition (40%. Female gender 1.24 (1.12 to 1.37 and poor health status(p<0.001 were the variables that remained associated with the presence of spinal pain in the final model. CONCLUSIONS: The prevalence of back pain is important as it is associated with activity limitation and with health care utilization.

  4. Nuclear power

    International Nuclear Information System (INIS)

    Abd Khalik Wood

    2005-01-01

    This chapter discussed the following topics related to the nuclear power: nuclear reactions, nuclear reactors and its components - reactor fuel, fuel assembly, moderator, control system, coolants. The topics titled nuclear fuel cycle following subtopics are covered: , mining and milling, tailings, enrichment, fuel fabrication, reactor operations, radioactive waste and fuel reprocessing. Special topic on types of nuclear reactor highlighted the reactors for research, training, production, material testing and quite detail on reactors for electricity generation. Other related topics are also discussed: sustainability of nuclear power, renewable nuclear fuel, human capital, environmental friendly, emission free, impacts on global warming and air pollution, conservation and preservation, and future prospect of nuclear power

  5. Avaliação da sensibilidade do questionário de triagem para dor orofacial e desordens temporomandibulares recomendado pela Academia Americana de Dor Orofacial The sensibility appreciation of the questionnaire for selection of orofacial pain and temporomandibular disorders recommended by the American Academy of Orofacial Pain

    Directory of Open Access Journals (Sweden)

    Ana Paula S. Manfredi

    2001-01-01

    Full Text Available Introdução: As Desordens Temporomandibulares têm interpretação muito ampla e descrevem uma população geral de pacientes sofrendo de disfunção dos músculos e articulações da mandíbula, usualmente dolorosa¹. Além da queixa de dor nos maxilares, dores de ouvido, cabeça e face, os pacientes com essas desordens muitas vezes têm movimentos mandibulares limitados ou assimétricos, e os sons da Articulação Temporomandibulares (ATM mais descritos são os estalos. Objetivo: Com o intuito de fazer uma análise qualitativa e quantitativa do uso de um instrumento de auxílio diagnóstico, foi aplicado o "Questionário para Triagem para Dor Orofacial e DTM", recomendado pela Academia Americana de Dor Orofacial (Anexo 1, ainda não testado no Brasil. A população alvo foi de pacientes com queixas de dor não-dental na região orofacial, cefaléia, otalgia e/ou nas ATM que procuraram o ambulatório médico e odontológico (CSS/CECOM mantido pela Unicamp para o atendimento de sua comunidade interna. Forma de estudo: Prospectivo clínico randomizado. Método: O questionário foi aplicado em 46 pacientes (40 mulheres e 6 homens, e posteriormente foi realizado um exame clínico específico para diagnóstico das DTM. Resultados: A análise estatística revelou que este questionário apresenta uma sensibilidade de 85.37% e uma especificidade de 80% para pacientes portadores de desordens musculares da região orofacial (Kappa = 0,454 e uma baixa sensibilidade e especificidade para desordens intra-articulares (Kappa = 0,043. Conclusão: O questionário é útil e viável para uma pré-triagem das chamadas DTM, principalmente para os distúrbios miogênicos, mas não deve ser o único recurso utilizado para diagnóstico.Introduction: The Temporomandibular Joint Disorders (TMJ Disorders has very ample interpretation and describes a population of patients suffering from muscles dysfunctions and the muscles and toggles of jaw usually painful 1. Beyond

  6. Cicatrização da miotomia de Heller por acesso videolaparoscópico com e sem fundocardioplastia de dor associada, em porcos

    Directory of Open Access Journals (Sweden)

    João Luiz Moreira Coutinho Azevedo

    Full Text Available OBJETIVO: Comparar a cicatrização da miotomia esofagiana laparoscópica associada ou não à fundocardioplastia de Dor. MÉTODO: Foram utilizados 18 porcos, em três grupos de seis animais. No grupo A foi realizada miotomia esofagiana. No grupo B associou-se plicatura gástrica à miotomia. O grupo C foi sem miotomia. No 21º dia pós-operatório houve moldagem do lume para obter índices de estenose (IE na região da miotomia (RM e na transição esôfago-gástrica (I'E'. Foram também estudados aspectos macro e microscópicos. RESULTADOS: Duração maior (t de Student no grupo B (93,6 minutos que no A (45 minutos. Considerando- se o IE dos grupos A e B, não houve estenose e eles se equivaleram - Mann-Withney (-11.1% no grupo A e -12.7% no grupo B. O I'E' foi sempre maior que o IE - Wilcoxon (18% versus -11,1% no grupo A e 37,7 % versus -12.7% no grupo B. O I'E' do grupo B (37,7% foi o maior entre os grupos (Kruskal-Wallis: A: 18%; C: 15,5%. Houve regularidade macroscópica da região da miotomia do grupo A e deformidades com inflamação aguda persistente e granulomas no B. No grupo A houve epitelização mesotelial e no B a superfície cruenta permaneceu granulada. Na RM do grupo B, leucócitos (22 versus 8,6 do A e vasos (18,7 versus 9,7 da A foram mais numerosos. A fibrose foi mais profusa no grupo B (25,85 fibras versus 15,6 no A. CONCLUSÕES: A plicatura gástrica sobre a miotomia esofagiana propicia cicatrização menos adequada e é mais demorada que a miotomia isolada.

  7. Nuclear science

    International Nuclear Information System (INIS)

    1989-01-01

    This fact sheet answers specific questions about the Department of Energy's possible acquisition and conversion of a partially completed commercial nuclear power plant to a nuclear materials production facility. The nuclear power plant is the Washington Nuclear Plant number sign 1 owned by the Washington Public Power Supply System and is located on DOE's Hanford Reservation near Richland, Washington

  8. Nuclear science

    International Nuclear Information System (INIS)

    1989-04-01

    This report answers questions about the Department of Energy's possible acquisition and conversion of a partially completed commercial nuclear power plant to a nuclear materials production facility. The nuclear power plant is the Washington Nuclear Plant No.1 owned by the Washington Public Power Supply System and is located on DOE's Hanford Reservation near Richland, Washington

  9. Nuclear medicine

    International Nuclear Information System (INIS)

    Lentle, B.C.

    1986-01-01

    Several growth areas for nuclear medicine were defined. Among them were: cardiac nuclear medicine, neuro-psychiatric nuclear medicine, and cancer diagnosis through direct tumor imaging. A powerful new tool, Positron Emission Tomography (PET) was lauded as the impetus for new developments in nuclear medicine. The political environment (funding, degree of autonomy) was discussed, as were the economic and scientific environments

  10. Nuclear option

    Energy Technology Data Exchange (ETDEWEB)

    Kemm, K R

    1978-05-01

    The global outlook is that nuclear reactors are here to stay and South Africa has already entered the nuclear power stakes. This article discusses the rocketing oil prices, and the alternatives that can be used in power generation, the good safety record of the nuclear industry and the effect that South Africa's first nuclear power station should have on the environment.

  11. Nuclear resisters

    International Nuclear Information System (INIS)

    1981-01-01

    The booklet contains six papers by different authors, under the headings: dangers along the nuclear fuel cycle; the nuclear profiteers; the nuclear state is a police state; a non-disposable future (renewable energy sources, energy conservation); nuclear weapons - out of control; man made madness. (U.K.)

  12. Real-time Continuous Esophageal High-resolution Manometry (HRM) During Laparoscopic Heller Myotomy and Dor Fundoplication for the Treatment of Achalasia. A Promising Novelty in Regards of Perfecting Surgical Technique: Could It Guide Surgical Technique Toward Excellent Results?

    Science.gov (United States)

    Triantafyllou, Tania; Doulami, Georgia; Papailiou, Joanna; Mantides, Apostolos; Zografos, Georgios; Theodorou, Dimitrios

    2016-12-01

    High-resolution manometry (HRM) is the gold-standard diagnostic tool for achalasia of the esophagus. Laparoscopic Heller-Dor technique is the preferred surgical approach with success rate estimated 90%. The use of intraoperative HRM provides real-time estimation of intraluminal esophageal pressures and identifies the exact points of esophageal luminal pressure during laparoscopy. Ten patients with achalasia underwent surgery. All patients preoperatively completed 1 manometric study and Quality of Life questionnaires (EORTC QLQ-C30 version 3.0) with Eckardt scores. We collected intraoperative manometry data and repeated manometric studies, EORTC QLQ-C30, and Eckardt scores postoperatively. Median Eckardt score was decreased from 7.5 to 0.5, mean resting pressure decreased from 51.4 to 11.9 mm Hg, whereas mean residual pressure diminished from 45.9 to 9.5 mm Hg postoperatively. The simultaneous use of HRM during the Heller-Dor technique may lead to an individualized management of the disease.

  13. Dor muscular em cabeça e pescoço e medidas vocais acústicas de fonte glótica Head and neck muscles pain and glottic source acoustical vocal measures

    Directory of Open Access Journals (Sweden)

    Luane de Moraes Boton

    2012-02-01

    Full Text Available OBJETIVO: verificar a relação entre a presença de dor na musculatura da cabeça, face, boca e pescoço envolvidos no processo fisiológico da função mastigatória e nos aspectos lateral e posterior da articulação temporomandibular (ATM e medidas vocais acústicas da fonte glótica. MÉTODO: amostra de 24 mulheres com idades entre 16 e 56 anos com queixas e sintomatologia de Disfunção Temporomandibular (DTM. Aplicação de um questionário de anamnese, exame clínico específico para verificação da presença de dor na musculatura da cabeça, face, boca e pescoço e nas ATM; avaliações otorrinolaringológica, do sistema estomatognático, audiológica e gravação digital da voz com análise vocal acústica da fonte glótica por meio do software Multi Dimensional Voice Program Advanced da KayPENTAX. Os resultados obtidos foram analisados estatisticamente pelo teste do qui-quadrado ao nível de significância de 0,05. RESULTADOS: houve significância estatística entre: ausência de dor no masseter superficial e alteração do índice de turbulência vocal (VTI; ausência de dor no aspecto posterior da ATM e alteração do coeficiente de perturbação do pitch (PPQ e alteração da variação da frequência fundamental (vf0; presença de dor no pterigóideo medial e normalidade do grau de quebra vocal (DVB. CONCLUSÃO: verificou-se que não houve relação entre as medidas de voz alteradas e a presença de dor nos músculos avaliados, mas algumas medidas alteradas se relacionaram com a ausência de dor muscular, sugerindo que outros aspectos da DTM, que não a dor, podem ocasionar alteração de medidas vocais acústicas.PURPOSE: to check the relationship between pain presence in head, face, mouth and neck muscles involved in the physiological process of chewing function and in the lateral and posterior aspects of temporomandibular joint (ATM and acoustical glottic source vocal measures. METHOD: 24 women with ages varying between 16 and

  14. A enfermagem no manejo da dor em pessoas com úlcera venosa: revisão integrativa Nursing in the management of pain in people with venous ulcer: integrative review

    Directory of Open Access Journals (Sweden)

    Samilly Márjore Dantas Liberato

    2016-04-01

    Full Text Available Objetivo: sintetizar o conhecimento produzido sobre as intervenções utilizadas para o manejo da dor em pessoas com úlcera venosa. Métodos: revisão integrativa da literatura realizada em junho de 2013 nas bases de dados PubMed, CINAHL, ISI Web of Knowledge, SCOPUS, The Cochrane Library e LILACS. Para o levantamento das publicações foram utilizados descritores do vocabulário MeSH – Medical Subject Headings: “Venous ulcers”; “Pain Management” e “Nursing”.  Resultados: foram selecionados sete artigos e estes apresentaram intervenções do tipo farmacológicas - curativos contendo ibuprofeno, técnicas como musicoterapia, aromoterapia e laserterapia e participação em grupos de apoio. Conclusão: concluiu-se que existe um déficit de estudos sobre o manejo da dor, contudo sugere-se a implementação das atividades de intervenção encontradas para realização de uma assistência eficaz e holística.

  15. Dor e parestesias nos membros superiores e diagnóstico da síndrome do túnel do carpo Pain and numbness in the arms and hands and carpal tunnel syndrome diagnosis

    Directory of Open Access Journals (Sweden)

    Valéria Ribeiro Nogueira Barbosa

    2006-12-01

    Full Text Available Nós avaliamos a freqüência e localização de dor e parestesias em pacientes com síndrome do túnel do carpo (STC e em indivíduos da população geral, pareados por gênero e idade. Determinamos a sensibilidade e a especificidade desses sintomas para o diagnóstico de STC. Dor foi um sintoma comum nos dois grupos de pacientes. Parestesia ocorreu com mais freqüência em pacientes com STC (p75% quando são localizadas nas mãos.We studied the frequency and localization of pain and numbness in patients with carpal tunnel syndrome (CTS, in comparison with individuals of the general population, matched for sex and age, and we determined the sensitivity and the specificity of these symptoms for the CTS diagnosis. Pain was a common symptom in the two groups of patients. Numbness occurred more frequently in CTS group (p<0.05. In CTS patients, pain complaints were present in neck (42.8%, arms (36.8% and hands (82.8%. Among controls, pain was more common in head (11.4%, trunk (37.1%, legs (22.8%. In our casuistics, in relation to the CTS diagnosis, the presence of pain and numbness have low sensitivity and high specificity when they occur in the arms, and high sensitivity and specificity when they occur in the hands.

  16. Nuclear links

    International Nuclear Information System (INIS)

    1981-01-01

    The subject is dealt with in sections: introduction; energy and the third world; world energy consumption 1978; oil -the energy dilemma; nuclear chains - introduction; uranium; Namibia; enrichment and reprocessing; countries with enrichment and reprocessing facilities; waste; conclusion; why take the nuclear option; third world countries with nuclear reactors; the arms connection; government spending and human resources 1977 (by countries); nuclear power - the final solution; the fascists; world bank; campaigns; community action in Plogoff; Australian labour movement; NUM against nuclear power; Scottish campaign; students against nuclear energy; anti-nuclear campaign; partizans; 3W1 disarmament and development; campaign ATOM; CANUC; 3W1; SANE. (U.K.)

  17. Tolerância à dor no infarto do miocárdio Tolerancia al dolor en infarto del miocárdio Pain tolerance during myocardium infarction

    Directory of Open Access Journals (Sweden)

    Fernanda Carneiro Mussi

    2010-01-01

    Full Text Available OBJETIVO: Analisar a tolerância à dor como sintoma prodrômico do infarto do miocárdio na perspectiva dos gêneros masculino e feminino em pacientes que vivenciaram esse evento cardiovascular. MÉTODOS: Estudo exploratório de natureza quanti-qualitativa. Entrevistou-se 43 mulheres e 54 homens em hospital público. Os dados sóciodemográficos foram analisados em percentuais e os qualitativos com base na análise de conteúdo e da categoria gênero. RESULTADOS: A mediana de idade para homens foi 55,3 e mulheres de 61,5 anos. Predominou para os gêneros a baixa escolaridade e inatividade profissional. Os homens tinham renda familiar maior e viviam mais em companhia de alguém. Evidenciou-se que homens e mulheres demonstraram igualmente enfrentamento e resistência à dor, visando manter o controle da própria existência e reproduzindo construções sociais sobre o masculino e o feminino em suas vidas cotidianas. CONCLUSÃO: O desafio profissional é atuar no plano simbólico dos gêneros para reduzir o retardo na decisão de buscar atenção médica e possibilitar os benefícios imediatos das terapias de reperfusão coronária.OBJETIVO: Analizar la tolerancia al dolor como síntoma prodrómico del infarto del miocardio en la perspectiva de los géneros masculino y femenino en pacientes que experimentaron ese evento cardiovascular. MÉTODOS: Estudio exploratorio de naturaleza cuantitativa cualitativa. Se entrevistaron 43 mujeres y 54 hombres en un hospital público. Los datos sociodemográficos fueron analizados en porcentajes y los cualitativos con base en el análisis de contenido y de la categoría género. RESULTADOS: El promedio de edad para hombres fue 55,3 y mujeres de 61,5 años. Predominó para los dos géneros la baja escolaridad e inactividad profesional. Los hombres tenían renta familiar mayor y vivían más en compañía de alguien. Se evidenció que los hombres y mujeres demostraron igualmente enfrentamiento y resistencia al

  18. Dor crônica e a crença de auto-eficácia El dolor crónico y la creencia de la auto-eficacia Chronic pain and the belief in self-efficacy

    Directory of Open Access Journals (Sweden)

    Marina de Góes Salvetti

    2007-03-01

    Full Text Available O tratamento de doentes com dor crônica inclui a modificação de crenças, atitudes, valores e com-portamentos pouco adaptativos. Crenças disfuncionais podem se tornar o problema central e determinar os resultados do tra-tamento. Dentre as crenças importantes para a vivência e manejo da dor crônica, a de auto-eficácia merece destaque. Auto-eficácia, de acordo com Bandura, é a crença sobre a habilidade pessoal de desempenhar com sucesso determinadas tarefas ou comportamentos para produzir um resultado desejável. Este estudo é uma revisão crítica da literatura sobre a crença de auto-eficácia relacionada à dor crônica e sobre os métodos para sua avaliação. Estudos existentes nas ba-ses Medline (1992 a 2002, Lilacs e Dedalus (toda a base foram analisados. Os descritores utilizados foram pain and self-efficacy, dor e auto-eficácia.El tratamiento de enfermos con dolor crónico incluye la modi-ficación de creencias, actitudes, valores y comportamientos poco adaptativos. Las creencias disfuncionales pueden volverse el problema central y determinar los resultados del tratamiento. De las creencias importantes para la vivencia y manejo del dolor crónico, la de auto eficacia merece ser destacado. La auto eficacia, de acuerdo con Bandura, es la creencia sobre la habilidad personal de desempeñar con éxito determinadas tareas o comportamientos para producir un resultado deseable. Este estudio es una revisión crítica de la literatura sobre la creencia de la auto eficacia relacionada al dolor crónico y sobre los métodos para su evaluación. Los estudios existentes en las bases Medline (1992 a 2002, Lilacs y Dedalus (toda la base fueron analizados. Los descriptores utilizados fueron pain and self-efficacy, dolor y auto eficacia.The treatment of chronic pain patients includes beliefs, attitudes, values and behavior modifications. Dysfunctional beliefs about pain and management can become the central problem and determine the treatment

  19. Acupuntura como recurso terapêutico na dor e na gravidade da desordem temporomandibular Acupuncture as therapeutic resource in the pain and in the severity of the temporomandibular disorder

    Directory of Open Access Journals (Sweden)

    Graciele da Silva Borin

    2011-09-01

    Full Text Available Este estudo avaliou o efeito da acupuntura no nível de dor e gravidade da Desordem Temporomandibular (DTM. Participaram dele 40 mulheres entre 20 e 40 anos com DTM diagnosticada pelo Research Diagnostic Criteria (RDC/TMD. A dor foi avaliada pela escala visual analógica e a gravidade da desordem pelos Índices de Disfunção Craniomandibular e de Fonseca. As 20 primeiras participantes foram submetidas a acupuntura duas vezes na semana por cinco semanas ininterruptas e, após o período, foram reavaliadas. Os dados destas participantes constituíram os resultados para o grupo acupuntura. As demais voluntárias receberam o tratamento após o primeiro grupo e seus dados, coletados no início e após cinco semanas sem tratamento, foram utilizados para controle. Na análise estatística foram levados em conta os testes de Wilcoxon para o nível de dor e Índice Craniomandibular e Teste t de Student para o Índice de Fonseca, com nível de significância de 5%. Houve redução significante no nível de dor (p=0,000 e na gravidade da DTM pelos Índices Craniomandibular (p=0,004 e de Fonseca (p=0,000 após o tratamento. O grupo controle não apresentou melhora. A efetividade da acupuntura foi demonstrada pela melhora no nível da dor e na gravidade da DTM.This study assessed the effect of acupuncture on the pain level and severity of the temporomandibular disorder (TMD. Forty women with TMD diagnosed by Research Diagnostic Criteria, from 20 and 40 years old, took part in the study. Pain was assessed by visual analogue scale and severity by the Craniomandibular Dysfunction and Fonseca Indexes. The first 20 volunteers were undergone to acupuncture twice a week for five weeks without interruption, and after they were reassessed. The results of these participants constituted acupuncture group. The other volunteers received the treatment after the first group and their data, collected in the beginning and after five weeks without treatment, were utilized as

  20. Abordagem fisioterapêutica no pré-parto: proposta de protocolo e avaliação da dor Physiotherapeutic approach in the pre-partum: proposed protocol and evaluate pain

    Directory of Open Access Journals (Sweden)

    Amanda de Souza Castro

    2012-09-01

    Full Text Available O objetivo deste estudo foi avaliar os efeitos da abordagem fisioterapêutica no pré-parto e propor um protocolo de intervenção baseado na escala visual analógica (EVA de dor. Dez parturientes, na primeira fase do trabalho de parto, foram questionadas quanto à dor através da EVA e, com base nas respostas, foi proposto um protocolo, EVA 1-3: cinesioterapia, técnicas respiratórias, relaxamento e estímulo à deambulação; EVA 4-7: massoterapia, técnicas respiratórias, relaxamento e estímulo à deambulação; EVA 8-10: técnicas respiratórias, relaxamento e eletroestimulação nervosa transcutânea. Após as intervenções, as voluntárias foram questionadas novamente através da EVA. Os dados da EVA pré- e pós-intervenção foram submetidos ao teste t pareado, atingindo valor médio de 8,8 pré-intervenção e 8,2 pós-intervenção, sem diferença estatística. Os resultados obtidos por meio da análise quantitativa de dor demonstraram que não houve aumento da mesma até uma hora após a intervenção, fato considerado positivo, uma vez que em função da crescente dilatação é esperado um aumento da dor. O protocolo fisioterapêutico proposto mostrou ser de fácil aplicabilidade, podendo auxiliar o fisioterapeuta na escolha da conduta mais adequada à realidade da sala de pré-parto. A abordagem fisioterapêutica no pré-parto parece interferir positivamente sobre a dor e o desconforto materno no grupo estudado.The aim of this study was to evaluate the effects of physical therapy approach in the antepartum and to propose an intervention protocol based on the visual analogue scale (VAS of pain. Ten parturients in the first stage of labor were questioned about the pain by VAS. Based on the responses, we proposed a protocol VAS 1-3: kinesiotherapy, breathing techniques, relaxation and stimulation of walking; VAS 4-7: massage therapy, breathing techniques, relaxation and stimulation of walking; VAS 8-10: breathing techniques

  1. Aplicação do laser 808nm na dor articular crônica de ratos Wistar Aplication of 808nm laser in chronic joint pain in Wistar rats

    Directory of Open Access Journals (Sweden)

    Gladson Ricardo Flor Bertolini

    2009-08-01

    Full Text Available Durante o processo inflamatório, alguns tipos de células predominam e estão envolvidos com a produção de dor. O laser de baixa potência mostra-se útil no controle de mediadores inflamatórios, mas a ampla divergência nos parâmetros dosimétricos, conduz a variações nos resultados positivos. O objetivo deste estudo foi analisar o uso do laser 808nm, na dor articular crônica e edema de ratos Wistar submetidos a sinovite. Foram utilizados 10 ratos Wistar, divididos em dois grupos: GC - indução de sinovite em joelho direito e tratamento placebo; GT - indução de sinovite e irradiado com laser 10J/cm². Para a produção de sinovite foram injetados 100µl de formalina a 5%, no espaço articular tibiofemoral direito. A avaliação da dor ocorreu pelo tempo de elevação da pata (TEP. No 10º dia após a indução de sinovite, iniciou-se o tratamento com laser sobre a face articular medial do joelho, procedimento mantido no decorrer de 10 dias. Os resultados mostraram que o laser apresentou efeitos analgésicos, visto que, para o grupo tratado, houve redução significativa nos valores de TEP, indicando redução da dor, quando comparados os valores pós-tratamento com os pré-tratamento, o que não ocorreu para o grupo que recebeu tratamento placebo; para o edema, o laser também mostrou redução significativa do mesmo. Concluiu-se que o laser 808nm, com 10J/cm², é eficaz na redução da dor articular crônica e edema, em animais submetidos a sinovite experimental.During the inflammatory process some kinds of cells are predominant and are involved with pain production. Low power laser seems to be useful in the control of inflammatory mediators, but wide divergence in the dosemetric parameters leads to variations in its positive results. The aim of this study was to assess the use of the 808nm laser in the chronic joint pain and edema of Wistar rats submitted to synovitis. Sample was composed of 10 Wistar rats divided in two groups

  2. Hipnose, dor e subjetividade: considerações teóricas e clínicas Hipnosis, dolor y subjetividad: consideraciones teóricas y clínicas Hypnosis, pain and subjectivity: theoretical and clinical considerations

    Directory of Open Access Journals (Sweden)

    Maurício da Silva Neubern

    2009-06-01

    Full Text Available O presente artigo visa propor uma abordagem clínica e qualitativa para a compreensão das relações entre hipnose e dor a partir da noção de subjetividade. Partindo de uma crítica às metodologias estatísticas, três pontos são discutidos nesse sentido. Primeiramente, a dor é concebida como um processo subjetivo organizado em termos de configurações, sentidos, emoções e significados que são construídos a partir das ações do sujeito em seus respectivos cenários de inserção social. Em seguida, é ressaltada a relação entre hipnose e dor, conferindo-se destaque aos processos intersubjetivos da comunicação e da relação entre terapeuta e sujeito. O terceiro tópico destaca a importância da singularidade, que deve abranger tanto a compreensão da dor quanto a construção das intervenções hipnóticas. O artigo é concluído enfatizando a relevância das noções de subjetividade e sujeito no que se refere às complexas relações entre dor e hipnose no contexto clínico.El presente artículo tiene por objetivo proponer um abordaje clínico y cualitativo para la comprensión de las relaciones entre hipnosis y dolor a partir de la noción de subjetividad. Partiendo de una crítica a las metodologías estadísticas, se discuten básicamente tres puntos. En primer lugar, se considera el dolor como un proceso subjetivo organizado en términos de configuraciones, sentidos, emociones y significados, los cuales son construidos a partir de las propias acciones del sujeto en sus diversos escenarios de inserción social. A continuación, se tematiza la relación entre hipnosis y dolor, destacándose los procesos intersubjetivos de la comunicación y de la relación entre terapeuta y sujeto. En el tercer tópico se destaca la importancia de la singularidad que debe alcanzar tanto la comprensión del dolor como la construcción de las intervenciones hipnóticas. El artículo termina enfatizando la relevancia de las nociones de

  3. Structure and reconstitution of yeast Mpp6-nuclear exosome complexes reveals that Mpp6 stimulates RNA decay and recruits the Mtr4 helicase

    Energy Technology Data Exchange (ETDEWEB)

    Wasmuth, Elizabeth V. [Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States; Zinder, John C. [Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States; Tri-Institutional Training Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, United States; Zattas, Dimitrios [Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States; Das, Mom [Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States; Lima, Christopher D. [Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States; Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, United States

    2017-07-25

    Nuclear RNA exosomes catalyze a range of RNA processing and decay activities that are coordinated in part by cofactors, including Mpp6, Rrp47, and the Mtr4 RNA helicase. Mpp6 interacts with the nine-subunit exosome core, while Rrp47 stabilizes the exoribonuclease Rrp6 and recruits Mtr4, but it is less clear if these cofactors work together. Using biochemistry with Saccharomyces cerevisiae proteins, we show that Rrp47 and Mpp6 stimulate exosome-mediated RNA decay, albeit with unique dependencies on elements within the nuclear exosome. Mpp6-exosomes can recruit Mtr4, while Mpp6 and Rrp47 each contribute to Mtr4-dependent RNA decay, with maximal Mtr4-dependent decay observed with both cofactors. The 3.3 Å structure of a twelve-subunit nuclear Mpp6 exosome bound to RNA shows the central region of Mpp6 bound to the exosome core, positioning its Mtr4 recruitment domain next to Rrp6 and the exosome central channel. Genetic analysis reveals interactions that are largely consistent with our model.

  4. A Novel Nonsense Variant in Nav1.5 Cofactor MOG1 Eliminates Its Sodium Current Increasing Effect and May Increase the Risk of Arrhythmias

    DEFF Research Database (Denmark)

    Olesen, Morten S; Jensen, Niels F; Holst, Anders G

    2011-01-01

    at a lower frequency (1.8% vs 0.4%, P = 0.078). Electrophysiological investigation showed that the p.E61X variant completely eliminates the sodium current-increasing effect of MOG1 and thereby causes loss of function in the sodium current. When mimicking heterozygosity by coexpression of Nav1.5 with wild......BACKGROUND: The protein MOG1 is a cofactor of the cardiac sodium channel, Nav1.5. Overexpression of MOG1 in Nav1.5-expressing cells increases sodium current markedly. Mutations in the genes encoding Nav1.5 and its accessory proteins have been associated with cardiac arrhythmias of significant...... and 23 were patients with Brugada syndrome. The effect of one variant was investigated functionally by patch-clamping CHO-K1 cells coexpressing Nav1.5 with MOG1. RESULTS: We uncovered a novel heterozygous nonsense variant, c.181G>T (p.E61X), that, however, was also present in control subjects, albeit...

  5. Roles of the active site residues and metal cofactors in noncanonical base-pairing during catalysis by human DNA polymerase iota.

    Science.gov (United States)

    Makarova, Alena V; Ignatov, Artem; Miropolskaya, Nataliya; Kulbachinskiy, Andrey

    2014-10-01

    Human DNA polymerase iota (Pol ι) is a Y-family polymerase that can bypass various DNA lesions but possesses very low fidelity of DNA synthesis in vitro. Structural analysis of Pol ι revealed a narrow active site that promotes noncanonical base-pairing during catalysis. To better understand the structure-function relationships in the active site of Pol ι we investigated substitutions of individual amino acid residues in its fingers domain that contact either the templating or the incoming nucleotide. Two of the substitutions, Y39A and Q59A, significantly decreased the catalytic activity but improved the fidelity of Pol ι. Surprisingly, in the presence of Mn(2+) ions, the wild-type and mutant Pol ι variants efficiently incorporated nucleotides opposite template purines containing modifications that disrupted either Hoogsteen or Watson-Crick base-pairing, suggesting that Pol ι may use various types of interactions during nucleotide addition. In contrast, in Mg(2+) reactions, wild-type Pol ι was dependent on Hoogsteen base-pairing, the Y39A mutant was essentially inactive, and the Q59A mutant promoted Watson-Crick interactions with template purines. The results suggest that Pol ι utilizes distinct mechanisms of nucleotide incorporation depending on the metal cofactor and reveal important roles of specific residues from the fingers domain in base-pairing and catalysis. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Insight into Coenzyme A cofactor binding and the mechanism of acyl-transfer in an acylating aldehyde dehydrogenase from Clostridium phytofermentans.

    Science.gov (United States)

    Tuck, Laura R; Altenbach, Kirsten; Ang, Thiau Fu; Crawshaw, Adam D; Campopiano, Dominic J; Clarke, David J; Marles-Wright, Jon

    2016-02-22

    The breakdown of fucose and rhamnose released from plant cell walls by the cellulolytic soil bacterium Clostridium phytofermentans produces toxic aldehyde intermediates. To enable growth on these carbon sources, the pathway for the breakdown of fucose and rhamnose is encapsulated within a bacterial microcompartment (BMC). These proteinaceous organelles sequester the toxic aldehyde intermediates and allow the efficient action of acylating aldehyde dehydrogenase enzymes to produce an acyl-CoA that is ultimately used in substrate-level phosphorylation to produce ATP. Here we analyse the kinetics of the aldehyde dehydrogenase enzyme from the fucose/rhamnose utilisation BMC with different short-chain fatty aldehydes and show that it has activity against substrates with up to six carbon atoms, with optimal activity against propionaldehyde. We have also determined the X-ray crystal structure of this enzyme in complex with CoA and show that the adenine nucleotide of this cofactor is bound in a distinct pocket to the same group in NAD(+). This work is the first report of the structure of CoA bound to an aldehyde dehydrogenase enzyme and our crystallographic model provides important insight into the differences within the active site that distinguish the acylating from non-acylating aldehyde dehydrogenase enzymes.

  7. The MoxR ATPase RavA and its cofactor ViaA interact with the NADH:ubiquinone oxidoreductase I in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Keith S Wong

    Full Text Available MoxR ATPases are widespread throughout bacteria and archaea. The experimental evidence to date suggests that these proteins have chaperone-like roles in facilitating the maturation of dedicated protein complexes that are functionally diverse. In Escherichia coli, the MoxR ATPase RavA and its putative cofactor ViaA are found to exist in early stationary-phase cells at 37 °C at low levels of about 350 and 90 molecules per cell, respectively. Both proteins are predominantly localized to the cytoplasm, but ViaA was also unexpectedly found to localize to the cell membrane. Whole genome microarrays and synthetic lethality studies both indicated that RavA-ViaA are genetically linked to Fe-S cluster assembly and specific respiratory pathways. Systematic analysis of mutant strains of ravA and viaA indicated that RavA-ViaA sensitizes cells to sublethal concentrations of aminoglycosides. Furthermore, this effect was dependent on RavA's ATPase activity, and on the presence of specific subunits of NADH:ubiquinone oxidoreductase I (Nuo Complex, or Complex I. Importantly, both RavA and ViaA were found to physically interact with specific Nuo subunits. We propose that RavA-ViaA facilitate the maturation of the Nuo complex.

  8. TcoF-DB v2: update of the database of human and mouse transcription co-factors and transcription factor interactions

    KAUST Repository

    Schmeier, Sebastian

    2016-10-17

    Transcription factors (TFs) play a pivotal role in transcriptional regulation, making them crucial for cell survival and important biological functions. For the regulation of transcription, interactions of different regulatory proteins known as transcription co-factors (TcoFs) and TFs are essential in forming necessary protein complexes. Although TcoFs themselves do not bind DNA directly, their influence on transcriptional regulation and initiation, although indirect, has been shown to be significant, with the functionality of TFs strongly influenced by the presence of TcoFs. In the TcoF-DB v2 database, we collect information on TcoFs. In this article, we describe updates and improvements implemented in TcoF-DB v2. TcoF-DB v2 provides several new features that enables exploration of the roles of TcoFs. The content of the database has significantly expanded, and is enriched with information from Gene Ontology, biological pathways, diseases and molecular signatures. TcoF-DB v2 now includes many more TFs; has substantially increased the number of human TcoFs to 958, and now includes information on mouse (418 new TcoFs). TcoF-DB v2 enables the exploration of information on TcoFs and allows investigations into their influence on transcriptional regulation in humans and mice. TcoF-DB v2 can be accessed at http://tcofdb.org/.

  9. TcoF-DB v2: update of the database of human and mouse transcription co-factors and transcription factor interactions

    KAUST Repository

    Schmeier, Sebastian; Alam, Tanvir; Essack, Magbubah; Bajic, Vladimir B.

    2016-01-01

    Transcription factors (TFs) play a pivotal role in transcriptional regulation, making them crucial for cell survival and important biological functions. For the regulation of transcription, interactions of different regulatory proteins known as transcription co-factors (TcoFs) and TFs are essential in forming necessary protein complexes. Although TcoFs themselves do not bind DNA directly, their influence on transcriptional regulation and initiation, although indirect, has been shown to be significant, with the functionality of TFs strongly influenced by the presence of TcoFs. In the TcoF-DB v2 database, we collect information on TcoFs. In this article, we describe updates and improvements implemented in TcoF-DB v2. TcoF-DB v2 provides several new features that enables exploration of the roles of TcoFs. The content of the database has significantly expanded, and is enriched with information from Gene Ontology, biological pathways, diseases and molecular signatures. TcoF-DB v2 now includes many more TFs; has substantially increased the number of human TcoFs to 958, and now includes information on mouse (418 new TcoFs). TcoF-DB v2 enables the exploration of information on TcoFs and allows investigations into their influence on transcriptional regulation in humans and mice. TcoF-DB v2 can be accessed at http://tcofdb.org/.

  10. Cofactor Balance by Nicotinamide Nucleotide Transhydrogenase (NNT) Coordinates Reductive Carboxylation and Glucose Catabolism in the Tricarboxylic Acid (TCA) Cycle*♦

    Science.gov (United States)

    Gameiro, Paulo A.; Laviolette, Laura A.; Kelleher, Joanne K.; Iliopoulos, Othon; Stephanopoulos, Gregory

    2013-01-01

    Cancer and proliferating cells exhibit an increased demand for glutamine-derived carbons to support anabolic processes. In addition, reductive carboxylation of α-ketoglutarate by isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) was recently shown to be a major source of citrate synthesis from glutamine. The role of NAD(P)H/NAD(P)+ cofactors in coordinating glucose and glutamine utilization in the tricarboxylic acid (TCA) cycle is not well understood, with the source(s) of NADPH for the reductive carboxylation reaction remaining unexplored. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial enzyme that transfers reducing equivalents from NADH to NADPH. Here, we show that knockdown of NNT inhibits the contribution of glutamine to the TCA cycle and activates glucose catabolism in SkMel5 melanoma cells. The increase in glucose oxidation partially occurred through pyruvate carboxylase and rendered NNT knockdown cells more sensitive to glucose deprivation. Importantly, knocking down NNT inhibits reductive carboxylation in SkMel5 and 786-O renal carcinoma cells. Overexpression of NNT is sufficient to stimulate glutamine oxidation and reductive carboxylation, whereas it inhibits glucose catabolism in the TCA cycle. These observations are supported by an impairment of the NAD(P)H/NAD(P)+ ratios. Our findings underscore the role of NNT in regulating central carbon metabolism via redox balance, calling for other mechanisms that coordinate substrate preference to maintain a functional TCA cycle. PMID:23504317

  11. The solution structure of the N-terminal zinc finger of GATA-1 reveals a specific binding face for the transcriptional co-factor FOG

    International Nuclear Information System (INIS)

    Kowalski, K.; Czolij, R.; King, G.F.; Crossley, M.; Mackay, J.P.

    1999-01-01

    Zinc fingers (ZnFs) are generally regarded as DNA-binding motifs. However, a number of recent reports have implicated particular ZnFs in the mediation of protein-protein interactions. The N-terminal ZnF of GATA-1 (NF) is one such finger, having been shown to interact with a number of other proteins, including the recently discovered transcriptional co-factor FOG. Here we solve the three-dimensional structure of the NF in solution using multidimensional 1H/15N NMR spectroscopy, and we use 1H/15N spin relaxation measurements to investigate its backbone dynamics. The structure consists of two distorted β-hairpins and a single α-helix, and is similar to that of the C-terminal ZnF of chicken GATA-1. Comparisons of the NF structure with those of other C4-type zinc binding motifs, including hormone receptor and LIM domains, also reveal substantial structural homology. Finally, we use the structure to map the spatial locations of NF residues shown by mutagenesis to be essential for FOG binding, and demonstrate that these residues all lie on a single face of the NF. Notably, this face is well removed from the putative DNA- binding face of the NF, an observation which is suggestive of simultaneous roles for the NF; that is, stabilisation of GATA-1 DNA complexes and recruitment of FOG to GATA-1-controlled promoter regions

  12. Homeotic function of Drosophila Bithorax-Complex miRNAs mediates fertility by restricting multiple Hox genes and TALE cofactors in the central nervous system

    Science.gov (United States)

    Garaulet, Daniel L.; Castellanos, Monica; Bejarano, Fernando; Sanfilippo, Piero; Tyler, David M.; Allan, Douglas W.; Sánchez-Herrero, Ernesto; Lai, Eric C.

    2014-01-01

    The Drosophila Bithorax-Complex (BX-C) Hox cluster contains a bidirectionally-transcribed miRNA locus, and a deletion mutant (∆mir) lays no eggs and is completely sterile. We show these miRNAs are expressed and active in distinct spatial registers along the anterior-posterior axis in the central nervous system. ∆mir larvae derepress a network of direct homeobox gene targets in the posterior ventral nerve cord (VNC), including BX-C genes and their TALE cofactors. These are phenotypically critical targets, since sterility of ∆mir mutants was substantially rescued by heterozygosity of these genes. The posterior VNC contains Ilp7+ oviduct motoneurons, whose innervation and morphology are defective in ∆mir females, and substantially rescued by heterozygosity of ∆mir targets, especially within the BX-C. Collectively, we reveal (1) critical roles for Hox miRNAs that determine segment-specific expression of homeotic genes, which are not masked by transcriptional regulation, and (2) that BX-C miRNAs are essential for neural patterning and reproductive behavior. PMID:24909902

  13. Estimating HIV Incidence during Pregnancy and Knowledge of Prevention of Mother-to-Child Transmission with an Ad Hoc Analysis of Potential Cofactors

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    Thomas Obinchemti Egbe

    2016-01-01

    Full Text Available Background. We determined the incidence of HIV seroconversion during the second and third trimesters of pregnancy and ad hoc potential cofactors associated with HIV seroconversion after having an HIV-negative result antenatally. We also studied knowledge of PMTCT among pregnant women in seven health facilities in Fako Division, South West Region, Cameroon. Method. During the period between September 12 and December 4, 2011, we recruited a cohort of 477 HIV-negative pregnant women by cluster sampling. Data collection was with a pretested interviewer-administered questionnaire. Sociodemographic information, knowledge of PMTCT, and methods of HIV prevention were obtained from the study population and we did Voluntary Counselling and Testing (VCT for HIV. Results. The incidence rate of HIV seroconversion during pregnancy was 6.8/100 woman-years. Ninety percent of the participants did not use condoms throughout pregnancy but had a good knowledge of PMTCT of HIV. Only 31.9% of participants knew their HIV status before the booking visit and 33% did not know the HIV status of their partners. Conclusion. The incidence rate of HIV seroconversion in the Fako Division, Cameroon, was 6.8/100 woman-years. No risk factors associated with HIV seroconversion were identified among the study participants because of lack of power to do so.

  14. Estimating HIV Incidence during Pregnancy and Knowledge of Prevention of Mother-to-Child Transmission with an Ad Hoc Analysis of Potential Cofactors.

    Science.gov (United States)

    Egbe, Thomas Obinchemti; Tazinya, Rose-Mary Asong; Halle-Ekane, Gregory Edie; Egbe, Eta-Nkongho; Achidi, Eric Akum

    2016-01-01

    We determined the incidence of HIV seroconversion during the second and third trimesters of pregnancy and ad hoc potential cofactors associated with HIV seroconversion after having an HIV-negative result antenatally. We also studied knowledge of PMTCT among pregnant women in seven health facilities in Fako Division, South West Region, Cameroon. During the period between September 12 and December 4, 2011, we recruited a cohort of 477 HIV-negative pregnant women by cluster sampling. Data collection was with a pretested interviewer-administered questionnaire. Sociodemographic information, knowledge of PMTCT, and methods of HIV prevention were obtained from the study population and we did Voluntary Counselling and Testing (VCT) for HIV. The incidence rate of HIV seroconversion during pregnancy was 6.8/100 woman-years. Ninety percent of the participants did not use condoms throughout pregnancy but had a good knowledge of PMTCT of HIV. Only 31.9% of participants knew their HIV status before the booking visit and 33% did not know the HIV status of their partners. The incidence rate of HIV seroconversion in the Fako Division, Cameroon, was 6.8/100 woman-years. No risk factors associated with HIV seroconversion were identified among the study participants because of lack of power to do so.

  15. Nuclear Power

    International Nuclear Information System (INIS)

    Douglas-Hamilton, J.; Home Robertson, J.; Beith, A.J.

    1987-01-01

    In this debate the Government's policy on nuclear power is discussed. Government policy is that nuclear power is the safest and cleanest way of generating electricity and is cheap. Other political parties who do not endorse a nuclear energy policy are considered not to be acting in the people's best interests. The debate ranged over the risks from nuclear power, the UK safety record, safety regulations, and the environmental effects of nuclear power. The Torness nuclear power plant was mentioned specifically. The energy policy of the opposition parties is strongly criticised. The debate lasted just over an hour and is reported verbatim. (UK)

  16. Spectroscopic investigations of the B12-binding subunit of glutamate mutase: refined solution structure of the complex with the B12-nucleotide, dynamics and binding studies with two corrinoid cofactors

    International Nuclear Information System (INIS)

    Eichmueller, C.

    2002-06-01

    Glutamate mutase is an enzyme isolated from Clostridium tetanomorphum and Clostridium cochlearum. It catalyses the reversible rearrangement of (2S)-glutamate to (2S,3S)-3-methylaspartate. Coenzyme B12 is required as cofactor for an active enzyme, as the first step of the catalytic cycle is the homolytic cleavage of the cobalt-carbon bond. The rearrangement itself follows a radical mechanism. The holoenzyme is an alpha2beta2 heterotetramer containing two identical catalytic and two B12 binding domains, as well as two coenzyme B12 molecules. The smaller B12 binding domain from Clostridium tetanomorphum, MutS, is known to bind coenzyme B12 in its unusual 'base-off' form. A conserved histidine residue coordinates to the cobalt atom instead of the normally coordinated dimethlybenzimidole in free coenzyme B12. In the present work a refined solution structure of the B12 binding subunit from Clostridium tetanomorphum (MutS) in complex with the detached nucleotide loop of coenzyme B12 has been determined using nuclear magnetic resonance. The found topology is almost identical to the crystal structure of glutamate mutase from C.cochlearum [Reitzer et al., 1999], in contrast to the solution structures obtained for apo-MutS [Hoffmann et al., 2001; Tollinger et al., 1998] and apo-GlmS [Hoffmann et al., 1999]. In these two structures a helix at one side of the B12 nucleotide loop binding pocket is mostly unstructured and shows motions on a microsecond to millisecond timescale. The previously found stabilization of this helix upon B12-nucleotide binding [Tollinger et al., 2001] was confirmed using 13C and 15N labeled MutS. Some differences are found in the structure of the binding pocket and the bound nucleotide loop compared to the crystal structure. This indicates that additional conformational changes occur upon binding of the corrin ring of coenzyme B12. NMR-relaxation measurements performed on apo-MutS showed interesting slow molecular motions not only in the mainly

  17. Dor muscular e atividade de creatina quinase após ações excêntricas: uma análise de cluster

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    Felipe Romano Damas Nogueira

    2014-07-01

    Full Text Available INTRODUÇÃO: O exercício excêntrico máximo promove queda da capacidade de geração de força, aumento de dor muscular de início tardio (DMIT e extravasamento de creatina quinase (CK no sangue. No entanto, essas respostas ao exercício excêntrico demonstram alta variabilidade interindivíduos. OBJETIVOS: Classificar e analisar essas respostas segundo a vulnerabilidade individual, por meio da magnitude da redução dos níveis de força após exercício excêntrico. MÉTODOS: Dezoito sujeitos (11 homens e sete mulheres com idade entre 18 e 71 anos saudáveis realizaram cinco séries de seis ações excêntricas máximas para flexores do cotovelo em dinamômetro isocinético (90°s- 1, amplitude de movimento de 80 a 20°. Foram analisadas contração voluntária muscular concêntrica máxima (CVM, DMIT e CK pré, pós (exceto CK, 24 h, 48 h, 72 h e 96 h após o protocolo. Os indivíduos foram classificados como "baixos" (BR e "altos" respondedores (AR ao pico de queda de CVM pós-exercício seguindo-se uma análise de cluster e comparação entre grupos para CVM, DMIT e CK com teste-t independente. RESULTADOS: A comparação entre BR e AR indicou maiores valores de queda de CVM para o grupo AR (AR: -30,7 ± 3,3%; BR: -14,1 ± 2,2%, p < 0,001 e maior DMIT também para o grupo AR (AR: 33,0 ± 8,6 mm; BR: 10,2 ± 2,5 mm, p = 0,033; no entanto, os valores de pico de atividade de CK não diferiram entre os grupos (AR: 232,1 ± 54,8 UI.L- 1; BR: 306,1 ± 82,3 UI.L- 1, p = 0,490. CONCLUSÃO: A classificação dos indivíduos em grupos de baixos e altos respondedores foi importante para demonstrar que o grupo mais responsivo à queda de força após exercício excêntrico também evidencia maiores níveis de DMIT; contudo, para a CK essa relação não pôde ser estabelecida.

  18. Efeito da rotação do quadril na síndrome da dor femoropatelar Effect of hip rotation on patellofemoral pain syndrome

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    K Gramani-Say

    2006-01-01

    Full Text Available Objetivo: A proposta desse trabalho foi investigar o efeito da rotação do quadril na atividade elétrica dos músculos Vasto Medial Oblíquo (VMO, Vasto Lateral Oblíquo (VLO e Vasto Lateral Longo (VLL no agachamento a 45º de flexão do joelho associado à posição neutra, rotação lateral a 45º e rotação medial a 15 e 30º de quadril. Materiais e Método: Foram avaliadas 27 mulheres, sendo 15 mulheres normais do grupo Controle (21,1±2,1 anos e 12 portadoras de Síndrome da Dor Femoropatelar (SDFP (21,0±2,3 anos. A atividade elétrica do músculo quadríceps foi captada por eletrodos ativos diferenciais simples de superfície, eletromiógrafo de 8 canais e programa Aqdados 7.2.6. Os dados foram normalizados pela porcentagem da média do agachamento a 75º com o quadril em posição neutra RMS (µV. A análise estatística utilizada foi a ANOVA two way com medidas repetidas e Turkey post hoc (pObjective: The purpose of this study was to evaluate the effect of hip rotation on the electrical activity of the Vastus Medialis Obliquus (VMO, Vastus Lateralis Obliquus (VLO and Vastus Lateralis Longus (VLL muscles when squatting with 45º knee flexion, in association with the neutral position, 45º lateral rotation and 15 and 30º medial hip rotation. Method: 27 women were evaluated: 15 healthy women as a control group (21.1 ± 2.1 years and 12 subjects with patellofemoral pain syndrome (PFPS (21.0 ± 2.3 years. The electrical activity of the quadriceps muscle was detected using simple active differential surface electrodes, an eight-channel electromyography system and the Aqdados 7.2.6 software. The data were normalized by the mean squatting percentage at 75º with the hip in the neutral position RMS (µV. Two-way ANOVA with repeated measurements followed by the Tukey post hoc test (p<0.05 was used for statistical analysis. Results: The results revealed interaction between groups and muscles (p=0.00, independent of hip position (p=0.39, and

  19. Documentation et conservation-restauration d’un autel bouddhique en bois laqué et doré, provenant du Japon

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    Violaine Brard

    2010-11-01

    Full Text Available Un petit autel bouddhique en bois laqué et doré était conservé dans un carton d’emballage au sein du musée Georges-Labit à Toulouse. Tout l’enjeu de ce travail fut de collecter les informations relatives au pays d’origine de la pièce, à son époque de création ainsi que son rôle dans son pays d’origine. La recherche visait ensuite à comprendre la manière dont cet objet est passé d’une culture japonaise à une collection française, élaborée par un voyageur et collectionneur de la fin du XIXe siècle, Georges Labit. L’autel est le fruit d’un support et d’une polychromie japonaise initiale et de surpeints européens appliqués au cours du XIXe siècle. Ces surpeints témoignent de son passage laborieux d’un pays à un autre. Les nouveaux acquéreurs de l’objet ont très certainement voulu, par leur intervention, réparer les altérations, causées par le voyage de la pièce, et l’adapter à une esthétique occidentale. Dans le cadre de mon étude, je me suis contentée d’intervenir sur la stricte conservation curative de la pièce. Elle vise, de manière générale, à retrouver une lisibilité cohérente et à redonner à la structure une unité.A small gilded and lacquered wooden Buddhist altar has been  kept for years in a cardboard box in the storage rooms of the Georges Labit museum in Toulouse. The challenge of this project  was to collect information on the origins of the altar, its time of creation and its specific function  in the  country of origin. The research focused on raising understanding  how this object has been transferred from  the Japanese culture  into a French collection that has been developed by Georges Labit a traveller and collector of the late nineteenth century. Examinations  showed that the altar with its original Japanese wooden support and polychromy showes over paints that have been applied in Europe  during the nineteenth century. These over paints demonstrate its

  20. Retrospective evaluation of bone pain palliation after samarium-153-EDTMP therapy Avaliação retrospectiva do tratamento da dor óssea metastática com Samário-153-EDTMP

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    Marcelo Tatit Sapienza

    2004-01-01

    Full Text Available PURPOSE: The aim of this study was to evaluate the degree of metastatic bone pain palliation and medullar toxicity associated with samarium-153-EDTMP treatment. METHODS: Seventy-three patients with metastatic bone pain having previously undergone therapy with samarium-153-EDTMP (1 mCi/kg were retrospectively evaluated. Routine follow-up included pain evaluation and blood counts for 2 months after treatment. Pain was evaluated using a subjective scale (from 0 to 10 before and for 8 weeks after the treatment. Blood counts were obtained before treatment and once a week for 2 months during follow-up. Dosimetry, based upon the urinary excretion of the isotope, was estimated in 41 individuals, and the resulting radiation absorbed doses were correlated with hematological data. RESULTS: Reduction in pain scores of 75% to 100% was obtained in 36 patients (49%, with a decrease of 50% to 75%, 25% to 50%, and 0% to 25% in, respectively, 20 (27%, 10 (14%, and 7 (10% patients. There was no significant relationship between the pain response and location of the primary tumor (breast or prostate cancer. Mild to moderate myelosuppression was noted in 75.3% of patients, usually with hematological recovery at 8 weeks. The mean bone marrow dose was 347 ± 65 cGy, and only a weak correlation was found between absorbed dose and myelosuppression (Pearson coefficient = .4. CONCLUSIONS: Samarium-153-EDTMP is a valuable method for metastatic bone pain palliation. A mild to moderate and transitory myelosuppression is the main toxicity observed after samarium therapy, showing a weak correlation with dosimetric measures.OBJETIVO: O presente trabalho teve por objetivo avaliar o efeito paliativo da dor e a toxicidade medular associados ao tratamento com Samário-153-EDTMP em pacientes com metástases ósseas. MÉTODOS: O estudo foi realizado de forma retrospectiva, a partir do levantamento de prontuário de 178 pacientes submetidos a tratamento com 1mCi/kg de 153Sm