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  1 / 20182 MEDLINE  
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[PMID]:29378242
[Au] Autor:Wang X; Xue M; Zhao M; He F; Li C; Li X
[Ad] Endereço:Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
[Ti] Título:Identification of a novel mutation (Ala66Thr) of SRY gene causes XY pure gonadal dysgenesis by affecting DNA binding activity and nuclear import.
[So] Source:Gene;651:143-151, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Sex-determining region of the Y chromosome (SRY) gene plays a crucial role in male sexual differentiation and development. Several mutations in the SRY gene have been reported in the high mobility group (HMG) box domain and can cause gonadal dysgenesis symptoms. In this study, we report that a novel missense mutation in the SRY gene, a G to A transition within the HMG box, causes the Ala66Thr amino acid substitution in a female patient presenting 46,XY karyotype with pure gonadal dysgenesis. The G to A base transition was not found in the SRY sequence after the screening of 100 normal males. Furthermore, Ala66Thr mutation drastically reduced the binding capacity of SRY to DNA sequences, whereas wild-type SRY protein showed the normal binding capacity to DNA sequences in vitro. We also found that the mutant SRY protein was partly localized in cytoplasm, whereas wild-type SRY protein was strictly localized in cell nucleus. In addition, we analyzed the three-dimensional structure of SRY protein by homology modeling methods. In conclusion, we identified a novel SRY mutation in a 46,XY female patient with pure gonadal dysgenesis, demonstrating the importance of the Ala66Thr mutation in DNA binding activity and nuclear transport.
[Mh] Termos MeSH primário: Disgenesia Gonadal 46 XY/genética
Mutação de Sentido Incorreto
Proteína da Região Y Determinante do Sexo/genética
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular
Adolescente
Adulto
Alanina
DNA/metabolismo
Feminino
Células HEK293
Seres Humanos
Cariotipagem
Masculino
Ligação Proteica
Conformação Proteica
Análise de Sequência de DNA
Proteína da Região Y Determinante do Sexo/química
Proteína da Região Y Determinante do Sexo/metabolismo
Treonina
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Sex-Determining Region Y Protein); 2ZD004190S (Threonine); 9007-49-2 (DNA); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180130
[St] Status:MEDLINE


  2 / 20182 MEDLINE  
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[PMID]:29410408
[Au] Autor:Kuncha SK; Mazeed M; Singh R; Kattula B; Routh SB; Sankaranarayanan R
[Ad] Endereço:CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500007, India.
[Ti] Título:A chiral selectivity relaxed paralog of DTD for proofreading tRNA mischarging in Animalia.
[So] Source:Nat Commun;9(1):511, 2018 02 06.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:D-aminoacyl-tRNA deacylase (DTD), a bacterial/eukaryotic trans-editing factor, removes D-amino acids mischarged on tRNAs and achiral glycine mischarged on tRNA . An invariant cross-subunit Gly-cisPro motif forms the mechanistic basis of L-amino acid rejection from the catalytic site. Here, we present the identification of a DTD variant, named ATD (Animalia-specific tRNA deacylase), that harbors a Gly-transPro motif. The cis-to-trans switch causes a "gain of function" through L-chiral selectivity in ATD resulting in the clearing of L-alanine mischarged on tRNA (G4•U69) by eukaryotic AlaRS. The proofreading activity of ATD is conserved across diverse classes of phylum Chordata. Animalia genomes enriched in tRNA (G4•U69) genes are in strict association with the presence of ATD, underlining the mandatory requirement of a dedicated factor to proofread tRNA misaminoacylation. The study highlights the emergence of ATD during genome expansion as a key event associated with the evolution of Animalia.
[Mh] Termos MeSH primário: Alanina/química
Aminoaciltransferases/química
Aminoacil-RNA de Transferência/química
Treonina/química
Aminoacilação de RNA de Transferência/genética
[Mh] Termos MeSH secundário: Alanina/genética
Alanina/metabolismo
Sequência de Aminoácidos
Aminoaciltransferases/genética
Aminoaciltransferases/metabolismo
Animais
Apicomplexa/genética
Apicomplexa/metabolismo
Bactérias/genética
Bactérias/metabolismo
Sítios de Ligação
Evolução Biológica
Clonagem Molecular
Cristalografia por Raios X
Expressão Gênica
Seres Humanos
Modelos Moleculares
Ligação Proteica
Conformação Proteica em alfa-Hélice
Conformação Proteica em Folha beta
Domínios e Motivos de Interação entre Proteínas
Aminoacil-RNA de Transferência/genética
Aminoacil-RNA de Transferência/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Alinhamento de Sequência
Homologia de Sequência de Aminoácidos
Especificidade por Substrato
Treonina/genética
Treonina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA, Transfer, Amino Acyl); 0 (Recombinant Proteins); 2ZD004190S (Threonine); EC 2.3.2.- (Aminoacyltransferases); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180208
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02204-w


  3 / 20182 MEDLINE  
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[PMID]:27778166
[Au] Autor:Fan R; Yuan Y; Zhang Q; Zhou XR; Jia L; Liu Z; Yu C; Luo SZ; Chen L
[Ad] Endereço:Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, People's Republic of China.
[Ti] Título:Isoleucine/leucine residues at "a" and "d" positions of a heptad repeat sequence are crucial for the cytolytic activity of a short anticancer lytic peptide.
[So] Source:Amino Acids;49(1):193-202, 2017 01.
[Is] ISSN:1438-2199
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Many lytic peptides contain a heptad sequence with leucine or isoleucine residues at "a" and "d" positions. However, their roles in the peptide-induced cytolytic process remain unclear. We have recently reported an anticancer lytic peptide ZXR-2 (FKIGGFIKKLWRSLLA), which contains a shortened zipper-like sequence with Ile/Leu at "a" and "d" positions. To understand the roles of these Ile/Leu residues, a series of analogs were constructed by sequentially replacing the Ile or Leu residue with alanine (Ala). Significant reduction of the cytolytic activity was observed when the Ile (3rd and 7th) and Leu (10th and 14th) residues at the "a" and "d" positions were substituted, while the replacement of the separate Leu (15th) residue had less effect. Based on the quenching of the intrinsic fluorescence of the peptides and their induced surface pressure changes of lipid monolayer, it was conjectured that the peptide ZXR-2 might insert into cell membranes from the C-terminal and to a depth of the W position. Accordingly, I , I , and L residues which mainly exposed in aqueous solution were more responsible for the peptide self-association on cell membranes, while L , together with L , might help peptide insert and anchor to cell membranes. These results are significant to elucidate the crucial roles of such Ile/Leu residues at "a" and "d" positions in peptide-peptide and peptide-membrane interactions to exert the membrane disruption activity of lytic peptides. With further understanding about the structure-activity relationship of lytic peptides, it would be helpful for designing novel anticancer lytic peptides.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Isoleucina/química
Leucina/química
Peptídeos/farmacologia
[Mh] Termos MeSH secundário: 1,2-Dipalmitoilfosfatidilcolina/análogos & derivados
1,2-Dipalmitoilfosfatidilcolina/química
Alanina/química
Sequência de Aminoácidos
Substituição de Aminoácidos
Antineoplásicos/síntese química
Linhagem Celular Tumoral
Membrana Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Colesterol/química
Células HEK293
Células HeLa
Seres Humanos
L-Lactato Desidrogenase/secreção
Lipossomos/química
Peptídeos/síntese química
Fosfatidilserinas/química
Engenharia de Proteínas
Estrutura Secundária de Proteína
Eletricidade Estática
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Liposomes); 0 (Peptides); 0 (Phosphatidylserines); 04Y7590D77 (Isoleucine); 2644-64-6 (1,2-Dipalmitoylphosphatidylcholine); 3036-82-6 (dipalmitoylphosphatidylserine); 319X2NFW0A (colfosceril palmitate); 97C5T2UQ7J (Cholesterol); EC 1.1.1.27 (L-Lactate Dehydrogenase); GMW67QNF9C (Leucine); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1007/s00726-016-2350-9


  4 / 20182 MEDLINE  
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[PMID]:29386430
[Au] Autor:Hanawa T; Kawano Y; Satoh M
[Ad] Endereço:Faculty of Pharmaceutical Sciences, Tokyo University of Science.
[Ti] Título:[Development of "Patient Friendly Formulations" to Counter the Side Effects of Cancer Chemotherapy].
[So] Source:Yakugaku Zasshi;138(2):169-175, 2018.
[Is] ISSN:1347-5231
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo: Anticancer drug-induced stomatitis develops in 30% to 40% of cancer patients undergoing chemotherapy. However, medications for this condition are not commercially available in Japan. The "hospital formulation" is a customized medicine which hospital pharmacists prepare when doctors cannot carry out the medical therapy most suitable for a patient using commercial medicines. However, as the duties of pharmacists increase, use of the "hospital fomulation" decreases. Therefore, development of "hospital fomulations" based on individual evidence has a limit. Irsogladine maleate (IM) is a drug with gastric mucosal protective properties. IM increases intracellular cAMP levels in the gastric mucosa and activates communication between cells. It has been reported that the oral administration of IM reduces the incidence of 5-FU-based chemotherapy-induced stomatitis. However, there have been no reports on the effect of the direct use of IM in treating stomatitis. Therefore, we studied the development of an IM oral spray for stomatitis treatment, and obtained evidence of a direct effect in an animal experiment using a stomatitis model. Next, rebamipide mouthwash was administered to patients who had stomatitis caused by cancer chemotherapy. The total scores were classified into Grades 0 to 4 and evaluated as a stomatitis evaluation score (SES). When comparing SES and changes in the stomatitis area in patients, gradual reductions in the extent of stomatitis were observed, even during the period when SES did not change. Having patients fill in an observation chart was effective for grasping changes in symptoms in outpatients.
[Mh] Termos MeSH primário: Alanina/análogos & derivados
Antineoplásicos/efeitos adversos
Composição de Medicamentos
Quinolonas/administração & dosagem
Estomatite/induzido quimicamente
Estomatite/tratamento farmacológico
Triazinas/administração & dosagem
Triazinas/farmacologia
[Mh] Termos MeSH secundário: Administração Oral
Alanina/administração & dosagem
Animais
Comunicação Celular/efeitos dos fármacos
AMP Cíclico/metabolismo
Modelos Animais de Doenças
Medicina Baseada em Evidências
Mucosa Gástrica/citologia
Mucosa Gástrica/metabolismo
Seres Humanos
Antissépticos Bucais
Estomatite/prevenção & controle
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Mouthwashes); 0 (Quinolones); 0 (Triazines); E0399OZS9N (Cyclic AMP); LR583V32ZR (rebamipide); OF5P57N2ZX (Alanine); QBX79NZC1D (irsogladine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180202
[St] Status:MEDLINE
[do] DOI:10.1248/yakushi.17-00174-2


  5 / 20182 MEDLINE  
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[PMID]:28456568
[Au] Autor:Yin J; Zhu F; Hao W; Xu Q; Chang J; Wang H; Guo B
[Ad] Endereço:Key Laboratory of Environmental Biotechnology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China.
[Ti] Título:Acylamino acid chiral fungicides on toxiciepigenetics in lambda DNA methylation.
[So] Source:Food Chem Toxicol;109(Pt 1):735-745, 2017 Nov.
[Is] ISSN:1873-6351
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Acylamino acid chiral fungicides (AACFs) are low-toxicity pesticides and considered as non-carcinogenic chemicals to laboratory animals. Though AACFs have potential toxicological effects on mammals by non-genotoxic mechanisms, the toxicoepigenomics of AACFs has not been documented. In this article, we explored toxiciepigenetics of metalaxyl, benalaxyl and furalaxyl through epigenetics research on lambda DNA under different concentration exposure. The toxicoepigenomic difference of stereoisomers was examined also. Our results showed that AACFs would affect methyltransferase activity resulting in modulating DNA methylation levels and pattern. The LOAEL of R-metalaxyl and S-metalaxyl were 30 mM and 0.3 mM, respectively. The LOAEL of (R, S)-benalaxyl and (R, S)-furalaxyl were 0.3 Mm and 30 mM, respectively. A significant dose-response effect between (R, S)-benalaxyl and global methylation level was observed. Global methylation level was more susceptible to S-enantiomer compared to R-enantiomer, which indicated enantiomers of AACFs have the enantioselectivity in toxiciepigenetics. Moreover, the dependence of the methylation inhibition on the chiral center of metalaxyl may suggest a considerable specificity of the compound of AACFs for DNA methyltransferases. The inhibition effect between R-enantiomer and S-enantiomer of AACFs on DNA methylation levels generated in this study is important for low-toxicity pesticides toxicoepigenomics evaluation.
[Mh] Termos MeSH primário: Bacteriófago lambda/efeitos dos fármacos
Fungicidas Industriais/toxicidade
[Mh] Termos MeSH secundário: Alanina/análogos & derivados
Alanina/toxicidade
Bacteriófago lambda/genética
Bacteriófago lambda/metabolismo
Metilação de DNA/efeitos dos fármacos
DNA Viral/genética
DNA Viral/metabolismo
Epigenômica
Furanos/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Viral); 0 (Fungicides, Industrial); 0 (Furans); 0 (furalaxyl); 16K4M187IF (metalaxyl); 18TH6NY90J (benalaxyl); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


  6 / 20182 MEDLINE  
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[PMID]:28926819
[Au] Autor:Heerema JL; Helbing CC; Pyle GG
[Ad] Endereço:Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada T1K 6T5. Electronic address: jody.heerema@gmail.com.
[Ti] Título:Use of electro-olfactography to measure olfactory acuity in the North American bullfrog (Lithobates (Rana) catesbeiana) tadpole.
[So] Source:Ecotoxicol Environ Saf;147:643-647, 2018 Jan.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Olfaction is an important sense for aquatic organisms because it provides information about their surroundings, including nearby food, mates, and predators. Electro-olfactography (EOG) is an electrophysiological technique that measures the response of olfactory tissue to olfactory stimuli, and responses are indicative of olfactory acuity. Previous studies have used this technique on a variety of species including frogs, salamanders, daphniids and, most extensively, fish. In the present study, we introduce a novel modified EOG method for use on Lithobates (Rana) catesbeiana tadpoles. Responses to a number of olfactory stimuli including amino acids, an algal extract (Spirulina), and taurocholic acid were tested, as measured by EOG. Tadpoles exhibited consistent and reliable responses to L-alanine and Spirulina extract. Tadpoles also exhibited concentration-dependent responses to Spirulina extract. These findings indicate that tadpole EOG is a viable electrophysiology technique that can be used in future research to study olfactory physiology and impairment in tadpoles.
[Mh] Termos MeSH primário: Fenômenos Eletrofisiológicos
Larva/fisiologia
Percepção Olfatória/fisiologia
Olfato/fisiologia
[Mh] Termos MeSH secundário: Alanina/química
Animais
Técnicas Eletroquímicas
Microeletrodos
Rana catesbeiana
Spirulina/química
Ácido Taurocólico/química
Estados Unidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
5E090O0G3Z (Taurocholic Acid); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE


  7 / 20182 MEDLINE  
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[PMID]:29315328
[Au] Autor:Hatazawa Y; Qian K; Gong DW; Kamei Y
[Ad] Endereço:Laboratory of Molecular Nutrition, Graduate School of Life and Environmental Science, Kyoto Prefectural University, Kyoto, Japan.
[Ti] Título:PGC-1α regulates alanine metabolism in muscle cells.
[So] Source:PLoS One;13(1):e0190904, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The skeletal muscle is the largest organ in the human body, depositing energy as protein/amino acids, which are degraded in catabolic conditions such as fasting. Alanine is synthesized and secreted from the skeletal muscle that is used as substrates of gluconeogenesis in the liver. During fasting, the expression of PGC-1α, a transcriptional coactivator of nuclear receptors, is increased in the liver and regulates gluconeogenesis. In the present study, we observed increased mRNA expression of PGC-1α and alanine aminotransferase 2 (ALT2) in the skeletal muscle during fasting. In C2C12 myoblast cells overexpressing PGC-1α, ALT2 expression was increased concomitant with an increased alanine level in the cells and medium. In addition, PGC-1α, along with nuclear receptor ERR, dose-dependently enhanced the ALT2 promoter activity in reporter assay using C2C12 cells. In the absence of glucose in the culture medium, mRNA levels of PGC-1α and ALT2 increased. Endogenous PGC-1α knockdown in C2C12 cells reduced ALT2 gene expression level, induced by the no-glucose medium. Taken together, in the skeletal muscle, PGC-1α activates ALT2 gene expression, and alanine production may play roles in adaptation to fasting.
[Mh] Termos MeSH primário: Alanina/metabolismo
Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/fisiologia
[Mh] Termos MeSH secundário: Alanina Transaminase/genética
Animais
Linhagem Celular
Jejum
Regulação da Expressão Gênica
Fígado/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
Músculo Esquelético/metabolismo
Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética
Regiões Promotoras Genéticas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha); 0 (Ppargc1a protein, mouse); EC 2.6.1.2 (Alanine Transaminase); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190904


  8 / 20182 MEDLINE  
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[PMID]:29294327
[Au] Autor:Ren C; Liu J; Zhou J; Liang H; Wang Y; Sun Y; Ma B; Yin Y
[Ad] Endereço:Departments of Human Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China.
[Ti] Título:Low levels of serum serotonin and amino acids identified in migraine patients.
[So] Source:Biochem Biophys Res Commun;496(2):267-273, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Migraine is a highly disabling primary headache associated with a high socioeconomic burden and a generally high prevalence. The clinical management of migraine remains a challenge. This study was undertaken to identify potential serum biomarkers of migraine. Using Liquid Chromatography coupled to Mass Spectrometry (LC-MS), the metabolomic profile of migraine was compared with healthy individuals. Principal component analysis (PCA) and Orthogonal partial least squares-discriminant analysis (orthoPLS-DA) showed the metabolomic profile of migraine is distinguishable from controls. Volcano plot analysis identified 10 serum metabolites significantly decreased during migraine. One of these was serotonin, and the other 9 were amino acids. Pathway analysis and enrichment analysis showed tryptophan metabolism (serotonin metabolism), arginine and proline metabolism, and aminoacyl-tRNA biosynthesis are the three most prominently altered pathways in migraine. ROC curve analysis indicated Glycyl-l-proline, N-Methyl-dl-Alanine and l-Methionine are potential sensitive and specific biomarkers for migraine. Our results show Glycyl-l-proline, N-Methyl-dl-Alanine and l-Methionine may be as specific or more specific for migraine than serotonin which is the traditional biomarker of migraine. We propose that therapeutic manipulation of these metabolites or metabolic pathways may be helpful in the prevention and treatment of migraine.
[Mh] Termos MeSH primário: Alanina/análogos & derivados
Dipeptídeos/sangue
Metionina/sangue
Transtornos de Enxaqueca/diagnóstico
Serotonina/sangue
[Mh] Termos MeSH secundário: Adulto
Alanina/sangue
Arginina/sangue
Biomarcadores/sangue
Estudos de Casos e Controles
Cromatografia Líquida de Alta Pressão/métodos
Análise Discriminante
Feminino
Seres Humanos
Masculino
Metaboloma
Transtornos de Enxaqueca/sangue
Transtornos de Enxaqueca/fisiopatologia
Análise de Componente Principal
Prolina/sangue
Aminoacil-RNA de Transferência/sangue
Curva ROC
Triptofano/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers); 0 (Dipeptides); 0 (RNA, Transfer, Amino Acyl); 333DO1RDJY (Serotonin); 600-21-5 (N-methylalanine); 704-15-4 (glycylproline); 8DUH1N11BX (Tryptophan); 94ZLA3W45F (Arginine); 9DLQ4CIU6V (Proline); AE28F7PNPL (Methionine); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180103
[St] Status:MEDLINE


  9 / 20182 MEDLINE  
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[PMID]:28458352
[Au] Autor:Matsuda T; Hiraoka S; Urashima H; Ogura A; Ishida T
[Ad] Endereço:Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University.
[Ti] Título:Preparation of an Ultrafine Rebamipide Ophthalmic Suspension with High Transparency.
[So] Source:Biol Pharm Bull;40(5):665-674, 2017.
[Is] ISSN:1347-5215
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:A 2% commercially available, milky-white, rebamipide micro-particle suspension is used to treat dry eyes, and it causes short-term blurring of the patient's vision. In the current study, to improve the transparency of a rebamipide suspension, we attempted to obtain a clear rebamipide suspension by transforming the rebamipide particles to an ultrafine state. In the initial few efforts, various rebamipide suspensions were prepared using a neutralizing crystallization method with additives, but the suspensions retained their opaque quality. However, as a consequence of several critical improvements in the neutralizing crystallization methods such as selection of additives for crystallization, process parameters during crystallization, the dispersion method, and dialysis, we obtained an ultrafine rebamipide suspension (2%) that was highly transparent (transmittance at 640 nm: 59%). The particle size and transparency demonstrated the fewest level of changes at 25°C after 3 years, compared to initial levels. During that period, no obvious particle sedimentation was observed. The administration of this ultrafine rebamipide suspension (2%) increased the conjunctival mucin, which was comparable to the commercially available micro-particle suspension (2%). The corneal and conjunctival concentration of rebamipide following ocular administration of the ultrafine suspension was slightly higher than that of the micro-particle suspension. The ultrafine rebamipide suspension (eye-drop formulation) with a highly transparent ophthalmic clearness should improve a patient's QOL by preventing even a shortened period of blurred vision.
[Mh] Termos MeSH primário: Alanina/análogos & derivados
Antiulcerosos/administração & dosagem
Antiulcerosos/química
Soluções Oftálmicas/química
Quinolonas/administração & dosagem
Quinolonas/química
[Mh] Termos MeSH secundário: Administração Oftálmica
Alanina/administração & dosagem
Alanina/química
Animais
Túnica Conjuntiva/efeitos dos fármacos
Túnica Conjuntiva/metabolismo
Córnea/efeitos dos fármacos
Córnea/metabolismo
Cristalização
Diálise
Masculino
Mucinas/metabolismo
Tamanho da Partícula
Coelhos
Suspensões
Difração de Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Ulcer Agents); 0 (Mucins); 0 (Ophthalmic Solutions); 0 (Quinolones); 0 (Suspensions); LR583V32ZR (rebamipide); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1248/bpb.b16-00962


  10 / 20182 MEDLINE  
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[PMID]:28459139
[Au] Autor:Tang Q; Alontaga AY; Holyoak T; Fenton AW
[Ad] Endereço:Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, Kansas.
[Ti] Título:Exploring the limits of the usefulness of mutagenesis in studies of allosteric mechanisms.
[So] Source:Hum Mutat;38(9):1144-1154, 2017 Sep.
[Is] ISSN:1098-1004
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The outcome of structure-guided mutational analyses is often used in support of postulated mechanisms of protein allostery. However, the limits of how informative mutations can be in understanding allosteric mechanisms are not completely clear. Here, we report an exercise to evaluate whether mutational data can support a simplistic mechanistic model, developed with minimal data inputs. Due to the lack of a mechanism to explain how alanine allosterically modifies the affinity of human liver pyruvate kinase (approved symbol PKLR) for its substrate, phosphoenolpyruvate, we proposed a speculative allosteric mechanism for this system. Within the allosteric amino-acid-binding site (something in the effector site must, of necessity, contribute to the allosteric mechanism), we implemented multiple mutational strategies: (1) site-directed random mutagenesis at positions that contact bound alanine and (2) mutations to probe specific questions. Despite acknowledged inadequacies used to formulate the speculative mechanism, many mutations modified the allosteric coupling constant (Q ) consistent with that mechanism. The observed support for this speculative mechanism leaves us to ponder the best use of mutational data in structure-function studies of allosteric mechanisms. The mutational databank derived from this exercise has an independent value for training and testing algorithms specific to allostery.
[Mh] Termos MeSH primário: Alanina/metabolismo
Mutagênese Sítio-Dirigida/métodos
Piruvato Quinase/genética
[Mh] Termos MeSH secundário: Algoritmos
Regulação Alostérica
Sítio Alostérico
Domínio Catalítico
Seres Humanos
Modelos Moleculares
Fosfoenolpiruvato
Conformação Proteica
Piruvato Quinase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
73-89-2 (Phosphoenolpyruvate); EC 2.7.1.40 (Pyruvate Kinase); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1002/humu.23239



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