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[PMID]:29446584
[Au] Autor:Sosedova LM; Novikov MA; Titov EA; Rukavishnikov VS
[Ti] Título:[Induction of apoptosis in neurons of white rats under exposure of nanobiocomposite based on ag (0) nanoparticles and arabinogalactan].
[So] Source:Gig Sanit;95(12):1210-13, 2016.
[Is] ISSN:0016-9900
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:There are presented results of the immunohistochemical study of neural tissue of outbred albino rats exposed for 9 days to the influence of the silver nanobiocomposite consisted of silver nanoparticles encapsulated into a matrix of a natural polymer - arabinogalactan. The research of albino rats was performed in 2 stages: half of the rats in each groups were decapitated immediately after the exposure (early period) and the rest animals - 6 months after the end of exposure (remote period). The impact of the studied substance was proved to cause functional changes in cells of the nervous tissue. After the subacute administration of the nanobiocomposite - argentum-arabinogalactan (nano-Ag-AG) in cells of the nervous tissue of the brain of albino rats the expression of apoptotic and anti-apoptotic protein (caspase-3 and bcl-2) was established to be changed. The number of normal neurons producing protein caspase-3 sharply increases. Herewith the number of immunonegative neurons fairly declines. Along with this there is noted the high level of bcl-2 content, one function ofwhich is the preclusion ofapoptosis. In preparations there is revealed a significant gain in the number of bcl-2 expressing neurons, however, the protective effect of the protein is not fully realized, that leads to the significantly increase in the content of damaged hyperchromatic cells. The evaluation of results of the immunohistochemical study of the nervous tissue of albino rats according to data concerning the proteins caspase-3 and bcl-2 expression permits to make a conclusion about the capability of nanoargentum encapsulated into polymer matrix by passing the blood-brain barrier to induce the triggering apoptosis cascade in neurons of the cerebral cortex.
[Mh] Termos MeSH primário: Encéfalo
Galactanos/farmacologia
Larix
Nanopartículas Metálicas/efeitos adversos
Prata
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Biopolímeros/farmacologia
Barreira Hematoencefálica/metabolismo
Encéfalo/efeitos dos fármacos
Encéfalo/patologia
Encéfalo/fisiopatologia
Caspase 3/metabolismo
Imuno-Histoquímica
Modelos Animais
Preparações de Plantas/farmacologia
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Ratos
Prata/efeitos adversos
Prata/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biopolymers); 0 (Galactans); 0 (Plant Preparations); 0 (Proto-Oncogene Proteins c-bcl-2); 3M4G523W1G (Silver); EC 3.4.22.- (Caspase 3); SL4SX1O487 (arabinogalactan)
[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:180216
[St] Status:MEDLINE


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[PMID]:29247857
[Au] Autor:Yin L; Li H; Liu W; Yao Z; Cheng Z; Zhang H; Zou H
[Ad] Endereço:Key Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.
[Ti] Título:A highly potent CDK4/6 inhibitor was rationally designed to overcome blood brain barrier in gliobastoma therapy.
[So] Source:Eur J Med Chem;144:1-28, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Glioblastoma multiforme (GBM) is the most common and deadliest of malignant brain tumors in adults. Disease development is associated with dysregulation of the cyclin D-CDK4/6-INK4-Rb pathway, resulting in increased proliferation; thus, CDK4/6 kinase inhibitors are promising candidates for GBM treatment. The recently developed CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, are effective in subcutaneous glioma models, but their blood-brain barrier (BBB) permeability is poor, limiting drug delivery to the central nervous system. Here, we designed and synthesized a series of novel CDK4/6 inhibitors with favorable BBB permeability for the treatment of GBM. Compound 11 exhibited a favorable pharmacological profile and significant penetration of the BBB with the K value of 4.10 and the K value of 0.23 in mice after an oral dose of 10 mg/kg. IC values for CDK4/cyclin D1 and CDK6/cyclin D3 were 3 nM and 1 nM, respectively. In vivo studies with an orthotopic xenograft mouse model of GBM showed that 11 had tumor growth inhibition values ranging from 62% to 99% for doses ranging from 3.125 to 50 mg/kg, and no significant body weight loss was observed. The increase in life span based on the median survival time of vehicle-treated animals in mice administered a dose of 50 mg/kg was significant at 162% (p < 0.0001). These results suggest that compound 11 is a promising candidate for further investigation as an effective drug for the treatment of GBM.
[Mh] Termos MeSH primário: Neoplasias Encefálicas/tratamento farmacológico
Quinase 4 Dependente de Ciclina/antagonistas & inibidores
Quinase 6 Dependente de Ciclina/antagonistas & inibidores
Desenho de Drogas
Glioblastoma/tratamento farmacológico
Inibidores de Proteínas Quinases/farmacocinética
Inibidores de Proteínas Quinases/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Barreira Hematoencefálica/metabolismo
Barreira Hematoencefálica/patologia
Neoplasias Encefálicas/metabolismo
Neoplasias Encefálicas/patologia
Linhagem Celular Tumoral
Quinase 4 Dependente de Ciclina/metabolismo
Quinase 6 Dependente de Ciclina/metabolismo
Cães
Glioblastoma/metabolismo
Glioblastoma/patologia
Seres Humanos
Células Madin Darby de Rim Canino
Masculino
Camundongos
Inibidores de Proteínas Quinases/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protein Kinase Inhibitors); EC 2.7.11.22 (Cyclin-Dependent Kinase 4); EC 2.7.11.22 (Cyclin-Dependent Kinase 6)
[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:171217
[St] Status:MEDLINE


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[PMID]:29441969
[Au] Autor:Lin S; Wu J; Guo W; Zhu Y
[Ti] Título:Effects of leonurine on intracerebral haemorrhage by attenuation of perihematomal edema and neuroinflammation the JNK pathway.
[So] Source:Pharmazie;71(11):644-650, 2016 11 02.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Perihematomal edema plays a critical role in secondary brain injury in intracerebral hemorrhage (ICH), which is associated with inflammation, hematoma toxicity and oxidative stress. In this work, we investigated the protective effects of leonurine, an alkaloid of Herbal Leonuri, and possible mechanisms to provide a basis for a new therapeutic approach for ICH treatment. In in vivo studies, we demonstrated for the first time that leonurine treatment substantially decreased perihematomal edema, ameliorated neurobehavioral function deficits, reduced apoptosis and protected injured cerebral tissue after ICH. These benefits appear to be ascribed to leonurine effectively attenuating bloodbrain barrier (BBB) breakdown in vivo, by inhibiting degradation of hemoglobin and alleviating inflammatory mediator release. In this study, BV-2 cells were exposed in vitro to oxyhemoglobin (OxyHb) at a concentration of 10 µM to mimic neuroinflammation after ICH. Consistent with the results of the in vivo study, leonurine significantly inhibited OxyHbinduced inflammatory proteins expression in BV-2 cells, mainly through inhibiting the c-Jun N-terminal kinase (JNK) signaling pathway. This is the first time that leonurine is proved to be capable to protect the injured cerebral tissue after ICH, based on alleviating neuroinflammation and attenuating BBB breakdown to ameliorate perihematomal edema.
[Mh] Termos MeSH primário: Edema Encefálico/tratamento farmacológico
Hemorragia Cerebral/tratamento farmacológico
Encefalite/tratamento farmacológico
Ácido Gálico/análogos & derivados
Hematoma/tratamento farmacológico
Proteínas Proto-Oncogênicas c-jun/efeitos dos fármacos
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Comportamento Animal/efeitos dos fármacos
Barreira Hematoencefálica/efeitos dos fármacos
Água Corporal/metabolismo
Edema Encefálico/patologia
Edema Encefálico/psicologia
Hemorragia Cerebral/psicologia
Encefalite/psicologia
Ácido Gálico/farmacologia
Hematoma/patologia
Hematoma/psicologia
Mediadores da Inflamação/metabolismo
Masculino
Metaloproteinase 9 da Matriz/metabolismo
Oxiemoglobinas/metabolismo
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Inflammation Mediators); 0 (Oxyhemoglobins); 0 (Proto-Oncogene Proteins c-jun); 09Q5W34QDA (leonurine); 632XD903SP (Gallic Acid); EC 3.4.24.35 (Matrix Metalloproteinase 9); EC 3.4.24.35 (Mmp9 protein, rat)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6692


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[PMID]:27778404
[Au] Autor:Menzel L; Kleber L; Friedrich C; Hummel R; Dangel L; Winter J; Schmitz K; Tegeder I; Schäfer MK
[Ad] Endereço:Department of Anesthesiology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
[Ti] Título:Progranulin protects against exaggerated axonal injury and astrogliosis following traumatic brain injury.
[So] Source:Glia;65(2):278-292, 2017 02.
[Is] ISSN:1098-1136
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In response to traumatic brain injury (TBI) microglia/macrophages and astrocytes release inflammatory mediators with dual effects on secondary brain damage progression. The neurotrophic and anti-inflammatory glycoprotein progranulin (PGRN) attenuates neuronal damage and microglia/macrophage activation in brain injury but mechanisms are still elusive. Here, we studied histopathology, neurology and gene expression of inflammatory markers in PGRN-deficient mice (Grn ) 24 h and 5 days after experimental TBI. Grn mice displayed increased perilesional axonal injury even though the overall brain tissue loss and neurological consequences were similar to wild-type mice. Brain inflammation was elevated in Grn mice as reflected by increased transcription of pro-inflammatory cytokines TNFα, IL-1ß, IL-6, and decreased transcription of the anti-inflammatory cytokine IL-10. However, numbers of Iba1 microglia/macrophages and immigrated CD45 leukocytes were similar at perilesional sites while determination of IgG extravasation suggested stronger impairment of blood brain barrier integrity in Grn compared to wild-type mice. Most strikingly, Grn mice displayed exaggerated astrogliosis 5 days after TBI as demonstrated by anti-GFAP immunohistochemistry and immunoblot. GFAP astrocytes at perilesional sites were immunolabelled for iNOS and TNFα suggesting that pro-inflammatory activation of astrocytes was attenuated by PGRN. Accordingly, recombinant PGRN (rPGRN) attenuated LPS- and cytokine-evoked iNOS and TNFα mRNA expression in cultured astrocytes. Moreover, intracerebroventricular administration of rPGRN immediately before trauma reduced brain damage and neurological deficits, and restored normal levels of cytokine transcription, axonal injury and astrogliosis 5 days after TBI in Grn mice. Our results show that endogenous and recombinant PGRN limit axonal injury and astrogliosis and suggest therapeutic potential of PGRN in TBI. GLIA 2017;65:278-292.
[Mh] Termos MeSH primário: Axônios/patologia
Lesões Encefálicas Traumáticas/complicações
Lesões Encefálicas Traumáticas/patologia
Gliose/etiologia
Gliose/prevenção & controle
Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Astrócitos/efeitos dos fármacos
Astrócitos/patologia
Axônios/metabolismo
Barreira Hematoencefálica/patologia
Proteínas de Ligação ao Cálcio/metabolismo
Células Cultivadas
Citocinas/genética
Citocinas/metabolismo
Modelos Animais de Doenças
Expressão Gênica/efeitos dos fármacos
Expressão Gênica/genética
Regulação da Expressão Gênica/efeitos dos fármacos
Regulação da Expressão Gênica/genética
Gliose/patologia
Peptídeos e Proteínas de Sinalização Intercelular/genética
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
Lipopolissacarídeos/farmacologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Proteínas dos Microfilamentos/metabolismo
Proteínas do Tecido Nervoso/metabolismo
Doenças do Sistema Nervoso/etiologia
Doenças do Sistema Nervoso/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aif1 protein, mouse); 0 (Calcium-Binding Proteins); 0 (Cytokines); 0 (Grn protein, mouse); 0 (Intercellular Signaling Peptides and Proteins); 0 (Lipopolysaccharides); 0 (Microfilament Proteins); 0 (Nerve Tissue Proteins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1002/glia.23091


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[PMID]:29232607
[Au] Autor:Chowdhury EA; Alqahtani F; Bhattacharya R; Mehvar R; Bickel U
[Ad] Endereço:Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA; Center for Blood-Brain Barrier Research, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA.
[Ti] Título:Simultaneous UPLC-MS/MS analysis of two stable isotope labeled versions of sucrose in mouse plasma and brain samples as markers of blood-brain barrier permeability and brain vascular space.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1073:19-26, 2018 Jan 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Blood Brain Barrier (BBB) permeability is frequently compromised in the course of diseases affecting the central nervous system (CNS). Sucrose is a low molecular weight, hydrophilic marker with slow permeability at the naive BBB and therefore one of the widely used indicators of barrier integrity. Our laboratory recently developed a highly sensitive UPLC-MS/MS method for stable isotope labeled [ C ]sucrose in biological matrices. Correction of total brain concentration for contribution of intravascular space is required in such experiments in order to accurately measure BBB permeability, and it is often accomplished by vascular perfusion with buffer solutions prior to brain sampling. The purpose of the present study was to develop a UPLC-MS/MS method, which allows simultaneous analysis of two different stable isotope labeled sucrose variants, one of which can be utilized as a vascular marker. The first analyte, [ C ]sucrose, serves to quantify brain uptake clearance as a measure of BBB permeability, while the second analyte, [ C ]sucrose, is administered just before termination of the animal experiment and is considered as the vascular marker. [ H ]sucrose is used as the internal standard for both C labeled compounds. Because the majority of recent studies on CNS diseases employ mice, another objective was to validate the new technique in this species. The UPLC-MS/MS method was linear (r ≥ 0.99) in the tested concentration ranges, from 10 to 1000 ng/mL for both analytes in plasma, from 2 to 400 ng/g [ C ]sucrose in brain and from 10 to 400 ng/g [ C ]sucrose in brain. It was also validated in terms of acceptable intra and inter run accuracy and precision values (n = 5). The dual analyte technique was applied in a study in mice. One group received intravenous bolus injections of 10 mg/kg [ C ]sucrose at time 0, and 10 mg/kg [ C ]sucrose at 14.5 min, and subsequent terminal blood and brain sampling was performed at 15 min. For comparison, another group received an intravenous bolus dose of 10 mg/kg [ C ]sucrose and was submitted to transcardiac perfusion with buffer after 15 min. We demonstrate that the two alternative techniques to correct for intravascular content deliver equivalent values for brain concentration and brain uptake clearance.
[Mh] Termos MeSH primário: Barreira Hematoencefálica/metabolismo
Isótopos de Carbono/análise
Cromatografia Líquida de Alta Pressão/métodos
Sacarose/análise
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Animais
Biomarcadores/análise
Biomarcadores/sangue
Biomarcadores/metabolismo
Química Encefálica/fisiologia
Permeabilidade Capilar/fisiologia
Isótopos de Carbono/sangue
Isótopos de Carbono/farmacocinética
Feminino
Limite de Detecção
Modelos Lineares
Camundongos
Camundongos Endogâmicos C57BL
Reprodutibilidade dos Testes
Sacarose/sangue
Sacarose/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Carbon Isotopes); 57-50-1 (Sucrose)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE


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[PMID]:28471166
[Au] Autor:Batarseh YS; Bharate SS; Kumar V; Kumar A; Vishwakarma RA; Bharate SB; Kaddoumi A
[Ad] Endereço:Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe , Monroe, Louisiana 71201, United States.
[Ti] Título:Crocus sativus Extract Tightens the Blood-Brain Barrier, Reduces Amyloid ß Load and Related Toxicity in 5XFAD Mice.
[So] Source:ACS Chem Neurosci;8(8):1756-1766, 2017 08 16.
[Is] ISSN:1948-7193
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Crocus sativus, commonly known as saffron or Kesar, is used in Ayurveda and other folk medicines for various purposes as an aphrodisiac, antispasmodic, and expectorant. Previous evidence suggested that Crocus sativus is linked to improving cognitive function in Alzheimer's disease (AD) patients. The aim of this study was to in vitro and in vivo investigate the mechanism(s) by which Crocus sativus exerts its positive effect against AD. The effect of Crocus sativus extract on Aß load and related toxicity was evaluated. In vitro results showed that Crocus sativus extract increases the tightness of a cell-based blood-brain barrier (BBB) model and enhances transport of Aß. Further in vivo studies confirmed the effect of Crocus sativus extract (50 mg/kg/day, added to mice diet) on the BBB tightness and function that was associated with reduced Aß load and related pathological changes in 5XFAD mice used as an AD model. Reduced Aß load could be explained, at least in part, by Crocus sativus extract effect to enhance Aß clearance pathways including BBB clearance, enzymatic degradation and ApoE clearance pathway. Furthermore, Crocus sativus extract upregulated synaptic proteins and reduced neuroinflammation associated with Aß pathology in the brains of 5XFAD mice. Crocin, a major active constituent of Crocus sativus and known for its antioxidant and anti-inflammatory effect, was also tested separately in vivo in 5XFAD mice. Crocin (10 mg/kg/day) was able to reduce Aß load but to a lesser extent when compared to Crocus sativus extract. Collectively, findings from this study support the positive effect of Crocus sativus against AD by reducing Aß pathological manifestations.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Peptídeos beta-Amiloides/efeitos dos fármacos
Barreira Hematoencefálica/efeitos dos fármacos
Crocus
Fármacos Neuroprotetores/farmacologia
Extratos Vegetais/farmacologia
[Mh] Termos MeSH secundário: Administração Oral
Doença de Alzheimer/metabolismo
Doença de Alzheimer/patologia
Peptídeos beta-Amiloides/metabolismo
Peptídeos beta-Amiloides/toxicidade
Animais
Anti-Inflamatórios não Esteroides/química
Anti-Inflamatórios não Esteroides/farmacologia
Barreira Hematoencefálica/metabolismo
Barreira Hematoencefálica/patologia
Linhagem Celular
Crocus/química
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Células Endoteliais/efeitos dos fármacos
Células Endoteliais/metabolismo
Células Endoteliais/patologia
Inflamação/tratamento farmacológico
Inflamação/metabolismo
Inflamação/patologia
Masculino
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Microvasos/efeitos dos fármacos
Microvasos/metabolismo
Microvasos/patologia
Fármacos Neuroprotetores/química
Fitoterapia
Extratos Vegetais/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Neuroprotective Agents); 0 (Plant Extracts)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1021/acschemneuro.7b00101


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[PMID]:29275231
[Au] Autor:Pastor M; Fernández-Calle R; Di Geronimo B; Vicente-Rodríguez M; Zapico JM; Gramage E; Coderch C; Pérez-García C; Lasek AW; Puchades-Carrasco L; Pineda-Lucena A; de Pascual-Teresa B; Herradón G; Ramos A
[Ad] Endereço:Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28925, Alcorcón, Madrid, Spain.
[Ti] Título:Development of inhibitors of receptor protein tyrosine phosphatase ß/ζ (PTPRZ1) as candidates for CNS disorders.
[So] Source:Eur J Med Chem;144:318-329, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A new series of blood-brain barrier permeable molecules designed to mimic the activity of Pleiotrophin in the CNS has been designed and synthesized. These compounds exert their action by interacting with the intracellular domain PD1 of the Protein Tyrosine-Phosphatase Receptor Z1 (PTPRZ1), and inhibiting its tyrosine phosphatase activity. The most potent compounds 10a and 12b (IC = 0,1 µM) significantly increase the phosphorylation of key tyrosine residues of PTPRZ1 substrates involved in neuronal survival and differentiation, and display protective effects against amphetamine-induced toxicity. Docking and molecular dynamics experiments have been used to analyze the binding mode and to explain the observed selectivity against PTP1B. An In vivo experiment has demonstrated that 10a can cross the BBB, thus promoting the possibility of moving forward these candidates for the development of drugs for the treatment of CNS disorders, such as drug addiction and neurodegenerative diseases.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/farmacologia
Proteínas de Transporte/farmacologia
Doenças do Sistema Nervoso Central/tratamento farmacológico
Citocinas/farmacologia
Inibidores Enzimáticos/farmacologia
Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios não Esteroides/síntese química
Anti-Inflamatórios não Esteroides/química
Barreira Hematoencefálica/efeitos dos fármacos
Barreira Hematoencefálica/metabolismo
Proteínas de Transporte/síntese química
Proteínas de Transporte/química
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Doenças do Sistema Nervoso Central/metabolismo
Citocinas/síntese química
Citocinas/química
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/química
Seres Humanos
Camundongos
Modelos Moleculares
Estrutura Molecular
Ratos
Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Carrier Proteins); 0 (Cytokines); 0 (Enzyme Inhibitors); 134034-50-7 (pleiotrophin); EC 3.1.3.48 (PTPRZ1 protein, human); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 5)
[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:171225
[St] Status:MEDLINE


  8 / 23409 MEDLINE  
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[PMID]:29183383
[Au] Autor:Schaefer CP; Tome ME; Davis TP
[Ad] Endereço:Department of Pharmacology, University of Arizona, P.O. Box 245050, Tucson, AZ, 85724, USA.
[Ti] Título:The opioid epidemic: a central role for the blood brain barrier in opioid analgesia and abuse.
[So] Source:Fluids Barriers CNS;14(1):32, 2017 Nov 29.
[Is] ISSN:2045-8118
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Opioids are currently the primary treatment method used to manage both acute and chronic pain. In the past two to three decades, there has been a surge in the use, abuse and misuse of opioids. The mechanism by which opioids relieve pain and induce euphoria is dependent on the drug crossing the blood-brain barrier and accessing the central nervous system. This suggests the blood brain barrier plays a central role in both the benefits and risks of opioid use. The complex physiological responses to opioids that provide the benefits and drive the abuse also needs to be considered in the resolution of the opioid epidemic.
[Mh] Termos MeSH primário: Analgésicos Opioides/farmacologia
Barreira Hematoencefálica/efeitos dos fármacos
Encéfalo/efeitos dos fármacos
Transtornos Relacionados ao Uso de Opioides/epidemiologia
[Mh] Termos MeSH secundário: Epidemias
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Analgesics, Opioid)
[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:171130
[St] Status:MEDLINE
[do] DOI:10.1186/s12987-017-0080-3


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[PMID]:29274777
[Au] Autor:Tong M; He Z; Lin X; Zhou Y; Wang Q; Zheng Z; Chen J; Xu H; Tian N
[Ad] Endereço:Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China.
[Ti] Título:Lithium chloride contributes to blood-spinal cord barrier integrity and functional recovery from spinal cord injury by stimulating autophagic flux.
[So] Source:Biochem Biophys Res Commun;495(4):2525-2531, 2018 01 22.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Blood-spinal cord barrier (BSCB) disruption following spinal cord injury (SCI) significantly compromises functional neuronal recovery. Autophagy is a potential therapeutic target when seeking to protect the BSCB. We explored the effects of lithium chloride (LiCl) on BSCB permeability and autophagy-induced SCI both in a rat model of SCI and in endothelial cells subjected to oxygen-glucose deprivation. We evaluated BSCB status using the Evans Blue dye extravasation test and measurement of tight junction (TJ) protein levels; we also assessed functional locomotor recovery. We detected autophagy-associated proteins in vivo and in vitro using both Western blotting and immunofluorescence staining. We found that, in a rat model of SCI, LiCl attenuated the elevation in BSCB permeability, improved locomotor recovery, and inhibited the degradation of TJ proteins including occludin and claudin-5. LiCl significantly induced the extent of autophagic flux after SCI by increasing LC3-II and ATG-5 levels, and abolishing p62 accumulation. In addition, a combination of LiCl and the autophagy inhibitor chloroquine not only partially eliminated the BSCB-protective effect of LiCl, but also exacerbated TJ protein degradation both in vivo and in vitro. Together, these findings suggest that LiCl treatment alleviates BSCB disruption and promotes locomotor recovery after SCI, partly by stimulating autophagic flux.
[Mh] Termos MeSH primário: Proteínas Relacionadas à Autofagia/metabolismo
Autofagia/efeitos dos fármacos
Barreira Hematoencefálica/efeitos dos fármacos
Cloreto de Lítio/administração & dosagem
Traumatismos da Medula Espinal/tratamento farmacológico
Traumatismos da Medula Espinal/fisiopatologia
Regeneração da Medula Espinal/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Barreira Hematoencefálica/patologia
Barreira Hematoencefálica/fisiopatologia
Relação Dose-Resposta a Droga
Feminino
Fármacos Neuroprotetores/administração & dosagem
Ratos
Ratos Sprague-Dawley
Recuperação de Função Fisiológica/efeitos dos fármacos
Recuperação de Função Fisiológica/fisiologia
Traumatismos da Medula Espinal/patologia
Regeneração da Medula Espinal/fisiologia
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Autophagy-Related Proteins); 0 (Neuroprotective Agents); G4962QA067 (Lithium Chloride)
[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:171225
[St] Status:MEDLINE


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[PMID]:28744122
[Au] Autor:Zou D; Wang W; Lei D; Yin Y; Ren P; Chen J; Yin T; Wang B; Wang G; Wang Y
[Ad] Endereço:Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, People's Republic of China.
[Ti] Título:Penetration of blood-brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system.
[So] Source:Int J Nanomedicine;12:4879-4889, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:For the treatment of glioma and other central nervous system diseases, one of the biggest challenges is that most therapeutic drugs cannot be delivered to the brain tumor tissue due to the blood-brain barrier (BBB). The goal of this study was to construct a nanodelivery vehicle system with capabilities to overcome the BBB for central nervous system administration. Doxorubicin as a model drug encapsulated in ganglioside GM1 micelles was able to achieve up to 9.33% loading efficiency and 97.05% encapsulation efficiency by orthogonal experimental design. The in vitro study demonstrated a slow and sustainable drug release in physiological conditions. In the cellular uptake studies, mixed micelles could effectively transport into both human umbilical vein endothelial cells and C6 cells. Furthermore, biodistribution imaging of mice showed that the DiR/GM1 mixed micelles were accumulated sustainably and distributed centrally in the brain. Experiments on zebrafish confirmed that drug-loaded GM1 micelles can overcome the BBB and enter the brain. Among all the treatment groups, the median survival time of C6-bearing rats after administering DOX/GM1 micelles was significantly prolonged. In conclusion, the ganglioside nanomicelles developed in this work can not only penetrate BBB effectively but also repair nerves and kill tumor cells at the same time.
[Mh] Termos MeSH primário: Barreira Hematoencefálica/efeitos dos fármacos
Neoplasias Encefálicas/tratamento farmacológico
Doxorrubicina/farmacologia
Gangliosídeo G(M1)/química
Glioma/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Antibióticos Antineoplásicos/administração & dosagem
Antibióticos Antineoplásicos/farmacologia
Doxorrubicina/administração & dosagem
Doxorrubicina/farmacocinética
Sistemas de Liberação de Medicamentos/métodos
Gangliosídeos/química
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Masculino
Micelas
Regeneração Nervosa/efeitos dos fármacos
Ratos Wistar
Distribuição Tecidual
Peixe-Zebra/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (Gangliosides); 0 (Micelles); 0 (sialogangliosides); 37758-47-7 (G(M1) Ganglioside); 80168379AG (Doxorubicin)
[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:170727
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S138257



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