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Pesquisa : B01.050.150.900.649.313.988.400.112.199.120.610.050 [Categoria DeCS]
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[PMID]:28724769
[Au] Autor:Termini JM; Magnani DM; Maxwell HS; Lauer W; Castro I; Pecotte J; Barber GN; Watkins DI; Desrosiers RC
[Ad] Endereço:Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA.
[Ti] Título:Simian T Lymphotropic Virus 1 Infection of Papio anubis: Sequence Heterogeneity and T Cell Recognition.
[So] Source:J Virol;91(20), 2017 Oct 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Baboons naturally infected with simian T lymphotropic virus (STLV) are a potentially useful model system for the study of vaccination against human T lymphotropic virus (HTLV). Here we expanded the number of available full-length baboon STLV-1 sequences from one to three and related the T cell responses that recognize the immunodominant Tax protein to the sequences present in two individual baboons. Continuously growing T cell lines were established from two baboons, animals 12141 and 12752. Next-generation sequencing (NGS) of complete STLV genome sequences from these T cell lines revealed them to be closely related but distinct from each other and from the baboon STLV-1 sequence in the NCBI sequence database. Overlapping peptides corresponding to each unique Tax sequence and to the reference baboon Tax sequence were used to analyze recognition by T cells from each baboon using intracellular cytokine staining (ICS). Individual baboons expressed more gamma interferon and tumor necrosis factor alpha in response to Tax peptides corresponding to their own STLV-1 sequence than in response to Tax peptides corresponding to the reference baboon STLV-1 sequence. Thus, our analyses revealed distinct but closely related STLV-1 genome sequences in two baboons, extremely low heterogeneity of STLV sequences within each baboon, no evidence for superinfection within each baboon, and a ready ability of T cells in each baboon to recognize circulating Tax sequences. While amino acid substitutions that result in escape from CD8 T cell recognition were not observed, premature stop codons were observed in 7% and 56% of sequences from peripheral blood mononuclear cells from animals 12141 and 12752, respectively. It has been estimated that approximately 100,000 people suffer serious morbidity and 10,000 people die each year from the consequences associated with human T lymphotropic virus (HTLV) infection. There are no antiviral drugs and no preventive vaccine. A preventive vaccine would significantly impact the global burden associated with HTLV infections. Here we provide fundamental information on the simian T lymphotropic virus (STLV) naturally transmitted in a colony of captive baboons. The limited viral sequence heterogeneity in individual baboons, the identity of the viral gene product that is the major target of cellular immune responses, the persistence of viral amino acid sequences that are the major targets of cellular immune responses, and the emergence of truncated variants in the major target of cellular immune responses all parallel what are seen with HTLV infection of humans. These results justify the use of STLV-infected baboons as a model system for vaccine development efforts.
[Mh] Termos MeSH primário: Produtos do Gene tax/química
Produtos do Gene tax/genética
Infecções por HTLV-I/virologia
Vírus 1 Linfotrópico T de Símios/isolamento & purificação
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
DNA Viral/genética
Produtos do Gene tax/imunologia
Genoma Viral
Infecções por HTLV-I/imunologia
Infecções por HTLV-I/transmissão
Sequenciamento de Nucleotídeos em Larga Escala
Imunidade Celular
Interferon gama/biossíntese
Interferon gama/imunologia
Papio anubis
Filogenia
Reação em Cadeia da Polimerase
Vírus 1 Linfotrópico T de Símios/imunologia
Linfócitos T/virologia
Fator de Necrose Tumoral alfa/biossíntese
Fator de Necrose Tumoral alfa/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Viral); 0 (Gene Products, tax); 0 (Tumor Necrosis Factor-alpha); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE


  2 / 271 MEDLINE  
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[PMID]:28686693
[Au] Autor:Wanji S; Eyong EJ; Tendongfor N; Ngwa CJ; Esuka EN; Kengne-Ouafo AJ; Datchoua-Poutcheu FR; Enyong P; Agnew D; Eversole RR; Hopkins A; Mackenzie CD
[Ad] Endereço:Parasites and Vectors Research Unit, Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, South West Region, Cameroon.
[Ti] Título:Ivermectin treatment of Loa loa hyper-microfilaraemic baboons (Papio anubis): Assessment of microfilarial load reduction, haematological and biochemical parameters and histopathological changes following treatment.
[So] Source:PLoS Negl Trop Dis;11(7):e0005576, 2017 Jul.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Individuals with high intensity of Loa loa are at risk of developing serious adverse events (SAEs) post treatment with ivermectin. These SAEs have remained unclear and a programmatic impediment to the advancement of community directed treatment with ivermectin. The pathogenesis of these SAEs following ivermectin has never been investigated experimentally. The Loa/baboon (Papio anubis) model can be used to investigate the pathogenesis of Loa-associated encephalopathy following ivermectin treatment in humans. METHODS: 12 baboons with microfilarial loads > 8,000mf/mL of blood were randomised into four groups: Group 1 (control group receiving no drug), Group 2 receiving ivermectin (IVM) alone, Group 3 receiving ivermectin plus aspirin (IVM + ASA), and Group 4 receiving ivermectin plus prednisone (IVM + PSE). Blood samples collected before treatment and at Day 5, 7 or 10 post treatment, were analysed for parasitological, hematological and biochemical parameters using standard techniques. Clinical monitoring of animals for side effects took place every 6 hours post treatment until autopsy. At autopsy free fluids and a large number of standard organs were collected, examined and tissues fixed in 10% buffered formalin and processed for standard haematoxylin-eosin staining and specific immunocytochemical staining. RESULTS: Mf counts dropped significantly (p<0.05) in all animals following ivermectin treatment with reductions as high as (89.9%) recorded; while no significant drop was observed in the control animals. Apart from haemoglobin (Hb) levels which recorded a significant (p = 0.028) drop post treatment, all other haematological and biochemical parameters did not show any significant changes (p>0.05). All animals became withdrawn 48 hours after IVM administration. All treated animals recorded clinical manifestations including rashes, itching, diarrhoea, conjunctival haemorrhages, lymph node enlargement, pinkish ears, swollen face and restlessness; one animal died 5 hours after IVM administration. Macroscopic changes in post-mortem tissues observed comprised haemorrhages in the brain, lungs, heart, which seen in all groups given ivermectin but not in the untreated animals. Microscopically, the major cellular changes seen, which were present in all the ivermectin treated animals included microfilariae in varying degrees of degeneration in small vessels. These were frequently associated with fibrin deposition, endothelial changes including damage to the integrity of the blood vessel and the presence of extravascular erythrocytes (haemorrhages). There was an increased presence of eosinophils and other chronic inflammatory types in certain tissues and organs, often in large numbers and associated with microfilarial destruction. Highly vascularized organs like the brain, heart, lungs and kidneys were observed to have more microfilariae in tissue sections. The number of mf seen in the brain and kidneys of animals administered IVM alone tripled that of control animals. Co-administration of IVM + PSE caused a greater increase in mf in the brain and kidneys while the reverse was noticed with the co-administration of IVM + ASA. CONCLUSIONS: The treatment of Loa hyper-microfilaraemic individuals with ivermectin produces a clinical spectrum that parallels that seen in Loa hyper-microfilaraemic humans treated with ivermectin. The utilization of this experimental model can contribute to the improved management of the adverse responses in humans.
[Mh] Termos MeSH primário: Sangue/parasitologia
Filaricidas/efeitos adversos
Ivermectina/efeitos adversos
Loa/isolamento & purificação
Loíase/tratamento farmacológico
Loíase/patologia
Carga Parasitária
[Mh] Termos MeSH secundário: Estruturas Animais/patologia
Animais
Análise Química do Sangue
Modelos Animais de Doenças
Filaricidas/uso terapêutico
Histocitoquímica
Ivermectina/uso terapêutico
Loíase/parasitologia
Papio anubis
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Filaricides); 70288-86-7 (Ivermectin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170809
[Lr] Data última revisão:
170809
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005576


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[PMID]:28573721
[Au] Autor:Isbell LA; Bidner LR; Crofoot MC; Matsumoto-Oda A; Farine DR
[Ad] Endereço:Department of Anthropology, University of California, Davis, California.
[Ti] Título:GPS-identified, low-level nocturnal activity of vervets (Chlorocebus pygerythrus) and olive baboons (Papio anubis) in Laikipia, Kenya.
[So] Source:Am J Phys Anthropol;164(1):203-211, 2017 Sep.
[Is] ISSN:1096-8644
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Except for owl monkeys (Aotus spp.), all anthropoid primates are considered strictly diurnal. Recent studies leveraging new technologies have shown, however, that some diurnal anthropoids also engage in nocturnal activity. Here we examine the extent to which vervets (Chlorocebus pygerythrus) and olive baboons (Papio anubis) are active at night. MATERIALS AND METHODS: We deployed GPS collars with tri-axial accelerometer data loggers on 18 free-ranging adult females: 12 vervets spread among 5 social groups, and 6 olive baboons spread among 4 groups. Their locations were recorded every 15 min, and their activity levels, for 3 s/min over 7.5 months. We also used camera traps that were triggered by heat and movement at seven sleeping sites. RESULTS: Travel was detected on 0.4% of 2,029 vervet-nights involving 3 vervets and 1.1% of 1,109 baboon-nights involving 5 baboons. Travel was mainly arboreal for vervets but mainly terrestrial for baboons. During the night, vervets and baboons were active 13% and 15% of the time, respectively. Activity varied little throughout the night and appeared unaffected by moon phase. DISCUSSION: Our results confirm the low nocturnality of vervets and olive baboons, which we suggest is related to living near the equator with consistent 12-hr days, in contrast to other anthropoids that are more active at night. Since anthropoid primates are thought to have evolved in northern latitudes, with later dispersal to tropical latitudes, our results may have implications for understanding the evolution of anthropoid diurnality.
[Mh] Termos MeSH primário: Cercopithecus aethiops/fisiologia
Ritmo Circadiano/fisiologia
Papio anubis/fisiologia
[Mh] Termos MeSH secundário: Animais
Antropologia Física
Evolução Biológica
Sistemas de Informação Geográfica
Quênia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.1002/ajpa.23259


  4 / 271 MEDLINE  
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[PMID]:28408624
[Au] Autor:Healy LD; Puy C; Fernández JA; Mitrugno A; Keshari RS; Taku NA; Chu TT; Xu X; Gruber A; Lupu F; Griffin JH; McCarty OJT
[Ad] Endereço:From the Departments of Cell, Developmental & Cancer Biology and healyl@ohsu.edu.
[Ti] Título:Activated protein C inhibits neutrophil extracellular trap formation and activation .
[So] Source:J Biol Chem;292(21):8616-8629, 2017 May 26.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Activated protein C (APC) is a multifunctional serine protease with anticoagulant, cytoprotective, and anti-inflammatory activities. In addition to the cytoprotective effects of APC on endothelial cells, podocytes, and neurons, APC cleaves and detoxifies extracellular histones, a major component of neutrophil extracellular traps (NETs). NETs promote pathogen clearance but also can lead to thrombosis; the pathways that negatively regulate NETosis are largely unknown. Thus, we studied whether APC is capable of directly inhibiting NETosis via receptor-mediated cell signaling mechanisms. Here, by quantifying extracellular DNA or myeloperoxidase, we demonstrate that APC binds human leukocytes and prevents activated platelet supernatant or phorbol 12-myristate 13-acetate (PMA) from inducing NETosis. Of note, APC proteolytic activity was required for inhibiting NETosis. Moreover, antibodies against the neutrophil receptors endothelial protein C receptor (EPCR), protease-activated receptor 3 (PAR3), and macrophage-1 antigen (Mac-1) blocked APC inhibition of NETosis. Select mutations in the Gla and protease domains of recombinant APC caused a loss of NETosis. Interestingly, pretreatment of neutrophils with APC prior to induction of NETosis inhibited platelet adhesion to NETs. Lastly, in a nonhuman primate model of -induced sepsis, pretreatment of animals with APC abrogated release of myeloperoxidase from neutrophils, a marker of neutrophil activation. These findings suggest that the anti-inflammatory function of APC at therapeutic concentrations may include the inhibition of NETosis in an EPCR-, PAR3-, and Mac-1-dependent manner, providing additional mechanistic insight into the diverse functions of neutrophils and APC in disease states including sepsis.
[Mh] Termos MeSH primário: Armadilhas Extracelulares/imunologia
Ativação de Neutrófilo/imunologia
Neutrófilos/imunologia
Proteína C/imunologia
[Mh] Termos MeSH secundário: Animais
Antígenos CD/imunologia
Antígenos CD/metabolismo
Modelos Animais de Doenças
Receptor de Proteína C Endotelial
Escherichia coli
Infecções por Escherichia coli/sangue
Infecções por Escherichia coli/imunologia
Armadilhas Extracelulares/metabolismo
Feminino
Seres Humanos
Antígeno de Macrófago 1/imunologia
Antígeno de Macrófago 1/metabolismo
Masculino
Ativação de Neutrófilo/efeitos dos fármacos
Neutrófilos/metabolismo
Papio anubis
Proteína C/metabolismo
Receptores de Superfície Celular/imunologia
Receptores de Superfície Celular/metabolismo
Sepse/sangue
Sepse/imunologia
Acetato de Tetradecanoilforbol/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (Endothelial Protein C Receptor); 0 (Macrophage-1 Antigen); 0 (PROCR protein, human); 0 (Protein C); 0 (Receptors, Cell Surface); NI40JAQ945 (Tetradecanoylphorbol Acetate)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170415
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.768309


  5 / 271 MEDLINE  
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[PMID]:28324014
[Au] Autor:Rotwein P
[Ad] Endereço:Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech Health University Health Sciences Center, El Paso, Texas 79905.
[Ti] Título:Variation in the Insulin-Like Growth Factor 1 Gene in Primates.
[So] Source:Endocrinology;158(4):804-814, 2017 Apr 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Insulin-like growth factor 1 (IGF1) is a multifunctional peptide that is involved in a wide range of physiological and pathophysiological processes in many animal species, ranging from somatic growth in children to metabolism and tissue regeneration and repair in adults. The IGF1 gene is under multifactorial regulation in the few species in which it has been studied, with major control being exerted by growth hormone through a gene expression pathway involving inducible binding of the STAT5b transcription factor to dispersed enhancer elements. In this study, using resources available in public genomic databases, genes encoding IGF1 have been analyzed in a cohort of six nonhuman primate species representing >60 million years of evolutionary diversification from a common ancestor: chimpanzee, gorilla, macaque, olive baboon, marmoset, and mouse lemur. The IGF1 gene has been well conserved among these primates. Similar to human IGF1, each gene appears to be composed of six exons and five introns, and contains recognizable tandem promoters, each with a unique leader exon. Exon and intron lengths are very similar, and DNA sequence conservation is high, not only in orthologous exons and promoter regions, but also in putative growth hormone-activated STAT5b-binding enhancers that are found in analogous locations in IGF1 intron 3 and in 5' distal intergenic DNA. Taken together, the high level of organizational and nucleotide sequence similarity in the IGF1 gene and locus among these seven species supports the contention that common regulatory paradigms had existed prior to the onset of primate speciation >85 million years ago.
[Mh] Termos MeSH primário: Evolução Molecular
Variação Genética
Fator de Crescimento Insulin-Like I/genética
Regiões Promotoras Genéticas
[Mh] Termos MeSH secundário: Animais
Callithrix/genética
Cheirogaleidae/genética
Bases de Dados Genéticas
Elementos Facilitadores Genéticos
Éxons
Gorilla gorilla/genética
Íntrons
Macaca/genética
Pan troglodytes/genética
Papio anubis/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
67763-96-6 (Insulin-Like Growth Factor I)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1210/en.2016-1920


  6 / 271 MEDLINE  
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[PMID]:28323851
[Au] Autor:Fedurek P; Lehmann J
[Ad] Endereço:Department of Life Sciences, University of Roehampton, London, United Kingdom.
[Ti] Título:The effect of excluding juveniles on apparent adult olive baboons (Papio anubis) social networks.
[So] Source:PLoS One;12(3):e0173146, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In recent years there has been much interest in investigating the social structure of group living animals using social network analysis. Many studies so far have focused on the social networks of adults, often excluding younger, immature group members. This potentially may lead to a biased view of group social structure as multiple recent studies have shown that younger group members can significantly contribute to group structure. As proof of the concept, we address this issue by investigating social network structure with and without juveniles in wild olive baboons (Papio anubis) at Gashaka Gumti National Park, Nigeria. Two social networks including all independently moving individuals (i.e., excluding dependent juveniles) were created based on aggressive and grooming behaviour. We used knockout simulations based on the random removal of individuals from the network in order to investigate to what extent the exclusion of juveniles affects the resulting network structure and our interpretation of age-sex specific social roles. We found that juvenile social patterns differed from those of adults and that the exclusion of juveniles from the network significantly altered the resulting overall network structure. Moreover, the removal of juveniles from the network affected individuals in specific age-sex classes differently: for example, including juveniles in the grooming network increased network centrality of adult females while decreasing centrality of adult males. These results suggest that excluding juveniles from the analysis may not only result in a distorted picture of the overall social structure but also may mask some of the social roles of individuals belonging to different age-sex classes.
[Mh] Termos MeSH primário: Agressão/psicologia
Asseio Animal
Papio anubis/psicologia
[Mh] Termos MeSH secundário: Envelhecimento/psicologia
Animais
Análise por Conglomerados
Simulação por Computador
Feminino
Masculino
Modelos Psicológicos
Caracteres Sexuais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170823
[Lr] Data última revisão:
170823
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0173146


  7 / 271 MEDLINE  
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[PMID]:28238494
[Au] Autor:Orellana R; García-Solares J; Donnez J; van Kerk O; Dolmans MM; Donnez O
[Ad] Endereço:Pôle de Gynécologie, Institut de Recherche Expérimentale, Université Catholique de Louvain, Brussels, Belgium.
[Ti] Título:Important role of collective cell migration and nerve fiber density in the development of deep nodular endometriosis.
[So] Source:Fertil Steril;107(4):987-995.e5, 2017 Apr.
[Is] ISSN:1556-5653
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To evaluate deep nodular endometriotic lesions induced in baboons over 12 months and analyze collective cell migration and nerve fiber density. DESIGN: Morphologic and immunohistochemical analysis of endometriotic lesions induced in baboons over the course of 1 year. SETTING: Academic research unit. ANIMAL(S): Three female baboons (Papio anubis). INTERVENTION(S): Recovery of induced deep nodular endometriotic nodules from baboons. MAIN OUTCOME MEASURE(S): Evaluation of the morphology of glands by analysis of the center of lesions and the invasion front; immunohistochemical staining with Ki67, E-cadherin, and ß-catenin for investigation of mitotic activity and cell-cell junctions, and with protein gene product 9.5 and nerve growth factor (NGF) for study of nerve fiber density (NFD). RESULT(S): All (100%) of the lesions were invasive 1 year after induction, compared with 42.29% after 6 months. Glands from the invasion front showed significantly reduced thickness but significantly higher mitotic activity. E-Cadherin and ß-catenin expression were similar between the center and front. NFD was significantly higher in lesions induced after 1 year than after 6 months, and NGF expression was significantly lower in 1-year lesions than in 6-month lesions. CONCLUSION(S): Nodular endometriotic lesions induced in the baboon model were found to be significantly more invasive and innervated after 12 months than after 6 months. The invasive phenotype was highly expressed in glands at the invasion front, and our study suggests that nerve fibers play a role in the development of lesions as observed in women.
[Mh] Termos MeSH primário: Movimento Celular
Endometriose/patologia
Endométrio/patologia
Fibras Nervosas/patologia
[Mh] Termos MeSH secundário: Animais
Biomarcadores/metabolismo
Caderinas/metabolismo
Modelos Animais de Doenças
Endometriose/metabolismo
Endométrio/inervação
Endométrio/metabolismo
Feminino
Imuno-Histoquímica
Antígeno Ki-67/metabolismo
Mitose
Fibras Nervosas/metabolismo
Fator de Crescimento Neural/metabolismo
Papio anubis
Fenótipo
Fatores de Tempo
Ubiquitina Tiolesterase/metabolismo
beta Catenina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Cadherins); 0 (Ki-67 Antigen); 0 (beta Catenin); 9061-61-4 (Nerve Growth Factor); EC 3.4.19.12 (Ubiquitin Thiolesterase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170605
[Lr] Data última revisão:
170605
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170228
[St] Status:MEDLINE


  8 / 271 MEDLINE  
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[PMID]:27493269
[Au] Autor:Tournier N; Goutal S; Auvity S; Traxl A; Mairinger S; Wanek T; Helal OB; Buvat I; Soussan M; Caillé F; Langer O
[Ad] Endereço:Imagerie Moléculaire In Vivo, IMIV, CEA, INSERM, CNRS, Université Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France nicolas.tournier@cea.fr.
[Ti] Título:Strategies to Inhibit ABCB1- and ABCG2-Mediated Efflux Transport of Erlotinib at the Blood-Brain Barrier: A PET Study on Nonhuman Primates.
[So] Source:J Nucl Med;58(1):117-122, 2017 Jan.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The tyrosine kinase inhibitor erlotinib poorly penetrates the blood-brain barrier (BBB) because of efflux transport by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), thereby limiting its utility in the treatment of non-small cell lung cancer metastases in the brain. Pharmacologic strategies to inhibit ABCB1/ABCG2-mediated efflux transport at the BBB have been successfully developed in rodents, but it remains unclear whether these can be translated to humans given the pronounced species differences in ABCG2/ABCB1 expression ratios at the BBB. We assessed the efficacy of two different ABCB1/ABCG2 inhibitors to enhance brain distribution of C-erlotinib in nonhuman primates as a model of the human BBB. METHODS: Papio anubis baboons underwent PET scans of the brain after intravenous injection of C-erlotinib under baseline conditions (n = 4) and during intravenous infusion of high-dose erlotinib (10 mg/kg/h, n = 4) or elacridar (12 mg/kg/h, n = 3). RESULTS: Under baseline conditions, C-erlotinib distribution to the brain (total volume of distribution [V ], 0.22 ± 0.015 mL/cm ) was markedly lower than its distribution to muscle tissue surrounding the skull (V , 0.86 ± 0.10 mL/cm ). Elacridar infusion resulted in a 3.5 ± 0.9-fold increase in C-erlotinib distribution to the brain (V , 0.81 ± 0.21 mL/cm , P < 0.01), reaching levels comparable to those in muscle tissue, without changing C-erlotinib plasma pharmacokinetics. During high-dose erlotinib infusion, C-erlotinib brain distribution was also significantly (1.7 ± 0.2-fold) increased (V , 0.38 ± 0.033 mL/cm , P < 0.05), with a concomitant increase in C-erlotinib plasma exposure. CONCLUSION: We successfully implemented ABCB1/ABCG2 inhibition protocols in nonhuman primates resulting in pronounced increases in brain distribution of C-erlotinib. For patients with brain tumors, such inhibition protocols may ultimately be applied to create more effective treatments using drugs that undergo efflux transport at the BBB.
[Mh] Termos MeSH primário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo
Acridinas/administração & dosagem
Barreira Hematoencefálica/metabolismo
Cloridrato de Erlotinib/farmacocinética
Imagem Molecular/métodos
Tetra-Hidroisoquinolinas/administração & dosagem
[Mh] Termos MeSH secundário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores
Animais
Antineoplásicos/administração & dosagem
Antineoplásicos/farmacocinética
Barreira Hematoencefálica/diagnóstico por imagem
Barreira Hematoencefálica/efeitos dos fármacos
Relação Dose-Resposta a Droga
Cloridrato de Erlotinib/administração & dosagem
Masculino
Papio anubis
Inibidores de Proteínas Quinases/administração & dosagem
Inibidores de Proteínas Quinases/farmacocinética
Transporte Proteico/efeitos dos fármacos
Transporte Proteico/fisiologia
Compostos Radiofarmacêuticos/administração & dosagem
Compostos Radiofarmacêuticos/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Acridines); 0 (Antineoplastic Agents); 0 (Protein Kinase Inhibitors); 0 (Radiopharmaceuticals); 0 (Tetrahydroisoquinolines); DA87705X9K (Erlotinib Hydrochloride); N488540F94 (Elacridar)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160806
[St] Status:MEDLINE
[do] DOI:10.2967/jnumed.116.178665


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[PMID]:27328754
[Au] Autor:Stephenson AR; Edler MK; Erwin JM; Jacobs B; Hopkins WD; Hof PR; Sherwood CC; Raghanti MA
[Ad] Endereço:Department of Anthropology, Kent State University, Kent, Ohio, 44242.
[Ti] Título:Cholinergic innervation of the basal ganglia in humans and other anthropoid primates.
[So] Source:J Comp Neurol;525(2):319-332, 2017 Feb 01.
[Is] ISSN:1096-9861
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cholinergic innervation of the basal ganglia is important in learning and memory. Striatal cholinergic neurons integrate cognitive and motivational states with behavior. Given these roles, it is not surprising that deficits in cortical cholinergic innervation have been correlated with loss of cognitive function in Alzheimer's disease and schizophrenia. Such evidence suggests the potential significance of subcortical cholinergic innervation in the evolution of the human brain. To compare humans with other closely related primates, the present study quantified axons and interneurons immunoreactive for choline acetyltransferase (ChAT) in regions of the executive and motor loops of the basal ganglia of humans, great apes, and monkeys. We also compared ChAT-immunoreactive (ir) interneuron morphological types among species within striatal regions. The results indicate that humans and great apes differ from monkeys in having a preponderance of multipolar ChAT-ir interneurons in the caudate nucleus and putamen, whereas monkeys have a more heterogeneous representation of multipolar, bipolar, and unipolar interneurons. Cholinergic innervation, as measured by axon and interneuron densities, did not differ across species in the medial caudate nucleus. Differences were detected in the dorsal caudate nucleus, putamen, and globus pallidus but the observed variation did not associate with the phylogenetic structure of the species in the sample. However, combining the present results with previously published data for dopamine revealed a unique pattern of innervation for humans, with higher amounts of dopamine compared with acetylcholine in the striatum. Taken together, these findings indicate a potential evolutionary shift in basal ganglia neurotransmission in humans that may favor increased synaptic plasticity. J. Comp. Neurol. 525:319-332, 2017. © 2016 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Gânglios da Base/citologia
Neurônios Colinérgicos/citologia
Vias Neurais/citologia
[Mh] Termos MeSH secundário: Animais
Cebus
Gorilla gorilla
Seres Humanos
Processamento de Imagem Assistida por Computador
Imuno-Histoquímica
Macaca nemestrina
Pan troglodytes
Papio anubis
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160623
[St] Status:MEDLINE
[do] DOI:10.1002/cne.24067


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[PMID]:27287424
[Au] Autor:Sommer V; Lowe A; Jesus G; Alberts N; Bouquet Y; Inglis DM; Petersdorf M; van Riel E; Thompson J; Ross C
[Ad] Endereço:Department of Anthropology, University College London, London, UK.
[Ti] Título:Antelope Predation by Nigerian Forest Baboons: Ecological and Behavioural Correlates.
[So] Source:Folia Primatol (Basel);87(2):67-90, 2016.
[Is] ISSN:1421-9980
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Baboons are well studied in savannah but less so in more closed habitats. We investigated predation on mammals by olive baboons (Papio anubis) at a geographical and climatic outlier, Gashaka Gumti National Park (Nigeria), the wettest and most forested site so far studied. Despite abundant wildlife, meat eating was rare and selective. Over 16 years, baboons killed 7 bushbuck (Tragelaphus scriptus) and 3 red-flanked duiker (Cephalophus rufilatus), mostly still-lying 'parked' infants. Taking observation time into account, this is 1 predation per group every 3.3 months - far lower than at other sites. Some features of meat eating resemble those elsewhere; predation is opportunistic, adult males monopolize most prey, a targeted killing bite is lacking and begging or active sharing is absent. Carcass owners employ evasive tactics, as meat is often competed over, but satiated owners may tolerate others taking meat. Other features are unusual; this is only the second study site with predation records for bushbuck and the only one for red-flanked duiker. The atypical prey and rarity of eating mammals probably reflects the difficulty of acquiring prey animals when vegetation cover is dense. Our data support the general prediction of the socioecological model that environments shape behavioural patterns, while acknowledging their intraspecific or intrageneric plasticity.
[Mh] Termos MeSH primário: Antílopes
Papio anubis/fisiologia
Comportamento Predatório
[Mh] Termos MeSH secundário: Animais
Ecossistema
Feminino
Masculino
Nigéria
Papio anubis/psicologia
Comportamento Social
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170131
[Lr] Data última revisão:
170131
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160612
[St] Status:MEDLINE
[do] DOI:10.1159/000445830



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