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[PMID]:27775977
[Au] Autor:Grey KR; Hanson JL; Hagen SL; Hylwa SA; Warshaw EM
[Ad] Endereço:From the *University of Minnesota Medical School; †Parkside Occupational and Contact Dermatitis Clinic, Hennepin County Medical Center; ‡Department of Dermatology, Minneapolis Veterans Affairs Medical Center; and §Department of Dermatology, University of Minnesota Medical School, Minneapolis, MN.
[Ti] Título:Epidemiology and Co-Reactivity of Novel Surfactant Allergens: A Double-Blind Randomized Controlled Study.
[So] Source:Dermatitis;27(6):348-354, 2016 Nov/Dec.
[Is] ISSN:2162-5220
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Surfactants are cleansing agents used in products such as shampoos and soaps. OBJECTIVES: The aims of this study were to identify positivity rates to 3 novel amide-containing surfactants (sodium lauroyl sarcosinate, isostearamidopropyl morpholine lactate, and disodium lauroamphodiacetate) and evaluate co-reactivity with other surfactants in patients with known surfactant sensitivity. METHODS: Previously patch-tested, surfactant-positive patients were identified via chart review and invited to participate. Participants were patch tested to screening surfactants (cocamidopropyl betaine, amidoamine, dimethylaminopropylamine, cocamide diethanolamine [DEA], oleamidopropyl dimethylamine, and decyl glucoside), as well as 3 novel surfactants: sodium lauroyl sarcosinate 0.5% and 1.0% aq, isostearamidopropyl morpholine lactate 0.5% and 1.0% aq, disodium lauroamphodiacetate 1.0 and 2.0% aq, and a hypoallergenic liquid cleanser (tested semiopen). Participants and clinicians were blinded. The order of tested allergens was randomized. RESULTS: Forty-seven participants completed the study. Excluding doubtful reactions, positive reactions were most common to oleamidopropyl dimethylamine (34%) and dimethylaminopropylamine (34%), followed by isostearamidopropyl morpholine lactate (23%). Reactivity was not associated with history of childhood eczema. Co-reactivity was high among oleamidopropyl dimethylamine, dimethylaminopropylamine, cocamidopropyl betaine, amidoamine, and isostearamidopropyl morpholine lactate. None of the participants who reacted to cocamide DEA reacted to an additional surfactant. CONCLUSIONS: Isostearamidopropyl morpholine lactate may be an important emerging allergen with sensitivity rates comparable with those of oleamidopropyl dimethylamine and dimethylaminopropylamine. Co-reactivity among surfactants was frequent except for cocamide DEA.
[Mh] Termos MeSH primário: Alérgenos/efeitos adversos
Dermatite Alérgica de Contato/etiologia
Tensoativos/efeitos adversos
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Dermatite Alérgica de Contato/diagnóstico
Dermatite Alérgica de Contato/epidemiologia
Método Duplo-Cego
Feminino
Seres Humanos
Masculino
Meia-Idade
Testes do Emplastro
Sarcosina/efeitos adversos
Sarcosina/análogos & derivados
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Allergens); 0 (Surface-Active Agents); 632GS99618 (sarkosyl); Z711V88R5F (Sarcosine)
[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:161025
[St] Status:MEDLINE


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[PMID]:29040295
[Au] Autor:Chang TW; Wei SY; Wang SH; Wei HM; Wang YJ; Wang CF; Chen C; Liao YD
[Ad] Endereço:Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
[Ti] Título:Hydrophobic residues are critical for the helix-forming, hemolytic and bactericidal activities of amphipathic antimicrobial peptide TP4.
[So] Source:PLoS One;12(10):e0186442, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Antimicrobial peptides are important components of the host innate defense mechanism against invading pathogens, especially for drug-resistant bacteria. In addition to bactericidal activity, the 25 residue peptide TP4 isolated from Nile tilapia also stimulates cell proliferation and regulates the innate immune system in mice. In this report, TP4 hyperpolarized and depolarized the membrane potential of Pseudomonas aeruginosa at sub-lethal and lethal concentrations. It also inhibited and eradicated biofilm formation. The in vitro binding of TP4 to bacterial outer membrane target protein, OprI, was markedly enhanced by a membrane-like surfactant sarkosyl and lipopolysaccharide, which converted TP4 into an α-helix. The solution structure of TP4 in dodecylphosphocholine was solved by NMR analyses. It contained a typical α-helix at residues Phe10-Arg22 and a distorted helical segment at Ile6-Phe10, as well as a hydrophobic core at the N-terminus and a cationic patch at the C-terminus. Residues Ile16, Leu19 and Ile20 in the hydrophobic face of the main helix were critical for the integrity of amphipathic structure, other hydrophobic residues played important roles in hemolytic and bactericidal activities. A model for the assembly of helical TP4 embedded in sarkosyl vesicle is proposed. This study may provide valuable insight for engineering AMPs to have potent bactericidal activity but low hemolytic activity.
[Mh] Termos MeSH primário: Peptídeos Catiônicos Antimicrobianos/química
Proteínas de Bactérias/metabolismo
Biofilmes/efeitos dos fármacos
Proteínas de Peixes/química
Lipoproteínas/metabolismo
Pseudomonas aeruginosa/efeitos dos fármacos
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Peptídeos Catiônicos Antimicrobianos/síntese química
Peptídeos Catiônicos Antimicrobianos/isolamento & purificação
Peptídeos Catiônicos Antimicrobianos/farmacologia
Proteínas de Bactérias/química
Biofilmes/crescimento & desenvolvimento
Candida albicans/efeitos dos fármacos
Candida albicans/crescimento & desenvolvimento
Permeabilidade da Membrana Celular/efeitos dos fármacos
Ciclídeos/metabolismo
Eritrócitos/efeitos dos fármacos
Proteínas de Peixes/síntese química
Proteínas de Peixes/isolamento & purificação
Proteínas de Peixes/farmacologia
Interações Hidrofóbicas e Hidrofílicas
Lipopolissacarídeos/química
Lipoproteínas/química
Listeria monocytogenes/efeitos dos fármacos
Listeria monocytogenes/crescimento & desenvolvimento
Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento
Camundongos
Camundongos Endogâmicos C57BL
Testes de Sensibilidade Microbiana
Modelos Moleculares
Ressonância Magnética Nuclear Biomolecular
Fosforilcolina/análogos & derivados
Fosforilcolina/química
Ligação Proteica
Conformação Proteica em alfa-Hélice
Pseudomonas aeruginosa/crescimento & desenvolvimento
Pseudomonas aeruginosa/metabolismo
Sarcosina/análogos & derivados
Sarcosina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimicrobial Cationic Peptides); 0 (Bacterial Proteins); 0 (Fish Proteins); 0 (Lipopolysaccharides); 0 (Lipoproteins); 107-73-3 (Phosphorylcholine); 125691-83-0 (outer membrane lipoprotein I, Bacteria); 53949-18-1 (dodecylphosphocholine); 632GS99618 (sarkosyl); Z711V88R5F (Sarcosine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171018
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186442


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[PMID]:28542385
[Au] Autor:Zemanová V; Pavlík M; Pavlíková D
[Ad] Endereço:Isotope Laboratory, Institute of Experimental Botany, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
[Ti] Título:Cadmium toxicity induced contrasting patterns of concentrations of free sarcosine, specific amino acids and selected microelements in two Noccaea species.
[So] Source:PLoS One;12(5):e0177963, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cadmium (Cd) toxicity affects numerous metabolic processes in plants. In the presence of Cd, plants accumulate specific amino acids which may be beneficial to developing Cd tolerance. Our study aimed to characterize the changes in the metabolism of selected free amino acids that are associated with Cd tolerance, and investigate the levels of selected microelements in order to relate these changes to the adaptation strategies of two metallophytes-Noccaea caerulescens (Redlschlag, Austria) and Noccaea praecox (Mezica, Slovenia). The plants were exposed to Cd contamination (90 mg Cd/kg soil) for 120 days in a pot experiment. Our results showed higher Cd accumulation in N. praecox compared to N. caerulescens. Cadmium contamination reduced the zinc and nickel levels in both species and a mixed effect was determined for copper and manganese content. Differences in free amino acid metabolism were observed between the two metallophytes growing under Cd-free and Cd-loaded conditions. Under Cd-free conditions, aromatic amino acids (phenylalanine, tryptophan and tyrosine) and branched-chain amino acids (leucine, isoleucine and valine) were accumulated more in the leaves of N. praecox than in N. caerulescens. Cd stress increased the content of these amino acids in both species but this increase was significant only in N. caerulescens leaves. Marked differences in the responses of the two species to Cd stress were shown for alanine, phenylalanine, threonine and sarcosine. Cadmium contamination also induced an increase of threonine as alanine and sarcosine decrease, which was larger in N. caerulescens than in N. praecox. All these factors contribute to the higher adaptation of N. praecox to Cd stress.
[Mh] Termos MeSH primário: Aminoácidos/metabolismo
Brassicaceae/classificação
Brassicaceae/metabolismo
Cádmio/toxicidade
Redes e Vias Metabólicas/efeitos dos fármacos
Sarcosina/metabolismo
Oligoelementos/metabolismo
[Mh] Termos MeSH secundário: Brassicaceae/efeitos dos fármacos
Brassicaceae/crescimento & desenvolvimento
Folhas de Planta/efeitos dos fármacos
Folhas de Planta/crescimento & desenvolvimento
Folhas de Planta/metabolismo
Estresse Fisiológico/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Trace Elements); 00BH33GNGH (Cadmium); Z711V88R5F (Sarcosine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177963


  4 / 1301 MEDLINE  
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[PMID]:28302759
[Au] Autor:Piert M; Shao X; Raffel D; Davenport MS; Montgomery J; Kunju LP; Hockley BG; Siddiqui J; Scott PJH; Chinnaiyan AM; Rajendiran T
[Ad] Endereço:Department of Radiology, University of Michigan, Ann Arbor, Michigan mpiert@umich.edu.
[Ti] Título:Preclinical Evaluation of C-Sarcosine as a Substrate of Proton-Coupled Amino Acid Transporters and First Human Application in Prostate Cancer.
[So] Source:J Nucl Med;58(8):1216-1223, 2017 Aug.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sarcosine is a known substrate of proton-coupled amino acid transporters (PATs), which are overexpressed in selected tissues and solid tumors. Sarcosine, an -methyl derivative of the amino acid glycine and a metabolic product of choline, plays an important role for prostate cancer aggressiveness and progression. C-radiolabeled sarcosine was tested as a new PET imaging probe in comparison with C-choline in 2 prostate cancer tumor xenograft models (DU-145 and PC-3). We characterized C-sarcosine transport in PC-3 and LNCaP tumor cells and performed C-sarcosine PET with CT in the first human subject with localized Gleason 4 + 3 prostate cancer. Target metabolite analyses of sarcosine and its natural precursors, glycine and choline, were performed from independent human prostate tissues. In vitro assays indicated blockage of C-sarcosine uptake into PC-3 and LNCaP tumor cells by excess unlabeled (cold) sarcosine. 5-hydroxy-l-tryptophan, but not 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid, competitively inhibited C-sarcosine tumor cell uptake, confirming PAT-mediated transport. In vivo tumor-to-background ratios (TBRs) obtained from C-sarcosine PET were significantly elevated compared with C-choline in DU-145 (TBR: 1.92 ± 0.11 for C-sarcosine vs. 1.41 ± 0.13 for C-choline [ = 10; < 0.002]) and PC-3 tumors (TBR: 1.89 ± 0.2 for C-sarcosine vs. 1.34 ± 0.16 for C-choline [ = 7; < 0.002]). C-sarcosine produced high-contrast images in 1 case of localized clinically significant prostate cancer. Target metabolite analyses revealed significant stepwise increases of sarcosine, glycine, and choline tissue levels from benign prostate tissue to localized prostate cancer and subsequently metastatic disease. C-sarcosine showed a favorable radiation dosimetry with an effective dose estimate of 0.0045 mSv/MBq, resulting in 2.68 mSv for a human subject (600-MBq dose). C-sarcosine is a novel radiotracer for PATs and shows initial utility for prostate cancer imaging, with potential benefit over commonly used C-choline.
[Mh] Termos MeSH primário: Sistemas de Transporte de Aminoácidos/metabolismo
Radioisótopos de Carbono
Neoplasias da Próstata/diagnóstico por imagem
Neoplasias da Próstata/metabolismo
Prótons
Sarcosina/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Seres Humanos
Masculino
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
Radiometria
Sarcosina/farmacocinética
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acid Transport Systems); 0 (Carbon Radioisotopes); 0 (Protons); Z711V88R5F (Sarcosine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170318
[St] Status:MEDLINE
[do] DOI:10.2967/jnumed.116.173179


  5 / 1301 MEDLINE  
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[PMID]:28302446
[Au] Autor:Oyama M; Kuraoka S; Watanabe S; Iwai T; Tanabe M
[Ad] Endereço:Laboratory of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan; Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
[Ti] Título:Electrophysiological evidence of increased glycine receptor-mediated phasic and tonic inhibition by blockade of glycine transporters in spinal superficial dorsal horn neurons of adult mice.
[So] Source:J Pharmacol Sci;133(3):162-167, 2017 Mar.
[Is] ISSN:1347-8648
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:To understand the synaptic and/or extrasynaptic mechanisms underlying pain relief by blockade of glycine transporter subtypes GlyT1 and GlyT2, whole-cell recordings were made from dorsal horn neurons in spinal slices from adult mice, and the effects of NFPS and ALX-1393, selective GlyT1 and GlyT2 inhibitors, respectively, on phasic evoked or miniature glycinergic inhibitory postsynaptic currents (eIPSCs or mIPSCs) were examined. NFPS and ALX-1393 prolonged the decay phase of eIPSCs without affecting their amplitude. In the presence of tetrodotoxin to record mIPSCs, NFPS and ALX-1393 induced a tonic inward current that was reversed by strychnine. Although NFPS had no statistically significant influences on mIPSCs, ALX-1393 significantly increased their frequency. We then further explored the role of GlyTs in the maintenance of glycinergic IPSCs. To facilitate vesicular release of glycine, repetitive high-frequency stimulation (HFS) was applied at 10 Hz for 3 min during continuous recordings of eIPSCs at 0.1 Hz. Prominent suppression of eIPSCs was evident after HFS in the presence of ALX-1393, but not NFPS. Thus, it appears that phasic and tonic inhibition may contribute to the analgesic effects of GlyT inhibitors. However, reduced glycinergic inhibition due to impaired vesicular refilling could hamper the analgesic efficacy of GlyT2 inhibitors.
[Mh] Termos MeSH primário: Proteínas da Membrana Plasmática de Transporte de Glicina/fisiologia
Células do Corno Posterior/fisiologia
[Mh] Termos MeSH secundário: Animais
Proteínas da Membrana Plasmática de Transporte de Glicina/antagonistas & inibidores
Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos
Masculino
Camundongos
Células do Corno Posterior/efeitos dos fármacos
Sarcosina/análogos & derivados
Sarcosina/farmacologia
Serina/análogos & derivados
Serina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ALX 1393); 0 (Glycine Plasma Membrane Transport Proteins); 0 (N-(3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)-3-(4'-phenylphenoxy)propyl)sarcosine); 0 (Slc6a5 protein, mouse); 0 (Slc6a9 protein, mouse); 452VLY9402 (Serine); Z711V88R5F (Sarcosine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170318
[St] Status:MEDLINE


  6 / 1301 MEDLINE  
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[PMID]:28245819
[Au] Autor:Lee MY; Lin YR; Tu YS; Tseng YJ; Chan MH; Chen HH
[Ad] Endereço:Master/PhD Program in Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 97004, Taiwan.
[Ti] Título:Effects of sarcosine and N, N-dimethylglycine on NMDA receptor-mediated excitatory field potentials.
[So] Source:J Biomed Sci;24(1):18, 2017 Feb 28.
[Is] ISSN:1423-0127
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Sarcosine, a glycine transporter type 1 inhibitor and an N-methyl-D-aspartate (NMDA) receptor co-agonist at the glycine binding site, potentiates NMDA receptor function. Structurally similar to sarcosine, N,N-dimethylglycine (DMG) is also N-methyl glycine-derivative amino acid and commonly used as a dietary supplement. The present study compared the effects of sarcosine and DMG on NMDA receptor-mediated excitatory field potentials (EFPs) in mouse medial prefrontal cortex brain slices using a multi-electrode array system. RESULTS: Glycine, sarcosine and DMG alone did not alter the NMDA receptor-mediated EFPs, but in combination with glutamate, glycine and its N-methyl derivatives significantly increased the frequency and amplitude of EFPs. The enhancing effects of glycine analogs in combination with glutamate on EFPs were remarkably reduced by the glycine binding site antagonist 7-chlorokynurenate (7-CK). However, DMG, but not sarcosine, reduced the frequency and amplitude of EFPs elicited by co-application of glutamate plus glycine. D-cycloserine, a partial agonist at the glycine binding site on NMDA receptors, affected EFPs in a similar manner to DMG. Furthermore, DMG, but not sarcosine, reduced the frequencies and amplitudes of EFPs elicited by glutamate plus D-serine, another endogenous ligand for glycine binding site. CONCLUSIONS: These findings suggest that sarcosine acts as a full agonist, yet DMG is a partial agonist at glycine binding site of NMDA receptors. The molecular docking analysis indicated that the interactions of glycine, sarcosine, and DMG to NMDA receptors are highly similar, supporting that the glycine binding site of NMDA receptors is a critical target site for sarcosine and DMG.
[Mh] Termos MeSH primário: Potenciais da Membrana/efeitos dos fármacos
Receptores de N-Metil-D-Aspartato/agonistas
Receptores de N-Metil-D-Aspartato/metabolismo
Sarcosina/análogos & derivados
Sarcosina/farmacologia
[Mh] Termos MeSH secundário: Animais
Masculino
Camundongos
Camundongos Endogâmicos ICR
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, N-Methyl-D-Aspartate); 7797M4CPPA (dimethylglycine); Z711V88R5F (Sarcosine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170310
[Lr] Data última revisão:
170310
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170302
[St] Status:MEDLINE
[do] DOI:10.1186/s12929-016-0314-8


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[PMID]:28236690
[Au] Autor:Rudra S; Dasmandal S; Mahapatra A
[Ad] Endereço:Department of Chemistry, Jadavpur University, Kolkata 700 032, India.
[Ti] Título:Binding interaction of sodium-N-dodecanoyl sarcosinate with hemoglobin and myoglobin: Physicochemical and spectroscopic studies with molecular docking analysis.
[So] Source:J Colloid Interface Sci;496:267-277, 2017 06 15.
[Is] ISSN:1095-7103
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The interaction of an amino acid surfactant, sodium-N-dodecanoyl sarcosinate (SDDS), with two heme proteins, hemoglobin (Hb) and myoglobin (Mb), has been studied employing various physicochemical and spectroscopic techniques like tensiometry, UV-Vis spectroscopy, steady-state fluorometry, time-resolved fluorometry, circular dichroism (CD) spectroscopy, calorimetry and stopped flow kinetics at physiological pH of 7.2 and 298K. Tensiometric and fluorometric analysis suggest that the interaction between SDDS and protein starts with the monomer form of the surfactant which produces small induced micelles. The micelles bind to protein backbone causing denaturation of the protein structure, and finally free micelles are formed on further addition of surfactant. Life-time measurements have been performed to shed light on the binding of surfactant around the tryptophan moieties present in the heme proteins. The changes in protein secondary structure induced by AAS collected from CD measurements reveals that the proteins are quite perturbed upon action of SDDS. The enthalpy change values of each stepwise interaction process have been found from isothermal titration calorimetry (ITC). The kinetics of the protein-surfactant interaction process has been studied using stopped flow technique. Quantum mechanical calculations involving density functional theory (DFT) and molecular docking analysis have been performed to highlight the interactive phenomenon between the surfactant and heme proteins. Thus the entire study shows a total inspection of an amino acid surfactant-heme protein interaction.
[Mh] Termos MeSH primário: Hemoglobinas/química
Mioglobina/química
Sarcosina/análogos & derivados
[Mh] Termos MeSH secundário: Fenômenos Biofísicos
Seres Humanos
Cinética
Micelas
Simulação de Acoplamento Molecular
Ligação Proteica
Desnaturação Proteica
Estrutura Secundária de Proteína
Sarcosina/química
Tensoativos
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Hemoglobins); 0 (Micelles); 0 (Myoglobin); 0 (Surface-Active Agents); 0 (dodecanoylsarcosinate); Z711V88R5F (Sarcosine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170226
[St] Status:MEDLINE


  8 / 1301 MEDLINE  
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[PMID]:28202787
[Au] Autor:Irimia C; Buczynski MW; Natividad LA; Laredo SA; Avalos N; Parsons LH
[Ad] Endereço:Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California 92037, and cristin4@stanford.edu.
[Ti] Título:Dysregulated Glycine Signaling Contributes to Increased Impulsivity during Protracted Alcohol Abstinence.
[So] Source:J Neurosci;37(7):1853-1861, 2017 Feb 15.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Persons with alcoholism who are abstinent exhibit persistent impairments in the capacity for response inhibition, and this form of impulsivity is significantly associated with heightened relapse risk. Brain-imaging studies implicate aberrant prefrontal cortical function in this behavioral pathology, although the underlying mechanisms are not understood. Here we present evidence that deficient activation of glycine and serine release in the ventral medial prefrontal cortex (vmPFC) contributes to increased motor impulsivity during protracted abstinence from long-term alcohol exposure. Levels of 12 neurotransmitters were monitored in the rat vmPFC during the performance of a challenging variant of the five-choice serial reaction time task (5-CSRTT) in which alcohol-exposed rats exhibit excessive premature responding. Following long-term ethanol exposure, rats showed blunted task-related recruitment of vmPFC glycine and serine release, and the loss of an inverse relationship between levels of these neurotransmitters and premature responding normally evident in alcohol-naive subjects. Intra-vmPFC administration of the glycine transport inhibitor ALX5407 prevented excessive premature responding by alcohol-exposed rats, and this was reliant on NMDA glycine site availability. Alcohol-exposed rats and controls did not differ in their premature responding and glycine and serine levels in vmPFC during the performance of the standard 5-CSRTT. Collectively, these findings provide novel insight into cortical neurochemical mechanisms contributing to increased impulsivity following long-term alcohol exposure and highlight the NMDA receptor coagonist site as a potential therapeutic target for increased impulsivity that may contribute to relapse risk. Persons with alcoholism demonstrate increased motor impulsivity during abstinence; however, the neuronal mechanisms underlying these behavioral effects remain unknown. Here, we took advantage of an animal model that shows deficiencies in inhibitory control following prolonged alcohol exposure to investigate the neurotransmitters that are potentially responsible for dysregulated motor impulsivity following long-term alcohol exposure. We found that increased motor impulsivity is associated with reduced recruitment of glycine and serine neurotransmitters in the ventromedial prefrontal cortex (vmPFC) cortex in rats following long-term alcohol exposure. Administration of glycine transport inhibitor ALX5407 in the vmPFC alleviated deficits in impulse control.
[Mh] Termos MeSH primário: Abstinência de Álcool
Consumo de Bebidas Alcoólicas/fisiopatologia
Glicina/metabolismo
Comportamento Impulsivo/fisiologia
Transdução de Sinais/fisiologia
[Mh] Termos MeSH secundário: Animais
Depressores do Sistema Nervoso Central/efeitos adversos
Comportamento de Escolha/efeitos dos fármacos
Modelos Animais de Doenças
Etanol/efeitos adversos
Antagonistas de Aminoácidos Excitatórios/farmacologia
Transportador 2 de Aminoácido Excitatório/antagonistas & inibidores
Masculino
Neurotransmissores/metabolismo
Estimulação Luminosa
Quinolonas/farmacologia
Ratos
Ratos Wistar
Tempo de Reação/efeitos dos fármacos
Sarcosina/análogos & derivados
Sarcosina/farmacologia
Serina/metabolismo
Serina/farmacologia
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 ((R)-(N-(3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl))sarcosine); 0 (Central Nervous System Depressants); 0 (Excitatory Amino Acid Antagonists); 0 (Excitatory Amino Acid Transporter 2); 0 (Neurotransmitter Agents); 0 (Quinolones); 3K9958V90M (Ethanol); 452VLY9402 (Serine); I9WY146163 (L 701324); TE7660XO1C (Glycine); Z711V88R5F (Sarcosine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170217
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.2466-16.2017


  9 / 1301 MEDLINE  
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[PMID]:28174298
[Au] Autor:Safar F; Hurdiss E; Erotocritou M; Greiner T; Lape R; Irvine MW; Fang G; Jane D; Yu R; Dämgen MA; Biggin PC; Sivilotti LG
[Ad] Endereço:From the Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
[Ti] Título:The Startle Disease Mutation E103K Impairs Activation of Human Homomeric α1 Glycine Receptors by Disrupting an Intersubunit Salt Bridge across the Agonist Binding Site.
[So] Source:J Biol Chem;292(12):5031-5042, 2017 Mar 24.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glycine receptors (GlyR) belong to the pentameric ligand-gated ion channel (pLGIC) superfamily and mediate fast inhibitory transmission in the vertebrate CNS. Disruption of glycinergic transmission by inherited mutations produces startle disease in man. Many startle mutations are in GlyRs and provide useful clues to the function of the channel domains. E103K is one of few startle mutations found in the extracellular agonist binding site of the channel, in loop A of the principal side of the subunit interface. Homology modeling shows that the side chain of Glu-103 is close to that of Arg-131, in loop E of the complementary side of the binding site, and may form a salt bridge at the back of the binding site, constraining its size. We investigated this hypothesis in recombinant human α1 GlyR by site-directed mutagenesis and functional measurements of agonist efficacy and potency by whole cell patch clamp and single channel recording. Despite its position near the binding site, E103K causes hyperekplexia by impairing the efficacy of glycine, its ability to gate the channel once bound, which is very high in wild type GlyR. Mutating Glu-103 and Arg-131 caused various degrees of loss-of-function in the action of glycine, whereas mutations in Arg-131 enhanced the efficacy of the slightly bigger partial agonist sarcosine ( -methylglycine). The effects of the single charge-swapping mutations of these two residues were largely rescued in the double mutant, supporting the possibility that they interact via a salt bridge that normally constrains the efficacy of larger agonist molecules.
[Mh] Termos MeSH primário: Hiperecplexia/genética
Mutação Puntual
Receptores da Glicina/genética
Receptores da Glicina/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Cristalografia por Raios X
Glicina/metabolismo
Células HEK293
Seres Humanos
Hiperecplexia/metabolismo
Modelos Moleculares
Mutagênese Sítio-Dirigida
Receptores da Glicina/química
Sarcosina/metabolismo
Alinhamento de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Glycine); 0 (glycine receptor alpha1); TE7660XO1C (Glycine); Z711V88R5F (Sarcosine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170209
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.767616


  10 / 1301 MEDLINE  
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[PMID]:28166625
[Au] Autor:Sano K; Ohashi M; Kanazaki K; Makino A; Ding N; Deguchi J; Kanada Y; Ono M; Saji H
[Ad] Endereço:Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshida, Shimoadachi-cho, Sakyo-ku, Kyoto, Japan , 606-8501.
[Ti] Título:Indocyanine Green-Labeled Polysarcosine for in Vivo Photoacoustic Tumor Imaging.
[So] Source:Bioconjug Chem;28(4):1024-1030, 2017 Apr 19.
[Is] ISSN:1520-4812
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Photoacoustic (PA) imaging has been considered an attractive imaging modality for sensitive and in-depth imaging of biomolecules with a high resolution in vivo. PA imaging probes utilizing fluorescence dyes, including indocyanine green (ICG), have been proposed to enhance PA signal intensity. On the other hand, nanomicelles modified with polysarcosine (PSar), a biocompatible hydrophilic polymer, on their surface have previously achieved rapid tumor uptake, suggesting active transport of PSar into tumor tissues. Thus, we hypothesized that PSar-based materials might be utilized as diagnostic probes for targeting tumors and therefore evaluated the potential of PSar labeled with an ICG derivative, ICG-PSar, as a PA imaging probe for targeting cancer. In this study, ICG-PSars with differing molecular weights (10, 20, and 30 kDa) were synthesized. In vitro cellular uptake studies using ICG-PSar demonstrated rapid uptake in colon26 tumor cells partially via macropinocytosis-mediated endocytosis. In vivo fluorescence imaging and biodistribution study indicated that ICG-PSar30k exhibited high accumulation in the tumor (8.4% dose/g), with high tumor-to-blood ratios reaching 4.6 at 24 h post injection of the probe. Finally, in vivo PA imaging studies showed that PA signal increased in tumors (251%) but not in blood vessels, achieving high contrast tumor imaging at 24 h after ICG-PSar30k probe injection. These results suggest that ICG-PSar has potential as a tumor-targeting PA imaging probe.
[Mh] Termos MeSH primário: Neoplasias/diagnóstico por imagem
Peptídeos/farmacocinética
Sarcosina/análogos & derivados
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Endocitose
Seres Humanos
Verde de Indocianina
Camundongos
Técnicas Fotoacústicas
Sarcosina/farmacocinética
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Peptides); 25951-24-0 (polysarcosine); IX6J1063HV (Indocyanine Green); Z711V88R5F (Sarcosine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170208
[St] Status:MEDLINE
[do] DOI:10.1021/acs.bioconjchem.6b00715



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